Nevirapine Side Effects

Some side effects of nevirapine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to nevirapine: oral suspension, oral tablet, oral tablet extended release

Get emergency medical help if you have any of these signs of an allergic reaction while taking nevirapine: tired feeling, joint or muscle pain, muscle weakness, skin rash, bruising, severe tingling, numbness, mouth sores, trouble breathing, or swelling of your face, lips, tongue, or throat.

Stop taking nevirapine and call your doctor at once if you have a serious side effect such as:

• nausea, pain in your upper stomach, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• fever, chills, body aches, flu symptoms;

• any other signs of new infection; or

• the first sign of any skin rash, no matter how mild.

Less serious side effects of nevirapine may include:

• mild nausea, vomiting, diarrhea, or stomach pain;

• muscle pain;

• headache, tired feeling; or

• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

For Healthcare Professionals

Applies to nevirapine: oral suspension, oral tablet, oral tablet extended release

General

Serious adverse effects can occur with nevirapine. The most serious side effects have included 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.

The first 18 weeks of therapy with nevirapine are a critical period during which it is essential that patients be monitored intensively to detect potentially life-threatening hepatotoxicity or skin reactions. Nevirapine should not be restarted following clinical hepatitis, or transaminase elevations combined with rash or other systemic symptoms, or following severe skin rash or hypersensitivity reactions.

Side effects reported during postmarketing experience were associated with use of the immediate-release formulation.

Dermatologic

The most common clinical toxicity was rash. Rashes were usually mild to moderate, maculopapular erythematous cutaneous eruptions, with or without pruritus, located on the face, trunk, and extremities. Rash has occurred most often during the first 6 weeks of therapy. Utilization of the 14-day lead-in period with immediate-release nevirapine has been shown to reduce the frequency of rash.

During clinical trials, Grade 1 and 2 rashes were reported in 13% of patients taking immediate-release nevirapine during the first 6 weeks of therapy. Grade 3 and 4 rashes were reported in 2% of immediate-release nevirapine-treated patients.

During one study, side effects of at least moderate intensity included rash (including rash, maculopapular rash, erythema nodosum, erythematous rash, papular rash, skin reaction, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms) in 4% of patients using the immediate-release formulation and 5% of patients using the extended-release formulation.

Severe and life-threatening skin reactions, including fatal cases, have been reported. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction.

Women tended to be at greater risk of nevirapine-associated rash.

Rash was reported in about half of patients with symptomatic hepatic side effects.

Very common (10% or more): Rash (including maculopapular erythematous cutaneous eruptions, with or without pruritus)
Common (1% to 10%): Moderate or severe rash (including rash, maculopapular rash, erythema nodosum, erythematous rash, papular rash, skin reaction, Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms; up to 7%)
Frequency not reported: Severe and life-threatening skin reactions (including fatal cases), toxic epidermal necrolysis, allergic dermatitis

Hepatic

Risk of symptomatic hepatic events (regardless of severity) was greatest in the first 6 weeks and continued to be greater in the nevirapine groups compared to controls through 18 weeks of therapy.

Female gender and higher CD4+ cell counts at the start of therapy place patients at increased risk of hepatic events (including potentially fatal events). Women with CD4+ cell counts greater than 250 cells/mm3 (including pregnant women using nevirapine with other antiretrovirals to treat HIV-1 infection) are at greatest risk. However, nevirapine-associated hepatotoxicity can develop in both genders, all CD4+ cell counts, and at any time during therapy. Coinfection with hepatitis B or C and/or increased transaminases at the start of nevirapine therapy are associated with a greater risk of later symptomatic events (6 weeks or more after starting nevirapine) and asymptomatic increases in AST or ALT.

Rash was reported in about half of patients with symptomatic hepatic side effects. Fever and influenza-like symptoms accompanied some hepatic events.

Following the lead-in period, the incidence of any hepatic event was 9% with the immediate-release formulation and 6% with the extended-release formulation. Symptomatic hepatic events (anorexia, jaundice, vomiting) were reported in 3% and 2% of patients using the immediate-release and extended-release formulations, respectively. The incidence of Grade 3 or 4 ALT/AST elevation was 8% with each formulation.

