Atazanavir

Name: Atazanavir

Administration

Oral Administration

Take capsule or oral powder with food

Do not open capsules

Take atazanavir and ritonavir in a single dose

When coadministered with H2-receptor antagonists or proton-pump inhibitors, dose separation may be required

Oral powder must be taken with ritonavir and is not recommended for use in children who weigh <5 kg or aged <3 months (risk of kernicterus)

Instructions for mixing oral powder

Determine the number of packets that are needed

Prior to mixing, tap the packet to settle the powder

It is preferable to mix oral powder with food (eg, applesauce, yogurt)

Mixing oral powder with a beverage (milk, infant formula, or water) may be used for infants who can drink from a cup

For young infants (aged <6 months) who cannot eat solid food or drink from a cup, mix oral powder with infant formula and administer using an oral dosing syringe

Administration in infant formula using an infant bottle is not recommended because full dose may not be delivered

Administer ritonavir immediately following atazanavir oral powder administration

Administer the entire oral powder dose (mixed in the food or beverage) within 1 hr of preparation (may leave the mixture at room temperature during this 1 hr period)

Ensure that the patient eats or drinks all the food or beverage that contains the powder

Additional food may be given after consumption of the entire mixture

Mixing with food

  • Using a spoon, mix the recommended number of oral powder packets with a minimum of 1 tablespoon of food (eg, applesauce, yogurt)
  • Feed the mixture to the infant or young child
  • Add an additional 1 tablespoon of food to the small container, mix, and feed the child the residual mixture

Mixing with beverage

  • Using a spoon, mix the recommended number of oral powder packets with a minimum of 30 mL of beverage (eg, milk, water) in a small beverage cup
  • Have the child drink the mixture
  • Add an additional 15 mL more of beverage to the drinking cup, mix, and have the child drink the residual mixture
  • If water is used, food should also be taken at the same time

Mixing with infant formula

  • Using a spoon, mix the recommended number oral powder packets with 10 mL of prepared liquid infant formula
  • Draw up the full amount of the mixture into an oral syringe and administer into either right or left inner cheek of infant
  • Pour another 10 mL of formula into the medicine cup to rinse off remaining oral powder in cup, draw up residual mixture into the syringe and administer into either right or left inner cheek of infant

Atazanavir Overview

Atazanavir is a prescription medication used in combination with other medications to treat human immunodeficiency virus (HIV) infection. Atazanavir belongs to a group of medications called protease inhibitors which work by stopping the virus from replicating.

This medication comes in capsule form and is taken once daily, with food.

Atazanavir is also available as an oral powder and is taken with food or liquid.

Common side effects of atazanavir include nausea, stomach pain, and headaches.

Atazanavir Food Interactions

Grapefruit and grapefruit juice may interact with atazanavir and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

What is the most important information I should know about atazanavir?

Tell your doctor about all your current medicines and any you start or stop using. Many drugs can interact with atazanavir, and some drugs should not be used together.

What should I discuss with my healthcare provider before taking atazanavir?

You should not use this medicine if you have ever had a severe allergic reaction to atazanavir.

Some medicines can cause unwanted or dangerous effects when used with atazanavir. Your doctor may need to change your treatment plan if you use any of the following drugs:

  • alfuzosin;

  • cisapride;

  • irinotecan;

  • rifampin;

  • sildenafil (Revatio, for treating pulmonary arterial hypertension);

  • St. John's wort;

  • antipsychotic medicine--lurasidone, pimozide;

  • ergot medicines--dihydroergotamine, ergotamine, ergonovine, methylergonovine;

  • HIV medicines--indinavir, nevirapine;

  • medicine to lower cholesterol--lovastatin, simvastatin; or

  • sedative medicines--triazolam, oral midazolam.

To make sure atazanavir is safe for you, tell your doctor if you have ever had:

  • liver disease (especially hepatitis B or C);

  • kidney disease (or if you are on dialysis);

  • kidney stones or gallstones;

  • diabetes;

  • a bleeding disorder such as hemophilia; or

  • a heart rhythm disorder, a heart condition called "AV block."

Atazanavir oral powder may contain phenylalanine. Talk to your doctor before using this form of atazanavir if you have phenylketonuria (PKU).

