Note: This document contains side effect information about nevirapine. Some dosage forms listed on this page may not apply to the brand name Viramune XR.

Summary

Common side effects of Viramune XR include: nausea and skin rash. Other side effects include: severe dermatological reaction, abnormal hepatic function tests, fever, and headache. Continue reading for a comprehensive list of adverse effects.

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

Serious side effects of Viramune XR

Along with its needed effects, nevirapine (the active ingredient contained in Viramune XR) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking nevirapine:

Less common

• Decreased appetite
• swelling of the feet or lower legs

Rare

• Pain, numbness, or tingling of the hands, arms, legs, or feet
• sleepiness or unusual drowsiness
• stomach pain
• tingling, burning, or prickly sensations

Incidence not known

• Black, tarry stools
• blistering, peeling, or loosening of the skin
• bone pain
• chest pain
• chills
• clay-colored stools
• cough
• dark urine
• diarrhea
• difficulty swallowing
• dizziness
• fast heartbeat
• fever
• general tiredness and weakness
• headache
• hives, itching, skin rash
• joint or muscle pain
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or genitals
• loss of appetite
• lower back or side pain
• muscle cramps, spasms, pain, or stiffness
• nausea
• painful or difficult urination
• pale skin
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• red skin lesions, often with a purple center
• red, irritated eyes
• seizures
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• stomach pain, continuing
• swollen glands
• tightness in the chest
• trouble breathing
• troubled breathing with exertion
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting
• vomiting of blood
• yellow eyes and skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking nevirapine:

Symptoms of overdose

• Chest pain
• cough
• decrease in weight
• dizziness or lightheadedness
• feeling of constant movement of self or surroundings
• headache
• pain in the ankles or knees
• painful, red lumps under the skin, mostly on the legs
• sensation of spinning
• trouble sleeping

Other side effects of Viramune XR

Some side effects of nevirapine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Difficulty with moving
• pain in the joints

For Healthcare Professionals

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

General

Serious side effects have occurred with this drug. The most serious side effects have included hepatitis, hepatic failure, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and hypersensitivity reactions. Hepatitis/hepatic failure have been isolated or associated with signs of hypersensitivity which have included severe rash or rash accompanied by fever, general malaise, fatigue, muscle/joint aches, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction.

The most commonly reported side effects were rash, allergic reactions, nausea, abnormal liver function tests, headache, fatigue, somnolence, hepatitis, abdominal pain, vomiting, diarrhea, pyrexia, and myalgia.^[Ref]

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 an immediate-release formulation has been shown to reduce the frequency of rash.

During clinical trials, grade 1 and 2 rashes were reported in 13% of patients using an immediate-release formulation during the first 6 weeks of therapy; grade 3 and 4 rashes were reported in 2% of patients using an immediate-release formulation.

During 1 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, DRESS) in 4% and 5% of patients using the immediate-release and extended-release formulations, respectively. DRESS was characterized by rash with constitutional symptoms (e.g., fever, arthralgia, myalgia, lymphadenopathy) plus visceral involvement (e.g., hepatitis, eosinophilia, granulocytopenia, renal dysfunction).

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.

Rash was reported in about half of patients with symptomatic hepatic side effects.^[Ref]

Very common (10% or more): Rash (including maculopapular erythematous cutaneous eruptions, with or without pruritus)

Common (1% to 10%): Moderate/severe rash (including rash, maculopapular rash, erythema nodosum, erythematous rash, papular rash, skin reaction, Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms [DRESS])

Uncommon (0.1% to 1%): Toxic epidermal necrolysis, urticaria, angioedema

Frequency not reported: Severe and life-threatening skin reactions (including fatal cases), allergic dermatitis^[Ref]

Other

Very common (10% or more): Decreased phosphate (up to 38%), elevated cholesterol (up to 19%), elevated low-density lipoprotein (LDL) (up to 15%)

Common (1% to 10%): Fatigue, pyrexia

Frequency not reported: Asthenia, influenza-like symptoms, elevated alkaline phosphatase, elevated total cholesterol, elevated triglycerides

Postmarketing reports: Fever, drug withdrawal (as a result of drug interactions), decreased serum phosphorus^[Ref]

Grade 2 decreased phosphate was reported in 38% and 33% of patients using the immediate-release and extended-release formulations, respectively. Grade 3 decreased phosphate was reported in 6% and 7% of patients using the immediate-release and extended-release formulations, respectively. 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% and 19% of patients using the immediate-release and extended-release formulations, respectively. Grade 3 elevated cholesterol (greater than 300 mg/dL) was reported in 4% and 3% of patients using the immediate-release and extended-release formulations, respectively.

The incidence of grade 2 elevated LDL (160 to 190 mg/dL) was 15% with each formulation. The incidence of grade 3 elevated LDL (greater than 190 mg/dL) was 5% with each formulation.

