Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. After ingestion of acarbose, the majority of active unchanged drug remains in the lumen of the gastrointestinal tract to exert its pharmacological activity and is metabolised by intestinal enzymes and by the microbial flora. However, everolimus may induce hyperglycaemia which may require an increase in the dose of acarbose.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to form salicylic acid and then further metabolized by glucuronidation (by several UGT, major UGT1A6). Everolimus does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as agomelatine is metabolised predominantly via CYP1A2. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Alendronate is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, alendronate should be separated from food or other medicinal products and patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product. Osteonecrosis of the jaw has been reported in an increasing number of renal cell cancer patients since the use of combined therapies consisting of nitrogen-containing bisphosphonates and antiangiogenic targeted agents. This suggests that angiogenesis suppression might increase the risk of osteonecrosis of the jaw when coadministered with bisphosphonates.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfentanil undergoes extensive CYP3A4 metabolism but everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alfuzosin is metabolized by CYP3A. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied. Aliskiren is minimally metabolized and is mainly excreted unchanged in faeces. However, P-glycoprotein is a major determinant of aliskiren bioavailability. Therefore, inhibition of P-gp by everolimus may increase aliskiren concentrations. No effect on everolimus concentrations is expected.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Allopurinol is converted to oxipurinol by xanthine oxidase and aldehyde oxidase. Everolimus not interfere with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that alosetron is metabolized by CYP2C9, 3A4 and 1A2. Everolimus does not inhibit of induce CYPs. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Alprazolam is mainly metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as aluminium hydroxide is unlikely to alter everolimus absorption.

Coadministration has not been studied. Ambrisentan is metabolised by glucuronidation via UGTs 1A3, 1A9 and 2B7, and to a lesser extent by CYP3A4 and CYP2C19. Ambrisentan is also a substrate of P-gp. Everolimus is an inhibitor of P-gp and may increase concentrations of ambrisentan. As the clinical relevance of this interaction is unknown, monitoring for ambrisentan toxicity may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amikacin is eliminated by glomerular filtration therefore no pharmacokinetic interaction is expected with everolimus.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiloride is eliminated unchanged in the kidney. In vitro data indicate that amiloride is a substrate of OCT2. Everolimus is unlikely to significantly inhibit amiloride renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Concentrations of everolimus may increase due to weak inhibition of CYP3A4 but this is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally (possibly via OCT). Everolimus is unlikely to significantly impair amisulpride elimination. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. E Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amlodipine is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as amoxicillin is mainly excreted in the urine by glomerular filtration and tubular secretion. In vitro data indicate that amoxicillin is a substrate of OAT3. Everolimus is unlikely to interfere with amoxicillin renal elimination.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as amphotericin B is not appreciably metabolized and is eliminated to a large extent in the bile. Everolimus does not interfere with amphotericin B elimination pathway. However, the European SPC for amphotericin states that concomitant use of amphotericin B and antineoplastic agents can increase the risk of renal toxicity, bronchospasm and hypotension. Monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion. About 20 to 40% of an oral dose may be excreted unchanged in the urine in 6 hours. After parenteral use about 60 to 80% is excreted in the urine within 6 hours. Everolimus is unlikely to significantly inhibit ampicillin renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as anidulafungin is not metabolised hepatically but undergoes chemical degradation at physiological temperature. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as antacids is unlikely to alter everolimus absorption.

Coadministration has not been studied. Apixaban is metabolized by CYP3A4 and to a lesser extent by CYP1A2, CYP2C8, CYP2C9 and CYP2C19. Everolimus does not inhibit or induce CYPs. However, apixaban is a substrate of P-gp and BCRP and concentrations may increase due to the inhibition of P-gp and BCRP by everolimus. No effect on everolimus concentrations is expected. 

Coadministration has not been studied but should be approached with caution. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Everolimus does not inhibit or induce CYPs. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of everolimus during the three days of coadministration. Therefore, coadministration is not recommended. If coadministration is unavoidable, reduce the everolimus dose by 50% during the few days of coadministration. Monitor closely for everolimus toxicity. Furthermore, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of everolimus may decrease due to weak induction of CYP3A4, but this is not considered to be clinically relevant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (CYP1A2 (major)) and CYP3A4, 2D6 (minor). Everolimus does not inhibit or induce UGTs or CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as astemizole is metabolized by CYPs 2D6, 2J2 and 3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atenolol is mainly eliminated unchanged in the kidney, predominantly by glomerular filtration. 

Atorvastatin is metabolized by CYP3A4 and is a substrate of P-gp. Everolimus does not inhibit or induce CYPs. Although inhibition of P-gp by everolimus may increase atorvastatin concentrations, this is unlikely to be clinically significant. Coadministration was generally safe and showed no pharmacokinetic interaction.

Coadministration has not been studied, but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is metabolized analogously to natural purines. Everolimus does not interfere with this metabolic pathway. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration showed a reduced clearance of everolimus and concentrations of everolimus may increase due to inhibition of CYP3A4 by azithromycin. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-gp and MRP2. Concentrations of everolimus may increase due to inhibition of CYP3A4 by azithromycin. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50% and the everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beclometasone is a pro-drug which is not metabolised by CYP450, but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone -17-monopropionate. Everolimus does not interact with beclomethasone metabolism. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as bedaquiline is metabolised by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%) and excreted unchanged in the urine (30%) via OAT1 and OAT3. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically significant interaction is unlikely in the range of observed clinical concentrations. In addition, there is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes and therefore is unlikely to impact everolimus.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bepridil is metabolized by CYP2D6 (major) and 3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betamethasone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as half of bezafibrate dose is eliminated unchanged in the urine. In vitro data suggest that bezafibrate inhibits the renal transporter OAT1. Everolimus does not interact with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bisacodyl is converted to an active metabolite by intestinal and bacterial enzymes. Absorption from the gastrointestinal tract is minimal and the small amount absorbed is excreted in the urine as the glucuronide. 

Coadministration has not been studied. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Everolimus does not inhibit or induce CYPs. However, bisoprolol is a substrate for P-gp and concentrations may potentially increase due to inhibition of P-gp by everolimus.

Coadministration has not been studied. Bosentan is a substrate and inducer of CYP3A4 and CYP2C9. Bosentan could potentially decrease everolimus exposure. Therefore, if the combination of everolimus and bosentan appears necessary, close monitoring is needed.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may play a role. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Budesonide is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Buprenorphine undergoes both N-dealkylation to form norbuprenorphine (via CYP3A4) and glucuronidation (via UGT2B7 and UGT1A1). Everolimus does not inhibit or induce CYPs or UGTs. However, buprenorphine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bupropion is primarily metabolized by CYP2B6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Calcium is eliminated through faeces, urine and sweat. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Candesartan is mainly eliminated unchanged via urine and bile. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capreomycin is predominantly excreted via the kidneys as unchanged drug. Renal toxicity has been reported during capreomycin treatment. Everolimus does not interfere with capreomycin renal elimination.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Captopril is largely excreted in the urine by OAT1. However, coadministration with captopril could increase the risk of angioneurotic oedema-type reactions.

