Dosing and uses of Reyataz (atazanavir)
Adult dosage forms and strengths
capsule
- 100mg
- 150mg
- 200mg
- 300mg
HIV-1 Infection
Treatment-naive
- 400 mg PO qDay, OR
- 300 mg PO with 100 mg ritonavir qDay
- With 600 mg efavirenz: 400 mg PO with 100 mg ritonavir qDay administered at different times (ritonavir and atazanavir with food in morning; efavirenz on an empty stomach, preferably at bedtime)
Treatment-experienced or with tenofovir
- 300 mg PO (with ritonavir 100 mg) PO qDay with tenofovir
Dosing during pregnancy and postpartum period
- Administer atazanavir with ritonavir
- Only administer to pregnant women with HIV-1 strains susceptible to atazanavir
- Dosage adjustments are not required in pregnant patients except with the following exceptions: treatment-experienced pregnant women during the second or third trimester, when atazanavir is coadministered with either an H2-receptor antagonist or tenofovir, atazanavir 400 mg with ritonavir 100 mg once daily is recommended; insufficient data to recommend an atazanavir dose for use with both an H2-receptor antagonist and tenofovir in treatment-experienced pregnant women
- No dose adjustment is required for postpartum patients; closely monitor patients for adverse events because atazanavir exposures may be increased during first 2 months after delivery
Dosage modifications
Hepatic impairment
- Child-Pugh score 7-9: 300 mg PO qDay
- Child-Pugh score >9: Not recommended
- Ritonavir boosting NOT recommended with Child-Pugh score 7 or above
Renal impairment
- No dose adjustment necessary including those with severe renal impairment who are not managed with hemodialysis
- Hemodialysis (treatment-naive): 300 mg PO (with ritonavir 100 mg) qDay
- Antiretroviral-experienced patients: Not recommended
Pediatric dosage forms and strengths
capsule
- 150mg
- 200mg
- 300mg
oral powder
- 50mg/packet
HIV-1 Infection
Oral capsules
- 6-18 years (treatment naïve and treatment experienced)
- 15 to <20 kg (33 to <44 lbs): 150 mg (+ 100 mg ritonavir) PO qDay
- 20 to <40 kg (44 to <88 lbs): 200 mg (+ 100 mg ritonavir) PO qDay
- ≥40 kg (≥88 lbs): 300 mg (+ 100 mg ritonavir) PO qDay
- ≥13 years (treatment naïve and cannot tolerate ritonavir)
- ≥40 kg (≥88 lbs): 400 mg PO qDay
Oral powder
- 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
- 5 kg to <15 kg: 200 mg (4 packets) plus 80 mg ritonavir PO qDay
- 15 kg to <25 kg: 250 mg (5 packets) plus 80 mg ritonavir PO qDay
- ≥25 kg and unable to swallow capsule: 300 mg (6 packets) plus 100 mg ritonavir PO qDay
- NOTE: Children unable to tolerate 200 mg/day dose who weigh 5 kg to <10 kg and have not previously taken an HIV protease inhibitor may take 150 mg (3 packets) daily with close HIV viral load monitoring
Dosing Considerations
Use of atazanavir with ritonavir in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions
Reyataz (atazanavir) adverse (side) effects
Incidence based on combination therapy
>10%
Total bilirubin increased (35-49%)
Fever (19%)
Rash (3-21%)
Cholesterol is increased (6-25%)
Nausea (4-14%)
CPK increased (6-11%)
Cough (21%)
Diarrhea (3-11%)
1-10%
Neutrophils decrease (6-10%)
Jaundice (5-9%)
Headache (1-7%)
Peripheral neuropathy (1-4%)
Insomnia (1-3%)
Fever (2%)
Vomiting (3-7%)
Dizziness (1-2%)
Myalgia (4%)
Abdominal pain (2-4%)
Depression (1-2%)
<1%
Prolonged PR intervaL
New onset diabetes mellitus, exacerbation of diabetes mellitus & hyperglycemia
Postmarketing Reports
Body as a whole: Edema
Cardiovascular system: Second-degree AV block, third-degree AV block, left bundle branch block, QTc prolongation
Gastrointestinal system: Pancreatitis
Hepatic system: Hepatic function abnormalities
Hepatobiliary disorders: Cholelithiasis, cholecystitis, cholestasis
Metabolic system and nutrition disorders: Diabetes mellitus, hyperglycemia
