Lamivudine and zidovudine

Do not take this medicine if you have ever had an allergic reaction to any medicine that contains lamivudine or zidovudine.

Zidovudine can weaken your immune system and cause signs of infection (fever, mouth sores, skin sores, flu symptoms, pale skin). Your blood will need to be tested often. Long-term use of zidovudine can cause muscle weakness, or loss of muscle tissue similar to "wasting syndrome" caused by HIV.

This medicine may cause a serious condition called lactic acidosis. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

If you have hepatitis B you may develop liver symptoms after you stop taking medicine that contains lamivudine. Your doctor may want to check your liver function for several months after you stop using lamivudine and zidovudine.

Usual Adult Dose for HIV Infection:

1 tablet orally twice a day

Use: In combination with other antiretrovirals, for the treatment of HIV-1 infection

Usual Adult Dose for Nonoccupational Exposure:

US CDC recommendations: 1 tablet orally every twice a day
Duration of therapy: 28 days

Comments:
-Recommended as part of a preferred NNRTI-based or protease inhibitor-based regimen for nonoccupational postexposure prophylaxis of HIV infection; also recommended as part of alternative regimens (NNRTI-based, protease inhibitor-based, or triple NRTI)
-Prophylaxis should be started as soon as possible, within 72 hours of exposure.
-Current guidelines should be consulted for additional information.

Usual Adult Dose for Occupational Exposure:

US Public Health Service working group recommendations: 1 tablet orally twice a day
Duration of therapy: 28 days, if tolerated

Comments:
-Recommended as part of alternative regimens for HIV postexposure prophylaxis
-Prophylaxis should be started as soon as possible, preferably within hours after exposure.
-The optimal duration of prophylaxis is unknown and may differ based on the institution protocol.
-Current guidelines should be consulted for additional information.

Usual Pediatric Dose for HIV Infection:

At least 30 kg: 1 tablet orally twice a day

Comments:
-Use of the individual components is recommended for patients less than 30 kg; the manufacturer product information for lamivudine and zidovudine should be consulted.

Use: In combination with other antiretrovirals, for the treatment of HIV-1 infection

Use lamivudine and zidovudine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• It is important that you do not miss or skip a dose of lamivudine and zidovudine during treatment.
• If you have trouble swallowing, talk with your doctor.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

• AZT + 3TC (error-prone abbreviation)
• Lamivudine/Zidovudine
• Zidovudine and Lamivudine

The combination of zidovudine and lamivudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance

Hypersensitivity to lamivudine or zidovudine, or any component of the formulation.

Canadian labeling: Additional contraindications (not in US labeling): Neutrophil count <750/mm3) or hemoglobin <7.5 g/dL (4.65 mmol/L)

Store between 2°C and 30°C (36°F and 86°F).

Acyclovir-Valacyclovir: May enhance the CNS depressant effect of Zidovudine. Monitor therapy

Amodiaquine: Zidovudine may enhance the neutropenic effect of Amodiaquine. Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

Clarithromycin: May enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Consider therapy modification

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Dexketoprofen: May enhance the adverse/toxic effect of Zidovudine. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

DOXOrubicin (Conventional): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Conventional) may diminish the therapeutic effect of Zidovudine. Consider therapy modification

DOXOrubicin (Liposomal): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Liposomal) may diminish the therapeutic effect of Zidovudine. Consider therapy modification

Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Avoid combination

Fluconazole: May decrease the metabolism of Zidovudine. Monitor therapy

Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Zidovudine. Specifically, hematologic toxicity may be enhanced. Monitor therapy

Interferons: May enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Monitor therapy

Methadone: May increase the serum concentration of Zidovudine. Monitor therapy

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

Probenecid: May decrease the metabolism of Zidovudine. Monitor therapy

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Protease Inhibitors: May decrease the serum concentration of Zidovudine. Monitor therapy

Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of Zidovudine. Monitor therapy

Ribavirin (Oral Inhalation): Zidovudine may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Specifically, the risk/severity of anemia may be increased. Management: Due to significantly increased risk of anemia, consider even closer monitoring for anemia than routinely recommended. Alternative therapies should be considered when clinically possible, particularly for patients with other risk factors. Consider therapy modification

Ribavirin (Systemic): Zidovudine may enhance the adverse/toxic effect of Ribavirin (Systemic). Specifically, the risk/severity of anemia may be increased. Management: Due to significantly increased risk of anemia, consider even closer monitoring for anemia than routinely recommended for ribavirin. Alternative therapies should be considered when clinically possible, particularly for patients with other risk factors. Consider therapy modification

Rifamycin Derivatives: May decrease the serum concentration of Zidovudine. Exceptions: Rifabutin. Monitor therapy

Stavudine: Zidovudine may diminish the therapeutic effect of Stavudine. Avoid combination

Tenoxicam: May enhance the adverse/toxic effect of Zidovudine. Monitor therapy

Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy

Trimethoprim: May increase the serum concentration of LamiVUDine. Monitor therapy

Valproate Products: May increase the serum concentration of Zidovudine. Monitor therapy

Zidovudine, a component of lamivudine/zidovudine tablets, has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced HIV-1 disease.

Prolonged use of zidovudine has been associated with symptomatic myopathy.

Severe, acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine, a component of lamivudine/zidovudine. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue lamivudine/zidovudine and are coinfected with HIV-1 and HBV. If appropriate, initiation of antihepatitis B therapy may be warranted.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of nucleoside analogues and other antiretrovirals. Discontinue lamivudine/zidovudine if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.

Concerns related to adverse effects:

• Fat redistribution: May cause redistribution of fat (eg, buffalo hump, peripheral wasting with increased abdominal girth, cushingoid appearance).

• Hematologic toxicity: [US Boxed Warning]: Zidovudine is associated with hematologic toxicity, including neutropenia and severe anemia. Use with caution in patients with bone marrow compromise (granulocytes <1,000 cells/mm3 or hemoglobin <9.5 g/dL).

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.

• Lactic acidosis/hepatomegaly: [U.S Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Use with caution in patients with risk factors for liver disease (risk may be increased with female gender, obesity, pregnancy, or prolonged exposure) and discontinue in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).

• Myopathy: [US Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy.

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HBV and HIV-1 when therapy is discontinued; monitor patients with clinical and laboratory follow-up for at least several months after treatment discontinuation. Emergence of hepatitis B virus lamivudine-resistant variants has been reported in patients with concurrent HBV infection who received a lamivudine-containing regimen for HIV-1 treatment.

• Hepatic impairment: Use is not recommended in patients with hepatic impairment.

• Pancreatitis: Use with caution in patients with a history of pancreatitis or other significant risk factors for pancreatitis development. Discontinue immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur.

• Renal impairment: Use is not recommended in patients with renal impairment (CrCl <50 mL/minute).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

At least 30 kg: 1 tablet orally twice a day

Comments:
-Use of the individual components is recommended for patients less than 30 kg; the manufacturer product information for lamivudine and zidovudine should be consulted.

Use: In combination with other antiretrovirals, for the treatment of HIV-1 infection