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Zidovudine with lamivudine oral


Tablets containing zidovudine and lamivudine.

Drugs List

  • COMBIVIR film coated tablets
  • zidovudine 300mg and lamivudine 150mg film coated tablets
  • Therapeutic Indications


    HIV infection-combined with other antiretrovirals

    Treatment of Human Immunodeficiency Virus (HIV) infection in combination with other antiretrovirals in adults and children weighing over 14 kg.


    When discontinuation of one of the active substances or a dose reduction is required, individual preparations of lamivudine and zidovudine should be considered.


    Adults weighing at least 30 kg
    One tablet taken twice daily.

    Adults weighing less than 30 kg
    (See Dosage; Children).


    Adults weighing at least 30 kg
    One tablet taken twice daily.

    Adults weighing less than 30 kg
    (See Dosage; Children).

    Consideration should be given to age associated changes such as reduced renal function and alteration of haematological parameters.


    Children or patients weighing at least 30 kg
    One tablet taken twice daily.

    Children or patients weighing between 21 kg and 30 kg
    One half tablet in the morning and one whole tablet in the evening.

    An alternative dose regimen of one half tablet three times a day is recommended if patients weighing between 21 and 30 kg develop gastrointestinal intolerance.

    Children or patients weighing between 14 kg and 21 kg
    One half tablet twice a day.

    Children or patients weighing less than 14 kg

    Patients with Renal Impairment

    Decreased clearance leads to increased concentrations of zidovudine and lamivudine in patients with renal impairment. Dosage adjustment may therefore be necessary in these patients (with creatinine clearance equal to or less than 50 ml/minute) and it is recommended that separate preparations of lamivudine and zidovudine are used to allow this. Individual prescribing information for lamivudine and zidovudine should be consulted.

    Patients with Hepatic Impairment

    Limited data in patients with cirrhosis suggests that zidovudine accumulation may occur in patients with hepatic impairment due to decreased glucuronidation.

    Data obtained in patients with moderate to severe hepatic impairment indicates that lamivudine pharmacokinetics are not significantly affected by hepatic impairment. However, as zidovudine accumulation may occur, dosage adjustments may be needed. It is therefore recommended that separate preparations of lamivudine and zidovudine are used to allow this. Individual prescribing information for lamivudine and zidovudine should be consulted.

    Additional Dosage Information

    Patients with Haematological Adverse Reactions
    Dosage adjustment of zidovudine may be required if the haemoglobin level falls below 9 g/dl or 5.59 mmol/l, or the neutrophil count falls below 1.0 x 10 to the power of 9 /l. It is recommended that separate preparations of lamivudine and zidovudine are used to allow this dose adjustment. Individual prescribing information for lamivudine and zidovudine should be consulted.


    Children weighing less than 14kg
    Haemoglobin concentration below 7.5g / dL
    Neutrophil count below 0.75 x 10 to the power of 9 / L

    Precautions and Warnings

    Haemoglobin concentration below 9g/dl
    Neutrophil count below 1.0 x 10 to the power of 9 / L
    Predisposition to hepatic disorder
    Predisposition to hepatic steatosis
    Weight between 14kg and 30kg
    Abnormal liver function test
    Hepatic impairment
    Hepatic steatosis
    Hepatitis C treated with alpha interferon and ribavirin
    Renal impairment
    Vitamin B12 deficiency

    Switch to more suitable alternative if lipoatrophy occurs
    Treatment does not prevent risk of transmission of HIV
    Treatment should be initiated by doctor experienced in HIV management
    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 for development of lactic acidosis
    Monitor for signs of osteonecrosis
    Monitor haematological parameters regularly throughout treatment
    Monitor patients at risk of hepatic disease
    On discontinuation, may cause recurrence of hepatitis B
    Advise patient to seek medical advice if joint aches or pain occur
    Advise patient to seek medical advice if movement becomes difficult
    Autoimmune diseases may occur during treatment
    Discontinue if raised LFTs/hepatomegaly/lactic acidosis occur
    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 pancreatitis occurs
    Discontinue if symptomatic hyperlactataemia occurs
    Discontinue or interrupt dose if anaemia, neutropenia or leucopenia occur

    Haematological reactions are to be expected with zidovudine treatment and generally occur after 4 to 6 weeks of therapy. Reactions include anaemia, neutropenia and leucopenia (usually secondary to neutropenia), and are more likely to occur in patients receiving higher zidovudine doses (1200 to 1500 mg/day) and in patients with poor bone marrow reserve prior to treatment, particularly with advanced HIV disease. Careful monitoring of haematological parameters is recommended. In patients with advanced symptomatic HIV infection, blood tests should be performed at least every 2 weeks for the first 3 months of treatment and at least once a month after that.

