Duovir

Lamivudine / Zidovudine tablets

WHAT IS Duovir?

Duovir-N is a combination of 3 drugs commonly used in the management of Human Immunodeficiency Virus (HIV) infection. Both zidovudine and lamivudine belong to the nucleoside analogue class of antiretroviral drugs. Both drugs act by terminating the growth of the DNA chain and inhibiting the reverse transcriptase enzyme of HIV. Nevirapine is a non-nucleoside reverse transcriptase inhibitor. It acts by directly inhibiting reverse transcriptase.

Each tablet of Duovir-N contains half of the commonly prescribed daily doses of zidovudine, lamivudine and nevirapine. All three drugs are to be administered twice daily, permitting a fixed-dose combination to be formulated. With the availability of this combination formulation, patients may be better able to adhere to triple drug regimens, thereby enhancing compliance.

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Warning

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including lamivudine, zidovudine and other antiretrovirals(see Warnings and Precautions section). Zidovudine has been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced disease (see warnings). Prolonged use of zidovudine has been associated with symptomatic myopathy.

Severe, life-threatening skin reactions, including fatal cases, have occurred in patients treated with nevirapine. These have included cases of Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings and organ dysfunction. Patients developing signs or symptoms of severe skin reactions or hypersensitivity reactions must discontinue nevirapine as soon as possible (see Warnings).severe and life-threatening hepatotoxicity, including fatal hepatic necrosis, has occurred in patients treated with nevirapine (see Warnings).

Composition

Each film-coated tablet contains:

• Lamivudine 150mg
• Zidovudine USP 300mg
• Nevirapine 200 mg

Colour: Titanium Dioxide

Side Effects:

Lamivudine
Pancreatitis has been reported with the use of lamivudine.

Lactic acidosis and hepatic steatosis, hepatitis and liver failure have been reported with the use of antiretroviral nucleoside analogs, alone or in combination.

Other side effects associated with the use of lamivudine are diarrhea, malaise and fatigue, headache, nausea and vomiting, abdominal pain and discomfort, peripheral neuropathy, arthralgias, myalgias, skin rash, pruritus, transient neutropenia and thrombocytopenia and rarely, pancreatitis. Transiently elevated levels of hepatic enzymes and bilirubin (> 5 times the normal level) have also been observed occasionally during treatment with the drug. Resolution of transient neutropenia and raised hepatic and bilirubin levels occurred without dosage modification or discontinuation of therapy.

Zidovudine
The anaemia reported in patients with advanced HIV disease receiving zidovudine appears to be the result of impaired erythrocyte maturation. Thrombocytopenia has also been reported in patients with advanced disease. Mild drug-associated elevations in total bilirubin levels have been reported as an uncommon occurrence in patients treated for asymptomatic HIV infection.

Clinical adverse events or symptoms which occurred in at least 5% of all patients with advanced HIV disease treated with 1,500 mg/day of zidovudine were: fever, headache, nausea, vomiting, anorexia, myalgia, insomnia, dizziness, paraesthesias, dyspnoea and rash. Malaise, gastrointestinal pain, dyspepsia and taste perversion were also reported.

Nevirapine
The most clinically important adverse events associated with nevirapine therapy are rash and increases in liver function tests. Cases of hypersensitivity reactions have been observed.

The major clinical toxicity of nevirapine is rash, with nevirapine-attributable rash occurring in 16% of patients in combination regimens in Phase II/III controlled studies. Thirty-five percent of patients treated with nevirapine experienced rash compared with 19% of patients treated in control groups of either zidovudine + didanosine or zidovudine alone. Severe or life-threatening rash occurred in 6.6% of nevirapine-treated patients compared with 1.3% of patients treated in the control groups.

Rashes are usually mild to moderate, maculopapular erythematous cutaneous eruptions; with or without pruritus, located on the trunk, face and extremities. The majority of severe rashes occurred within the first 28 days of treatment. 25% of the patients with severe rashes required hospitalization, and one patient required surgical intervention. Overall, 7% of patients discontinued nevirapine due to rash.

With respect to laboratory abnormalities, asymptomatic elevations in GGT levels are more frequent in nevirapine recipients than in controls. Because clinical hepatitis has been reported in nevirapine-treated patients, monitoring of ALT (SGPT) and AST (SGOT) is strongly recommended, especially during the first six months of nevirapine treatment (See Warnings and Precautions). Decreased neutrophils (< 750/mm3), platelets (< 50,000/mm3) and Hb (< 8.0 g/dL), and increased total bilirubin (> 2.5 mg/dL) have also been reported.

Overdosage

Lamivudine
There is no known antidote for 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. It is not known whether lamivudine can be removed by peritoneal dialysis or hemodialysis.

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 one 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 is enhanced.

Nevirapine
There is no known antidote for nevirapine overdosage. Cases of nevirapine overdosage at doses ranging from 800 to 1800 mg per day for up to 15 days have been reported. Patients have experienced events including edema, erythema nodosum, fatigue, fever, headache, imsomnia, nausea, pulmonary infiltrates, rash, vertigo, vomiting and weight decrease. All events subsided following discontinuation of nevirapine.