Viramune XR

Nevirapine can cause life-threatening effects on the liver. Call your doctor at once if you have any of these liver symptoms while taking nevirapine: skin rash, nausea, stomach pain, loss of appetite, low fever, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Nevirapine may also cause severe or life-threatening skin reactions. Contact your doctor at once if you have fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling. This type of reaction is a medical emergency.

Do not use this medication if you are allergic to nevirapine, or if you have moderate to severe liver disease.

The following drugs should not be used while you are taking nevirapine:

• atazanavir (Reyataz);
• efavirenz (Sustiva, Atripla);
• itraconazole (Sporanox);
• ketoconazole (Nizoral);
• rifampin (Rifater, Rifamate, Rifater); or
• St. John's wort.

To make sure you can safely take nevirapine, tell your doctor if you have any of these other conditions:

• skin problems;
• liver disease (or a history of hepatitis);
• kidney disease (or if you are on dialysis); or
• if you have ever taken delavirdine (Rescriptor) or efavirenz (Sustiva, Atripla) and they were not effective in treating your condition.

FDA pregnancy category B. Nevirapine is not expected to be harmful to an unborn baby. However, nevirapine may be more likely to cause liver damage in a pregnant woman. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection.

Nevirapine can make birth control pills less effective. Ask your doctor about using a non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while taking nevirapine.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of nevirapine on the baby.

Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

• Boehringer Ingelheim Pharmaceuticals, Inc.

Tell your doctor and pharmacist about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Viramune XR may affect the way other medicines work, and other medicines may affect how Viramune XR works.

You should not take Viramune XR if you also take:

• St. John's Wort.  St. John's Wort can lower the amount of Viramune XR in your body.
• efavirenz (Sustiva, Atripla). Efavirenz may cause you to have an increased chance of side effects.
• atazanavir (Reyataz)
• boceprevir (Victrelis)
• telaprevir (Incivek)
• lopinavir and ritonavir (Kaletra)
• fosamprenavir calcium (Lexiva)
• itraconazole (Sporanox)
• ketoconazole (Nizoral)
• rifampin (Rifadin, Rifamate, Rifater)
• Birth control pills. Birth control pills taken by mouth (oral contraceptives) and other hormone types of birth control may not work to prevent pregnancy. Talk with your doctor about other types of birth control that you can use to prevent pregnancy during treatment with Viramune XR.

Also tell your doctor if you take:

• clarithromycin (Biaxin)
• fluconazole (Diflucan)
• indinavir sulfate (Crixivan)
• methadone
• nelfinavir mesylate (Viracept)
• rifabutin (Mycobutin)
• warfarin (Coumadin, Jantoven)
• saquinavir mesylate (Invirase)

If you are not sure if you take a medicine above, ask your doctor or pharmacist. Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine.

Viramune XR is always taken in combination with other anti-HIV medications.

• Take Viramune XR exactly as your doctor tells you to take it. Do not change your dose unless your doctor tells you to.
• You should never take more than one form of Viramune at the same time. Talk to your doctor if you have any questions.
• Do not crush or chew Viramune XR tablets.
• You may take Viramune XR with or without food.
• Do not miss a dose of Viramune XR, because this could make HIV harder to treat. If you miss a dose of Viramune XR, take the missed dose as soon as you remember. If it is almost time for your next dose, do not take the missed dose, just take the next dose at your regular time. Do not take two doses at the same time.
• If you stop taking Viramune XR for more than 7 days, ask your doctor how much to take before you start taking it again. You may need to begin taking the Viramune XR starting dose again, which is taken 1 time each day for 14 days.

1. Starting Viramune XR tablets extended-release tablets) and this is the first time you are taking any form of Viramune:

• Your doctor should start you with 1 dose each day to lower your chance of getting a serious rash. It is important that you only take 1 dose of Viramune each day for the first 14 days.
• Call your doctor right away if you get a skin rash during the first 14 days of Viramune treatment and do not increase your dose to 2 times a day.
• You should never take your starting dose for longer than 28 days. If after 28 days you are still receiving this starting dose because you have a rash, you and your doctor should talk about prescribing another HIV medicine for you instead of Viramune.
• Do not increase your dose to 2 times a day if you have a rash.
• Day 15, you will take 1 Viramune XR tablet once daily. 

​2. Switching from Viramune immediate release tablets to Viramune XR (extended-release tablets):

• Adult patients already on a regimen of immediate release Viramune twice daily can be switched to Viramune XR 400 mg once daily without the 14-day lead-in period of immediate-release Viramune.

If you take too much Viramune XR, call your local Poison Control Center or seek emergency medical attention right away.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

The recommended dose for Viramune (nevirapine) is one 200 mg tablet daily for the first 14 days, followed by Viramune XR (nevirapine extended release tablets) (400 mg once daily). You must never take more than one form of Viramune at the same time.

The recommended oral dose for children 15 days of age and older is 150 mg/m2 once daily for 14 days followed by 150 mg/m2 twice daily thereafter. The total daily dose should not exceed 400 mg for any patient.

Nevirapine is an antiviral medicine that prevents human immunodeficiency virus (HIV) from multiplying in your body.

Nevirapine is used to treat HIV, the virus that can cause acquired immunodeficiency syndrome (AIDS). Nevirapine is not a cure for HIV or AIDS, and should not be used to prevent HIV.

Nevirapine oral solution (liquid) is for use in adults and children as young as 15 days old. Nevirapine extended-release tablets are for use in adults and children who are at least 6 years old.

Nevirapine may also be used for purposes not listed in this medication guide.

Get emergency medical help if you have signs of an allergic reaction: joint or muscle pain, fever, mouth sores, facial swelling, blistering skin rash, flu symptoms, swollen glands, feeling weak or tired, severe tingling or numbness, pain or burning when you urinate, swelling in your legs or feet, cough, chest pain, trouble breathing, or swelling in your lips, tongue, or throat.

Nevirapine can cause life-threatening effects on the liver, especially in women. Call your doctor at once if you have any of these liver symptoms while taking nevirapine: nausea, loss of appetite, upper stomach pain, tiredness, fever, unexplained muscle pain or weakness, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Nevirapine may also cause severe or life-threatening skin reactions. Stop taking this medicine and get emergency medical help if you have: a fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, and a red or purple skin rash that spreads and causes blistering and peeling. This type of reaction is a medical emergency.

Nevirapine may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with nevirapine. Tell your doctor if you have:

• signs of a new infection--fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

• chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

• cold sores, sores on your genital or anal area;

• rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

• trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

• swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Common side effects may include:

• skin rash; 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. You may report side effects to FDA at 1-800-FDA-1088.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach.
• You may see something that looks like the tablet in your stool. This is normal and not a cause for concern. If you have questions, talk with your doctor.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

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

General

Serious adverse effects can occur with nevirapine (the active ingredient contained in Viramune XR) 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.[Ref]

Dermatologic

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 reaction 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[Ref]

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 reaction 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.[Ref]

Hepatic

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 upper limit of normal [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[Ref]

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.[Ref]

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.[Ref]

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[Ref]

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, drug reaction with eosinophilia and systemic symptoms plus hepatitis, eosinophilia, granulocytopenia, lymphadenopathy, and/or renal dysfunction)[Ref]

Metabolic

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[Ref]

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.[Ref]

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[Ref]

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.[Ref]

Other

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.[Ref]

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)[Ref]

Nervous system

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

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.[Ref]

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.[Ref]

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[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

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

Psychiatric

Frequency not reported: Depression[Ref]

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