Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amiodarone is metabolised by CYP3A4 and CYP2C8. Lenalidomide does not inhibit or induce CYPs. Furthermore, the major metabolite of amiodarone, desethylamiodarone, is an inhibitor of CYPs 3A4 (weak), 2C9 (moderate), 2D6 (moderate), 2C19 (weak), 1A1 (strong) and 2B6 (moderate) and P-gp (strong). Lenalidomide is not metabolised by CYPs. Lenalidomide is an in vitro P-gp substrate. Coadministration of 600 mg twice daily quinidine, a strong P-gp inhibitor, did not have a clinically relevant effect on the exposure of lenalidomide. Therefore, no clinically significant effect on lenalidomide exposure is expected after coadministration with amoidarone.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Amphotericin B is not appreciably metabolised but is eliminated to a large extent in the bile. Lenalidomide does not interfere with this metabolic or 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, and so monitoring may be required.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Azathioprine is converted to 6-mercaptopurine which is metabolised analogously to natural purines. Lenalidomide does not interact with this metabolic pathway. 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. Calcium is eliminated through faeces, urine and sweat. Lenalidomide is unlikely to interfere with these elimination pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and additional metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. Lenalidomide does not inhibit or induce CYPs or UGTs.

Based on metabolism and clearance a clinically significant interaction is unlikely. Clarithromycin is metabolised by CYP3A4. Lenalidomide does not inhibit or induce CYPs. Furthermore, clarithromycin is an inhibitor of CYP3A4 (strong) and P-gp. Lenalidomide is a P-gp substrate in vitro but a clinically relevant interaction is not expected. Coadministration of lenalidomide and clarithromycin showed no effect on the AUC of lenalidomide.

Based on metabolism and clearance a clinically significant interaction is unlikely. Dexamethasone is a substrate of CYP3A4. Lenalidomide does not inhibit or induce CYPs. Dexamethasone has also been described as a weak inducer of CYP3A4. However, the clinical relevance of CYP3A4 induction by dexamethasone is unknown as the mechanism has yet to be established. Lenalidomide is not metabolised by CYPs. Furthermore, coadministration of lenalidomide and dexamethasone resulted in no clinically relevant effect on lenalidomide exposure.

Based on metabolism and clearance a clinically significant interaction is unlikely. Digoxin is renally eliminated via OATP4C1 and P-gp. Lenalidomide does not inhibit or induce P-gp or OATP4C1. Coadministration of lenalidomide and digoxin showed no clinically relevant effect on the exposure of digoxin. Digoxin Cmax increased by 14% and there was no clinically relevant increase in digoxin AUC.

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 the disposition of lenalidomide or to be affected if coadministered with lenalidomide.

Coadministration has not been studied but is contraindicated. Ethinylestradiol undergoes oxidation (CYP3A4>CYP2C9), sulfation and glucuronidation (UGT1A1). Lenalidomide does not inhibit or induce CYPs or UGTs. However, coadministration of combined contraception is contraindicated with lenalidomide. Lenalidomide is unlikely to have a clinically releavnt effect on the pharmacokinetics of combined oral contraceptives, but the effect of oral contraceptives can be reduced by the registered comedication dexamethasone. Furthermore, an increased risk of venous thromboembolism was observed in patients taking lenalidomide in combination therapy. Therefore, a switch to another effective contraception method is recommended. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The following can be considered examples of suitable methods of contraception: medroxyprogesterone acetate depot; tubal sterilization; sexual intercourse with a vasectomised male partner only (vasectomy must be confirmed by two negative semen analyses); ovulation inhibitory progesterone-only pills (i.e. desogestrel); implant (please note: risk of infection); levonorgestrel-releasing intrauterine system (please note: risk of infection).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosaprepitant is rapidly, almost completely, converted to the active metabolite aprepitant. Aprepitant is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2C19. Lenalidomide does not inhibit or induce CYPs. Furthermore, during treatment aprepitant is a moderate inhibitor of CYP3A4 but after treatment aprepitant is a weak inducer of CYP3A4, CYP2C9 and UGT. Lenalidomide is not metabolised by CYPs or UGTs.

