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Atazanavir with cobicistat oral


Oral formulations of atazanavir (as sulfate) with cobicistat.

Drugs List

  • atazanavir 300mg and cobicistat 150mg tablets
  • EVOTAZ 300mg+150mg tablets
  • Therapeutic Indications


    HIV infection-combined with other antiretrovirals

    Treatment of HIV infected adults and adolescents (aged 12 years and older weighing at least 35kg) without known mutations associated with resistance to atazanavir.


    Atazanavir with cobicistat is used in combination with other antiretrovirals, therefore the product information of any other co-administered products should be consulted.


    One tablet, once daily with food.


    Children aged 12 to 18 years weighing at least 35kg
    One tablet, once daily with food.

    Patients with Renal Impairment

    Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. Atazanavir with cobicistat should not be initiated in patients with creatinine clearance less than 70 ml/minute if any co-administered agent requires dose adjustment based on creatinine clearance.

    Additional Dosage Information

    Missed doses

    If atazanavir with cobicistat is missed within 12 hours of the time it is usually taken, patients should be instructed to take the prescribed dose with food as soon as possible. If this is noticed later than 12 hours of the time it is usually taken, the missed dose should not be taken and the patient should resume the usual dosing schedule.


    Children under 12 years
    Children weighing less than 35kg
    Long QT syndrome
    Moderate hepatic impairment
    Torsade de pointes

    Precautions and Warnings

    Family history of long QT syndrome
    Females of childbearing potential
    Electrolyte imbalance
    Hepatitis B
    Hepatitis C
    History of hepatic disorder
    History of torsade de pointes
    Mild hepatic impairment

    Correct electrolyte disorders before treatment
    Switch to more suitable alternative before planned pregnancy
    Treatment does not prevent risk of transmission of HIV
    Advise patient dizziness may affect ability to drive or operate machinery
    Combination therapy: refer to information for concomitant agent
    HIV therapy: Must be used in combination with other antiretrovirals
    Perform viral resistance testing before initiating therapy
    Treatment should be initiated by doctor experienced in HIV management
    Advise patient to take with or after food
    Autoimmune disorders can occur many months after initiation of treatment
    Blood lipid and glucose levels may increase requiring treatment
    Consider monitoring ECG in patients at risk of QT prolongation
    Monitor for signs of osteonecrosis
    Monitor renal function regularly
    Monitor serum electrolytes
    Advise patient to report skin reaction, pain, erythema, pruritus
    Advise patient to seek medical advice if joint aches or pain occur
    Advise patient to seek medical advice if movement becomes difficult
    Consider discontinuation if symptoms of cholelithiasis occur
    Discontinue or interrupt therapy if nephrolithiasis occurs
    Inflammatory symptoms should be evaluated and treated appropriately
    May cause hyperbilirubinaemia
    May develop immune reactivation syndrome
    Risk of developing opportunistic infections
    Advise patient to seek advice at first indications of pregnancy
    Discontinue if hepatic function deteriorates in pts with hepatic impairment
    Advise patient not to take St John's wort concurrently
    Advise patient to avoid antacids 1 hour before and 2 hours after dose
    Advise patient grapefruit products may increase plasma level
    Female: Barrier or non-hormonal contraception advised during treatment
    Female: Oral contraception may not be adequate during treatment

    The choice of therapy should be based on individual viral resistance testing and the treatment history of the patient.


    Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted. If hepatic disease worsens in these patients, interruption or discontinuation of therapy should be considered.

    Haemophiliac patients

    Increased bleeding, including spontaneous skin haematomas and haemarthroses, have been reported in type A and B haemophiliac patients treated with protease inhibitors. Additional factor VIII was required in some patients. In more than half of all reported cases, treatment was continued or reintroduced after discontinuation. Haemophiliac patients should be made aware of the possibility of increased bleeding.

    Weight and metabolic parameters

    Weight, blood lipid and glucose levels may increase during antiretroviral therapy. This may be linked to disease control and lifestyle. Refer to established HIV treatment guidelines for monitoring and manage lipid and glucose level disorders as appropriate.


    Reversible elevations of indirect bilirubin have occurred in patients receiving atazanavir, any rise in hepatic transaminase that occurs with bilirubin elevations should be evaluated for alternative causes.
    Alternative antiretroviral therapy should be considered if the patient views jaundice or scleral icterus as unacceptable.

