Agenerase Capsules (Amprenavir)
Amprenavir is a non-peptidic competitive inhibitor of HIV-1 protease. It blocks the ability of viral protease to process gag and gag-pol polyproteins necessary for viral replication.
Absorption and Bioavailability: Amprenavir was rapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (t max) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established.
Increases in the area under the plasma concentration versus time curve (AUC) after single oral doses between 150 and 1200 mg were slightly greater than dose-proportional. Increases in AUC were dose-proportional after 3 weeks of dosing with doses from 300 to 1200mg twice daily.
The relative bioavailability of amprenavir capsules and oral solution was assessed in healthy adults. Amprenavir oral solution was 14% less bioavailable compared to the capsules.
Effects of Food on Oral Absorption: The relative bioavailability of amprenavir capsules was assessed in the fasting and fed states in healthy volunteers (standardized high-fat meal: 967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate). Administration of a single 1200mg dose of amprenavir in the fed state compared to the fasted state was associated with changes in C max (fed: 6.18±2.92 µg/mL, fasted: 9.72±2.75 µg/mL), T max (fed: 1.51±0.68 h, fasted 1.05±0.63h), and AUC (fed: 22.06±11.6 µg.h/mL, fasted: 28.05±10.1 µg.h/mL). Amprenavir may be taken with or without food, but should not be taken with a high-fat meal (see Dosage).
Special Populations: Adults with Impaired Renal Function: This population has not been studied. The renal elimination of unchanged amprenavir represents <3% of the administered dose.
Adults with Impaired Hepatic Function: Amprenavir has been studied in adult patients with impaired hepatic function using a single oral dose of 600 mg. The AUC 0-¥ was significantly greater in patients with moderate cirrhosis (25.76±14.68 µg.h/mL) compared with healthy volunteers (12.00±4.38 µg.h/mL). The AUC 0-¥ and C max were significantly greater in patients with severe cirrhosis (AUC 0-¥: 38.66±16.08 µg.h/mL; C max: 9.43±2.61 µg/mL) compared with healthy volunteers (AUC 0-¥: 12.00±4.38 µg.h/mL; C max: 4.90±1.39 µg/mL). Patients with impaired hepatic function require dosage adjustment (see Dosage).
Pediatric Patients: The pharmacokinetics of amprenavir have been studied after either single or repeat doses of amprenavir capsules or oral solution in 84 pediatric patients. Twenty HIV-1-infected children ranging in age from 4 to 12 years received single doses from 5 mg/kg to 20 mg/kg using 25 mg or 150 mg capsules. The C max of amprenavir increased less than proportionally, with dose. The AUC 0Ã¥ increased proportionally at doses between 5 and 20 mg/kg.
At present, the use of amprenavir in children is not recommended, however, if amprenavir capsules are used in this population, an oral dose of 20 mg/kg twice a day or 15 mg/kg 3 times a day, in combination with other antiretroviral agents, up to a maximum daily dose of 2400 mg should be used.
The pharmacokinetic interactions between amprenavir and low doses of ritonavir or other protease inhibitors, have not been evaluated in children. Therefore, such combinations should be avoided in children.
Amprenavir is 14% less bioavailable from the liquid formulation than from the capsules; therefore amprenavir capsules and amprenavir oral solution are not interchangeable on a mg/mg basis.
Amprenavir oral solution is contraindicated in infants and children below the age of 4 years due to the potential risk of toxicity from the large amount of the excipient propylene glycol. Please see the Product Monograph for amprenavir oral solution for full information.
Geriatric Patients: The pharmacokinetics of amprenavir have not been studied in patients over 65 years of age.
Gender: The pharmacokinetics of amprenavir do not differ in males and females.
Amprenavir Is A Non-peptidic Competitive Inhibitor Of HIV-1 Protease. It Blocks The Ability Of Viral Protease To Process Gag And Gag-pol Polyproteins Necessary For Viral Replication.
Absorption And Bioavailability: Amprenavir Was Rapidly Absorbed After Oral Administration In HIV-1-infected Patients With A Time To Peak Concentration (t Max) Typically Between 1 And 2 Hours After A Single Oral Dose. The Absolute Oral Bioavailability Of Amprenavir In Humans Has Not Been Established.
