Lamivudine and Zidovudine

Lamivudine and zidovudine is an antiviral combination used to treat HIV-1 infection. It is always used as part of a larger antiretroviral regimen — not alone.

• Combivir (lamivudine and zidovudine) tablet is approved for the treatment of HIV-1 infection in adults and adolescents weighing at least 30 kg, in combination with other antiretroviral medicines.
• Combivir tablet is also approved for pediatric patients weighing at least 30 kg who are able to swallow tablets, in combination with other antiretroviral agents.
• Lamivudine and zidovudine tablets (generic) are approved for the treatment of HIV-1 infection in adults, adolescents, and eligible pediatric patients weighing at least 30 kg, always alongside other antiretrovirals.

This tablet combines two antivirals — lamivudine and zidovudine — that both belong to a class called nucleoside analogue reverse transcriptase inhibitors (NRTIs). HIV needs an enzyme called reverse transcriptase to make copies of itself inside your cells. Lamivudine and zidovudine each mimic the building blocks HIV normally uses, and when the virus incorporates them, the copying process is halted. This slows HIV replication and helps keep viral levels low in the blood.

Because this medicine targets a specific step in HIV's life cycle, it must be combined with other antiretroviral drugs that act at different steps to provide effective, durable HIV control.

Lamivudine and zidovudine tablets are taken by mouth twice daily — typically once in the morning and once in the evening. They can be taken with or without food. This is a fixed-dose tablet, meaning the amounts of each drug are set and cannot be adjusted.

• Adults, adolescents, and children weighing at least 30 kg: one tablet twice daily.
• Children must be able to reliably swallow a tablet — if not, separate liquid formulations should be prescribed instead.
• This tablet is not recommended for people with significant kidney or liver impairment, or those who need a dose adjustment for any reason.

Always follow your prescriber's instructions exactly, and do not stop taking this medicine without talking to your doctor first.

The most common side effects reported in clinical studies include:

• Headache
• Nausea
• Tiredness or general malaise (feeling unwell)
• Diarrhea
• Nasal symptoms (runny or stuffy nose)
• Cough
• Muscle aches, joint pain, or myalgia
• Trouble sleeping

Serious reactions — including severe anemia, dangerously low white blood cell counts, muscle disease (myopathy), lactic acidosis, and severe liver problems — require prompt medical attention. If you notice unusual tiredness, pale skin, muscle weakness, stomach pain, difficulty breathing, or yellowing of the skin or eyes, contact your doctor immediately or go to an emergency room.

• Blood cell toxicity: Zidovudine can cause severe drops in red blood cells (anemia) and white blood cells (neutropenia), especially in advanced HIV. Blood counts should be checked regularly throughout treatment.
• Muscle disease (myopathy): Long-term use of zidovudine has been linked to muscle weakness and pain. Tell your doctor about any new or worsening muscle symptoms.
• Lactic acidosis and liver swelling: Both drugs have been associated with a rare but potentially fatal buildup of lactic acid in the blood and severe liver enlargement with fat deposits. Risk appears higher in women and people with obesity or prolonged nucleoside use. Stop the medicine and seek emergency care if you develop rapid breathing, stomach pain, vomiting, or unusual weakness.
• Hepatitis B flare: If you have both HIV-1 and hepatitis B and you stop this medicine, hepatitis B can suddenly worsen — sometimes severely. Liver function must be monitored closely for months after stopping.
• Pancreatitis: Use with caution in children with a history of pancreatitis. Stop the medicine immediately if signs of pancreatitis appear.
• Immune reconstitution syndrome: As your immune system recovers on HIV treatment, it may react to hidden infections (such as tuberculosis or cytomegalovirus), causing new inflammation. This is a known part of recovery but should be evaluated by your doctor.
• Fat redistribution: Changes in body fat distribution (such as belly fat increase or facial fat loss) have been reported with antiretroviral therapy, though a direct cause has not been established.

Several medicines can interact dangerously with lamivudine and zidovudine — always tell your doctor and pharmacist about everything you take:

• Stavudine: Directly opposes how zidovudine works — avoid this combination.
• Zalcitabine: Can block the activation of both drugs inside cells — avoid together.
• Doxorubicin (chemotherapy): May reduce zidovudine's effectiveness — avoid if possible.
• Ribavirin: Can interfere with how both lamivudine and zidovudine work, and the combination raises the risk of severe anemia and liver damage in people with HIV/HCV co-infection.
• Interferon-alfa: When used with ribavirin in HIV/HCV co-infected patients, adds serious risk of liver decompensation (liver failure) and worsened blood counts.
• Ganciclovir and other bone marrow-suppressing drugs: Increase the risk of dangerous drops in blood cell counts when used with zidovudine.
• Other lamivudine-, zidovudine-, or emtricitabine-containing products: Must not be taken at the same time — this would result in dangerous double-dosing of the same active ingredients.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Do not take this medicine if you have ever had a serious allergic reaction (such as anaphylaxis or Stevens-Johnson syndrome) to lamivudine or zidovudine.
• Tell your doctor if you have kidney disease — this fixed-dose tablet cannot be adjusted and is not recommended if your kidney clearance (creatinine clearance) is below a certain threshold.
• Tell your doctor if you have liver disease or hepatitis B co-infection — close liver monitoring is essential, especially if you ever need to stop treatment.
• Tell your doctor if you are pregnant or trying to become pregnant — your doctor can enroll you in the Antiretroviral Pregnancy Registry (APR) to track outcomes. Both drugs cross the placenta.
• Women with HIV should not breastfeed, as HIV can be passed to the baby through breast milk.
• Children must weigh at least 30 kg and be able to reliably swallow tablets — younger or smaller children should use separate liquid formulations.
• Tell your doctor if you or your child has a history of pancreatitis or significant risk factors for it.
• Share a complete list of all your medicines — including over-the-counter drugs and supplements — to catch any dangerous interactions before starting.

There is no specific antidote for an overdose of lamivudine and zidovudine. In reported cases of zidovudine overdose, the most common symptoms were nausea and vomiting; other reported effects included headache, dizziness, drowsiness, and confusion — and all patients in reported cases recovered. If you suspect an overdose, contact a poison control center or seek emergency medical care immediately.

After taking the tablet by mouth, both lamivudine and zidovudine are rapidly absorbed and widely distributed throughout the body. Lamivudine is mostly eliminated unchanged through the urine, with very little broken down by the liver. Zidovudine is mainly processed by the liver into an inactive metabolite called GZDV, which is then excreted in the urine. Neither drug is significantly metabolized by the cytochrome P450 enzyme system, which reduces the likelihood of many common drug-drug interactions. One lamivudine and zidovudine combination tablet has been shown to deliver the same amount of each drug as taking the two medicines separately.

Store at 20º to 25ºC (68º to 77ºF); excursions permitted to 15º to 30ºC (59º to 86ºF) Preserve in well-closed containers, protected from light.