Ritonavir use while Breastfeeding
Drugs containing Ritonavir: Kaletra, Norvir, Norvir Soft Gelatin, AccessPak for HIV PEP Expanded with Kaletra
Ritonavir Levels and Effects while Breastfeeding
Summary of Use during Lactation
In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, exclusive breastfeeding for 6 months is recommended for HIV-infected mothers to reduce the risk of HIV transmission from the mother to the infant compared with mixed feeding. In these settings, abrupt weaning at 4 months does not reduce the risk of HIV transmission or produce an overall health benefit compared to continued breastfeeding, and increases the risk of infant death in HIV-infected infants. Ritonavir has been successfully used as part of a regimen that decreases mother-to-child transmission of HIV, usually in low doses as a boosting agent. Extended antiretroviral prophylaxis in breastfed infants with antiretroviral drugs appears to reduce the rate of HIV transmission during breastfeeding by about half, but the optimal regimen and duration of prophylaxis has not yet been defined. Breastfed infants whose mothers receive highly active antiretroviral therapy (HAART) have higher rates of neutropenia during the first month and severe anemia during the first 6 months of life.
Maternal Levels. One study measured ritonavir in breastmilk samples from nursing mothers who had been randomized to receive the drug as part of a clinical trial to evaluate maternal to child transmission of HIV infection. The dosages, dosage regimens and time of breastmilk sample collection times were not reported. Ritonavir was not detected in any of 60 breastmilk samples.
Nine mothers who were receiving lopinavir 400 mg plus ritonavir 100 mg twice daily as part of a combination antiretroviral regimen provided a total of 23 milk samples at birth, 1 month, 3 months and/or 6 months postpartum. Milk samples were collected at a median of 4.5 hours (range 3.5 to 6 hours) after the previous dose. The median breastmilk ritonavir concentration was 79 mcg/L (range 31 to 193 mcg/L).
Thirty women were studied at 6, 12 or 24 weeks postpartum (10 at each time). Each mother was taking zidovudine 300 mg, lamivudine 150 mg, lopinavir 400 mg, and ritonavir 100 mg twice daily by mouth starting at delivery. On the study day, at a median of 14.9 hours after the previous evening's dose, maternal plasma and breastmilk samples were obtained prior to the morning dose and 2, 4 and 6 hours after the dose. One hundred twelve of the 121 breastmilk samples contained detectable quantities (10 mcg/L or greater) of ritonavir, with a median breastmilk concentration of 79 mcg/L over the 6 hours.
Infant Levels. Breastfed infants of 9 mothers who were receiving lopinavir 400 mg plus ritonavir 100 mg twice daily as part of a combination antiretroviral regimen had a total of 6 blood samples analyzed at 1 month, 3 months and/or 6 months postpartum. Samples were collected at a median of 4.5 hours (range 3.5 to 6 hours) after the previous maternal dose and a median of 30 minutes (range 20 to 60 minutes) after the previous nursing. The infants' median ritonavir plasma concentrations was 7 mcg/L (range 0 to 138 mcg/L), which was a median of 12% (range 11 to 40%) of the maternal serum concentration.
Ritonavir was measured in 117 breastfed (90% exclusive) infants whose mothers were taking lopinavir plus ritonavir for HIV infection during pregnancy and postpartum. At 8 and 12 weeks postpartum, none of the infants had detectable ritonavir in their plasma; 91% of infants had detectable ritonavir in their hair samples at 12 weeks postpartum at a mean concentration of 0.15 ng/mg of hair (range 0.03 to 0.42 ng/mg). The authors interpreted the results to mean that infants receive negligible exposure to ritonavir during breastfeeding.
Thirty nursing mothers were studied at 6, 12 or 24 weeks postpartum (10 at each time). Each mother was taking ritonavir 100 mg twice daily by mouth starting at delivery. Infant plasma samples were obtained before their mother's first dose and at 2, 4 and 6 hours after the mother's dose. Infants were allowed to breastfeed ad libitum during the study period. Ritonavir was undetectable (<10 mcg/L) in all of the 115 infant plasma samples.
Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
Possible Effects on Lactation
Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
Alternate Drugs to Consider
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CAS Registry Number
- Antiinfective Agents
- Anti-HIV Agents
- Antiviral Agents
- Anti-Retroviral Agents
- HIV Protease Inhibitors
LactMed Record Number
Information from the National Library of Medicine's LactMed Database.
Last Revision Date
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