Coadministration has not been studied but should be avoided. Carbamazepine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2C8. Everolimus does not interact with this pathway. However, carbamazepine is an inducer of CYPs 2C8 (strong), 2C9 (strong), 3A4 (strong), 1A2 (weak), 2B6 and UGT1A1. Concentrations of everolimus may decrease due to induction of CYP3A4. Therefore, coadministration should be avoided. If coadministration is unavoidable, monitor closely for everolimus efficacy. For patients with renal cell carcinoma, neuroendocrine tumor, mammacarcinoma or renal angiomyolipoma, consider a dose increment from 10 mg/day to 20 mg/day in 5 mg increments at day 4 and day 8 after start of the inducer, with careful monitoring of tolerability. Consider everolimus trough level monitoring of ~14 ng/ml. For patients with SEGA, dosing should be titrated to attain trough concentrations of 5 to 15 ng/ml. If concentrations are below 5 ng/ml, increase the daily dose by increments of 2.5 mg per day every two weeks, checking the trough level and assessing tolerability before increasing the dose. After discontinuation of the inducer the CYP3A4 inducing effect may persist for over a week (mostly 2 weeks), so everolimus dose should be decreased accordingly.

Coadministration has not been studied. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additionally metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Everolimus does not inhibit or induce UGTs or CYPs. However, carvedilol is a substrate for P-gp and concentrations may potentially increase due to inhibition of P-gp by everolimus.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caspofungin undergoes spontaneous chemical degradation and metabolism via a non CYP-mediated pathway. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Everolimus does not interfere with cefalexin renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly excreted unchanged in the urine, mainly by glomerular filtration with some renal tubular secretion via OAT3. Everolimus does not interfere with cefazolin renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cefixime is renally excreted predominantly by glomerular filtration. Everolimus does not interfere with cefixime renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is partially metabolized by non-specific esterases. Most of a dose of cefotaxime is excreted in the urine - about 60% as unchanged drug and a further 24% as desacetyl-cefotaxime, an active metabolite. In vitro studies indicate that OAT3 participates in the renal elimination of cefotaxime. Everolimus does not interfere with cefotaxime renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ceftazidime is excreted predominantly by renal glomerular filtration. Everolimus does not interfere with ceftazidime renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is eliminated mainly as unchanged drug, approximately 60% of the dose being excreted in the urine predominantly by glomerular filtration and the remainder via the biliary and intestinal tracts. Everolimus does not interfere with ceftriaxone renal elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is primarily metabolized by CYP2C9. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetirizine is only metabolised to a limited extent and is eliminated unchanged in the urine through both glomerular filtration and tubular secretion. In vitro data indicate that cetirizine inhibits OCT2. Everolimus is unlikely to interact with cetirizine renal elimination.

Coadministration has not been studied. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4. Coadministration of chloramphenicol may potentially increase levels of everolimus via this mechanism, increasing the risk of adverse events. The clinical significance of this interaction is unknown. Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlordiazepoxide is extensively metabolised by CYP3A4, but does not inhibit or induce cytochromes. Everolimus does not inhibit or induce CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlortalidone is mainly excreted unchanged in the urine and faeces. 

Ciclosporin is substrate for CYP3A4 and P-gp and inhibits CYP3A4 and OATP1B1. Coadministration increased everolimus AUC by 2.7-fold and showed an increased risk of nephrotoxicity. Coadministration is not recommended and should be approached with caution. If coadministration is unavoidable, close monitoring for nephrotoxicity and everolimus toxicity is recommended. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 ng/ml.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Cilazapril is mainly eliminated unchanged by the kidneys. However, coadministration with cilazapril could increase the risk of angioneurotic oedema-type reactions

Coadministration has not been studied. In vitro data indicate that cimetidine inhibits OAT1 and OCT2 but at concentrations much higher than the observed clinical concentrations. Everolimus does not interact with this pathway. However, concentrations of everolimus may increase due to inhibition of CYP3A4 by cimetidine. Coadministration should be approached with caution. If coadministation is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but should be approached with caution. Ciprofloxacin is primarily eliminated unchanged in the kidneys by glomerular filtration and tubular secretion via OAT3. Ciprofloxacin is also metabolised and partially cleared through the bile and intestine. Everolimus does not interfere with ciprofloxacin elimination. However, ciprofloxacin is a weak to moderate inhibitor of CYP3A4 and a strong inhibitor of CYP1A2. Concentrations of everolimus may increase due to inhibition of CYP3A4. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumor, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day. Consider everolimus trough plasma concentration monitoring to maintain a minimal trough concentration of ~14 ng/ml. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5 to 15 ng/ml.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as cisapride is unlikely to alter everolimus absorption.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Citalopram is metabolized by CYP2C19 (38%), 2D6 (31%) and 3A4 (31%). Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied and is not recommended. Clarithromycin may increase everolimus concentrations due to inhibition of CYP3A4 and P-gp. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50% and the everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clavulanic acid is extensively metabolized (likely non-CYP mediated pathway) and excreted in the urine by glomerular filtration. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clemastine is predominantly metabolized in the liver via CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Clindamycin is metabolized by CYP3A4 and in vitro data suggest that it is a CYP3A4 inhibitor, which could increase everolimus concentrations. No a priori dosage adjustment is recommended for everolimus. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of clobetasol.

Coadministration has not been studied. In vitro data suggest that clofazimine is a CYP3A4 inhibitor, which could increase everolimus concentrations. No a priori dosage adjustment is recommended for everolimus. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clofibrate is hydrolyzed to an active metabolite, clofibric acid. Excretion of clofibric acid glucuronide is possibly performed via OAT1. Everolimus does not interfere with clofibrate elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clomipramine is metabolized by CYP3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 70% of administered clonidine is excreted in the urine, mainly in form of the unchanged parent drug (40-60% of the dose). Clonidine is a weak inhibitor of OCT2 but is unlikely to interact with everolimus elimination. In addition, everolimus does not interfere with clonidine elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Clorazepate is rapidly converted to nordiazepam which is then metabolized to oxazepam by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Clozapine is metabolised mainly by CYP1A2 and CYP3A4, and to a lesser extent by CYP2C19 and CYP2D6. Everolimus does not inhibit or induce CYPs. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied. Codeine is converted via CYP2D6 to morphine, an active metabolite with analgesic and opioid properties. Morphine is further metabolised by conjugation with glucuronic acid to morphine-3-glucuronide (inactive) and morphine-6-glucuronide (active). Morphine is also a substrate of P-gp. Everolimus is an inhibitor of P-gp and may increase concentrations of morphine. The clinical relevance of this interaction is unknown. Furthermore, codeine is converted via CYP3A4 to norcodeine, an inactive metabolite. Everolimus does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied. Colchicine is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. However, colchicine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected. Clinical monitoring is recommended due to the narrow therapeutic window of colchicine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied. Dabigatran is a substrate of P-gp and is excreted renally. Dabigatran concentrations may increase due to inhibition of P-gp by everolimus. The clinical relevance of this interaction is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dalteparin is excreted largely unchanged via the kidneys. Everolimus does not interfere with the renal excretion of dalteparin. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP450 enzymes. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as desipramine is metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Dexamethasone has been described as a weak inducer of CYP3A4 and could possibly decrease everolimus plasma concentrations. However, the clinical relevance of CYP3A4 induction by dexamethasone has not been established yet. Monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dextropropoxyphene is mainly metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Diamorphine is rapidly metabolized by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Morphine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Diazepam is metabolized to nordiazepam (by CYP3A4 and 2C19) and to temazepam (mainly by CYP3A4). Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9. Everolimus does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied. Digoxin is eliminated renally via the renal transporters OATP4C1 and P-gp. Everolimus is an inhibitor of P-gp and may possibly increase digoxin concentrations. It is recommended that the lowest possible dose of digoxin should initially be given to patients on everolimus. The digoxin dose should be carefully titrated to obtain the desired clinical effect while assessing the overall clinical state of the subject.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dihydrocodeine undergoes predominantly direct glucuronidation, with CYP3A4 mediated metabolism accounting for only 5-10% of the overall metabolism. Everolimus does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied. Diltiazem is metabolized by CYP3A4 and CYP2D6. Concentrations of everolimus may increase due to inhibition of CYP3A4 by diltiazem. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diphenhydramine is mainly metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Everolimus is unlikely to interfere with this pathway. However, everolimus concentrations may increase by inhibition of P-gp by dipyridamole. The clinical relevance of this interaction is not known yet.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Domperidone is mainly metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase to inactive compounds. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals. There is little potential for dopamine to affect disposition of everolimus, or to be affected by everolimus.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxazosin is metabolized mainly by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxepin is metabolized to nordoxepin (a metabolite with comparable pharmacological activity as the parent compound) mainly by CYP2C19. In addition, doxepin and nordoxepin are metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxycycline is excreted in the urine and faeces as unchanged active substance. Between 40%-60% of an administered dose can be accounted for in the urine. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dronabinol is mainly metabolized by CYP2C9 and to a lesser extent by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as dulaglutide is degraded by endogenous endopeptidases. Dulaglutide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of this interaction is unknown. Everolimus may induce hyperglycaemia which may require an increase in the dose of dulaglutide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Duloxetine is metabolized by CYP2D6 and CYP1A2. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dutasteride is mainly metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Increases in edoxaban plasma concentrations cannot be excluded via inhibition of P-gp. The clinical relevance of this interaction is not known.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Eltrombopag is metabolised by cleavage conjugation (via UGT1A1, UGT1A3) and oxidation (via CYP1A2 and CYP2C8). Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Enalapril is hydrolysed to enalaprilat which is eliminated renally (possibly via OATs). However, coadministration with enalapril could increase the risk of angioneurotic oedema-type reactions.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Enoxaparin does not undergo cytochrome metabolism but is desulphated and depolymerised in the liver, and is excreted predominantly renally. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as eprosartan is largely excreted in bile and urine as unchanged drug. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ertapenem is mainly eliminated through the kidneys by glomerular filtration with tubular secretion playing a minor component. Everolimus does not interact with this metabolic pathway.