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 renally eliminated unchanged (via OATs). In vitro data indicate that furosemide is an inhibitor of the renal transporters OAT1/OAT3. Lenalidomide does not interact with this pathway.

Coadministration has not been studied but is contraindicated. Gestodene is metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Lenalidomide does not inhibit or induce CYPs. However, coadministration of combined contraception is contraindicated with lenalidomide. Lenalidomide is unlikely to have a clinically relevant effect on the pharmacokinetics of combined oral contraceptives, but the effect of oral contraceptives can be reduced by the registered comedication dexamethasone. Furthermore, an increased risk of venous thromboembolism was observed in patients taking lenalidomide in combination therapy. Therefore, a switch to another effective contraception method is recommended. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The following can be considered examples of suitable methods of contraception: medroxyprogesterone acetate depot; tubal sterilization; sexual intercourse with a vasectomised male partner only (vasectomy must be confirmed by two negative semen analyses); ovulation inhibitory progesterone-only pills (i.e. desogestrel); implant (please note: risk of infection); levonorgestrel-releasing intrauterine system (please note: risk of infection).

Coadministration has not been studied but care should be taken. Heparin is thought to be eliminated via the reticuloendothelial system. Lenalidomide does not interact with this metabolic pathway. Heparin may be indicated to treat thrombosis due to the increased risk from lenalidomide administration. However, the use of heparin with lenalidomide may increase the risk of bleeding. Therefore, care should be taken. Advise patients to observe for signs and symptoms of bleeding (e.g. petechiae, epistaxes) or bruising if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Indapamide is extensively metabolised by CYPs. Furthermore, OAT1/3 are the major transporters of loop and thiazide diuretics. Secretion of these diuretics into the urinary tract by transporters in the proximal tubular cells is necessary for the diuretic effect in later tubule segments. Lenalidomide does not inhibit or induce CYPs or OATs.

Coadministration has not been studied but is contraindicated. Levonorgestrel mainly is metabolised by CYP3A4 and is glucuronidated to a minor extent. Lenalidomide does not inhibit or induce CYPs or UGTs. However, coadministration of combined contraception is contraindicatedwith lenalidomide. Lenalidomide is unlikely to have a clinically relevant effect on the pharmacokinetics of combined oral contraceptives, but the effect of oral contraceptives can be reduced by the registered comedication dexamethasone. Furthermore, an increased risk of venous thromboembolism was observed in patients taking lenalidomide in combination therapy. Therefore, a switch to another effective contraception method is recommended. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The following can be considered examples of suitable methods of contraception: medroxyprogesterone acetate depot; tubal sterilization; sexual intercourse with a vasectomised male partner only (vasectomy must be confirmed by two negative semen analyses); ovulation inhibitory progesterone-only pills (i.e. desogestrel); implant (please note: risk of infection); levonorgestrel-releasing intrauterine system (please note: risk of infection).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Mometasone is metabolised by CYP3A4. Lenalidomide does not inhibit or induce CYPs. Note: No clinically relevant interactions are expected with the topical use of mometasone.

Coadministration has not been studied but care should be taken. Nadroparin is renally excreted by a nonsaturable mechanism. Lenalidomide does not interact with this elimination pathway. Nadroparin may be indicated to treat thrombosis due to the increased risk from lenalidomide administration. However, the use of nadroparin with lenalidomide may increase the risk of bleeding. Therefore, care should be taken. Advise patients to observe for signs and symptoms of bleeding (e.g. petechiae, epistaxes) or bruising if coadministered.

