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Product
Antiretroviral products (Nelvir)
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Antiretroviral products (Nelvir)
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Nelvir
Nelfinavir Tablets
COMPOSITION
Each uncoated tablet contains Nelfinavir mesylate equivalent to
Nelfinavir 250 mg
DESCRIPTION
NELVIR (nelfinavir mesylate) is an inhibitor of the human immunodeficiency virus (HIV) protease.
PHARMACOLOGY
Pharmacodynamics
Nelfinavir is an inhibitor of the HIV-1 protease. Inhibition of the viral protease prevents cleavage of the gag-pol polyprotein resulting in the production of immature, non-infectious virus.
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Table 1. Pharmacokinetic Study in HIV-positive Patients
Effect of Food on Oral Absorption
Food increases nelfinavir exposure and decreases nelfinavir pharmacokinetic variability relative to the fasted state. In one study, healthy volunteers received a single dose of 1250 mg of nelfinavir 250 mg tablets (5 tablets) under fasted or fed conditions (three different meals). In a second study, healthy volunteers received single doses of 1250 mg nelfinavir (5 x 250 mg tablets) under fasted or fed conditions (two different fat content meals). The results from the two studies are summarized in Table 2 and Table 3, respectively.
Table 2: Increase in AUC, Cmax and Tmax for Nelfinavir in Fed State Relative to Fasted State Following 1250 mg nelfinavir (5 x 250 mg tablets)
Table 3: Increase in Nelfinavir AUC, Cmax and Tmax in Fed Low Fat (20%) versus High fat (50%) State Relative to Fasted State Following 1250 mg nelfinavir (5 x 250 mg tablets)
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 14 C-nelfinavir. In vitro, multiple cytochrome P-450 enzymes including CYP3A and CYP2C19 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. After single oral dose of 750mg the 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.
Renal Insufficiency: The pharmacokinetics of nelfinavir has not been studied in patients with renal insufficiency; however, less than 2% of nelfinavir is excreted in the urine, so the impact of renal impairment on nelfinavir elimination should be minimal.
INDICATIONS
NELVIR in combination with other antiretroviral agents is indicated for the treatment of HIV infection.
DOSAGE AND ADMINISTRATION
Adults: The recommended dose is 1250 mg (five 250 mg tablets) twice daily or 750 mg (three 250 mg tablets) three times daily. NELVIR should be taken with a meal.
Pediatrics: In children 2 years of age and older, the recommended oral dose of NELVIR 250 mg tablet is 45 to 55 mg/kg twice daily or 25 to 30 mg/kg three times daily. All doses should be taken with a meal.
Table 4: Dosing for Children ≥ 2 Years of Age (Tablets)
CONTRAINDICATIONS
NELVIR is contraindicated in patients with clinically significant hypersensitivity to any of its components.
Co-administration of nelfinavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. These drugs are listed in Table 5.
Table 5: Drugs That Are Contraindicated With Nelfinavir
| Drug Class Drug Class |
Drugs Within Class That Are Contraindicated With Nelfinavir |
| Antiarrhythmics |
Amiodarone, Quinidine
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| Ergot Derivatives |
Dihydroergotamine, Ergonovine, Ergotamine, Methylergonovine |
| Neuroleptic |
Pimozide |
| Sedative/Hypnotics |
Midazolam, Triazolam |
WARNINGS AND PRECAUTIONS
Diabetes Mellitus/Hyperglycemia
New onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus and hyperglycemia have been reported during post-marketing surveillance in HIV-infected patients receiving protease inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for treatment of these events. In some cases diabetic ketoacidosis has occurred. In those patients who discontinued protease inhibitor therapy, hyperglycemia persisted in some cases. Because these events have been reported voluntarily during clinical practice, estimates of frequency cannot be made and a causal relationship between protease inhibitor therapy and these events has not been established.
Resistance/Cross-Resistance
HIV cross-resistance between protease inhibitors has been observed .
Hemophilia
There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthrosis, in patients with hemophilia type A and B treated with protease inhibitors. In some patients, additional factor VIII was given. In more than half of the reported cases, treatment with protease inhibitors was continued or reintroduced. A causal relationship has not been established.
Fat Redistribution
Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
Immune Reconstitution Syndrome
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy including nelfinavir. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Drug Interactions
Nelfinavir is an inhibitor of CYP3A (cytochrome P450 3A). Co-administration of NELVIR and drugs primarily metabolized by CYP3A (e.g., dihydropyridine calcium channel blockers, HMGCoA reductase inhibitors, immunosuppressants and sildenafil) may result in increased plasma concentrations of the other drug that could increase or prolong both its therapeutic and adverse effects. Caution should be exercised when inhibitors of CYP3A, including nelfinavir, are co-administered with drugs that are metabolized by CYP3A and that prolong the QT interval. Nelfinavir is metabolised by CYP3A and CYP2C19. Co-administration of NELVIR and drugs that induce CYP3A, or CYP2C19 such as rifampin, may decrease nelfinavir plasma concentrations and reduce its therapeutic effect. Co-administration of NELVIR and drugs that inhibit CYP3A or CYP2C19, may increase nelfinavir plasma concentrations.
Concomitant use of NELVIR with lovastatin or simvastatin is not recommended. Caution should be exercised if NELVIR is used concurrently with other HMG-CoA reductase inhibitors that are also metabolised by the CYP3A pathway. The risk of myopathy including rhabdomyolysis may be increased when protease inhibitors including nelfinavir, are used in combination with these drugs.
Co-administration of a protease inhibitor with sildenafil is expected to substantially increase sildenafil concentrations and may result in an increase in sildenafil-associated adverse events including hypotension, visual changes and priapism.
St. John`s wort : Concomitant use of St. John`s wort (hypericum perforatum) or St. John`s wort-containing products and NELVIR is not recommended. Coadministration of St. John`s wort with protease inhibitors, including nelfinavir, is expected to substantially decrease protease inhibitor concentrations and may result in sub-optimal levels of nelfinavir and lead to loss of virologic response and possible resistance to nelfinavir or to the class of protease inhibitors.
Presentation
Nelvir
1box =100 tablets
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