TRIOMUNE-30
Each tablet contains
Stavudine 30 mg
Lamivudine 150 mg
Nevirapine 200 mg

TRIOMUNE – 40
Each tablet contains
Stavudine 40 mg
Lamivudine 150 mg
Nevirapine 200 mg

TRIOMUNE is indicated for the treatment of HIV infection, once patients have been stabilized on the maintenance regimen of nevirapine 200 mg b.d, and have demonstrated adequate tolerability to nevirapine.

Additional important information regarding the use of nevirapine for the treatment of HIV-1 infection:

• Based on serious and life-threatening hepatotoxicity observed in controlled and uncontrolled studies, TRIOMUNE should not be initiated in adult females with CD4+ cell counts greater than 250 cells/mm 3 or in adult males with CD4+ cell counts greater than 400 cells/mm 3 unless the benefit outweighs the risk (see WARNINGS AND PRECAUTIONS ).
• The 14-day lead-in period with nevirapine 200 mg daily dosing has been demonstrated to reduce the frequency of rash (see WARNINGS; DOSAGE AND ADMINISTRATION ).
• If rash persists beyond the 14 day lead-in period, do not dose escalate to 200 mg twice daily. The 200 mg once daily dosing regimen should not be continued beyond 28 days at which point an alternative regimen should be sought.

Adults

TRIOMUNE – 30
1 tablet twice daily for patients weighing < 60 kg

TRIOMUNE – 40
1 tablet twice daily for patients weighing = 60 kg

TRIOMUNE 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 b.d 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
Intensive clinical and laboratory monitoring, including liver function tests, is essential at baseline and during the first 18 weeks of treatment with nevirapine. The optimal frequency of monitoring during this period has not been established. Some experts recommend clinical and laboratory monitoring more often than once per month, and in particular, would include monitoring of liver function tests at baseline, prior to dose escalation, and at two weeks post dose escalation. After the initial 18-week period, frequent clinical and laboratory monitoring should continue throughout nevirapine treatment (See WARNINGS AND PRECAUTIONS ). In some cases, hepatic injury has progressed despite discontinuation of treatment.

Dosage Adjustment
Because it is a fixed-dose tablet, TRIOMUNE should not be prescribed for patients requiring dosage adjustment or those experiencing dose-limiting adverse events.

Lamivudine
Because it is a fixed-dose combination, TRIOMUNE should not be prescribed for patients requiring dosage adjustment, such as if creatinine clearance < 50 mL/min.

Stavudine
Peripheral neuropathy : Patients should be monitored for the development of peripheral neuropathy, which is usually characterised by numbness, tingling, or pain in the feet or hands. If these symptoms develop during treatment, TRIOMUNE therapy should be interrupted. Symptoms may resolve if therapy is withdrawn promptly. In some cases, symptoms may worsen temporarily following discontinuation of therapy. If symptoms resolve completely, patients may tolerate resumption of treatment at one-half the recommended dose.

If peripheral neuropathy recurs after resumption of TRIOMUNE , permanent discontinuation of TRIOMUNE should be considered.

Since TRIOMUNE is a fixed-dose combination, it cannot be used under these circumstances.

Nevirapine
TRIOMUNE should be discontinued if patients experience severe rash or a rash accompanied by constitutional findings (see WARNINGS AND PRECAUTIONS ). Patients experiencing rash during the 14-day lead-in period of 200 mg/day should not have their nevirapine dose increased or start therapy with TRIOMUNE until the rash has resolved (see WARNINGS AND PRECAUTIONS ).If rash persists beyond the 14 day lead-in period, do not dose escalate to TRIOMUNE twice daily. The TRIOMUNE once daily dosing regimen should not be continued beyond 28 days at which point an alternative regimen should be sought.

If clinical hepatitis occurs, nevirapine should be permanently discontinued and not restarted after recovery

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 TRIOMUNE in the absence of any signs of hypersensitivity.

TRIOMUNE is contraindicated in patients with clinically significant hypersensitivity to any of the components contained in the formulation.

TRIOMUNE is contraindicated in patients with moderate or severe (Child Pugh Class B or C, respectively) hepatic impairment [ see WARNINGS AND PRECAUTIONS ].

TRIOMUNE is also contraindicated in 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 ).

The 14-day lead-in period with TRIOMUNE daily dosing has been demonstrated to reduce the frequency of rash [ see WARNINGS AND PRECAUTIONS ].

If rash persists beyond the 14 day lead-in period, do not dose escalate to TRIOMUNE twice daily. The 200 mg nevirapine once daily dosing regimen should not be continued beyond 28 days at which point an alternative regimen should be sought.