What to Know About Viramune (Nevirapine)

Viramune (nevirapine) is an antiretroviral drug used to treat HIV in adults and some children. Approved by the Food and Drug Administration (FDA) in 1996, Viramune is included on the World Health Organization's List of Essential Medicines and is used in some countries to prevent the transmission of HIV from mother to child during pregnancy.

When used in combination antiretroviral therapy, Viramune can suppress the virus to undetectable levels and prevent disease progression.

Viramune was the first in a class of drugs called non-nucleoside transferase inhibitors (NNRTIs) that works by blocking an enzyme—called reverse transcriptase—that HIV uses to translate its viral RNA into DNA. Without the means to do so, HIV cannot "hijack" the genetic machinery of an infected cell and generate new copies of itself.

Viramune is available as a low-cost generic under the name nevirapine.

Uses

Viramune is approved for the treatment of HIV in adults and children when used in combination with at least two other antiretroviral drugs. Although Viramune was once granted preferred status for the first-line treatment of HIV, it is typically used today in second-line or subsequent therapies when other treatments fail.

Other Uses

Viramune has long been used in the prevention of mother-to-child transmission of HIV (PMTCT) since it was discovered in 1999 that a single dose could reduce the risk of transmission by 50%.

Viramune is no longer used for this purpose in the United States, even as an alternative to preferred first-line drugs. With that said, Viramune can be used in pregnant women who were already on the drug prior to conceiving.

Viramune is still used for PMTCT in the developing world, where it is given to newborns as prophylactic (preventative) therapy for six weeks following birth.

Before Taking

Even though Viramune remains an essential drug in the treatment of HIV, it is far more complicated to use compared to newer-generation antiretrovirals.

In fact, many of the more serious concerns involve people with stronger immune systems (defined as a CD4 count of 500 or more). These include potentially life-threatening hepatotoxicity (liver poisoning) as well as an increased risk of severe hypersensitivity reactions, particularly in women.

For this reason, Viramune is only approved for use in:

• HIV-positive men with a CD4 count under 400 cells/mm³
• HIV-positive women with a CD4 count under 250 cells/mm³

The same concerns do not apply to children with HIV.

Precautions and Contraindications

Viramune is metabolized by the liver and can cause hepatotoxicity in people with impaired liver function. People with moderate to severe liver dysfunction (as measured by a Child-Pugh score of B or C) should not use Viramune. This includes people with cirrhosis and advanced chronic hepatitis.

Viramune is also contraindicated for use in people with a prior hypersensitivity reaction to nevirapine. Even if the initial drug reaction was mild, re-challenging a person with Viramune can lead to a potentially life-threatening, whole-body allergy known as anaphylaxis.

Other NNRTIs

Viramune was the first NNRTI approved by the FDA but was soon followed by four other drugs of the same class:

• Sustiva (efavirenz), approved in 1998
• Intelence (etravirine), approved in 2008
• Edurant (rilpivirine), approved in 2011
• Pifeltro (doravirine), approved in 2018

An extended-release version of Viramune, called Viramune XR, was approved by the FDA in 2011, and reduces the daily pill burden to one tablet rather than two.

Dosage

Viramune is available as an oral tablet or liquid suspension, either in an immediate-release formulation (Viramune) or extended-release formulation (Viramune XR). Depending on your age and/or weight, you may be given:

• Viramune tablets: 200 milligrams (mg)
• Viramune XR tablets: 100 mg and 400 mg
• Viramune suspension: 50 mg per 5 milliliters (10 mg/mL)

To reduce the risk of a hypersensitivity reaction, Viramune is given at a reduced dose for the first 14 days before increasing to full strength. Referred to as the induction dose, it allows your body to adapt to the drug gradually and avoid an immune overreaction; this 14-day lead-in period must be strictly followed.

If a mild allergy occurs, you may be able to continue treatment at the lower dose for up to 28 days until the symptoms resolve. If they do not, your healthcare provider may need to change treatment.

Pediatric Dosage

The recommended dose for children varies by the body surface area (BSA). The BSA is based on the child's height and weight and is expressed in meters squared (m²). Based on the BSA, the dosage can be calculated in milligrams per meters squared (mg/m²).

As with adults, children are given an induction dose.

The total Viramune dose in children should never exceed 400 mg daily.

Viramune XR can be used in children age 6 and over if their BSA is over 1.17 m². Viramune XR should never be used in children under 6 years of age.