Coadministration increased everolimus AUC by 4.4-fold, due to inhibition of CYP3A4 by erythromycin. Avoid concurrent use of potent CYP3A4 inhibitors, because everolimus is relatively toxic. Coadministration should be approached with caution. If combination is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50% and the everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Escitalopram is metabolized by CYP2C19 (37%), 2D6 (28%) and 3A4 (35%) to form N-desmethylescitalopram. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as esomeprazole is unlikely to alter everolimus absorption.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Estazolam is metabolized to its major metabolite 4-hydroxyestazolam via CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Everolimus does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethambutol is partly metabolized by alcohol dehydrogenase (20%) and partly eliminated unchanged in the faeces (20%) and in the urine (50%). Everolimus does not interact with this metabolic pathway.

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethionamide is extensively metabolized in the liver, animal studies suggest involvement of flavin-containing monooxygenases. Everolimus does not interfere with this pathway. 

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as exenatide is cleared mainly by glomerular filtration. Exenatide delays gastric emptying and could possibly decrease the absorption rate of concomitantly administered oral drugs. The clinical relevance of this interaction is unknown. Everolimus may induce hyperglycaemia which may require an increase in the dose of exenatide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ezetimibe is glucuronidated by UGTs 1A1 and 1A3 and to a lesser extent by UGTs 2B15 and 2B7. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as famotidine is unlikely to alter everolimus absorption.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Felodipine is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fenofibrate is hydrolyzed to an active metabolite, fenofibric acid. In vitro data suggest that fenofibric acid inhibits OAT3. Everolimus does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fentanyl undergoes extensive CYP3A4 metabolism. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied. Fexofenadine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Finasteride is metabolised by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flecainide is metabolized mainly via CYP2D6, with a proportion (approximately 30%) of the parent drug also eliminated unchanged renally. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied. Flucloxacillin is mainly eliminated renally partly by glomerular filtration and partly by active secretion via OAT1. Everolimus does not interact with this metabolic pathway. However, flucloxacillin was shown to induce CYP3A4 and P-gp and therefore could potentially decrease everolimus exposure. Use with caution.

Coadministration has not been studied but may increase plasma concentrations of everolimus via inhibition of CYP3A4 by fluconazole. Coadministration of everolimus and ketoconazole increased total everolimus AUC by 15-fold, however, the effect of fluconazole is expected to be much lower than of ketoconazole. No a priori dose adjustment is needed for everolimus.

Coadministration has not been studied. Flucytosine is metabolised to 5-fluorouracil (5-FU). 5-FU is further metabolised by dihydropyrimidine dehydrogenase (DPD) to an inactive metabolite. Everolimus does not interfere with this elimination pathway. However, 5-FU binds to the enzyme thymidylate synthase resulting in DNA damage. This mechanism occurs in all fast dividing cells including bone marrow cells, resulting in haematological toxicity. Everolimus also induces haematological toxicity which could be enhanced by the use of flucytosine. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fludrocortisone is metabolized in the liver to inactive metabolites, possibly via CYP3A. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Flunitrazepam is metabolized mainly via CYP3A4 and 2C19. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluoxetine is metabolized by CYP2D6 and 2C9 and to a lesser extent by 2C19 and 3A4 to form norfluoxetine. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluphenazine is metabolised by CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. The metabolism of flurazepam is most likely CYP-mediated. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluticasone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluvastatin is mainly metabolized by CYP2C9. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Fluvoxamine is metabolized mainly by CYP2D6 and to a lesser extent by CYP1A2. Everolimus does not inhibit or induce CYPs. Fluvoxamine inhibits CYPs 1A2, 2C19, 3A4, 2C9. Therefore, everolimus concentrations may be slightly increased if coadministered with fluvoxamine. The clinical relevance of this interaction is unknown. Coadministration should be approached with caution. If coadministration is unavoidable, monitor closely for everolimus toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Formoterol is eliminated primarily by direct glucuronidation, with O-demethylation (by CYPs 2D6, 2C19, 2C9, and 2A6) followed by further glucuronidation being another pathway. As multiple CYP450 and UGT enzymes catalyze the transformation the potential for a pharmacokinetic interaction is low. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but should be approached with caution. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Everolimus does not interact with this metabolic pathway. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Everolimus does not inhibit or induce CYPs. However, during treatment aprepitant is a moderate inhibitor of CYP3A4 and may increase concentrations of everolimus during the three days of coadministration. Therefore, coadministration is not recommended. If coadministration is unavoidable, reduce the everolimus dose by 50% during the few days of coadministration. Monitor closely for everolimus toxicity. Furthermore, after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Concentrations of everolimus may decrease due to weak induction of CYP3A4, but this is not considered to be clinically relevant.

