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. |
| What are the dosage and administration of this medicine? |
Adults
1 tablet twice daily
Duovir-N should not be administered to patients who have just initiated therapy with nevirapine. This is because an initial lead-in dosing of 200 mg nevirapine once daily for 2 weeks is recommended. Following this lead-in dose, a dose escalation (maintenance dose) to 200 mg nevirapine bd may be carried out in the absence of any hypersensitivity reactions (e.g. rash, liver function test abnormalities; see Warnings and Precautions).
Monitoring of patients
Clinical chemistry tests, which include liver function tests, should be performed prior to initiating lead-in nevirapine therapy and at appropriate intervals during therapy (see Warnings and Precautions).
Dosage Adjustment
Because it is a fixed-dose combination, Duovir-N should not be prescribed for patients requiring dosage adjustment, such as those with low body weight (<50 kg), reduced renal function (creatinine clearance < 50 ml/min) or those experiencing dose-limiting adverse events.
Duovir-N should be discontinued if patients experience severe rash or a rash accompanied by constitutional findings. Patients experiencing mild to moderate rash during the 14-day lead-in period of 200 mg/day should not have their nevirapine dose increased or start therapy with Duovir-N until the rash has resolved
Duovir-N administration should be interrupted in patients experiencing moderate or severe liver function tests abnormalities (excluding GGT), until the liver function test elevations have returned to baseline. Nevirapine (using Nevimune Tablets) may then be restarted at 200 mg per day. Increasing the daily dose to 200 mg twice daily (using Duovir-N) should be done with caution, after extended observation. Nevirapine should be permanently discontinued if moderate or severe liver function test abnormalities recur.
Patients who interrupt nevirapine dosing for more than 7 days should restart the recommended dosing, using one 200 mg Nevimune tablet daily for the first 14 days (lead-in) in combination with the other antiretrovirals, followed by 200 mg twice daily using Duovir-N in the absence of any signs of hypersensitivity.
Impaired renal and hepatic function
No data are available to recommend a dosage of nevirapine in patients with hepatic dysfunction, renal insufficiency or undergoing dialysis. |
| What are the side effects of this medicine? |
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. |
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