TROVIR 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 200mg nevirapinebd 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

Lamivudine

Because it is a fixed-dose combination, TROVIR should not be prescribed for patients requiring dosage adjustment, such as those with low body weight (<50 kg).

 

Zidovudine

Because it is a fixed-dose combination, this formulation should not be prescribed for patients requiring dosage adjustment such as those with reduced renal function (creatinine clearance <50ml/min) or those experiencing dose-limiting adverse events.

 

Nevirapine

TROVIR should be discontinued if patients experience severe rash or a rash accompanied by constitutional findings (see Warnings and Precautions). Patients experiencing mild to moderate rash during the 14-day lead-in period of 200mg/day should not have their nevirapine dose increased or start therapy with TROVIR until the rash has resolved (see Warnings and Precautions).

 

TROVIR 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 Nivepin Tablets) may then be restarted at 200mg per day. Increasing the daily dose to 200mg twice daily(using TROVIR) should be done with caution, after extended observation. Nevirapine should be parmanently discontinued if moderate or severe liver function test abnormalities recur (see Warnings and Precautions).

 

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 200mg twice daily using VIROZEN-S in the absence of any signs of hypersensitivity.

 

No data are available to recommend a dosage of nevirapine in patients with hepatic dysfunction, renal insufficiency or undergoing dialysis.[more]

 

CONTRAINDICATIONS:

TROVIR is contraindicated in patients with clinically significant hypersensitivity to any of the components contained in the formulation.[more]

 

TROVIR is also contraindicated for patients who are just initiating therapy with nevirapine. These patients require a lead-in dose of nevirapine 200 mg o.d., whereas this formulation contains the maintenance dose of nevirapine 200 mg b.d. (see Indications).

 

Thus, it is recommended that patients initiate therapy using a combination of LASOVIR and NIVEPIN during the first two weeks, and then switch to TROVIR once adequate tolerability is demonstrated.

A majority of these cases have been in women. Obestiy and prolonged nucleoside exposure may be risk factors. Caution should be exercised when administering stavudine to any patient, and particularly to those with no known risk factors for liver disease. Cases have also been reported in patients with no known risk factors. Treatment shuld be disscontinued in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked amino-transferase elevations.

 

BONE MARROW SUPRESSION TROVIR should be used with caution in patients who have bone marrow compromise evidenced by granulocyte count<1000 cells/mm3 or hemoglobin<9.5 g/dl(see Side Effects).

 

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 TROVIR.

 

TROVIR should be used during pregnancy only if the potential benefits outweigh the potential risk.

 

Lactation: It is recommended that HIV -infected mothers do not breast-feed their infants to avoid risking postnatal transmission of HIV infection. It is not known whether lamivudine is excreted in human milk. Nevirapine and zidovudineare present in breast milk.

 

Paediatrics:TROVIR is not intended for use in paediatric patients.

WITH ZIDOVUDINE Co-administration of ganciclovir, interferon-alpha, and other bone marrow suppressive or cytotoxic agents may increase the hematologic toxicity of zidovudine.

WITH NEVIRAPINE Rifampin/Rifabutin, Ketoconazole, Oral Contraceptives, Methadone.

vomiting, abdominal pain and discomfort, peripheral neuropathy, arthralgias, myalgias, skin rash, pruritus, transient neutropenia and thrombocytopenia and rarely, pancreatitis.

ZIDOVUDINEFever, headache, nausea, vomiting, anorexia, myalgia, insomnia, dizziness, paraesthesias, dyspnoea and rash. Malaise, gastrointestinal pain, dyspepsia and taste perversion neutropenia, lucopenia.

NEVIRAPINErash and increases in liver enzymes, hypersensitivity reactions mild to moderate, maculopapular erythematous cutaneous eruptions