    Immune reactivation syndrome

    An inflammatory reaction to asymptomatic or residual opportunistic pathogens, causing serious clinical conditions or aggravation of symptoms, could be expected in HIV-infected patients with severe immune deficiency at the time of the initiation of combination antiretroviral therapy (CART). Such reactions have been usually observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jirovecii pneumonia. Any inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune disorders, such as Graves' disease and autoimmune hepatitis, have also been observed. The reported time to onset is more variable in theses cases and can occur many months after initiation of treatment.


    Cases of osteonecrosis have been reported especially in patients with advance HIV-disease and/or long-term exposure to combination antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience joint aches and pain, join stiffness or difficulty in movement.

    Rash and associated syndromes

    Mild to moderate maculopapular skin eruptions can occur usually within the first 3 weeks of starting therapy with atazanavir. Patients should be monitored closely and advised of the signs and symptoms of more serious rashes. Atazanavir should be discontinued if severe rash develops. If the patient develops Stevens-Johnson syndrome or DRESS due to atazanavir with cobicistat, atazanavir with cobicistat may not be restarted. Patients should be advised of the signs and symptoms to watch out for and be monitored closely for skin reactions, the best results in managing these events come from early diagnosis and immediate interruption of any suspect medicines.

    Pregnancy and Lactation


    Atazanavir with cobicistat is contraindicated during pregnancy.

    At the time of writing, there are limited data from the use of atazanavir with cobicistat in pregnant women.

    The manufacturer advises that treatment with atazanavir with cobicistat should not be initiated during pregnancy, and women who become pregnant during therapy with this agent should be switched to an alternative regime.

    Animal studies with atazanavir with cobicistat are insufficient with respect to reproductive toxicity.

    Because pregnancy is a risk factor for hyperglycaemia, there is a concern that antiviral agents would exacerbate this risk.

    Since some reviews conclude that the expected benefit of the treatment to the HIV-positive mother outweighs the unknown risk to the fetus, it is suggested (Briggs 2015) that protease inhibitors should not be withheld.

    Known effects of atazanavir during pregnancy

    Treatment with atazanavir and cobicistat during the second and third trimester has been shown to result in low atazanavir exposure, compared to postpartum.

    Animal data suggest low risk to the developing fetus.

    It is not known if administration of atazanavir to pregnant women will exacerbate physiological hyperbilirubinaemia, which may lead to kernicterus in neonates and infants.

    Known effects of cobicistat during pregnancy

    As plasma levels of cobicistat and consequently of atazanavir (lower exposures of co-administered antiretroviral agents) may decrease significantly during pregnancy, which may result in virological failure and increase the risk of transmission of HIV from the mother to infant.


    Atazanavir with cobicistat is contraindicated in breastfeeding.

    The manufacturer does not recommend breastfeeding whilst taking atazanavir with cobicistat because of both the potential for HIV transmission and the risk of serious adverse reactions in the nursing infant.

    Atazanavir is excreted into human breast milk. The effect on a nursing infant from this exposure is unknown. It is not known also, if metabolites of cobicistat are excreted in human milk. Animal studies have shown excretion of cobicistat/metabolites in milk.


    Advise patient to take tablet with food. Swallow tablet whole, it must not be chewed, broken or crushed.

    Advise patient to avoid antacids 1 hour before and 2 hours after dose.

    Advise patient to avoid taking St John's wort concurrently.

    Advise patient to avoid grapefruit products.

    Advise patient to seek medical advice if movement becomes difficult or joint aches or pains occur.

    Advise patient to report any rashes that occur during treatment for assessment.

    Advise patient dizziness may affect ability to drive or operate machinery.

    Advise the patient to seek advice at first indications of pregnancy.

    Side Effects

    Abdominal distension
    Abdominal pain
    Alanine aminotransferase increased
    Aspartate aminotransferase increased
    Autoimmune hepatitis
    Blood lipid changes
    Chest pain
    Chronic kidney disease
    Creatine kinase increased
    Decrease in creatinine clearance
    Dream abnormalities
    Drug rash with eosinophilia and systemic symptoms (DRESS)
    Dry mouth
    Elevated serum lipase
    Erythema multiforme
    Gait abnormality
    Graves' disease
    Hypersensitivity reactions
    Increased appetite
    Interstitial nephritis
    Low neutrophil count
    Muscular atrophy
    Peripheral neuropathy
    Prolongation of QT interval
    Renal disorders
    Renal pain
    Scleral icterus
    Skin eruption
    Sleep disturbances
    Stevens-Johnson syndrome
    Torsades de pointes
    Vesiculo-bullous reactions
    Weight changes


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: March 2020.

    Reference Sources

    Summary of Product Characteristics: Evotaz 300mg/150mg tablets. Bristol-Myers Squibb Pharmaceuticals Ltd. Revised July 2021.

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

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