Increases In The Area Under The Plasma Concentration Versus Time Curve (AUC) After Single Oral Doses Between 150 And 1200 Mg Were Slightly Greater Than Dose-proportional. Increases In AUC Were Dose-proportional After 3 Weeks Of Dosing With Doses From 300 To 1200mg Twice Daily.
The Relative Bioavailability Of Amprenavir Capsules And Oral Solution Was Assessed In Healthy Adults. Amprenavir Oral Solution Was 14% Less Bioavailable Compared To The Capsules.
Effects Of Food On Oral Absorption: The Relative Bioavailability Of Amprenavir Capsules Was Assessed In The Fasting And Fed States In Healthy Volunteers (standardized High-fat Meal: 967 Kcal, 67 G Fat, 33 G Protein, 58 G Carbohydrate). Administration Of A Single 1200mg Dose Of Amprenavir In The Fed State Compared To The Fasted State Was Associated With Changes In C Max (fed: 6.18±2.92 µg/mL, Fasted: 9.72±2.75 µg/mL), T Max (fed: 1.51±0.68 H, Fasted 1.05±0.63h), And AUC (fed: 22.06±11.6 µg.h/mL, Fasted: 28.05±10.1 µg.h/mL). Amprenavir May Be Taken With Or Without Food, But Should Not Be Taken With A High-fat Meal (see Dosage).
Special Populations: Adults With Impaired Renal Function: This Population Has Not Been Studied. The Renal Elimination Of Unchanged Amprenavir Represents <3% Of The Administered Dose.
Adults With Impaired Hepatic Function: Amprenavir Has Been Studied In Adult Patients With Impaired Hepatic Function Using A Single Oral Dose Of 600 Mg. The AUC 0-¥ Was Significantly Greater In Patients With Moderate Cirrhosis (25.76±14.68 µg.h/mL) Compared With Healthy Volunteers (12.00±4.38 µg.h/mL). The AUC 0-¥ And C Max Were Significantly Greater In Patients With Severe Cirrhosis (AUC 0-¥: 38.66±16.08 µg.h/mL; C Max: 9.43±2.61 µg/mL) Compared With Healthy Volunteers (AUC 0-¥: 12.00±4.38 µg.h/mL; C Max: 4.90±1.39 µg/mL). Patients With Impaired Hepatic Function Require Dosage Adjustment (see Dosage).
Pediatric Patients: The Pharmacokinetics Of Amprenavir Have Been Studied After Either Single Or Repeat Doses Of Amprenavir Capsules Or Oral Solution In 84 Pediatric Patients. Twenty HIV-1-infected Children Ranging In Age From 4 To 12 Years Received Single Doses From 5 Mg/kg To 20 Mg/kg Using 25 Mg Or 150 Mg Capsules. The C Max Of Amprenavir Increased Less Than Proportionally, With Dose. The AUC 0Ã¥ Increased Proportionally At Doses Between 5 And 20 Mg/kg.
At Present, The Use Of Amprenavir In Children Is Not Recommended, However, If Amprenavir Capsules Are Used In This Population, An Oral Dose Of 20 Mg/kg Twice A Day Or 15 Mg/kg 3 Times A Day, In Combination With Other Antiretroviral Agents, Up To A Maximum Daily Dose Of 2400 Mg Should Be Used.
The Pharmacokinetic Interactions Between Amprenavir And Low Doses Of Ritonavir Or Other Protease Inhibitors, Have Not Been Evaluated In Children. Therefore, Such Combinations Should Be Avoided In Children.
Amprenavir Is 14% Less Bioavailable From The Liquid Formulation Than From The Capsules; Therefore Amprenavir Capsules And Amprenavir Oral Solution Are Not Interchangeable On A Mg/mg Basis.
Amprenavir Oral Solution Is Contraindicated In Infants And Children Below The Age Of 4 Years Due To The Potential Risk Of Toxicity From The Large Amount Of The Excipient Propylene Glycol. Please See The Product Monograph For Amprenavir Oral Solution For Full Information.
Geriatric Patients: The Pharmacokinetics Of Amprenavir Have Not Been Studied In Patients Over 65 Years Of Age.
Gender: The Pharmacokinetics Of Amprenavir Do Not Differ In Males And Females.