Coadministration has not been studied but should be avoided. Fosphenytoin is rapidly converted to the active metabolite phenytoin. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Everolimus does not interact with this pathway. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of everolimus may decrease due to induction of CYP3A4 and P-gp. Therefore, coadministration should be avoided. If coadministration is unavoidable, monitor closely for everolimus efficacy. For patients with renal cell carcinoma, neuroendocrine tumor, mammacarcinoma or renal angiomyolipoma, consider a dose increment from 10 mg/day to 20 mg/day in 5 mg increments at day 4 and day 8 after starting phenytoin, with careful monitoring of tolerability. Consider everolimus trough level monitoring of ~14 ng/mL. For patients with SEGA, dosing should be titrated to attain trough concentrations of 5-15 ng/mL. If concentrations are below 5 ng/mL, the daily dose may be increased by increments of 2.5 mg per day every two weeks, checking the trough level and assessing tolerability before increasing the dose. After discontinuation of phenytoin the CYP3A4 inducing effect may persist for over a week (mostly 2 weeks) and the everolimus dose should be decreased accordingly.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Furosemide is glucuronidated mainly in the kidney (UGT1A9) and to a lesser extent in the liver (UGT1A1). A large proportion of furosemide is also eliminated unchanged renally (via OATs). In vitro data indicate that furosemide is an inhibitor of the renal transporters OAT1/OAT3. Everolimus does not interfere with furosemide elimination.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gabapentin is cleared mainly by glomerular filtration. Everolimus is unlikely to interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gemfibrozil is metabolised by UGT2B7. Everolimus does not inhibit or induce UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gentamicin is eliminated unchanged predominantly via glomerular filtration. Everolimus does not interact with this metabolic pathway. 

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Glibenclamide is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C9. Everolimus does not inhibit or induce CYPs. However, everolimus may induce hyperglycaemia which may require an increase in the dose of glibenclamide.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Gliclazide is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C19. Everolimus does not inhibit or induce CYPs. However, everolimus may induce hyperglycaemia which may require an increase in the dose of gliclazide.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Glimepiride is mainly metabolized by CYP2C9. Everolimus does not inhibit or induce CYPs. However, everolimus may induce hyperglycaemia which may require an increase in the dose of glimepiride.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Glipizide is mainly metabolized by CYP2C9. Everolimus does not inhibit or induce CYPs. However, everolimus may induce hyperglycaemia which may require an increase in the dose of glipizide.

Coadministration has not been studied. Granisetron is metabolized by CYP3A4. Everolimus does not inhibit of induce CYPs. However, granisetron is substrate of P-gp and concentrations may potentially increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Coadministration has not been studied, but grapefruit juice is known to inhibit CYP3A4 and could potentially increase everolimus concentrations. However, the magnitude of this potential interaction is difficult to predict as the effect of grapefruit juice is concentration, dose and preparation dependent and varies widely across brands. Coadministration is not recommended. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 ng/ml.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 

Coadministration has not been studied. Less than 1% of a griseofulvin dose is excreted unchanged via the kidneys. Everolimus does not interfere with griseofulvin elimination pathway. However, griseofulvin is a liver microsomal enzyme inducer and may lower plasma levels, and therefore reduce the efficacy of concomitantly administered medicinal products that are metabolized by CYP3A4, such as everolimus.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Haloperidol has a complex metabolism as it undergoes glucuronidation (UGT2B7>1A4, 1A9), carbonyl reduction as well as oxidative metabolism (CYP3A4, 2D6). Everolimus does not inhibit or induce UGTs or CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydralazine is metabolised via primary oxidative metabolism and acetylation. Although in vitro studies have suggested that hydralazine is a mixed enzyme inhibitor, which may weakly inhibit CYP3A4 and CYP2D6, it is not expected that this will lead to a clinical relevant interaction with everolimus. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrochlorothiazide is not metabolized and is cleared by the kidneys via OAT1. In vitro data indicate that hydrochlorothiazide is unlikely to inhibit OAT1 in the range of clinically significant concentrations. Significant interactions are not expected with everolimus.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocodone is metabolised by CYP2D6 to hydromorphone and by CYP3A4 to norhydrocodone, both of which have analgesic effects. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydrocortisone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with the topical use of hydrocortisone.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Hydromorphone is eliminated via glucuronidation, mainly by UGT2B7. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea is not a substrate of CYP enzymes or P-gp. However, coadministration may increase risk of gastro-intestinal toxicity or mucositis. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Hydroxyzine is partly metabolized by alcohol dehydrogenase and partly by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied. Ibandronic acid is not metabolised and is cleared from the plasma by uptake into bone and elimination via renal excretion. Although no pharmacokinetic interaction is expected, ibandronic acid should be taken after an overnight fast (at least 6 hours) and before the first food or drink of the day. Medicinal products and supplements should be similarly avoided prior to taking ibandronic acid. Fasting should be continued for at least 30 minutes after taking ibandronic acid. Osteonecrosis of the jaw has been reported in an increasing number of renal cell cancer patients since the use of combined therapies consisting of nitrogen-containing bisphosphonates and antiangiogenic targeted agents. This suggests that angiogenesis suppression might increase the risk of osteonecrosis of the jaw when coadministered with bisphosphonates.

Coadministration has not been studies. However, based on metabolism and clearance a clinically significant interaction is unlikely. Ibuprofen is metabolized mainly by CYP2C9 and to a lesser extent by CYP2C8 and direct glucuronidation. Everolimus does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Iloperidone is metabolized by CYP3A4 and CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipenem/cilastatin are eliminated by glomerular filtration and to a lesser extent, active tubular secretion. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Imipramine is metabolized by CYPs 3A4, 2C19 and 1A2 to desipramine. Imipramine and desipramine are both metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indapamide is extensively metabolized by CYP450. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Everolimus can lead to hyperglycaemia and reduced insulin secretion which may require an increase in the dose of insulin. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, coadministration may increase risk of neutropenia, fatigue, and thrombocytopenia. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied, but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Interleukin-2 is mainly eliminated by glomerular filtration. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A small proportion of an inhaled ipratropium dose is systemically absorbed (6.9%). Metabolism is via ester hydrolysis and conjugation. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Irbesartan is metabolized by glucuronidation and oxidation (mainly CYP2C9). Everolimus does not inhibit or induce UGTs or CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Isoniazid is acetylated in the liver to form acetylisoniazid which is then hydrolysed to isonicotinic acid and acetylhydrazine. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest that CYP3A4 has a role in nitric oxide formation from isosorbide dinitrate. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but may increase of plasma concentrations of everolimus via inhibition of CYP3A4 by itraconazole. The effect of itraconazole is expected to be comparable to that of ketoconazole (total everolimus AUC increased by 15-fold). Concurrent use of CYP3A4 inhibitors is not recommended, because everolimus is relatively toxic. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 2.5 mg/day or 5 mg every other day, and thereafter if tolerated increment to 5 mg/day. Consider everolimus trough concentration monitoring to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ivabradine is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Kanamycin is eliminated unchanged predominantly via glomerular filtration therefore no pharmacokinetic interaction is expected with everolimus. Everolimus does not interact with this metabolic pathway. 

Coadministration may increase everolimus concentrations via inhibition of CYP3A4. Coadministration of everolimus and ketoconazole increased total everolimus AUC by 15-fold. Concurrent use of CYP3A4 inhibitors is not recommended, because everolimus is relatively toxic. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 2.5 mg/day or 5 mg every other day, and thereafter if tolerated increment to 5 mg/day. Consider everolimus trough concentration monitoring to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Labetalol is mainly glucuronidated (via UGT1A1 and 2B7). Everolimus does not inhibit or induce UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lacidipine is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metabolism of lactulose to lactic acid occurs via gastro-intestinal microbial flora only. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as lansoprazole is unlikely to alter everolimus absorption.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lercanidipine is mainly metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as less than 14% of a dose of levocetirizine is metabolised. Levocetirizine is mainly eliminated unchanged in the urine through both glomerular filtration and tubular secretion. Everolimus does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Levofloxacin is eliminated renally mainly by glomerular filtration and active secretion (possibly OCT2). Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levomepromazine is metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Everolimus does not inhibit or induce CYPs or UGTs.

