Adult Dosing

Treatment of HIV infection

• 1 tablet (lamivudine/zidovudine 150/300 mg) PO bid

Pediatric Dosing

Treatment of HIV infection

• Child and adolescents 30 kgs
• 1 tablet (lamivudine/zidovudine 150/300 mg) PO bid

• <30 kgs: Should not be administered (because it is a fixed-dose combination that cannot be adjusted)

[Outline]

• Adult Dosing
• Pediatric Dosing

• Combination with other antiretroviral agents for the treatment of HIV-1 infection

• Hypersensitivity to any of the ingredients of the product
• Hepatic impairment
• CrCl <50 mL/min

• Zidovudine component is associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced (HIV-1) disease
• Prolonged use of zidovudine is associated with symptomatic myopathy
• Lactic acidosis and hepatomegaly with steatosis, including fatal cases, have occurred with the use of nucleoside analogues alone or in combination, including lamivudine, zidovudine, and other antiretrovirals. Consider suspension of therapy if clinical or laboratory findings suggest lactic acidosis or pronounced hepatotoxicity
• In patients co-infected with HIV/Hepatitis B, stopping this drug may lead to a severe acute exacerbation of hepatitis B; closely monitor hepatic function (laboratory and clinical) for at least several months. Initiate anti-hepatitis B therapy if needed

Renal Dose Adjustment (Based on CrCl)

• <50 mL/min: Contraindicated as dose adjustments are necessary and this combination is a fixed-dose combination

Hepatic Dose Adjustment

• Patients with impaired hepatic function/cirrhosis: Contraindicated as dose adjustments may be necessary and this combination is a fixed-dose combination

• Zidovudine component is associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced (HIV-1) disease [US Black Box Warning]
• Frequently monitor blood counts in patients with advanced HIV-1 disease undergoing therapy with this combination drug. Periodically perform blood counts for other HIV-1-infected patients. On occurrence of anemia or neutropenia consider interruption of dosage
• Myopathy and myositis, with pathological changes similar to that produced by HIV-1 disease, have occurred in association with prolonged use of zidovudine, and can occur in patients treated with this combination drug
• Lactic acidosis and hepatomegaly with steatosis, including fatal cases, have occurred with the use of nucleoside analogues alone or in combination, including lamivudine, zidovudine, and other antiretrovirals. Consider suspension of therapy if clinical or laboratory findings suggests lactic acidosis or pronounced hepatotoxicity (may include hepatomegaly and steatosis even in the absence of marked transaminase elevations) [US Black Box Warning]. Obesity and prolonged nucleoside exposure are risk factors
• In patients co-infected with HIV/Hepatitis B, stopping this drug may lead to a severe acute exacerbation of hepatitis B; closely monitor hepatic function (laboratory and clinical) for at least several months. Initiate anti-hepatitis B therapy if needed [US Black Box Warning]
• Avoid administration with other lamivudine or zidovudine containing products or emtricitabine containing products
• Fatal hepatic decompensation has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin. Closely monitor patients receiving interferon alfa with or without ribavirin and lamivudine/zidovudine for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia. Discontinue therapy as medically appropriate and consider reduction of dosage or discontinuation of interferon alfa, ribavirin, or both on observing worsening of clinical toxicities
• Exacerbation of anemia has occurred in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine. Co-administration of ribavirin and zidovudine is not recommended
• Immediately cease therapy if clinical signs, symptoms, or laboratory abnormalities suggest pancreatitis
• Immune reconstitution syndrome have occurred in patients treated with combination antiretroviral therapy
• Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have occurred in patients

Cautions: Use cautiously in

• Risk of hepatic disease
• HBV co-infection
• History of pancreatitis
• Obesity
• Female patients
• Myelosuppression
• Prolong nucleoside treatment
• Granulocyte count <1,000 cells/mm³
• Hemoglobin <9.5 g/dL

Pregnancy Category:C

Breastfeeding: HIV-infected mothers should generally not breastfeed their infants. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, exclusive breastfeeding for 6 months is recommended for HIV-infected mothers to reduce the risk of HIV transmission from the mother to the infant compared with mixed feeding. In these settings, abrupt weaning at 4 months does not reduce the risk of HIV transmission or produce an overall health benefit compared to continued breastfeeding, and increases the risk of infant death in HIV-infected infants. Extended antiretroviral prophylaxis in breastfed infants with antiretrovirals reduces the rate of HIV transmission during breastfeeding by about half, but the optimal regimen and duration of prophylaxis has not yet been defined. Lamivudine/zidovudine has been successfully used as part of a regimen that decreases mother-to-child transmission to half. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT last accessed 28 January 2011). Centers for disease control and prevention recommends mothers avoiding breast-feeding their infants as risk for postnatal transmission of HIV-1 infection exists. Lamivudine and zidovudine is excreted in human milk. Manufacturer advises to instruct infected mothers to avoid breast-feeding during therapy because of both the potential for HIV-1 transmission and the potential for serious adverse reactions in nursing infants.

