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Viramune (Nevirapine) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Clinical Trials in Adults

The most serious adverse reactions associated with VIRAMUNE are hepatitis, hepatic failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions. Hepatitis/hepatic failure may be isolated or associated with signs of hypersensitivity which may include severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction [ see Boxed Warning and Warnings and Precautions (5.1, 5.2) ].

Hepatic Reaction

In controlled clinical trials, symptomatic hepatic events regardless of severity occurred in 4.0% (range 0% to 11.0%) of patients who received VIRAMUNE and 1.2% of patients in control groups. Female gender and higher CD4 counts (>250 cells/mm3 in women and >400 cells/mm3 in men) place patients at increased risk of these events [ see Boxed Warning and Warnings and Precautions ].

Asymptomatic transaminase elevations (AST or ALT > 5X ULN) were observed in 5.8% (range 0% to 9.2%) of patients who received VIRAMUNE and 5.5% of patients in control groups. Co-infection with hepatitis B or C and/or increased transaminase elevations at the start of therapy with VIRAMUNE are associated with a greater risk of later symptomatic events (6 weeks or more after starting VIRAMUNE) and asymptomatic increases in AST or ALT.

Liver enzyme abnormalities (AST, ALT, GGT) were observed more frequently in patients receiving VIRAMUNE than in controls (see Table 3).

Skin Reaction

The most common clinical toxicity of VIRAMUNE is rash, which can be severe or life-threatening [ see Boxed Warning and Warnings and Precautions ]. Rash occurs most frequently within the first 6 weeks of therapy. Rashes are usually mild to moderate, maculopapular erythematous cutaneous eruptions, with or without pruritus, located on the trunk, face and extremities. In controlled clinical trials (Trials 1037, 1038, 1046, and 1090), Grade 1 and 2 rashes were reported in 13.3% of patients receiving VIRAMUNE compared to 5.8% receiving placebo during the first 6 weeks of therapy. Grade 3 and 4 rashes were reported in 1.5% of VIRAMUNE recipients compared to 0.1% of subjects receiving placebo. Women tend to be at higher risk for development of VIRAMUNE associated rash [ see Boxed Warning and Warnings and Precautions ].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Treatment related, adverse experiences of moderate or severe intensity observed in >2% of patients receiving VIRAMUNE in placebo-controlled trials are shown in Table 2.

Table 2 Percentage of Patients with Moderate or Severe Drug Related Events in Adult Placebo Controlled Trials
1 Background therapy included 3TC for all patients and combinations of NRTIs and PIs. Patients had CD4+ cell counts <200 cells/mm3.
2 Background therapy included ZDV and ZDV+ddI; VIRAMUNE monotherapy was administered in some patients. Patients had CD4+ cell count ≥200 cells/mm3.
  Trial 1090 1 Trials 1037, 1038, 1046 2
  VIRAMUNE Placebo VIRAMUNE Placebo
  (n=1121) (n=1128) (n=253) (n=203)
Median exposure (weeks)58522828
Any adverse event14.5% 11.1%31.6%13.3%
Rash5.11.86.71.5
Nausea0.51.18.73.9
Granulocytopenia1.82.80.40
Headache0.70.43.60.5
Fatigue0.20.34.73.9
Diarrhea0.20.82.00.5
Abdominal pain0.10.42.00
Myalgia0.201.22.0

Laboratory Abnormalities

Liver enzyme test abnormalities (AST, ALT) were observed more frequently in patients receiving VIRAMUNE than in controls (Table 3). Asymptomatic elevations in GGT occur frequently but are not a contraindication to continue VIRAMUNE therapy in the absence of elevations in other liver enzyme tests. Other laboratory abnormalities (bilirubin, anemia, neutropenia, thrombocytopenia) were observed with similar frequencies in clinical trials comparing VIRAMUNE and control regimens (see Table 3).

Table 3 Percentage of Adult Patients with Laboratory Abnormalities
1 Background therapy included 3TC for all patients and combinations of NRTIs and PIs. Patients had CD4+ cell counts <200 cells/mm3
2 Background therapy included ZDV and ZDV+ddI; VIRAMUNE monotherapy was administered in some patients. Patients had CD4+ cell count > 200 cells/mm3.
  Trial 1090 1 Trials 1037, 1038, 1046 2
  VIRAMUNE Placebo VIRAMUNE Placebo
Laboratory Abnormality (n=1121) (n=1128) (n=253) (n=203)
Blood Chemistry     
  SGPT (ALT) >250 U/L5.34.414.04.0
  SGOT (AST) >250 U/L3.72.57.61.5
  Bilirubin >2.5 mg/dL1.72.21.71.5
Hematology     
  Hemoglobin <8.0 g/dL3.24.100
  Platelets <50,000/mm31.31.00.41.5
  Neutrophils <750/mm313.313.53.61.0