    Lactic acidosis, usually associated with hepatomegaly and hepatic steatosis, has been reported with the use of nucleoside analogues. This generally occurs after a few or several months of treatment.
    Caution should be exercised and close monitoring is advisable when administering nucleoside analogues to at risk patients (particularly obese women) with hepatomegaly, hepatic enzyme abnormalities, hepatitis, or any known risk factors for hepatic disease and hepatic steatosis.

    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.

    Patients with pre-existing hepatic impairment, including chronic active hepatitis, have an increased risk of developing hepatic function abnormalities during therapy. These patients should be closely monitored and treatment should be interrupted or discontinued if hepatic disease worsens in these patients.

    If lamivudine with zidovudine is discontinued in patients co-infected with the hepatitis B virus, liver function tests and markers of HBV replication should be monitored for 4 months, as lamivudine withdrawal may result in acute exacerbation of hepatitis.

    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. Reports have predominatly concerned treatments containing zidovudine. 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.

    Zidovudine containing regimens have been associated with loss of subcutaneous fat, which, in turn, has been linked to mitochondrial toxicity. Fat loss in the face, limbs and buttocks is most evident and may not be reversible when switching to a regimen without zidovudine. Assess patient for lipoatrophy regularly and switch to an alternative, zidovudine-free, therapy if lipoatrophy is suspected.

    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.

    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.

    Pregnancy and Lactation


    Use zidovudine with lamivudine with caution in pregnancy.

    When considering the treatment of a 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. Lamivudine and zidovudine cross the placenta and foetal levels have been found to be similar to, or higher than, the maternal levels. The use of zidovudine in pregnant women over 14 weeks of gestation, with subsequent treatment of their newborn infants, has been shown to reduce the rate of maternal-foetal transmission of HIV significantly. Pregnant women should be advised that transmission may still occur in some cases despite therapy.

    Lamivudine and zidovudine are not teratogenic in animals except at very high doses (zidovudine), and the experience in humans shows no pattern of birth defects Briggs (2011). Zidovudine is known to cause neonatal anaemia. Mitochondrial dysfunction in neonates following in utero zidovudine exposure has also been reported. It is unknown whether there are any long term consequences of in utero and infant exposure to zidovudine. 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.

    Animal studies on rats showed that lamivudine and zidovudine are toxic to rodent embryos, by preventing blastocyst development, if given before implantation occurs. Briggs (2011) reports that there is some experience that lamivudine and zidovudine may affect human trophoblast cell growth and function in a dose related manner. Therefore, lamivudine and zidovudine should only be used in pregnancy prior to the second trimester if the potential benefit to the mother outweighs the risk to the foetus.

    The efficacy of zidovudine to reduce the maternal foetal transmission in women with previously prolonged treatment with zidovudine or other antiretroviral agents or women infected with HIV strains with reduced sensitivity to zidovudine is unknown.

    Based on the animal carcinogenicity/mutagenicity findings a carcinogenic risk to humans cannot be excluded. The relevance of these findings to both infected and uninfected infants exposed to lamivudine and zidovudine is unknown. Pregnant women should be made aware of these findings when considering lamivudine and zidovudine treatment.

    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 ( ) or if this is unavailable at the backup site ( ).


    Zidovudine and Lamivudine are contraindicated while breastfeeding.

    Lamivudine and zidovudine are excreted into breast milk. HIV can be transmitted from mother to child through breast milk. Therefore it is recommended that HIV-infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.

    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

    Side Effects

    Abdominal cramps
    Abdominal pain
    Aplastic anaemia
    Autoimmune disorders
    Autoimmune hepatitis
    Bone marrow hypoplasia
    Chest pain
    Elevated amylase levels
    Graves' disease
    Hepatic disorders
    Hepatic steatosis
    Hypersensitivity reactions
    Immune Reactivation/Reconstitution Syndrome
    Increase in serum ALT/AST
    Influenza-like syndrome
    Insulin resistance
    Lactic acidosis
    Loss of mental acuity
    Metabolic disorders
    Muscle disorders
    Nasal symptoms
    Pain - generalised
    Peripheral neuropathy
    Pigmentation of nails, skin and oral mucosa
    Red cell aplasia
    Respiratory tract infection
    Serum bilirubin increased
    Severe hepatomegaly
    Taste disturbances
    Urinary frequency


    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: August 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.

    Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press Accessed on August 6, 2014.

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

    Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications Accessed on August 6, 2014.

    Summary of Product Characteristics: Combivir Film Coated Tablets. ViiV Healthcare UK Ltd. Revised January 2019.

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

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Lamivudine Last revised: February 4, 2014
    Last accessed: August 6, 2014

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at:
    Zidovudine Last revised: February 4, 2014
    Last accessed: August 6, 2014

    The Norwegian Porphyria Centre (NAPOS).
    Available at:
    Last revised:
    Last accessed: August 6, 2014

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