Atazanavir and cobicistat

Name: Atazanavir and cobicistat

Atazanavir and Cobicistat Overview

Atazanavir/cobicistat is a prescription medication used to treat human immunodeficiency virus (HIV) infection in adults.

It is a single product containing 2 medications: atazanavir and cobicistat.

Atazanavir belongs to a group of drugs called protease inhibitors. It works by decreasing the amount of HIV in the blood.

Cobicistat belongs to a group of drugs called pharmacokinetic enhancers. Cobicistat helps to keep atazanavir in the body longer so that the medication will have a greater effect.

This medication comes in tablet form and is taken typically once a day, with food. Common side effects of atazanavir/cobicistat include yellowing of the skin or eyes and nausea.

Uses of Atazanavir and Cobicistat

Atazanavir/cobicistat is a prescription medication used to treat human immunodeficiency virus (HIV) infection in adults.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Atazanavir and Cobicistat Interactions

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • medications that use the enzyme CYP3A4 such as budesonide (Entocort), astemizole (Hismanal), cisapride (Propulsid), cyclosporine (Neoral, Gengraf, Sandimmune), darifenacin (Enablex), dihydroergotamine (Migranal), fentanyl (Abstral, Fentora, Onsolis, Actiq), pimozide (Orap), quinidine (Cardioquin, Duraquin, Quinact), sirolimus (Rapamune), tacrolimus (Prograf), terfenadine (Seldane), fluticasone (Flovent HFA, Flonase), eletriptan (Relpax), lovastatin (Mevacor), quetiapine (Seroquel), sildenafil (Viagra, Revatio), and simvastatin (Zocor)
  • medications that use an enzyme CYP2C8 such as amiodarone (Cordarone), cabazitaxel (Jevtana), carbamazepine (Tegretol), chloroquine (Aralen), diclofenac (Voltaren), ibuprofen (Advil), paclitaxel (Taxol), rosiglitazone (Avandia), repaglinide (Prandin), treprostinil (Tyvaso)
  • medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), St John's wort, and nimodipine (Nimotop)
  • medications that block a protein in the body (CYPA4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone
  • anticoagulant (blood thinner) medications such as warfarin (Coumadin, Jantoven), heparin, enoxaparin (Lovenox), fondaparinux (Arixtra), rivaroxaban (Xarelto), and apixaban (Eliquis) 
  • medications that reduce the acid level in your stomach such as esomeprazole (Nexium), lansoprazole (Prevacid), omeprazole (Prilosec), pantoprazole (Protonix), rabeprazole (Aciphex), cimetidine (Tagamet), famotidine (Pepcid), nizatidine (Axid), ranitidine (Zantac)
  • anti-arrhythmia medications such as procainamide (Procanbid, Procan), disopyramide (Norpace, Rythmodan), lidocaine (Xylocaine, Lidoderm), phenytoin (Dilantin), mexiletine (Mexitil), flecainide (Tambocor), propafenone (Rythmol), amiodarone (Cordarone, Pacerone), sotalol (Betapace), dofetilide (Tikosyn), dronedarone (Multaq), digoxin (Lanoxin), and adenosine (Adenocard)

This is not a complete list of drug interactions. Ask your doctor or pharmacist for more information.

Atazanavir and Cobicistat Precautions

Serious side effects have been reported with atazanavir/cobicistat including the following:

  • Heart rhythm abnormalities. Tell your healthcare provider right away if you get dizzy or lightheaded. These could be symptoms of a heart problem.
  • Severe Rash. Skin rash is common with atazanavir/cobicistat but can sometimes be severe. Skin rash usually goes away within 2 weeks without any change in treatment. Severe rash may develop with other symptoms which could be serious. If you develop a severe rash or a rash with any of the following symptoms, call your healthcare provider or go to the nearest hospital emergency room right away.
    • general feeling of discomfort or “flu-like” symptoms
    • fever
    • muscle or joint aches
    • swelling of your face
    • red or inflamed eyes, like “pink eye”
    • (conjunctivitis)
    • blisters
    • mouth sores
    • painful, warm, or red lump under your skin
  • Kidney damage. Atazanavir/cobicistat when taken with certain other medicines, can cause new or worse kidney problems, including kidney failure. Your healthcare provider should check your kidneys before you start and while you are taking atazanavir/cobicistat.
  • Kidney stones have happened in some people who take atazanavir. Tell your healthcare provider right away if you get symptoms of kidney stones, which may include pain in your low back or low stomach area, blood in your urine, or pain when you urinate.
  • Gallstones have happened in some people who take atazanavir. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include:
    • pain in the right or middle upper stomach area
    • fever
    • nausea and vomiting
    • your skin or the white part of your eyes turns yellow
  • Liver damage. If you have liver problems, including hepatitis B or C infection, your liver problems may get worse when you takeatazanavir/cobicistat. Your healthcare provider will do blood tests to check your liver before you start atazanavir/cobicistat and during treatment. Tell yourhealthcare provider right away if you get any of the following symptoms:
    • your skin or the white part of your eyes turns yellow
    • dark (tea-colored) urine
    • light colored stools
    • nausea
    • itching
    • stomach-area pain
  • Diabetes or rises in blood sugar ave happened and worsened in some people who take protease inhibitor medicines like atazanavir/cobicistat. Some people have had to start taking medicine to treat diabetes or have had to change their diabetes medicine
  • Increased bleeding problems in in people with hemophilia have happened when taking protease inhibitors including atazanavir/cobicistat.
  • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider if you start having new symptoms after starting your HIV-1 medicine.
  • Changes in body fat can happen in people taking HIV-1 medicines. These changes may include increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known.
  • Yellowing of the skin or the white part of your eyes is common with atazanavir/cobicistat but may be a symptom of a serious problem. These effects may be due to increases in bilirubin levels in the blood (bilirubin is made by the liver). Although these effects may not be damaging to your liver, skin, or eyes, tell your healthcare provider right away if your skin or the white part of your eyes turns yellow.

