Prozei - General Information
Prozei is a protease inhibitor used to treat HIV infection.
Pharmacology of Prozei
Prozei is a protease inhibitor with activity against Human Immunodeficiency Virus Type 1 (HIV-1). Protease inhibitors block the part of HIV called protease. HIV-1 protease is an enzyme required for the proteolytic cleavage of the viral polyprotein precursors into the individual functional proteins found in infectious HIV-1. Prozei binds to the protease active site and inhibits the activity of the enzyme. This inhibition prevents cleavage of the viral polyproteins resulting in the formation of immature non-infectious viral particles. Protease inhibitors are almost always used in combination with at least two other anti-HIV drugs.
Prozei 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 Capsules is available for patient information.
Patients treated with AGENERASE Capsules should be cautioned against switching to AGENERASE Oral Solution because of the increased risk of adverse events from the large amount of propylene glycol in AGENERASE Oral Solution. Please see the complete prescribing information for AGENERASE Oral Solution for full information.
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.
Some drugs should not be used with AGENERASE. Therefore, patients should be advised that they must 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 didanosine) should take AGENERASE 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 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 protease inhibitors 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 Capsules and Oral Solution exceeds the Reference Daily Intake (adults 30 IU, pediatrics approximately 10 IU).
Please read this information before you start taking AGENERASE (pronounced ah-GEN-er-ase), and reread it each time you receive your prescription, just in case something has changed. Remember that this information does not take the place of careful discussions with your doctor when you start this medication and at checkups. You should not change or stop your anti-HIV treatment without first talking with your doctor. You should tell your doctor about any drug you are taking or planning to take because taking AGENERASE with some medications can result in serious or life-threatening problems.
What is AGENERASE?
AGENERASE is a medication used to treat HIV infection. HIV is the virus that causes AIDS (acquired immune deficiency syndrome). AGENERASE is taken by mouth as a soft gel capsule or oral solution. It belongs to a class of anti-HIV medicines called protease inhibitors.
How does AGENERASE work?
AGENERASE is used only in combination with other anti-HIV medicines. When used in combination therapy, AGENERASE may help lower the amount of HIV found in your blood, raise CD4 (T) cell count, and keep your immune system as healthy as possible so that it can help fight infection. However, AGENERASE does not have these effects in all patients.
What are the side effects of AGENERASE?
Common side effects of AGENERASE are nausea, vomiting, diarrhea, rash, and a tingling sensation around the mouth. Severe or life-threatening rash has been reported.
Contact your doctor if you have nausea, vomiting, diarrhea, or rash. Your doctor may be able to help you manage these symptoms. Your doctor will advise you whether your symptoms can be managed on therapy or whether AGENERASE should be stopped.
This list of side effects is not complete. Your doctor or pharmacist can discuss with you a more complete list of possible side effects with AGENERASE. Talk to your doctor promptly about any side effects you have.
How should I take AGENERASE?
Take AGENERASE exactly as your doctor prescribes it. The usual dosage for adults and adolescents (at least 13 years of age) is eight 150-mg soft gel capsules twice a day (morning and night), in combination with other anti-HIV medicines.
AGENERASE can be taken with or without food. However, you should not take AGENERASE with a highfat meal because this could reduce the effectiveness of AGENERASE.
What should I do if I miss a dose of AGENERASE?
To help make sure that your anti-HIV therapy is as effective as possible, be very careful to take all of your medication exactly as your doctor prescribed it and do not skip any doses.
If you miss a dose of AGENERASE by more than 4 hours, wait and take the next dose at the regularly scheduled time. However, if you miss a dose by fewer than 4 hours, take your missed dose immediately. Then take your next dose at the regularly scheduled time. Do not take more or less than your prescribed dose of AGENERASE at any one time.
When your supply of AGENERASE or other anti-HIV drugs starts to run low, arrange to get more from your doctor or pharmacy. It is very important that you take anti-HIV drugs as prescribed by your doctor because the amount of virus in your blood may increase if one or more of the drugs is stopped, even for a short time.
Can AGENERASE be taken with other medications?
Protease inhibitors, including AGENERASE, may interact with other drugs, including those you take without a prescription. Before you take AGENERASE, tell your doctor about any drugs that you are taking or planning to take including non-prescription drugs.
• You should not take any of the following medications with AGENERASE because serious or life-threatening problems could occur.*
Halcion ® (triazolam) Propulsid ® (cisapride) Hismanal ® (astemizole) Versed ® (midazolam) Ergot medications (Cafergot ® and others) Vascor ® (bepridil)
• You should also not take rifampin with AGENERASE because this drug reduces the effectiveness of AGENERASE. Rifampin is also known as: Rifadin ®, Rifamate ®, Rifater ®, and Rimactane ®.
