An Overview of Combivir (AZT/3TC)

la-MI-vyoo-deen, zye-DOE-vyoo-deen

Brand Name: Combivir
Other Name(s): ZDV/3TC

Drug Class: Nucleoside Reverse Transcriptase Inhibitors

Lamivudine/zidovudine is a fixed-dose combination tablet of two antiretroviral medicines, called nucleoside reverse transcriptase inhibitors (NRTIs). Lamivudine/zidovudine works by disrupting one of the early steps in the HIV life cycle, called reverse transcription. During normal reverse transcription, HIV's reverse transcriptase enzyme (a type of protein) converts HIV's RNA -- a single strand of genetic information -- into DNA -- a double strand of genetic information. It does this by recoding the RNA building blocks into complimentary DNA building blocks. As the HIV life cycle proceeds, the newly formed DNA is used to make more copies of HIV virus.

When lamivudine/zidovudine is present, however, it competes with two of the available DNA building blocks called deoxycytidine triphosphate and thymidine triphosphate. By replacing these building blocks in the newly developing HIV DNA, lamivudine/zidovudine is able to stop reverse transcriptase from completing its job. This prevents the HIV DNA strand from being formed and halts the HIV life cycle.

Indications and Usage

Lamivudine/zidovudine (Combivir) was originally approved by the U.S. Food and Drug Administration (FDA) on September 27, 1997. It is currently approved for use in combination with other antiretroviral agents for the treatment of HIV infection in adults and children weighing greater than or equal to 30 kg (66 pounds).

Lamivudine/stavudine does not cure or prevent HIV infection or AIDS and does not reduce the risk of passing the virus to other people.

Dosage Form/Administration

Always take this medication as your doctor instructs. Lamivudine/zidovudine is taken by mouth, without regard to food, and it is always used with other anti-HIV medications.

Dosage forms and strengths:

• Tablet: lamivudine 150 mg and zidovudine 300 mg

What storage conditions are needed for this medication?

• Store lamivudine/zidovudine tablets between 36°F to 86°F (2°C to 30°C).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

In case of emergency/overdose:

In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.

What other information should I know?

• Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
• It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Recommended Daily Dose

The recommended dose of lamivudine/zidovudine in HIV-1-infected adults and children weighing greater than or equal to 30 kg (66 pounds) is 1 tablet (containing 150 mg of lamivudine and 300 mg of zidovudine) taken twice daily by mouth.

Note:

• Depending on certain factors, such as kidney function, liver problems, and possible side effects of the medicine, lamivudine/zidovudine may not be right for you. Your doctor will determine if it is appropriate for you to take this medicine. Always take lamivudine/zidovudine exactly as prescribed by your doctor.
• Because lamivudine/zidovudine is a fixed-dose combination tablet, it should not be used in children weighing less than 30 kg (66 pounds).

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed dose.

Contraindications

What special precautions should I follow?

Before taking lamivudine/zidovudine,

• Tell your doctor and pharmacist if you are allergic to lamivudine, zidovudine, or any other medications.
• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Your doctor may need to change the doses of your medications or monitor you more carefully for side effects.
• Note that lamivudine/zidovudine should not be used if you are taking certain other medicines (see Drug Interactions).
• Tell your doctor if you are pregnant or plan to become pregnant. If you become pregnant while taking lamivudine/zidovudine, call your doctor. Tell your doctor if you are breastfeeding. You should not breastfeed if you are infected with HIV or if you are taking lamivudine/zidovudine.
• Tell your doctor about any medical problems you may have had or currently have, including kidney or liver problems (such as hepatitis or cirrhosis), pancreas problems (pancreatitis), alcohol use, and low red/white blood cell counts.

Possible Side Effects

Lamivudine/zidovudine may cause side effects.

