Atazanavir
Looking up MedlinePlus…
From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
Testing Prior to Initiation and During Treatment with REYATAZ Renal laboratory testing should be performed in all patients prior to initiation of REYATAZ and continued during treatment with REYATAZ. Renal laboratory testing should include serum creatinine, estimated creatinine clearance, and urinalysis with microscopic examination [see Warnings and Precautions (5.5 , 5.6) ] .
Hepatic laboratory testing should be performed in patients with underlying liver disease prior to initiation of REYATAZ and continued during treatment with REYATAZ [see Warnings and Precautions ] .
Dosage in Patients with Renal Impairment For patients with renal impairment, including those with severe renal impairment who are not managed with hemodialysis, no dose adjustment is required for REYATAZ. Treatment-naive patients with end-stage renal disease managed with hemodialysis should receive REYATAZ 300 mg with ritonavir 100 mg.
REYATAZ is not recommended in treatment-experienced patients with HIV-1 who have end-stage renal disease managed with hemodialysis [see Use in Specific Populations ] .
Dosing in liver impairment
Dosage Adjustments in Patients with Hepatic Impairment Table 5 displays the recommended REYATAZ dosage in treatment-naive patients with hepatic impairment. The use of REYATAZ in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. The coadministration of REYATAZ with ritonavir in patients with any degree of hepatic impairment is not recommended. [See table below.]
| REYATAZ 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) | REYATAZ with or without ritonavir is not recommended |
Preparation and administration
Dosage and Administration of REYATAZ Oral Powder in Pediatric Patients REYATAZ oral powder is for use in treatment-naive or treatment-experienced pediatric patients who are at least 3 months of age and weighing at least 5 kg. REYATAZ oral powder must be mixed with food or a beverage for administration and ritonavir must be given immediately afterwards.
Table 3 displays the recommended dosage of REYATAZ oral powder and ritonavir. [See table below.] 15 kg to less than 25 kg 250 mg (5 packets) d 80 mg When transitioning between formulations, a change in dose may be needed. Consult the dosing table for the specific formulation. Instructions for Mixing REYATAZ Oral Powder [see FDA-approved Instructions for Use]
Determine the number of packets (3, 4, 5 or 6 packets) that are needed.
Prior to mixing, tap the packet to settle the powder.
It is preferable to mix REYATAZ oral powder with food such as applesauce or yogurt. Mixing REYATAZ oral powder with a beverage (milk, infant formula, or water) may be used for infants who can drink from a cup. For young infants (less than 6 months) who cannot eat solid food or drink from a cup, REYATAZ oral powder should be mixed with infant formula and given using an oral dosing syringe.
Administration of REYATAZ and infant formula using an infant bottle is not recommended because full dose may not be delivered.
Use a clean pair of scissors to cut each packet along the dotted line.
Mixing with food: Using a spoon, mix the recommended number of REYATAZ oral powder packets with a minimum of one tablespoon of food (such as applesauce or yogurt). Feed the mixture to the infant or young child. Add an additional one tablespoon of food to the small container, mix, and feed the child the residual mixture.
Mixing with a beverage such as milk or water in a small drinking cup: Using a spoon, mix the recommended number of REYATAZ oral powder packets with a minimum of 30 mL of the beverage. 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 liquid infant formula using an oral dosing syringe and a small medicine cup: Using a spoon, mix the recommended number of REYATAZ 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 REYATAZ oral powder in cup. Draw up residual mixture into the syringe and administer into either right or left inner cheek of infant.
Administer ritonavir immediately following REYATAZ powder administration.
Administer the entire dosage of REYATAZ oral powder (mixed in the food or beverage) within one hour of preparation [may leave the mixture at a temperature of 68°F to 86°F (20°C to 30°C) for up to one hour]. 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.
