Pitavastatin is actively transported into human hepatocytes by multiple hepatic transporters (including organic anion transporting polypeptide, OATP), which may be involved in some of the following interactions.
Ciclosporin: Co-administration of a single dose of ciclosporin with LIVALO at steady state resulted in a 4.6-fold increase in pitavastatin AUC. The effect of steady state ciclosporin on steady state LIVALO is not known. LIVALO is contraindicated in patients being treated with ciclosporin (see Contraindications).
Erythromycin: Co-administration with LIVALO resulted in a 2.8-fold increase in pitavastatin AUC. A temporary suspension of LIVALO is recommended for the duration of treatment with erythromycin or other macrolide antibiotics.
Gemfibrozil and other fibrates: The use of fibrates alone is occasionally associated with myopathy. Co-administration of fibrates with statins may cause severe myositis and myoglobinuria, and has been associated with increased myopathy and rhabdomyolysis. LIVALO should be administered with caution when used concomitantly with fibrates (see Precautions). In Pharmacokinetic studies, co-administration of LIVALO with Gemfibrozil resulted in a 1.4-fold increase in pitavastatin AUC; with Fenofibrate, AUC increased 1.2-fold.
Niacin: Interaction studies with LIVALO and niacin have not been conducted. The use of niacin alone has been associated with myopathy and rhabdomyolysis when used as a monotherapy. Thus LIVALO should be administered with caution when used concomitantly with niacin.
Fusidic acid: The risk of myopathy including rhabdomyolysis may be increased by the concomitant administration of systemic fusidic acid with statins. The mechanism of this interaction (whether it is pharmacodynamic or pharmacokinetic, or both) is yet unknown. There have been reports of rhabdomyolysis (including some fatalities) in patients receiving this combination. If treatment with systemic fusidic acid is necessary, LIVALO treatment should be discontinued throughout the duration of the fusidic acid treatment (see Precautions).
Rifampicin: Co-administration with LIVALO at the same time resulted in a 1.3-fold increase in pitavastatin AUC due to reduced hepatic uptake.
Protease inhibitors and Non-nucleoside reverse transcriptase inhibitors: Co-administration of lopinavir/ritonavir, darunavir/ritonavir, atazanavir, or efavirenz with LIVALO at the same time may result in minor changes in pitavastatin AUC.
Ezetimibe and its glucuronide metabolite inhibit the absorption of dietary and biliary cholesterol. Co-administration of LIVALO had no effect on plasma ezetimibe or the glucuronide metabolite concentrations and ezetimibe had no impact on pitavastatin plasma concentrations.
Inhibitors of CYP3A4: Interaction studies with itraconazole and grapefruit juice, known inhibitors of CYP3A4, had no clinically significant effect on the plasma concentrations of pitavastatin.
Digoxin, a known P-gp substrate, did not interact with LIVALO. During co-administration there was no significant change in either pitavastatin or digoxin concentrations.
Warfarin: The steady-state pharmacokinetics and pharmacodynamics (INR and PT) of warfarin in healthy volunteers was unaffected by the co-administration of LIVALO 4mg daily. However, as for other statins, patients receiving warfarin should have their prothrombin time or INR monitored when LIVALO is added to their therapy.
Use in Children: Drug-drug interaction studies have only been performed in adults. The extent of interactions in the paediatric population is not known