Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Treatment of human immunodeficiency virus (HIV-1) infection in combination with low dose ritonavir and other antiretroviral agents.

Contraindications

Children under 6 years
Children weighing less than 15kg
Breastfeeding
Galactosaemia
Haemodialysis
Long QT syndrome
Moderate hepatic impairment
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Cardiac conduction defects
Chronic hepatic disorder
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Haemophilia
Hepatitis B
Hepatitis C
History of torsade de pointes
Lactose intolerance
Mild hepatic impairment
Post partum
Pregnancy

Correct electrolyte disorders before treatment
Treatment does not prevent risk of transmission of HIV
Advise patient dizziness may affect ability to drive or operate machinery
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
Contains lactose
Advise patient on concurrent use of proton pump inhibitors
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
May prolong PR interval
Monitor cardiac function in paediatric patients
Monitor closely for skin reactions
Monitor hepatic function in patients with history of hepatic disease
Monitor renal function regularly
Monitor serum electrolytes
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
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently
Avoid antacids 1 hour after or 2 hours before dose
Female: Barrier or non-hormonal contraception advised during treatment
Female: Oral contraception may not be adequate during treatment
Advise haemophiliac patients of possibility of increased bleeding

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.

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.

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, a dose reduction of atazanavir is not recommended as a loss of therapeutic effect and development of resistance may occur.

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. Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome has been reported in patients receiving atazanavir. If the patient develops Stevens-Johnson syndrome or DRESS due to atazanavir, atazanavir must not be restarted.
When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or Pneumocystis jirovecii pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately. Autoimmune disorders such as Graves' disease have also occurred in the context of immune reactivation after initiation of treatment though with a more variable time to onset sometimes after many months of treatment.

Pregnancy and Lactation

Pregnancy

Use atazanavir with caution during pregnancy.

The manufacturer recommends that atazanavir may be considered during pregnancy only if the potential benefit justifies the potential risk. At the time of writing, a moderate amount of data in pregnant women (between 300-1000 pregnancy outcomes) indicate no malformative toxicity of atazanavir. Animal studies do not indicate reproductive toxicity.

Briggs (2015) states that the potential maternal benefit far outweighs any potential embryo-foetal risk. It is unknown if atazanavir crosses the human placenta. The molecular weight and moderately long elimination half-life suggest that it may occur. There is limited data to assess the risk in pregnancy of atazanavir, however the animal data implies a low risk to the foetus.

It is not known if administration of atazanavir to pregnant women will exacerbate physiological hyperbilirubinaemia, which may lead to kernicterus in neonates and infants. In the period immediately before delivery additional monitoring should also be considered.

Lactation

Atazanavir is contraindicated during breastfeeding.

The manufacturer advises that atazanavir is contraindicated during breastfeeding. It is recommended that HIV infected women should not breastfeed their infants in order to avoid transmission of HIV. Atazanavir has been detected in human breast milk.

Side Effects

Abdominal distension
Abdominal pain
Allergic reaction
Alopecia
Amnesia
Angioedema
Anorexia
Anxiety
Aphthous stomatitis
Arthralgia
Asthenia
Atrioventricular block
Autoimmune hepatitis
Blood lipid changes
Chest pain
Cholecystitis
Cholelithiasis
Cholestasis
Chronic kidney disease
Creatine kinase increased
Depression
Diarrhoea
Disorientation
Dizziness
Dream abnormalities
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Eczema
Elevated serum lipase
Erythema multiforme
Fatigue
Fever
Flatulence
Gait abnormality
Gastritis
Graves' disease
Gynaecomastia
Haematuria
Headache
Hepatic impairment
Hepatitis
Hepatosplenomegaly
Hyperglycaemia
Hypersensitivity reactions
Hypertension
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Increased appetite
Increased spontaneous bleeding (haemophiliacs)
Increases in hepatic enzymes
Insomnia
Interstitial nephritis
Jaundice
Ketoacidosis
Malaise
Metabolic disorders
Mouth ulcers
Muscular atrophy
Myalgia
Myopathy
Nausea
Nephrolithiasis
Oedema
Osteonecrosis
Palpitations
Pancreatitis
Peripheral neuropathy
Pollakiuria
Prolongation of PR interval
Prolongation of QT interval
Proteinuria
Pruritus
Rash
Reduced neutrophil count
Renal impairment
Renal pain
Scleral icterus
Serum bilirubin increased
Sleep disturbances
Somnolence
Stevens-Johnson syndrome
Syncope
Torsades de pointes
Toxic skin reaction
Urticaria
Vasodilation
Vesiculo-bullous reactions
Vomiting
Weight gain
Weight loss

Presentation

Oral formulations of atazanavir sulfate.

Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Treatment of human immunodeficiency virus (HIV-1) infection in combination with low dose ritonavir and other antiretroviral agents.

Dosage

The atazanavir capsule should be swallowed whole, taken at the same time as ritonavir, and both taken with food.

If used in combination with ritonavir, consult product information.

