NEL-250 TABLETS

(Nelfinavir Tablets 250mg)

Composition:
Each Tablet contains:
Nelfinavir Mesylate
Eq. to Nelfinavir 250mg

Presentation:
10x10's

Description:
Nelfinavir meyslate is an inhibitor of the human immunodeficiency virus (HIV) protease. Nelfinavir tablets are formulated as meyslate salt and available for oral administration in strength of 250mg of Nelfinavir.

Mechanism of Action:
Nelfinavir is competitive inhibitor of HIV protease, an enzyme involved in the replication of HIV. protease inhibitor renders the virus non-infectious. Nelfinavir inhibits both HIV-1 and HIV-2 proteases.

Pharmacokinetics:
The pharmacokinetic properties of nelfinavir were evaluated in healthy volunteers and HIV-infected patients; no substantial differences were observed between the two groups.

Absorption:
After single and multiple oral doses of 500 to 750 mg (two to three 250 mg tablets) with food, peak nelfinavir plasma concentrations were typically achieved in 2 to 4 hours. After multiple dosing with 750 mg three times daily (TID) for 28 days (steady-state), peak plasma concentrations (Cmax) averaged 3-4 µg/mL and plasma concentrations prior to the morning dose (trough) were 1-3 µg/mL (trough sample collection times averaged 11 hours after the previous evening dose). A greater than dose-proportional increase in nelfinavir plasma concentrations was observed after single doses; however, this was not observed after multiple dosing.

Effect of Food on Oral Absorption:
Maximum plasma concentrations and area under the plasma concentration-time curve (AUC) were 2- to 3-fold higher under fed conditions compared to fasting. The effect of food on nelfinavir absorption was evaluated in two studies (n=14, total). The meals evaluated contained 517 to 759 Kcal, with 153 to 313 Kcal derived from fat.

Distribution:
The apparent volume of distribution following oral administration of nelfinavir was 2-7 L/kg. Nelfinavir in serum is extensively protein-bound (>98%).

Metabolism:
Unchanged nelfinavir comprised 82-86% of the total plasma radioactivity after a single oral 750 mg dose of 14C-nelfinavir. In vitro, multiple cytochrome P-450 isoforms including CYP3A are responsible for metabolism of nelfinavir. One major and several minor oxidative metabolites were found in plasma. The major oxidative metabolite has in vitro antiviral activity comparable to the parent drug.
Elimination: The terminal half-life in plasma was typically 3.5 to 5 hours. The majority (87%) of an oral 750 mg dose containing 14C-nelfinavir was recovered in the feces; fecal radioactivity consisted of numerous oxidative metabolites (78%) and unchanged nelfinavir (22%). Only 1-2% of the dose was recovered in urine, of which unchanged nelfinavir was the major component.

Indications:
Nelfinavir in combination with antiretroviral agents preferably in combination with nucleoside anologs in the treatment of HIV infection.

Contra-indications:
Nelfinavir Mesylate is contraindicated in patients with clinically significant hypersensitivity to any of the components.

Warnings:
Protease inhibitors causing high blood sugar and diabetes. Symptoms to watch out for include increased thirst and hunger, unexplained weight loss, increased urination, fatigue, and dry, itchy skin. There have been 83 cases of this problem reported so far, usually 10-11 weeks after starting the protease inhibitor, although in one case symptoms started just four days afterwards. There are also reports of protease inhibitors causing high levels of fats (called cholesterol and triglycerides) in the blood. Because this can lead to heart problems, fat levels should be closely monitored in people taking protease inhibitors.

Dosage and directions for use:

Adults/Adolescents:
Orally 1,250 mg (five 250-mg tablets or two 625-mg tablets) twice daily or 750 mg (three tablets) three times daily, with a meal or light snack.

Pediatric:
Children aged 2 to 13 years, 20 to 30 mg/kg three times daily with a meal or light snack.

Neonates:
Not determined.

Drugs requiring dose modification Rifabutin :
The coadministration of nelfinavir 750 mg every 8 hours with refibutin should be half that of the normal dose.
Nelfinavir plasma concentrations may increase in presence of Indinavir resulting in potential increases in side effects (the safety of these combinations have not been established. Caution is advised if sildenafil is prescribed in patients receiving proteases inhibitors.
Use an alternative method of contraception from birth control pills during nelfinavir therapy.

Concomitant therapy:
Nelfinavir's effectiveness may be decreased with concomitant nevirapine.

Drugs not requiring dose modification:
Nucleoside analogue antiretroviral agents. Administration of Nelfinavir (750 mg every 8 hours) with Lamivudine (150 mg every 12 hours) and Zidovudine (300 every 12 hours) not require dose modification.

Side-effects and special precautions:
The most frequent side effect associated with nelfinavir therapy is diarrhea, with moderate or severe diarrhea occurring in up to 20% of those taking the drug. Metabolic (lipid and glucose) and morphologic (fat accumulation and fat atrophy) abnormalities have been associated with protease inhibitors in general.

Precautions:

Pregnancy :
There are no adequate and well-controlled studies in pregnant women. Nelfinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mother :

Animal studies suggest that nelfinavir may be excreted in milk. Hence advise against breast feeding by HIV infected mothers to avoid postnatal transmission of the virus to the infant.

Drug Interactions:
Hypersensitivity to nelfinavir or product components concurrent therapy with the following drugs are contraindicated astemizole, cisapride, triazolam, midazolam, ergot derivatives or nevirapine.
Rifampin decreases nelfinavir plasma AUC BY - 82%, the two drugs should not be administered.
Concomitant administration of nelfinavir with lovastatin or simvastatin is not recommended because the risk of myopathy.
The risk of Myopathy may be increased when protease inhibitors are used in combination with Atorvastatin, cerivastatin, lovastatin, or simvastatin.
Unlike other protease inhibitors,Nelfin may be administered with dapsone, trimethoprim / sulfamethoxazole, clarithromycin, itraconazole and fluconazole.

Known symptoms of overdosage and particulars of its treatment:
No data available. However, unabsorbed drug should be removed via gastric lavage and activated charcoal: Significant symptoms beyond gastrointestinal disturbance is likely following acute overdose, hemodialysis will not be effective due to high protein binding of nelfinavir.

Storage conditions and period.
Store in cool, dry & dark place, preferably below 25°C. Shelf life is 2 years.

Package: 10 tablets packed in blister strip, 10 such blisters packed in a carton.