The following life-threatening or serious side effects have been reported. Contact your doctor immediately if you experience:

• Low White and Red Blood Cell Counts (Neutropenia and Anemia). Because zidovudine, one of the active ingredients of lamivudine/zidovudine, has been associated with blood cell problems, it is extremely important to have frequent tests to monitor blood cell counts while taking lamivudine/zidovudine. If you experience any of the following symptoms, let your doctor know right away:
  • fatigue
  • shortness of breath
  • dizziness or light-headedness
  • headache
  • chest pain
  • pale skin
  • rapid heart rate
  • fever
  • sores (ulcers) around the mouth
  • chills
  • cough
• Serious Allergic Reaction (Hypersensitivity Reaction). If you develop symptoms of an allergic reaction, seek medical attention immediately:
  • rash
  • itching or swelling of the face, tongue, or throat
  • severe dizziness
  • trouble breathing
  • peeling skin
• Lactic acidosis (buildup of lactic acid in the blood). This can be a medical emergency and may require treatment in the hospital. Call your healthcare provider right away if you experience any of the following symptoms of lactic acidosis:
  • feeling weak or tired
  • unusual muscle pain
  • trouble breathing
  • unusual stomach pain or discomfort
  • nausea
  • vomiting
  • a cold sensation, especially in your arms or legs
  • dizziness or lightheadedness
  • fast or irregular heart beat
  • unexplained weight loss
• Hepatotoxicity (serious liver problem). Hepatotoxicity with hepatomegaly (liver enlargement) and steatosis (fat in the liver) has been reported in patients taking nucleoside antiretroviral medicines, including lamivudine and zidovudine. Call your healthcare provider right away if you experience the following signs/symptoms of liver problems:
  • skin or white part of the eyes appearing yellow (jaundice)
  • dark colored urine
  • bowel movements turning light in color
  • loss of appetite
  • nausea
  • lower stomach area pain
• Pancreatitis (dangerous inflammation of the pancreas). Tell your doctor if you have ever had pancreatitis, regularly drink alcoholic beverages, or have gallstones, as pancreatitis occurs more often in patients with these conditions. Call your doctor immediately if you develop any of the following symptoms of pancreatitis:
  • stomach pain
  • nausea
  • vomiting
• Myopathy and myositis (muscle disorders and inflammation of muscles). Contact your doctor if you develop:
  • muscle weakness
  • muscle cramps
  • muscle stiffness or spasms
• Worsening of liver disease. Patients co-infected with HIV and HBV may experience a worsening of their liver disease upon discontinuation of lamivudine, an active ingredient of Combivir. Talk to your doctor about any changes in your antiretroviral medicines.
• Changes in Body Fat. Changes may include an increased amount of fat in the upper back and neck (buffalo hump), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also occur. The exact cause and long-term health effects of these problems are not known.
• Changes in your Immune System (Immune Reconstitution Syndrome). This can occur when you start HIV medicines. As your immune system becomes stronger, your body may begin to fight infections that have been "hidden" in your body for a long time. Call your doctor immediately if you start having any new symptoms after starting your HIV medicine.

Common side effects that may be associated with lamivudine/zidovudine include the following. Let your doctor know if any of these side effects do not go away or worsen:

• headache
• nausea
• fatigue
• diarrhea
• cough
• nasal symptoms (such as stuffy nose)
• general feeling of discomfort, illness, or lack of well-being

Lamivudine/zidovudine may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the U.S. FDA's MedWatch Adverse Event Reporting program online at www.fda.gov/Safety/MedWatch or by phone at 1-800-332-1088.

Drug Interactions

Lamivudine/zidovudine may interact with other medicines. Before taking lamivudine/zidovudine, it is important to tell your doctor about any prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

You should not take lamivudine/zidovudine with the following:

• other medicines containing lamivudine, zidovudine, or emtricitabine (such as, Epivir, Epivir-HBV, Retrovir, Epzicom, Trizivir, Atripla, Emtriva, and Truvada)

Other medicines that may interact with lamivudine/zidovudine and should be used with caution include the following:

• interferon alfa
• ribavirin
• doxorubicin
• ganciclovir

In addition to the lists above, there are other medicines that may interact with lamivudine/zidovudine. For a complete list of all medicines that may interact with lamivudine/zidovudine, talk with your doctor or pharmacist and check the manufacturer's Web site for the full prescribing information.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet. Lamivudine/zidovudine can be taken with or without food.

Clinical Trials

Click here to search ClinicalTrials.gov for trials that use Lamivudine/Zidovudine.

Manufacturer Information

Combivir
GlaxoSmithKline
5 Moore Drive
Research Triangle Park, NC 27709
Phone: 888-825-5249

Lamivudine/Zidovudine
GlaxoSmithKline
5 Moore Drive
Research Triangle Park, NC 27709
Phone: 888-825-5249

Lamivudine/Zidovudine
Teva Pharmaceuticals USA
1090 Horsham Rd. P.O.B. 1090
North Wales, PA 19454
Phone: 888-TEVA-USA (838-2872)