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Basic Drug Info
Drug Name:AGENERASE
Manufacturer:GlaxoSmithKline
Other Info:



Clinical Trials:


Indications and Usage

AGENERASE (amprenavir) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection.

The following points should be considered when initiating therapy with AGENERASE:In a study of NRTI-experienced, protease inhibitor-naive patients, AGENERASE was found to be significantly less effective than indinavir (see Description of Clinical Studies).

Mild to moderate gastrointestinal adverse events led to discontinuation of AGENERASE primarily during the first 12 weeks of therapy (see ADVERSE REACTIONS).

There are no data on response to therapy with AGENERASE in protease inhibitor-experienced patients.

AGENERASE Oral Solution should be used only when AGENERASE Capsules or other protease inhibitor formulations are not therapeutic options.
HIV Infections -- any state of infection accompanied by evidence of HIV in the body (positive test for HIV genome, cDNA, proteins, antigens, or antibodies); may be medically asymptomatic or symptomatic; use AIDS when appropriate.

Contraindications

Because of the potential risk of toxicity from the large amount of the excipient, propylene glycol, AGENERASE Oral Solution is contraindicated in infants and children below the age of 4 years, pregnant women, patients with hepatic or renal failure, and patients treated with disulfiram or metronidazole (see WARNINGS and PRECAUTIONS). Coadministration of AGENERASE is contraindicated with drugs that are highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events.

These drugs are listed in Table 6.Table 6.

Drugs That Are Contraindicated With AGENERASE Oral Solution Drug ClassDrugs Within Class That Are CONTRAINDICATED with AGENERASE Alcohol-dependence treatmentDisulfiram AntibioticMetronidazole Ergot derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine GI motility agentCisapride NeurolepticPimozide Sedatives/hypnoticsMidazolam, triazolam If AGENERASE Capsules are coadministered with ritonavir capsules, the antiarrhythmic agents flecainide and propafenone are also contraindicated. AGENERASEis contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product.
Kidney Failure -- A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal failure, either acute (KIDNEY FAILURE, ACUTE) or chronic (KIDNEY FAILURE, CHRONIC), requires HEMODIALYSIS.

Hypersensitivity -- Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.

Warnings

ALERT: Find out about medicines that should not be taken with AGENERASE.

Because of the potential risk of toxicity from the large amount of the excipient, propylene glycol, AGENERASE Oral Solution is contraindicated in infants and children below the age of 4 years, pregnant women, patients with hepatic or renal failure, and patients treated with disulfiram or metronidazole (see CLINICAL PHARMACOLOGY, CONTRAINDICATIONS, and PRECAUTIONS). Because of the possible toxicity associated with the large amount of propylene glycol and the lack of information on chronic exposure to large amounts of propylene glycol, AGENERASE Oral Solution should be used only when AGENERASE Capsules or other protease inhibitor formulations are not therapeutic options.

Certain ethnic populations (Asians, Eskimos, Native Americans) and women may be at increased risk of propylene glycol-associated adverse events due to diminished ability to metabolize propylene glycol; no data are available on propylene glycol metabolism in these groups (see CLINICAL PHARMACOLOGY: Special Populations: Gender and Race). If patients require treatment with AGENERASE Oral Solution, they should bemonitored closely for propylene glycol-associated adverse events, including seizures, stupor, tachycardia, hyperosmolality, lactic acidosis, renal toxicity, and hemolysis.

Patients should be switched from AGENERASE Oral Solution to AGENERASE Capsules as soon as they are able to take the capsule formulation.Concurrent use of AGENERASE Oral Solution and NORVIR (ritonavir) Oral Solution is not recommended because the large amount of propylene glycol in AGENERASE Oral Solution and ethanol in NORVIR Oral Solution may compete for the same metabolic pathway for elimination. Use of alcoholic beverages is not recommended in patients treated with AGENERASE Oral Solution. Serious and/or life-threatening drug interactions could occur between amprenavir and amiodarone, lidocaine (systemic), tricyclic antidepressants, and quinidine.

Concentration monitoring of these agents is recommended if these agents are used concomitantly with AGENERASE (see CONTRAINDICATIONS). Rifampin should not be used in combination with amprenavir because it reduces plasma concentrations and AUC of amprenavir by about 90%. A drug interaction study in healthy subjects has shown that ritonavir significantly increases plasma fluticasone propionate exposures, resulting in significantly decreased serum cortisol concentrations. Concomitant use of AGENERASE with ritonavir and fluticasone propionate is expected to produce the same effects.

Systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression have been reported during postmarketing use in patients receiving ritonavir and inhaled or intranasally administered fluticasone propionate.

Therefore, coadministration of fluticasone propionate and AGENERASE/ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects (see PRECAUTIONS: Drug Interactions). Concomitant use of AGENERASE and St.

John's wort (hypericum perforatum) or products containing St.

John's wort is not recommended.

Coadministration of protease inhibitors, including AGENERASE, with St.

John's wort is expected to substantially decrease protease inhibitor concentrations and may result in suboptimal levels of amprenavir and lead to loss of virologic response and possible resistance to AGENERASE or to the class of protease inhibitors. Concomitant use of AGENERASE with lovastatin or simvastatin is not recommended.

Caution should be exercised if HIV protease inhibitors, including AGENERASE, are used concurrently with other HMG-CoA reductase inhibitors that are also metabolized by the CYP3A4 pathway (e.g., atorvastatin).

The risk of myopathy, including rhabdomyolysis, may be increased when HIV protease inhibitors, including amprenavir, are used in combination with these drugs. Particular caution should be used when prescribing sildenafil in patients receiving amprenavir. Coadministration of AGENERASE 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 (see PRECAUTIONS: Drug Interactions and Information for Patients, and the complete prescribing information for sildenafil). Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, have occurred in patients treated with AGENERASE (see ADVERSE REACTIONS). Acute hemolytic anemia has been reported in a patient treated with AGENERASE. 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 causal relationships between protease inhibitor therapy and these events have not been established.

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