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. However, the use of levonorgestrel as emergency contraception is a relative contraindication due to the risk of a pregnancy while having a hormone-sensitive tumour. Therefore, the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levonorgestrel is metabolized by CYP3A4 and is glucuronidated to a minor extent. Everolimus does not inhibit or induce CYPs or UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Levothyroxine is metabolized by deiodination (by enzymes of deiodinase family) and glucuronidation. Everolimus does not interact with levothyroxine metabolism. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. CYP1A2 is the predominant enzyme involved in lidocaine metabolism in the range of therapeutic concentrations with a minor contribution from CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied. Linagliptin is mainly eliminated as parent compound in faeces with metabolism by CYP3A4 representing a minor elimination pathway. Linagliptin is a substrate for P-gp and is an inhibitor of CYP3A4. Linagliptin may increase everolimus concentrations due to inhibition of CYP3A4. Avoid concurrent use of CYP3A4 inhibitors, because everolimus is relatively toxic. Additionally, linagliptin concentrations may potentially increase due to inhibition of P-gp by everolimus. Additionally, everolimus might induce hyperglycaemia, which may require an increase in the dose of linagliptin. Close monitoring is recommended.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Linezolid undergoes non CYP mediated metabolism. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as liraglutide is degraded by endogenous endopeptidases. However, everolimus may induce hyperglycaemia which may require an increase in the dose of liraglutide.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Lisinopril is eliminated unchanged renally via glomerular filtration. However, coadministration with lisinopril could increase the risk of angioneurotic oedema-type reactions.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lithium is mainly eliminated unchanged through the kidneys. Lithium is freely filtered at a rate that is dependent upon the glomerular filtration rate therefore no pharmacokinetic interaction is expected. 

Coadministration of live vaccines (such as BCG vaccine; measles, mumps and rubella vaccines; varicella vaccines; typhoid vaccines; rotavirus vaccines; yellow fever vaccines; oral polio vaccine) has not been studied. In patients, who are receiving cytotoxics or other immunosuppressant drugs, use of live vaccines for immunisation is contraindicated. If coadministration is judged clinically necessary, use with extreme caution since generalized infections can occur.

Coadministration has not been studied. Loperamide is mainly metabolized by CYP3A4 and CYP2C8. Everolimus does not interact with this pathway. However, loperamide is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Loratadine is metabolized mainly by CYP3A4 and to a lesser extent by CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on non-CYP-mediated elimination pathways for lorazepam, no effect on plasma concentrations is expected upon coadministration with everolimus. 

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Lormetazepam is mainly glucuronidated. Everolimus does not inhibit or induce UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Losartan is converted to its active metabolite mainly by CYP2C9 in the range of clinical concentrations. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lovastatin is metabolised by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Macitentan is metabolized mainly by CYP3A4 and to a lesser extent by CYPs 2C19, 2C9 and 2C8. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Magnesium is eliminated in kidney, mainly by glomerular filtration. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Maprotiline is mainly metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Medroxyprogesterone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mefenamic acid is metabolized by CYP2C9 and glucuronidated by UGT2B7 and UGT1A9. Everolimus does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Megestrol acetate is mainly eliminated in the urine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Meropenem is primarily eliminated by the kidney and in vitro data suggest that it is a substrate of the renal transporters OAT3>OAT1. Everolimus does not interfere with this elimination pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mesalazine is metabolized to N-acetyl-mesalazine by N-acetyltransferase. Everolimus does not interfere with this pathway. 

Coadministration has not been studied, but should be approached with caution. Metamizole may decrease everolimus concentrations due to induction of CYP3A4. Decreases in everolimus exposure can lead to decreased efficacy. Selection of an alternative concomitant medication with no or minimal enzyme or transporter induction potential is recommended. The clinical relevance of this interaction is unknown; monitoring and dose adjustment may be required.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Metformin is mainly eliminated unchanged in the urine (via OCT2). Everolimus does not interact with metformin metabolic pathway. However, everolimus may induce hyperglycaemia which may require an increase in the dose of metformin.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methadone is demethylated by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methyldopa is excreted in urine largely by glomerular filtration, primarily unchanged and as the mono-O-sulfate conjugate. It is unlikely to affect the disposition of everolimus, or to be altered by everolimus.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylphenidate is not metabolized by cytochrome P450 to a clinically relevant extent and does not inhibit cytochrome P450s. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Methylprednisolone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoclopramide is partially metabolized by CYP450 system (mainly CYP2D6). Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely as metolazone is largely excreted unchanged in the urine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but elevated plasma concentrations have been reported for some CYP3A substrates (e.g. tacrolimus, ciclosporin) with metronidazole. However, metronidazole did not increase concentrations of several CYP3A probe drugs (e.g. midazolam, alprazolam). Since the mechanism of the interaction with CYP3A has not yet been identified, an interaction with everolimus cannot be excluded. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mexiletine is metabolized mainly by CYP2D6 and to a lesser extent CYP1A2. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mianserin is metabolized by CYPs 2D6 and 1A2, and to a lesser extent by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied. Miconazole inhibits CYPs 2C9 and 3A4 and could potentially increase everolimus concentrations. Oromucosal application: Coadministration should be approached with caution. If combination is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 2.5 mg/day or 5 mg every other day, and thereafter if tolerated increment to 5 mg/day. Consider everolimus trough concentration monitoring to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L. Dermal application: No a priori dosage adjustment is recommended for everolimus, since miconazole is used topically and systemic exposure is limited. 

Coadministration of oral midazolam and everolimus in a phase I study increased midazolam Cmax and AUC by 25% and 30%. Everolimus might affect the bioavailability but not the clearance, but this is unlikely to be clinically significant. Midazolam is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Midazolam is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Milnacipran is mainly eliminated unchanged (50%), and as glucuronides (30%) and oxidative metabolites (20%). Everolimus is unlikely to interfere with this pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mirtazapine is metabolised to 8-hydroxymirtazapine by CYP2D6 and CYP1A2, and to N-desmethylmirtazapine mainly by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Montelukast is mainly metabolized by CYP2C8 and to a lesser extent by CYPs 3A4 and 2C9. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Everolimus does not interact with this metabolic pathway. However, morphine is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Moxifloxacin is predominantly glucuronidated by UGT1A1. Everolimus is unlikely to interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Mycophenolate is mainly glucuronidated by UGT1A9 and 2B7. Everolimus does not interact with this metabolic pathway. In addition, inhibition of OAT1/OAT3 renal transporters by mycophenolic acid (active metabolite) is unlikely to interfere with everolimus elimination. However, due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nadroparin is renally excreted by a nonsaturable mechanism. Everolimus does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nandrolone is metabolized in the liver by alpha-reductase. Everolimus does not interact with nandrolone metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Naproxen is mainly glucuronidated by UGT2B7 (major) and demethylated to desmethylnaproxen by CYP2C9 (major) and CYP1A2. Everolimus does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Nateglinide is mainly metabolized by CYP2C9 (70%) and to a lesser extent CYP3A4 (30%). Everolimus does not inhibit or induce CYPs. However, everolimus may induce hyperglycaemia which may require an increase in the dose of nateglinide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nebivolol metabolism involves CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Nefazodone is metabolized mainly by CYP3A4 and is an inhibitor of CYP3A4. Nefazodone could potentially increase everolimus exposure. Coadministration is not recommended. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50% and the everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied. Nicardipine is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6 and 2C8. Everolimus does not inhibit or induce CYPs. However, nicardipine inhibits CYP3A4 and could potentially increase everolimus concentrations. No a priori dosage adjustment is recommended for everolimus. Monitoring of everolimus tolerability is recommended. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nicotinamide is converted to N-methylnicotinamide by nicotinamide methyltransferase which in turn is metabolized by xanthine oxidase and aldehyde oxidase. Everolimus does not interact with this metabolic pathway. In addition, nicotinic acid and its metabolites do not inhibit CYP-mediated reactions in vitro and therefore are unlikely to impact everolimus exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nifedipine is metabolised mainly by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nimesulide is extensively metabolized in the liver following multiple pathways including CYP2C9. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nisoldipine is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrendipine is extensively metabolized mainly by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nitrofurantoin is partly metabolized in the liver via glucuronidation and N-acetylation and partly eliminated in the urine as unchanged drug (30-40%). Everolimus does not interact with this metabolic pathway. 