Do not take atazanavir/cobicistat if you:

  • are allergic to atazanavir, cobicistat or to any of its ingredients 
  • have had severe, life-threatening rashes in the past
  • take medications that can interact with atazanavir or cobicistat

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Atazanavir and cobicistat side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

This medicine may increase your risk of certain infections or autoimmune disorders by changing the way your immune system works. Symptoms may occur weeks or months after you start treatment with atazanavir and cobicistat. Tell your doctor if you have:

  • signs of a new infection--fever, night sweats, swollen glands, mouth sores, diarrhea, stomach pain, weight loss;

  • chest pain (especially when you breathe), dry cough, wheezing, feeling short of breath;

  • cold sores, sores on your genital or anal area;

  • rapid heart rate, feeling anxious or irritable, weakness or prickly feeling, problems with balance or eye movement;

  • trouble speaking or swallowing, severe lower back pain, loss of bladder or bowel control; or

  • swelling in your neck or throat (enlarged thyroid), menstrual changes, impotence, loss of interest in sex.

Call your doctor at once if you have:

  • severe dizziness, fainting, irregular heartbeats;

  • liver problems--upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  • high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss;

  • signs of a kidney stone--pain in your side or lower back, painful or difficult urination, blood in your urine;

  • signs of inflammation in your body--swollen glands, flu symptoms, easy bruising or bleeding, severe tingling or numbness, muscle weakness, upper stomach pain, jaundice (yellowing of the skin or eyes), chest pain, new or worsening cough with fever, trouble breathing; or

  • severe skin reaction--fever, sore throat, swelling in your face or tongue, burning or redness in your eyes, skin pain, warmth or redness under your skin, red or purple skin rash that spreads and causes blistering and peeling.

You may need to stop taking this medicine permanently if you have a severe skin reaction.

Common side effects may include:

  • rash;

  • nausea; or

  • jaundice.

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.

Atazanavir and cobicistat dosing information

Usual Adult Dose for HIV Infection:

1 tablet orally once a day with food

Comments:
-For therapy-naive and therapy-experienced patients
-The number of baseline primary protease inhibitor resistance substitutions should guide use in therapy-experienced patients.

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Uses of Atazanavir and Cobicistat

  • It is used to treat HIV infection.

How is this medicine (Atazanavir and Cobicistat) best taken?

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take atazanavir and cobicistat with food.
  • Do not take antacids within 2 hours of this medicine.
  • If you are also taking didanosine, take it at least 1 hour before or 2 hours after atazanavir and cobicistat.
  • If you take cimetidine, dexlansoprazole, esomeprazole, famotidine, lansoprazole, nizatidine, omeprazole, pantoprazole, rabeprazole, or ranitidine, ask your doctor or pharmacist how to take it with this medicine.
  • It is important that you do not miss or skip a dose of atazanavir and cobicistat during treatment.
  • Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.
  • If you are not sure what to do if you miss a dose, call your doctor.

Pharmacology

Atazanavir binds to the site of HIV-1 protease activity and inhibits cleavage of viral Gag-Pol polyprotein precursors into individual functional proteins required for infectious HIV. This results in the formation of immature, noninfectious viral particles.

Cobicistat is a mechanism-based inhibitor of cytochrome P450 3A (CYP3A). Inhibition of CYP3A-mediated metabolism by cobicistat and increases the systemic exposure of CYP3A substrates (eg, atazanavir).

