Impavido Pregnancy Warnings
Animal studies have revealed evidence of embryofetal toxicity, including death and fetal malformations. In pregnant rats and pregnant rabbits, this drug was administered in oral doses of 0.6 to 24 mg/kg/day during organogenesis; in rats, at dosages at least 1.2 mg/kg/day (0.06 times the maximum recommended human dose [MRHD] based on body surface area [BSA] comparison), embryofetal toxicity including death and fetal malformations (including undeveloped cerebrum hemorrhagic fluid filling lumina of the skull, cleft palate, generalized edema) were observed, while in rabbits, abortion and fetal resorption occurred with 1 dam given 2.4 mg/kg/day (0.2 times the MRHD based on BSA comparison) and fetal resorptions were seen with all dams given at least 6 mg/kg/day. In rats and rabbits, no viable litters were observed at doses at least 6 mg/kg/day (0.3 and 0.6 times the MRHD based on BSA comparisons, respectively). In female rats, this drug was administered orally for 4 weeks before mating and up to day 7 of pregnancy; numerous visceral (misshapen cerebral structures, dilated ventricles filled with brown masses, misshapen spinal cord, misshapen and malpositioned eyes, hypophysis, absent inner ear) and skeletal (cleft palate, dumbbell-shaped ossification of thoracic vertebral centers, markedly enlarged skull bones, markedly dilated suturae) fetal malformations were observed at doses at least 6.81 mg/kg/day (0.3 times the MRHD based on BSA comparison). There are no controlled data in human pregnancy.
Based on animal fertility studies (and postmarketing studies in males), this drug may impair fertility in females and males of reproductive potential. The effects of this drug on human female fertility have not been formally studied; it is unknown if this drug affects male fertility.
In an uncontrolled study assessing effects of this drug on sperm parameters, 58 adult males with cutaneous or mucosal leishmaniasis were administered this drug for 28 days (target dose: 2.5 mg/kg/day) and underwent semen analysis testing before therapy, at the end of therapy, at 3 months after the last dose, and if needed, at 6 months after the last dose. This drug was associated with reductions in all sperm parameters at the end of therapy. On follow-up assessments at 3 and 6 months after the last dose, all sperm parameters (except sperm concentration) had recovered; for sperm concentration, small mean decreases persisted, with about 26% of patients showing posttherapy sperm level reductions of at least 50% and reductions to the lower limit of normal (less than 20 million/mL) persisting in up to 8% of patients on their last observed assessment. Semen analyses were not conducted beyond 6 months in any patient; the duration of effect of this drug on sperm concentration after therapy is unknown. No clinically relevant changes in serum testosterone or follicle-stimulating hormone levels were observed. The effect of this drug on spermatogenesis may persist for an unknown duration.
In an observational study of male patients given this drug, reductions in ejaculate volume and temporary absence of ejaculate were reported; these side effects resolved in all patients when therapy was completed.
US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.
Use is contraindicated.
US FDA pregnancy category: Not assigned.
Risk summary: Based on animal data, this drug may cause embryofetal toxicity when administered to pregnant patients; no data available on use of this drug in pregnant women to inform a drug-related risk.
Comments:
-A pregnancy exposure registry is available.
-If the patient becomes pregnant while taking this drug, the drug should be discontinued and the patient should be apprised of the potential harm to the fetus.
-Pregnancy status should be verified before starting this drug in patients of childbearing potential.
-Patients of childbearing potential should be advised to use effective contraception during therapy and for 5 months after the last dose; if vomiting and/or diarrhea occur during therapy (which may affect absorption of oral contraceptives and thus weaken their efficacy), patients should be advised to use an additional non-oral method of effective contraception.
See references
