Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Administration

Tablets should be swallowed whole without crushing. For patients unable to swallow tablets, consider oral solution. Alternatively, tablets may be crushed and added to a small amount of semi-solid food or liquid, all of which should be consumed immediately.

Contraindications

Neonates under 1 month
Breastfeeding

Precautions and Warnings

Children aged 1 to 3 months
Abnormal liver function test
Diabetes mellitus
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hepatitis B
Hepatitis C
Hereditary fructose intolerance
Pregnancy
Renal impairment

Reduce dose in patients with renal impairment
Treatment does not prevent risk of transmission of HIV
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Oral solution contains sucrose and hydroxybenzoates
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 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
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

A high rate of virological failure and early resistance has been reported when lamivudine was combined with tenofovir disoproxil fumarate and abacavir, and also with tenofovir disoproxil fumarate and didanosine.

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.

Other lamivudine formulations are indicated for hepatitis B, see relevant monograph and product details for more information.
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 is discontinued in patients co-infected with the hepatitis B virus, liver function tests and markers of HBV replication should be monitored periodically 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. 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.

The oral solution contains sucrose. Diabetic patients should be advised that each dose (150 mg = 15 ml) of oral solution contains 3 g sucrose.

Pregnancy and Lactation

Pregnancy

Use lamivudine with caution in pregnancy.

Briggs suggests if indicated, lamivudine should not be withheld because of pregnancy. The manufacturer suggests lamivudine can be used in pregnancy if clinically indicated.

Animal studies in rabbits have shown an increase in early embryonic deaths however this was not seen in rats. No teratogenic effects were observed in rats and rabbits administered up to 130 and 60 times the usual adult dose.

More than 1000 pregnancies exposed to lamivudine did not indicate malformative toxicity. Lamivudine crosses the placenta and foetal levels have been found to be similar to or higher than the maternal levels.
Animal and human data suggest low risk to the developing foetus for structural malformations. Impaired fertility as a result of embryonic cytotoxicity could occur with but this has not been studied in humans.

Mitochondrial dysfunction in neonates following in utero exposure to treatment regimens containing nucleoside and nucleotide analogue has been reported. It is unknown whether there are any long term consequences of in utero and infant exposure to lamivudine. 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 co-infected with hepatitis who become pregnant and withdraw lamivudine may have a re-occurrence of hepatitis.

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

Lamivudine is contraindicated while breastfeeding.

It is recommended that HIV infected women do not breastfeed in order to avoid transmission of HIV.

Lamivudine is excreted into breast milk. Based on more than 200 mother and child pairs treated for HIV, serum concentrations of lamivudine in breastfed infants of treated mothers were low (less than 4% of maternal serum concentrations) and progressively decreased to undetectable levels when infants reached 24 weeks old. The low levels ingested by the infant are likely to result in sub-optimal antiviral effect. At the time of writing there are no evidence that the low concentrations in human milk leads to adverse reactions in the breastfed 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 https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal cramps
Abdominal pain
Alopecia
Anaemia
Angioedema
Arthralgia
Autoimmune disorders
Autoimmune hepatitis
Behavioural disturbances
Blood disorders
Convulsions
Cough
Diarrhoea
Elevated amylase levels
Fatigue
Fever
Graves' disease
Headache
Hepatitis
Hypertonia
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Insomnia
Lactic acidosis
Malaise
Metabolic disorders
Muscle disorders
Nasal symptoms
Nausea
Neutropenia
Osteonecrosis
Pancreatitis
Paraesthesia
Peripheral neuropathy
Rash
Red cell aplasia
Rhabdomyolysis
Thrombocytopenia
Vomiting

Presentation

Tablets and oral solution containing lamivudine.

Drugs List

Therapeutic Indications

Uses

HIV infection-combined with other antiretrovirals

Dosage

Therapy should be initiated by a physician experienced in the management of HIV infection and must be used as part of combination therapy.

Patients changing to the once daily regimen should take their last twice a day dose and switch to the once a day dose 12 hours after taking the last twice a day dose. If reverting back to twice a day dosing, take the twice daily dose approximately 24 hours after the last once a day dose.