Amprenavir should not be administered concurrently with astemizole, cisapride, diazepam, dihydroergotamine, ergotamine, flurazepam, midazolam, pimozide, terfenadine, or triazolam. Although these drugs have not been specifically studied, coadministration may result in competitive inhibition of metabolism of these products and may cause serious or life-threatening adverse events.
Due to the potential risk of toxicity from the high propylene glycol content of amprenavir oral solution, that formulation is contraindicated in infants and children younger than 4 years of age, pregnant women, patients with hepatic or renal failure, and patients treated with disulfiram or metronidazole. Consult the Product Monograph for amprenavir oral solution for full information.
Amprenavir should not be given with rifampin. Rifampin reduces trough plasma concentrations of amprenavir by approximately 92% (see Precautions, Drug Interactions, Antibiotics).
Amprenavir is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of the products.
Serious and/or life-threatening drug interactions could occur between amprenavir and amiodarone, lidocaine (systemic), tricyclic antidepressants, quinidine or warfarin (monitor INR). Concentration monitoring of these agents is recommended if these agents are used concomitantly with amprenavir. Phenobarbital and phenytoin may decrease amprenavir concentrations.
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 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 relationship between protease inhibitor therapy and these events has not been established.
HMG-CoA reductase inhibitors (statins) may interact with protease inhibitors and increase the risk of myopathy including rhabdomyolysis. Concomitant use of protease inhibitors with lovastatin or simvastatin is not recommended. Other HMG-CoA reductase inhibitors (statins), may also interact with protease inhibitors. This warning is based on clinical reports, and on indirect evidence from studies on the cytochrome P450 CYP3A4 metabolism pathway.
Particular caution should be used when prescribing sildenafil in patients receiving protease inhibitors, including amprenavir. Coadministration of protease inhibitors 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, Information to Be Provided to the Patient, Drug Interactions and the complete prescribing information for sildenafil).
Concomitant use of St. John's wort (Hypericum perforatum) or St. John's wort-containing products and amprenavir is not recommended. Coadministration of St. John's wort with protease inhibitors, including amprenavir, is expected to substantially decrease protease inhibitor concentrations and may result in sub-optimal levels of amprenavir and lead to loss of virologic response and possible resistance to amprenavir or the class of protease inhibitors.
Because of the potential toxicity from the large amount of the excipient propylene glycol contained in amprenavir oral solution, that formulation is contraindicated in certain patient populations and should be used with caution in others. Consult the Product Monograph for Agenerase oral solution for full information.
Severe and life-threatening skin reactions, including Stevens-Johnson syndrome, have occurred in patients treated with amprenavir (see Adverse Effects).
Acute hemolytic anemia has been reported in a patient treated with amprenavir.
General: Formulations of amprenavir provide high daily doses of vitamin E. 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. Each 150 mg capsule contains 109 IU vitamin E. The maximum daily dose of amprenavir capsules corresponds to vitamin E intake of approximately 1750 IU/day.
Amprenavir capsules and oral solution are not interchangeable on a mg/mg basis (see Pharmacology, Pediatric Patients).
Amprenavir is a sulfonamide. The potential for cross-sensitivity between drugs in the sulfonamide class and amprenavir is unknown. Patients with a known sulfonamide allergy should be treated with caution.
Amprenavir is principally metabolized by the liver; therefore, caution should be exercised when administering this drug to patients with hepatic impairment (see Dosage).
Preliminary data from long-term carcinogenicity studies with amprenavir has revealed histopathological evidence for hepatocellular adenomas in both male mice and rats, and hepatocellular carcinomas have been seen in male mice only. The clinical relevance of these findings is unknown.
Patients with Hemophilia: There have been reports of increased bleeding, including spontaneous skin hematomas and hemarthroses, in hemophiliac patients 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 were continued or reintroduced if treatment had been discontinued. A causal relationship has been evoked, although the mechanism of action has not been elucidated. Hemophiliac patients should therefore be made aware of the possibility of increased bleeding.
Fat Redistribution: Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, breast enlargement, and “cushingoid appearance,” have been observed in patients receiving antiretroviral therapies. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established.
Contraceptives: Because of the potential for metabolic interactions with amprenavir, the efficacy of hormonal contraceptives may be reduced. Therefore, additional reliable barrier methods of contraception are recommended for women of childbearing potential.