• Serious and/or life-threatening drug interactions can also occur if you take AGENERASE with any of the following drugs.* If you need to take any of these drugs, your doctor may closely monitor the amount of drug in your blood to minimize potential problems. Cordarone ® (amiodarone) Phenobarbital Dilantin ® (phenytoin) Lidocaine Coumadin ® (warfarin) (quinidine) Quinaglute ®, Cardioquin ®, Quinidex ® Antidepressants such as Elavil ® (amitriptyline), Norpramin ® (desipramine), Pamelor ® (nortriptyline), Tofranil ® (imipramine)
• Before you take Viagra ® (sildenafil) with AGENERASE, talk to your doctor about possible drug interactions and side effects. If you take Viagra and AGENERASE together, you may be at increased risk of side effects of Viagra such as low blood pressure, visual changes, and penile erection lasting more than 4 hours. If an erection lasts longer than 4 hours, you should seek immediate medical assistance to avoid permanent damage to your penis. Your doctor can explain these symptoms to you.
• If you use birth control pills, talk to your doctor about choosing a different type of contraceptive, since AGENERASE may reduce the effectiveness of some birth control pills.
• Because AGENERASE Capsules and Oral Solution contain large amounts of vitamin E, you should not take additional vitamin E while taking AGENERASE.
• Special considerations:*
If you take AGENERASE with Mycobutin ® (rifabutin), your doctor will lower the dose of Mycobutin. If you take AGENERASE with Videx ® (didanosine, ddI), take them at least 1 hour apart. If you take AGENERASE with antacids, take them at least 1 hour apart.
Does AGENERASE cure HIV infection or AIDS?
AGENERASE does not cure HIV infection or AIDS. At this time we do not know if AGENERASE will help you live longer or have fewer of the medical problems (opportunistic infections) that are associated with HIV infection or AIDS. Because of this, you must be sure to be seen regularly by your healthcare professional.
Does AGENERASE reduce the risk of passing HIV to others?
No. AGENERASE, as well as other anti-HIV medications, has not been shown to reduce the risk of passing HIV to others through sexual contact or blood contamination. Continue to practice safe sex and do not use or share dirty needles.
Who should not take AGENERASE?
Do not take AGENERASE if you have had a serious allergic reaction to AGENERASE or any of its ingredients. If you have liver disease, your dosage of AGENERASE may have to be adjusted.
If you are allergic to sulfa drugs, you should inform your doctor.
Can children take AGENERASE?
Children from 4 to 12 years of age can also take AGENERASE. Your doctor will tell you if the oral solution or capsule is best for your child. Your childís doctor will decide the right dose based on your childís weight and age. AGENERASE has not been studied in children under 4 years of age.
Can pregnant women and nursing mothers take AGENERASE?
AGENERASE has not been studied in pregnant women and the risk to the unborn child is not known. Talk to your doctor if you are pregnant or if you become pregnant while taking AGENERASE.
Mothers with HIV should not breastfeed their infants because HIV in the breast milk can infect the infant.
What other medical conditions should I discuss with my doctor?
Talk to your doctor if you are pregnant or if you become pregnant while you are taking AGENERASE. Also talk to your doctor if you have hemophilia or problems with your liver.
How should I store AGENERASE Capsules and Oral Solution?
AGENERASE Capsules and Oral Solution should be stored at room temperature and should not be refrigerated.
This medication is prescribed for a particular condition. Do not use it for any other condition or give it to anybody else. Keep AGENERASE and all medicines out of the reach of children.
Ask a healthcare professional any questions you may have about AGENERASE. AGENERASE is a trademark of the Glaxo Wellcome group of companies. *The brands listed are trademarks of their respective owners and are not trademarks of the Glaxo Wellcome group of companies. The makers of these brands are not affiliated with and do not endorse Glaxo Wellcome or its products.
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, or potentially toxic medications that are metabolized by CYP3A4. Amprenavir does not inhibit CYP2D6, CYP1A2, CYP2C9, CYP2C19, CYP2E1, or uridine glucuronosyltransferase (UDPGT).
HIV Protease Inhibitors: The effect of amprenavir on total drug concentrations of other HIV protease inhibitors in subjects receiving both agents was evaluated using comparisons to historical data. Indinavir steady-state Cmax, A.C. and Cmin were decreased by 22%, 38%, and 27%, respectively, by concomitant amprenavir. Similar decreases in Cmax and AUC were seen after the first dose. Saquinavir steady-state Cmax, A.C. and Cmin were increased 21%, decreased 19%, and decreased 48%, respectively, by concomitant amprenavir. Nelfinavir steady-state Cmax, A.C. and Cmin were increased by 12%, 15%, and 14%, respectively, by concomitant amprenavir.
Methadone: Coadministration of amprenavir and methadone can decrease plasma levels ofmethadone.
Coadministration of amprenavir and methadone as compared to a non-matched historicalcontrol group resulted in a 30%, 27%, and 25% decrease in serum amprenavir AUC, Cmax, andCmin, respectively.
Amprenavir is an inhibitor of cytochrome P450 C.P.A. metabolism and therefore should not be administered concurrently with medications with narrow therapeutic windows that are substrates of CYP3A4. There are other agents that may result in serious and/or life-threatening drug interactions.
