Drugs List

Therapeutic Indications

Uses

Treatment of HIV infected adults

Contraindications

Children weighing less than 30kg
Haemoglobin concentration below 7.5g / dL
Neutrophil count below 0.75 x 10 to the power of 9 / L
Breastfeeding
End stage renal disease
Hepatic impairment

Precautions and Warnings

Children weighing more than 30kg
Haemoglobin concentration below 9g/dl
Neutrophil count below 1.0 x 10 to the power of 9 / L
Patients over 65 years
Predisposition to hepatic disorder
Predisposition to hepatic steatosis
Risk factors for cardiovascular disorder
Abnormal liver function test
Hepatic steatosis
Hepatitis
Hepatitis B
Hepatitis C
Hepatitis C treated with alpha interferon and ribavirin
Hepatomegaly
Myelosuppression
Pregnancy
Renal impairment - creatinine clearance below 50ml/minute
Vitamin B12 deficiency

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Confirm negative HLA-B 5701 allele status in all patients
Intermittent therapy increases the risk of hypersensitivity reactions
Treatment should be initiated by doctor experienced in HIV management
Never rechallenge treatment after a hypersensitivity reaction
Reintroduction to the drug must be carried out in a medical setting
Monitor blood glucose before treatment, after 3 to 6 months, then annually
Monitor serum lipids before treatment, after 3 to 6 months, then annually
Autoimmune disorders can occur many months after initiation of treatment
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Evaluate for physical signs of fat redistribution
Monitor children exposed in utero for mitochondrial impairment
Monitor for development of lactic acidosis
Monitor haematological parameters periodically
On discontinuation, may cause recurrence of hepatitis B
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
Discontinue if raised LFTs/hepatomegaly/lactic acidosis occur
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if hypersensitivity reactions occur
Discontinue if pancreatitis occurs
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

When one of the active substances needs to be discontinued or when dosage needs to be reduced, separate preparations of abacavir, lamivudine, and zidovudine should be used. For further information, refer to the individual summary of products characteristics of these medicinal products.

Pregnancy and Lactation

Pregnancy

All treatment options require careful assessment by a specialist.

When considering the treatment of an HIV infected women during pregnancy, the present and future health of the mother, the prevention of maternal to foetal transmission and the limitations from the drug toxicity to the HIV-exposed foetus should be considered. The optimal antiretroviral therapy regimen for each patient depends on their, HIV RNA levels, previous disease history, and obstetric history.

The safety of abacavir administration in human pregnancy has not been established. In animals, the placental transfer of abacavir and/or its related metabolites has occurred. Animal studies have observed embryo toxicity, foetal malformations and foetal growth toxicity in rats, however no developmental toxicity or malformations have been observed in rabbits. Animal data suggests a risk for malformations and toxicity in human pregnancy. However, retrospective studies of exposed pregnancies reported in Briggs (2011) and Schaefer (2007) do not show a marked increase in the number of birth defects nor a discernible pattern. Further study is required for the potential of developmental toxicities. Abacavir crosses the human placenta.

Animal and human data suggest that lamivudine presents a low risk of structural malformations to the developing foetus. Mitochondrial dysfunction in the offspring has been suggested, but this requires further confirmation. Briggs concludes that the risk of mortality and morbidity from HIV infection far outweighs the risk of mitochondrial dysfunction (Briggs 2011). Lamivudine is believed to cross the human placenta by simple diffusion.

Briggs concludes that in the incidence of pregnancy occurring during therapy of HIV-1, combined antiretroviral therapy should not be withheld because the expected benefit to the mother outweighs the unknown risk to the foetus. Withdrawal or interruption of therapy may increase the emergence of resistant viral strains. Treatment of the pregnant mother with monotherapy is considered inadequate. Briggs recommends the use of zidovudine during the intrapartum period regardless of current regimen, as this may prevent vertical transmission of HIV to the newborn (Briggs 2011).

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 with zidovudine and lamivudine is contraindicated in breastfeeding.

Lamivudine and zidovudine are excreted in human breast milk at similar concentrations to those found in serum. 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.

HIV can be transmitted from mother to child through breast milk. HIV-infected mothers should not breastfeed their infants in order to avoid transmission of HIV. However, guidelines recommend exclusive breastfeeding for 6 months in regions where a lack of clean water for preparing infant formula and feeding equipment could pose a greater risk to the infant.

