Mytesi

8.1        Pregnancy

Risk Summary

Crofelemer is minimally absorbed systemically by the oral route of administration and maternal use is not expected to result in fetal exposure to the drug [see Clinical Pharmacology ].

In pregnant rats, no adverse fetal effects were observed with oral administration of crofelemer at doses up to 177 times the recommended clinical dose during the period of organogenesis. In pregnant rabbits, an increase in fetal resorptions and abortions compared to controls were observed with crofelemer at a dose of 96 times the recommended clinical dose. However, it is not clear whether these effects in rabbits are related to the maternal toxicity (decreased body weight and decreased food consumption) observed at this dose (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

Crofelemer was not teratogenic and did not produce embryofetal toxicity in pregnant rats following oral administration at doses up to 738 mg/kg/day during the period of organogenesis. The 738 mg/kg/day dose is 177 times the recommended daily human dose of 4.2 mg/kg/day.

Crofelemer was not teratogenic in pregnant rabbits following oral administration at doses up to 400 mg/kg/day during the period of organogenesis. At a dose level of 400 mg/kg/day, which is 96 times the recommended daily human dose of 4.2 mg/kg/day, crofelemer produced an increase in fetal resorptions and abortions compared to controls. However, it is not clear whether these effects are related to the maternal toxicity (decreased body weight and decreased food consumption) observed.

8.2        Lactation

Risk Summary

The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV-1.

There are no data on the presence of crofelemer in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for HIV transmission and adverse effects on a breastfed infant, instruct mothers not to breastfeed if they are taking MYTESI.

8.4        Pediatric Use

The safety and effectiveness of MYTESI have not been established in pediatric patients.

8.5        Geriatric Use

Clinical studies with MYTESI did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients.

8.6        Use in Patients with Low CD4 Counts and High Viral Loads

No dose modifications are recommended with respect to CD4 cell count and HIV viral load, based on the findings in subgroups of patients defined by CD4 cell count and HIV viral load.

The safety profile of MYTESI was similar in patients with baseline CD4 cell count less than 404 cells/microL (lower limit of normal range) (N=388) and patients with baseline CD4 cell counts greater than or equal to 404 cells/microL (N=289).

The safety profile of crofelemer was similar in patients with baseline HIV viral loads less than 400 copies/mL (N = 412) and patients with baseline HIV viral loads greater than or equal to 400 copies/mL (N = 278).

5. 1        Risks of Treatment in Patients with Infectious Diarrhea

Before starting MYTESI, rule out infectious etiologies of diarrhea. If infectious etiologies are not considered, and MYTESI is initiated based on a presumptive diagnosis of non-infectious diarrhea, then there is a risk that patients with infectious etiologies will not receive the appropriate treatments, and their disease may worsen. MYTESI is not indicated for the treatment of infectious diarrhea.