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. Your dose needs may be different during pregnancy and for a short time after childbirth.

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 atazanavir on the baby.

Atazanavir can make birth control pills, patches, injections, or vaginal rings less effective. Ask your doctor about using a non-hormone method of birth control (such as a condom, diaphragm, spermicide) to prevent pregnancy while taking atazanavir.

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.

Atazanavir should not be given to a child younger than 3 months old and weighing less than 11 pounds (5 kilograms).

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if your next dose is less than 6 hours away. Do not take extra medicine to make up the missed dose.

What other drugs will affect atazanavir?

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective.

Many drugs can interact with atazanavir, and some drugs should not be used together. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide. Tell your doctor about all your current medicines and any medicine you start or stop using.

Uses For atazanavir

Atazanavir is used together with other medicines for the treatment of the infection caused by the human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS).

Atazanavir will not cure or prevent HIV infection or AIDS. It helps keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay problems that are usually related to AIDS or HIV disease from occurring. Atazanavir will not keep you from spreading HIV to other people. People who receive atazanavir may continue to have other problems usually related to AIDS or HIV disease.

atazanavir is available only with your doctor's prescription.

Proper Use of atazanavir

Take atazanavir exactly as directed by your doctor. Do not change the dose or stop using atazanavir without checking first with your doctor. When your supply of atazanavir is running low, contact your doctor or pharmacist ahead of time. Do not allow yourself to run out of atazanavir.

atazanavir comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor or pharmacist if you have any questions.

atazanavir may be taken in combination with other medicines that are used to treat HIV infection. Take all of the medicines your doctor has prescribed at the right time of day and in the correct order. Do not stop using your medicine unless your doctor tells you to.

atazanavir is available in 2 forms. You may use a capsule or an oral powder. Your doctor may adjust your dose if you need to switch from one form to another.

It is important that atazanavir be taken with food.

Swallow the capsule whole. Do not open it.

For patients using the oral powder:

  • Determine the number of packets that are needed. Do not open a packet until ready to use it.
  • Mix the oral powder with food (eg, applesauce or yogurt) or a beverage (milk, infant formula, water). You may mix it in a container or a cup and use an oral dosing syringe or small medicine cup to give it to a child.
  • After mixing your medicine with food or liquid, use the mixture right away or up to 1 hour. Be sure to drink or swallow all of the mixture.

If you are also using antacids or didanosine (Videx®), take atazanavir 2 hours before or 1 hour after these medicines.

Dosing

The dose of atazanavir will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of atazanavir. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • For oral dosage form (capsules):
    • For HIV infection (patient already had HIV treatment):
      • Adults—300 milligrams (mg) with 100 mg of ritonavir (Norvir®) once a day. For patients who are also taking atazanavir in combination with both H2RA and tenofovir, the dose is usually 400 mg with 100 mg of ritonavir (Norvir®) once a day.
      • Pregnant patients—300 mg with 100 mg of ritonavir (Norvir®) once a day. For pregnant patients who are also taking atazanavir in combination with both H2RA or tenofovir, the dose is usually 400 mg with 100 mg of ritonavir (Norvir®) once a day.
      • Children 6 to 17 years and weighing 35 kilograms (kg) or more—Dose is based on body weight and must be determined by your doctor. However, the dose is usually 300 mg with 100 mg of ritonavir (Norvir®) once a day.
      • Children 6 to 17 years and weighing 15 to less than 35 kg—Dose is based on body weight and must be determined by your doctor. However, the dose is usually 200 mg with 100 mg of ritonavir (Norvir®) once a day.
      • Children 6 to 17 years and weighing less than 15 kg—Use of capsules is not recommended.
    • For HIV infection (patient never had HIV treatment):
      • Adults—300 milligrams (mg) with 100 mg of ritonavir (Norvir®) once a day. For patients who are unable to tolerate ritonavir, the dose is usually 400 mg (without ritonavir) once day. For patients who are also taking atazanavir in combination with efavirenz, the dose is usually 400 mg with 100 mg of ritonavir (Norvir®) once a day.
      • Pregnant patients—300 mg with 100 mg of ritonavir (Norvir®) once a day.
      • Children 6 to 17 years and weighing 35 kilograms (kg) or more—Dose is based on body weight and must be determined by your doctor. However, the dose is usually 300 mg with 100 mg of ritonavir (Norvir®) once a day. For children at least 13 years old and weighing 40 kilograms (kg) who are unable to tolerate ritonavir, the dose is usually 400 mg (without ritonavir) once day.
      • Children 6 to 17 years and weighing 15 to less than 35 kg—Dose is based on body weight and must be determined by your doctor. However, the dose is usually 200 mg with 100 mg of ritonavir (Norvir®) once a day.
      • Children 6 to 17 years and weighing less than 15 kg—Use of capsules is not recommended.
  • For oral dosage form (oral powder):
    • For HIV infection:
      • Children 3 months of age and older and weighing at least 25 kilograms (kg) who are unable to swallow the capsule—Dose is based on body weight and must be determined by your doctor. However, the dose is usually 300 milligrams (mg) (6 packets) with 100 mg of ritonavir (Norvir®) once a day.
      • Children 3 months of age and older and weighing 15 to less than 25 kg—Dose is based on body weight and must be determined by your doctor. However, the dose is usually 250 mg (5 packets) with 80 mg of ritonavir (Norvir®) once a day.
      • Children 3 months of age and older and weighing 5 to less than 15 kg—Dose is based on body weight and must be determined by your doctor. However, the dose is usually 200 mg (4 packets) with 80 mg of ritonavir (Norvir®) once a day. For children weighing 5 to less than 10 kg and cannot tolerate the 200 mg dose and have not taken an HIV protease inhibitor, may take 150 mg (3 packets) once a day.
      • Children younger than 3 months of age or weighing less than 5 kg—Use is not recommended.