Musculoskeletal system: Arthralgia
Renal system: Nephrolithiasis
Skin and appendages: Alopecia, angioedema, maculopapular rash, pruritus
Warnings
Contraindications
Previously demonstrated hypersensitivity including Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions
Treatment-experienced patients with ESRD receiving hemodialysis
Severe hepatic impairment (Child-Pugh Class C); hepatic impairment and concomitant ritonavir
Indinavir; both atazanavir and indinavir are associated with indirect hyperbilirubinemia
Inhibits CYP3A4 and UGT1A1
- Do not coadminister with drugs highly dependent on CYP3A or UGT1A1 for clearance
- Atazanavir may elevated plasma concentrations of the following drugs and lead to serious and/or life-threatening events
- Alfuzosin
- Irinotecan
- Triazolam, midazolam PO
- Ergot derivatives
- Cisapride
- Lovastatin
- Simvastatin
- Lurasidone
- Pimozide
- Sildenafil (when used for PAH)
- Coadministration with the following drugs that strongly induce CYP3A and may result in loss of therapeutic effect of atazanavir
- Rifampin
- St. John’s wort
- Nevirapine
Cautions
Do not use proton-pump inhibitors in treatment-experienced patients
Discontinue if severe rash; Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions reported, including drug rash, eosinophilia, and systemic symptoms (DRESS) syndrome
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance” have been observed in patients receiving antiretroviral therapy
Spontaneous bleeding may occur and additional factor VIII may be required
Discontinue if severe rash develops
PR interval prolongation may occur in some patients; ECG monitoring should be considered in patients with preexisting conduction system disease or when administered with other drugs that may prolong the PR intervaL
Most patients experience asymptomatic increases in indirect bilirubin, which is reversible upon discontinuation; do not dose reduce; if concomitant transaminase increase occurs, evaluate for alternative etiologies
Nephrolithiasis and cholelithiasis reported; consider temporary interruption or discontinuation
Treatment-experienced patients with prior virologic failure: without ritonavir not recommended
Patients receiving atazanavir may develop new onset or exacerbations of diabetes mellitus/hyperglycemia, immune reconstitution syndrome, and redistribution/accumulation of body fat
Use caution in mild-moderate hepatic impairment
Patients with hepatitis B or C infection are at risk of increased transaminases or hepatic decompensation; monitor hepatic laboratory tests prior to therapy and during treatment
Most patients experience asymptomatic increases in indirect bilirubin, which is reversible upon discontinuation; do not dose reduce; if a concomitant transaminase increase occurs, evaluate for alternative etiologies.
Oral powder contains phenylalanine which can be harmful to patients with phenylketonuria
Pregnancy and lactation
Pregnancy category: B
Administer atazanavir with ritonavir
Only administer to pregnant women with HIV-1 strains susceptible to atazanavir
Lactation: It is not known whether atazanavir is excreted in 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 taking this drug.
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Reyataz (atazanavir)
Mechanism of action
Protease Inhibitor; inhibits cleavage of Gag-Pol polyprotein precursors, which in turn causes the formation of immature, noninfectious viral particles.
Absorption
Peak Plasma Time: 2-3 hr
Distribution
Protein Bound: 86%
Metabolism
Via hepatic P450 enzyme CYP3A4
Enzymes inhibited: CYP3A4
Elimination
Half-life: 7-8 hr (unboosted therapy); 9-18 hr (boosted therapy)
Excretion: 79% feces; 13% urine
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