During one study, side effects of at least moderate intensity included clinical hepatitis (including hepatitis, hepatotoxicity, acute hepatitis, liver disorder, toxic hepatitis, hepatic failure, jaundice) in 4% of patients using the immediate-release formulation and 2% of patients using the extended-release formulation.

In controlled studies, liver enzyme abnormalities (AST, ALT) occurred more frequently in patients receiving nevirapine.

Elevated SGPT/ALT (greater than 250 units/L: up to 14%) has been reported with the immediate-release formulation. Grade 2 elevated SGPT/ALT (2.6 to 5 times ULN) was reported in 13% of patients using the immediate-release formulation and 10% of patients using the extended-release formulation. Grade 3 elevated SGPT/ALT (5.1 to 10 times ULN) was reported in 3% of patients using the immediate-release formulation and 4% of patients using the extended-release formulation. Grade 4 elevated SGPT/ALT (greater than 10 times ULN) was reported in 4% of patients using the immediate-release formulation and 2% of patients using the extended-release formulation.

Elevated SGOT/AST (greater than 250 units/L: up to 8%) has been reported with the immediate-release formulation. Grade 2 elevated SGOT/AST (2.6 to 5 times ULN) was reported in 9% of patients using the immediate-release formulation and 7% of patients using the extended-release formulation. Grade 3 elevated SGOT/AST (5.1 to 10 times ULN) was reported in 2% of patients using the immediate-release formulation and 3% of patients using the extended-release formulation. Grade 4 elevated SGOT/AST (greater than 10 times ULN) was reported in 2% of patients using the immediate-release formulation and 2% of patients using the extended-release formulation.

Severe, life-threatening, and in some cases fatal, hepatotoxicity (including fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure) has been reported. In some cases, patients presented with nonspecific prodromal signs or symptoms of hepatitis (including fatigue, malaise, anorexia, nausea, jaundice, liver tenderness or hepatomegaly, with or without initially abnormal transaminase levels). Some events (particularly those with rash and other symptoms) progressed to hepatic failure with transaminase elevation, with or without hyperbilirubinemia, hepatic encephalopathy, prolonged partial thromboplastin time, or eosinophilia. Patients without HIV using nevirapine for postexposure prophylaxis have reported serious hepatotoxicity, including hepatic failure.

Very common (10% or more): Elevated SGPT/ALT (up to 14%), symptomatic hepatic events (regardless of severity: up to 11%)
Common (1% to 10%): Elevated SGOT/AST (up to 9%), asymptomatic transaminase elevations (AST or ALT greater than 5 times ULN: up to 9%), clinical hepatitis (including hepatitis, hepatotoxicity, acute hepatitis, liver disorder, toxic hepatitis, hepatic failure, jaundice; up to 4%), elevated bilirubin (greater than 2.5 mg/dL: 2%), asymptomatic elevations in gamma-glutamyltransferase
Frequency not reported: Liver enzyme abnormalities (AST, ALT), elevated alkaline phosphatase, severe and life-threatening hepatotoxicity (including fatal cases), progression to hepatic failure (with transaminase elevation, with or without hyperbilirubinemia, hepatic encephalopathy, prolonged partial thromboplastin time, or eosinophilia)
Postmarketing reports: Jaundice, fulminant and cholestatic hepatitis, hepatic necrosis, hepatic failure

Hematologic

Grade 2 decreased neutrophils (750 to 999/mm3) was reported in 7% of patients using the immediate-release formulation and 4% of patients using the extended-release formulation. Grade 3 decreased neutrophils (500 to 749/mm3) was reported in 2% of patients using the immediate-release formulation and 2% of patients using the extended-release formulation. Grade 4 decreased neutrophils (less than 500/mm3) was reported in 1% of patients using the immediate-release formulation and 1% of patients using the extended-release formulation.

