Lamivudine / Zidovudine

Pronunciation: la-MIV-ue-deen/zye-DOE-vue-deen
Class: Nucleoside analog reverse transcriptase inhibitor combination

Trade Names

Combivir
- Tablets lamivudine 150 mg/zidovudine 300 mg

Pharmacology

Inhibits replication of HIV by incorporating into HIV DNA and producing an incomplete, nonfunctional DNA.

Slideshow: Flashback: FDA Drug Approvals 2013

Indications and Usage

Treatment of HIV-1 infection in combination with other antiretroviral agents.

Contraindications

Hypersensitivity to any component of the product.

Dosage and Administration

Adults and children weighing at least 30 kg

PO 1 tablet 2 times daily.

Renal function impairment

Do not administer to patients with CrCl less than 50 mL/min.

Hepatic function impairment

Not recommended for patients with impaired hepatic function.

General Advice

  • Administer without regard to food. Administer with food if GI upset occurs.
  • Because this product is a fixed-dose combination, the dose cannot be adjusted for patients weighing less than 30 kg.

Storage/Stability

Store at 36° to 86°F.

Drug Interactions

Atovaquone, fluconazole, methadone, probenecid, valproic acid

Zidovudine blood concentrations may be elevated, increasing the pharmacologic effects and adverse reactions.

Doxorubicin, ribavirin, stavudine

Avoid because antagonism of zidovudine has been demonstrated in vitro.

Ganciclovir, interferon-alpha, ribavirin, other bone marrow–suppressive or cytotoxic agents

Hematologic toxicity of zidovudine may be increased.

Nelfinavir, ritonavir

Zidovudine blood concentrations may be reduced.

Trimethoprim/Sulfamethoxazole

Lamivudine blood concentrations may be elevated, increasing the pharmacologic effects and adverse reactions.

Zalcitabine

Concurrent use is not recommended.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Cardiomyopathy (postmarketing).

CNS

Headache (35%); malaise/fatigue (27%); neuropathy (12%); insomnia/other sleep disorders (11%); dizziness (10%); depressive disorders (9%); paresthesia, peripheral neuropathy, seizures (postmarketing).

Dermatologic

Skin rash (9%); alopecia, erythema multiforme, Stevens-Johnson syndrome, urticaria (postmarketing).

EENT

Nasal signs and symptoms (20%).

GI

Nausea (33%); diarrhea (18%); nausea/vomiting (13%); anorexia/decreased appetite (10%); abdominal pain (9%); abdominal cramps (6%); dyspepsia (5%); oral mucosal pigmentation, pancreatitis, stomatitis (postmarketing).

Genitourinary

Gynecomastia (postmarketing).

Hematologic-Lymphatic

Anemia, lymphadenopathy, splenomegaly (postmarketing).

Hepatic

Hepatic steatosis, posttreatment exacerbation of hepatitis B (postmarketing).

Lab Tests

Neutropenia (7%); increased ALT, increased amylase (4%); anemia (3%); increased AST (2%); increased bilirubin (1%).

Metabolic-Nutritional

Hyperglycemia, lactic acidosis (postmarketing).

Musculoskeletal

Musculoskeletal pain (12%); myalgia (8%); arthralgia (5%); CPK elevation, muscle weakness, rhabdomyolysis (postmarketing).

Respiratory

Cough (18%); abnormal breathing sounds/wheezing (postmarketing).

Miscellaneous

Fever/chills (10%); redistribution/accumulation of body fat, sensitization reactions including anaphylaxis, vasculitis, weakness (postmarketing).

Precautions

Warnings

Zidovudine has been associated with neutropenia and anemia, particularly in patients with advanced HIV disease. Myopathy has been associated with prolonged use. Lactic acidosis and hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs alone or in combination with other antiretroviral agents. Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus and HIV and who have discontinued lamivudine.


Monitor

Frequent blood cell counts are recommended when using this drug combination in patients with advanced HIV disease; periodic blood cell counts are recommended when using in patients with asymptomatic or early HIV disease; monitor hepatic function for several months after discontinuation. Closely monitor patients receiving interferon alfa with or without ribavirin and lamivudine/zidovudine for treatment-associated toxicities, especially hepatic decompensation, neutropenia, and anemia.


Pregnancy

Category C .

Lactation

Excreted in breast milk. HIV-infected mothers should not breast-feed infants.

Children

Not indicated for children weighing less than 30 kg because this fixed-dose combination cannot be adjusted for this patient population.

Elderly

Select the dose with caution because of the greater frequency of decreased cardiac, hepatic, or renal function, and concomitant diseases or other drug therapy.

Renal Function

Dosage reduction is recommended in patients with impaired renal function. Do not administer to patients whose CrCl is less than 50 mL/min.

Hepatic Function

Dose reduction may be necessary in patients with mild to moderate hepatic function impairment or cirrhosis. Not recommended for patients with hepatic function impairment.

Bone marrow suppression

Use with caution in patients who have bone marrow compromise evidenced by granulocyte count less than 1,000 cells/mm 3 or Hgb less than 9.5 g/dL.

Fat redistribution

Redistribution and accumulation of body fat, including breast enlargement, central obesity, cushingoid appearance, dorsocervical fat enlargement (buffalo hump), facial wasting, and peripheral wasting, have occurred in patients receiving antiretroviral therapy.

Fixed-dose combination

Does not allow for dose reduction; do not use in patients requiring lamivudine or zidovudine dose reduction (eg, children weighing less than 30 kg, renal function impairment with CrCl less than 50 mL/min, hepatic function impairment, low body weight, patients experiencing dose-limiting adverse reactions).

Immune reconstitution syndrome

During the initial phase of treatment, patients may develop an inflammatory response to indolent or residual opportunistic infections.

Lactic acidosis/hepatomegaly with steatosis

Fatal cases have been reported.

Pancreatitis

Use with caution in patients with a history of pancreatitis or other risk factors for development of pancreatitis.

Overdosage

Symptoms

Confusion, dizziness, drowsiness, generalized tonic-clonic seizure, headache, hematologic changes (zidovudine), lethargy, nausea, vomiting.

Patient Information

  • Provide patient information leaflet.
  • Inform patient that this medication is for oral use only and to take only as prescribed.
  • Stress the importance of regular exams and laboratory work.
  • Inform patient that this medication is not a cure for the HIV infection and that the patient may continue to develop opportunistic infections and other complications of HIV infection. Patients will need to remain under the close observation of health care providers experienced in the treatment of patients with HIV-associated diseases.
  • Caution patient not to discontinue use of drug even when feeling better.
  • Caution patient that long-term effects of this medicine are not known.
  • Advise patient to notify health care provider of signs of infection, including sore throat, fever, cough, and respiratory congestion.
  • Advise family to notify health care provider of changes in neurological status, such as memory loss or confusion.
  • Advise patient that it may take at least 4 wk for max effect.
  • Warn patient that the risk of transmission of HIV to others through sexual contact or exposure to the patient's blood is still present. Instruct patient on methods to prevent transmission of HIV.
  • Instruct HIV-infected mothers not to breast-feed. Inform HIV-infected mothers that breast-feeding could pass HIV infection or this drug to the baby.
  • Advise women to inform health care provider immediately if pregnancy is suspected.
  • Inform patient that the major toxicities are neutropenia and anemia and to have blood cell counts monitored closely.

Copyright © 2009 Wolters Kluwer Health.

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