The following list of side effects caused by some common HIV / AIDS medications is quoted from the National Institutes of Health manual, Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, May 4, 2006, page 77.

Table 19. Adverse Drug Reactions and Related “Black Box Warnings” in Product Labeling for Antiretroviral Agents

The Food and Drug Administration can require that warnings regarding special problems associated with a prescription drug, including those that might lead to death or serious injury, be placed in a prominently displayed box, commonly known as a “black box.”

Please note that other serious toxicities associated with antiretroviral agents are not listed in this table...

Abacavir (Ziagen®, or as combination products in Epzicom® and Trizivir®)
• Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir:
– This is a multi-organ clinical syndrome, characterized by two or more groups of the following signs or symptoms including (1) fever, (2) rash, (3) gastrointestinal (e.g., nausea, vomiting, diarrhea, or abdominal pain), (4) constitutional (including generalized malaise, fatigue, or achiness), and (5) respiratory symptoms (including dyspnea, cough, or pharyngitis).
– Abacavir should be discontinued as soon as hypersensitivity reaction is suspected.
– Any product containing abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible – because more severe symptoms can occur within hours after restarting abacavir and may include life-threatening hypotension and death.
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of
antiretroviral nucleoside analogues alone or in combination.

Amprenavir (Agenerase®)
Oral Solution
• Because of the potential risk of toxicity from substantial amounts of the excipient propylene glycol in Agenerase Oral Solution, it is contraindicated for the following patient populations:
– children age <4 years
– pregnant women
– patients with renal or hepatic failure
– patients treated with disulfiram or metronidazole
• Oral solution should be used only when amprenavir capsules or other protease inhibitors cannot be used.

Didanosine (Videx® or Videx-EC®)
• Fatal and nonfatal pancreatitis have occurred with didanosine alone or in combination with other antiretroviral agents.
– Didanosine should be withheld if pancreatitis is suspected.
– Didanosine should be discontinued if pancreatitis is confirmed.
• Fatal lactic acidosis has been reported among pregnant women who received a combination of didanosine and
stavudine with other antiretroviral combinations.
– Didanosine and stavudine combination should only be used during pregnancy if the potential benefit clearly outweighs the potential risks.
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of
antiretroviral nucleoside analogues alone or in combination.

Emtricitabine (Emtriva™); or in combination product with tenofovir DF
(Truvada™)
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of
nucleoside analogues alone or in combination with other antiretrovirals.
• Emtricitabine is not indicated for the treatment of hepatitis B infection (HBV), the safety and efficacy have not been established in patients with HIV/HBV co-infection.
• Severe acute exacerbations of hepatitis B have been reported in patients who discontinued emtricitabine –
hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuation of tenofovir in HIV/HBV co-infected patients.
• If appropriate, initiation of anti-HBV therapy may be warranted after discontinuation of tenofovir.

Lamivudine (Epivir®), or in combination products Combivir®, Epizicom®, and Trizivir®)
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of
antiretroviral nucleoside analogues alone or in combination.
• Epivir tablets and oral solution (used to treat HIV infection) contain a higher dose of lamivudine than Epivir-HBV tablets and oral solution (used to treat chronic hepatitis B). Patients with HIV infection should receive only dosage and formulations appropriate for treatment of HIV.
• Severe acute exacerbations of hepatitis B infection have been reported in HBV/HIV co-infected patients upon discontinuation of lamivudine-containing products. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuation of lamivudine in patients with HIV/HBV co-infection.
• If appropriate, initiation of anti-hepatitis B therapy may be warranted.

Nevirapine
(Viramune®)
• Severe, life-threatening, and in some cases fatal hepatotoxicity, including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure, has been reported. Patients may present with non-specific prodromes of hepatitis and
progress to hepatic failure.
• Women with CD4 counts > 250 cells/mm3, including pregnant women receiving chronic treatment for HIV infection are at considerably higher risk of hepatotoxicities.
• Severe, life-threatening, and even fatal skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis,
and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction have occurred with
nevirapine treatment.
• Patients should be monitored intensively during the first 18 weeks of nevirapine therapy to detect potentially lifethreatening
hepatotoxicity or skin reactions.
• A 14-day lead-in period with nevirapine 200 mg daily must be followed strictly.
• Nevirapine should not be restarted after severe hepatic, skin, or hypersensitivity reactions.

Ritonavir (Norvir®)
• Co-administration of ritonavir with certain non-sedating antihistamines, sedative hypnotics, antiarrhythmics, or ergot
alkaloids may result in potentially serious or life-threatening adverse events because of possible effects of ritonavir on
hepatic metabolism of certain drugs.

Saquinavir (Fortovase®, Invirase®)
• INVIRASE (saquinavir mesylate) hard gelatin capsules and tablets and FORTOVASE (saquinavir) soft gelatin capsules are
not bioequivalent and cannot be used interchangeably.
• INVIRASE may be used only if it is combined with ritonavir, which significantly inhibits saquinavir's metabolism to
provide plasma saquinavir levels at least equal to those achieved with FORTOVASE.
• When using saquinavir as the sole protease inhibitor in an antiviral regimen, FORTOVASE is the recommended formulation.
Stavudine (Zerit®) • Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of
antiretroviral nucleoside analogues alone or in combination.
• Fatal lactic acidosis has been reported among pregnant women who received combination of stavudine and didanosine with
other antiretroviral combinations.
• Stavudine and didanosine combination should only be used during pregnancy if the potential benefit clearly outweighs the
potential risks.
• Fatal and non-fatal pancreatitis have occurred when stavudine was part of a combination regimen with didanosine with or
without hydroxyurea.

Tenofovir (Viread®) or in combination product with emtricitabine
(Truvada™)
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside
analogs alone or in combination with other antiretrovirals.
• Tenofovir is not indicated for the treatment of chronic hepatitis B (HBV) infection, safety and efficacy in patients with
HIV/HBV co-infection have not been established.
• Severe acute exacerbations of hepatitis B have been reported in patients who discontinued tenofovir – hepatic function
should be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuation of
tenofovir in HIV/HBV co-infected patients.
• If appropriate, initiation of anti-HBV therapy may be warranted after discontinuation of tenofovir.

Tipranavir (Aptivus®)
• Tipranavir co-adminstered with 200mg twice daily ritonavir has been associated with reports of clinical hepatitis and hepatic decompensation including some fatalities.
• Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C co-infection, as these patients have an increased risk of hepatotoxicity.

Zalcitabine (Hivid®)
• Zalcitabine can cause severe peripheral neuropathy, use with caution among patients with pre-existing neuropathy.
• In rare cases, zalcitabine can cause pancreatitis, therapy should be withheld until pancreatitis is excluded.
• Rare cases of hepatic failure and death have been reported among patients with underlying hepatitis B infection.
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of
antiretroviral nucleoside analogues alone or in combination.

Zidovudine (Retrovir®), or in combination products Combivir® and Trizivir®
• Zidovudine can be associated with hematologic toxicities, including granulocytopenia and severe anemia, including
among advanced HIV patients.
• Prolonged zidovudine use has been associated with symptomatic myopathy.
• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of
antiretroviral nucleoside analogues alone or in combination.

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