Modifications

People on hemodialysis for kidney failure should be given an additional dose of Viramune at the end of every dialysis session. This is because dialysis causes a rapid drop in the concentration of Viramune in the blood, something that the additional dose can compensate for.

How to Take and Store

Viramune can be taken with or without food. To maintain the optimal blood concentration, Viramune should be taken at the same time every day.

Viramune tablets should be swallowed whole; do not crush, split, or chew. If using Viramune suspension, shake well before use, and take it with a dosing spoon or syringe rather than a regular spoon.

Viramune tablets and suspension can be stored safely at room temperature, ideally between 59 to 86 degrees F (15 to 30 degrees C). Never use Viramune that has expired.

Side Effects

As with all drugs, Viramune may cause side effects. Most are mild to moderate and tend to resolve as your body adapts to treatment. Other side effects may be severe and even life-threatening.

Let your healthcare provider know if you experience any side effects after starting Viramune, particularly if they persist or worsen.

Common

The most common side effect of Viramune is rash. Most cases are mild to moderate (Grade 1/2) and do not require the discontinuation of treatment. According to premarket studies, around 13% of users experience rash, mostly on the trunk, arms, legs, or face.

Other common side effects include:

• Nausea
• Headache
• Fatigue
• Diarrhea
• Stomach pain
• Muscle aches

Severe

While most Viramine side effects are tolerable, others can be severe and require the immediate discontinuation of treatment. These side effects tend to occur within six weeks of starting treatment and often start mildly enough, only to progressively get worse.

Hepatotoxicity

Chief among the concerns is Viramune-induced hepatotoxicity, typically experienced within the six weeks of starting treatment. Symptoms may include:

• Fatigue
• A general feeling of unwellness
• Loss of appetite
• Nausea
• Jaundice (yellowing of the eyes and/or skin)
• Hepatomegaly (swelling of the liver)
• Abdominal tenderness
• Rash

In some cases, the hepatotoxic reaction can lead to serious and potentially life-threatening complications, including encephalopathy, rhabdomyolysis, and liver failure.

Severe Hypersensitivity

Many drug-induced rashes develop soon after Viramune is started and tend to be manageable. Those that develop weeks after starting Viramune are typically severe and can lead to potentially life-threatening reactions known as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

There is no way to know who might experience SJS or TEN after taking Viramune. Although there is evidence that genetics can predispose certain people to severe hypersensitivity, there are no tests that can conclusively predict this.

SJS and TEN are both considered medical emergencies.

Warnings and Interactions

In 2000, the FDA issued a black box warning advising consumers of the risk of Viramune-induced liver toxicity and skin reactions. According to the FDA, as many as 4% of users will develop drug-induced hepatitis, while 1.5% will develop a severe Grade 3/4 rash as a result of Viramune use.

There are no adequate and well-controlled studies of Viramune in pregnant women, however, animal studies have not shown a potential for fetal harm. According to ongoing surveillance from the Antiretroviral Pregnancy Register (APR), Viramune poses no greater risk of birth defects or miscarriage in women who take the drug compared to women in the general population.

Even so, it is important to speak with your healthcare provider about the potential risks of treatment if you are pregnant or planning to get pregnant.

Drug Interactions

Viramune is metabolized by an enzyme known as cytochrome P450 (CYP450). This is the same enzyme that many other drugs use for metabolization. If taken together, the competition for CYP450 can cause a drug's concentration to drop (reducing its efficacy) or rise (increasing the risk of toxicity).

In some cases, separating or adjusting the doses can compensate for this effect. In others, a drug substitution may be needed.

Let your healthcare provider know if you take any of the following drugs prior to starting Viramune:

• Antibiotics like clarithromycin
• Anticonvulsants like Klonopin (clonazepam) and Tegretol (carbamazepine)
• Antifungals like Diflucan (fluconazole), Nizoral (ketoconazole), and Sporonox (itraconazole)
• Blood thinners like Coumadin (warfarin)
• Calcium channel blockers like Procardia (nifedipine) and Verelan (verapamil)
• Cardiac arrhythmia drugs like Pacerone (amiodarone) and lidocaine
• Chemotherapy drugs like Cytoxan (cyclophosphamide)
• Immunosuppressants like Sandimmune (cyclosporine) and Protopic (tacrolimus)
• Opioid drugs like fentanyl and methadone
• Oral contraceptives like ethinyl estradiol and norethindrone
• Tuberculosis drugs like Mycobutin (rifabutin) and Rifadin (rifampin)