Chemical formula: C₈H₁₁N₃O₃S Molecular mass: 229.256 g/mol PubChem compound: 60825
Lamivudine interacts in the following cases:
Lamivudine concentrations are increased in patients with moderate – severe renal impairment due to decreased clearance. The dose should therefore be adjusted, using oral solution presentation of lamivudine for patients whose creatinine clearance falls below 30 ml/min (see tables).
Dosing recommendations – Adults, adolescents and children (weighing at least 25 kg):
| Creatinine clearance (ml/min) | First dose | Maintenance dose |
|---|---|---|
| ≥50 | 300 mg or 150 mg | 300 mg once daily or 150 mg twice daily |
| 30 - <50 | 150 mg | 150 mg once daily |
| <30 As doses below 150 mg are needed the use of the oral solution is recommended | ||
| 15 to <30 | 150 mg | 100 mg once daily |
| 5 to <15 | 150 mg | 50 mg once daily |
| <5 | 50 mg | 25 mg once daily |
There are no data available on the use of lamivudine in children with renal impairment. Based on the assumption that creatinine clearance and lamivudine clearance are correlated similarly in children as in adults; it is recommended that the dosage in children with renal impairment be reduced according to their creatinine clearance by the same proportion as in adults. The lamivudine 10 mg/mL oral solution may be the most appropriate formulation to achieve the recommended dose in children with renal impairment aged at least 3 months and weighing less than 25kg.
Dosing recommendations – Children aged at least 3 months and weighing less than 25 kg:
| Creatinine clearance (ml/min) | First dose | Maintenance dose |
|---|---|---|
| ≥50 | 10 mg/kg or 5 mg/kg | 10 mg/kg once daily or 5 mg/kg twice daily |
| 30 to <50 | 5 mg/kg | 5 mg/kg once daily |
| 15 to <30 | 5 mg/kg | 3.3 mg/kg once daily |
| 5 to <15 | 5 mg/kg | 1.6 mg/kg once daily |
| <5 | 1.6 mg/kg | 0.9 mg/kg once daily |
Administration of trimethoprim/sulfamethoxazole 160 mg/800 mg results in a 40% increase in lamivudine exposure, because of the trimethoprim component; the sulfamethoxazole component did not interact. However, unless the patient has renal impairment, no dosage adjustment of lamivudine is necessary. Lamivudine has no effect on the pharmacokinetics of trimethoprim or sulfamethoxazole. When concomitant administration is warranted, patients should be monitored clinically. Co-administration of lamivudine with high doses of co-trimoxazole for the treatment of Pneumocystis jirovecii pneumonia (PCP) and toxoplasmosis should be avoided.
Coadministration of sorbitol solution (3.2 g, 10.2 g, 13.4 g) with a single 300 mg dose of lamivudine oral solution resulted in dose-dependent decreases of 14%, 32%, and 36% in lamivudine exposure (AUC∞) and 28%, 52%, and 55% in the Cmax of lamivudine in adults. When possible, avoid chronic coadministration of lamivudine with medicinal products containing sorbitol or other osmotic acting poly-alcohols or monosaccharide alcohols (e.g. xylitol, mannitol, lactitol, maltitol). Consider more frequent monitoring of HIV-1 viral load when chronic coadministration cannot be avoided.
A modest increase in Cmax (28%) was observed for zidovudine when administered with lamivudine, however overall exposure (AUC) is not significantly altered. Zidovudine has no effect on the pharmacokinetics of lamivudine.
Patients with chronic hepatitis B or C and treated with combination antiretroviral therapy are at an increased risk of severe and potentially fatal hepatic adverse events. In case of concomitant antiviral therapy for hepatitis B or C, please refer also to the relevant product information for these medicinal products.
If lamivudine is discontinued in patients co-infected with hepatitis B virus, periodic monitoring of liver function tests and markers of HBV replication is recommended, as withdrawal of lamivudine may result in an acute exacerbation of hepatitis.
Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy, and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.
As a general rule, when deciding to use antiretroviral agents for the treatment of HIV infection in pregnant women and consequently for reducing the risk of HIV vertical transmission to the newborn, the animal data as well as the clinical experience in pregnant women should be taken into account. Animal studies with lamivudine showed an increase in early embryonic deaths in rabbits but not in rats. Placental transfer of lamivudine has been shown to occur in humans.
More than 1000 outcomes from first trimester and more than 1000 outcomes from second and third trimester exposure in pregnant women indicate no malformative and foeto/neonatal effect. Lamivudine can be used during pregnancy if clinically needed. The malformative risk is unlikely in humans based on those data.
For patients co-infected with hepatitis who are being treated with lamivudine and subsequently become pregnant, consideration should be given to the possibility of a recurrence of hepatitis on discontinuation of lamivudine.
Nucleoside and nucleotide analogues have been demonstrated in vitro and in vivo to cause a variable degree of mitochondrial damage. There have been reports of mitochondrial dysfunction in infants exposed in utero and/or post-natally to nucleoside analogues.
Following oral administration lamivudine was excreted in breast milk at similar concentrations to those found in serum. Based on more than 200 mother/child pairs treated for HIV, serum concentrations of lamivudine in breastfed infants of mothers treated for HIV are very low (<4% of maternal serum concentrations) and progressively decrease to undetectable levels when breastfed infants reach 24 weeks of age. There are no data available on the safety of lamivudine when administered to babies less than three months old. It is recommended that HIV infected women do not breast-feed their infants under any circumstances in order to avoid transmission of HIV.
Studies in animals showed that lamivudine had no effect on fertility.
No studies on the effects on the ability to drive and use machines have been performed.
The following adverse reactions have been reported during therapy for HIV disease with lamivudine.
The adverse reactions considered at least possibly related to the treatment are listed below by body system, organ class and absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Uncommon: Neutropenia and anaemia (both occasionally severe), thrombocytopenia
Very rare: Pure red cell aplasia
Very rare: Lactic acidosis
Common: Headache, insomnia
Very rare: Peripheral neuropathy (or paraesthesia)
Common: Cough, nasal symptoms
Common: Nausea, vomiting, abdominal pain or cramps, diarrhoea
Rare: Pancreatitis, elevations in serum amylase
Uncommon: Transient elevations in liver enzymes (AST, ALT)
Rare: Hepatitis
Common: Rash, alopecia
Rare: Angioedema
Common: Arthralgia, muscle disorders
Rare: Rhabdomyolysis
Common: Fatigue, malaise, fever
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy.
In HIV-infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term combined antiretroviral exposure (CART). The frequency of which is unknown.
1206 HIV-infected paediatric patients aged 3 months to 17 years were enrolled in the ARROW Trial (COL105677), 669 of whom received abacavir and lamivudine either once or twice daily. No additional safety issues have been identified in paediatric subjects receiving either once or twice daily dosing compared to adults.
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