Combivir (Lamivudine / Zidovudine) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

No drug interaction studies have been conducted using COMBIVIR Tablets [see Clinical Pharmacology].

Antiretroviral Agents

Lamivudine: Zalcitabine: Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of COMBIVIR in combination with zalcitabine is not recommended.

Zidovudine: Stavudine: Concomitant use of COMBIVIR with stavudine should be avoided since an antagonistic relationship with zidovudine has been demonstrated in vitro.

Nucleoside Analogues Affecting DNA Replication: Some nucleoside analogues affecting DNA replication, such as ribavirin, antagonize the in vitro antiviral activity of zidovudine against HIV-1; concomitant use of such drugs should be avoided.

Doxorubicin

Zidovudine: Concomitant use of COMBIVIR with doxorubicin should be avoided since an antagonistic relationship with zidovudine has been demonstrated in vitro.

Hematologic/Bone Marrow Suppressive/Cytotoxic Agents

Zidovudine: Coadministration of ganciclovir, interferon alfa, ribavirin, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.

Interferon- and Ribavirin-Based Regimens

Lamivudine: Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV-1/HCV virologic suppression) was seen when ribavirin was coadministered with lamivudine in HIV-1/HCV co-infected patients, hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see Warnings and Precautions (5.5), Clinical Pharmacology].

Trimethoprim/Sulfamethoxazole (TMP/SMX)

Lamivudine: No change in dose of either drug is recommended. There is no information regarding the effect on lamivudine pharmacokinetics of higher doses of TMP/SMX such as those used to treat PCP.

OVERDOSAGE

COMBIVIR: There is no known antidote for COMBIVIR.

Lamivudine: One case of an adult ingesting 6 grams of lamivudine was reported; there were no clinical signs or symptoms noted and hematologic tests remained normal. Because a negligible amount of lamivudine was removed via (4-hour) hemodialysis, continuous ambulatory peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuous hemodialysis would provide clinical benefit in a lamivudine overdose event.

Zidovudine: Acute overdoses of zidovudine have been reported in pediatric patients and adults. These involved exposures up to 50 grams. The only consistent findings were nausea and vomiting. Other reported occurrences included headache, dizziness, drowsiness, lethargy, confusion, and 1 report of a grand mal seizure. Hematologic changes were transient. All patients recovered. Hemodialysis and peritoneal dialysis appear to have a negligible effect on the removal of zidovudine, while elimination of its primary metabolite, 3′-azido-3′-deoxy-5′- O -β- D -glucopyranuronosylthymidine (GZDV), is enhanced.

CONTRAINDICATIONS

COMBIVIR Tablets are contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., anaphylaxis, Stevens-Johnson syndrome) to any of the components of the product.