Adults

Children

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 6 years
Children weighing less than 15kg
Breastfeeding
Galactosaemia
Haemodialysis
Long QT syndrome
Moderate hepatic impairment
Torsade de pointes

Precautions and Warnings

Family history of long QT syndrome
Cardiac conduction defects
Chronic hepatic disorder
Electrolyte imbalance
Glucose-galactose malabsorption syndrome
Haemophilia
Hepatitis B
Hepatitis C
History of torsade de pointes
Lactose intolerance
Mild hepatic impairment
Post partum
Pregnancy

Correct electrolyte disorders before treatment
Treatment does not prevent risk of transmission of HIV
Advise patient dizziness may affect ability to drive or operate machinery
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
Contains lactose
Advise patient on concurrent use of proton pump inhibitors
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
May prolong PR interval
Monitor cardiac function in paediatric patients
Monitor closely for skin reactions
Monitor hepatic function in patients with history of hepatic disease
Monitor renal function regularly
Monitor serum electrolytes
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
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if severe skin reaction occurs
Advise patient not to take St John's wort concurrently
Avoid antacids 1 hour after or 2 hours before dose
Female: Barrier or non-hormonal contraception advised during treatment
Female: Oral contraception may not be adequate during treatment
Advise haemophiliac patients of possibility of increased bleeding

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.

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.

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, a dose reduction of atazanavir is not recommended as a loss of therapeutic effect and development of resistance may occur.

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. Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome has been reported in patients receiving atazanavir. If the patient develops Stevens-Johnson syndrome or DRESS due to atazanavir, atazanavir must not be restarted.
When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or Pneumocystis jirovecii pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately. Autoimmune disorders such as Graves' disease have also occurred in the context of immune reactivation after initiation of treatment though with a more variable time to onset sometimes after many months of treatment.

Pregnancy and Lactation

Pregnancy

Use atazanavir with caution during pregnancy.

The manufacturer recommends that atazanavir may be considered during pregnancy only if the potential benefit justifies the potential risk. At the time of writing, a moderate amount of data in pregnant women (between 300-1000 pregnancy outcomes) indicate no malformative toxicity of atazanavir. Animal studies do not indicate reproductive toxicity.

Briggs (2015) states that the potential maternal benefit far outweighs any potential embryo-foetal risk. It is unknown if atazanavir crosses the human placenta. The molecular weight and moderately long elimination half-life suggest that it may occur. There is limited data to assess the risk in pregnancy of atazanavir, however the animal data implies a low risk to the foetus.

It is not known if administration of atazanavir to pregnant women will exacerbate physiological hyperbilirubinaemia, which may lead to kernicterus in neonates and infants. In the period immediately before delivery additional monitoring should also be considered.

Lactation

Atazanavir is contraindicated during breastfeeding.

The manufacturer advises that atazanavir is contraindicated during breastfeeding. It is recommended that HIV infected women should not breastfeed their infants in order to avoid transmission of HIV. Atazanavir has been detected in human breast milk.

Side Effects

Abdominal distension
Abdominal pain
Allergic reaction
Alopecia
Amnesia
Angioedema
Anorexia
Anxiety
Aphthous stomatitis
Arthralgia
Asthenia
Atrioventricular block
Autoimmune hepatitis
Blood lipid changes
Chest pain
Cholecystitis
Cholelithiasis
Cholestasis
Chronic kidney disease
Creatine kinase increased
Depression
Diarrhoea
Disorientation
Dizziness
Dream abnormalities
Drug rash with eosinophilia and systemic symptoms (DRESS)
Dry mouth
Dysgeusia
Dyspepsia
Dyspnoea
Eczema
Elevated serum lipase
Erythema multiforme
Fatigue
Fever
Flatulence
Gait abnormality
Gastritis
Graves' disease
Gynaecomastia
Haematuria
Headache
Hepatic impairment
Hepatitis
Hepatosplenomegaly
Hyperglycaemia
Hypersensitivity reactions
Hypertension
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Increased appetite
Increased spontaneous bleeding (haemophiliacs)
Increases in hepatic enzymes
Insomnia
Interstitial nephritis
Jaundice
Ketoacidosis
Malaise
Metabolic disorders
Mouth ulcers
Muscular atrophy
Myalgia
Myopathy
Nausea
Nephrolithiasis
Oedema
Osteonecrosis
Palpitations
Pancreatitis
Peripheral neuropathy
Pollakiuria
Prolongation of PR interval
Prolongation of QT interval
Proteinuria
Pruritus
Rash
Reduced neutrophil count
Renal impairment
Renal pain
Scleral icterus
Serum bilirubin increased
Sleep disturbances
Somnolence
Stevens-Johnson syndrome
Syncope
Torsades de pointes
Toxic skin reaction
Urticaria
Vasodilation
Vesiculo-bullous reactions
Vomiting
Weight gain
Weight loss

Overdosage

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 ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: April 2014

Reference Sources

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.

Summary of Product Characteristics: Atazanavir 150mg Hard Capsules. Zentiva Pharma UK Ltd. Revised June 2020.

Summary of Product Characteristics: Reyataz 100mg 150mg, 200mg and 300mg Hard Capsules. Bristol-Myers Squibb Pharmaceuticals Ltd. Revised February 2019.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 21 January 2022

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Atazanavir. Last revised: September 7, 2013.
Last accessed: March 14, 2014.