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HIV Protease Inhibitor + Pharmacokinetic Enhancer (Antiretroviral) Pregnancy: US labelling 8.1 and 2.5: EVOTAZ is not recommended for use during pregnancy and should not be initiated in pregnant individuals, because of substantially lower exposures of cobicistat and consequently lower exposures of atazanavir during the second and third trimesters; an alternative regimen is recommended for individuals who become pregnant during therapy. Atazanavir use in a limited number of pregnancies showed no increase in the risk of overall major birth defects compared with the background rate; in animal reproduction studies no adverse developmental outcomes were observed with atazanavir or cobicistat in rats and rabbits. Infants exposed to atazanavir in utero may develop severe hyperbilirubinemia during the first few days of life. An Antiretroviral Pregnancy Registry exists (1-800-258-4263). The fetched section is truncated, so the remainder of 8.1 and sections 8.2 onward are not reproduced.

Atazanavir with Cobicistat

Brand names: Evotaz

A fixed-dose combination of the HIV protease inhibitor atazanavir with the pharmacokinetic enhancer cobicistat, taken once daily as part of combination antiretroviral therapy for HIV-1 infection.

Adult dose

Dose: HIV-1 infection, in combination with other antiretroviral agents, in both treatment-naive and treatment-experienced adults: one tablet (fixed-dose tablet containing atazanavir 300 mg and cobicistat 150 mg) taken once daily orally with food
Route: Oral - one tablet once daily with food, in combination with other antiretroviral agents
Frequency: Once daily with food
Every figure below is from the EVOTAZ label; no ritonavir-boosted REYATAZ figure is used. VERBATIM (US label 2.2): 'EVOTAZ is a fixed-dose tablet containing 300 mg of atazanavir and 150 mg of cobicistat. The recommended dosage of EVOTAZ is one tablet taken once daily orally with food in both treatment-naive and treatment-experienced patients with HIV-1: Adult patients; Pediatric patients weighing at least 35 kg. Administer EVOTAZ in conjunction with other antiretroviral agents. Dose separation may be required when taken with H2-receptor antagonists or proton-pump inhibitors.' LIMITATION OF USE (1.2): 'Use of EVOTAZ in treatment-experienced patients should be guided by the number of baseline primary protease inhibitor resistance substitutions.' MAXDOSE LEFT EMPTY: the label gives one fixed tablet daily and prints no separate maximum. NOT RECOMMENDED: EVOTAZ is not recommended with ritonavir or products containing ritonavir, or with other antiretrovirals that require CYP3A inhibition for adequate exposure (e.g. other protease inhibitors and elvitegravir) (5.9, highlights); not recommended during pregnancy and should not be initiated in pregnant individuals (2.5); not recommended in patients with any degree of hepatic impairment (2.4); not recommended in treatment-experienced patients with end-stage renal disease managed with hemodialysis (2.3); EVOTAZ with tenofovir DF is not recommended when estimated creatinine clearance is below 70 mL/min or with concomitant or recent nephrotoxic agent use (2.3). PRETREATMENT TESTING (2.1): renal laboratory testing (estimated creatinine clearance, serum creatinine, urinalysis with microscopic examination) in all patients before initiation and continued during treatment; hepatic testing in patients with underlying liver disease before initiation and during treatment. Cobicistat decreases estimated creatinine clearance by inhibiting tubular secretion of creatinine without affecting actual glomerular function. With tenofovir DF, assess estimated creatinine clearance, urine glucose and urine protein at baseline and routinely during treatment, and serum phosphorus in chronic kidney disease. The acid-reducing-agent and other antiretroviral dose-separation rules sit in Drug Interactions Table 5, which is TRUNCATED in the fetched text, so they are not stated here - consult the full label. PAEDIATRIC: see paedDose (patients weighing at least 35 kg only). No UK SPC for atazanavir/cobicistat is listed on eMC — this dose is from US prescribing information (EVOTAZ) and must be verified against UK practice.

