HIV Infection Medications
Definition of HIV Infection: HIV infection is a viral infection caused by the human immunodeficiency virus (HIV) that gradually destroys the immune system, resulting in infections that are hard for the body to fight.
Drugs associated with HIV InfectionThe following drugs and medications are in some way related to, or used in the treatment of HIV Infection. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.
Learn more about HIV InfectionMicromedex Care Notes:
Human Immunodeficiency Virus And Acquired Immune Deficiency SyndromeSexually Transmitted DiseasesSexually Transmitted Diseases In AdolescentsMedical Encyclopedia:
AIDSHIV infectionDrugs.com Health Center:
HIV/AIDS CenterDrug List:Accesspak-For-Hiv-Pep-BasicAccesspak-For-Hiv-Pep-Expanded-With-KaletraAccesspak-For-Hiv-Pep-Expanded-With-ViraceptAgeneraseAptivusAtriplaCarimune-IgivCombivirCompleraCrixivanEdurantEmtrivaEpivirEpivir-HbvEpzicomFlebogammaFortovaseFuzeonGamimuneGamimune-N-10-IgivGammagardGammagard-S-D-IgivGammaplex-IgivGammar-PivHividIntelenceInviraseIsentressIveegam-En-IgivKaletraLexivaNorvirOctagamPanglobulin-NfPolygam-S-D-IgivPrezistaPrivigenRescriptorRetrovirReyatazSandoglobulin-IgivSelzentrySustivaTrizivirTruvadaVidex-Chewable-Dispersible-Buffered-TabletsVidex-Ec-Delayed-Release-Enteric-Coated-CapsulesViraceptViramuneViramune-Xr-Extended-Release-TabletsVireadZeritZiagen
maraviroc
Generic Name: maraviroc (ma RAV i rok)
Brand Names: Selzentry
Maraviroc is an antiviral medication that prevents certain viral cells from multiplying in your body.
Maraviroc is used together with other medications. to treat CCR5-tropic human immunodeficiency virus (HIV) type 1.
Maraviroc is not a cure for HIV or AIDS.
Maraviroc may also be used for purposes not listed in this medication guide.
What is the most important information I should know about maraviroc? You should not take maraviroc if you have severe kidney disease and you are also using certain drugs. Tell your doctor about all other medications you use.Before taking this medication, tell your doctor if you have kidney disease, liver disease (especially hepatitis B or C), heart disease, low blood pressure, any type of allergy, circulation problems, or if you have ever had a stroke.
Call your doctor at once if you have signs of liver damage: low fever, itching, nausea, upper stomach pain, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes). There are many other drugs that can interact with maraviroc. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Keep a list of all your medicines and show it to any healthcare provider who treats you.HIV/AIDS is usually treated with a combination of different drugs. Maraviroc must be given in combination with other antiviral medications. Use all medications as directed by your doctor.
Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. What should I discuss with my health care provider before taking maraviroc? You should not use this medication if you are allergic to it.To make sure you can safely take maraviroc, tell your doctor if you have any of these other conditions:
kidney disease;
liver disease, especially hepatitis B or C;
heart disease;
low blood pressure;
any type of allergy;
circulation problems; or
if you have ever had a stroke.
FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby, but HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection.If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of maraviroc on the baby.
Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk. How should I take maraviroc?Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
You may take maraviroc with or without food. Maraviroc is usually taken twice per day. Follow your doctor's instructions.
Do not crush, chew, or break the maraviroc tablet. Swallow the pill whole.Use maraviroc regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.
HIV/AIDS is usually treated with a combination of different drugs. Maraviroc must be given in combination with other antiviral medications and it should not be used alone. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.
Store at room temperature away from moisture and heat.See also: Maraviroc dosage (in more detail)
What happens if I miss a dose?Take the missed dose as soon as you remember. If you are more than 6 hours late in taking your maraviroc, skip the missed dose and take the next regularly scheduled dose. Do not take extra medicine to make up the missed dose.
What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.Overdose symptoms may include feeling like you might pass out.
What should I avoid while taking maraviroc? Maraviroc may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. Maraviroc side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Maraviroc may also cause severe liver symptoms. Stop taking maraviroc and call your doctor at once if you have any of these liver symptoms:low fever, itching;
nausea, upper stomach pain, loss of appetite;
dark urine, clay-colored stools; or
jaundice (yellowing of the skin or eyes).
Call your doctor at once if you have any other serious side effect, such as:skin rash, bruising, severe tingling, numbness, pain, muscle weakness;
sudden numbness, tingling, or weakness anywhere in your body;
chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;
cold sores, sores on your genital or anal area;
white patches or sores inside your mouth or on your lips; or
signs of a new infection, such as fever or chills, cough, or flu symptoms.
Less serious side effects may include:
cold symptoms such as stuffy nose, sneezing, cough, sore throat;
diarrhea, constipation;
sleep problems (insomnia);
swelling;
problems with urination;
muscle or joint pain;
dizziness; or
mild skin rash.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Maraviroc Dosing InformationUsual Adult Dose for HIV Infection:
With potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer) including protease inhibitors (except tipranavir/ritonavir), delavirdine, ketoconazole, itraconazole, clarithromycin, and other potent CYP450 3A inhibitors (e.g., nefazodone, telithromycin): 150 mg orally twice a day
With other concomitant medications, including tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, and enfuvirtide: 300 mg orally twice a day
With potent CYP450 3A inducers (without a potent CYP450 3A inhibitor) including efavirenz, rifampin, etravirine, carbamazepine, phenobarbital, and phenytoin: 600 mg orally twice a day
Usual Pediatric Dose for HIV Infection:
16 years or older:
With potent CYP450 3A inhibitors (with or without a potent CYP450 3A inducer) including protease inhibitors (except tipranavir/ritonavir), delavirdine, ketoconazole, itraconazole, clarithromycin, and other potent CYP450 3A inhibitors (e.g., nefazodone, telithromycin): 150 mg orally twice a day
With other concomitant medications, including tipranavir/ritonavir, nevirapine, raltegravir, all NRTIs, and enfuvirtide: 300 mg orally twice a day
With potent CYP450 3A inducers (without a potent CYP450 3A inhibitor) including efavirenz, rifampin, etravirine, carbamazepine, phenobarbital, and phenytoin: 600 mg orally twice a day
Many drugs can interact with maraviroc. Below is just a partial list. Tell your doctor if you are using:
bosentan (Tracleer);
conivaptan (Vaprisol);
dexamethasone (Cortastat, Dexasone, Solurex, DexPak);
imatinib (Gleevec);
isoniazid (for treating tuberculosis);
nefazodone;
St. John's wort;
an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), rifapentine (Priftin), or telithromycin (Ketek);
antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), miconazole (Oravig), or voriconazole (Vfend);
a barbiturate such as butabarbital (Butisol), secobarbital (Seconal), pentobarbital (Nembutal), or phenobarbital (Solfoton);
heart or blood pressure medication such as nicardipine (Cardene) or quinidine (Quin-G);
HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), didanosine (Videx), efavirenz (Atripla, Sustiva), emtricitabine (Emtriva), enfuvirtide (Fuzeon), etravirine (Intelence), fosamprenavir (Lexiva), indinavir (Crixivan), lamivudine (Epivir, Combivir, Trizivir), nelfinavir (Viracept), nevirapine (Viramune), ritonavir (Norvir, Kaletra), saquinavir (Invirase), stavudine (Zerit), tipranavir (Aptivus), zalcitabine (Hivid), zidovudine (Retrovir);
medicines to treat narcolepsy, such as armodafinil (Nuvigil) or modafinil (Progivil); or
seizure medication such as carbamazepine (Carbatrol, Equetro, Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenytoin (Dilantin), or primidone (Mysoline).
This list is not complete and there are many other drugs that can interact with maraviroc. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. More maraviroc resources Maraviroc Side Effects (in more detail) Maraviroc Dosage Maraviroc Use in Pregnancy & Breastfeeding Maraviroc Drug Interactions Maraviroc Support Group 1 Review for Maraviroc - Add your own review/rating maraviroc Advanced Consumer (Micromedex) - Includes Dosage Information Maraviroc Professional Patient Advice (Wolters Kluwer) Maraviroc MedFacts Consumer Leaflet (Wolters Kluwer) Maraviroc Monograph (AHFS DI) Selzentry Prescribing Information (FDA) Selzentry Consumer Overview Compare maraviroc with other medications HIV Infection Where can I get more information? Your pharmacist can provide more information about maraviroc.See also: maraviroc side effects (in more detail)
Selzentry
Generic Name: Maraviroc
Class: HIV Entry and Fusion Inhibitors
VA Class: AM800
Chemical Name: 4,4 - Difluoro - N - {(1S) - 3 - [exo - 3 - (3 - isopropyl - 5 - methyl - 4H - 1,2,4 - triazol - 4 - yl) - 8 - azabicyclo[3.2.1]oct - 8 - yl] - 1 - phenylpropyl}cyclohexanecarboxamide
Molecular Formula: C29H41F2N5O
CAS Number: 376348-65-1
Hepatotoxicity reported;1 may be preceded by signs of a systemic allergic reaction (e.g., pruritic rash, eosinophilia, elevated IgE antibody levels).1 (See Hepatic Effects under Cautions.)
Immediately evaluate signs or symptoms of hepatitis or allergic reactions.1
IntroductionAntiretroviral; HIV entry inhibitor and1 6 8 9 CC chemokine receptor 5 (CCR5) antagonist.1 6 8 9
Uses for Selzentry Treatment of HIV InfectionTreatment of HIV-1 infection in adults infected with CCR5-tropic HIV-1.1
Coreceptor tropism testing (assay detects CCR5- and CXCR4-using virus; results reported as CCR5-tropic, CXCR4-tropic, or dual/mixed tropic HIV-1) is required for appropriate use of maraviroc.1 (See Laboratory Testing under Cautions.)
