What to Know About Epzicom (Abacavir + Lamivudine)

Epzicom is a combination antiretroviral drug used to treat human immunodeficiency virus (HIV) infection in adults and some children. It is taken by mouth in tablet form.

It contains two antiretroviral agents called abacavir (sold under the brand name Ziagen) and lamivudine (sold under the brand name Epivir). Epzicom is taken in combination with at least one other antiretroviral drug to ensure complete viral suppression.

Epzicom was approved for use by the Food and Drug Administration (FDA) in 2004. Despite its ease of use and proven efficacy, Epzicom may cause severe and potentially life-threatening side effects in some people.

Several generic versions of Epzicom are available in the United States, sold simply as "abacavir + lamivudine" or "abacavir/lamivudine."

Uses

The two antiretroviral agents in Epzicom belong to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). They work by blocking a stage of HIV's life cycle and, by doing so, prevent the virus from replicating, or making copies of itself.

When used in combination with other antiretroviral drugs, Epzicom can reduce the viral load to undetectable levels. NRTIs block an enzyme called reverse transcriptase that the virus uses to translate its viral RNA into DNA, the genetic coding that is then integrated into the host cell's nucleus to turn into an HIV-producing factory.

NRTIs were the first class of drugs able to inhibit the replication cycle of the virus. They continue to be an important part of combination antiretroviral therapy.

The FDA has approved Epzicom for use in adults as well as children who weigh at least 55 pounds. Because Epzicom comes as a fixed-dose tablet, it cannot be used in people whose abacavir or lamivudine dose needs to be adjusted. For these people, the drugs would need to be prescribed individually.

There are no off-label uses for Epzicom.

Before Taking

Epzicom may be used as a first-line treatment of HIV, although it is more often used as an alternative to preferred first-line agents. If abacavir and lamivudine are used, they are more likely to be prescribed in the three-in-one HIV drug Triumeq (abacavir + dolutegravir + lamivudine).

Pretreatment Evaluation

When you are diagnosed with HIV or your treatment of it has changed, your healthcare provider will order a series of tests to evaluate the characteristics of your virus. HIV is ultimately not one virus; rather, it consists of a multitude of genetic variants within the "viral pool," some of which may be drug resistant.

Because drug resistance can be transmitted—that is, passed from one person to the next—drug resistance testing is crucial to determine which drugs will be most effective in fighting the virus in its current form within your body.

The tests include:

• Genetic resistance testing: Also known as genotyping or genotypic testing, this blood test detects genetic mutations that are known to confer resistance.
• Phenotypic testing: More commonly used after treatment failure, this test, also known as phenotyping, directly exposes the virus to all available antiretroviral drugs to see which are best able to fully suppress the virus.

Precautions and Contraindications

There are certain instances in which Epzicom is avoided, or contraindicated, for use. This may be related to abacavir, lamivudine, or both.

As well as being avoided for use in people who test positive for the HLA-B*5701 allele, Epzicom is contraindicated for use in anyone who has had a prior hypersensitive reaction to abacavir or lamivudine. Some hypersensitive reactions, particularly those related to abacavir, can lead to anaphylaxis, multi-organ failure, and death.

In addition, lamivudine can cause potentially severe liver complications, including liver failure, in people with preexisting liver disease. Because the dosage of each drug cannot be adjusted with fixed-dose combination drugs, people with moderate to severe liver disease (Child-Pugh score 7-15) should never take Epzicom.

Because Epzicom is excreted via the kidneys as well as the liver, people with severe kidney impairment (defined as a creatinine clearance of less than 50 milliliters per minute) should also avoid the drug.

Other NRTIs

There are three other antiretroviral drugs classified as nucleoside reverse transcriptase inhibitors, as well as six fixed-dose combination drugs containing abacavir and/or lamivudine:

• Emtriva (lamivudine)
• Combivir (lamivudine + zidovudine)
• Delstrigo (doravirine + lamivudine + tenofovir disproxil fumarate)
• Dovato (lamivudine + dolutegravir)
• Retrovir (AZT, zidovudine)
• Symfi (efavirenz + lamivudine + tenofovir disoproxil fumarate)
• Symfi Lo (efavirenz + lamivudine + tenofovir disoproxil fumarate)
• Triumeq (abacavir + dolutegravir + lamivudine)
• Viread (tenofovir disoproxil fumarate)

Dosage

Each Epzicom tablet contains 600 milligrams (mg) of abacavir and 200 mg of lamivudine. The tablets are oblong, orange, film coated, and embossed with "GS FC2" on one side only.

The recommended dosage of Epzicom is as follows:

• Adults: One tablet daily with or without food
• Children 55 pounds or over: One tablet daily with or without food

Epzicom is never used on its own. It must be used in combination with at least one other antiretroviral drug of another class. For first-line therapies, this typically involves an integrase inhibitor like Tivicay (dolutegravir).

How to Take and Store

Epzicom must be taken daily to ensure complete viral suppression. Skipping or missing doses can decrease the therapeutic concentration of the drug in the bloodstream. This not only allows the viral population to grow but may also speed the development of drug resistance.