Adults

Children

Patients with Renal Impairment

Administration

Tablets should be swallowed whole without crushing. For patients unable to swallow tablets, consider oral solution. Alternatively, tablets may be crushed and added to a small amount of semi-solid food or liquid, all of which should be consumed immediately.

Contraindications

Neonates under 1 month
Breastfeeding

Precautions and Warnings

Children aged 1 to 3 months
Abnormal liver function test
Diabetes mellitus
Glucose-galactose malabsorption syndrome
Hepatic impairment
Hepatitis B
Hepatitis C
Hereditary fructose intolerance
Pregnancy
Renal impairment

Reduce dose in patients with renal impairment
Treatment does not prevent risk of transmission of HIV
Must be used in combination with other antiretrovirals
Treatment should be initiated by doctor experienced in HIV management
Oral solution contains sucrose and hydroxybenzoates
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 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
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

A high rate of virological failure and early resistance has been reported when lamivudine was combined with tenofovir disoproxil fumarate and abacavir, and also with tenofovir disoproxil fumarate and didanosine.

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.

Other lamivudine formulations are indicated for hepatitis B, see relevant monograph and product details for more information.
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 is discontinued in patients co-infected with the hepatitis B virus, liver function tests and markers of HBV replication should be monitored periodically 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. 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.

The oral solution contains sucrose. Diabetic patients should be advised that each dose (150 mg = 15 ml) of oral solution contains 3 g sucrose.

Pregnancy and Lactation

Pregnancy

Use lamivudine with caution in pregnancy.

Briggs suggests if indicated, lamivudine should not be withheld because of pregnancy. The manufacturer suggests lamivudine can be used in pregnancy if clinically indicated.

Animal studies in rabbits have shown an increase in early embryonic deaths however this was not seen in rats. No teratogenic effects were observed in rats and rabbits administered up to 130 and 60 times the usual adult dose.

More than 1000 pregnancies exposed to lamivudine did not indicate malformative toxicity. Lamivudine crosses the placenta and foetal levels have been found to be similar to or higher than the maternal levels.
Animal and human data suggest low risk to the developing foetus for structural malformations. Impaired fertility as a result of embryonic cytotoxicity could occur with but this has not been studied in humans.

Mitochondrial dysfunction in neonates following in utero exposure to treatment regimens containing nucleoside and nucleotide analogue has been reported. It is unknown whether there are any long term consequences of in utero and infant exposure to lamivudine. 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 co-infected with hepatitis who become pregnant and withdraw lamivudine may have a re-occurrence of hepatitis.

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

Lamivudine is contraindicated while breastfeeding.

It is recommended that HIV infected women do not breastfeed in order to avoid transmission of HIV.

Lamivudine is excreted into breast milk. Based on more than 200 mother and child pairs treated for HIV, serum concentrations of lamivudine in breastfed infants of treated mothers were low (less than 4% of maternal serum concentrations) and progressively decreased to undetectable levels when infants reached 24 weeks old. The low levels ingested by the infant are likely to result in sub-optimal antiviral effect. At the time of writing there are no evidence that the low concentrations in human milk leads to adverse reactions in the breastfed 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 https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal cramps
Abdominal pain
Alopecia
Anaemia
Angioedema
Arthralgia
Autoimmune disorders
Autoimmune hepatitis
Behavioural disturbances
Blood disorders
Convulsions
Cough
Diarrhoea
Elevated amylase levels
Fatigue
Fever
Graves' disease
Headache
Hepatitis
Hypertonia
Immune Reactivation/Reconstitution Syndrome
Increase in serum ALT/AST
Insomnia
Lactic acidosis
Malaise
Metabolic disorders
Muscle disorders
Nasal symptoms
Nausea
Neutropenia
Osteonecrosis
Pancreatitis
Paraesthesia
Peripheral neuropathy
Rash
Red cell aplasia
Rhabdomyolysis
Thrombocytopenia
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: February 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, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Epivir 150 mg and 300 mg film-coated tablets. ViiV Healthcare UK Ltd. Revised February 2019.
Summary of Product Characteristics: Epivir oral solution. ViiV Healthcare UK Ltd. Revised February 2019.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 09 May 2019

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
Lamivudine Last revised: 10 March, 2015.
Last accessed: 18 February, 2016.