Composition:

LAZID - N
Each film-coated tablet contains:
Zidovudine IP300 mg
Lamivudine IP150 mg
Nevirapine IP200 mg

Indications:

Lazid - N is indicated for the treatment of HIV infection, once patients have been stabilized on the nevirapine 200 mg twice daily, and have demonstrated adequate tolerability to nevirapine.


Contraindications:

Hypersensitive to any of the components of the formulation and in patients who are just initiating therapy with nevirapine.


Warnings and Precautions:

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues including zidovudine, lamivudine alone or in combination with other antiretrovirals. Use with caution in patients with known risk factors for liver disease. Treatment should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity. Zidovudine should be used with caution in patients who have bone marrow compromise. Frequent blood counts are strongly recommended in patients with advanced HIV disease who are treated with Lazid-N. Severe or life-threatening hepatotoxicity, including fatal fulminant hepatitis and severe life-threatening skin reactions have occurred in patients receiving Nevirapine. Monitoring of hepatic transaminases is strongly recommended during first six months of Nevirapine treatment. Treatment with Nevirapine should be withheld in patients with moderate or severe AST and ALT abnormalities and in patients developing signs or symptoms of severe skin reactions. Therapy with nevirapine must be initiated with a 14-day lead-in period of 200 mg/day which has been shown to reduce the frequency of rash.


Pregnancy:

Category C.
Nursing mother: Lamivudine, Zidovudine and Nevirapine are excreted in breast milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breastfeed if they are receiving Lazid-N


Drug Interactions:

emtri3040

Concomitant use of Zidovudine with stavudine and Zidovudine with doxorubicin should be avoided since an antagonistic relationship has been demonstrated. Some nucleoside analogues affecting DNA replication, such as ribavirin, antagonize the in vitro antiviral activity of Zidovudine against HIV; concomitant use of such drugs should be avoided. Coadministration of ganciclovir, interferon-alpha, and other bone marrow suppressive or cytotoxic agents may increase the hematological toxicity of Zidovudine. For patients experiencing pronounced anemia or other severe Zidovudine-associated events while receiving chronic administration of Zidovudine and

some of the drugs (e.g., fluconazole, valproic acid), Zidovudine dose reduction may be considered. Trimethoprim 160 mg and sulfamethoxazole 800 mg once daily has been shown to increase lamivudine exposure (AUC).

The effect of higher doses of trimethoprim and sulfamethoxazole on lamivudine pharmacokinetics has not been investigated. Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of lamivudine in combination with zalcitabine is not recommended. Nevirapine is an inducer of CYP450 enzymes. Cimetidine and macrolides antibiotics elevate steady-state Nevirapine trough concentrations. Nevirapine may decrease the plasma concentrations of oral contraceptives, ketokonazole, Rifampicin, indinavir and Saquinavir.


Adverse Effects:

Headache, diarrhea, nausea, other gastrointestinal disturbances, fatigue, insomnia, arthralgias, myalgias, neuropathy, nasal signs and symptoms, elevated liver enzymes, skin rash, fever or chills, anemia, occasional hepatotoxicity, peripheral neuropathy, myositis, skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis, hepatitis, granulocytopaenia.


Dosage and Administration:

Adults: One tablet to be taken orally twice daily.
Because Lazid-N is a fixed-dose combination it should not be given to patients who require dosage adjustment of lamivudine (such as those with body weight <50 kg) or zidovudine (such as those with creatinine clearance <50 ml/min or those experiencing dose-limiting adverse events) or to patients who have just initiated therapy with nevirapine (This is because an initial lead-in dosing of 200 mg of nevirapine once daily for 2 weeks is recommended. Following this lead-in dose, a dose escalation to 200 mg nevirapine twice daily may be carried out in the absence of any hypersensitivity reactions).