How do you administer this medicine?
What is 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.
In combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from controlled studies of 96 weeks duration in antiretroviral-naive and 48 weeks duration in antiretroviral treatment-experienced patients.
The following points should be considered when initiating therapy with Atazanavir: In study AI424-045 Atazanavir/ritonavir and lopinavir/ritonavir were similar for the primary efficacy outcome measure of time-averaged difference in change from baseline in HIV RNA level. This study was not large enough to reach a definitive conclusion that Atazanavir/ritonavir and lopinavir/ritonavir are equivalent on the secondary efficacy outcome measure of proportions below the HIV RNA lower limit of detection.
The number of baseline primary PI mutations affects the virologic response to Atazanavir/ritonavir.
How should I use Atazanavir?
Give Atazanavir powder for oral suspension as directed by the doctor. Check the label on the medicine for exact dosing instructions.
- An extra patient leaflet is available with Atazanavir powder for oral suspension. Talk to your pharmacist if you have questions about this information.
- Give Atazanavir powder for oral suspension by mouth with food.
- Before giving, mix the powder with soft food (eg, applesauce, yogurt). If you cannot do this, mix with a drink (eg, milk, infant formula, water). Mix Atazanavir powder for oral suspension as the doctor has told you or read the package insert.
- If you use infant formula to mix the powder, give the medicine using an oral dosing syringe. Do not give using an infant bottle.
- Give Atazanavir powder for oral suspension within 1 hour of mixing.
- If your child also takes an Hantagonist (eg, cimetidine) or a proton pump inhibitor (PPI) (eg, omeprazole), talk with the doctor about how to give it with Atazanavir powder for oral suspension.
- If your child also takes an antacid or didanosine, give Atazanavir powder for oral suspension at least 2 hours before or 1 hour after the antacid or didanosine.
- Give Atazanavir powder for oral suspension on a regular schedule to be sure your child gets the most benefit from it.
- Giving Atazanavir powder for oral suspension at the same time each day will help you remember to give it.
- Continue to give Atazanavir powder for oral suspension even if your child feels well. Do not miss giving your child any doses.
- If you miss giving your child a dose of Atazanavir powder for oral suspension, give it as soon as possible. If it is almost time for your child's next dose, skip the missed dose and go back to your child's regular dosing schedule. Do not give 2 doses at once.
Ask the health care provider any questions you may have about how to give Atazanavir powder for oral suspension.
Uses of Atazanavir in details
Atazanavir is used in combination with other anti-retroviral medicines for the treatment of human immunodeficiency virus (HIV-1) infection.
Each capsule also contains the following inactive ingredients: Crospovidone, lactose monohydrate and magnesium stearate. Capsule Shell: 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 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 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 capsules and oral powder must be taken with food.
- Do not open the capsules.
- The recommended oral dosage of Atazanavir depends on the treatment history of the patient and the use of other coadministered drugs. When coadministered with H2-receptor antagonists or proton-pump inhibitors, dose separation may be required.
- Atazanavir capsules without ritonavir are not recommended for treatment-experienced adult or pediatric patients with prior virologic failure.
- Atazanavir oral powder must be taken with ritonavir and is not recommended for use in children who weigh less than 10 kg or who weigh 25 kg or more.
- Efficacy and safety of Atazanavir with ritonavir when ritonavir is administered in doses greater than 100 mg once daily have not been established. The use of higher ritonavir doses may alter the safety profile of Atazanavir (cardiac effects, hyperbilirubinemia) and, therefore, is not recommended. Prescribers should consult the complete prescribing information for ritonavir when using ritonavir.
Dosage In Adult Patients
Table 1 displays the recommended dosage of Atazanavir capsules in treatment-naive and treatment-experienced adults. Table 1 also displays recommended dosage of Atazanavir and ritonavir when given concomitantly with other antiretroviral drugs and H2-receptor antagonists (H2RA). Ritonavir is required with several Atazanavir dosage regimens. The use of Atazanavir in treatment-experienced adult patients without ritonavir is not recommended.
Table 1: Recommended Atazanavir and Ritonavir Dosage in Adultsa
|Atazanavir Once Daily Dosage||Ritonavir Once Daily Dosage|
|Treatment-Naive Adult Patients|
|recommendedregimen||300 mg||100 mg|
|unable to tolerate ritonavir||400 mg||N/A|
|in combination with efavirenz||400 mg||100 mg|
|Treatment-Experienced Adult Patients|
|recommendedregimen||300 mg||100 mg|
|in combination with both H2RA and tenofovir||400 mg||100 mg|
|Atazanavir is not recommended for treatment-experienced pregnant patients during the second and third trimester taking Atazanavir with both tenofovir and H2RA.|
For patients with renal impairment, including those with severe renal impairment who are not managed with hemodialysis, no dose adjustment is required for Atazanavir. Treatment-naive patients with end stage renal disease managed with hemodialysis should receive Atazanavir 300 mg with ritonavir 100 mg. Atazanavir should not be administered to HIV-treatmentexperienced patients with end stage renal disease managed with hemodialysis.
Dosage Adjustments In Patients With Hepatic Impairment
Table 5 displays the recommended Atazanavir dosage in treatment-naive patients with hepatic impairment. The use of Atazanavir in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. The coadministration of Atazanavir with ritonavir in patients with any degree of hepatic impairment is not recommended.