Consider the following when initiating therapy.1 Only adults infected with CCR5-tropic HIV-1 should receive maraviroc.1 Use a highly sensitive assay to identify appropriate patients; low levels of CXCR4-tropic or dual/mixed HIV-1 not detected at screening are associated with virologic failure.1
Not recommended in patients with dual/mixed or CXCR4-tropic HIV-1 infection; viral response was minimal in such patients in phase 2 study.1
Safety and efficacy not yet established in pediatric patients <16 years of age.1
In clinical studies, more treatment-naive individuals receiving maraviroc experienced virologic failure and developed resistence to lamivudine than individuals receiving efavirenz.1
Selzentry Dosage and Administration Administration Oral AdministrationAdminister orally without regard to food.1
DosageDosage depends on whether maraviroc is administered concomitantly with drugs affecting hepatic metabolism or the P-glycoprotein transport system.1 9
Must be given in combination with other antiretrovirals.1
Pediatric Patients Treatment of HIV Infection Adolescents Receiving a CYP3A Inhibitor (with or without a CYP3A Inducer) OralAdolescents ?16 years of age receiving concomitant therapy with a CYP3A inhibitor (e.g., protease inhibitors [PIs] [except ritonavir-boosted tipranavir], delavirdine, ketoconazole, itraconazole, clarithromycin, other potent CYP3A inhibitors [nefazodone, telithromycin]): 150 mg twice daily.1 9
Not necessary to alter dosage if therapy also includes a CYP3A inducer.1 9
Adolescents Receiving Drugs that are not CYP3A Inhibitors or Inducers OralAdolescents ?16 years of age receiving concomitant therapy with ritonavir-boosted tipranavir, nevirapine, nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs), enfuvirtide, raltegravir, or other drugs that are not potent CYP3A inhibitors or inducers: 300 mg twice daily.1 9
Adolescents Receiving a CYP3A Inducer (without a Potent CYP3A Inhibitor) OralAdolescents ?16 years of age receiving concomitant therapy with a CYP3A inducer (e.g., efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, phenytoin) and the regimen does not include a potent CYP3A inhibitor: 600 mg twice daily.1 9
Adults Treatment of HIV Infection Adults Receiving a CYP3A Inhibitor (with or without a CYP3A Inducer) OralPatients receiving concomitant therapy with a CYP3A inhibitor (e.g., PIs [except ritonavir-boosted tipranavir], delavirdine, ketoconazole, itraconazole, clarithromycin, other potent CYP3A inhibitors [nefazodone, telithromycin]): 150 mg twice daily.1 9
Not necessary to alter dosage if therapy also includes a CYP3A inducer.1 9
Adults Receiving Drugs that are not CYP3A Inhibitors or Inducers OralPatients receiving concomitant therapy with ritonavir-boosted tipranavir, nevirapine, NRTIs, enfuvirtide, raltegravir, other drugs that are not potent CYP3A inhibitors or inducers: 300 mg twice daily.1 9
Adults Receiving a CYP3A Inducer (without a Potent CYP3A Inhibitor) OralPatients receiving concomitant therapy with a CYP3A inducer (e.g., efavirenz, etravirine, rifampin, carbamazepine, phenobarbital, phenytoin) and the regimen does not include a potent CYP3A inhibitor: 600 mg twice daily.1 9
Special Populations Hepatic ImpairmentDosage recommendations not available.9
Renal ImpairmentDosage recommendations not available.9
Cautions for Selzentry ContraindicationsManufacturer states none known.1
Warnings/Precautions Warnings Hepatic EffectsHepatotoxicity reported.1 (See Boxed Warning.)
Adverse hepatic effects also reported.1
Immediately evaluate signs and symptoms of hepatitis or elevated transaminase concentrations accompanied by rash or other systemic symptoms; consider discontinuance of maraviroc.1
Sensitivity ReactionsSigns of a systemic allergic reaction may develop prior to an adverse hepatotoxic event.1 (See Boxed Warning.)
Other Warnings and Precautions Cardiovascular EffectsCardiovascular events (i.e., myocardial ischemia and/or MI) reported.1 Events generally occurred in individuals with cardiac disease or risk factors for cardiac disease.1 Use with caution in patients at increased risk for cardiovascular events.1
Symptomatic postural hypotension reported in healthy individuals receiving higher than recommended dosages of maraviroc.1 Caution in patients with a history of postural hypotension and those receiving a drug that lowers BP.1
Immune Reconstitution SyndromeDuring initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii], herpes simplex virus, varicella-zoster virus [VZV]); this may necessitate further evaluation and treatment.1
Infectious ComplicationsPossible increased risk of infection with agents that bind to CCR5 receptors (e.g., maraviroc).1 11 Monitor for infection.1
MalignanciesPossible increased risk of malignancy with agents that bind to CCR5 receptors (e.g., maraviroc).1 11 Risk not fully evaluated.1
Laboratory TestingCoreceptor tropism testing with a highly sensitive tropism assay is required for appropriate use of maraviroc.1 In addition, consider this test in patients who exhibit virologic failure while receiving a CCR5 antagonist.9
Specific Populations PregnancyCategory B.1
Antiretroviral Pregnancy Registry at 800-258-4263.1
Some experts state that safety and pharmacokinetic data are insufficient to recommend maraviroc in pregnant women.13
LactationDistributed into milk in rats; not known whether distributed into human milk.1
Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.1
Pediatric UseSafety and efficacy not established in pediatric patients <16 years of age.1
Not recommended for use in pediatric patients <16 years of age.1 Data insufficient to make recommendations for initial therapy in children.19
Geriatric UseInsufficient experience in patients ?65 years of age to determine whether they respond differently than younger adults.1
Use with caution and monitor because of age-related decreases in hepatic, renal, and/or concomitant disease and drug therapy.1
Hepatic ImpairmentUse caution; maraviroc concentrations increased in individuals with mild or moderate hepatic impairment.1
Not evaluated in patients with severe hepatic impairment.1
Monitor individuals with moderate hepatic impairment receiving maraviroc 150 mg twice daily and a drug that strongly inhibits CYP3A for maraviroc-associated adverse effects.1
Insufficient data available to determine whether patients with coexisting hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are at increased risk for adverse hepatic effects.1
Renal ImpairmentUse caution:1 9 safety and efficacy in patients with renal impairment not specifically evaluated.1
Plasma maraviroc concentrations may be increased, especially in those receiving concomitant therapy with a CYP3A inhibitor.1
Individuals with a Clcr <50 mL/minute receiving concomitant therapy with a CYP3A inhibitor may be at increased risk for adverse effects (e.g., dizziness, postural hypotension) due to increased plasma concentrations of maraviroc.1 Use this combination in individuals with Clcr <50 mL/minute only if potential benefits outweigh risks; monitor for adverse effects.1
Common Adverse EffectsCough, pyrexia, upper respiratory tract infections, rash, dizziness.1
Interactions for SelzentryMetabolized by CYP3A.1
Does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, or 3A; may inhibit CYP2D6 at higher than recommended dosage.1 Does not induce CYP1A2.1
A p-glycoprotein substrate.1
Drugs Affecting or Metabolized by Hepatic Microsomal EnzymesPotential pharmacokinetic interactions with drugs that induce or inhibit CYP3A with possible altered metabolism of maraviroc.1
Drugs Affecting or Affected by P-Glycoprotein TransportPharmacokinetic interactions likely with drugs that are p-glycoprotein inhibitors or inducers with possible altered metabolism of maraviroc.1
Inhibits the P-glycoprotein transport system; may affect bioavailability of certain other drugs.1
Specific DrugsDrug
Interaction
Comments
Abacavir
No in vitro evidence of antagonistic antiretroviral effects 1
Recommended dosage of maraviroc is 300 mg twice daily when used in conjunction with NRTIs, provided the regimen does not include a CYP3A inhibitor or inducer1 16
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)
Possible decreased maraviroc concentrations9
Carbamazepine, phenobarbital, phenytoin: Recommended dosage of maraviroc is 600 mg twice daily, provided the regimen does not include a potent CYP3A inhibitor;1 9 16 consider alternative anticonvulsants9
Antifungals, azoles (itraconazole, ketoconazole, voriconazole)
Itraconazole: Possible increased maraviroc concentrations 9
Ketoconazole: Increased maraviroc concentrations1 9 21
Voriconazole: Possible increased maraviroc concentrations 9
Itraconazole: Recommended dosage of maraviroc is 150 mg twice daily1 9
Ketoconazole: Recommended dosage of maraviroc is 150 mg twice daily1 9
Voriconazole: Consider using maraviroc 150 mg twice daily9
Antimycobacterials (rifabutin, rifampin, rifapentine)
Rifabutin: Possible decreased maraviroc concentrations9
Rifampin: Decreased maraviroc concentrations1 9 22
Rifabutin: Recommended dosage of maraviroc is 300 mg twice daily if regimen does not include a potent CYP3A inducer or inhibitor9
Rifabutin: Recommended dosage of maraviroc is 150 mg twice daily if regimen includes a potent CYP3A inhibitor9
Rifampin: Recommended dosage of maraviroc is 600 mg twice daily if regimen does not include a potent CYP3A inhibitor1 9 16
Rifampin: Recommended dosage of maraviroc is 300 mg twice daily if regimen includes a potent CYP3A inhibitor9
Rifapentine: Concomitant use not recommended 9
Atazanavir
Atazanavir or ritonavir-boosted atazanavir: Increased maraviroc concentrations1 9
No in vitro evidence of antagonistic antiretroviral effects1
Atazanavir or ritonavir-boosted atazanavir: Recommended dosage of maraviroc is 150 mg twice daily1 9
Clarithromycin
Possible increased maraviroc concentrations9
Recommended dosage of maraviroc is 150 mg twice daily1 9
Co-trimoxazole
Pharmacokinetic interaction unlikely; no change in the pharmacokinetics of maraviroc1
Darunavir
Ritonavir-boosted darunavir: Increased maraviroc concentrations1 9
No in vitro evidence of antagonistic antiretroviral effects1
Ritonavir-boosted darunavir: Recommended dosage of maraviroc is 150 mg twice daily1 9
Delavirdine
Possible increased maraviroc concentrations 9
No in vitro evidence of antagonistic antiretroviral effects1
Recommended dosage of maraviroc is 150 mg twice daily1 9
Didanosine
No in vitro evidence of antagonistic antiretroviral effects1
Recommended dosage of maraviroc is 300 mg twice daily when used in conjunction with NRTIs, provided the regimen does not include a CYP3A inhibitor or inducer1 16
Efavirenz
Efavirenz: Decreased maraviroc concentrations1 9 22
Efavirenz and lopinavir/ritonavir: Increased maraviroc concentrations1 9 16
Efavirenz and ritonavir-boosted saquinavir: Increased maraviroc concentrations1 9
Efavirenz: No in vitro evidence of antagonistic antiretroviral effects1
Efavirenz: Recommended dosage of maraviroc is 600 mg twice daily, provided the regimen does not include a potent CYP3A inhibitor1 9
Regimens that include efavirenz and lopinavir/ritonavir: Recommended dosage of maraviroc is 150 mg twice daily9
Regimens that include efavirenz and ritonavir-boosted saquinavir: Recommended dosage of maraviroc is 150 mg twice daily9
Emtricitabine
No in vitro evidence of antagonistic antiretroviral effects 1
Recommended dosage of maraviroc is 300 mg twice daily when used in conjunction with NRTIs, provided the regimen does not include a CYP3A inhibitor or inducer1 16
Enfuvirtide
In vitro evidence of additive to synergistic antiretroviral effects1
Recommended dosage of maraviroc is 300 mg twice daily, provided the regimen does not include a CYP3A inhibitor or inducer1
Estrogens or Progestins
Oral contraceptives: Pharmacokinetic interaction unlikely;1 9 no change in the pharmacokinetics of ethinyl estradiol and levonorgestrel1