• GI: Hepatic failure, lactic acidosis, hepatomegaly with steatosis, hepatotoxicity, pancreatitis, nausea, diarrhea, vomiting, anorexia, abdominal pain, mouth ulceration, dyspepsia
• GU: Renal failure
• CNS: Headache, nausea, malaise, fatigue, insomnia, dizziness, seizures, depression
• NEURO: Paresthesia, peripheral neuropathy
• RESP: Cough
• MUSC: Myopathy, rhabdomyolysis, myalgia, arthralgia, musculoskeletaL pain
• DERM: Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, rash, urticaria
• IMMU: Immune reconstitution syndrome
• METABOLIC: Lipodystrophy, lactic acidosis
• EENT: Nasal symptoms
• LAB TESTS: Anemia, neutropenia elevated LFTs, amylase
• MISC: Hypersensitivity reactions, fatal anaphylaxis, death, HBV exacerbation, fever, chills

Lamivudine

• Nucleoside analog reverse transcriptase inhibitor; after intracellular conversion to its active form (lamivudine-5-triphosphate), inhibits viral DNA synthesis by inhibiting the enzyme reverse transcriptase
• Bioavailability: 86 +/- 16 %
• Metabolism is a minor route of elimination; its active metabolite is trans-sulfoxide
• Renally excreted 71% (primarily unchanged)
• Half life: 5-7 hrs

Zidovudine

• Nucleoside analog reverse transcriptase inhibitor; inhibits replication of HIV by incorporating into HIV DNA and production of incomplete nonfunctional DNA
• Bioavailability: 64 +/- 10 %
• Metabolized by liver, CYP450: unknown
• Renally excreted: 95%
• Half life: 0.5-3 hrs

US Trade Name(s)

• Combivir

US Availability

lamivudine/zidovudine (generic)

• TABS: 150 mg/300 mg

Combivir (lamivudine/zidovudine)

• TABS: 150 mg/300 mg

Canadian Trade Name(s)

• Combivir

Canadian Availability

Combivir (lamivudine/zidovudine)

• TABS: 150 mg/300 mg

UK Trade Name(s)

• Combivir

UK Availability

Combivir (lamivudine/zidovudine)

• TABS: 150 mg/300 mg

Australian Trade Name(s)

• Combivir

Australian Availability

Combivir (lamivudine/zidovudine)

• TABS: 150 mg/300 mg

[Outline]

Antimicrobials

Antiviral Agents

Antiviral Combinations

Infectious Disease

Antiviral Agents

Antiviral Combinations

Pricing data from www.DrugStore.com in U.S.A.

• Lamivudine-Zidovudine 150-300 MG TABS [Bottle] (TEVA PHARMACEUTICALS USA)
  30 mg = $425.99
  90 mg = $1249.97
• Combivir 150-300 MG TABS [Bottle] (VIIV HEALTHCARE)
  30 mg = $488.01
  60 mg = $949.93

Warning: This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit drugstore.com.

Drug Name: Combivir (lamivudine 150 MG / zidovudine 300 MG) Oral Tablet

Pill Image:

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Ingredient(s): Lamivudine mixture with Zidovudine

Imprint: GXFC3

Color(s): White

Shape: Oval

Size (mm): 17.00

Score: 2

Inactive Ingredient(s): colloidal silicon dioxide / hypromellose / magnesium stearate / cellulose, microcrystalline / polyethylene glycol / polysorbate 80 / sodium starch glycolate type a potato / titanium dioxide

Drug Label Author:
GlaxoSmithKline LLC

DEA Schedule:
Non-Scheduled

Drug Name: Combivir (lamivudine 150 MG / zidovudine 300 MG) Oral Tablet

Ingredient(s): Lamivudine mixture with Zidovudine

Imprint: GXFC3

Color(s): White

Shape: Oval

Size (mm): 17.00

Score: 2

Inactive Ingredient(s): N/A

Drug Label Author:
Stat Rx USA

DEA Schedule:
Non-Scheduled