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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: July 31, 2012; last reviewed: July 31, 2012)

Panel's Recommendation

Panel's Recommendation

  • Altered dosing during pregnancy may be required for some protease inhibitors, such as lopinavir/ritonavir (see Table 5) (AII)
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion

Physiologic changes that occur during pregnancy can affect drug absorption, distribution, biotransformation, and elimination, thereby also affecting requirements for drug dosing and potentially altering the susceptibility of pregnant women 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 cellular transporters and drug metabolizing enzymes in the liver and intestine. 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 agents in pregnancy are summarized in Table 5. In general, the PKs of nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors are similar in pregnant and non-pregnant women, whereas protease inhibitor (PI) PKs are more variable, particularly in later pregnancy. Current data suggest that with standard adult dosing, plasma concentrations of lopinavir/ritonavir, atazanavir, darunavir, and nelfinavir are reduced during the second and/or third trimesters (see Table 5). The need for a dose adjustment depends on the PI, an individual patient’s treatment experience, and use (if any) of concomitant medications with potential for drug interactions.3-10

References

  1. Mirochnick M, Capparelli E. Pharmacokinetics of antiretrovirals in pregnant women. Clin Pharmacokinet. 2004;43(15):1071-1087. Available at http://www.ncbi.nlm.nih.gov/pubmed/15568888.
  2. Roustit M, Jlaiel M, Leclercq P, Stanke-Labesque F. Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women. Br J Clin Pharmacol. Aug 2008;66(2):179-195. Available at http://www.ncbi.nlm.nih.gov/pubmed/18537960.
  3. Bristol-Myers Squibb. Reyataz drug label, 2/4/2011. Available at http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s025lbl.pdf. Accessed on June 26, 2012.
  4. Stek AM, Mirochnick M, Capparelli E, et al. Reduced lopinavir exposure during pregnancy. AIDS. Oct 3 2006;20(15):1931-1939. Available at http://www.ncbi.nlm.nih.gov/pubmed/16988514.
  5. Villani P, Floridia M, Pirillo MF, et al. Pharmacokinetics of nelfinavir in HIV-1-infected pregnant and nonpregnant women. Br J Clin Pharmacol. Sep 2006;62(3):309-315. Available at http://www.ncbi.nlm.nih.gov/pubmed/16934047.
  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. Mar-Apr 2008;9(2):115-125. Available at http://www.ncbi.nlm.nih.gov/pubmed/18474496.
  7. Mirochnick M, Best BM, Stek AM, et al. Lopinavir exposure with an increased dose during pregnancy. J Acquir Immune Defic Syndr. Dec 15 2008;49(5):485-491. Available at http://www.ncbi.nlm.nih.gov/pubmed/18989231.
  8. Read JS, Best BM, Stek AM, et al. Pharmacokinetics of new 625 mg nelfinavir formulation during pregnancy and postpartum. HIV Med. Nov 2008;9(10):875-882. Available at http://www.ncbi.nlm.nih.gov/pubmed/18795962.
  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. Jun 2009;63(6):1223-1232. Available at http://www.ncbi.nlm.nih.gov/pubmed/19389715.
  10. Best BM, Stek AM, Mirochnick M, et al. Lopinavir tablet pharmacokinetics with an increased dose during pregnancy. J Acquir Immune Defic Syndr. Aug 2010;54(4):381-388. Available at http://www.ncbi.nlm.nih.gov/pubmed/20632458

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