Samsca Drug Interactions

Effects of drugs on SAMSCA: Ketoconazole and Other Strong CYP3A Inhibitors: SAMSCA is metabolized primarily by CYP 3A. Ketoconazole is a strong inhibitor of CYP 3A and also an inhibitor of P-gp. Co-administration of SAMSCA and ketoconazole 200 mg daily results in a 5-fold increase in exposure to SAMSCA. Co-administration of SAMSCA with 400 mg ketoconazole daily or with other strong CYP 3A inhibitors (e.g., clarithromycin, itraconazole, telithromycin, saquinavir, nelfinavir, ritonavir and nefazodone) at the highest labeled dose would be expected to cause an even greater increase in SAMSCA exposure. Thus, SAMSCA and strong CYP 3A inhibitors should not be co-administered [see Co-Administration with CYP 3A Inhibitors, CYP 3A Inducers and P-gp Inhibitors under Dosage & Administration and Concomitant use of strong CYP3A inhibitors under Contraindications].
Moderate CYP3A Inhibitors: The impact of moderate CYP 3A inhibitors (e.g., erythromycin, fluconazole, aprepitant, diltiazem and verapamil) on the exposure to co-administered SAMSCA has not been assessed. A substantial increase in the exposure to SAMSCA would be expected when SAMSCA is co-administered with moderate CYP 3A inhibitors. Co-administration of moderate CYP3A inhibitors with SAMSCA should generally be avoided [see Co-Administration with CYP 3A Inhibitors, CYP 3A Inducers and P-gp Inhibitors under Dosage & Administration and Drug Interactions under Precautions].
Grapefruit Juice: Co-administration of grapefruit juice and SAMSCA results in a 1.9-fold increase in exposure to SAMSCA. Patients taking SAMSCA should avoid ingesting grapefruit juice [see Co-Administration with CYP 3A Inhibitors, CYP 3A Inducers and P-gp Inhibitors under Dosage & Administration and Drug Interactions under Precautions].
P-gp Inhibitors: Reduction in the dose of SAMSCA may be required in patients concomitantly treated with P-gp inhibitors, such as e.g., cyclosporine, based on clinical response [see Co-Administration with CYP 3A Inhibitors, CYP 3A Inducers and P-gp Inhibitors under Dosage & Administration and Drug Interactions under Precautions].
Rifampin and Other CYP 3A Inducers: Rifampin is an inducer of CYP 3A and P-gp. Co-administration of rifampin and SAMSCA reduces exposure to SAMSCA by 85%. Therefore, the expected clinical effects of SAMSCA in the presence of rifampin and other inducers (e.g., rifabutin, rifapentin, barbiturates, phenytoin, carbamazepine and St. John's Wort) may not be observed at the usual dose levels of SAMSCA. The dose of SAMSCA may have to be increased [see Co-Administration with CYP 3A Inhibitors, CYP 3A Inducers and P-gp Inhibitors under Dosage & Administration and Drug Interactions under Precautions].
Lovastatin, Digoxin, Furosemide, and Hydrochlorothiazide: Co-administration of lovastatin, digoxin, furosemide, and hydrochlorothiazide with SAMSCA has no clinically relevant impact on the exposure to SAMSCA.
Effects of SAMSCA on Other Drugs: Digoxin: Digoxin is a P-gp substrate and SAMSCA is a P-gp inhibitor. Co-administration of SAMSCA with digoxin increased digoxin AUC by 20% and Cmax by 30%.
Warfarin, Amiodarone, Furosemide, and Hydrochlorothiazide: Co-administration of SAMSCA does not appear to alter the pharmacokinetics of warfarin, furosemide, hydrochlorothiazide, or amiodarone (or its active metabolite, desethylamiodarone) to a clinically significant degree.
Lovastatin: SAMSCA is a weak inhibitor of CYP 3A. Co-administration of lovastatin and SAMSCA increases the exposure to lovastatin and its active metabolite lovastatin-β hydroxy acid by factors of 1.4 and 1.3, respectively. This is not a clinically relevant change.
Pharmacodynamic Interactions: SAMSCA produces a greater 24 hour urine volume and 24 hour excretion rate than does furosemide or hydrochlorothiazide. Concomitant administration of SAMSCA with furosemide or hydrochlorothiazide results in a 24 hour urine volume and 24 hour excretion rate that is similar to the rate after SAMSCA administration alone.
Although specific interaction studies were not performed, in clinical studies SAMSCA was used concomitantly with beta-blockers, angiotensin receptor blockers, angiotensin converting enzyme inhibitors and potassium sparing diuretics. Adverse reactions of hyperkalemia were approximately 1-2% higher when SAMSCA was administered with angiotensin receptor blockers, angiotensin converting enzyme inhibitors and potassium sparing diuretics compared to administration of these medications with placebo. Serum potassium levels should be monitored during concomitant drug therapy.
As a V2 receptor antagonist, SAMSCA may interfere with the V2 agonist activity of desmopressin (dDAVP). In a male subject with mild Von Willebrand (vW) disease, intravenous infusion of dDAVP 2 hours after administration of oral SAMSCA did not produce the expected increases in vW Factor Antigen or Factor VIII activity. It is not recommended to administer SAMSCA with a V2 agonist.