Missed Dose

If you miss a dose of atazanavir, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose or forget to use your medicine, use it as soon as you can. If your next regular dose is less than 6 hours away, wait until then to use the medicine and skip the missed dose.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Index Terms

  • Atazanavir Sulfate
  • ATV
  • BMS-232632

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as sulfate:

Reyataz: 150 mg, 200 mg, 300 mg [contains fd&c blue #2 (indigotine)]

Packet, Oral, as sulfate:

Reyataz: 50 mg (30 ea) [contains aspartame; orange-vanilla flavor]

Special Populations Renal Function Impairment

The mean Cmax was 9% lower, AUC was 19% higher, and Cmin was 96% higher in subjects with severe renal impairment not undergoing hemodialysis. When atazanavir was administered prior to or following hemodialysis, the Cmax, AUC, and Cmin were ~25% to 43% lower compared with subjects with healthy renal function.

Dietary Considerations

Must be taken with food; enhances absorption.

Indications and Usage for Atazanavir

Atazanavir is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection for patients 3 months and older weighing at least 5 kg.

Limitations of Use:

• Atazanavir is not recommended for use in pediatric patients below the age of 3 months due to the risk of kernicterus. • Use of atazanavir/ritonavir in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions [see Microbiology (12.4)].

Contraindications

Atazanavir is contraindicated:

• in patients with previously demonstrated clinically significant hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of Atazanavir capsules or Atazanavir (REYATAZ) oral powder [see Warnings and Precautions (5.2)]. • when coadministered 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 (see Table 6). • when coadministered with drugs that strongly induce CYP3A and may lead to lower exposure and loss of efficacy of Atazanavir (see Table 6).

Table 6 displays drugs that are contraindicated with atazanavir.

Table 6:  Drugs that are Contraindicated with Atazanavir (Information in the table applies to Atazanavir with or without ritonavir, unless otherwise indicated)
a  See Drug Interactions, Table 16 (7) for parenterally administered midazolam.
b  See Drug Interactions, Table 16 (7) for sildenafil when dosed as VIAGRA® for erectile dysfunction.

Drug Class

Drugs within class that are contraindicated with atazanavir

Clinical Comment

Alpha 1-Adrenoreceptor Antagonist

Alfuzosin

Potential for increased alfuzosin concentrations, which can result in hypotension.

Antimycobacterials

Rifampin

Rifampin substantially decreases plasma concentrations of atazanavir, which may result in loss of therapeutic effect and development of resistance.