Paediatric dose

Dose: One tablet (atazanavir 300 mg / cobicistat 150 mg) taken once daily orally with food, in pediatric patients weighing at least 35 kg
Route: Oral - with food, in combination with other antiretroviral agents
Frequency: Once daily with food
FIXED DOSE, NOT WEIGHT-BASED - dosePerKg is deliberately null; the label gives one fixed tablet for patients weighing at least 35 kg and no per-kg figure. Do not scale. VERBATIM (US label 8.4): 'Safety and effectiveness of EVOTAZ in the pediatric population weighing less than 35 kg have not been established. Atazanavir, a component of EVOTAZ, is not recommended for use in pediatric patients below the age of 3 months due to the risk of kernicterus.' Use in pediatric patients weighing at least 35 kg is supported by pharmacokinetic, safety and virologic data from an open-label trial of components of EVOTAZ (Study GS-US-216-0128) in participants aged 12 years and older. Verify any under-18 use against a children's formulary.

Dose adjustments

Renal

No dose adjustment figure is given, but: EVOTAZ is not recommended in treatment-experienced patients with HIV-1 who have end-stage renal disease managed with hemodialysis; coadministered with tenofovir DF it is not recommended when estimated creatinine clearance is below 70 mL/min, nor with concomitant or recent use of a nephrotoxic agent. Cobicistat decreases estimated creatinine clearance without affecting actual glomerular function; dosage recommendations are not available for drugs that require adjustment in cobicistat-treated patients with renal impairment, so consider alternatives not requiring renal adjustment (US labelling 2.3, 5.3, 5.4).

Hepatic

EVOTAZ is not recommended in patients with any degree of hepatic impairment (US labelling 2.4). Hepatic laboratory testing should be performed in patients with underlying liver disease before initiation and continued during treatment; patients with hepatitis B or C are at risk of increased transaminases or hepatic decompensation (US labelling 2.1, 5.7).

Dose independently re-sourced from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

  • Previously demonstrated clinically significant hypersensitivity (e.g. Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to any of the components of the product (US labelling 4)
  • Coadministration with drugs that strongly induce CYP3A4 - potential loss of therapeutic effect and development of possible resistance (US labelling 4, Table 5)
  • Coadministration with drugs highly dependent on CYP3A or UGT1A1 for clearance whose elevated plasma concentrations are associated with serious and/or life-threatening events (US labelling 4, Table 5)
  • Contraindicated drugs (Table 1; the list is 'not limited to'): alfuzosin; ranolazine; dronedarone; carbamazepine, phenobarbital, phenytoin; colchicine (when used in patients with hepatic and/or renal impairment); rifampin; apalutamide, encorafenib, irinotecan, ivosidenib; lurasidone, pimozide; dihydroergotamine, ergotamine, methylergonovine; elbasvir/grazoprevir, glecaprevir/pibrentasvir; St. John's wort; drospirenone/ethinyl estradiol; lomitapide, lovastatin, simvastatin; nevirapine; sildenafil (when administered for the treatment of pulmonary arterial hypertension); indinavir; triazolam and orally administered midazolam (US labelling 4, Table 1)

Side effects

  • Most common adverse reactions (Grades 2-4, 5% or more) with atazanavir coadministered with cobicistat: jaundice (6%) and rash (5%); also ocular icterus (4%) and nausea, diarrhea and headache (2% each) in treatment-naive adults at Week 144 (US labelling 6.1)
  • Hyperbilirubinemia: most patients experience asymptomatic increases in indirect bilirubin, reversible on discontinuation; if a concomitant transaminase increase occurs, evaluate for alternative etiologies (US labelling 5.10)
  • Cardiac conduction abnormalities: PR interval prolongation, generally first-degree AV block, with reports of second-degree AV block (US labelling 5.1)
  • Severe skin reactions including Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions and DRESS - discontinue if severe rash develops (US labelling 5.2)
  • Effects on the kidney: cobicistat raises serum creatinine and lowers estimated creatinine clearance without affecting glomerular function; acute renal failure and Fanconi syndrome reported with cobicistat plus tenofovir DF; chronic kidney disease, nephrolithiasis and cholelithiasis reported with atazanavir (US labelling 5.3-5.6)
  • Hepatotoxicity in patients with hepatitis B or C; immune reconstitution syndrome; new onset or exacerbation of diabetes mellitus/hyperglycemia; redistribution/accumulation of body fat; spontaneous bleeding in hemophilia (US labelling 5.7, 5.11-5.14)

