Tacrolimus (topical)

Drug Interactions Formal topical drug interaction studies with Tacrolimus Ointment have not been conducted. Based on its extent of absorption, interactions of Tacrolimus Ointment with systemically administered drugs are unlikely to occur but cannot be ruled out (see CLINICAL PHARMACOLOGY ). The concomitant administration of known CYP3A4 inhibitors in patients with widespread and/or erythrodermic disease should be done with caution. Some examples of such drugs are erythromycin, itraconazole, ketoconazole, fluconazole, calcium channel blockers and cimetidine.

Pregnancy Teratogenic Effects: There are no adequate and well-controlled studies of topically administered tacrolimus in pregnant women. The experience with Tacrolimus Ointment when used by pregnant women is too limited to permit assessment of the safety of its use during pregnancy. Reproduction studies were carried out with systemically administered tacrolimus in rats and rabbits. Adverse effects on the fetus were observed mainly at oral dose levels that were toxic to dams. Tacrolimus at oral doses of 0.32 and 1.0 mg/kg (0.04×-0.12× MRHD based on BSA) during organogenesis in rabbits was associated with maternal toxicity as well as an increase in incidence of abortions.

At the higher dose only, an increased incidence of malformations and developmental variations was also seen. Tacrolimus, at oral doses of 3.2 mg/kg during organogenesis in rats, was associated with maternal toxicity and caused an increase in late resorptions, decreased numbers of live births, and decreased pup weight and viability. Tacrolimus, given orally at 1.0 and 3.2 mg/kg (0.04×-0.12× MRHD based on BSA) to pregnant rats after organogenesis and during lactation, was associated with reduced pup weights. No reduction in male or female fertility was evident. There are no adequate and well-controlled studies of systemically administered tacrolimus in pregnant women.

Tacrolimus is transferred across the placenta. The use of systemically administered tacrolimus during pregnancy has been associated with neonatal hyperkalemia and renal dysfunction. Tacrolimus Ointment should be used during pregnancy only if the potential benefit to the mother justifies a potential risk to the fetus.

Nursing Mothers Although systemic absorption of tacrolimus following topical applications of Tacrolimus Ointment is minimal relative to systemic administration, it is known that tacrolimus is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from tacrolimus, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.