Antineoplastics

Irinotecan

Atazanavir inhibits UGT1A1 and may interfere with the metabolism of irinotecan, resulting in increased irinotecan toxicities.

Antipsychotics

Lurasidone

Potential for serious and/or life-threatening reactions if Atazanavir is coadministered with ritonavir.

Pimozide

Potential for serious and/or life-threatening reactions such as cardiac arrhythmias.

Benzodiazepines

Triazolam, orally administered midazolama

Triazolam and orally administered midazolam are extensively metabolized by CYP3A4. Coadministration of triazolam or orally administered midazolam with Atazanavir may cause large increases in the concentration of these benzodiazepines. Potential for serious and/or life-threatening events such as prolonged or increased sedation or respiratory depression.

Ergot Derivatives

Dihydroergotamine, ergotamine, ergonovine, methylergonovine

Potential for serious and/or life-threatening events such as acute 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.

Hepatitis C Direct-

Acting Antivirals

Elbasvir/grazoprevir

May increase the risk of ALT elevations due to a significant increase in grazoprevir plasma concentrations.

Herbal Products

St. John’s wort (Hypericum perforatum)

Coadministration of St. John’s wort and Atazanavir may result in loss of therapeutic effect and development of resistance.

HMG-CoA Reductase Inhibitors

Lovastatin, simvastatin

Potential for serious reactions such as myopathy, including rhabdomyolysis.

PDE5 Inhibitor

Sildenafilb when dosed as REVATIO® for the treatment of pulmonary arterial hypertension

Potential for sildenafil-associated adverse events (which include visual disturbances, hypotension, priapism, and syncope).

Protease Inhibitors

Indinavir

Both Atazanavir and indinavir are associated with indirect (unconjugated) hyperbilirubinemia.

Non-nucleoside Reverse Transcriptase Inhibitors

Nevirapine

Nevirapine substantially decreases Atazanavir exposure which may result in loss of therapeutic effect and development of resistance. Potential risk for nevirapine-associated adverse reactions due to increased nevirapine exposures.

Atazanavir Description

The active ingredient in Atazanavir capsules and Atazanavir (REYATAZ) oral powder is Atazanavir sulfate, which is an HIV-1 protease inhibitor.

The chemical name for Atazanavir sulfate is (3S,8S,9S,12S)-3,12-Bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-[[4-(2-pyridinyl)phenyl]methyl]-2,5,6,10,13-pentaazatetradecanedioic acid dimethyl ester, sulfate (1:1). Its molecular formula is C38H52N6O7•H2SO4, which corresponds to a molecular weight of 802.9 (sulfuric acid salt). The free base molecular weight is 704.9. Atazanavir sulfate has the following structural formula:

Atazanavir sulfate is a white to pale-yellow crystalline powder. It is slightly soluble in water (4-5 mg/mL, free base equivalent) with the pH of a saturated solution in water being about 1.9 at 24 ± 3°C.

Atazanavir capsules are available for oral administration in strengths of 150 mg, 200 mg, or 300 mg of atazanavir, which are equivalent to 170.8 mg, 227.8 mg, or 341.69 mg of Atazanavir sulfate, respectively. The capsules also contain the following inactive ingredients: crospovidone, lactose monohydrate, and magnesium stearate. The capsule shells contain the following inactive ingredients: gelatin, FD&C Blue No. 2, titanium dioxide, black iron oxide, red iron oxide, and yellow iron oxide. The capsules are printed with ink containing shellac, titanium dioxide, FD&C Blue No. 2, isopropyl alcohol, ammonium hydroxide, propylene glycol, n-butyl alcohol, simethicone, and dehydrated alcohol.

Atazanavir (REYATAZ) oral powder comes in a packet containing 50 mg of Atazanavir equivalent to 56.9 mg of Atazanavir sulfate in 1.5 g of powder. The powder is off-white to pale yellow and contains the following inactive ingredients: aspartame, sucrose, and orange-vanilla flavor.

Atazanavir 200 mg Capsules Representative Packaging

NDC 59762-0409-6
60 Capsules
GREENSTONE
Atazanavir
Capsules
200 mg
Rx only
Note to pharmacist: Do not cover ALERT box with pharmacy label.
ALERT: Find out about medicines that should NOT be taken with Atazanavir

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