Table 5: Recommended Dosage of Atazanavir Capsules in Treatment-Naive Adults with Hepatic Impairment
|Atazanavir Once Daily Dosage|
|Mild hepatic impairment (Child-Pugh Class A)||400 mg|
|Moderate hepatic impairment (Child-Pugh Class B)||300 mg|
|Severe hepatic impairment (Child-Pugh Class C)||Atazanavir with or without ritonavir is not recommended|
Dosage Forms And Strengths
- 150 mg capsule with blue cap and powder blue body, printed with white ink “BMS 150 mg” on the cap and with blue ink “3624” on the body.
- 200 mg capsule with blue cap and blue body, printed with white ink “BMS 200 mg” on the cap and with white ink “3631” on the body.
- 300 mg capsule with red cap and blue body, printed with white ink “BMS 300 mg” on the cap and with white ink “3622” on the body.
- 50 mg of Atazanavir as an oral powder in a packet.
Storage And Handling
Atazanavir® (Atazanavir) capsules are available in the following strengths and configurations of plastic bottles with child-resistant closures.
|Product Strength*||Capsule Shell Color (cap/body)||Markings on Capsule (ink color)||Capsules per Bottle||NDC Number|
|150 mg||blue/powder blue||BMS 150 mg (white)||3624 (blue)||60||0003-3624-12|
|200 mg||blue/blue||BMS 200 mg (white)||3631 (white)||60||0003-3631-12|
|300 mg||red/blue||BMS 300 mg (white)||3622 (white)||30||0003-3622-12|
|* 150 mg Atazanavir equivalent to 170.8 mg Atazanavir sulfate. 200 mg Atazanavir equivalent to 227.8 mg Atazanavir sulfate. 300 mg Atazanavir equivalent to 341.69 mg Atazanavir sulfate.|
Store Atazanavir capsules at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F).
Atazanavir oral powder is an orange-vanilla flavored powder, packed in child-resistant packets. Each packet contains 50 mg of Atazanavir equivalent to 56.9 mg of Atazanavir sulfate in 1.5 g of powder. Atazanavir oral powder is supplied in cartons (NDC 0003-3638-10) of 30 packets each.
Store Atazanavir oral powder below 30°C (86°F). Once the Atazanavir oral powder is mixed with food or beverage, it may be kept at room temperature 20°C to 30°C (68°F-86°F) for up to 1 hour prior to administration. Store Atazanavir oral powder in the original packet and do not open until ready to use.
Distributed by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA. Issued: June 2014
See also Contraindications and Pharmacokinetics under Actions.
Potential for Atazanavir to Affect Other Drugs: Atazanavir is an inhibitor of CYP3A and UGT1A1. Co-administration of Atazanavir and drugs primarily metabolized by CYP3A or UGT1A1 may result in increased plasma concentrations of the other drug that could increase or prolong its therapeutic and adverse effects.
Atazanavir is a weak inhibitor of CYP2C8. Caution should be used when Atazanavir without ritonavir is co-administered with drugs highly dependent on CYP2C8 with narrow therapeutic indices (eg, paclitaxel and repaglinide). When Atazanavir with ritonavir is co-administered with substrates of CYP2C8, clinically significant interactions are not expected.
The magnitude of CYP3A-mediated drug interactions on co-administered drug may change when Atazanavir is co-administered with ritonavir.
Potential for Other Drugs to Affect Atazanavir: Atazanavir is a CYP3A4 substrate; therefore, drugs that induce CYP3A4 may decrease Atazanavir plasma concentrations and reduce Atazanavir’s therapeutic effect.
Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of Atazanavir are expected if PPIs, antacids, buffered medications or H2-receptor antagonists are administered with Atazanavir.
Established and Other Potentially Significant Drug Interactions: Table 21 provides dosing recommendations as a result of drug interactions with Atazanavir. These recommendations are based on either drug interaction studies or predicted interactions due to the expected magnitude of interaction and potential for serious events or loss of efficacy.
Drugs with No Observed or Predicted Interactions with Atazanavir: Clinically significant interactions are not expected between Atazanavir and substrates of CYP2C19, CYP2C9, CYP2D6, CYP2B6, CYP2A6, CYP1A2 or CYP2E1. Clinically significant interactions are not expected between Atazanavir when administered with ritonavir and substrates of CYP2C8.
Based on known metabolic profiles, clinically significant drug interactions are not expected between Atazanavir (Atazanavir) and fluvastatin, pravastatin, dapsone, trimethoprim/sulfamethoxazole, azithromycin or erythromycin. Atazanavir does not interact with substrates of CYP2D6 (eg, nortriptyline, desipramine, metoprolol). Additionally, no clinically significant drug interactions were observed when Atazanavir was co-administered with methadone, fluconazole, acetaminophen or atenolol.
Atazanavir side effects
The following adverse reactions are discussed in greater detail in other sections of the labeling:
- cardiac conduction abnormalities
- nephrolithiasis and cholelithiasis
Because 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 practice.
Clinical Trial Experience In Adults
Treatment-Emergent Adverse Reactions in Treatment-Naive Patients
The safety profile of Atazanavir in treatment-naive adults is based on 1625 HIV-1 infected patients in clinical trials. 536 patients received Atazanavir 300 mg with ritonavir 100 mg and 1089 patients received Atazanavir 400 mg or higher (without ritonavir).
The most common adverse reactions were nausea, jaundice/scleral icterus, and rash.
Selected clinical adverse reactions of moderate or severe intensity reported in ≥ 2% of treatment-naive patients receiving combination therapy including Atazanavir 300 mg with ritonavir 100 mg and Atazanavir 400 mg (without ritonavir) are presented in Tables 7 and 8, respectively.
Table 7: Selected Treatment-Emergent Adverse ReactionsFasting.