Contraindications

Hypersensitivity (previously demonstrated and clinically significant [eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions]) to atazanavir, cobicistat, or any component of the formulation; coadministration with drugs that are highly dependent on CYP3A or UGT1A1 for clearance (and for which elevated plasma concentrations of the interacting drugs are associated with serious and/or life-threatening events) or coadministration with drugs that strongly induce CYP3A and may lead to lower exposure and loss of efficacy of atazanavir or cobicistat; coadministered drugs that are contraindicated include (but are not limited to) alfuzosin, carbamazepine, cisapride, colchicine (in patients with renal and/or hepatic impairment), dronedarone, elbasvir/grazoprevir, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine), indinavir, irinotecan, lovastatin, lurasidone, midazolam (oral), nevirapine, phenobarbital, phenytoin, pimozide, ranolazine, rifampin, sildenafil (when used for pulmonary artery hypertension), simvastatin, St. John's wort, or triazolam

Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with quinidine, ritonavir or products containing ritonavir, salmeterol

Monitoring Parameters

Vital signs, ECG, serum creatinine (at baseline and when clinically indicated); liver function tests (baseline and periodically during treatment) in patients at risk for hepatic impairment. When coadministered with tenofovir disoproxil fumarate, creatinine clearance, urine glucose, and urine protein prior to initiation and as clinically indicated during therapy; assess serum phosphorus in patients with or at risk for renal impairment. Patients who experience a confirmed increase in serum creatinine >0.4 mg/dL from baseline should have renal function monitored closely. Testing for HBV is recommended prior to the initiation of antiretroviral therapy.

For the Consumer

Applies to atazanavir / cobicistat: oral tablet, tablet oral

Along with its needed effects, atazanavir / cobicistat may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking atazanavir / cobicistat:

More common
  • Abdominal or stomach pain
  • chills
  • clay-colored stools
  • dark urine
  • dizziness
  • fever
  • headache
  • itching or rash
  • loss of appetite
  • nausea
  • unpleasant breath odor
  • unusual tiredness or weakness
  • vomiting of blood
  • yellow eyes or skin
Incidence not known
  • Abdominal or stomach fullness or tenderness
  • black, tarry stools
  • blistering, peeling, or loosening of the skin
  • blood in the urine
  • chest pain
  • clay colored stools
  • decreased appetite
  • diarrhea
  • gaseous abdominal or stomach pain
  • joint or muscle pain
  • pain in the groin or genitals
  • painful or difficult urination
  • recurrent fever
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • sharp back pain just below the ribs
  • sore throat
  • sores, ulcers, or white spots in the mouth or on the lips
  • swelling of the feet or lower legs
  • swollen glands
  • unusual bleeding or bruising

Precautions

Safety and efficacy have not been established in patients younger than 18 years; this drug is not recommended for use in patients younger than 3 months (due to risk of kernicterus).

Consult WARNINGS section for additional precautions.

Atazanavir / cobicistat Pregnancy Warnings

Animal studies have failed to reveal evidence of teratogenicity with atazanavir at maternal doses producing systemic drug exposure levels 0.7 (rabbits) or 1.2 (rats) times those at the human clinical dose (atazanavir 300 mg/day boosted with ritonavir 100 mg/day); at an exposure level causing maternal toxicity, body weight loss or weight gain suppression was observed in rat offspring. Animal studies have failed to reveal evidence of teratogenicity, embryofetal toxicity, or an effect on reproductive function with cobicistat. Atazanavir/ritonavir has been evaluated in a limited number of women during pregnancy and postpartum. Available data suggest atazanavir does not increase risk of major birth defects overall (compared with background rate); however, human studies cannot rule out the possibility of harm. For cobicistat and atazanavir-cobicistat, there are no controlled data in human pregnancy. Symptomatic hyperlactatemia and lactic acidosis syndrome (in some cases fatal) have been reported in pregnant women using atazanavir in combination with nucleoside analogs, which are known to have greater risk of lactic acidosis. Hyperbilirubinemia has been reported frequently during atazanavir therapy; it is not known whether maternal use would lead to neonatal kernicterus. All infants (including newborns exposed to atazanavir in utero) should be monitored for severe hyperbilirubinemia during the first few days of life. To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com As of January 2010, the APR had received prospective reports of 635 exposures to atazanavir-containing regimens (425, 160, and 50 first, second, and third trimester exposures, respectively). Birth defects occurred in 9 of 393 live births with first trimester exposure and 5 of 212 live births with second or third trimester exposure. The background rate of birth defects among pregnant women in the US reference population is 2.7%. There was no association between atazanavir and overall birth defects observed in the APR. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus; this drug should not be used in therapy-experienced patients taking an H2-receptor antagonist and/or tenofovir during the second and third trimesters. US FDA pregnancy category: B Comments: The manufacturer product information for atazanavir should be consulted for information regarding its use with ritonavir during pregnancy.

(web3)