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norelgestromin is metabolized to norgestrel (possibly by CYP3A4). Everolimus does not inhibit or induce CYPs.

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norethisterone is extensively biotransformed, first by reduction and then by sulfate and glucuronide conjugation. Everolimus does not interact with this metabolic pathway.

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolized via CYP450. Everolimus does not interact with this metabolic pathway.

Coadministration is contraindicated if everolimus is used for treatment of hormone-sensitive cancer. If used for hormone-insensitive tumours the following information is applicable: Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolised by CYP3A4 and is glucuronidated to a minor extent. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Nortriptyline is metabolized mainly by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Systemic absorption of nystatin from oral or topical dosage forms is not significant, therefore no drug interactions are expected.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ofloxacin is eliminated unchanged renally by glomerular filtration and active tubular secretion via both cationic and anionic transport systems. Everolimus is unlikely to interfere with this pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olanzapine is metabolized mainly by CYP1A2, but also by glucuronidation (UGT1A4). Everolimus does not inhibit or induce CYPs or UGTs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Olmesartan medoxomil is de-esterified to the active metabolite olmesartan which is eliminated in the faeces and urine. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as omeprazole is unlikely to alter everolimus absorption.

Coadministration has not been studied. Ondansetron is metabolized mainly by CYP1A2 and CYP3A4 and to a lesser extent by CYP2D6. Everolimus does not inhibit of induce CYPs. However, ondansetron is substrate of P-gp and concentrations may potentially increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Oxazepam is mainly glucuronidated. Everolimus does not inhibit or induce UGTs.

Coadministration has not be studied and should be avoided as it may cause significant decreases in the plasma concentrations of everolimus via induction of CYP3A4. If coadministration is unavoidable, monitor closely for everolimus efficacy. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose increase from 10 mg/day to 20 mg/day in 5 mg increments at day 4 and day 8 after starting oxcarbazepine, with careful monitoring of tolerability. Monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, dosing should be titrated to attain trough concentrations of 5-15 µg/L. If concentrations are below 5 µg/L, the daily dose may be increased by increments of 2.5 mg per day every two weeks, checking the trough level and assessing tolerability before increasing the dose. After discontinuation of oxcarbazepine the CYP3A4 inducing effect may persist for over a week (mostly 2 weeks) and the everolimus dose should be decreased accordingly.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxprenolol is largely metabolized via glucuronidation Everolimus does not inhibit or induce UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxycodone is metabolised principally to noroxycodone via CYP3A and oxymorphone via CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied. Paliperidone is primarily eliminated renally (possibly via OCT) with minimal metabolism occurring via CYP2D6 and 3A4. Everolimus does not inhibit or induce CYPs. However, paliperidone is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected

Coadministration has not been studied. Palonosetron is metabolized mainly by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Everolimus does not inhibit of induce CYPs. However, palonosetron is substrate of P-gp and concentrations may potentially increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Osteonecrosis of the jaw has been reported in an increasing number of renal cell cancer patients since the use of combined therapies consisting of nitrogen-containing bisphosphonates and antiangiogenic targeted agents. This suggests that angiogenesis suppression might increase the risk of osteonecrosis of the jaw when coadministered with bisphosphonates.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as pantoprazole is unlikely to alter everolimus absorption.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Para-aminosalicylic acid and its acetylated metabolite are mainly excreted in the urine by glomerular filtration and tubular secretion. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paracetamol is mainly metabolized by glucuronidation (via UGT1A9 (major), UGT1A6, UGT1A1, UGT2B15) and sulfation and, to a lesser extent, by oxidation (CYP2E1 (major), 1A2, 3A4 and 2D6). There is no evidence that everolimus inhibits or induces UGTs and CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Paroxetine is mainly metabolized by CYP2D6 and CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied, but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, coadministration may increase risk of neutropenia, fatigue, and thrombocytopenia. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Penicillins are mainly eliminated in the urine (20% by glomerular filtration and 80% by tubular secretion via OAT). Everolimus does not interfere with elimination of penicillins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perazine is demethylated via CYP3A4 and to a lesser extent by CYP2C9, and oxidated via FMO3. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of periciazine has not been well characterized but is likely to involve CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Perindopril is hydrolysed to the active metabolite perindoprilat and is metabolized to other inactive metabolites. Elimination occurs predominantly via the urine. Everolimus does not interact with this elimination pathway. However, coadministration with perindopril could increase the risk of angioneurotic oedema-type reactions.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perphenazine is metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pethidine is metabolized mainly by CYP2B6 and to a lesser extent by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenelzine is primarily metabolized by oxidation via monoamine oxidase and to a lesser extent acetylation. Everolimus does not interact with this metabolic pathway.

Coadministration has not be studied and should be avoided as it may cause significant decreases in the plasma concentrations of everolimus via induction of CYP3A4. If coadministration is unavoidable, monitor closely for everolimus efficacy. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose increase from 10 mg/day to 20 mg/day in 5 mg increments at day 4 and day 8 after starting phenobarbital, with careful monitoring of tolerability. Monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, dosing should be titrated to attain trough concentrations of 5-15 µg/L. If concentrations are below 5 µg/L, the daily dose may be increased by increments of 2.5 mg per day every two weeks, checking the trough level and assessing tolerability before increasing the dose. After discontinuation of phenobarbital the CYP3A4 inducing effect may persist for over a week (mostly 2 weeks) and the everolimus dose should be decreased accordingly.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Phenprocoumon is metabolised by CYP2C9 and CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but should be avoided. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Everolimus does not inhibit or induce CYPs. However, phenytoin is a potent inducer of CYP3A4, UGT and P-gp. Concentrations of everolimus may decrease due to induction of CYP3A4 and P-gp. Therefore, coadministration should be avoided. If coadministration is unavoidable, close monitoring of everolimus efficacy is recommended. For patients with renal cell carcinoma, neuroendocrine tumor, mammacarcinoma or renal angiomyolipoma, consider a dose increment from 10 mg/day to 20 mg/day in 5 mg increments at day 4 and day 8 after starting phenytoin, with careful monitoring of tolerability. Consider everolimus trough level monitoring of ~14 ng/mL. For patients with SEGA, dosing should be titrated to attain trough concentrations of 5-15 ng/mL. If concentrations are below 5 ng/mL, the daily dose may be increased by increments of 2.5 mg per day every two weeks, checking the trough level and assessing tolerability before increasing the dose. After discontinuation of phenytoin the CYP3A4 inducing effect may persist for over a week (mostly 2 weeks) and the everolimus dose should be decreased accordingly.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An in vitro study found that the only CYP450 enzyme involved in phytomenadione metabolism was CYP4F2. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely as pimozide is mainly metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pindolol is partly metabolized to hydroxymetabolites (possibly via CYP2D6) and partly eliminated unchanged in the urine. Everolimus is not expected to interfere with pindolol elimination. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Pioglitazone is metabolized mainly by CYP2C8 and to a lesser extent by CYPs 3A4, 1A2 and 2C9. Everolimus does not inhibit or induce CYPs. However, everolimus may induce hyperglycaemia which may require an increase in the dose of pioglitazone.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of pipotiazine has not been well described but may involve CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Piroxicam is primarily metabolized by CYP2C9. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pitavastatin is metabolized by UGTs 1A3 and 2B7 with minimal metabolism by CYPs 2C9 and 2C8. Everolimus does not inhibit or induce UGTs or CYPs.