Considered safe to use maraviroc with oral contraceptive preparations9
Etravirine
Etravirine: Decreased maraviroc concentrations9
Etravirine and ritonavir-boosted darunavir: Increased maraviroc concentrations9
Etravirine: Recommended dosage of maraviroc is 600 mg twice daily9
Regimens that include etravirine and ritonavir-boosted darunavir: Recommended dosage of maraviroc is 150 mg twice daily9
Fosamprenavir
Fosamprenavir: Possible increased maraviroc concentrations1 9
No in vitro evidence of antagonistic antiretroviral effects between amprenavir and maraviroc1
Fosamprenavir: Recommended dosage of maraviroc is 150 mg twice daily1 9
Indinavir
Possible increased maraviroc concentrations9
No in vitro evidence of antagonistic antiretroviral effects1
Recommended dosage of maraviroc is 150 mg twice daily1 9
Lamivudine
Pharmacokinetic interaction unlikely1
No in vitro evidence of antagonistic antiretroviral effects1
Recommended dosage of maraviroc is 300 mg twice daily when used in conjunction with NRTIs, provided the regimen does not include a CYP3A inhibitor or inducer1 16
Lopinavir
Lopinavir/ritonavir: Substantially increased maraviroc concentrations1 9 21
Lopinavir/ritonavir and efavirenz: Increased maraviroc concentrations1 9
No in vitro evidence of antagonistic antiretroviral effects 1
Lopinavir/ritonavir: Recommended dosage of maraviroc is 150 mg twice daily1 9
Regimens that include lopinavir/ritonavir and efavirenz: Recommended dosage of maraviroc is 150 mg twice daily1 9
Midazolam
No change in the pharmacokinetics of midazolam1
Nefazodone
Possible pharmacokinetic interaction 1
Recommended dosage of maraviroc is 150 mg twice daily1
Nelfinavir
No in vitro evidence of antagonistic antiretroviral effects 1
Recommended dosage of maraviroc is 150 mg twice daily1
Nevirapine
No change in maraviroc concentrations1 9
No in vitro evidence of antagonistic antiretroviral effects1
Recommended dosage of maraviroc is 300 mg twice daily if the regimen does not include a PI or other potent CYP3A inhibitor;9 recommended dosage of maraviroc is 150 mg twice daily if the regimen includes a PI (except ritonavir-boosted tipranavir)9
Raltegravir
Decreased concentrations of raltegravir1
Not considered clinically important1
Ritonavir
Low-dose ritonavir (ritonavir 100 mg twice daily): Increased maraviroc concentrations 1 9 21
No in vitro evidence of antagonistic antiretroviral effects1
Regimens that include low-dose ritonavir (except ritonavir-boosted tipranavir): Recommended dosage of maraviroc is 150 mg twice daily 1 9
Saquinavir
Ritonavir-boosted saquinavir (saquinavir 1 g twice daily with ritonavir 100 mg twice daily): Substantially increased maraviroc concentrations9 21
Ritonavir-boosted saquinavir and efavirenz: Increased maraviroc concentrations1 9
Saquinavir: No in vitro evidence of antagonistic antiretroviral effects 1
Ritonavir-boosted saquinavir: Recommended dosage of maraviroc is 150 mg twice daily 1 9
Regimens that include ritonavir-boosted saquinavir and efavirenz: Recommended dosage of maraviroc is 150 mg twice daily 9
Stavudine
No in vitro evidence of antagonistic antiretroviral effects1
Recommended dosage of maraviroc is 300 mg twice daily when used in conjunction with NRTIs, provided the regimen does not include a CYP3A inhibitor or inducer1 16
St. John’s wort (Hypericum perforatum)
Potential decreased maraviroc concentrations and loss of virologic response1
Concomitant use not recommended1 9
Telithromycin
Possible pharmacokinetic interaction 1
Recommended dosage of maraviroc is 150 mg twice daily1
Tenofovir
No change in maraviroc concentrations1
No in vitro evidence of antagonistic antiretroviral effects 1
Recommended dosage of maraviroc is 300 mg twice daily when used in conjunction with NRTIs, provided the regimen does not include a CYP3A inhibitor or inducer1 16
Tipranavir
Ritonavir-boosted tipranavir: Pharmacokinetic interaction unlikely 9
No in vitro evidence of antagonistic antiretroviral effects1
Ritonavir-boosted tipranavir: Recommended dosage of maraviroc is 300 mg twice daily, provided the regimen does not include a CYP3A inhibitor or inducer1 9 16
Zidovudine
Pharmacokinetic interaction unlikely1
No in vitro evidence of antagonistic antiretroviral effects 1
Recommended dosage of maraviroc is 300 mg twice daily when used in conjunction with NRTIs, provided the regimen does not include a CYP3A inhibitor or inducer1 16
Selzentry Pharmacokinetics Absorption BioavailabilityAbsolute bioavailability of a 100-mg oral dose is 23%; absolute bioavailability of a 300-mg dose predicted to be 33%.1 20
Following oral administration, peak plasma concentrations attained in 0.5–4 hours.1
FoodWhen a 300-mg tablet was administered with a high fat meal, AUC was decreased by 33%.1
Special PopulationsIncreased plasma concentrations expected in patients with renal impairment, especially in those receiving concomitant therapy with a CYP3A inhibitor.1
Increased plasma concentrations reported in individuals with mild or moderate hepatic impairment, especially in those with moderate hepatic impairment receiving concomitant therapy with a potent CYP3A inhibitor.1
Distribution ExtentDistributed into milk in rats; not known whether distributed into human milk.1
Plasma Protein Binding76%.1
Elimination MetabolismPrincipally metabolized by CYP3A to inactive metabolites.1
Elimination RouteApproximately 20% eliminated in urine (8% as unchanged maraviroc) and 76% excreted in feces (25% as unchanged maraviroc).1
Half-life14–18 hours.1 20
Special PopulationsPharmacokinetics not studied in patients with severe hepatic impairment.1
Stability Storage Oral Tablets25°C (may be exposed to 15–30°C).1
ActionsActionsActive against HIV-1;1 antiviral activity against HIV-2 not evaluated.1
CCR5 antagonist;1 6 8 9 CCR5 is a co-receptor for the most commonly transmitted HIV-1 strains that predominate during the early stages of infection6 9 and remains the dominant form in many patients with late-stage infection.6
Selectively binds to CCR5 on the cell membrane and prevents the interaction of HIV-1 glycoprotein 120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.1 6
Does not inhibit CXCR4-tropic and dual/mixed-tropic HIV-1 entry into cells.1
Active against some strains of HIV-1 resistant to NRTIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs), PIs, and HIV entry and fusion inhibitors (enfuvirtide).1
Advice to PatientsCritical nature of compliance with HIV therapy.1 Used in conjunction with other antiretrovirals; do not use for monotherapy.1
Antiretroviral therapy is not a cure for HIV infection, and opportunistic infections still may occur.1 HIV transmission via sexual contact or sharing needles is not prevented by antiretrovirals.1
Importance of reading patient information provided by the manufacturer.1
If a dose is missed, administer as soon as possible and resume the regular schedule.1 If there are <6 hours before the next scheduled dose when the missed dose is remembered, omit the dose and take the next dose at the scheduled time.1
Advise patients that hepatitis and allergic reactions have occurred.1 Importance of discontinuing maraviroc and seeking medical attention if signs or symptoms of these adverse events (e.g., rash, yellow skin or eyes, dark urine, vomiting, abdominal pain) occur.1
Possibility of dizziness.1 Advise patients to avoid driving a motor vehicle or operating hazardous machinery if they experience dizziness.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products (e.g., St. John’s wort), and any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of advising patients of other important precautionary information.1 (See Cautions.)
PreparationsExcipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
MaravirocRoutes
Dosage Forms
Strengths
Brand Names
Manufacturer
Oral
Tablets, film-coated
150 mg
Selzentry
Pfizer
300 mg
Selzentry
Pfizer
DisclaimerThis report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.
The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.
AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions April 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
References1. Pfizer. Selzentry (maraviroc) tablets prescribing information. New York, NY; 2009 Nov.
2. Nelson M, F?tkenheuer G, Konourina I et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic, ART-experienced patients infected with CCR5-tropic HIV-1 in Europe, Australia, and North America: 24-week results. 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA. 2007 Feb 25-28. Abstract 104aLB. From website.
3. Lalezari J, Goodrich J, DeJesus E et al. Efficacy and safety of maraviroc plus optimized background therapy in viremic ART-experienced patients infected with CCR5-tropic HIV-1: 24-week results of a phase 2b/3 study in the United States and Canada. 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, CA. 2007 Feb 25-28. Abstract 104bLB. From website.
4. Mayer H, van der Ryst E, Saag M et al. Safety and efficacy of maraviroc (MVC), a novel CCR5 antagonist, when used in combination with optimized background therapy (OBT) for the treatment of antiretroviral-experienced subjects infected with dual/mixed-tropic HIV-1: 24-week results of a phase 2b exploratory trial. XVI International AIDS Conference, Toronto, Canada. 2006 Aug 13-18. Abstract. From website.
5. Daar ES, Kesler KL, Petropoulos J et al. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clin Infect Dis. 2007; 45:643-9. [PubMed 17683002]
6. Dorr P, Westby M, Dobbs S et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother. 2005; 49:4721-32. [PubMed 16251317]
7. Stephenson J. Researchers buoyed by novel HIV drugs: will expand drug arsenal against resistant virus. JAMA. 2007; 297:1535-6. [PubMed 17426263]
8. Lederman MM, Penn-Nicholson A, Cho M et al. Biology of CCR5 and its role in HIV infection and treatment. JAMA. 2006; 296:815-26. [PubMed 16905787]
9. Panel on Antiretroviral Guidelines for Adults and Adolescents of the Department of Health and Human Services (DHHS). Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (November 3, 2008). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website.
10. Hammer SM, Saag MS, Schechter M et al. Treatment of adult HIV infection: 2006 recommendations of the International AIDS Society–USA panel. JAMA. 2006; 296:827-43. [PubMed 16905788]
11. Anon. Two new drugs for HIV infection. Med Lett Drugs Ther. 2008; 50:2-4.
12. F?tkenheuer G, Konourina I, Nelson M et al. Efficacy and safety of maraviroc (MCV) plus optimized background therapy (OBT) in viraemic, antiretroviral treatment-experienced patients infected with CCR5-tropic (R5) HIV-1 in Europe, Australia, and North America (MOTIVATE 2): 48-week results. 11th European AIDS Conference, Madrid, Spain. 2007 Oct 24-27. Abstract PS3/5.
13. Perinatal HIV Guidelines Working Group. Public Health Service task force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States (April 29, 2009). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website.
14. Hitt E. Maraviroc misses noninferiority endpoint compared with efavirenz in antiretroviral-naive patients. Medscape Medical News. From website. Accessed 29 Jan 2008.
15. Saag M, I’ve P, Heera J et al. A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine [ZDV]/lamivudine [3TC]) for the treatment of antiretroviral naive patients infected with R5 HIV1: week 48 results of the MERIT study. 4th IAS Conference, Sydney, Australia. 2007 Jul 22-25. Abstract.
16. Pfizer, New York, NY: Personal communication.
17. Gulick RM, Lalezari J, Goodwich J et al. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008; 359:1429-41. [PubMed 18832244]
18. Heera J, Ive P, Botes M et al. The MERIT study of maraviroc in antiretroviral-naive patients with R5 HIV-1: 96-week results. 5th IAS Conference, Cape Town, South Africa. 2009 Jul 19-22.Abstract.
