Abacavir with lamivudine oral
- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Oral formulation containing abacavir (as sulfate) and lamivudine
HIV infection - combination therapy
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 be avoided in patients carrying the HLA-B*5701 allele unless no other therapeutic option is available based on treatment history and resistance testing.
When one of the active substances needs to be discontinued or when dosage needs to be adjusted, separate preparations of abacavir and lamivudine should be used. For further information, refer to the individual summary of products characteristics of these medicinal products.
Bodyweight equal to or greater than 25 kg
One tablet daily.
Abacavir with lamivudine as a once daily regimen is mainly based on studies of abacavir with lamivudine in therapy-experienced patients and in combination with efavirenz in antiretroviral-naive adult patients.
Bodyweight equal to or greater than 25 kg
One tablet daily.
No pharmacokinetic data is currently available in patients over 65 years of age.
Special care is advised due to age associated changes such as decreased renal function and changes in haematological parameters.
Bodyweight equal to or greater than 25 kg
One tablet daily.
Children weighing less than 25kg
Renal impairment - creatinine clearance below 50ml/minute
Precautions and Warnings
Patients over 65 years
Risk factors for cardiovascular disorder
Abnormal liver function test
Mild hepatic impairment
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
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Contains sunset yellow (E110) - may cause allergic reaction
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
Avoid sorbitol or other polyalcohols, may reduce lamivudine efficacy
Blood lipid and glucose levels may increase requiring treatment
Monitor patients with hepatic impairment
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
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
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
Carriage of the HLA-B*5701 allele is associated with a significantly increased risk of a hypersensitivity reaction to abacavir, which can be life-threatening and fatal, despite taking precautions. Before treatment with abacavir, all patients irrespective of racial origin should be screened for the carriage of HLA-B*5701 allele. 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. See details below regarding hypersensitivity reactions.
A high rate of virological failure and the early emergence of resistance has been reported when abacavir with lamivudine was combined with tenofovir as a once daily regimen.
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.
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.
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. If hepatic disease worsens in these patients, interruption or discontinuation of therapy should be considered.
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.
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).
Reactions are characterised by symptoms indicating multi-organ system involvement. Almost all reactions include the symptoms of fever and/or rash. Special care is needed in patients taking concurrent products known to induce skin toxicity (e.g. non nucleoside reverse transcriptase inhibitors) as it is difficult to differentiate between rashes caused by these products and abacavir related hypersensitivity.
Other signs and symptoms may include respiratory symptoms (such as dyspnoea, sore throat, cough, abnormal chest X-ray) and gastrointestinal symptoms (such as nausea, vomiting, diarrhoea, abdominal pain). These may lead to a misdiagnosis of hypersensitivity as being a respiratory disease (pneumonia, bronchitis, pharyngitis, etc.) or gastroenteritis. Other symptoms of hypersensitivity reactions that are observed frequently include lethargy or malaise and musculoskeletal symptoms such as myalgia, myolysis (rare), or arthralgia.
Symptoms of hypersensitivity worsen with continued treatment and can become life-threatening. Symptoms usually resolve once treatment is discontinued.
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.
If a hypersensitivity reaction is diagnosed during therapy, this product must be discontinued immediately, regardless of HLA-B*5701 status, and must never be restarted.
Abacavir with lamivudine must be permanently discontinued if hypersensitivity cannot be ruled out, even if other diagnoses are possible (e.g. respiratory disease, gastroenteritis, reactions to other medication, etc.. This action avoids delay in diagnosis and minimises the risk of potentially life-threatening reactions. Reintroduction can only be considered if previous discontinuation was not due to a hypersensitivity reaction.
Very rarely cases of erythema multiforme, Stevens Johnson syndrome and toxic epidermal necrolysis have occurred and abacavir hypersensitivity could not be excluded. If these symptoms occur, products containing abacavir should be permanently discontinued.
Hypersensitivity symptoms return within hours if abacavir is restarted. The symptoms are usually more severe than the previous reaction and may lead to life-threatening hypotension and death.
Possible life-threatening hypersensitivity reactions with rapid onset have occurred when therapy is restarted in patients who had only one of the key symptoms of hypersensitivity (such as skin rash, fever, gastrointestinal, respiratory or constitutional symptoms such as malaise and lethargy) before abacavir treatment was stopped.
On very rare occasions, hypersensitivity reactions have been reported when therapy was restarted in patients who had no preceding symptoms of a hypersensitivity reaction. If the reintroduction of abacavir is ever judged necessary, it must be done in a setting where medical assistance is readily available.
Screening for carriage of the HLA B*5701 allele is recommended prior to re-initiation of abacavir in patients of unknown HLA-B*5701 status who have previously tolerated abacavir. Re-initiation of abacavir in such patients who test positive for the HLA B*5701 allele is not recommended and should be considered only under exceptional circumstances where potential benefit outweighs the risk and with close medical supervision.
Pregnancy and Lactation
Use abacavir with lamivudine with caution in pregnancy.
Animal data suggests that abacavir is a moderate risk. Although the human pregnancy does not suggest structural anomalies, other potential development toxicities require study. Antiretroviral nucleosides have been shown to have a direct dose-related cytotoxic effect on pre-implantation mouse embryos. This toxicity has not been studied in humans. Mitochondrial dysfunction in offspring exposed in utero or postnatally to nucleoside analogue reverse transcriptase inhibitors (NRTIs) has been reported. Abacavir crosses the human placenta. Animal and human data suggest that lamivudine is a low risk to the developing foetus for structural malformations. Theoretically, exposure to agents in this class at the time of implantation could result in impaired fertility as a result of embryonic cytotoxicity, but this has not been studied in humans. The risk of mitochondrial dysfunction needs confirmation. Lamivudine is believed to cross the human placenta. The risk of mortality and morbidity from HIV infection outweighs the risk of mitochondrial dysfunction. If indicated, the drug should not be withheld because of pregnancy (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 ).
Abacavir with lamivudine is contraindicated during breastfeeding.
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.
Lamivudine is 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.
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
Adult respiratory distress syndrome
Altered liver function tests
Creatine phosphokinase increased
Elevated amylase levels
Immune Reactivation/Reconstitution Syndrome
Increase in creatinine
Increase in serum ALT/AST
Red cell aplasia
Toxic epidermal necrolysis
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 ).
Last Full Review Date: February 2015
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.
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. Accessed on 11 February 2015.
Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 11 February 2015.
Summary of Product Characteristics: Kivexa film-coated tablets. ViiV Healthcare UK Ltd. Revised October 2018.
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
Abacavir and lamivudine. Last revised: 01 August 2014
Last accessed: 12 February 2015.
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