During 1 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.^[Ref]

Hepatic

Very common (10% or more): Elevated ALT (up to 14%), symptomatic hepatic events (up to 11%)

Common (1% to 10%): Elevated AST, asymptomatic transaminase elevations (AST/ALT), clinical hepatitis (including hepatitis, hepatotoxicity, acute hepatitis, liver disorder, toxic hepatitis, hepatic failure, jaundice), elevated bilirubin, asymptomatic elevations in GGT, abnormal liver function tests (included increased ALT, increased transaminases, increased AST, increased GGT, increased hepatic enzyme, hypertransaminasemia)

Frequency not reported: Liver enzyme abnormalities (AST, ALT, GGT), 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), hepatic-renal failure syndromes

Postmarketing reports: Jaundice, fulminant and cholestatic hepatitis, hepatic necrosis, hepatic failure^[Ref]

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

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

In clinical trials, symptomatic hepatic events (regardless of severity) were reported in up to 11% of patients. Rash was reported in about half of patients with symptomatic hepatic side effects. Fever and influenza-like symptoms accompanied some hepatic events.

In 1 study, after 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 1 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% and 2% of patients using the immediate-release and extended-release formulations, respectively.

Asymptomatic transaminase elevations (AST/ALT greater than 5 x ULN) have been reported in up to 9% of patients. Elevated bilirubin (greater than 2.5 mg/dL) has been reported in 2% of patients.

Liver enzyme abnormalities (AST, ALT, GGT) occurred more often in patients using this drug than in controls.

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/symptoms of hepatitis (including fatigue, malaise, anorexia, nausea, jaundice, liver tenderness/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 this drug for postexposure prophylaxis have reported serious hepatotoxicity, including hepatic failure.^[Ref]

Hematologic

Very common (10% or more): Decreased neutrophils (up to 13%)

Common (1% to 10%): Decreased hemoglobin, granulocytopenia

Uncommon (0.1% to 1%): Decreased platelets

Frequency not reported: Thrombocytopenia

Postmarketing reports: Anemia, neutropenia, eosinophilia^[Ref]

Decreased neutrophils (less than 750/mm3), hemoglobin (less than 8 g/dL), and platelets (less than 50,000/mm3) have been reported in up to 13%, up to 3%, and up to 1% of patients, respectively.

Grade 2 decreased neutrophils (750 to 999/mm3) was reported in 7% and 4% of patients using the immediate-release and extended-release formulations, respectively. The incidence of grade 3 decreased neutrophils (500 to 749/mm3) was 2% with each formulation. The incidence of grade 4 decreased neutrophils (less than 500/mm3) was 1% with each formulation.^[Ref]

Hypersensitivity

Common (1% to 10%): Hypersensitivity (including anaphylactic reaction, angioedema, urticaria)

Uncommon (0.1% to 1%): Anaphylactic reaction

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/joint aches, general malaise, fatigue, or significant hepatic abnormalities, drug reaction with eosinophilia and systemic symptoms, plus hepatitis, eosinophilia, granulocytopenia, lymphadenopathy, and/or renal dysfunction)^[Ref]

Gastrointestinal

Common (1% to 10%): Nausea, elevated amylase, diarrhea, abdominal pain

Frequency not reported: Pancreatitis

Postmarketing reports: Vomiting^[Ref]

During 1 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 x ULN) was reported in 4% and 5% of patients using the immediate-release and extended-release formulations, respectively. Grade 3 elevated amylase (2.1 to 5 x ULN) was reported in 4% and 2% of patients using the immediate-release and extended-release formulations, respectively. Grade 4 elevated amylase (greater than 5 x ULN) was reported in less than 1% of patients using the extended-release formulation.^[Ref]

Nervous system

During 1 study, side effects of at least moderate intensity included headache; incidence was 4% with each formulation.^[Ref]

Common (1% to 10%): Headache

Frequency not reported: Neuropathy, peripheral neuropathy

Postmarketing reports: Somnolence, paresthesia^[Ref]

Musculoskeletal

During 1 study, side effects of at least moderate intensity included arthralgia; incidence was 2% with each formulation.^[Ref]

Common (1% to 10%): Arthralgia, myalgia

Frequency not reported: Arthromyalgia, arthritis

Postmarketing reports: Rhabdomyolysis (associated with skin and/or liver reactions), arthralgia

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis^[Ref]

Cardiovascular

Uncommon (0.1% to 1%): Increased blood pressure

Metabolic

Frequency not reported: Hyperlactatemia, unspecified metabolic alterations, anorexia, acute porphyria

Postmarketing reports: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")^[Ref]

Immunologic

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

Respiratory

Frequency not reported: Dry cough, dyspnea, interstitial pulmonary infiltration^[Ref]

Psychiatric

Frequency not reported: Depression^[Ref]