19. Working Group on Antiretroviral Therapy and Medical Management of HIV-infected Children of the National Pediatric and Family HIV Resource Center (NPHRC), Health Resources and Services Administration (HRSA), and National Institutes of Health (NIH). Guidelines for the use of antiretroviral agents in pediatric HIV infection (February 23, 2009). From the US Department of Health and Human Services HIV/AIDS Information Services (AIDSinfo) website.
20. Abel S, Russell D, Whitlock LA et al. Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects. Br J Clin Pharmacol. 2008; 65(Suppl 1):60-7. [PubMed 18333867]
21. Abel S, Russell D, Taylor-Worth RJ et al. Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol. 2008; 65(Suppl 1):27-37. [PubMed 18333863]
22. Abel S, Jenkins TM, Whitlock LA et al. Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol. 2008; 65(Suppl 1):38-46. [PubMed 18333864]
More Selzentry resources Selzentry Side Effects (in more detail) Selzentry Dosage Selzentry Use in Pregnancy & Breastfeeding Selzentry Drug Interactions Selzentry Support Group 1 Review for Selzentry - Add your own review/rating Selzentry Prescribing Information (FDA) Selzentry Consumer Overview Selzentry Advanced Consumer (Micromedex) - Includes Dosage Information Selzentry MedFacts Consumer Leaflet (Wolters Kluwer) Maraviroc Professional Patient Advice (Wolters Kluwer) Compare Selzentry with other medications HIV InfectionSustiva
Generic Name: efavirenz (e FAV ir enz)
Brand Names: Sustiva
Efavirenz is an antiviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in your body.
Efavirenz is used to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS). Efavirenz is not a cure for HIV or AIDS.
Efavirenz may also be used for purposes not listed in this medication guide.
What is the most important information I should know about efavirenz? Do not use efavirenz if you are pregnant. It could harm the unborn baby. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide gel) while you are taking efavirenz, and for at least 12 weeks after your treatment ends. Tell your doctor if you become pregnant during treatment.Efavirenz may cause serious psychiatric symptoms including confusion, severe depression, suicidal thoughts, aggression, extreme fear, hallucinations, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.
Do not take efavirenz with cisapride (Propulsid), pimozide (Orap), midazolam (Versed), triazolam (Halcion), or ergot medicines such as dihydroergotamine (D.H.E. 45), ergonovine (Ergotrate), ergotamine (Ergomar, Cafergot, Wigraine), or methylergonovine (Methergine). These drugs can cause life-threatening side effects if you use them while you are taking efavirenz.There are many other medicines that can interact with efavirenz, or make it less effective. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
Taking this medication will not prevent you from passing HIV to other people. Talk with your doctor about safe methods of preventing HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. What should I discuss with my healthcare provider before taking efavirenz? You should not use this medication if you are allergic to efavirenz, if you have moderate to severe liver problems, or if you are using any of the following drugs:cisapride (Propulsid);
midazolam (Versed) or triazolam (Halcion);
pimozide (Orap); or
ergot medicine such as ergotamine (Ergomar, Ergostat, Cafergot, Ercaf, Wigraine), dihydroergotamine (D.H.E. 45, Migranal Nasal Spray), ergonovine (Ergotrate), or methylergonovine (Methergine).
Using any of these medicines while you are taking efavirenz can cause serious medical problems or death.To make sure you can safely take efavirenz, tell your doctor if you have any of these other conditions:
liver disease (including hepatitis B or C);high cholesterol or triglycerides; or
if you have ever taken delavirdine (Rescriptor) or nevirapine (Viramune) and they were not effective in treating your condition.
FDA pregnancy category D. Do not use efavirenz if you are pregnant. It could harm the unborn baby. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide gel) while you are taking efavirenz, and for at least 12 weeks after your treatment ends. Tell your doctor if you become pregnant during treatment. HIV can be passed to the baby if the mother is not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection while you are pregnant.If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of efavirenz on the baby.
Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk. How should I take efavirenz?Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Take efavirenz on an empty stomach at bedtime, unless your doctor tells you otherwise.Efavirenz can cause side effects such as mood or behavior changes. These symptoms may improve the longer you take the medication. Taking efavirenz at bedtime may also lessen these effects. Contact your doctor if you have more serious symptoms such as severe depression or thoughts of hurting yourself.
Take efavirenz regularly to get the most benefit. Get your prescriptions refilled before you run out of medicine completely.
Do not take efavirenz as your only HIV medication. HIV/AIDS is usually treated with a combination of different drugs. Your disease may become resistant to efavirenz if you do not take it in combination with other HIV medicines your doctor has prescribed. Use all of your medications as directed by your doctor. Do not change your doses or medication schedule without advice from your doctor. Every person with HIV or AIDS should remain under the care of a doctor.To be sure efavirenz is helping your condition and not causing harmful effects, your blood and liver function may need to be tested often. Visit your doctor regularly.
This medication can cause you to have a false positive drug-screening test. If you provide a urine sample for drug-screening, tell the laboratory staff that you are taking efavirenz.
Store at room temperature away from moisture and heat. What happens if I miss a dose?Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.Overdose can cause confusion, lack of balance or coordination, severe mood or behavior changes, or thoughts of suicide.
What should I avoid while taking efavirenz? Efavirenz may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of efavirenz. Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. Efavirenz side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.Efavirenz may cause serious psychiatric symptoms including confusion, severe depression, suicidal thoughts, aggression, extreme fear, hallucinations, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.
Call your doctor at once if you have a serious side effect such as:fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;
nausea, stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
fever, chills, body aches, flu symptoms; or
any other signs of new infection.
Less serious side effects may include:
mild nausea, vomiting, or stomach pain, diarrhea or constipation;
cough;
blurred vision;
headache, tired feeling, dizziness, spinning sensation;
trouble concentrating, problems with balance or coordination;
muscle or joint pain;
sleep problems (insomnia), unusual dreams; or
changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What other drugs will affect efavirenz? Cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by efavirenz. Tell your doctor if you regularly use any of these medicines.There are many other medicines that can interact with efavirenz, or make it less effective. Before taking efavirenz, tell your doctor if you are using any of the following drugs:
bupropion (Aplenzin, Budeprion, Wellbutrin, Zyban);
cyclosporine (Gengraf, Neoral, Sandimmune);
itraconazole (Sporanox), posaconazole (Noxafil);
maraviroc (Selzentry);
sirolimus (Rapamune), tacrolimus (Prograf);
St. John's wort;
voriconazole (Vfend);
a blood thinner such as warfarin (Coumadin, Jantoven);
a cholesterol medication such as Lipitor or Zocor;
an antibiotic such as clarithromycin (Biaxin), rifabutin (Mycobutin), or rifampin (Rifadin, Rifater, Rifamate, Rimactane);
heart or blood pressure medications such as amlodipine (Norvasc), diltiazem (Tiazac, Cartia, Cardizem), felodipine (Plendil), nicardipine (Cardene), nifedipine (Procardia, Adalat), or verapamil (Calan, Covera, Isoptin, Verelan);
other HIV medicines such as atazanavir (Reyataz), indinavir (Crixivan), lopinavir/ritonavir (Kaletra), nevirapine (Viramune), ritonavir (Norvir), or saquinavir (Invirase); or
seizure medications such as phenytoin (Dilantin) or carbamazepine (Tegretol).
This list is not complete and there are many other drugs that can interact with efavirenz. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. More Sustiva resources Sustiva Side Effects (in more detail) Sustiva Use in Pregnancy & Breastfeeding Drug Images Sustiva Drug Interactions Sustiva Support Group 2 Reviews for Sustiva - Add your own review/rating Sustiva Prescribing Information (FDA) Sustiva Monograph (AHFS DI) Sustiva Advanced Consumer (Micromedex) - Includes Dosage Information Sustiva Consumer Overview Sustiva MedFacts Consumer Leaflet (Wolters Kluwer) Efavirenz Professional Patient Advice (Wolters Kluwer) Compare Sustiva with other medications HIV Infection Nonoccupational Exposure Occupational Exposure Where can I get more information? Your pharmacist can provide more information about efavirenz.See also: Sustiva side effects (in more detail)
efavirenz, emtricitabine, and tenofovir
Generic Name: efavirenz, emtricitabine, and tenofovir (ef AV ir enz, em trye SYE ta been, and ten OF oh vir)
Brand Names: Atripla
Efavirenz, emtricitabine, and tenofovir is an antiviral medication that prevents human immunodeficiency virus (HIV) from reproducing in your body.
Efavirenz, emtricitabine, and tenofovir treats HIV, which causes acquired immunodeficiency syndrome (AIDS). This medication is not a cure for HIV or AIDS.
Efavirenz, emtricitabine, and tenofovir may also be used for purposes not listed in this medication guide.
What is the most important information I should know about efavirenz, emtricitabine, and tenofovir? Do not use efavirenz, emtricitabine, and tenofovir if you are pregnant. It could harm the unborn baby. Do not take this medication if you are also taking cisapride (Propulsid), midazolam (Versed), triazolam (Halcion), St. John's wort, voriconazole (Vfend), or an ergot medicine such as dihydroergotamine (D.H.E. 45, Migranal), ergonovine (Ergotrate), ergotamine (Ergomar), or methylergonovine (Methergine). Do not take this medication with other medicines that also contain efavirenz, emtricitabine, or tenofovir (Complera, Sustiva, Emtriva, Truvada, Viread), or lamivudine (Combivir, Epivir, Epzicom, Trizivir).There are many other drugs that can cause serious or life-threatening medical problems if you take them together with efavirenz, emtricitabine, and tenofovir. Tell your doctor about all medications you use.
Some people develop lactic acidosis while taking efavirenz, emtricitabine, and tenofovir. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Efavirenz, emtricitabine, and tenofovir can cause severe or fatal liver problems. Call your doctor at once if you have symptoms such as nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes). What should I discuss with my healthcare provider before taking efavirenz, emtricitabine, and tenofovir? You should not take this medication if you are allergic to efavirenz (Sustiva), emtricitabine (Emtriva), or tenofovir (Viread), or if you are taking any of the following drugs:cisapride (Propulsid);
midazolam (Versed) or triazolam (Halcion);
St. John's wort;
voriconazole (Vfend);
an ergot medicine such as dihydroergotamine (D.H.E. 45, Migranal), ergonovine (Ergotrate), ergotamine (Ergomar), or methylergonovine (Methergine);
lamivudine (Combivir, Epivir, Epzicom, or Trizivir); or
any other medicines that also contain efavirenz, emtricitabine, or tenofovir (such as Complera, Sustiva, Emtriva, Truvada, or Viread).
To make sure you can safely take this medication, tell your doctor if you have any of these other conditions:
liver or kidney disease;a history of mental illness, use of antipsychotic medication, or injection drug use;
epilepsy or other seizure disorder;
osteopenia (low bone mineral density); or
hepatitis B or C infection.
