Management of Medication Toxicity or Intolerance

Gastrointestinal Effects

Table 15c. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Gastrointestinal Effects
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Nausea/ Vomiting All ARV drugs, but most notably RTV-boosted PIs Onset:
  • Early
Presentation:
  • Nausea and emesis, both of which may be associated with anorexia and/or abdominal pain
Varies by ARV agent; generally <15% Unknown Instruct patient to take PIs with food.

Monitor for weight loss and ARV adherence.
Reassure patient that these adverse effects generally improve over time (usually in 6–8 weeks).

Consider switching to ARV drugs with smaller tablet sizes (see Appendix A, Table 2).

Provide supportive care.

In extreme or persistent cases, use antiemetics or switch to another ARV regimen.
Diarrhea All ARV drugs, but most notably RTV-boosted PIs Onset:
  • Early
Presentation:
  • More frequent bowel movements and stools that are generally soft
Varies by ARV agent; generally <15% Unknown Monitor for weight loss and dehydration. In prolonged or severe cases, exclude infectious or noninfectious (e.g., lactose intolerance) causes of diarrhea.

Reassure patient that this adverse effect generally improves over time (usually in 6–8 weeks). Consider switching to another ARV regimen in persistent and severe cases.

Treatment data in children are lacking; however, the following strategies may be useful when the ARV regimen cannot be changed:
  • Dietary modification
  • Using bulk-forming agents (e.g., psyllium)
  • Using antimotility agents (e.g., loperamide)
  • Using crofelemer, which is approved by the FDA to treat ART-associated diarrhea in adults aged ≥18 years; no pediatric data are available.
Pancreatitis Rare, but may occur with NRTIs or RTV-boosted PIs Onset:
  • Any time, usually after months of therapy
Presentation:
  • Emesis, abdominal pain, elevated amylase and lipase levels (asymptomatic hyperamylasemia or elevated lipase do not in and of themselves indicate pancreatitis)
<2% in a recent case series Use of concomitant medications that are associated with pancreatitis (e.g., TMP-SMX, pentamidine, ribavirin)

Hypertriglyceridemia

Advanced HIV infection

Previous episode of pancreatitis

Alcohol use
Measure serum amylase and lipase concentrations if persistent abdominal pain develops. Discontinue offending agent and avoid reintroduction.

Manage symptoms of acute episodes.

If pancreatitis is associated with hypertriglyceridemia, consider using interventions to lower TG levels.
Key: ART = antiretroviral therapy; ARV = antiretroviral; FDA = Food and Drug Administration; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; RTV = ritonavir; TG = triglyceride; TMP-SMX = trimethoprim sulfamethoxazole  

References

  1. Buck WC, Kabue MM, Kazembe PN, Kline MW. Discontinuation of standard first-line antiretroviral therapy in a cohort of 1434 Malawian children. J Int AIDS Soc. 2010;13:31. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20691049.
  2. Nachman SA, Chernoff M, Gona P, et al. Incidence of noninfectious conditions in perinatally HIV-infected children and adolescents in the HAART era. Arch Pediatr Adolesc Med. 2009;163(2):164-171. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19188649.
  3. Hoffmann CJ, Fielding KL, Charalambous S, et al. Antiretroviral therapy using zidovudine, lamivudine, and efavirenz in South Africa: tolerability and clinical events. AIDS. 2008;22(1):67-74. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18090393.
  4. Malan N, Su J, Mancini M, et al. Gastrointestinal tolerability and quality of life in antiretroviral-naive HIV-1-infected patients: data from the CASTLE study. AIDS Care. 2010;22(6):677-686. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20467943.
  5. Manfredi R, Calza L. HIV infection and the pancreas: risk factors and potential management guidelines. Int J STD AIDS. 2008;19(2):99-105. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18334062.
  6. Tukei VJ, Asiimwe A, Maganda A, et al. Safety and tolerability of antiretroviral therapy among HIV-infected children and adolescents in Uganda. J Acquir Immune Defic Syndr. 2012;59(3):274-280. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22126740.
  7. Wegzyn CM, Fredrick LM, Stubbs RO, Woodward WC, Norton M. Diarrhea associated with lopinavir/ritonavir-based therapy: results of a meta-analysis of 1469 HIV-1-infected participants. J Int Assoc Physicians AIDS Care (Chic). 2012;11(4):252-259. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22544446.
  8. Oumar AA, Diallo K, Dembele JP, et al. Adverse drug reactions to antiretroviral therapy: prospective study in children in sikasso (mali). J Pediatr Pharmacol Ther. 2012;17(4):382-388. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23411444.
  9. Wattanutchariya N, Sirisanthana V, Oberdorfer P. Effectiveness and safety of protease inhibitor-based regimens in HIV-infected Thai children failing first-line treatment. HIV Med. 2013;14(4):226-232. Available at: http://www.ncbi.nlm.nih.gov/pubmed/23094820.
  10. Van Dyke RB, Wang L, Williams PL, Pediatric AIDS Clinical Trials Group C Team. Toxicities associated with dual nucleoside reverse-transcriptase inhibitor regimens in HIV-infected children. J Infect Dis. 2008;198(11):1599-1608. Available at: http://www.ncbi.nlm.nih.gov/pubmed/19000014.
  11. Clay PG, Crutchley RD. Noninfectious diarrhea in HIV seropositive individuals: a review of prevalence rates, etiology, and management in the era of combination antiretroviral therapy. Infect Dis Ther. 2014. Available at: http://www.ncbi.nlm.nih.gov/pubmed/25388760.
  12. Szoke D, Ridolfo A, Valente C, Galli M, Panteghini M. Frequency of pancreatic hyperamylasemia in human immunodeficiency virus-positive patients in the highly active antiretroviral therapy era. Am J Clin Pathol. 2016;145(1):128-133. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26712880.
  13. Castro JG, Chin-Beckford N. Crofelemer for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on anti-retroviral therapy. Expert Rev Clin Pharmacol. 2015;8(6):683-690. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26517110.
  14. Dikman AE, Schonfeld E, Srisarajivakul NC, Poles MA. Human Immunodeficiency virus-associated diarrhea: still an issue in the era of antiretroviral therapy. Dig Dis Sci. 2015;60(8):2236-2245. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25772777.
  15. Logan C, Beadsworth MB, Beeching NJ. HIV and diarrhoea: what is new? Curr Opin Infect Dis. 2016;29(5):486-494. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27472290.