Interactions

  • Ritonavir or ritonavir-containing products, and other antiretrovirals that require CYP3A inhibition to achieve adequate exposure (e.g. other protease inhibitors and elvitegravir) - not recommended (US labelling 5.9)
  • Atazanavir inhibits CYP3A and UGT1A1 and weakly CYP2C8; cobicistat inhibits CYP3A, CYP2D6, P-gp, BCRP, OATP1B1 and OATP1B3 - concentrations of co-administered substrates may rise and require dose adjustment or additional monitoring; not recommended with drugs highly dependent on CYP2C8 with narrow therapeutic indices (e.g. paclitaxel, repaglinide) (US labelling 7.1)
  • Atazanavir and cobicistat are CYP3A4 substrates - CYP3A4 inducers may reduce their concentrations and lead to resistance; CYP3A4 inhibitors may increase them (US labelling 7.2)
  • Acid-reducing agents - atazanavir solubility falls as pH rises; reduced atazanavir concentrations are expected with proton-pump inhibitors, antacids, buffered medications or H2-receptor antagonists, and dose separation may be required (US labelling 2.2, 7.2). The Table 5 specifics are truncated in the fetched text
  • Didanosine - give EVOTAZ with food 2 hours before or 1 hour after didanosine buffered formulations; didanosine EC and EVOTAZ should be given at different times (US labelling 7.3, Table 5)
  • Tenofovir DF - decreases atazanavir and raises tenofovir exposure; monitor for tenofovir-associated adverse reactions; not recommended if estimated creatinine clearance is below 70 mL/min or with a nephrotoxic agent (US labelling 5.4, 7.3)
  • Drugs that prolong the PR interval - consider ECG monitoring (US labelling 5.1)

Monitoring

  • Renal laboratory testing (estimated creatinine clearance, serum creatinine, urinalysis with microscopic examination) in all patients before initiation and during treatment (US labelling 2.1)
  • With tenofovir DF: estimated creatinine clearance, urine glucose and urine protein at baseline and routinely during treatment; serum phosphorus in patients with or at risk for renal impairment or chronic kidney disease (US labelling 2.1, 5.4)
  • Patients with a confirmed serum creatinine increase of more than 0.4 mg/dL from baseline should be closely monitored for renal safety (US labelling 5.3)
  • Hepatic laboratory tests before therapy and during treatment in patients with underlying liver disease or hepatitis B or C (US labelling 2.1, 5.7)
  • ECG monitoring in patients with preexisting conduction system disease or on other drugs that may prolong the PR interval (US labelling 5.1)

Clinical monograph

How it works

Atazanavir inhibits HIV protease, preventing cleavage of viral polyproteins into mature infectious virions, while cobicistat has no antiviral activity but inhibits CYP3A to boost and sustain atazanavir plasma concentrations.

Prescribing in practice

  • Cobicistat is a potent CYP3A inhibitor that causes numerous clinically important drug interactions, so a full interaction check is essential before co-prescribing and certain medicines are contraindicated.
  • Acid-reducing agents markedly reduce atazanavir absorption, so proton pump inhibitors and other antacids require careful timing or avoidance, and the combination should be taken with food.
  • Unconjugated hyperbilirubinaemia causing visible jaundice is common and benign but can be distressing, and atazanavir may also cause nephrolithiasis and cholelithiasis.

Monitoring

Monitor viral load, CD4 count, bilirubin, renal and hepatic function, and review concomitant medicines for interactions.

Counselling the patient

  • Take the tablets with food and keep a regular daily routine.
  • Yellowing of the eyes or skin can occur and is usually harmless, but report it so it can be assessed.
  • Check with the team before taking any antacid, indigestion remedy or new medicine.

Evidence & guidelines

Boosted atazanavir is an established protease-inhibitor option in UK HIV guidelines, with cobicistat providing pharmacokinetic enhancement comparable to ritonavir.

Reference: BHIVA HIV Treatment Guidelines (2022); Liverpool HIV Drug Interactions Checker; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Related

Curated clinical cross-links plus same-class fallbacks.

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