Anterovir® Capsules x 60 (LAMIVUDINE 150mg + ZIDOVUDINE 300mg)

AnterovirAnterovir® -NV Caplets
(LAMIVUDINE 150mg + ZIDOVUDINE 300mg +
NEVIRAPINE 200mg)
COMPOSITION
Each Anterovir® -NV Caplet contains:
Lamivudine150mg
Zidovudine 300mg
Nevirapine 200mg

 

ACTIONS
Anterovir® -NV Caplet is a combination of three 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 that 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 Anterovir® -NV Caplet contains half of the commonly prescribed daily doses of Lamivudine, Zidovudine and Nevirapine.
All the three drugs are to be administered twice daily, permitting a fixed-dose combination to be formulated. With the ability of this combination formulation, patients may be better able to comply with the dosage regimen thereby enhancing compliance.

INDICATIONS
Anterovir® -NV Caplet is indicated for the treatment of HIV infection in adults once patients have been stabilized on the maintenance regimen of Nevirapine 200mg twice daily and have demonstrated adequate tolerability to Nevirapine.

DOSAGE AND ADMINISTRATION
Adults and children above 12 years: 1 caplet twice daily.
Anterovir® -NV should not be administered to patients who have just initiated therapy with Nevirapine. Therapy should be initiated with Anterovir® one twice daily and Nevirapine one daily for the first 14 days.
When patients have demonstrated adequate tolerability to Nevirapine they can be switched to Anterovir®" -NV one twice daily.

Dosage Adjustment:
Lamivudine: Because it is a fixed dose combination, Anterovir® -NV caplet 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 ≤ 550ml/min) or those experiencing dose limiting adverse effects.

Nevirapine: Anterovir® -NV should be discontinued if patients experience severe rash. Patients experiencing mild to moderate rash during the 14 days lead-in period of 200mg/day of Nevirapine should not have their nevirapine dose increased or start therapy with Anterovir® -NV until the rash has resolved.

CONTRA-INDICATIONS
Anterovir® -NV is contra-indicated in patients with clinically significant hypersensitivity to any of the components contained in the formulation.
Anterovir® -NV is also contra-indicated for patients who are just initiating therapy with Nevirapine. These patients require a lead-in dose of Nevirapine 200mg once daily whereas Anterovir® -NV contains the maintenance dose of Nevirapine 200mg twice daily.

WARNINGS AND PRECAUTIONS
Lactic acidosis/severe hepatomeaalv with steatosis. including fatal cases, has been reported with the use of antiretroviral nucleoside analogues alone or in combination including Lamivudine and Zidovudine. Majority of these cases have been reported in women. Obesity and prolonged nucleoside exposure may be risk factors. Caution should be exercised when administering zidovudine and lamivudine to any patient and particularly to those with known risk factors for liver disease. Cases have also been reported in patients with no known risk factors.

Treatment should be discontinued 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 aminotransferase elevations.

Patients with HIV and hepatitis B virus co-infection: In clinical trials, some patients with HIV infection who have chronic liver disease due to hepatitis B virus infection experienced clinical or laboratory evidence of recurrent hepatitis upon discontinuation of Lamivudine. Consequences may be more severe in patients with decompensated liver disease.

Mvopathv: 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 of Anterovir® -NV caplet.
Hypersensitivity Reactions: Severe life-threatening skin reactions including fatal cases have occurred in patients treated with nevi rapine. 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.

KEEP OUT OF THE REACH OF CHILDREN!

DRUG INTERACTIONS
With Lamivudine: Trimethoprim 160mg/Sulphamethaxozole 800mg once daily
has been shown to increase lamivudine exposure.

With Zidovudine: Co-administration of ganciclovir, interferon-alpha and other bone marrow suppressive or cytotoxic agents may increase the haematologic toxicity of zidovudine.

Nevirapine: The induction of CYP3A by Nevirapine may result in lower plasma
concentrations of other concomitantly administered drugs that are extensively metabolized by CYP3A. If a patient has been stabilized on a dosage regimen for a drug metabolized by CYP3A and begins treatment with Nevirapine, dose adjustment may be necessary.

Impaired Renal Function: Reduction of the dosage of both Zidovudine and
Lamivudine is required in patients with a creatinine clearance of 50ml/min or less.

Hence. Anterovir®-NV Caplet cannot be used in this patient population.
Lactation: It is recommended that HIV - infected mothers do not breast-feed their infants to avoid risking post-natal transmission of HIV infection. It is not known whether Lamivudine is excreted in human milk. Zidovudine and Nevirapine is present in breast milk.

Paediatrics: Anterovir® -NV caplet is not intended for use in paediatric
patients.

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 analogue, alone or in combination. Other side effects associated with the use of Lamivudine are diarrhoea. malaise and fatigue, headache, nausea and vomiting. abdominal pain and discomfort, peripheral neuropathy, arthralgius, 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 effects or symptoms which occurred in at lest 5% of all patients with advanced HIV disease treated with 1,500mg/day of Zidovudine were: fever, headache, nausea, vomiting, anorexia, myalgia, insomnia, dizziness, paraesthesia, dysponoea 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.

OVER DOSAGE
Lamivudine: There is no known antidote for Lamivudine. One case of an adult ingesting 6g of Lamivudine was reported; there were no clinical signs or symptoms noted and haematologic tests remained normal. It is not known whether peritoneal dialysis or haemodialysis can remove lamivudine.

Zidovudine: Acute over dosage of Zidovudine has been reported in paediatric patients and adults. These involved exposures up to 50g. The only consistent findings were nausea and vomiting. Other reported occurrences included headache, dizziness, drowsiness, lethargy, confusion and one reported case of grandmal seizure. Haemodialysis 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.

STORAGE
Store in a cool dry place.

PRESENTATION
Anterovir® -NV is available as Caplets containing 150mg Lamivudine, 300mg
Zidovudine and 200mg Nevirapine in blister packs of 6 x 10's per pack.

NAFDAC REGISTRATION NUMBER: 04-8723

Manufactured by:
DRUGFILED PHARMACEUTICALS LIMITED
Lynson Chemical Avenue,
Km 38 Lagos- Abeokuta Expressway,
Sango- Otta, Nigeria
In co-operation with JULI PLC