Very common (10% or more): Decreased neutrophils (less than 750/mm3: up to 13%)
Common (1% to 10%): Decreased hemoglobin (less than 8 g/dL: up to 3%), granulocytopenia (moderate or severe intensity: up to 2%)
Uncommon (0.1% to 1%): Decreased platelets (less than 50,000/mm3: up to 1%)
Postmarketing reports: Anemia, neutropenia, eosinophilia

Hypersensitivity

Postmarketing reports: Allergic reactions (including anaphylaxis, angioedema, bullous eruptions, ulcerative stomatitis, urticaria), hypersensitivity syndrome, 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 plus hepatitis, eosinophilia, granulocytopenia, lymphadenopathy, and/or renal dysfunction)

Metabolic

Grade 2 decreased phosphate was reported in 38% of patients using the immediate-release formulation and 33% of patients using the extended-release formulation. Grade 3 decreased phosphate was reported in 6% of patients using the immediate-release formulation and 7% of patients using the extended-release formulation. Grade 4 decreased phosphate was reported in less than 1% of patients using the immediate-release formulation.

Grade 2 elevated cholesterol (240 to 300 mg/dL) was reported in 18% of patients using the immediate-release formulation and 19% of patients using the extended-release formulation. Grade 3 elevated cholesterol (greater than 300 mg/dL) was reported in 4% of patients using the immediate-release formulation and 3% of patients using the extended-release formulation.

Grade 2 elevated LDL (160 to 190 mg/dL) was reported in 15% of patients using the immediate-release formulation and 15% of patients using the extended-release formulation. Grade 3 elevated LDL (greater than 190 mg/dL) was reported in 5% of patients using the immediate-release formulation and 5% of patients using the extended-release formulation.

Very common (10% or more): Decreased phosphate (up to 38%), elevated cholesterol (up to 19%), elevated LDL (up to 15%)
Frequency not reported: Hyperlactatemia, unspecified metabolic alterations, elevated total cholesterol, elevated triglycerides, elevated alkaline phosphatase, acute porphyria
Postmarketing reports: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), decreased serum phosphorus

Gastrointestinal

Common (1% to 10%): Nausea (moderate or severe intensity: up to 9%), elevated amylase (up to 5%), diarrhea (moderate or severe intensity: up to 4%), abdominal pain (moderate or severe intensity: up to 3%)
Frequency not reported: Anorexia
Postmarketing reports: Vomiting

During one study, side effects of at least moderate intensity included diarrhea (immediate-release: 4%; extended-release: 4%), abdominal pain (immediate-release: 2%; extended-release: 3%), and nausea (immediate-release: 2%; extended-release: 1%).

Grade 2 elevated amylase (1.6 to 2 times ULN) was reported in 4% of patients using the immediate-release formulation and 5% of patients using the extended-release formulation. Grade 3 elevated amylase (2.1 to 5 times ULN) was reported in 4% of patients using the immediate-release formulation and 2% of patients using the extended-release formulation. Grade 4 elevated amylase (greater than 5 times ULN) was reported in less than 1% of patients using the extended-release formulation.

Other

Common (1% to 10%): Fatigue (moderate or severe intensity: up to 5%), pyrexia (moderate or severe intensity: up to 2%)
Frequency not reported: Fever, asthenia, influenza-like symptoms
Postmarketing reports: Fever, drug withdrawal (as a result of drug interactions)

During one study, side effects of at least moderate intensity included fatigue (immediate-release: 2%; extended-release: 2%) and pyrexia (immediate-release: 2%; extended-release: 1%).

Fever and influenza-like symptoms accompanied some hepatic events.

Nervous system

Common (1% to 10%): Headache (moderate or severe intensity: up to 4%)
Frequency not reported: Neuropathy
Postmarketing reports: Somnolence, paresthesia

During one study, side effects of at least moderate intensity included headache in 4% of patients using the immediate-release formulation and 4% of patients using the extended-release formulation.

Musculoskeletal

During one study, side effects of at least moderate intensity included arthralgia in 2% of patients using the immediate-release formulation and 2% of patients using the extended-release formulation.

Common (1% to 10%): Arthralgia (moderate or severe intensity: 2%)
Uncommon (0.1% to 1%): Myalgia (moderate or severe intensity: up to 1%)
Frequency not reported: Arthromyalgia, arthritis
Postmarketing reports: Rhabdomyolysis associated with skin and/or liver reactions, arthralgia

Immunologic

Frequency not reported: Immune reconstitution syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, and Guillain-Barre syndrome)

Respiratory

Rare (less than 0.1%): Dry cough, dyspnea, interstitial pulmonary infiltration

Psychiatric

Frequency not reported: Depression

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