FDA pregnancy category D. Do not use this medication if you are pregnant. It could harm the unborn baby. Tell your doctor if you become pregnant during treatment. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide) while you are using this medication and for at least 12 weeks after your treatment ends. HIV can be passed to your baby if you are not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection. Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk. Some people develop a life-threatening condition called lactic acidosis while taking efavirenz, emtricitabine, and tenofovir. You may be more likely to develop lactic acidosis if you are overweight or have liver disease, if you are a woman, or if you have taken HIV or AIDS medications for a long time. Talk with your doctor about your individual risk. How should I take efavirenz, emtricitabine, and tenofovir?Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results.
Take this medication on an empty stomach at bedtime.Use this medication regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.
To be sure this medicine is helping your condition, your blood will need to be tested often. Your liver function may also need to be tested. Visit your doctor regularly.
If you have hepatitis B you may develop liver symptoms after you stop taking this medication, even months after stopping. Your doctor may want to check your liver function for several months after you stop using efavirenz, emtricitabine, and tenofovir.This medication can cause you to have a false positive drug screening test. If you provide a urine sample for drug screening, tell the laboratory staff that you are taking efavirenz, emtricitabine, and tenofovir.
HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the medication guide or patient instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.
Store in the original container at room temperature, away from moisture, heat, and light. Keep the bottle tightly closed when not in use.See also: Efavirenz, emtricitabine, and tenofovir dosage (in more detail)
What happens if I miss a dose?Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Overdose can cause uncontrolled muscle movements. What should I avoid while taking efavirenz, emtricitabine, and tenofovir? Drinking alcohol can increase certain side effects of this medication. This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. Efavirenz, emtricitabine, and tenofovir side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. This medication may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired. Stop using this medication and call your doctor at once if you have any other serious side effects such as:signs of liver damage - nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
urinating less than usual or not at all;
fever, chills, body aches, flu symptoms;
unusual thoughts or behavior, anger, severe depression, thoughts of hurting yourself or others, hallucinations;
severe blistering, peeling, and red skin rash; or
seizure (convulsions).
Less serious side effects may include:
mild nausea, vomiting, diarrhea, gas, upset stomach;
headache, dizziness, drowsiness, tired feeling;
trouble concentrating;
sleep problems (insomnia), strange dreams;
darkened skin on the palms of your hands or the soles of your feet; or
changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Efavirenz, emtricitabine, and tenofovir Dosing InformationUsual Adult Dose for HIV Infection:
1 tablet orally once a day at bedtime on an empty stomach
What other drugs will affect efavirenz, emtricitabine, and tenofovir?Many drugs can interact with efavirenz, emtricitabine, and tenofovir. Below is just a partial list. Tell your doctor if you are using:
acyclovir (Zovirax), ganciclovir (Cytovene), valacyclovir (Valtrex), or valganciclovir (Valcyte);
adefovir (Hepsera) or cidofovir (Vistide);
maraviroc (Selzentry);
methadone (Methadose);
sertraline (Zoloft);
a blood thinner such as warfarin (Coumadin, Jantoven);
cholesterol medications such as atorvastatin (Lipitor, Caduet), pravastatin (Pravachol), or simvastatin (Zocor, Simcor, Vytorin);
an antibiotic such as clarithromycin (Biaxin), rifabutin (Mycobutin), or rifampin (Rifater, Rifamate);
antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), or posaconazole (Noxafil);
heart or blood pressure medication such as diltiazem (Cartia, Cardizem), felodipine (Plendil), nicardipine (Cardene), nifedipine (Procardia, Adalat), verapamil (Calan, Covera, Isoptin, Verelan), and others;
medicines used to prevent organ transplant rejection, such as cyclosporine (Gengraf, Neoral, Sandimmune), sirolimus (Rapamune), or tacrolimus (Prograf);
seizure medication such as carbamazepine (Carbatrol, Equetro, Tegretol), phenytoin (Dilantin), phenobarbital (Solfoton); or
certain other HIV medicines such as atazanavir (Reyataz), didanosine (Videx), indinavir (Crixivan), saquinavir (Invirase), lopinavir/ritonavir (Kaletra), fosamprenavir (Lexiva), or ritonavir (Norvir, Kaletra).
This list is not complete and there are many other drugs that can interact with efavirenz, emtricitabine, and tenofovir. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. More efavirenz, emtricitabine, and tenofovir resources Efavirenz, emtricitabine, and tenofovir Side Effects (in more detail) Efavirenz, emtricitabine, and tenofovir Dosage Efavirenz, emtricitabine, and tenofovir Use in Pregnancy & Breastfeeding Efavirenz, emtricitabine, and tenofovir Drug Interactions Efavirenz, emtricitabine, and tenofovir Support Group 34 Reviews for Efavirenz, emtricitabine, and tenofovir - Add your own review/rating Compare efavirenz, emtricitabine, and tenofovir with other medications HIV Infection Where can I get more information? Your pharmacist can provide more information about efavirenz, emtricitabine, and tenofovir.See also: efavirenz, emtricitabine, and tenofovir side effects (in more detail)
efavirenz
Generic Name: efavirenz (e FAV ir enz)
Brand Names: Sustiva
Efavirenz is an antiviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in your body.
Efavirenz is used to treat HIV, which causes the acquired immunodeficiency syndrome (AIDS). Efavirenz is not a cure for HIV or AIDS.
Efavirenz may also be used for purposes not listed in this medication guide.
What is the most important information I should know about efavirenz? Do not use efavirenz if you are pregnant. It could harm the unborn baby. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide gel) while you are taking efavirenz, and for at least 12 weeks after your treatment ends. Tell your doctor if you become pregnant during treatment.Efavirenz may cause serious psychiatric symptoms including confusion, severe depression, suicidal thoughts, aggression, extreme fear, hallucinations, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.
Do not take efavirenz with cisapride (Propulsid), pimozide (Orap), midazolam (Versed), triazolam (Halcion), or ergot medicines such as dihydroergotamine (D.H.E. 45), ergonovine (Ergotrate), ergotamine (Ergomar, Cafergot, Wigraine), or methylergonovine (Methergine). These drugs can cause life-threatening side effects if you use them while you are taking efavirenz.There are many other medicines that can interact with efavirenz, or make it less effective. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.
Taking this medication will not prevent you from passing HIV to other people. Talk with your doctor about safe methods of preventing HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. What should I discuss with my healthcare provider before taking efavirenz? You should not use this medication if you are allergic to efavirenz, if you have moderate to severe liver problems, or if you are using any of the following drugs:cisapride (Propulsid);
midazolam (Versed) or triazolam (Halcion);
pimozide (Orap); or
ergot medicine such as ergotamine (Ergomar, Ergostat, Cafergot, Ercaf, Wigraine), dihydroergotamine (D.H.E. 45, Migranal Nasal Spray), ergonovine (Ergotrate), or methylergonovine (Methergine).
Using any of these medicines while you are taking efavirenz can cause serious medical problems or death.To make sure you can safely take efavirenz, tell your doctor if you have any of these other conditions:
liver disease (including hepatitis B or C);high cholesterol or triglycerides; or
if you have ever taken delavirdine (Rescriptor) or nevirapine (Viramune) and they were not effective in treating your condition.
FDA pregnancy category D. Do not use efavirenz if you are pregnant. It could harm the unborn baby. Use two forms of birth control, including a barrier form (such as a condom or diaphragm with spermicide gel) while you are taking efavirenz, and for at least 12 weeks after your treatment ends. Tell your doctor if you become pregnant during treatment. HIV can be passed to the baby if the mother is not properly treated during pregnancy. Take all of your HIV medicines as directed to control your infection while you are pregnant.If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of efavirenz on the baby.
Women with HIV or AIDS should not breast-feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk. How should I take efavirenz?Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Take efavirenz on an empty stomach at bedtime, unless your doctor tells you otherwise.Efavirenz can cause side effects such as mood or behavior changes. These symptoms may improve the longer you take the medication. Taking efavirenz at bedtime may also lessen these effects. Contact your doctor if you have more serious symptoms such as severe depression or thoughts of hurting yourself.
Take efavirenz regularly to get the most benefit. Get your prescriptions refilled before you run out of medicine completely.
Do not take efavirenz as your only HIV medication. HIV/AIDS is usually treated with a combination of different drugs. Your disease may become resistant to efavirenz if you do not take it in combination with other HIV medicines your doctor has prescribed. Use all of your medications as directed by your doctor. Do not change your doses or medication schedule without advice from your doctor. Every person with HIV or AIDS should remain under the care of a doctor.To be sure efavirenz is helping your condition and not causing harmful effects, your blood and liver function may need to be tested often. Visit your doctor regularly.
This medication can cause you to have a false positive drug-screening test. If you provide a urine sample for drug-screening, tell the laboratory staff that you are taking efavirenz.
Store at room temperature away from moisture and heat.See also: Efavirenz dosage (in more detail)
What happens if I miss a dose?Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
What happens if I overdose? Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.Overdose can cause confusion, lack of balance or coordination, severe mood or behavior changes, or thoughts of suicide.
What should I avoid while taking efavirenz? Efavirenz may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of efavirenz. Taking this medication will not prevent you from passing HIV to other people. Avoid having unprotected sex or sharing razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person. Efavirenz side effects Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.Efavirenz may cause serious psychiatric symptoms including confusion, severe depression, suicidal thoughts, aggression, extreme fear, hallucinations, or unusual behavior. Contact your doctor at once if you have any of these side effects, even if you have had them before.
Call your doctor at once if you have a serious side effect such as:fever, sore throat, and headache with a severe blistering, peeling, and red skin rash;
nausea, stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
fever, chills, body aches, flu symptoms; or
any other signs of new infection.
Less serious side effects may include:
mild nausea, vomiting, or stomach pain, diarrhea or constipation;
cough;
blurred vision;
headache, tired feeling, dizziness, spinning sensation;
trouble concentrating, problems with balance or coordination;
muscle or joint pain;
sleep problems (insomnia), unusual dreams; or
changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Efavirenz Dosing InformationUsual Adult Dose for HIV Infection:
600 mg orally once a day
Usual Adult Dose for Nonoccupational Exposure:
(Not approved by FDA)
Centers for Disease Control and Prevention (CDC) recommendations: 600 mg orally once a day, in combination with (lamivudine or emtricitabine) plus (zidovudine or tenofovir)
Duration: 28 days
Prophylaxis should be initiated as soon as possible, within 72 hours of exposure.
Usual Adult Dose for Occupational Exposure:
(Not approved by FDA)
CDC recommendations:
Alternate expanded regimen for HIV postexposure prophylaxis: 600 mg orally once a day, in combination with (lamivudine plus zidovudine) or (emtricitabine plus zidovudine) or (lamivudine plus tenofovir) or (emtricitabine plus tenofovir)
Duration: Generally 28 days; however, the exact duration of therapy may differ based on the institution's protocol.
Prophylaxis should be initiated immediately, preferably within hours after exposure.
