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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Gastrointestinal Effects

(Last updated:February 12, 2014; last reviewed:February 12, 2014)

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Table 11c. 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 Principally ZDV and PIs (such as LPV/r, RTV) but can occur with all ARVs Onset:
  • Early
Presentation:
  • Nausea, emesis—may be associated with anorexia and/or abdominal pain
Varies with ARV agent;10%–30% in some series. Unknown Instruct patient to take PIs with food.

Generally improves with time; monitor for weight loss, ARV adherence.
Reassure patient/caretaker that nausea and vomiting will likely decrease over time.

Provide supportive care including instruction on dietary modification.


Although antiemetics are not generally indicated, they may be useful in extreme or persistent cases.
Diarrhea PIs (NFV, LPV/r, FPV/r), buffered ddI Onset:
  • Early
Presentation:
  • Generally soft, more frequent stools
Varies with ARV agent;
10%–30% in some series.
Unknown Generally improves with time (usually over 6-8 weeks); monitor for weight loss, dehydration. Exclude infectious causes of diarrhea.

Although data in children on treatment for ARV-associated diarrhea are lacking, dietary modification, use of calcium carbonate, bulk-forming agents (psyllium), or antimotility agents (loperamide) may be helpful.

While there are few published data on its use, crofelemer is FDA-approved for treatment of ART-associated diarrhea in adults but not in children.
Pancreatitis ddI, d4T (especially concurrently or with TDF), boosted PIs.

Reported, albeit rarely, with most ARVs.
Onset:
  • Any time, usually after months on therapy
Presentation:
  • Emesis, abdominal pain, elevated amylase and lipase (asymptomatic hyperamylasemia or elevated lipase do not in and of themselves indicate pancreatitis).
<1%–2% in recent series.

Frequency was higher in the past with higher dosing of ddI.
Concomitant treatment with other medications associated with pancreatitis (e.g., TMP-SMX, pentamidine, ribavirin).

Hypertriglyceridemia.

Advanced disease.

Previous episode of pancreatitis. 
Avoid use of ddI in patients with history of pancreatitis. Discontinue offending agent–avoid reintroduction.

Manage symptoms of acute episode.


If associated with hypertriglyceridemia, consider interventions to lower TG levels.

Key to Acronyms
: ARV = antiretroviral, d4T = stavudine, ddI = didanosine, FPV/r = fosamprenavir/ritonavir, LPV = lopinavir, LPV/r = lopinavir/ritonavir, NFV = nelfinavir, PI = protease inhibitor, RTV = ritonavir, TDF = tenofovir disoproxil fumarate, TG = triglyceride, TMP-SMX = trimethoprim sulfamethoxazole, ZDV = zidovudineavudine

References

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  12. 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. Oct 2012;17(4):382-388. Available at http://www.ncbi.nlm.nih.gov/pubmed/23411444.
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  14. Patel TS, Crutchley RD, Tucker AM, Cottreau J, Garey KW. Crofelemer for the treatment of chronic diarrhea in patients living with HIV/AIDS. Hiv/Aids. 2013;5:153-162. Available at http://www.ncbi.nlm.nih.gov/pubmed/23888120.
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