Drug interactions
Check atazanavir against a medication listLabel text (17 paragraphs)
Coadministration of REYATAZ can alter the concentration of other drugs and other drugs may alter the concentration of atazanavir. The potential drug-drug interactions must be considered prior to and during therapy. (4 , 7 , 12.3)
7.1 Potential for REYATAZ to Affect Other Drugs Atazanavir is an inhibitor of CYP3A and UGT1A1. Coadministration of REYATAZ 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. Use of REYATAZ without ritonavir is not recommended when coadministered with drugs highly dependent on CYP2C8 with narrow therapeutic indices (eg, paclitaxel, repaglinide). When REYATAZ with ritonavir is coadministered with substrates of CYP2C8, clinically significant interactions are not expected [see Clinical Pharmacology, Table 22 (12.3) ] .
The magnitude of CYP3A-mediated drug interactions on coadministered drug may change when REYATAZ is coadministered with ritonavir. See the complete prescribing information for ritonavir for information on drug interactions with ritonavir.
7.2 Potential for Other Drugs to Affect REYATAZ Atazanavir is a CYP3A4 substrate; therefore, drugs that induce CYP3A4 may decrease atazanavir plasma concentrations and reduce REYATAZ’s therapeutic effect ( see Table 16 ). Atazanavir solubility decreases as pH increases. Reduced plasma concentrations of atazanavir are expected if proton-pump inhibitors, antacids, buffered medications, or H 2 -receptor antagonists are administered with REYATAZ [see Dosage and Administration ( 2.3 , 2.4 , 2.5 and 2.6) ] .
7.3 Established and Other Potentially Significant Drug Interactions Table 16 provides dosing recommendations in adults as a result of drug interactions with REYATAZ. 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.
Table 16: Established and Other Potentially Significant Drug Interactions: Alteration in Dose or Regimen May Be Recommended Based on Drug Interaction Studies a or Predicted Interactions (Information in the table applies to REYATAZ with or without ritonavir, unless otherwise indicated) Concomitant Drug Class: Specific Drugs Effect on Concentration of Atazanavir or Concomitant Drug Clinical Comment a For magnitude of interactions see Clinical Pharmacology, Tables 21 and 22 (12.3) . b See Contraindications (4), Table 6 for orally administered midazolam. c In combination with atazanavir 300 mg with ritonavir 100 mg once daily. d In combination with atazanavir 400 mg once daily.
HIV Antiviral Agents Nucleoside Reverse Transcriptase Inhibitors (NRTIs): didanosine buffered formulations enteric coated (EC) capsules ↓ atazanavir ↓ didanosine It is recommended that REYATAZ be given (with food) 2 h before or 1 h after didanosine buffered formulations. Simultaneous administration of didanosine EC and REYATAZ with food results in a decrease in didanosine exposure. Thus, REYATAZ and didanosine EC should be administered at different times.
Nucleotide Reverse Transcriptase Inhibitors: tenofovir disoproxil fumarate (DF) ↓ atazanavir ↑ tenofovir When coadministered with tenofovir DF in adults, it is recommended that REYATAZ 300 mg be given with ritonavir 100 mg and tenofovir DF 300 mg (all as a single daily dose with food). The mechanism of this interaction is unknown. Higher tenofovir concentrations could potentiate tenofovir-associated adverse reactions, including renal disorders. Patients receiving REYATAZ and tenofovir DF should be monitored for tenofovir-associated adverse reactions. For pregnant patients taking REYATAZ with ritonavir and tenofovir DF, see Dosage and Administration (2.6) .
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs): efavirenz ↓ atazanavir In HIV-treatment-naive adult patients: If REYATAZ is combined with efavirenz, REYATAZ 400 mg (two 200-mg capsules) should be administered with ritonavir 100 mg simultaneously once daily with food, and efavirenz 600 mg should be administered once daily on an empty stomach, preferably at bedtime. In HIV-treatment-experienced adult patients: Coadministration of REYATAZ with efavirenz is not recommended.
nevirapine ↓ atazanavir ↑ nevirapine Coadministration of REYATAZ with nevirapine is contraindicated due to the potential loss of virologic response and development of resistance, as well as the potential risk for nevirapine-associated adverse reactions [see Contraindications (4) ] . Protease Inhibitors: saquinavir (soft gelatin capsules) ↑ saquinavir Appropriate dosing recommendations for this combination, with or without ritonavir, with respect to efficacy and safety have not been established.
