Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States
Special Considerations Regarding the Use of Antiretroviral Drugs by HIV-Infected Pregnant Women and their Infants
Pharmacokinetic Changes
(Last updated:9/14/2011)
Panel’s Recommendation:
• Altered dosing during pregnancy may be required for some protease inhibitors (PIs), such as lopinavir/ritonavir (see Table 5) (AII). |
Physiologic changes that occur during pregnancy can affect the kinetics of drug absorption, distribution, biotransformation, and elimination, thereby also affecting requirements for drug dosing and potentially altering the susceptibility of the pregnant woman to drug toxicity [1-2]. During pregnancy, gastrointestinal transit time becomes prolonged; body water and fat increase throughout gestation and are accompanied by increases in cardiac output, ventilation, and liver and renal blood flow; plasma protein concentrations decrease; renal sodium reabsorption increases; and changes occur in metabolic enzyme pathways in the liver. Placental transport of drugs, compartmentalization of drugs in the embryo/fetus and placenta, biotransformation of drugs by the fetus and placenta, and elimination of drugs by the fetus also can affect drug pharmacokinetics (PKs) in the pregnant woman.
Currently available data on the PKs of antiretroviral (ARV) agents in pregnancy are summarized in Table 5. In general, the PKs of nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) are similar in pregnant and nonpregnant women, although protease inhibitor (PI) PKs are more variable, particularly in later pregnancy. The current data suggest that in many women, exposure to lopinavir/ritonavir, atazanavir, and nelfinavir is decreased during the second and/or third trimester (see Table 5). The need for a dose adjustment depends on the PI, the treatment experience of a particular patient, and use (if any) of concomitant medications with potential for interaction [3-10].
References
1. Mirochnick M, Capparelli E. Pharmacokinetics of antiretrovirals in pregnant women. Clin Pharmacokinet. 2004;43(15):1071-1087.
2. Roustit M, Jlaiel M, Leclercq P, Stanke-Labesque F. Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women. Br J Clin Pharmacol. 2008 Aug;66(2):179-195.
3. Bristol-Myers Squibb. Reyataz drug label, 2/4/2011. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s025lbl.pdf.
4. Stek AM, Mirochnick M, Capparelli E, et al. Reduced lopinavir exposure during pregnancy. AIDS. 2006 Oct 3;20(15):1931-1939.
5. Villani P, Floridia M, Pirillo MF, et al. Pharmacokinetics of nelfinavir in HIV-1-infected pregnant and nonpregnant women. Br J Clin Pharmacol. 2006 Sep;62(3):309-315.
6. Bryson YJ, Mirochnick M, Stek A, et al. Pharmacokinetics and safety of nelfinavir when used in combination with zidovudine and lamivudine in HIV-infected pregnant women: Pediatric AIDS Clinical Trials Group (PACTG) Protocol 353. HIV Clin Trials. 2008 Mar-Apr;9(2):115-125.
7. Mirochnick M, Best BM, Stek AM, et al. Lopinavir exposure with an increased dose during pregnancy. J Acquir Immune Defic Syndr. 2008 Dec 15;49(5):485-491.
8. Read JS, Best BM, Stek AM, et al. Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum. HIV Med. 2008 Nov;9(10):875-882.
9. Bouillon-Pichault M, Jullien V, Azria E, et al. Population analysis of the pregnancy-related modifications in lopinavir pharmacokinetics and their possible consequences for dose adjustment. J Antimicrob Chemother. 2009 Jun;63(6):1223-1232.
10. Best BM, Stek AM, Mirochnick M, et al. Lopinavir tablet pharmacokinetics with an increased dose during pregnancy. J Acquir Immune Defic Syndr. 2010 Aug 1;54(4):381-388.