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 www.midlandsmedicines.nhs.uk/

Side Effects

Abdominal pain
Adult respiratory distress syndrome
Alopecia
Altered liver function tests
Anaemia
Anaphylaxis
Anorexia
Anxiety
Aplastic anaemia
Arthralgia
Asthenia
Autoimmune hepatitis
Bone marrow hypoplasia
Cardiomyopathy
Chest pain
Chills
Conjunctivitis
Convulsions
Cough
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Dyspepsia
Dyspnoea
Elevated amylase levels
Erythema multiforme
Fatigue
Fever
Flatulence
Graves' disease
Gynaecomastia
Headache
Hepatic failure
Hepatic steatosis
Hepatitis
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypotension
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in hepatic enzymes (transient)
Increase in serum ALT/AST
Influenza-like syndrome
Insomnia
Insulin resistance
Lactic acidosis
Lethargy
Leucopenia
Lipodystrophy
Loss of mental acuity
Lymphadenopathy
Lymphopenia
Maculopapular rash
Malaise
Metabolic disorders
Mouth ulcers
Muscle disorders
Myalgia
Myolysis
Myopathy
Nasal symptoms
Nausea
Neutropenia
Oedema
Osteonecrosis
Pain - generalised
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Pigmentation of nails, skin and oral mucosa
Pruritus
Rash
Red cell aplasia
Renal failure
Respiratory failure
Rhabdomyolysis
Serum bilirubin increased
Severe hepatomegaly
Somnolence
Sore throat
Stevens-Johnson syndrome
Sweating
Taste disturbances
Thrombocytopenia
Toxic epidermal necrolysis
Urinary frequency
Urticaria
Vomiting

Presentation

Oral formulations containing abacavir, zidovudine and lamivudine.

Drugs List

Therapeutic Indications

Uses

Treatment of HIV infected adults

Dosage

It is recommended that treatment is started with abacavir, lamivudine and zidovudine separately for the first 6 to 8 weeks.

Adults

Children

Contraindications

Children weighing less than 30kg
Haemoglobin concentration below 7.5g / dL
Neutrophil count below 0.75 x 10 to the power of 9 / L
Breastfeeding
End stage renal disease
Hepatic impairment

Precautions and Warnings

Children weighing more than 30kg
Haemoglobin concentration below 9g/dl
Neutrophil count below 1.0 x 10 to the power of 9 / L
Patients over 65 years
Predisposition to hepatic disorder
Predisposition to hepatic steatosis
Risk factors for cardiovascular disorder
Abnormal liver function test
Hepatic steatosis
Hepatitis
Hepatitis B
Hepatitis C
Hepatitis C treated with alpha interferon and ribavirin
Hepatomegaly
Myelosuppression
Pregnancy
Renal impairment - creatinine clearance below 50ml/minute
Vitamin B12 deficiency

Treatment does not prevent risk of transmission of HIV
Advise ability to drive/operate machinery may be affected by side effects
Confirm negative HLA-B 5701 allele status in all patients
Intermittent therapy increases the risk of hypersensitivity reactions
Treatment should be initiated by doctor experienced in HIV management
Never rechallenge treatment after a hypersensitivity reaction
Reintroduction to the drug must be carried out in a medical setting
Monitor blood glucose before treatment, after 3 to 6 months, then annually
Monitor serum lipids before treatment, after 3 to 6 months, then annually
Autoimmune disorders can occur many months after initiation of treatment
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Evaluate for physical signs of fat redistribution
Monitor children exposed in utero for mitochondrial impairment
Monitor for development of lactic acidosis
Monitor haematological parameters periodically
On discontinuation, may cause recurrence of hepatitis B
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
Discontinue if raised LFTs/hepatomegaly/lactic acidosis occur
Inflammatory symptoms should be evaluated and treated appropriately
Risk of developing opportunistic infections
Discontinue if hypersensitivity reactions occur
Discontinue if pancreatitis occurs
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

When one of the active substances needs to be discontinued or when dosage needs to be reduced, separate preparations of abacavir, lamivudine, and zidovudine should be used. For further information, refer to the individual summary of products characteristics of these medicinal products.

Pregnancy and Lactation

Pregnancy

All treatment options require careful assessment by a specialist.