In a clinical study, saquinavir 1200 mg coadministered with REYATAZ 400 mg and tenofovir DF 300 mg (all given once daily), and nucleoside analogue reverse transcriptase inhibitors did not provide adequate efficacy [see Clinical Studies (14.2) ] . indinavir Coadministration of REYATAZ with indinavir is contraindicated. Both REYATAZ and indinavir are associated with indirect (unconjugated) hyperbilirubinemia [see Contraindications (4) ] . ritonavir ↑ atazanavir If REYATAZ is coadministered with ritonavir, it is recommended that REYATAZ 300 mg once daily be given with ritonavir 100 mg once daily with food in adults.
See the complete prescribing information for ritonavir for information on drug interactions with ritonavir. Others ↑ other protease inhibitor Coadministration with other protease inhibitors is not recommended. Hepatitis C Antiviral Agents elbasvir/grazoprevir ↑ grazoprevir Coadministration of REYATAZ with grazoprevir is contraindicated due to the potential for increased risk of ALT elevations [see Contraindications (4) ] . glecaprevir/pibrentasvir ↑ glecaprevir ↑ pibrentasvir Coadministration of REYATAZ with glecaprevir/pibrentasvir is contraindicated due to the potential for increased the risk of ALT elevations [see Contraindications (4) ] .
voxilaprevir/sofosbuvir/velpatasvir ↑ voxilaprevir Coadministration with REYATAZ is not recommended. Other Agents Alpha 1-Adrenoreceptor Antagonist: alfuzosin ↑ alfuzosin Coadministration of REYATAZ with alfuzosin is contraindicated due to risk for hypotension [see Contraindications (4) ] . Antacids and buffered medications: ↓ atazanavir REYATAZ should be administered 2 hours before or 1 hour after antacids and buffered medications.
Antiarrhythmics: amiodarone, quinidine amiodarone, bepridil, lidocaine (systemic), quinidine ↑ amiodarone, bepridil, lidocaine (systemic), quinidine Concomitant use of REYATAZ with ritonavir and either quinidine or amiodarone is contraindicated due to the potential for serious or life-threatening reactions such as cardiac arrhythmias [see Contraindications (4) ] . Coadministration with REYATAZ without ritonavir has the potential to produce serious and/or life-threatening adverse events but has not been studied. Caution is warranted and therapeutic concentration monitoring of these drugs is recommended if they are used concomitantly with REYATAZ without ritonavir.
Anticoagulants: warfarin ↑ warfarin Coadministration with REYATAZ has the potential to produce serious and/or life-threatening bleeding and has not been studied. It is recommended that International Normalized Ratio (INR) be monitored. Direct-Acting Oral Anticoagulants: betrixaban, dabigatran, edoxaban ↑ betrixaban ↑ dabigatran ↑ edoxaban Concomitant use of REYATAZ with ritonavir, a strong CYP3A4/P-gp inhibitor, may result in an increased risk of bleeding. Refer to the respective DOAC prescribing information regarding dosing instructions for coadministration with P-gp inhibitors.
rivaroxaban REYATAZ with ritonavir ↑ rivaroxaban Coadministration of REYATAZ with ritonavir, a strong CYP3A4/P-gp inhibitor, and rivaroxaban is not recommended, as it may result in an increased risk of bleeding. REYATAZ ↑ rivaroxaban Coadministration of REYATAZ, a CYP3A4 inhibitor, and rivaroxaban may result in an increased risk of bleeding. Close monitoring is recommended when REYATAZ is coadministered with rivaroxaban. apixaban REYATAZ with ritonavir ↑ apixaban Concomitant use of REYATAZ with ritonavir, a strong CYP3A4/P-gp inhibitor, may result in an increased risk of bleeding.