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.
Information to Be Provided to the Patient: Patients treated with amprenavir capsules should be cautioned against switching to amprenavir oral solution because of the increased risk of adverse events from the large amount of propylene glycol in amprenavir oral solution. Please see the Product Monograph for amprenavir oral solution for full information.
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.
Patients should be advised of the importance of taking amprenavir exactly as prescribed. Amprenavir must always be used in combination with other antiretroviral drugs. Amprenavir is not a cure for HIV infection and patients may continue to experience illnesses associated with HIV infection, including opportunistic infections. Patients should be advised that the use of amprenavir has not been shown to reduce the risk of transmission of HIV. Patients should remain under the care of a physician when using amprenavir. The long-term effects of amprenavir are unknown at this time.
Amprenavir capsules are for oral ingestion only.
Amprenavir may interact with some drugs, therefore, patients should be advised to report to their doctor the use of any other prescription or non-prescription medication.
Patients taking antacids (or didanosine) should take amprenavir at least 1 hour before or after antacid (or didanosine) use.
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 receiving hormonal contraceptives should be instructed that alternate contraceptive measures should be used during therapy with amprenavir.
High-fat meals may decrease the absorption of amprenavir and should be avoided. Amprenavir 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 protease inhibitors and that the cause and long-term health effects of these conditions are not known at this time.
Given the vitamin E content of amprenavir capsules, patients should be advised that supplemental vitamin E is not recommended.
Geriatrics: Clinical studies of amprenavir did not include sufficient numbers of patients aged 65 and over to determine whether they 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.
Children: One hundred and eighteen patients 4 to 17 years of age have received amprenavir as single or multiple doses in Phase I to III studies. An adverse event profile similar to that seen in adults was seen in pediatric patients.
Amprenavir oral solution is contraindicated in infants and children below the age of 4 years due to the potential risk of toxicity from the large amount of the excipient propylene glycol. Please see the Product Monograph for amprenavir oral solution for full information.
The safety, effectiveness, and pharmacokinetics of amprenavir have not been evaluated in pediatric patients below the age of 4 years.
Pregnancy: There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response, therefore administration of amprenavir in pregnancy should be considered only if the benefit to the mother outweighs the possible risk to the fetus.
Amprenavir oral solution is contraindicated during pregnancy due to the potential risk of toxicity to the fetus from the high propylene glycol content.
Antiretroviral Pregnancy Registry: To monitor maternal-fetal outcomes of pregnant women exposed to amprenavir, an Antiretroviral pregnancy Registry has been established. Physicians are encouraged to register patients by calling GlaxoSmithKline's Drug Surveillance Department (1-800-387-7374).
Lactation: 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 possible adverse effects of amprenavir, mothers should be instructed not to breast-feed if they are receiving amprenavir.
Drug Interactions : Amprenavir is metabolized in the liver by the cytochrome P450 enzyme system. Amprenavir inhibits CYP3A4. Caution should be used when coadministering medications that are substrates, inhibitors, or inducers of CYP3A4. Amprenavir should not be administered concurrently with medications with narrow therapeutic windows which are substrates of CYP3A4. There are also other agents that may result in serious and/or life-threatening drug interactions (see Contraindications).
Drug interaction studies were performed with amprenavir capsules and other drugs likely to be coadministered or drugs commonly used as probes for pharmacokinetic interactions.
No dose recommendation can be given for the use of amprenavir in combination with other protease inhibitors in children and patients with renal impairment. Such combinations should be avoided in patients with hepatic impairment.
Nucleoside analogue reverse transcriptase inhibitors (NRTIs): Didanosine: no pharmacokinetic study has been performed with amprenavir in combination with didanosine, however, due to its antacid component, it is recommended that didanosine and amprenavir should be administered at least 1 hour apart (see Other Possible Interactions, Antacids).
Non-nucleoside reverse transcriptase inhibitors (NNRTIs): NNRTIs have the potential to increase (delavirdine) or decrease (efavirenz, nevirapine) serum concentrations of amprenavir.
Antibiotics/Antifungals: Dapsone and Erythromycin: Dapsone and erythromycin may have their plasma concentrations increased by amprenavir. Erythromycin may also increase amprenavir serum concentrations.