Usual Pediatric Dose for HIV Infection:
3 years or older:
10 to less than 15 kg: 200 mg orally once a day
15 to less than 20 kg: 250 mg orally once a day
20 to less than 25 kg: 300 mg orally once a day
25 to less than 32.5 kg: 350 mg orally once a day
32.5 to less than 40 kg: 400 mg orally once a day
40 kg or more: 600 mg orally once a day
There are many other medicines that can interact with efavirenz, or make it less effective. Before taking efavirenz, tell your doctor if you are using any of the following drugs:
bupropion (Aplenzin, Budeprion, Wellbutrin, Zyban);
cyclosporine (Gengraf, Neoral, Sandimmune);
itraconazole (Sporanox), posaconazole (Noxafil);
maraviroc (Selzentry);
sirolimus (Rapamune), tacrolimus (Prograf);
St. John's wort;
voriconazole (Vfend);
a blood thinner such as warfarin (Coumadin, Jantoven);
a cholesterol medication such as Lipitor or Zocor;
an antibiotic such as clarithromycin (Biaxin), rifabutin (Mycobutin), or rifampin (Rifadin, Rifater, Rifamate, Rimactane);
heart or blood pressure medications such as amlodipine (Norvasc), diltiazem (Tiazac, Cartia, Cardizem), felodipine (Plendil), nicardipine (Cardene), nifedipine (Procardia, Adalat), or verapamil (Calan, Covera, Isoptin, Verelan);
other HIV medicines such as atazanavir (Reyataz), indinavir (Crixivan), lopinavir/ritonavir (Kaletra), nevirapine (Viramune), ritonavir (Norvir), or saquinavir (Invirase); or
seizure medications such as phenytoin (Dilantin) or carbamazepine (Tegretol).
This list is not complete and there are many other drugs that can interact with efavirenz. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor. Keep a list of all your medicines and show it to any healthcare provider who treats you. More efavirenz resources Efavirenz Side Effects (in more detail) Efavirenz Dosage Efavirenz Use in Pregnancy & Breastfeeding Efavirenz Drug Interactions Efavirenz Support Group 2 Reviews for Efavirenz - Add your own review/rating efavirenz Advanced Consumer (Micromedex) - Includes Dosage Information Efavirenz Professional Patient Advice (Wolters Kluwer) Efavirenz MedFacts Consumer Leaflet (Wolters Kluwer) Efavirenz Monograph (AHFS DI) Sustiva Prescribing Information (FDA) Sustiva Consumer Overview Compare efavirenz with other medications HIV Infection Nonoccupational Exposure Occupational Exposure Where can I get more information? Your pharmacist can provide more information about efavirenz.See also: efavirenz side effects (in more detail)
Invirase
saquinavir mesylate
Dosage Form: tablet, film coated; capsules
FULL PRESCRIBING INFORMATION
Product identification in this document includes: Invirase in reference to saquinavir mesylate; saquinavir 200 mg soft gel capsule formulation1 in reference to saquinavir active base.
1 The term "saquinavir soft gel capsules" used in this label refers to the drug product formerly marketed as "Fortovase" (saquinavir 200 mg soft gel capsule formulation). This formulation has been withdrawn from the market. Indications and Usage for InviraseInvirase in combination with ritonavir and other antiretroviral agents is indicated for the treatment of HIV-1 infection in adults (over the age of 16 years).
The following points should be considered when initiating therapy with Invirase:
– The twice daily administration of Invirase in combination with ritonavir is supported by safety data from the MaxCmin 1 study [see Adverse Reactions (6.1)] and pharmacokinetic data [see Clinical Pharmacology (12.3)]. – The efficacy of Invirase with ritonavir has not been compared against the efficacy of antiretroviral regimens currently considered standard of care. – The number of baseline primary protease inhibitor mutations affects the virologic response to Invirase/ritonavir. Invirase Dosage and AdministrationInvirase must be used in combination with ritonavir, because it significantly inhibits saquinavir's metabolism to provide increased plasma saquinavir levels.
Adults (Over the Age of 16 Years) Invirase 1000-mg twice daily (5 ? 200-mg capsules or 2 ? 500-mg tablets) in combination with ritonavir 100-mg twice daily. Ritonavir should be taken at the same time as Invirase. Invirase and ritonavir should be taken within 2 hours after a meal. Concomitant Therapy: Invirase with Lopinavir/RitonavirWhen administered with lopinavir/ritonavir 400/100 mg twice daily, the appropriate dose of Invirase is 1000 mg twice daily (with no additional ritonavir).
Dosage Forms and StrengthsCapsules: 200 mg
Film-coated tablets: 500 mg
QT interval prolongation and torsades de pointes have been reported rarely with Invirase/ritonavir use. Do not use in patients with congenital long QT syndrome, those with refractory hypokalemia or hypomagnesemia, and in combination with drugs that both increase saquinavir plasma concentrations and prolong the QT interval [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.2)].
Invirase is contraindicated in patients with complete atrioventricular (AV) block without implanted pacemakers, or patients who are at high risk of complete AV block [see Warnings and Precautions (5.2)].
Invirase is contraindicated in patients with clinically significant hypersensitivity (e.g., anaphylactic reaction, Stevens-Johnson syndrome) to saquinavir, saquinavir mesylate, or any of its ingredients including ritonavir.
Invirase when administered with ritonavir is contraindicated in patients with severe hepatic impairment.
Coadministration of Invirase/ritonavir is contraindicated with drugs that are CYP3A substrates for which increased plasma levels may result in serious or life-threatening reactions. These drugs and potentially related adverse events are listed in Table 1.
Table 1 Drugs That Are Contraindicated With Invirase/Ritonavir Drug Class Drugs Within Class That Are Contraindicated With Invirase Clinical Comment Alpha 1-adrenoreceptor antagonist Alfuzosin Potentially increased alfuzosin concentrations can result in hypotension. Antiarrhythmics Amiodarone, bepridil, dofetilide, flecainide, lidocaine (systemic), propafenone, quinidine Potential for serious and/or life-threatening cardiac arrhythmia. Antidepressant Trazodone Increased trazodone concentrations can result in potentially life threatening cardiac arrhythmia. Antimycobacterial Agents Rifampin Rifampin should not be administered in patients taking ritonavir-boosted Invirase part of an ART regimen due to the risk of severe hepatocellular toxicity. Ergot Derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine Potential for serious and life threatening reactions such as ergot toxicity characterized by peripheral vasospasm and ischemia of the extremities and other tissues. GI Motility Agent Cisapride Potential for serious and/or life threatening reactions such as cardiac arrhythmias. HMG-CoA Reductase Inhibitors Lovastatin, Simvastatin Potential for myopathy including rhabdomyolysis. Neuroleptics Pimozide Potential for serious and/or life threatening reactions such as cardiac arrhythmias. PDE5 Inhibitors Sildenafil (Revatio®)[for treatment of pulmonary arterial hypertension] Increased potential for sildenafil-associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope). A safe and effective dose has not been established when used with Invirase/ritonavir. Sedative/Hypnotics Triazolam, orally administered midazolam Potential for serious and/or life threatening reactions such as prolonged or increased sedation or respiratory depression.Triazolam and orally administered midazolam are extensively metabolized by CYP3A4. Coadministration of triazolam and orally administered midazolam with Invirase/ritonavir may cause large increases in the concentration of these benzodiazepines. Warnings and Precautions
Invirase must be used in combination with ritonavir. Please refer to the ritonavir full prescribing information for additional precautionary measures.
If a serious or severe toxicity occurs during treatment with Invirase, Invirase should be interrupted until the etiology of the event is identified or the toxicity resolves. At that time, resumption of treatment with full-dose Invirase may be considered. For antiretroviral agents used in combination with Invirase, physicians should refer to the complete product information for these drugs for dose adjustment recommendations and for information regarding drug-associated adverse reactions.
Drug InteractionsThe combination Invirase/ritonavir is a potent inhibitor of CYP3A and may significantly increase the exposure of drugs primarily metabolized by CYP3A. See Table 1 for a listing of drugs that are contraindicated for use with Invirase/ritonavir due to potentially life-threatening adverse events or significant drug interactions [see Contraindications (4)]. See Table 3 for established and other potentially significant drug interactions [see Drug Interactions (7.3)].
5.2 PR Interval ProlongationSaquinavir/ritonavir prolongs the PR interval in a dose-dependent fashion. Cases of second or third degree atrioventricular block have been reported rarely. Patients with underlying structural heart disease, pre-existing conduction system abnormalities, cardiomyopathies and ischemic heart disease may be at increased risk for developing cardiac conduction abnormalities. ECG monitoring is recommended in these patients [see Warnings and Precautions (5.3)].
The impact on the PR interval of co-administration of saquinavir/ritonavir with other drugs that prolong the PR interval (including calcium channel blockers, beta-adrenergic blockers, digoxin and atazanavir) has not been evaluated. As a result, co-administration of saquinavir/ritonavir with these drugs should be undertaken with caution, particularly with those drugs metabolized by CYP3A, and clinical monitoring is recommended [see Clinical Pharmacology (12.2)].
5.3 QT Interval ProlongationSaquinavir/ritonavir causes dose-dependent QT prolongation. Torsades de pointes has been reported rarely post-marketing. Avoid saquinavir/ritonavir in patients with long QT syndrome. ECG monitoring is recommended if therapy is initiated in patients with congestive heart failure, bradyarrhythmias, hepatic impairment and electrolyte abnormalities. Correct hypokalemia or hypomagnesemia prior to initiating saquinavir/ritonavir and monitor these electrolytes periodically during therapy. Do not use in combination with drugs that both increase saquinavir plasma concentrations and prolong the QT interval (see Tables 1 and 3) [see Clinical Pharmacology (12.2)].
Patients initiating therapy with ritonavir-boosted Invirase:
An ECG should be performed prior to initiation of treatment. Patients with a QT interval > 450 msec should not receive ritonavir-boosted Invirase. For patients with a QT interval < 450 msec, an on-treatment ECG is suggested after approximately 3 to 4 days of therapy; patients with a QT interval > 480 msec or prolongation over pre-treatment by > 20 msec should discontinue ritonavir-boosted Invirase.
Patients requiring treatment with medications with the potential to increase the QT interval and concomitant ritonavir-boosted Invirase:
Such combinations should only be used where no alternative therapy is available and the potential benefits outweigh the potential risks. An ECG should be performed prior to initiation of the concomitant therapy, and patients with a QT interval > 450 msec should not initiate the concomitant therapy. If baseline QT interval < 450 msec, an on-treatment ECG should be performed after 3-4 days of therapy. For patients demonstrating a subsequent increase in QT interval to > 480 msec or increase by > 20 msec after commencing concomitant therapy, the physician should use best clinical judgment to discontinue either ritonavir-boosted Invirase or the concomitant therapy or both.
A cardiology consult is recommended if drug discontinuation or interruption is being considered on the basis of ECG assessment.
Diabetes Mellitus and HyperglycemiaNew onset diabetes mellitus, exacerbation of preexisting diabetes mellitus and hyperglycemia have been reported during postmarketing surveillance in HIV-1-infected patients receiving protease-inhibitor therapy. Some patients required either initiation or dose adjustments of insulin or oral hypoglycemic agents for the 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.
HepatotoxicityIn patients with underlying hepatitis B or C, cirrhosis, chronic alcoholism and/or other underlying liver abnormalities, there have been reports of worsening liver disease.
