Abacavir, Lamivudine, and Zidovudine

Pronunciation

 (a BAK a veer, la MI vyoo deen, & zye DOE vyoo deen)

U.S. Brand Names

 Trizivir

Synonyms

 Azidothymidine, Abacavir, and Lamivudine; AZT, Abacavir, and Lamivudine; Compound S, Abacavir, and Lamivudine; Lamivudine, Abacavir, and Zidovudine; 3TC, Abacavir, and Zidovudine; ZDV, Abacavir, and Lamivudine; Zidovudine, Abacavir, and Lamivudine

Generic Available

 No

Use

 Treatment of HIV infection (either alone or in combination with other antiretroviral agents) in patients whose regimen would otherwise contain the components of Trizivir

Pregnancy Risk Factor

 C

Pregnancy Implications

 See individual agents.

Lactation

 See individual agents.

Contraindications

 Hypersensitivity to abacavir, lamivudine, zidovudine, or any component of the formulation. Do not rechallenge patients who have experienced hypersensitivity to abacavir (as Trizivir or Ziagen); life-threatening and fatal reactions have been reported.

Warnings/Precautions

 Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir). Patients exhibiting symptoms of fever, skin rash, fatigue, respiratory symptoms (eg, pharyngitis, dyspnea, cough) and/or GI symptoms (eg, abdominal pain, nausea, vomiting, diarrhea) should discontinue therapy immediately and call for medical attention. Trizivir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Trizivir SHOULD NOT be restarted because more severe symptoms may occur within hours, including LIFE-THREATENING HYPOTENSION AND DEATH. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted (interruption in drug supply, temporary discontinuation while treating other conditions). Reactions occurred within hours. In some cases, signs of hypersensitivity may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, reactions to other medications). If Trizivir is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out. To report these events on Trizivir hypersensitivity, a registry has been established (1-800-270-0425). Trizivir, as a fixed-dose combination tablet, should not be used in patients <40 kg or those requiring dosage adjustment; should not be used in patients with Clcr 50 mL/minute; not intended for use in pediatric patients; should not be administered concomitantly with abacavir, lamivudine, or zidovudine. Prior liver disease, prolonged use, and obesity may be risk factors for development of lactic acidosis and severe hepatomegaly with steatosis. Dose reductions may be required for zidovudine in patients with hepatic impairment. Trizivir is a fixed-dose combination; it is not recommended (per manufacturer) in hepatic impairment. Use with caution in patients with bone marrow compromise; myopathy and myositis have been associated with prolonged use of zidovudine (in Trizivir).

Adverse Reactions

 Fatal hypersensitivity reactions have occurred in patients taking abacavir (in Trizivir). If Trizivir is to be restarted following an interruption in therapy, first evaluate the patient for previously unsuspected symptoms of hypersensitivity. Do not restart if hypersensitivity is suspected or if hypersensitivity cannot be ruled out.

The following information is based on CNAAB3003 study data concerning effects noted in patients receiving abacavir, lamivudine, and zidovudine. See individual agent monographs for additional information.

>10%:

Endocrine & metabolic: Triglycerides increased (25%)

Gastrointestinal: Nausea (47%), nausea and vomiting (16%), diarrhea (12%), loss of appetite/anorexia (11%)

1% to 10%:

Central nervous system: Insomnia (7%)

Miscellaneous: Hypersensitivity (5% based on abacavir component)

Other (frequency unknown): Pancreatitis, GGT increased

Postmarketing and/or case reports (limited to important or life-threatening): Redistribution/accumulation of body fat, anaphylaxis, cardiomyopathy, hepatic steatosis, lactic acidosis, Stevens-Johnson syndrome

Overdosage/Toxicology

 Symptoms of overdose with zidovudine include nausea, vomiting, headache, dizziness, drowsiness, lethargy, confusion, and hematologic changes. Myocardial degeneration has been documented in animals during long-term high-dose toxicology studies; clinical relevance is unknown. Peritoneal dialysis and hemodialysis have little to no effect on the removal of the components of Trizivir.

Drug Interactions

 See individual agents.

Stability

 Store at room temperature 25C (77F)

Mechanism of Action

 The combination of abacavir, lamivudine, and zidovudine 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

Pharmacodynamics/Kinetics

 Bioavailability studies of Trizivir show no difference in AUC or Cmax when compared to abacavir, lamivudine, and zidovudine given together as individual agents. See individual agents.

Dosage

 Oral: Adolescents and Adults: 1 tablet twice daily; Note: Not recommended for patients <40 kg

Dosage adjustment in renal impairment: Because lamivudine and zidovudine require dosage adjustment in renal impairment, Trizivir should not be used in patients with Clcr 50 mL/minute

Elderly: Use with caution

Administration

 Administer without regard to food or water.

Dietary Considerations

 May be taken without regard to food or water.

Patient Education

 This is not a cure for HIV infection, nor will it reduce the risk of transmission of HIV to others. Take exactly as prescribed without regard to food or water. Do not discontinue even if feeling better. You will need to have frequent blood tests to identify possible blood cell problems. You may experience headache, muscle pain, weakness, insomnia, unusual bleeding (eg, tarry stools, easy bruising, blood in stool, urine, or mouth), dizziness, or numbness; report these to your prescriber. Note: Trizivir contains abacavir (also called Ziagen). About 1 in 20 patients who take abacavir will have a serious allergic reaction that can result in death if the drug is not stopped right away. You may be having this reaction if you get a skin rash or if you get one or more symptoms from at least two of the following groups: fever; nausea, vomiting, diarrhea, stomach pain; extreme tiredness, achiness, general ill feeling; or sore throat, shortness of breath, cough. If you think you are having this reaction contact your prescriber immediately. If you stop Trizivir because of this reaction, never take Trizivir or Ziagen (abacavir) again or you could die within hours. If you stop Trizivir therapy for any other reason, consult your prescriber before restarting therapy. Pregnancy/breast-feeding precautions: Inform your prescriber if you are or intend to become pregnant. Breast-feeding is not recommended. HIV-infected mothers are discouraged from breast-feeding to decrease potential transmission of HIV.

Dental Health: Effects on Dental Treatment

 No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions

Mental Health: Effects on Mental Status

 May cause insomnia

Mental Health: Effects on Psychiatric Treatment

 Gastrointestinal side effects are common; these effects may be additive with concurrent use of SSRIs, lithium, or valproate. The hypnotic effect of the benzodiazepines may be diminished. Valproic acid may decrease the clearance of zidovudine. Increase in triglycerides is common and may be additive with clozapine, olanzapine, or quetiapine. May cause pancreatitis; use caution with valproic acid and atypical antipsychotics. May increase GGT; use caution with olanzapine and valproic acid. May cause aplastic anemia; use caution with clozapine and carbamazepine. Suspected Stevens-Johnson syndrome (SJS) has been reported in patients receiving abacavir in combination with medications known to be associated with SJS (lamotrigine).

Dosage Forms

 Tablet [film coated]: Abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg

References

"Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States," June 23, 2004. Available at: http://www.aidsinfo.nih.gov. Accessed July 1, 2004.
The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. 1997- A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.