Duovir-N

Chemical Name: LAMIVUDINE and ZIDOVUDINE and NEVIRAPINE

Composition

Each film-coated tablet contains
Lamivudine 150 mg and
Zidovudine USP 300 mg

Description

Duovir is a combination of two drugs commonly used in the management of Human Immunodeficiency Virus (HIV) infection. Both lamivudine and zidovudine belong to the nucleoside analogue class of antiretroviral drugs. Both drugs act by inhibiting the reverse transcriptase enzyme of HIV, and by terminating the growth of the DNA chain. Lamivudine in combination with zidovudine has been shown to have synergistic antiretroviral activity.

Each tablet of Duovir contains half of the commonly prescribed daily doses of both lamivudine and zidovudine. With the availability of this combination tablet, patients may be better able to adhere to complex drug treatment regimens, thereby enhancing compliance.

Indications

Duovir is indicated for the treatment of HIV infection.

Dosage and Administration

The recommended oral dose of Duovir for adults and adolescents (at least 12 years of age) is one tablet (containing 150 mg of lamivudine and 300 mg of zidovudine) twice daily with or without food.

Dose Adjustment: Because it is a fixed dose combination, Duovir should not be prescribed for patients requiring dosage adjustment such as those with reduced renal function (creatinine clearance < 50 mL/min), those with low body weight (< 50 kg or II 0 lb), or those experiencing dose-limiting adverse events.

Contraindications

Duovir tablets are contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of the product.

Warnings and Precautions

Since Duovir is a fixed-dose combination of lamivudine and zidovudine, it should ordinarily not be administered concomitantly with either lamivudine or zidovudine.

The complete prescribing information for all agents being considered for use with Duovir should be consulted before combination therapy with Duovir is initiated.

BONE MARROW SUPPRESSION

Duovir should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count < 1,000 cells/ mm³ or hemoglobin < 9.5 g/dl (See Side Effects).

Frequent blood counts are strongly recommended in patients with advanced HIV disease who are treated with Duovir. For HIVinfected individuals and patients with asymptomatic or early HIV disease, periodic blood counts are recommended.

LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of antiretroviral nucleoside analogues alone or in combination, including zidovudine and lamivudine. A majority of these cases have been in women. Caution should be exercised when administering Duovir to any patient, and particularly to those with known risk factors for liver disease. Treatment with Duovir should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity.

MYOPATHY

Myopathy and myositis, with pathological changes similar to that produced by HIV disease, have been associated with prolonged use of zidovudine and therefore may occur with therapy with Duovir.

PATIENTS WITH HIV AND HEPATITIS B VIRUS COINFECTION

In clinical trials and postmarketing experience, some patients with HIV infection who have chronic liver disease due to hepatitis B virus infection experienced clinical or laboratory evidence of recur-rent hepatitis upon discontinuation of lamivudine. Consequences may be more severe in patients with decompensated liver disease.

DRUG INTERACTIONS

Coadministration of ganciclovir, interferon-cc, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.

IMPAIRED RENAL FUNCTION

Reduction of the dosages of lamivudine and zidovudine is recommended for patients with impaired renal function. Patients with creatinine clearance < 50 ml/min should not receive Duovir.

PREGNANCY

Category C. There are no adequate and wellcontrolled studies of this combination in pregnant women. Duovir should be used during pregnancy only if the potential benefits outweigh the risks.

LACTATION

It is recommended that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV infection. Zidovudine is excreted in breast milk. No data are available on this combination or lamivudine. Therefore, there is a potential for adverse effects in nursing infants. Mothers should be instructed not to breast-feed if they are receiving Duovir.

PAEDIATRIC USE

Duovir should not be administered to paediatric patients less than 12 years of age because it is a fixed-dose combination that cannot be adjusted for this patient population.

OTHERS

Reduction of doses of lamivudine is recommended for patients with low body weight (less than 50 kg or 110 lb). Therefore patients with low body weight should not receive Duovir.

Side Effects

The most commonly observed side effects during clinical trials were headache, malaise and fatigue, nausea, vomiting, diarrhoea, anorexia, fever/chills, neuropathy, insomnia, dizziness, nasal signs and symptoms, cough, musculoskeletal pain and neutropenia.

Overdosage

There is no known antidote for Duovir.

Lamivudine: One case of an adult ingesting 6 gms of lamivudine has been reported. There were no clinical signs or symptoms noted and hematologic tests remained normal. It is not known whether lamivudine can be removed by peritoneal dialysis or hemodialysis.

Zidovudine: Acute overdoses of zidovudine have been reported in paediatric 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 one report of a grand mal seizure. Hematologic changes were transient. All patients recovered. Hemodialysis and peritoneal dialysis appear to have a negligible effeet on the removal of zidovudine, while elimination of its primary metabolite is enhanced.