HemophiliaThere 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 the majority of reported cases treatment with protease inhibitors was continued or restarted. A causal relationship between protease inhibitor therapy and these episodes has not been established.
HyperlipidemiaElevated cholesterol and/or triglyceride levels have been observed in some patients taking saquinavir in combination with ritonavir. Marked elevation in triglyceride levels is a risk factor for development of pancreatitis. Cholesterol and triglyceride levels should be monitored prior to initiating combination dosing regimen of Invirase with ritonavir, and at periodic intervals while on such therapy. In these patients, lipid disorders should be managed as clinically appropriate.
Lactose IntoleranceEach capsule contains lactose (anhydrous) 63.3 mg. This quantity should not induce specific symptoms of intolerance.
Fat RedistributionRedistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), facial wasting, peripheral wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy. A causal relationship between protease-inhibitor therapy and these events has not been established and the long-term consequences are currently unknown.
Immune Reconstitution SyndromeImmune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Invirase. 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 jiroveci pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.
Resistance/Cross-resistanceVarying degrees of cross-resistance among HIV-1 protease inhibitors have been observed. Continued administration of Invirase therapy following loss of viral suppression may increase the likelihood of cross resistance to other protease inhibitors [see Clinical Pharmacology (12.4)].
Adverse ReactionsThe following adverse reactions are discussed in greater detail in other sections of the labeling:
PR Interval Prolongation [see Warnings and Precautions (5.2)] QT Interval Prolongation [see Warnings and Precautions (5.3)] Clinical Trials ExperienceBecause clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The original Invirase safety database consisted of a total of 574 patients who received saquinavir 600 mg alone or in combination with ZDV or ddC. Combination dosing with ritonavir is based on 352 HIV-1 infected patients and 166 healthy subjects who received various combinations of either saquinavir (hard gel or soft-gel capsules) with ritonavir.
The recommended dose of Invirase is 1000 mg twice daily co-administered with ritonavir 100 mg twice daily, in combination with other antiretroviral agents. Table 2 lists grade 2, 3 and 4 adverse events that occurred in ?2% of patients receiving saquinavir soft gel capsules with ritonavir (1000/100 mg bid).
Table 2 Grade 2, 3 and 4 Adverse Events (All Causality*) Reported in ?2% of Adult Patients in the MaxCmin 1 Study of Saquinavir Soft Gel Capsules in Combination with Ritonavir 1000/100 mg bid Adverse Events Saquinavir soft gel capsules 1000 mg plus Ritonavir 100 mg bid (48 weeks)N=148
n (%=n/N) * Includes events with unknown relationship to study drug Endocrine Disorders Diabetes mellitus/hyperglycemia 4 (2.7) Lipodystrophy 8 (5.4) Gastrointestinal Disorders Nausea 16 (10.8) Vomiting 11 (7.4) Diarrhea 12 (8.1) Abdominal Pain 9 (6.1) Constipation 3 (2.0) General Disorders and Administration Site Conditions Fatigue 9 (6.1) Fever 5 (3.4) Musculoskeletal Disorders Back Pain 3 (2.0) Respiratory Disorders Pneumonia 8 (5.4) Bronchitis 4 (2.7) Influenza 4 (2.7) Sinusitis 4 (2.7) Dermatological Disorders Rash 5 (3.4) Pruritus 5 (3.4) Dry lips/skin 3 (2.0) Eczema 3 (2.0)
Limited experience is available from three studies investigating the pharmacokinetics of the Invirase 500 mg film-coated tablet compared to the Invirase 200 mg capsule in healthy volunteers (n=140). In two of these studies saquinavir was boosted with ritonavir; in the other study, saquinavir was administered as single drug. The Invirase tablet and the capsule formulations were similarly tolerated. The most common adverse events were gastrointestinal disorders (such as diarrhea). Similar bioavailability was demonstrated and no clinically significant differences in saquinavir exposures were seen. Thus, similar safety profiles are expected between the two Invirase formulations.
In a study investigating the drug-drug interaction of rifampin 600 mg/day daily and Invirase 1000 mg/ritonavir 100 mg twice daily (ritonavir-boosted Invirase) involving 28 healthy volunteers, 11 of 17 healthy volunteers (65%) exposed concomitantly to rifampin and ritonavir-boosted Invirase developed severe hepatocellular toxicity which presented as increased hepatic transaminases. In some subjects, transaminases increased up to >20-fold the upper limit of normal and were associated with gastrointestinal symptoms, including abdominal pain, gastritis, nausea, and vomiting. Following discontinuation of all three drugs, clinical symptoms abated and the increased hepatic transaminases normalized [see Contraindications (4)].
Additional Adverse Reactions Reported During Clinical Trials with Saquinavir
Blood and lymphatic system disorders: anemia, hemolytic anemia, leukopenia, lymphadenopathy, neutropenia, pancytopenia, thrombocytopenia
Cardiac disorders: heart murmur, syncope
Ear and labyrinth disorders: tinnitus
Eye disorders: visual impairment
Gastrointestinal disorders: abdominal discomfort, ascites, dyspepsia, dysphagia, eructation, flatulence, gastritis, gastrointestinal hemorrhage, intestinal obstruction, mouth dry, mucosal ulceration, pancreatitis
General disorders and administration site conditions: anorexia, asthenia, chest pain, edema, lethargy, wasting syndrome, weight increased
Hepatobiliary disorders: chronic active hepatitis, hepatitis, hepatomegaly, hyperbilirubinemia, jaundice, portal hypertension
Immune system disorders: allergic reaction
Investigations: ALT increase, AST increase, blood creatine phosphokinase increased, increased alkaline phosphatase, GGT increase, raised amylase, raised LDH
Metabolism and nutrition disorders: increased or decreased appetite, dehydration, hypertriglyceridemia
Musculoskeletal and connective tissue disorders: arthralgia, muscle spasms, myalgia, polyarthritis
Neoplasms benign, malignant and unspecified (incl cysts and polyps): acute myeloid leukemia, papillomatosis
Nervous system disorders: confusion, convulsions, coordination abnormal, dizziness, dysgeusia, headache, hypoaesthesia, intracranial hemorrhage leading to death, loss of consciousness, paresthesia, peripheral neuropathy, somnolence, tremor
Psychiatric disorders: anxiety, depression, insomnia, libido disorder, psychotic disorder, sleep disorder, suicide attempt
Renal and urinary disorders: nephrolithiasis
Respiratory, thoracic and mediastinal disorders: cough, dyspnea
Skin and subcutaneous tissue disorders: acne, alopecia, dermatitis bullous, drug eruption, erythema, severe cutaneous reaction associated with increased liver function tests, Stevens-Johnson syndrome, sweating increased, urticaria
Vascular disorders: hypertension, hypotension, thrombophlebitis, peripheral vasoconstriction
Postmarketing ExperienceAdditional adverse events that have been observed during the postmarketing period are similar to those seen in clinical trials with Invirase and saquinavir soft gel capsules alone or in combination with ritonavir. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Invirase exposure.
Drug InteractionsDrug interaction studies have been completed with both Invirase and saquinavir soft gel capsules. Observations from drug interaction studies with saquinavir soft gel capsules may not be predictive for Invirase/ritonavir. Because ritonavir is coadministered with Invirase, prescribers should also refer to the prescribing information for ritonavir regarding drug interactions associated with this agent.
Potential for Invirase to Affect Other DrugsThe combination Invirase/ritonavir is a potent inhibitor of CYP3A and may significantly increase the exposure of drugs primarily metabolized by CYP3A. Drugs that are contraindicated specifically due to the observed or expected magnitude of interaction and potential for serious or life-threatening adverse events are listed in Table 1 [see Contraindications (4)]. Coadministration with other CYP3A substrates may require a dose adjustment or additional monitoring (Table 3).
Potential for Other Drugs to Affect InviraseThe metabolism of saquinavir is mediated primarily by CYP3A. Additionally, saquinavir is a substrate for P-glycoprotein (P-gp). Therefore, drugs that affect CYP3A and/or P-gp may modify the pharmacokinetics of saquinavir. Coadministration with drugs that are potent inducers of CYP3A (e.g., phenobarbital, phenytoin, carbamazepine) may result in decreased plasma concentrations of saquinavir and reduced therapeutic effect.
Established and Other Potentially Significant Drug InteractionsBased on the finding of dose-dependent prolongations of QT and PR intervals in healthy volunteers receiving Invirase/ritonavir, additive effects on QT and/or PR interval prolongation may occur with certain members of the following drug classes: antiarrhythmics class IA or class III, neuroleptics, antidepressive agents, PDE5 inhibitors (when used for pulmonary arterial hypertension), antimicrobials, antihistaminics and others. This effect might lead to an increased risk of ventricular arrhythmias, notably torsades de pointes. Therefore, concurrent administration of these agents with Invirase/ritonavir is contraindicated [see Contraindications (4)].
Table 3 provides a listing of established or potentially clinically significant drug interactions. Alteration in dose or avoidance of the combination may be recommended depending on the interaction.
Table 3 Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies or on Predicted Interaction with Invirase/ritonavir Concomitant Drug Class:Drug Name Effect on Concentration of Saquinavir or Concomitant Drug Clinical Comment * Invirase/ritonavir interaction has not been evaluated. † See Drug Interactions (7), Table 5 and Table 6 for magnitude of interactions. HIV-1 Antiviral Agents Non-nucleoside reverse transcriptase inhibitor:
Delavirdine*
? Saquinavir
Effect on delavirdine is not well established Appropriate doses of the combination with respect to safety and efficacy have not been established. Non-nucleoside reverse transcriptase inhibitor:
Efavirenz†,
nevirapine* ? Saquinavir
? Efavirenz
Appropriate doses of the combination of efavirenz or nevirapine and Invirase/ritonavir with respect to safety and efficacy have not been established. HIV-1 protease inhibitor:
Atazanavir† Invirase/ritonavir
? Saquinavir
? Ritonavir
? Atazanavir Atazanavir in combination with Invirase/ritonavir should be used with caution. Additive effects on PR interval prolongation may occur with Invirase/ritonavir [see Warnings and Precautions (5.2)].
HIV-1 protease inhibitor:
Indinavir* ? Saquinavir
Effect on indinavir is not well established
Appropriate doses of the combination of indinavir and Invirase/ritonavir with respect to safety and efficacy have not been established. HIV-1 protease inhibitor:
Lopinavir/ritonavir† (coformulated tablet) ? Saquinavir
? Lopinavir
? Ritonavir
Evidence from several clinical trials indicates that saquinavir concentrations achieved with the saquinavir and lopinavir/ritonavir combination are similar to those achieved following saquinavir/ritonavir 1000/100 mg. The recommended dose for this combination is saquinavir 1000 mg plus lopinavir/ritonavir 400/100 mg bid.
Lopinavir/ritonavir in combination with Invirase should be used with caution. Additive effects on QT and/or PR interval prolongation may occur with Invirase [Warnings and Precautions (5.2, 5.3)].
HIV-1 protease inhibitor:
Tipranavir/ritonavir† ? Saquinavir
Combining saquinavir with tipranavir/ritonavir is not recommended.