Coadministration has not been studied but is contraindicated. Norelgestromin is metabolised to norgestrel (possibly by CYP3A4). Lenalidomide does not inhibit or induce CYPs. However, due to the increased risk of thrombosis, coadministration with norelgestromin should be approached with caution. If coadministration is clinically necessary, monitor closely for signs of thrombosis. Furthermore, coadministration of combined contraception is contraindicated with lenalidomide. Lenalidomide is unlikely to have a clinically relevant effect on the pharmacokinetics of combined oral contraceptives, but the effect of oral contraceptives can be reduced by the registered comedication dexamethasone. Additionally, an increased risk of venous thromboembolism was observed in patients taking lenalidomide in combination therapy. Therefore, a switch to another effective contraception method is recommended. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The following can be considered examples of suitable methods of contraception: medroxyprogesterone acetate depot; tubal sterilization; sexual intercourse with a vasectomised male partner only (vasectomy must be confirmed by two negative semen analyses); ovulation inhibitory progesterone-only pills (i.e. desogestrel); implant (please note: risk of infection); levonorgestrel-releasing intrauterine system (please note: risk of infection).

Coadministration has not been studied but is contraindicated. Norethisterone is extensively biotransformed, first by reduction and then by sulfate and glucuronide conjugation. Lenalidomide does not inhibit or induce UGTs. However, coadministration of combined contraception is contraindicated with lenalidomide. Lenalidomide is unlikely to have a clinically relevant effect on the pharmacokinetics of combined oral contraceptives, but the effect of oral contraceptives can be reduced by the registered comedication dexamethasone. Furthermore, an increased risk of venous thromboembolism was observed in patients taking lenalidomide in combination therapy. Therefore, a switch to another effective contraception method is recommended. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The following can be considered examples of suitable methods of contraception: medroxyprogesterone acetate depot; tubal sterilization; sexual intercourse with a vasectomised male partner only (vasectomy must be confirmed by two negative semen analyses); ovulation inhibitory progesterone-only pills (i.e. desogestrel); implant (please note: risk of infection); levonorgestrel-releasing intrauterine system (please note: risk of infection).

Coadministration has not been studied but is contraindicated. Norgestimate is rapidly deacetylated to the active metabolite which is further metabolised via CYP450. Lenalidomide does not inhibit or induce CYPs. However, coadministration of combined contraception is contraindicated with lenalidomide. Lenalidomide is unlikely to have a clinically relevant effect on the pharmacokinetics of combined oral contraceptives, but the effect of oral contraceptives can be reduced by the registered comedication dexamethasone. Furthermore, an increased risk of venous thromboembolism was observed in patients taking lenalidomide in combination therapy. Therefore, a switch to another effective contraception method is recommended. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The following can be considered examples of suitable methods of contraception: medroxyprogesterone acetate depot; tubal sterilization; sexual intercourse with a vasectomised male partner only (vasectomy must be confirmed by two negative semen analyses); ovulation inhibitory progesterone-only pills (i.e. desogestrel); implant (please note: risk of infection); levonorgestrel-releasing intrauterine system (please note: risk of infection).