Food does not affect the concentration of Epizcom in the blood. Crushing or splitting the tablet, however, can affect the absorption rate and should be avoided. If you or your child find it difficult to swallow tablets, let your healthcare provider know so that alternative forms of the medications can be prescribed.

Epzicom can be stored safely at temperatures of around 77 F. Although it is fine to expose the drug to higher temperatures for a short period of time, prolonged exposure should be avoided. This includes storing the tablets on a sunny windowsill or in your glove compartment.

It is best to keep the tablets in their original light-resistant container in a cool, dry cabinet or drawer. Always keep track of the expiration date and avoid taking tablets that have expired or deteriorated.

Seek emergency care in the event of an overdose, which can lead to a potentially severe complication known as lactic acidosis or other potential harms.

Side Effects

All drugs have side effects, and most of those associated with Epzicom tend to be mild and transient, or passing quickly. In rare instances, there may be serious side effects, some of which may develop soon after treatment is started and others of which occur as a result of prolonged use.

Common Side Effects

Abacavir and lamivudine are independently associated with a number of common side effects, some of which overlap. The most common, occurring in around 5%–10% of users, include:

Many of these side effects are short-lived and tend to resolve as your body adapts to treatment. If side effects persist or become intolerable, let your healthcare provider know. However, never stop treatment without first speaking with your healthcare provider.

Severe Side Effects

There are several side effects associated with Epzicom that can be severe and even life-threatening. Although rare, they may require the immediate termination of the drug and, in some cases, emergency medical intervention. These include:

• Abacavir hypersensitivity: Typically occurring within six weeks of starting treatment, symptoms include fever, rash, nausea, vomiting, diarrhea, abdominal pain, fatigue, and pneumonia-like symptoms. If left untreated, symptoms can worsen and lead to death.
• Lipodystrophy: The long-term use of NRTIs has been associated with lipodystrophy, the abnormal redistribution of body fat. Symptoms range from mild to severe and tend to be progressive.
• Lactic acidosis: Abnormal buildup of lactic acid is less common with abacavir and lamivudine than older-generation antiretrovirals. Yet it still can occur and appears as stomach pain, loss of appetite, diarrhea, muscle cramps, unusual sleepiness, and rapid, shallow breathing (tachypnea). In severe cases, lactic acidosis carries a 50% risk of death.
• Hepatomegaly: Epzicom can cause abnormal enlargement of the liver in people coinfected with HIV and hepatitis C. In addition to abdominal swelling, other symptoms include red hands, enlarged blood vessels beneath the skin's surface, and the yellowing of the skin and eyes (jaundice).

Warnings and Interactions

The FDA has issued several black box warnings advising consumers and healthcare professionals about potentially serious risks associated with Epzicom. The warnings are based on prior experience with abacavir and lamivudine among people with HIV over the course of 20-plus years.

The black box warnings include abacavir hypersensitivity in people with the HLA-B*5701 allele, lactic acidosis, and severe hepatomegaly. In addition, the FDA warns that Epzicom may cause a worsening of liver-related symptoms in people infected with both HIV and hepatitis B.

Epzicom is generally considered safe during pregnancy. Although animal studies have shown a potential for fetal harm, data from the Antiretroviral Pregnancy Registry have shown no difference in the rate of miscarriage and birth defects in mothers who use abacavir or lamivudine versus women in the general population.

Even so, people who are pregnant or able to become pregnant should speak with their healthcare providers to fully understand the benefits and risks of Epzicom. Mothers with HIV are also advised to avoid breastfeeding to reduce the risk of transmission to their baby.

Drug-Drug Interactions

There are several drugs that can interact with abacavir or lamivudine. In some cases, these interactions may increase or decrease the concentration of abacavir or lamivudine; in others, it may increase or decrease the concentration of the coadministered drug.

Abacavir

Alcohol can decrease the rate at which abacavir is excreted from the body. This can lead to increased blood concentrations and, in turn, an increased risk of side effects, including headache, loss of appetite, and nausea. Reduced alcohol intake can mitigate this effect.

On the flip side, abacavir can reduce the concentration of methadone in people undergoing methadone-maintenance therapy for opioid addiction. With that said, the dose used in Epzicom rarely requires an adjustment of the methadone dose.

Lamivudine

The artificial sweetener sorbitol can reduce the concentration of lamivudine in the bloodstream. The effect appears to be dose dependent, with a higher intake of sorbitol translating to a greater loss of lamivudine in the bloodstream. Whenever possible, avoid taking sorbitol (or laxatives containing sorbitol) at the same time as Epzicom.

The combination antibiotic trimethoprim and sulfamethoxazole (TMP-SMX) may also increase the concentration of lamivudine, although usually not to a level considered problematic.

Other commonly used drugs can increase lamivudine levels by inhibiting compounds called organic cation transporters (OCTs) that aid with the excretion of substances through the kidneys. Examples include:

• Benadryl (diphenhydramine)
• Glucophage (metformin)
• Prozac (fluoxetine)
• Tagamet (cimetidine)
• Verelan (verapamil)
• Zovirax (acyclovir)

The interaction between lamivudine and OCT inhibitors may or may not be significant. Even so, some healthcare providers may advise you to separate doses by several hours, while others may recommend a change of the accompanying drug.