Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Contraindications

Children under 3 months
Breastfeeding
End stage renal disease
Hereditary fructose intolerance

Precautions and Warnings

Patients over 65 years
Risk factors for cardiovascular disorder
Hepatic impairment
Pregnancy

Treatment does not prevent risk of transmission of HIV
Confirm negative HLA-B 5701 allele status in all patients
Intermittent therapy increases the risk of hypersensitivity reactions
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Never rechallenge treatment after a hypersensitivity reaction
Reintroduction to the drug must be carried out in a medical setting
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Monitor patients with hepatic impairment
Review patients every 2 weeks for the first 2 months
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Consider hypersensitivity if any of:rash/fever/G.I/flu-like or resp.dis.
Contact doctor immediately with any signs of hypersensitivity reactions
Inflammatory symptoms should be evaluated and treated appropriately
Neonate exposed in utero: Risk of mitochondrial dysfunction
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if hypersensitivity reactions occur
Advise if swallowing difficult may be crushed and added to soft food/liquid
Advise patient not to restart treatment without consulting their doctor
Advise patient to read the leaflet in the pack
Advise patient to return remaining medication to the pharmacy
Advise patients on the importance of taking treatment regularly
Advise patients that hypersensitivity reactions may be life threatening
Remind patient of importance of carrying Alert Card with them at all times

In patients with high viral load (greater than 100,000 copies/ml) the choice of triple combination with abacavir, lamivudine and zidovudine needs special consideration. A high rate of virological failure and the early emergence of resistance has been reported when abacavir was combined with tenofovir and lamivudine as a once daily regimen.

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.

Treatment regimens containing nucleoside or nucleotide analogues have been reported to cause mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally. Adverse reactions such as haematological (anaemia, neutropenia), metabolic (hyperlactataemia, hyperlipasemia) and neurological (hypertonia, convulsions, abnormal behaviour) have been reported. Consider in children exposed to nucleoside or nucleotide analogues in utero (including HIV-negative infants) and who present with neurological symptoms or severe clinical findings of unknown cause.

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 carinii 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.

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.

Caution is required in patients with a high risk of cardiovascular disease. Observational studies have shown an association between abacavir and myocardial infarction. At the time of writing there is no established biological mechanism to explain a potential increase in risk but when prescribing abacavir action should be taken to try and minimise all modifiable risk factors (such as smoking, hypertension and hyperlipidaemia).

Hypersensitivity Reactions

Hypersensitivity reactions usually appear within the first 6 weeks of treatment with abacavir, although the reactions may occur at any time during therapy. Patients should be monitored closely, especially during the first 2 months of treatment, with consultations every 2 weeks.

Pregnancy and Lactation

Pregnancy

Use abacavir with caution in pregnancy.

Briggs suggests abacavir should not be withheld in pregnancy as the expected benefit to the HIV infected mother overcomes the unknown risk to the foetus. Schaefer suggests the present and future health of the HIV-positive women should be considered as well as the prevention of maternal to foetal transmission as there is limited data of the drug toxicity on the foetus. The manufacturer suggests both animal data and clinical experience in pregnant women should be considered, however the malformative risk is unlikely in humans based on those data.

Toxicity to the developing embryo and foetus in rats, but not in rabbits have been shown in animal studies, however the clinical relevance of this data in humans is unknown.

Mitochondrial dysfunction
There have been reports of mitochondrial dysfunction in HIV negative infants exposed to nucleoside analogues in utero and/or post-natally. Variable degrees of mitochondrial damage have been demonstrated in vivo and in vitro caused by both nucleoside and nucleotide analogues.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Abacavir is contraindicated in breastfeeding.

It is recommended that HIV infected women should not breastfeed due to the risk of passing on the infection to the infant.

Abacavir and its metabolites are secreted into breast milk of lactating rats. It is expected that these will also be secreted into human breast milk and since no data are available on the administration to infants less than three months old, breast feeding should be avoided whilst receiving treatment with abacavir.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Adult respiratory distress syndrome
Altered liver function tests
Anaphylaxis
Anorexia
Arthralgia
Autoimmune hepatitis
Conjunctivitis
Cough
Creatine phosphokinase increased
Diarrhoea
Dizziness
Dyspnoea
Erythema multiforme
Fatigue
Fever
Flatulence
Graves' disease
Headache
Hepatic failure
Hepatitis
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypotension
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Insulin resistance
Lactic acidosis
Lethargy
Lymphadenopathy
Lymphopenia
Maculopapular rash
Malaise
Metabolic changes
Mouth ulcers
Myalgia
Myolysis
Nausea
Oedema
Osteonecrosis
Pancreatitis
Paraesthesia
Rash
Renal failure
Respiratory failure
Sore throat
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria
Vomiting

Presentation

Oral solution containing abacavir as abacavir sulfate.

Film-coated tablets containing abacavir as abacavir sulfate.

Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Dosage

Before treatment with abacavir, all patients irrespective of racial origin should be screened for the carriage of HLA-B*5701 allele. Screening is also recommended prior to re-initiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. Presence of this allele confers an increased risk of severe hypersensitivity reactions to abacavir. Abacavir should not be used in patients carrying the HLA-B*5701 allele unless no other therapeutic option is available based on treatment history and resistance testing.