Coadministration has not been studied but is contraindicated. Norgestrel is a racemic mixture with levonorgestrel being biologically active. Levonorgestrel is mainly metabolized by CYP3A4 and is glucuronidated to a minor extent. Lenalidomide does not inhibit or induce CYPs or UGTs. However, coadministration of combined contraception is contraindicated with lenalidomide. Lenalidomide is unlikely to have a clinically relevant effect on the pharmacokinetics of combined oral contraceptives, but the effect of oral contraceptives can be reduced by the registered comedication dexamethasone. Furthermore, an increased risk of venous thromboembolism was observed in patients taking lenalidomide in combination therapy. Therefore, a switch to another effective contraception method is recommended. The risk of venous thromboembolism continues for 4-6 weeks after discontinuing combined oral contraception. The following can be considered examples of suitable methods of contraception: medroxyprogesterone acetate depot; tubal sterilization; sexual intercourse with a vasectomised male partner only (vasectomy must be confirmed by two negative semen analyses); ovulation inhibitory progesterone-only pills (i.e. desogestrel); implant (please note: risk of infection); levonorgestrel-releasing intrauterine system (please note: risk of infection).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Omeprazole is mainly metabolised by CYP2C19 and to a lesser extent by CYP3A4. Lenalidomide does not inhibit or induce CYPs. Omeprazole is also an inducer of CYP1A2 and an inhibitor of CYP2C19. Lenalidomide is not metabolised by CYPs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Oxcarbazepine is extensively metabolised to the active metabolite monohydroxyderivate (MHD) through cystolic enzymes. Both oxcarbazepine and MHD are inducers of CYP3A4 (moderate) and CYP3A5, and are inhibitors of CYP2C19. Lenalidomide does not interact with this pathway. Furthermore, coadministration of lenalidomide with EIAEDs showed no clinically relevant effect on the AUC0-inf when compared to non-EIAEDs.

Coadministration has not been studied but care should be taken. Prasugrel is a prodrug and is converted to its active metabolite mainly by CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19. Lenalidomide does not inhibit or induce CYPs. However, the use of prasugrel with lenalidomide may increase the risk of bleeding. Therefore, care should be taken. Advise patients to observe for signs and symptoms of bleeding (e.g. petechiae, epistaxes) or bruising if coadministered.

Based on metabolism and clearance a clinically significant interaction is unlikely. Quinidine is mainly metabolised by CYP3A4 and to a lesser extent by CYP2C9 and CYP2E1. Quinidine is a substrate of P-gp. Lenalidomide does not inhibit or induce CYPs or P-gp. Quinidine is also an inhibitor of CYP2D6 (strong), CYP3A4 (weak) and P-gp (moderate). Lenalidomide is a P-gp substrate in vitro. Coadministration of lenalidomide and quinidine (multiple doses of 600 mg twice daily) did not have a clinically relevant effect on the exposure of lenalidomide.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Sirolimus is metabolised by CYP3A4 and is a substrate of P-gp. Lenalidomide does not inhibit or induce CYPs or P-gp. 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. Terbinafine is metabolised by CYPs 1A2, 2C9, 3A4 and to a lesser extent by CYP2C8 and CYP2C19. Lenalidomide does not inhibit or induce CYPs.

Coadministration has not been studied but care should be taken. Tinzaparin is renally excreted as unchanged or almost unchanged drug. Lenalidomide is unlikely to interfere with this elimination pathway. Tinzaparin may be indicated to treat thrombosis due to the increased risk from lenalidomide administration. However, the use of tinzaparin with lenalidomide may increase the risk of bleeding. Therefore, care should be taken. Advise patients to observe for signs and symptoms of bleeding (e.g. petechiae, epistaxes) or bruising if coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Trimethoprim is primarily eliminated by the kidneys through glomerular filtration and tubular secretion. To a lesser extent (approximately 30%) trimethoprim is metabolised by CYP-enzymes (in vitro data suggest CYPs3A4, 1A2 and 2C9). Trimethoprim is also a weak CYP2C8 inhibitor and in vitro data also suggest that trimethoprim is an inhibitor of OCT2 and MATE1. Sulfamethoxazole is metabolised via and is a weak inhibitor of CYP2C9. Lenalidomide does not interact with these pathways.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ulipristal is mainly metabolised by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6. Lenalidomide does not inhibit or induce CYPs. However, due to the increased risk of thrombosis, coadministration with ulipristal should be approached with caution. If coadministration is clinically necessary, monitor closely for signs of thrombosis.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Vildagliptin is inactivated via non-CYP mediated hydrolysis and is a substrate of P-gp. Lenalidomide is unlikely to interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Zaleplon is mainly metabolised by aldehyde oxidase and to a lesser extent by CYP3A4. Lenalidomide does not interact with this metabolic pathway.