 

Management of Medication Toxicity or Intolerance

Gastrointestinal Effects

Table 15c. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Gastrointestinal Effects
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Nausea/ Vomiting All ARV drugs, but most notably RTV-boosted PIs Onset:
  • Early
Presentation:
  • Nausea and emesis, both of which may be associated with anorexia and/or abdominal pain
Varies by ARV agent; generally <15% Unknown Instruct patient to take PIs with food.

Monitor for weight loss and ARV adherence.
Reassure patient that these adverse effects generally improve over time (usually in 6–8 weeks).

Consider switching to ARV drugs with smaller tablet sizes (see Appendix A, Table 2).

Provide supportive care.

In extreme or persistent cases, use antiemetics or switch to another ARV regimen.
Diarrhea All ARV drugs, but most notably RTV-boosted PIs Onset:
  • Early
Presentation:
  • More frequent bowel movements and stools that are generally soft
Varies by ARV agent; generally <15% Unknown Monitor for weight loss and dehydration. In prolonged or severe cases, exclude infectious or noninfectious (e.g., lactose intolerance) causes of diarrhea.

Reassure patient that this adverse effect generally improves over time (usually in 6–8 weeks). Consider switching to another ARV regimen in persistent and severe cases.

Treatment data in children are lacking; however, the following strategies may be useful when the ARV regimen cannot be changed:
  • Dietary modification
  • Using bulk-forming agents (e.g., psyllium)
  • Using antimotility agents (e.g., loperamide)
  • Using crofelemer, which is approved by the FDA to treat ART-associated diarrhea in adults aged ≥18 years; no pediatric data are available.
Pancreatitis Rare, but may occur with NRTIs or RTV-boosted PIs Onset:
  • Any time, usually after months of therapy
Presentation:
  • Emesis, abdominal pain, elevated amylase and lipase levels (asymptomatic hyperamylasemia or elevated lipase do not in and of themselves indicate pancreatitis)
<2% in a recent case series Use of concomitant medications that are associated with pancreatitis (e.g., TMP-SMX, pentamidine, ribavirin)

Hypertriglyceridemia

Advanced HIV infection

Previous episode of pancreatitis

Alcohol use
Measure serum amylase and lipase concentrations if persistent abdominal pain develops. Discontinue offending agent and avoid reintroduction.

Manage symptoms of acute episodes.

If pancreatitis is associated with hypertriglyceridemia, consider using interventions to lower TG levels.
Key: ART = antiretroviral therapy; ARV = antiretroviral; FDA = Food and Drug Administration; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; RTV = ritonavir; TG = triglyceride; TMP-SMX = trimethoprim sulfamethoxazole  
Updated
Reviewed
Apr. 14, 2020

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