Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Last Updated: May 22, 2018; Last Reviewed: May 22, 2018
|Ritonavir (RTV, Norvir)
For additional information see Drugs@FDA: https://www.accessdata.fda.gov/scripts/cder/daf/
|Oral Powder: 100 mg per packet
Oral Solution: 80 mg/mL. Oral solution contains 43% (v/v) ethanol and approximately 27% (w/v) propylene glycol.
Tablets: 100 mg
|Dosing Recommendations||Selected Adverse Events|
|Ritonavir as a Pharmacokinetic Enhancer:a
|a Ritonavir has antiviral activity, but it is not used as an antiviral agent (see text).|
- Metabolism: Ritonavir is extensively metabolized by (and is one of the most potent inhibitors of) hepatic cytochrome P (CYP) 450 3A. There is potential for multiple drug interactions with ritonavir.
- Before ritonavir is administered, a patient’s medication profile should be carefully reviewed for potential interactions with ritonavir and overlapping toxicities with other drugs.
- Ritonavir and cobicistat are not interchangeable and may result in different drug interactions.1
- Avoid concomitant use of intranasal or inhaled fluticasone, because adrenal insufficiency has been reported.2 Use caution when prescribing ritonavir with other inhaled steroids. Limited data suggest that beclomethasone may be a suitable alternative to fluticasone when a patient who is taking ritonavir requires an inhaled or intranasal corticosteroid.3,4 See Drug Interactions between Protease Inhibitors and Other Drugs in the Adult and Adolescent Guidelines for additional information.
- More common: Nausea, vomiting, diarrhea, headache, abdominal pain, anorexia, circumoral paresthesia, lipid abnormalities.
- Less common (more severe): Exacerbation of chronic liver disease, fat maldistribution.
- Rare: New-onset diabetes mellitus, hyperglycemia, ketoacidosis, exacerbation of preexisting diabetes mellitus, spontaneous bleeding in hemophiliacs, pancreatitis, and hepatitis (life-threatening in rare cases). Allergic reactions, including bronchospasm, urticaria, and angioedema. Toxic epidermal necrolysis and Stevens-Johnson syndrome have occurred.5
Resistance to ritonavir is not clinically relevant when the drug is used as a pharmacokinetic (PK) enhancer of other antiretroviral (ARV) medications.
Ritonavir has been approved by the Food and Drug Administration for use in the pediatric population.
Efficacy: Effectiveness in Practice
Use of ritonavir as the sole protease inhibitor (PI) in ARV therapy in children is not recommended. Although ritonavir has been well studied in children as an ARV agent, it is no longer used as a sole PI for therapy because ritonavir is associated with a higher incidence of gastrointestinal toxicity and has a greater potential for drug-drug interactions than other PIs. In addition, poor palatability of the liquid preparation and a large pill burden with the tablets (the adult dose is six tablets, twice daily) limit its use as a sole PI. However, in both children and adults, ritonavir is recommended as a PK enhancer for use with other PIs. Ritonavir is a CYP3A inhibitor and functions as a PK enhancer by slowing the metabolism of the PIs.
Pediatric dosing regimens, including boosted fosamprenavir, tipranavir, darunavir, atazanavir, and the PI co-formulation lopinavir/ritonavir (LPV/r), are available. For more information about individual PIs, see other sections of the Drug Appendix.
Full-dose ritonavir has been shown to prolong the PR interval in a study of healthy adults who were given ritonavir 400 mg twice daily.5 Potentially life-threatening arrhythmias have been reported in premature newborn infants treated with LPV/r; the use of LPV/r is not recommended until the gestational age of 42 weeks.6,7 Co-administration of ritonavir with other drugs that prolong the PR interval (e.g., macrolides, quinolones, methadone) should be undertaken with caution because it is unknown how co-administering any of these drugs with ritonavir will affect the PR interval. In addition, ritonavir should be used with caution in patients who may be at increased risk of developing cardiac conduction abnormalities, such as patients who have underlying structural heart disease, conduction system abnormalities, ischemic heart disease, or cardiomyopathy.
- Marzolini C, Gibbons S, Khoo S, Back D. Cobicistat versus ritonavir boosting and differences in the drug-drug interaction profiles with co-medications. J Antimicrob Chemother. 2016;71(7):1755-1758. Available at https://www.ncbi.nlm.nih.gov/pubmed/26945713.
- Bernecker C, West TB, Mansmann G, Scherbaum WA, Willenberg HS. Hypercortisolism caused by ritonavir associated inhibition of CYP 3A4 under inhalative glucocorticoid therapy. 2 case reports and a review of the literature. Exp Clin Endocrinol Diabetes. 2012;120(3):125-127. Available at http://www.ncbi.nlm.nih.gov/pubmed/22328106.
- Boyd SD, Hadigan C, McManus M, et al. Influence of low-dose ritonavir with and without darunavir on the pharmacokinetics and pharmacodynamics of inhaled beclomethasone. J Acquir Immune Defic Syndr. 2013;63(3):355-361. Available at http://www.ncbi.nlm.nih.gov/pubmed/23535292.
- Saberi P, Phengrasamy T, Nguyen DP. Inhaled corticosteroid use in HIV-positive individuals taking protease inhibitors: a review of pharmacokinetics, case reports and clinical management. HIV Med. 2013;14(9):519-529. Available at http://www.ncbi.nlm.nih.gov/pubmed/23590676.
- Changes to Norvir labeling. AIDS Patient Care STDS. 2008;22(10):834-835. Available at http://www.ncbi.nlm.nih.gov/pubmed/18924248.
- Lopriore E, Rozendaal L, Gelinck LB, Bokenkamp R, Boelen CC, Walther FJ. Twins with cardiomyopathy and complete heart block born to an HIV-infected mother treated with HAART. AIDS. 2007;21(18):2564-2565. Available at http://www.ncbi.nlm.nih.gov/pubmed/18025905.
- McArthur MA, Kalu SU, Foulks AR, Aly AM, Jain SK, Patel JA. Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy. Pediatr Infect Dis J. 2009;28(12):1127-1129. Available at http://www.ncbi.nlm.nih.gov/pubmed/19820426.