When considering the treatment of an HIV infected women during pregnancy, the present and future health of the mother, the prevention of maternal to foetal transmission and the limitations from the drug toxicity to the HIV-exposed foetus should be considered. The optimal antiretroviral therapy regimen for each patient depends on their, HIV RNA levels, previous disease history, and obstetric history.

The safety of abacavir administration in human pregnancy has not been established. In animals, the placental transfer of abacavir and/or its related metabolites has occurred. Animal studies have observed embryo toxicity, foetal malformations and foetal growth toxicity in rats, however no developmental toxicity or malformations have been observed in rabbits. Animal data suggests a risk for malformations and toxicity in human pregnancy. However, retrospective studies of exposed pregnancies reported in Briggs (2011) and Schaefer (2007) do not show a marked increase in the number of birth defects nor a discernible pattern. Further study is required for the potential of developmental toxicities. Abacavir crosses the human placenta.

Animal and human data suggest that lamivudine presents a low risk of structural malformations to the developing foetus. Mitochondrial dysfunction in the offspring has been suggested, but this requires further confirmation. Briggs concludes that the risk of mortality and morbidity from HIV infection far outweighs the risk of mitochondrial dysfunction (Briggs 2011). Lamivudine is believed to cross the human placenta by simple diffusion.

Briggs concludes that in the incidence of pregnancy occurring during therapy of HIV-1, combined antiretroviral therapy should not be withheld because the expected benefit to the mother outweighs the unknown risk to the foetus. Withdrawal or interruption of therapy may increase the emergence of resistant viral strains. Treatment of the pregnant mother with monotherapy is considered inadequate. Briggs recommends the use of zidovudine during the intrapartum period regardless of current regimen, as this may prevent vertical transmission of HIV to the newborn (Briggs 2011).

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 with zidovudine and lamivudine is contraindicated in breastfeeding.

Lamivudine and zidovudine are excreted in human breast milk at similar concentrations to those found in serum. 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.

HIV can be transmitted from mother to child through breast milk. HIV-infected mothers should not breastfeed their infants in order to avoid transmission of HIV. However, guidelines recommend exclusive breastfeeding for 6 months in regions where a lack of clean water for preparing infant formula and feeding equipment could pose a greater risk to the infant.

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 www.midlandsmedicines.nhs.uk/

Side Effects

Abdominal pain
Adult respiratory distress syndrome
Alopecia
Altered liver function tests
Anaemia
Anaphylaxis
Anorexia
Anxiety
Aplastic anaemia
Arthralgia
Asthenia
Autoimmune hepatitis
Bone marrow hypoplasia
Cardiomyopathy
Chest pain
Chills
Conjunctivitis
Convulsions
Cough
Creatine phosphokinase increased
Depression
Diarrhoea
Dizziness
Dyspepsia
Dyspnoea
Elevated amylase levels
Erythema multiforme
Fatigue
Fever
Flatulence
Graves' disease
Gynaecomastia
Headache
Hepatic failure
Hepatic steatosis
Hepatitis
Hypercholesterolaemia
Hyperglycaemia
Hyperlactataemia
Hypersensitivity reactions
Hypertriglyceridaemia
Hypotension
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in hepatic enzymes (transient)
Increase in serum ALT/AST
Influenza-like syndrome
Insomnia
Insulin resistance
Lactic acidosis
Lethargy
Leucopenia
Lipodystrophy
Loss of mental acuity
Lymphadenopathy
Lymphopenia
Maculopapular rash
Malaise
Metabolic disorders
Mouth ulcers
Muscle disorders
Myalgia
Myolysis
Myopathy
Nasal symptoms
Nausea
Neutropenia
Oedema
Osteonecrosis
Pain - generalised
Pancreatitis
Pancytopenia
Paraesthesia
Peripheral neuropathy
Pigmentation of nails, skin and oral mucosa
Pruritus
Rash
Red cell aplasia
Renal failure
Respiratory failure
Rhabdomyolysis
Serum bilirubin increased
Severe hepatomegaly
Somnolence
Sore throat
Stevens-Johnson syndrome
Sweating
Taste disturbances
Thrombocytopenia
Toxic epidermal necrolysis
Urinary frequency
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 ).

Further Information

Last Full Review Date: January 2014

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, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Trizivir film-coated tablets. ViiV Healthcare UK Ltd. Revised October 2018.

NICE - Evidence Services
Available at: www.nice.org.uk
Last accessed: 20 June 2017