HIV-1 fusion inhibitor:
Enfuvirtide† Saquinavir soft gel capsules/ritonavir
? enfuvirtide
No clinically significant interaction was noted from a study in 12 HIV-1 patients who received enfuvirtide concomitantly with saquinavir soft gel capsules/ritonavir 1000/100 mg bid. No dose adjustments are required.
HIV-1 CCR5 antagonist:
Maraviroc ? maraviroc Maraviroc dose should be 150 mg twice daily when coadministered with Invirase/ritonavir. For further details see complete prescribing information for Selzentry® (maraviroc).
Other Agents Ibutilide
Sotalol Use with caution. Additive effects on QT and/or PR interval prolongation may occur with Invirase/ritonavir [see Contraindications (4) and Warnings and Precautions (5.2, 5.3)].
Anticoagulant:
Warfarin* ? Warfarin Concentrations of warfarin may be affected. It is recommended that INR (international normalized ratio) be monitored.
Anticonvulsants:
Carbamazepine*, phenobarbital*, phenytoin* ? Saquinavir
Effect on carbamazepine, phenobarbital, and phenytoin is not well established
Use with caution. Saquinavir may be less effective due to decreased saquinavir plasma concentrations in patients taking these agents concomitantly. Anti-gout:
Colchicine ? Colchicine Treatment of gout flares-coadministration of colchicine in patients on Invirase/ritonavir:
0.6 mg (1 tablet) ? 1 dose, followed by 0.3 mg (half tablet) 1 hour later. Dose to be repeated no earlier than 3 days.
Treatment of familial Mediterranean fever (FMF) coadministration of colchicine in patients on Invirase/ritonavir:
Maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).
Prophylaxis of gout-flares-co-administration of colchicine in patients on Invirase/ritonavir:
If the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day.
If the original colchicine regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.
Patients with renal or hepatic impairment should not be given colchicine with Invirase/ritonavir.
Anti-infective:
Clarithromycin† ? Saquinavir
? Clarithromycin
Due to the known effect of ritonavir on clarithromycin concentrations, the following dose adjustments are recommended for patients with renal impairment: For patients with CLCR 30 to 60 mL/min the dose of clarithromycin should be reduced by 50%. For patients with CLCR <30 mL/min the dose of clarithromycin should be decreased by 75%. No dose adjustment for patients with normal renal function is necessary. Erythromycin
Halofantrine
Pentamidine Use with caution. Additive effects on QT and/or PR interval prolongation may occur with Invirase/ritonavir [see Contraindications (4) and Warnings and Precautions (5.2, 5.3)].
Antifungal:
Ketoconazole†,
itraconazole* ? Saquinavir
? Ritonavir
? Ketoconazole When Invirase/ritonavir and ketoconazole are coadministered, plasma concentrations of ketoconazole are increased (see Table 3). Hence, doses of ketoconazole or itraconazole >200 mg/day are not recommended.
Antimycobacterial:
Rifabutin† ? Saquinavir
? Rifabutin
? Ritonavir
No dose adjustment of Invirase/ritonavir (1000/100 mg bid) is required if ritonavir-boosted Invirase is administered in combination with rifabutin.
Dosage reduction of rifabutin by at least 75% of the usual dose of 300 mg/day is recommended (i.e., a maximum dose of 150 mg every other day or three times per week). Increased monitoring for adverse events is warranted in patients receiving the combination.
Consider monitoring rifabutin concentrations to ensure adequate exposure.
Benzodiazepines*:
Alprazolam, clorazepate, diazepam, flurazepam
? Benzodiazepines Clinical significance is unknown; however, a decrease in benzodiazepine dose may be needed.
Benzodiazepine*:
Intravenously administered Midazolam ? Midazolam Midazolam is extensively metabolized by CYP3A4. Increases in the concentration of midazolam are expected to be significantly higher with oral than parenteral administration. Therefore, Invirase should not be given with orally administered midazolam [see Contraindications (4)]. If Invirase is coadministered with parenteral midazolam, close clinical monitoring for respiratory depression and/or prolonged sedation should be exercised and dosage adjustment should be considered.
Calcium channel blockers*:
Diltiazem, felodipine, nifedipine, nicardipine, nimodipine, verapamil, amlodipine, nisoldipine, isradipine
? Calcium channel blockers Caution is warranted and clinical monitoring of patients is recommended. Corticosteroid:
Dexamethasone* ? Saquinavir
Use with caution. Saquinavir may be less effective due to decreased saquinavir plasma concentrations.
Digitalis Glycosides: Digoxin† ? Digoxin
Increases in serum digoxin concentration were greater in female subjects as compared to male subjects when digoxin was coadministered with Invirase/ritonavir.
Concomitant use of Invirase/ritonavir with digoxin results in a significant increase in serum concentrations of digoxin. Caution should be exercised when Invirase/ritonavir and digoxin are coadministered; serum digoxin concentrations should be monitored and the dose of digoxin may need to be reduced when coadministered with Invirase/ritonavir.
Endothelin receptor antagonists:
Bosentan ? Bosentan Coadministration of bosentan in patients on Invirase/ritonavir:
In patients who have been receiving Invirase/ritonavir for at least 10 days, start bosentan at 62.5 mg once daily or every other day based upon individual tolerability.
Coadministration of Invirase/ritonavir in patients on bosentan:
Discontinue use of bosentan at least 36 hours prior to initiation of Invirase/ritonavir.
After at least 10 days following the initiation of Invirase/ritonavir, resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability.
Inhaled beta agonist:
Salmeterol ? Salmeterol Concurrent administration of salmeterol with Invirase/ritonavir is not recommended. The combination may result in increased risk of cardiovascular adverse events associated with salmeterol, including QT prolongation, palpitations and sinus tachycardia.
Inhaled/nasal steroid:
Fluticasone* Invirase/ritonavir
? Fluticasone Concomitant use of fluticasone propionate and Invirase/ritonavir may increase plasma concentrations of fluticasone propionate, resulting in significantly reduced serum cortisol concentrations. Coadministration of fluticasone propionate and Invirase/ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.
HMG-CoA reductase inhibitors*:
Atorvastatin, rosuvastatin ? Atorvastatin
? Rosuvastatin
Use lowest possible dose of atorvastatin or rosuvastatin with careful monitoring, or consider other HMG-CoA reductase inhibitors such as fluvastatin in combination with Invirase/ritonavir.
Immunosuppressants*:
Cyclosporine, tacrolimus, rapamycin ? Immunosuppressants Therapeutic concentration monitoring is recommended for immunosuppressant agents when coadministered with Invirase/ritonavir.
Narcotic analgesic:
Methadone† ? Methadone Dosage of methadone may need to be increased when coadministered with Invirase/ritonavir.
Use with caution. Additive effects on QT and/or PR interval prolongation may occur with Invirase/ritonavir [see Contraindications (4) and Warnings and Precautions (5.2, 5.3)].
Neuroleptics:
Clozapine
Haloperidol
Mesoridazine
Phenothiazines
Thioridazine
Ziprasidone
Use with caution. Additive effects on QT and/or PR interval prolongation may occur with Invirase/ritonavir [see Contraindications (4) and Warnings and Precautions (5.2, 5.3)].
Oral contraceptives:
Ethinyl estradiol* ? Ethinyl estradiol Alternative or additional contraceptive measures should be used when estrogen-based oral contraceptives and Invirase/ritonavir are coadministered.
PDE5 inhibitors (phosphodiesterase type 5 inhibitors):
Sildenafil†, vardenafil*, tadalafil* ? Sildenafil
? Saquinavir
? Vardenafil
? Tadalafil
Only the combination of sildenafil with saquinavir soft gelatin capsules has been studied at doses used for treatment of erectile dysfunction.
May result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, syncope, visual disturbances, and priapism.
Use of PDE-5 inhibitors for pulmonary arterial hypertension (PAH): Use of sildenafil (Revatio) is contraindicated when used for the treatment of pulmonary arterial hypertension (PAH) [see Contraindications (4)]. The following dose adjustments are recommended for use of tadalafil (ADCIRCA®) with Invirase/ritonavir:
Coadministration of ADCIRCA in patients on Invirase/ritonavir:
In patients receiving Invirase/ritonavir for at least one week, start ADCIRCA at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
Coadministration of Invirase/ritonavir in patients on ADCIRCA:
Avoid use of ADCIRCA during the initiation of Invirase/ritonavir. Stop ADCIRCA at least 24 hours prior to starting Invirase/ritonavir. After at least one week following the initiation of Invirase/ritonavir, resume ADCIRCA at 20 mg once daily. Increase to 40 mg once daily based upon individual tolerability.
Use of PDE5 inhibitors for erectile dysfunction:
Use sildenafil with caution at reduced doses of 25 mg every 48 hours with increased monitoring of adverse events when administered concomitantly with Invirase/ritonavir.
Use vardenafil with caution at reduced doses of no more than 2.5 mg every 72 hours with increased monitoring of adverse events when administered concomitantly with Invirase/ritonavir.
Use tadalafil with caution at reduced doses of no more than 10 mg every 72 hours with increased monitoring of adverse events when administered concomitantly with Invirase/ritonavir.
Tricyclic antidepressants*: Amitriptyline, imipramine
? Tricyclics Therapeutic concentration monitoring is recommended for tricyclic antidepressants when coadministered with Invirase/ritonavir.
Proton pump inhibitors: Omeprazole† ? Saquinavir When Invirase/ritonavir is co-administered with omeprazole, saquinavir concentrations are increased significantly. If omeprazole or another proton pump inhibitor is taken concomitantly with Invirase/ritonavir, caution is advised and monitoring for potential saquinavir toxicities is recommended, particularly gastrointestinal symptoms, increased triglycerides, deep vein thrombosis, and QT prolongation.
Herbal Products:
St. John's wort* (hypericum perforatum) ? Saquinavir Coadministration may lead to loss of virologic response and possible resistance to Invirase or to the class of protease inhibitors.
Garlic Capsules* ? Saquinavir Coadministration of garlic capsules and saquinavir is not recommended due to the potential for garlic capsules to induce the metabolism of saquinavir which may result in sub-therapeutic saquinavir concentrations.
USE IN SPECIFIC POPULATIONS Pregnancy
Pregnancy Category B
Reproduction studies conducted with saquinavir have shown no embryotoxicity or teratogenicity in both rats and rabbits. Because of limited bioavailability of saquinavir in animals and/or dosing limitations, the plasma exposures (AUC values) in the respective species were approximately 29% (using rat) and 21% (using rabbit) of those obtained in humans at the recommended clinical dose boosted with ritonavir. Clinical experience in pregnant women is limited. Saquinavir should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Antiretroviral Pregnancy Registry
To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral medications, including Invirase, an Antiretroviral Pregnancy Registry has been established. Physicians are encouraged to register patients by calling 1-800-258-4263.
Nursing MothersThe Centers for Disease Control and Prevention recommend that HIV-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV. It is not known whether saquinavir is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast-feed if they are receiving Invirase.
Pediatric UseSafety and effectiveness of Invirase in HIV-1-infected pediatric patients younger than 16 years of age have not been established.
Geriatric UseClinical studies of Invirase did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from
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