Adults

Children

Additional Dosage Information

Contraindications

Children under 3 months
Breastfeeding
End stage renal disease
Hereditary fructose intolerance

Precautions and Warnings

Patients over 65 years
Risk factors for cardiovascular disorder
Hepatic impairment
Pregnancy

Treatment does not prevent risk of transmission of HIV
Confirm negative HLA-B 5701 allele status in all patients
Intermittent therapy increases the risk of hypersensitivity reactions
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Oral liquid contains hydroxybenzoate: caution in hypersensitivity
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Never rechallenge treatment after a hypersensitivity reaction
Reintroduction to the drug must be carried out in a medical setting
Autoimmune disorders can occur many months after initiation of treatment
Blood lipid and glucose levels may increase requiring treatment
Monitor patients with hepatic impairment
Review patients every 2 weeks for the first 2 months
Advise patient to seek medical advice if joint aches or pain occur
Advise patient to seek medical advice if movement becomes difficult
Consider hypersensitivity if any of:rash/fever/G.I/flu-like or resp.dis.
Contact doctor immediately with any signs of hypersensitivity reactions
Inflammatory symptoms should be evaluated and treated appropriately
Neonate exposed in utero: Risk of mitochondrial dysfunction
Risk of developing opportunistic infections
Discontinue if hepatic function deteriorates in pts with hepatic impairment
Discontinue if hypersensitivity reactions occur
Advise if swallowing difficult may be crushed and added to soft food/liquid
Advise patient not to restart treatment without consulting their doctor
Advise patient to read the leaflet in the pack
Advise patient to return remaining medication to the pharmacy
Advise patients on the importance of taking treatment regularly
Advise patients that hypersensitivity reactions may be life threatening
Remind patient of importance of carrying Alert Card with them at all times

In patients with high viral load (greater than 100,000 copies/ml) the choice of triple combination with abacavir, lamivudine and zidovudine needs special consideration. A high rate of virological failure and the early emergence of resistance has been reported when abacavir was combined with tenofovir and lamivudine as a once daily regimen.

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.

Treatment regimens containing nucleoside or nucleotide analogues have been reported to cause mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally. Adverse reactions such as haematological (anaemia, neutropenia), metabolic (hyperlactataemia, hyperlipasemia) and neurological (hypertonia, convulsions, abnormal behaviour) have been reported. Consider in children exposed to nucleoside or nucleotide analogues in utero (including HIV-negative infants) and who present with neurological symptoms or severe clinical findings of unknown cause.

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 carinii 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.

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.

Caution is required in patients with a high risk of cardiovascular disease. Observational studies have shown an association between abacavir and myocardial infarction. At the time of writing there is no established biological mechanism to explain a potential increase in risk but when prescribing abacavir action should be taken to try and minimise all modifiable risk factors (such as smoking, hypertension and hyperlipidaemia).

Hypersensitivity Reactions

Hypersensitivity reactions usually appear within the first 6 weeks of treatment with abacavir, although the reactions may occur at any time during therapy. Patients should be monitored closely, especially during the first 2 months of treatment, with consultations every 2 weeks.

Pregnancy and Lactation

Pregnancy

Use abacavir with caution in pregnancy.

Briggs suggests abacavir should not be withheld in pregnancy as the expected benefit to the HIV infected mother overcomes the unknown risk to the foetus. Schaefer suggests the present and future health of the HIV-positive women should be considered as well as the prevention of maternal to foetal transmission as there is limited data of the drug toxicity on the foetus. The manufacturer suggests both animal data and clinical experience in pregnant women should be considered, however the malformative risk is unlikely in humans based on those data.

Toxicity to the developing embryo and foetus in rats, but not in rabbits have been shown in animal studies, however the clinical relevance of this data in humans is unknown.

Mitochondrial dysfunction
There have been reports of mitochondrial dysfunction in HIV negative infants exposed to nucleoside analogues in utero and/or post-natally. Variable degrees of mitochondrial damage have been demonstrated in vivo and in vitro caused by both nucleoside and nucleotide analogues.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Abacavir is contraindicated in breastfeeding.

It is recommended that HIV infected women should not breastfeed due to the risk of passing on the infection to the infant.

Abacavir and its metabolites are secreted into breast milk of lactating rats. It is expected that these will also be secreted into human breast milk and since no data are available on the administration to infants less than three months old, breast feeding should be avoided whilst receiving treatment with abacavir.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

Advise patients that treatment does not prevent the risk of HIV transmission through sexual contact or blood contamination and that appropriate precautions should be continued.

Side Effects

Abdominal pain
Adult respiratory distress syndrome
Altered liver function tests
Anaphylaxis
Anorexia
Arthralgia
Autoimmune hepatitis
Conjunctivitis
Cough
Creatine phosphokinase increased
Diarrhoea
Dizziness
Dyspnoea
Erythema multiforme
Fatigue
Fever
Flatulence
Graves' disease
Headache
Hepatic failure
Hepatitis
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypotension
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Insulin resistance
Lactic acidosis
Lethargy
Lymphadenopathy
Lymphopenia
Maculopapular rash
Malaise
Metabolic changes
Mouth ulcers
Myalgia
Myolysis
Nausea
Oedema
Osteonecrosis
Pancreatitis
Paraesthesia
Rash
Renal failure
Respiratory failure
Sore throat
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Urticaria
Vomiting

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 ).

Shelf Life and Storage

Discard the oral solution two months after opening.

Further Information

Last Full Review Date: September 2016.

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) 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.

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 07 September 2016.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 07 September 2016.

Summary of Product Characteristics: Ziagen 300 mg film coated tablets. ViiV Healthcare UK Ltd. Revised December 2018.

Summary of Product Characteristics: Ziagen 20 mg/ml Oral Solution. ViiV Healthcare UK Ltd. Revised December 2018.