Agenerase Oral Solution
"The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended 150 mg lamivudine/300 mg raltegravir (Dutrebis, Merck Sharp & Dohme Limited) for the treatment of HIV 1 infection in adults, adolesce"...
Agenerase Oral Solution
(Generic versions may still be available.)
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 (amprenavir 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 (amprenavir 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 (amprenavir oral solution) , they should be monitored 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 (amprenavir oral solution) to AGENERASE Capsules as soon as they are able to take the capsule formulation.
Concurrent use of AGENERASE Oral Solution (amprenavir 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).
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.
General: AGENERASE Capsules and AGENERASE Oral Solution (amprenavir oral solution) are not interchangeable on a milligram-per-milligram basis(see CLINICAL PHARMACOLOGY: Pediatric Patients and CONTRAINDICATIONS).
Amprenavir is a sulfonamide. The potential for cross-sensitivity between drugs in the sulfonamide class and amprenavir is unknown. AGENERASE should be used with caution in patients with a known sulfonamide allergy.
AGENERASE is principally metabolized by the liver. AGENERASE, when used alone and in combination with low-dose ritonavir, has been associated with elevations of SGOT (AST) and SGPT (ALT) in some patients. Caution should be exercised when administering AGENERASE to patients with hepatic impairment (see DOSAGE AND ADMINISTRATION). Appropriate laboratory testing should be conducted prior to initiating therapy with AGENERASE and at periodic intervals during treatment.
Formulations of AGENERASE provide high daily doses of vitamin E (see INFORMATION FOR PATIENTS, DESCRIPTION, and DOSAGE AND ADMINISTRATION). The effects of long-term, high-dose vitamin E administration in humans is not well characterized and has not been specifically studied in HIV- infected individuals. High vitamin E doses may exacerbate the blood coagulation defect of vitamin K deficiency caused by anticoagulant therapy or malabsorption.
Patients with Hemophilia: There have been reports of spontaneous bleeding in patients with hemophilia A and B treated with protease inhibitors. In some patients, additional factor VIII was required. In many of the reported cases, treatment with protease inhibitors was continued or restarted. A causal relationship between protease inhibitor therapy and these episodes has not been established.
Immune Reconstitution Syndrome: Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including AGENERASE. 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.
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.
Lipid Elevations: Treatment with AGENERASE alone or in combination with ritonavir capsules has resulted in increases in the concentration of total cholesterol and triglycerides. Triglyceride and cholesterol testing should be performed prior to initiation of therapy with AGENERASE and at periodic intervals during treatment. Lipid disorders should be managed as clinically appropriate. See PRECAUTIONS Table 8: Established and Other Potentially Significant Drug Interactions for additional information on potential drug interactions with AGENERASE and HMG-CoA reductase inhibitors.
Resistance/Cross-Resistance: Because the potential for HIV cross-resistance among protease inhibitors has not been fully explored, it is unknown what effect amprenavir therapy will have on the activity of subsequently administered protease inhibitors. It is also unknown what effect previous treatment with other protease inhibitors will have on the activity of amprenavir (see MICROBIOLOGY).
Information for Patients: A statement to patients and healthcare providers is included on the product's bottle label: ALERT: Find out about medicines that should NOT be taken with AGENERASE. A Patient Package Insert (PPI) for AGENERASE Oral Solution (amprenavir oral solution) is available for patient information.
AGENERASE Oral Solution (amprenavir 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. AGENERASE Oral Solution (amprenavir oral solution) should be used only when AGENERASE Capsules or other protease inhibitor formulations are not therapeutic options.
Patients treated with AGENERASE Capsules should be cautioned against switching to AGENERASE Oral Solution (amprenavir oral solution) because of the increased risk of adverse events from the large amount of propylene glycol in AGENERASE Oral Solution (amprenavir oral solution) .
Women, Asians, Eskimos, or Native Americans, as well as patients who have hepatic or renal insufficiency, should be informed that they may be at increased risk of adverse events from the large amount of propylene glycol in AGENERASE Oral Solution.
Patients should be informed that AGENERASE is not a cure for HIV infection and that they may continue to develop opportunistic infections and other complications associated with HIV disease. The long-term effects of AGENERASE (amprenavir) are unknown at this time. Patients should be told that there are currently no data demonstrating that therapy with AGENERASE can reduce the risk of transmitting HIV to others through sexual contact.
Patients should remain under the care of a physician while using AGENERASE. Patients should be advised to take AGENERASE every day as prescribed. AGENERASE must always be used in combination with other antiretroviral drugs. Patients should not alter the dose or discontinue therapy without consulting their physician. If a dose is missed, patients should take the dose as soon as possible and then return to their normal schedule. However, if a dose is skipped, the patient should not double the next dose.
Patients should inform their doctor if they have a sulfa allergy. The potential for cross-sensitivity between drugs in the sulfonamide class and amprenavir is unknown.
AGENERASE may interact with many drugs; therefore, patients should be advised to report to their doctor the use of any other prescription or nonprescription medication or herbal products, particularly St. John's wort.