Coadministration has not been studied but may increase plasma concentrations of everolimus via inhibition of CYP3A4 by posaconazole. The effect of posaconazole is expected to be comparable to that of ketoconazole (total everolimus AUC increased by 15-fold). Concurrent use of CYP3A4 inhibitors is not recommended, because everolimus is relatively toxic. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 2.5 mg/day or 5 mg every other day, and thereafter if tolerated increment to 5 mg/day. Consider everolimus trough concentration monitoring to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50%. The everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but based on limited data available an interaction appears unlikely. Potassium is eliminated renally. 

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6. Everolimus does not inhibit or induce CYPs.

Pravastatin is minimally metabolised via CYP enzymes and is a substrate of OATP1B1. Everolimus is an inhibitor of OATP1B1 and may increase pravastatin concentrations. The clinical relevance of this interaction is unknown. Although coadministration of pravastatin and everolimus has been studied, no clinically significant interactions were observed. Coadministration resulted in a non-significant decrease in pravastatin exposure (5% decrease in AUC) and a non-significant decrease in everolimus exposure (6% decrease in AUC).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prazosin is extensively metabolized, primarily by demethylation and conjugation. Everolimus is unlikely to interact with prazosin. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisolone undergoes hepatic metabolism via CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prednisone is converted to the active metabolite prednisolone by 11-B-hydroxydehydrogenase. Prednisolone is then metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as pregabalin is cleared mainly by glomerular filtration. Everolimus is unlikely to interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prochlorperazine is metabolised by CYP2D6 and CYP2C19. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Promethazine is metabolized by CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propafenone is metabolized mainly by CYP2D6 and to a lesser extent CYP1A2 and CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Propranolol is metabolized by 3 routes (aromatic hydroxylation by CYP2D6, N-dealkylation followed by side chain hydroxylation via CYPs 1A2, 2C19, 2D6, and direct glucuronidation). Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Prucalopride is minimally metabolised and mainly eliminated renally, partly by active secretion by renal transporters. Prucalopride is a substrate of P-gp, but no clinically relevant interactions were observed when prucalopride was coadministered with inhibitors of renal P-gp, OAT and OCT transporters.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Pyrazinamide is mainly metabolized by xanthine oxidase. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Quetiapine is primarily metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Quinapril is de-esterified to the active metabolite quinaprilat which is eliminated primarily by renal excretion via OAT3. Everolimus does not impact this renal transporter. However, coadministration with quinapril could increase the risk of angioneurotic oedema-type reactions.

Coadministration has not been studied. Quinidine is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. Concentrations of everolimus may increase due to weak inhibition of P-gp, but this is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as rabeprazole is unlikely to alter everolimus absorption.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ramipril is hydrolysed to the active metabolite ramiprilat, and is metabolized to the diketopiperazine ester, diketopiperazine acid and the glucuronides of ramipril and ramiprilat. Everolimus is not expected to interfere with these metabolic pathways. However, coadministration with ramipril could increase the risk of angioneurotic oedema-type reactions.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as ranitidine is unlikely to alter everolimus absorption.

Coadministration has not been studied. Ranolazine is primarily metabolised by CYP3A4 and to a lesser extent by CYP2D6. Ranolazine is also a substrate of P-gp. Everolimus is an inhibitor of P-gp and may increase ranolazine concentrations. Furthermore, ranolazine is a weak inhibitor of P-gp, CYP3A4 and CYP2D6. Concentrations of everolimus may increase due to inhibition of CYP3A4 and P-gp, but this is unlikely to be clinically significant. No a priori dosage adjustment is recommended for everolimus and ranolazine, but monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Reboxetine is metabolized by CYP3A4. In vitro data indicate reboxetine to be a weak inhibitor of CYP3A4 but in vivo data showed no inhibitory effect on CYP3A4. Everolimus does not interact with reboxetine metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Repaglinide is metabolized by CYP2C8 and 3A4 and clinical data seem to indicate that it is a substrate of the hepatic transporter OATP1B1. Everolimus does not interact with this metabolic pathway. However, everolimus may induce hyperglycaemia which may require an increase in the dose of repaglinide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vitamin A esters are hydrolysed by pancreatic enzymes to retinol, which is then absorbed and re-esterified. Some retinol is stored in the liver. Retinol not stored in the liver undergoes glucuronide conjugation and subsequent oxidation to retinal and retinoic acid. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Coadministration has not been studied and should be avoided as significant decreases in everolimus plasma concentrations may occur due to induction of CYP3A4 and P-gp. Coadministration is not recommended. If coadministration is unavoidable, monitor closely for everolimus efficacy. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose increase from 10 mg/day to 20 mg/day in 5 mg increments at day 4 and day 8 after starting rifabutin, with careful monitoring of tolerability. Monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, dosing should be titrated to attain trough concentrations of 5-15 µg/L. If concentrations are below 5 µg/L, the daily dose may be increased by increments of 2.5 mg per day every two weeks, checking the trough level and assessing tolerability before increasing the dose. After discontinuation of rifabutin the CYP3A4 inducing effect may persist for over a week (mostly 2 weeks) and the everolimus dose should be decreased accordingly.

Coadministration should be avoided as significant decreases in everolimus plasma concentrations may occur due to induction of CYP3A4 and P-gp. Coadministration of everolimus and rifampicin decreased everolimus AUC by 63% and Cmax by 58%. Coadministration is not recommended. If combination is unavoidable, monitor closely for everolimus efficacy. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose increase from 10 mg/day to 20 mg/day in 5 mg increments at day 4 and day 8 after starting rifampicin, with careful monitoring of tolerability. Monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, dosing should be titrated to attain trough concentrations of 5-15 µg/L. If concentrations are below 5 µg/L, the daily dose may be increased by increments of 2.5 mg per day every two weeks, checking the trough level and assessing tolerability before increasing the dose. After discontinuation of rifampicin the CYP3A4 inducing effect may persist for over a week (mostly 2 weeks) and the everolimus dose should be decreased accordingly.

Coadministration has not been studied and should be avoided as significant decreases in everolimus plasma concentrations may occur due to induction of CYP3A4 and P-gp. Coadministration is not recommended. If coadministration is unavoidable, monitor closely for everolimus efficacy. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose increase from 10 mg/day to 20 mg/day in 5 mg increments at day 4 and day 8 after starting rifapentine, with careful monitoring of tolerability. Monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, dosing should be titrated to attain trough concentrations of 5-15 µg/L. If concentrations are below 5 µg/L, the daily dose may be increased by increments of 2.5 mg per day every two weeks, checking the trough level and assessing tolerability before increasing the dose. After discontinuation of rifapentine the CYP3A4 inducing effect may persist for over a week (mostly 2 weeks) and the everolimus dose should be decreased accordingly.