Refer to apixaban dosing instructions for coadministration with strong CYP3A4 and P-gp inhibitors in the apixaban prescribing information. REYATAZ ↑ apixaban Concomitant use of REYATAZ, a CYP3A4 inhibitor, and apixaban may result in an increased risk of bleeding. Close monitoring is recommended when apixaban is coadministered with REYATAZ. Antidepressants: tricyclic antidepressants ↑ tricyclic antidepressants Coadministration with REYATAZ has the potential to produce serious and/or life-threatening adverse events and has not been studied. Concentration monitoring of these drugs is recommended if they are used…
Contraindications
4 CONTRAINDICATIONS REYATAZ 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 REYATAZ capsules or 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 are strong inducers of CYP3A due to the potential for loss of therapeutic effect and development of resistance. Coadministration is contraindicated with, but not limited to, the following drugs listed in Table 6: Table 6: Drugs Contraindicated with REYATAZ (Information in the table applies to REYATAZ 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 REYATAZ Alpha 1-adrenoreceptor antagonist Alfuzosin Anticonvulsants Carbamazepine, phenobarbital, phenytoin Antiarrhythmics Amiodarone (with ritonavir), quinidine (with ritonavir) Antimycobacterials Rifampin Antineoplastics Apalutamide, encorafenib, irinotecan, ivosidenib Antipsychotics Lurasidone (with ritonavir), pimozide Benzodiazepines Orally administered midazolam a , triazolam Ergot Derivatives Dihydroergotamine, ergonovine, ergotamine, methylergonovine GI Motility Agent Cisapride Hepatitis C Direct-Acting Antivirals Elbasvir/grazoprevir; glecaprevir/pibrentasvir Herbal Products St.
John’s wort ( Hypericum perforatum ) Lipid-Modifying Agents: Lomitapide, lovastatin, simvastatin Phosphodiesterase-5 (PDE-5) Inhibitor Sildenafil b when dosed as REVATIO ® for the treatment of pulmonary arterial hypertension Protease Inhibitors Indinavir Non-nucleoside Reverse Transcriptase Inhibitors Nevirapine • In patients with previously demonstrated hypersensitivity (eg, Stevens-Johnson syndrome, erythema…
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to REYATAZ during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Atazanavir has been evaluated in a limited number of women during pregnancy. Available human and animal data suggest that atazanavir does not increase the risk of major birth defects overall compared to the background rate [see Data ] . In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. No treatment-related malformations were observed in rats and rabbits, for which the atazanavir exposures were 0.7-1.2 times of those at the human clinical dose (300 mg/day atazanavir boosted with 100 mg/day ritonavir). When atazanavir was administered to rats during pregnancy and throughout lactation, reversible neonatal growth retardation was observed [see Data ] . Clinical Considerations Dose Adjustments during Pregnancy and the Postpartum Period • REYATAZ must be administered with ritonavir in pregnant patients.
• For pregnant patients, no dosage adjustment is required for REYATAZ with the following exceptions: • For treatment-experienced pregnant women during the second or third trimester, when REYATAZ is coadministered with either an H 2 -receptor antagonist or tenofovir DF, REYATAZ 400 mg with ritonavir 100 mg once daily is recommended. There are insufficient data to recommend a REYATAZ dose for use with both an H 2 -receptor antagonist and tenofovir DF in treatment-experienced pregnant patients. • No dosage adjustment is required for postpartum patients.
However, patients should be closely monitored for adverse events because atazanavir exposures could be higher during the first 2 months after delivery [see Dosage and Administration (2.6) and Clinical Pharmacology (12.3) ] . Maternal Adverse Reactions Cases of lactic acidosis syndrome, sometimes fatal, and symptomatic hyperlactatemia have occurred in pregnant women using REYATAZ in combination with nucleoside analogues, which are associated with an increased risk of lactic acidosis syndrome. Hyperbilirubinemia occurs frequently in patients who take REYATAZ [see Warnings and Precautions (5.8) ] , including those who are pregnant [see Data ] .
Advise pregnant women of the potential risks of lactic acidosis syndrome and hyperbilirubinemia. Fetal/Neonatal Adverse Reactions All infants, including…
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.