Pharmorubicin CS Use In Pregnancy & Lactation

Effects on fertility: Studies in animals have shown reproductive toxicity. In fertility studies in rats, males were given epirubicin daily for 9 weeks and mated with females that were given epirubicin daily for 2 weeks prior to mating and through Day 7 of gestation. When 0.3 mg/kg/day (0.01-times the maximum recommended clinical dose based on body surface area, BSA) was administered to both sexes, no pregnancies resulted. No effects on mating behaviour or fertility were observed at 0.1 mg/kg/day, but male rats had atrophy of the testes and epididymis and reduced spermatogenesis. Multiple daily doses of epirubicin to rabbits and dogs also caused atrophy of male reproductive organs. Single intravenous doses of epirubicin 20.5 and 12 mg/kg caused testicular atrophy in mice and rats, respectively. A single dose of 16.7 mg/kg epirubicin caused uterine atrophy in rats.
In women, PHARMORUBICIN may cause amenorrhoea. After termination of therapy, ovulation and menstruation may be expected to return in a few months, often accompanied by normal fertility. Premature menopause may also occur.
In male patients, oligospermia or azoospermia may be permanent, although fertility may return several years after ceasing therapy. Given the mutagenic potential of PHARMORUBICIN, the drug could induce chromosomal damage in human spermatozoa; therefore, males undergoing PHARMORUBICIN treatment should be advised to use effective contraceptive methods during treatment and for at least 3.5 months after the last dose.
Based on animal studies, male and female fertility may be compromised. It is recommended to discuss fertility preservation with men and women prior to treatment.
Use in pregnancy - Category D: Women of childbearing potential should be advised to avoid becoming pregnant during treatment and to use effective contraceptive methods during treatment and for at least 6.5 months after last dose.
There is no specific information available at present concerning the use of PHARMORUBICIN in human pregnancy. However, as it has been shown to be embryotoxic and fetotoxic in animals, it should not be used in patients who are pregnant or are likely to become pregnant. Administration of 0.8 mg/kg/day intravenously (0.04-times the maximum recommended clinical dose based on body surface area) of epirubicin to rats during days 5 to 15 of gestation was embryotoxic (increased resorptions and post-implantation loss) and caused fetal growth retardation (decreased body weight), but was not teratogenic up to this dose. Administration of 2 mg/kg/day intravenously (0.08-times the maximum recommended clinical dose based on body surface area) of epirubicin to rats on days 9 and 10 of gestation was embryotoxic (increased late resorptions, post-implantation losses, and dead fetuses; and decreased live fetuses), retarded fetal growth (decreased body weight), and caused decreased placental weight. This dose was also teratogenic, causing numerous external (anal atresia, misshapen tail, abnormal genital tubercle), visceral (primarily gastrointestinal, urinary, and cardiovascular systems), and skeletal (deformed long bones and girdles, rib abnormalities, irregular spinal ossification) malformations. Administration of intravenous epirubicin to rabbits at doses up to 0.2 mg/kg/day (0.02-times the maximum recommended clinical dose based on body surface area) during days 6 to 18 of gestation was not embryotoxic or teratogenic, but a maternally toxic dose of 0.32 mg/kg/day increased abortions and delayed ossification. Administration of a maternally toxic intravenous dose of 1 mg/kg/day epirubicin (0.08-times the maximum recommended clinical dose based on body surface area) to rabbits on days 10 to 12 of gestation-induced abortion, but no other signs of embryofetal toxicity or teratogenicity were observed. When doses up to 0.5 mg/kg/day epirubicin (0.02-times the maximum recommended clinical dose based on body surface area) were administered to rat dams from Day 17 of gestation to Day 21 after delivery, no permanent changes were observed in the development, functional activity, behaviour, or reproductive performance of the offspring.
If epirubicin is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. There have been sporadic reports of fetal and/or neonatal transient ventricular hypokinesia, transient elevation of cardiac enzymes, and of fetal death from suspected anthracycline-induced cardiotoxicity following in utero exposure to epirubicin in 2^nd and/or 3^rd trimesters (see Precautions). Monitor the fetus and/or neonate for cardiotoxicity and perform testing consistent with community standards of care.
Use in lactation: In a peri- and post-natal study, epirubicin was present in milk of rats treated with 0.5 mg/kg/day epirubicin (0.02-times the maximum recommended clinical dose based on body surface area). It is likely that PHARMORUBICIN is excreted in breast milk, therefore, it is not recommended for nursing mothers unless the expected benefit outweighs any potential risk. Because of the potential for serious adverse reactions in nursing infants from epirubicin, lactating women should be advised not to breastfeed during treatment with epirubicin and for at least 7 days after last dose.