Patients taking antacids (or the buffered formulation of didanosine) should take AGENERASE at least 1 hour before or after antacid (or the buffered formulation of didanosine) use.
Patients should be advised that drinking alcoholic beverages is not recommended while taking AGENERASE Oral Solution (amprenavir oral solution) .
Patients receiving sildenafil should be advised that they may be at an increased risk of sildenafil-associated adverse events including hypotension, visual changes, and priapism, and should promptly report any symptoms to their doctor.
Patients taking AGENERASE should be instructed not to use hormonal contraceptives because some birth control pills (those containing ethinyl estradiol/norethindrone) have been found to decrease the concentration of amprenavir. Therefore, patients receiving hormonal contraceptives should be instructed to use alternate contraceptive measures during therapy with AGENERASE.
High- fat meals may decrease the absorption of AGENERASE and should be avoided. AGENERASE may be taken with meals of normal fat content.
Patients should be informed that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time.
Adult and pediatric patients should be advised not to take supplemental vitamin E since the vitamin E content of AGENERASE exceeds the Reference Daily Intake (adults 30 IU, pediatrics approximately 10 IU).
Laboratory Tests: The combination of AGENERASE and low-dose ritonavir has been associated with elevations of cholesterol and triglycerides, SGOT (AST), and SGPT (ALT) in some patients. Appropriate laboratory testing should be considered prior to initiating combination therapy with AGENERASE and ritonavir capsules and at periodic intervals or if any clinical signs or symptoms of hyperlipidemia or elevated liver function tests occur during therapy. For comprehensive information concerning laboratory test alterations associated with ritonavir, physicians should refer to the complete prescribing information for NORVIR (ritonavir).
Carcinogenesis and Mutagenesis: Amprenavir was evaluated for carcinogenic potential by oral gavage administration to mice and rats for up to 104 weeks. Daily doses of 50, 275 to 300, and 500 to 600 mg/kg/day were administered to mice and doses of 50, 190, and 750 mg/kg/day were administered to rats. Results showed an increase in the incidence of benign hepatocellular adenomas and an increase in the combined incidence of hepatocellular adenomas plus carcinoma in males of both species at the highest doses tested. Female mice and rats were not affected. These observations were made at systemic exposures equivalent to approximately 2 times (mice) and 4 times (rats) the human exposure (based on AUC0-24 hr measurement) at the recommended dose of 1,200 mg twice daily. Administration of amprenavir did not cause a statistically significant increase in the incidence of any other benign or malignant neoplasm in mice or rats. It is not known how predictive the results of rodent carcinogenicity studies may be for humans. However, amprenavir was not mutagenic or genotoxic in a battery of in vitro and in vivo assays including bacterial reverse mutation (Ames), mouse lymphoma, rat micronucleus, and chromosome aberrations in human lymphocytes.
Fertility: The effects of amprenavir on fertility and general reproductive performance were investigated in male rats (treated for 28 days before mating at doses producing up to twice the expected clinical exposure based on AUC comparisons) and female rats (treated for 15 days before mating through day 17 of gestation at doses producing up to 2 times the expected clinical exposure). Amprenavir did not impair mating or fertility of male or female rats and did not affect the development and maturation of sperm from treated rats. The reproductive performance of the F1 generation born to female rats given amprenavir was not different from control animals.
Pregnancy and Reproduction: AGENERASE Oral Solution (amprenavir oral solution) is contraindicated during pregnancy due to the potential risk of toxicity to the fetus from the high propylene glycol content. Therefore, if AGENERASE is used in pregnant women, the AGEN ERASE Capsules formulation should be used (see complete prescribing information for AGENERASE Capsules).
Antiretroviral Pregnancy Registry: To monitor maternal- fetal outcomes of pregnant women exposed to AGENERASE, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
Nursing Mothers: The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. Although it is not known if amprenavir is excreted in human milk, amprenavir is secreted into the milk of lactating rats. 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 AGENERASE.
Pediatric Use: AGENERASE Oral Solution (amprenavir oral solution) is contraindicated in infants and children below the age of 4 years due to the potential risk of toxicity from the excipient, propylene glycol (see CONTRAINDICATIONS and WARNINGS). Alcohol dehydrogenase (ADH), which metabolizes propylene glycol, is present in the human fetal liver at 2 months of gestational age, but at only 3% of adult activity. Although the data are limited, it appears tha t by 12 to 30 months of postnatal age, ADH activity is equal to or greater than that observed in adults.
Two hundred fifty-one patients aged 4 and above have received amprenavir as single or multiple doses in studies. An adverse event profile similar to that seen in adults was seen in pediatric patients.
Concurrent use of AGENERASE Oral Solution (amprenavir 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. This combination has not been studied in pediatric patients.
Geriatric Use: Clinical studies of AGENERASE did not include sufficient numbers of patients aged 65 and over to determine whether the y respond differently from younger adults. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Last reviewed on RxList: 7/18/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Agenerase Oral Solution Information
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