Clinical Trials in Pediatric Patients

Adverse events were assessed in BI Trial 1100.1032 (ACTG 245), a double-blind, placebo-controlled trial of VIRAMUNE (n=305) in which pediatric patients received combination treatment with VIRAMUNE. In this trial two patients were reported to experience Stevens-Johnson syndrome or Stevens-Johnson/toxic epidermal necrolysis transition syndrome. Safety was also assessed in trial BI 1100.882 (ACTG 180) an open-label trial of VIRAMUNE (n=37) in which patients were followed for a mean duration of 33.9 months (range: 6.8 months to 5.3 years, including long-term follow-up in 29 of these patients in trial BI 1100.892). The most frequently reported adverse events related to VIRAMUNE in pediatric patients were similar to those observed in adults, with the exception of granulocytopenia, which was more commonly observed in children receiving both zidovudine and VIRAMUNE. Cases of allergic reaction, including one case of anaphylaxis, were also reported.

The safety of VIRAMUNE was also examined in BI Trial 1100.1368, an open-label, randomized clinical study performed in South Africa in which 123 HIV-1 infected treatment naïve patients between 3 months and 16 years of age received combination treatment with VIRAMUNE oral solution, lamuvidine and zidovudine for 48 weeks [ see Use In Specific Populations and Clinical Pharmacology ]. Rash (all causality) was reported in 21% of the patients, 4 (3%) of whom discontinued drug due to rash. All 4 patients experienced the rash early in the course of therapy (< 4 weeks) and resolved upon nevirapine discontinuation. Other clinically important adverse events (all causality) include neutropenia (8.9%), anemia (7.3%) and hepatotoxicity (2.4%) [ see Use in Special Populations and Clinical Studies ].

Safety information on use of VIRAMUNE in combination therapy in pediatric patients 2 weeks to < 3 months of age was assessed in 36 patients from the BI 1100.1222 (PACTG 356) study. No unexpected safety findings were observed although granulocytopenia was reported more frequently in this age group compared to the older pediatric age groups and adults.

Post-Marketing Surveillance

In addition to the adverse events identified during clinical trials, the following adverse reactions have been identified during post-approval use of VIRAMUNE. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  •   Body as a Whole: fever, somnolence, drug withdrawal [ see Drug Interactions (7) ], redistribution/accumulation of body fat [ see Warnings and Precautions, (5.6) ]
  •   Gastrointestinal: vomiting
  •   Liver and Biliary: jaundice, fulminant and cholestatic hepatitis, hepatic necrosis, hepatic failure
  •   Hematology: anemia, eosinophilia, neutropenia
  •   Musculoskeletal: arthralgia, rhabdomyolysis associated with skin and/or liver reactions
  •   Neurologic: paraesthesia
  •   Skin and Appendages: allergic reactions including anaphylaxis, angioedema, bullous eruptions, ulcerative stomatitis and urticaria have all been reported. In addition, hypersensitivity syndrome and hypersensitivity reactions with rash associated with constitutional findings such as fever, blistering, oral lesions, conjunctivitis, facial edema, muscle or joint aches, general malaise, fatigue or significant hepatic abnormalities [ see Warnings and Precautions (5.1) ] plus one or more of the following: hepatitis, eosinophilia, granulocytopenia, lymphadenopathy and/or renal dysfunction have been reported with the use of VIRAMUNE.

In post-marketing surveillance anemia has been more commonly observed in children although development of anemia due to concomitant medication use cannot be ruled out.



REPORTS OF SUSPECTED VIRAMUNE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Viramune. The information is not vetted and should not be considered as verified clinical evidence.

Possible Viramune side effects / adverse reactions in 45 year old female

Reported by a health professional (non-physician/pharmacist) from United States on 2011-10-03

Patient: 45 year old female

Reactions: Viral Load Increased, Medication Residue

Suspect drug(s):
Viramune



Possible Viramune side effects / adverse reactions in 34 year old female

Reported by a health professional (non-physician/pharmacist) from Argentina on 2011-10-06

Patient: 34 year old female

Reactions: Maternal Exposure During Pregnancy, Abortion Spontaneous

Suspect drug(s):
Viramune
    Dosage: 800mgd per day
    Administration route: Oral
    Indication: HIV Infection
    Start date: 2009-09-04

Lamivudine + Zidovudine
    Dosage: 2tab per day
    Administration route: Oral
    Indication: HIV Infection

Efavirenz
    Dosage: 600mgd per day
    Administration route: Oral
    Indication: HIV Infection
    End date: 2009-09-04



Possible Viramune side effects / adverse reactions in 33 year old female

Reported by a pharmacist from United Kingdom on 2011-10-07

Patient: 33 year old female

Reactions: Rash, Abortion Induced

Suspect drug(s):
Abacavir Sulfate and Lamivudine
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication

Viramune
    Dosage: 200 mg
    Administration route: Oral
    Indication: HIV Infection
    Start date: 2007-08-16
    End date: 2007-08-30

Other drugs received by patient: Combivir; Efavirenz; Kaletra; Ziagen



See index of all Viramune side effect reports >>

Drug label data at the top of this Page last updated: 2008-07-09

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