/day also resulted in increased incidence of fetal gross external (domed head, malformed eyeballs or eyeholes), soft tissue (hydrocephalus internus, ventricular septal defects, major vessel malformations), and skeletal (dysplastic forelimb bones, malformed ribs and vertebrae, and pelvis shift) abnormalities. The dose of 0.75 mg/kg/day (4.5 mg/m2 body surface area) in rats is approximately 12% of the recommended dose for patients.
Following administration of radiolabeled copanlisib to pregnant rats approximately 1.5% of the radioactivity (copanlisib and metabolites) reached the fetal compartment.
8.2 Lactation
Risk Summary
There are no data on the presence of copanlisib and/or metabolites in human milk, the effects on the breastfed child, or on milk production. Following administration of radiolabeled copanlisib to lactating rats, approximately 2% of the radioactivity was secreted into milk; the milk to plasma ratio of radioactivity was 25-fold. Because of the potential for serious adverse reactions in a breastfed child from copanlisib, advise a lactating woman not to breastfeed during treatment with ALIQOPA and for at least 1 month after the last dose.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
ALIQOPA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Conduct pregnancy testing prior to initiation of ALIQOPA treatment.
Contraception
Females
Advise female patients of reproductive potential to use highly effective contraception (contraception with a failure rate <1% per year) during treatment with ALIQOPA and for at least one month after the last dose.
Males
Advise male patients with female partners of reproductive potential to use highly effective contraception during treatment with ALIQOPA and for at least one month after the last dose.
Infertility
There are no data on the effect of ALIQOPA on human fertility. Due to the mechanism of action of copanlisib, and findings in animal studies, adverse effects on reproduction, including fertility, are expected [see Nonclinical Toxicology (13.1)].
8.4 Pediatric Use
Safety and effectiveness have not been established in pediatric patients.
8.5 Geriatric Use
No dose adjustment is necessary in patients ≥65 years of age. Of 168 patients with follicular lymphoma and other hematologic malignancies treated with ALIQOPA, 48% were age 65 or older while 16% were age 75 or older. No clinically relevant differences in efficacy were observed between elderly and younger patients. In patients ≥65 years of age, 30% experienced serious adverse reactions and 21% experienced adverse reactions leading to discontinuation. In the patients <65 years of age, 23% experienced serious adverse reactions and 11% experienced adverse reactions leading to discontinuation.
11 DESCRIPTION
ALIQOPA (copanlisib) is a kinase inhibitor for intravenous infusion. The active pharmaceutical ingredient is copanlisib dihydrochloride which exists as a non-stoichiometric hydrate and has the molecular formula of C23H28N8O4 2HCl and a mol