Itraconazole: Itraconazole may have its plasma concentrations increased by amprenavir. Itraconazole may increase serum concentrations of amprenavir.
Rifampin: Rifampin should not be used in combination with amprenavir since it reduces plasma concentrations and AUC of amprenavir by approximately 92% (see Contraindications).
Rifabutin: Coadministration of amprenavir with rifabutin results in a 15% decrease in amprenavir plasma AUC and a 193% increase in rifabutin plasma AUC. A dosage reduction of rifabutin to at least half the recommended dose is required when amprenavir and rifabutin are coadministered. A complete blood count should be performed weekly and as clinically indicated in order to monitor for neutropenia in patients receiving amprenavir and rifabutin.
Other Possible Interactions : Other medications listed below are examples of substrates, inhibitors, or inducers of CYP3A4 that could have potential interactions, when used concomitantly with amprenavir. The clinical significance of these potential interactions are unknown and have not been studied. Patients should therefore be monitored for toxicities associated with such drugs when these are used in combination with amprenavir.
Antacids: Antacids (and didanosine secondary to the antacid content) have not been specifically studied. Based upon data with other protease inhibitors, it is advisable that antacids not be taken at the same time as amprenavir because of potential interference with absorption. It is recommended that their administration be separated by at least 1 hour.
Benzodiazepines: Alprazolam, clorazepate, diazepam, flurazepam, midazolam and triazolam may have their serum concentrations increased by amprenavir, which could increase their activity (see Contraindications).
Calcium Channel Blockers: Diltiazem, nicardipine, nifedipine, and nimodipine may have their serum concentrations increased by amprenavir, which could increase their activity.
Cholesterol-lowering Agents: HMG-CoA reductase inhibitors (statins) may interact with protease inhibitors and increase the risk of myopathy including rhabdomyolysis. Concomitant use of protease inhibitors with lovastatin or simvastatin is not recommended. Other HMG CoA reductase inhibitors (statins), may also interact with protease inhibitors. This warning is based on clinical reports, and on indirect evidence from studies on the cytochrome P450 CYP3A4 metabolism pathway.
Erectile Dysfunction Agents: Based on data for other protease inhibitors caution should be used when prescribing sildenafil to patients receiving amprenavir. Coadministration of amprenavir with sildenafil may substantially increase sildenafil plasma concentrations and may result in sildenafil-associated adverse events.
Methadone and Opiate Derivatives: Patients treated with methadone and opiate derivatives should be monitored carefully as the concurrent administration of amprenavir and opiate derivatives may result in a significant interaction.
Steroids: Estrogens, progestogens, and some glucocorticoids may have an interaction with amprenavir but there is insufficient information to predict the nature of the interaction. Because of this potential for metabolic interactions with amprenavir, the efficacy of hormonal contraceptives may be reduced. Alternate or additional reliable barrier methods of contraception are recommended for women of childbearing potential.
St. John's Wort: Patients on amprenavir should not use products containing St. John's Wort (Hypericum perforatum) since it may result in reduced plasma concentrations of amprenavir (see Warnings).
Other Agents: There are other agents that may have their plasma concentrations increased by amprenavir, and include but are not limited to: clozapine, carbamazepine, loratadine, pimozide, and warfarin. Cimetidine may increase amprenavir plasma concentrations.
Rates of discontinuation of randomized therapy due to adverse events were 15% in amprenavir vs 3% in placebo recipients from Study 3001, and 16% in amprenavir vs 8% in indinavir recipients from Study 3006. In these studies, adverse events leading to amprenavir discontinuation included gastrointestinal events (11%), rash (3%), and paresthesias (<1%).
Most gastrointestinal events (nausea, vomiting, diarrhea, and abdominal pain) that led to amprenavir discontinuation were graded as mild or moderate in severity.
In all multidose studies in HIV-infected patients, skin rash occurred in 28% of patients treated with amprenavir. Rashes were usually maculopapular and of mild or moderate intensity, some with pruritus. Rashes had onsets ranging from 7 to 73 days (median: 10 days) after amprenavir initiation. With mild or moderate rash, amprenavir dosing was often continued without interruption; if interrupted, reintroduction of amprenavir generally did not result in rash recurrence (Phase III studies).