Laboratory Tests: The combination of Amprenavir 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 Amprenavir and ritonavir 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).
AGENERASE should not be administered concurrently with astemizole, bepridil, cisapride, dihydroergotamine, ergotamine, midazolam, and 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.
AGENERASE is contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of this product.
Additional information about Prozei
Prozei Indication: For the treatment of HIV-1 infection in combination with other antiretroviral agents.
Mechanism Of Action: Prozei inhibits the HIV viral proteinase enzyme which prevents cleavage of the gag-pol polyprotein, resulting in noninfectious, immature viral particles.
Drug Interactions: Alprazolam Increases the effect and toxicity of benzodiazepine
Amiodarone The protease inhibitor increases the effect and toxicity of amiodarone
Anisindione Increases the anticoagulant effect
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atorvastatin Prozei can possibly increase the statin toxicity
Bepridil Increases the effect and toxicity of bepridil
Cisapride Increases the effect and toxicity of cisapride
Clorazepate Increases the effect and toxicity of benzodiazepine
Cyclosporine The protease inhibitor increases the effect of cyclosporine
Delavirdine Decreased levels of delavirdine with increased levels of amprenavir
Diazepam Increases the effect and toxicity of benzodiazepine
Dicumarol Increases the anticoagulant effect
Dihydroergotamine Increases the effect and toxicity of ergot derivative
Disulfiram Increased irsk of side effects (oral solution)
Ergotamine Increases the effect and toxicity of ergot derivative
Ethinyl Estradiol Ritonavir could decrease the contraceptive efficacy
Fentanyl The protease inhibitor increases the effect and toxicity of fentanyl
Flurazepam Increases the effect and toxicity of benzodiazepine
Methadone The protease inhibitor decreases the effect of methadone
Lovastatin Prozei can possibly increase the statin toxicity
Metronidazole Increased risk of side effects (oral solution)
Midazolam Increases the effect and toxicity of benzodiazepine
Acenocoumarol Increases the anticoagulant effect
Pimozide Increases the effect and toxicity of pimozide
Ranolazine Increased levels of ranolazine- risk of toxicity
Rifabutin Increases the effect and toxicity of rifabutin
Rifampin In presence of rifampin anticipate decrease of amprenavir efficiency
Sildenafil The protease inhibitor increases the effect and toxicity of sildenafil
Simvastatin Prozei can possibly increase the statin toxicity
St. John's Wort St. John's Wort decreases the effect of indinavir
Tacrolimus The protease inhibitor increase the effect and toxicity of tacrolimus
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Triazolam Increases the effect and toxicity of benzodiazepine
Vardenafil The protease inhibitor increases the effect adn toxicity of vardenafil
Vitamin E Increased serum levels of vitamin E
Warfarin Increases the anticoagulant effect
Aluminium The antiacid decreases the absorption of amprenavir
Bismuth Subsalicylate The antiacid decreases the absorption of amprenavir
Calcium The antiacid decreases the absorption of amprenavir
Dihydroxyaluminium The antiacid decreases the absorption of amprenavir
Magnesium oxide The antiacid decreases the absorption of amprenavir
Magnesium The antiacid decreases the absorption of amprenavir
Mestranol Ritonavir could decrease the contraceptive efficacy
Food Interactions: Take with or without food, however avoid lipid-rich meals.
Vitamin E increases amprenavir bioavailability.
Avoid alcohol, especially with the oral solution since it contains propylene glycol which competes with alcohol for alcohol dehydrogenase metabolism.
Generic Name: Amprenavir
Synonyms: AMP; AMV; APV; VX-478
Drug Category: Anti-HIV Agents; HIV Protease Inhibitors
Drug Type: Small Molecule; Approved
Other Brand Names containing Amprenavir: Agenerase; Prozei; Vertex;
Absorption: Rapidly absorbed after oral administration in HIV-1-infected patients with a time to peak concentration (Tmax) typically between 1 and 2 hours after a single oral dose. The absolute oral bioavailability of amprenavir in humans has not been established.
Toxicity (Overdose): Not Available
Protein Binding: Very high (90%). Amprenavir has the highest affinity for alpha(1)-acid glycoprotein.
Biotransformation: Hepatic. Amprenavir is metabolized in the liver by the cytochrome P450 3A4 (CYP3A4) enzyme system. The 2 major metabolites result from oxidation of the tetrahydrofuran and aniline moieties. Glucuronide conjugates of oxidized metabolites have been identified as minor metabolites in urine and feces.
Half Life: 7.1-10.6 hours
Dosage Forms of Prozei: Liquid Oral
Chemical IUPAC Name: [(3S)-oxolan-3-yl] N-[(2S,3R)-4-[(4-aminophenyl)sulfonyl-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]carbamate
Chemical Formula: C25H35N3O6S
Amprenavir on Wikipedia: https://en.wikipedia.org/wiki/Amprenavir
Organisms Affected: Human Immunodeficiency Virus