Coadministration has not been studied. Rifaximin is mainly excreted in faeces, almost entirely as unchanged drug. Rifaximin is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. No effect on everolimus concentrations is expected.

Coadministration has not been studied. Risperidone is metabolized by CYP2D6 and to a lesser extent by CYP3A4. Everolimus does not inhibit or induce CYPs. However, risperidone is a substrate for P-gp and concentrations may potentially increase due to inhibition of P-gp by everolimus.

Coadministration has not been studied. Rivaroxaban is partly metabolized in the liver (by CYP3A4, CYP2J2 and hydrolytic enzymes) and partly eliminated unchanged in urine (by P-gp and BCRP). Increases in rivaroxaban plasma concentrations cannot be excluded via inhibition of P-gp and BCRP. The clinical relevance of this interaction is not known.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Rosiglitazone is metabolized mainly by CYP2C8 and to a lesser extent 2C9. Everolimus does not inhibit or induce CYPs. However, everolimus may induce hyperglycaemia which may require an increase in the dose of rosiglitazone.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as rosuvastatin is largely excreted unchanged via the faeces. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salbutamol is metabolized to the inactive salbutamol-4’-O-sulphate. Everolimus does not interact with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Salmeterol is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied. Saxagliptin is mainly metabolized by CYP3A4 and is a substrate of P-gp. Saxagliptin concentrations may potentially increase due to inhibition of P-gp by everolimus. Additionally, everolimus may induce hyperglycaemia which may require an increase in the dose of saxagliptin. Monitoring for hyperglycaemia recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Senna glycosides are hydrolysed by colonic bacteria in the intestinal tract and the active anthraquinones liberated into the colon. Excretion occurs in the urine and the faeces and also in other secretions. No clinically significant drug interactions are known. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertindole is metabolized by CYP2D6 and CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sertraline is mainly metabolized by CYP2B6 and to a lesser extent by CYPs 2C9, 2C19, 2D6 and 3A4. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sildenafil is metabolized mainly by CYP3A4 and to a lesser extent by CYP2C9. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied and is not recommended. Since everolimus and sirolimus are both mTOR inhibitors, combination therapy is unlikely and would give additional toxicity. Sirolimus is metabolized by CYP3A4 and is substrate of P-gp. Everolimus does not inhibit or induce CYPs, but may increase sirolimus concentrations by inhibition of P-gp. Coadministration is not recommended. If coadministration is unavoidable, close monitoring is recommended. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied. Sitagliptin is primarily eliminated in urine as unchanged drug (active secretion by OAT3, OATP4C1, P-gp) and metabolism by CYP3A4 represents a minor elimination pathway. Sitagliptin concentrations may potentially increase due to inhibition of P-gp by everolimus. Additionally, everolimus may induce hyperglycaemia which may require an increase in the dose of sitagliptin. Monitoring for hyperglycaemia recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sodium nitroprusside is rapidly metabolised, likely by interaction with sulfhydryl groups in the erythrocytes and tissues. Cyanogen (cyanide radical) is produced which is converted to thiocyanate in the liver by the enzyme thiosulfate sulfurtransferase. There is little potential for sodium nitroprusside to affect the disposition of everolimus, or to be affected by everolimus. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sotalol is excreted unchanged via renal elimination.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Spectinomycin is predominantly eliminated unchanged in the kidneys via glomerular filtration. Everolimus does not interact with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Spironolactone is partly metabolized by the flavin containing monooxygenases. Everolimus does not interfere with this metabolic pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Stanozolol undergoes hepatic metabolism. Everolimus does not interact with stanozolol metabolic pathway.

Coadministration has not been studied and should be avoided. St John’s wort is an inducer of P-gp and CYP3A4 and may cause significant and unpredictable decreases in the plasma concentrations of everolimus. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Like other proteins, streptokinase is metabolised proteolytically in the liver and eliminated via the kidneys. Everolimus is unlikely to interfere with this pathway.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Streptomycin is eliminated by glomerular filtration therefore no pharmacokinetic interaction is expected with everolimus. 

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro studies suggest a role of CYP2C9 in sulfadiazine metabolism. Everolimus does not interfere with sulfadiazine metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Sulpiride is mainly excreted in the urine and faeces as unchanged drug. Everolimus is unlikely to significantly impair sulpiride elimination.

Coadministration has not been studied and is not recommended. Since everolimus and tacrolimus are both mTOR inhibitors, combination therapy is unlikely and would give additional toxicity. Everolimus is metabolised mainly by CYP3A4. Tacrolimus inhibits CYP3A4 and OATP1B1 in vitro but produced modest inhibition of CYP3A4 and OATP1B1 in the range of clinical concentrations. Tacrolimus could potentially increase everolimus concentrations although to a modest extent. No a priori dosage adjustment is recommended. Everolimus inhibits P-gp and may possibly increase tacrolimus concentrations. If coadministration is unavoidable, close monitoring is recommended. Due to the risk of additive haematological toxicity, haematological parameters should be monitored if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tadalafil is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tamsulosin is metabolised mainly by CYP3A4 and to a lesser extent by CYP2D6. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tazobactam is excreted as unchanged drug (approximately 80%) and inactive metabolite (approximately 20%) in the urine. Everolimus does not interact with this elimination pathway.

Coadministration has not been studied but may increase everolimus concentrations as telithromycin is a strong inhibitor of CYP3A4. Coadministration is should be approached with caution. If coadministration is unavoidable, monitor closely for everolimus toxicity. For patients with renal cell carcinoma, neuroendocrine tumour, mammacarcinoma or renal angiomyolipoma, consider a dose reduction from 10 mg/day to 5 mg/day and monitor everolimus trough plasma concentration to maintain a minimal trough concentration of ~14 µg/L. For patients with SEGA, consider a dose reduction of approximately 50% and the everolimus trough concentration should be assessed at least 1 week later. Dosing should be titrated to attain trough concentrations of 5-15 µg/L.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Telmisartan is mainly glucuronidated by UGT1A3. Everolimus not inhibit or induce UGTs.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Temazepam is mainly glucuronidated. Everolimus does not inhibit or induce UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Terbinafine is metabolized by CYP1A2, 2C9, 3A4 and to a lesser extent CYP2C8 and 2C19. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Testosterone is metabolized by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tetracycline is eliminated unchanged primarily by glomerular filtration. Everolimus does not interact with this elimination pathway. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Theophylline is mainly metabolized by CYP1A2. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thioridazine is metabolized by CYP2D6 and to a lesser extent by CYP3A4. Everolimus does not inhibit or induce CYPs. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as tiapride is excreted largely unchanged in urine. Everolimus is unlikely to significantly impair tiapride elimination.

Coadministration has not been studied. Ticagrelor undergoes extensive CYP3A4 metabolism and is a mild inhibitor of CYP3A4. Everolimus concentrations may be slightly increased if coadministered with ticagrelor. Ticagrelor is a substrate of P-gp and concentrations may increase due to inhibition of P-gp by everolimus. The clinical relevance of this interaction is unknown. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Timolol is predominantly metabolised in the liver by CYP2D6. Everolimus does not inhibit or induce CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tinzaparin is renally excreted as unchanged or almost unchanged drug. Everolimus does not interact with this elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolbutamide is mainly metabolized by CYP2C9 and to a lesser extent by CYPs 2C8 and 2C19. Everolimus does not interact with this metabolic pathway. However, everolimus may induce hyperglycaemia which may require an increase in the dose of tolbutamide.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Tolterodine is primarily metabolised by CYP2D6 with CYP3A4. Everolimus does not inhibit or induce CYPs.