Severe or life-threatening rash, including Stevens-Johnson syndrome, occurred in 1% of recipients of amprenavir (4% of recipients who developed rash) (see Warnings). Amprenavir therapy should be discontinued for severe or life-threatening rashes and for moderate rashes accompanied by systemic symptoms.
The most frequent clinical adverse events related to study drugs, of at least moderate intensity (Grade 2 or more), reported in 2 large clinical studies in adults are summarized in Table II. All events reported in at least 1% of subjects treated with amprenavir are included.
In phase III trials, in combination with various NRTIs, the most frequent treatment-emergent laboratory abnormalities (Grade 2 or more) were elevated transaminases (5%), hypertriglyceridemia (4%), elevated amylase (2.5%), hyperbilirubinemia (<1%) and hyperglycemia (<1%); almost all subjects with abnormal liver function tests were coinfected with Hepatitis B or C virus.
Increased CPK, myalgia, myositis and infrequently rhabdomyolysis have been reported with protease inhibitors particularly in combination with nucleoside analogues.
Symptoms and Treatment: There is no known antidote for amprenavir. It is not known whether amprenavir can be removed by peritoneal dialysis or hemodialysis. If overdosage occurs, the patient should be monitored for evidence of toxicity and standard supportive treatment applied as necessary. Although no data are available, administration of activated charcoal may be used to aid in removal of unabsorbed drug.
Amprenavir can be taken with or without food; however, a high-fat meal decreases the absorption of amprenavir and should be avoided.
Formulations of amprenavir provide high daily doses of vitamin E. Each 150 mg capsule contains 109 IU vitamin E. The maximum daily dose of amprenavir capsules corresponds to vitamin E intake of approximately 1750 IU/day.
Amprenavir is available as an oral solution for use in patients unable to swallow capsules (see Product Monograph for amprenavir oral solution for complete information). Patients should discontinue amprenavir oral solution as soon as they are able to swallow the capsule formulation (see Contraindications and Warnings). Amprenavir is 14% less bioavailable from the oral solution than from the capsules, therefore, amprenavir capsules and amprenavir oral solution are not interchangeable on a mg/mg basis.
Adults and Adolescents >12 years of age: Amprenavir with antiretroviral combinations excluding ritonavir: 1200 mg twice daily.
Amprenavir in combination with ritonavir plus other antiretroviral agents: 600 mg amprenavir with 100 mg ritonavir twice daily. Further evaluation of this regimen is ongoing in a confirmatory study.
Children from 4 to 12 years: At present, the use of amprenavir in children is not recommended although dosing recommendations are provided for information (see Pharmacology, Pediatric Patients).
The pharmacokinetic interactions between amprenavir and low doses of ritonavir or other protease inhibitors, have not been evaluated in children. Therefore, such combinations should be avoided in children.
Children <4 years: Amprenavir is not recommended in children <4years of age.
Patients with Hepatic Impairment: Amprenavir should be used with caution in patients with moderate or severe hepatic impairment. Patients with a Child-Pugh score ranging from 5 to 8 should receive a reduced dose of 450 mg twice daily, and patients with a Child-Pugh score ranging from 9 to 12 should receive 300 mg twice daily.
Patients with Renal Impairment: No initial dose adjustment is considered necessary in patients with renal impairment.
50 mg: Each oblong, opaque off-white to cream-colored soft gelatin capsule, printed with “GX CC1” on one side, contains: amprenavir 50 mg. Nonmedicinal ingredients: d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), polyethylene glycol 400 (PEG 400), and propylene glycol; capsule shell: d-sorbitol and sorbitans solution, gelatin, glycerin, and titanium dioxide. Soft gelatin capsules: printed with edible red ink. Bottles of 480.
150 mg: Each oblong, opaque off-white to cream-colored soft gelatin capsule, printed with “GX CC2” on one side, contains: amprenavir 150 mg. Nonmedicinal ingredients: d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS), polyethylene glycol 400 (PEG 400), and propylene glycol; capsule shell: d-sorbitol and sorbitans solution, gelatin, glycerin, and titanium dioxide. Soft gelatin capsules: printed with edible red ink. Bottles of 240.
Store between 15 and 30°C.
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Agenerase Capsules
Amprenavir
Antiretroviral Agent
