Version May 2024
Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine or discontinued anti-hepatitis B therapy (including lamivudine-HBV). Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue lamivudine and are coinfected with HIV-1 and HBV or who discontinue anti-hepatitis B therapy. If appropriate, initiation of anti-HBV therapy may be warranted.
Lamivudine tablets and oral solution (used to treat HIV-1 infection) contain a higher dose of lamivudine than lamivudine-HBV tablets and oral solution (used to treat chronic hepatitis B infection). Patients with HIV-1 infection should receive only dosage forms appropriate for treatment of HIV-1.
Lamivudine-HBV is not approved for the treatment of HIV-1 infection because the lamivudine dosage in lamivudine-HBV is subtherapeutic and monotherapy is inappropriate for the treatment of HIV-1 infection. HIV-1 resistance may emerge in chronic hepatitis B-infected patients with unrecognized or untreated HIV-1 infection. HIV counseling and testing should be offered to all patients before beginning treatment with lamivudine-HBV and periodically during treatment.
Note: Oral solution is available in 2 concentrations (10 mg/mL [eg, Epivir] and 5 mg/mL [Epivir-HBV]); use extra caution during calculations to ensure accurate mg of lamivudine administered.
HIV-1 perinatal transmission, presumptive treatment; high risk (3-drug regimen): Limited data available:
Note: Therapy should be initiated as soon as possible after birth (within 6 to 12 hours after delivery). Adjust dose throughout course as needed based on PNA. Lamivudine is recommended as part of a 3-drug regimen for empiric treatment of HIV in neonates at high risk of perinatal transmission and also serves as HIV prophylaxis; see guidelines for additional information on high-risk definitions. The full 3-drug regimen may be continued for 2 to 6 weeks depending on nucleic acid test results, maternal viral load at delivery, and additional risk factors for HIV transmission; zidovudine should be continued for 6 weeks even if the other two drugs are discontinued sooner (HHS [perinatal] 2023).
GA ≥32 weeks:
PNA <4 weeks: Oral solution: Oral: 2 mg/kg/dose twice daily (HHS [perinatal] 2023).
PNA 4 to 6 weeks: Oral solution: Oral: 4 mg/kg/dose twice daily (HHS [perinatal] 2023).
HIV-1 infection, treatment: Limited data available (HHS [pediatric] 2023; HHS [perinatal] 2023): Note: Use in combination with other antiretroviral (ARV) agents; adjust dose throughout course as needed based on PNA. Evaluate gene mutation and ARV resistance patterns (refer to https://www.iasusa.org and https://hivdb.stanford.edu for more information).
GA ≥32 weeks:
PNA <4 weeks: Oral solution: Oral: 2 mg/kg/dose twice daily.
PNA ≥4 weeks: Oral solution: Oral: 4 mg/kg/dose twice daily.
HIV-1 nonoccupational (nonperinatal) postexposure prophylaxis (nPEP): Limited data available: Note: Initiate therapy within 72 hours of exposure and continue for 28 days; use in combination with other ARV agents:
Neonates: Oral solution: Oral: 2 mg/kg/dose twice daily (HHS [nPEP] 2016).
Dosing adjustment in renal impairment: Insufficient data exist to recommend specific dosing adjustments for renal impairment; drug is renally eliminated; consider reducing the dose or increasing the dosing interval; use with caution; monitor closely.
Note: Oral solution is available in 2 concentrations (10 mg/mL [eg, Epivir] and 5 mg/mL [Epivir-HBV]); use extra caution during calculations to ensure accurate mg of lamivudine administered.
HIV-1 infection, treatment: Use in combination with other antiretroviral agents; evaluate gene mutation and antiretroviral resistance patterns (refer to https://www.iasusa.org and https://hivdb.stanford.edu for more information).
Infants <3 months: Limited data available:
Weight-directed dosing: Oral solution: Oral: 4 mg/kg/dose twice daily (HHS [pediatric] 2023; Tremoulet 2007).
Fixed dosing (HHS [pediatric] 2023): Oral solution:
3 to <6 kg: Oral: 30 mg twice daily.
6 to <10 kg: Oral: 40 mg twice daily.
10 to <14 kg: Oral: 60 mg twice daily.
Infants ≥3 months to Children <3 years:
Weight-directed dosing: Oral solution: Oral: 5 mg/kg/dose twice daily; maximum dose: 150 mg/dose (HHS [pediatric] 2023).
Fixed dosing: Limited data available (HHS [pediatric] 2023): Oral solution:
3 to <6 kg: Oral: 30 mg twice daily.
6 to <10 kg: Oral: 40 mg twice daily.
10 to <14 kg: Oral: 60 mg twice daily.
Children ≥3 years and Adolescents: Note: Scored tablet is preferred formulation in patients weighing ≥14 kg who are able to swallow a solid oral dosage form.
Twice-daily dosing:
Oral tablet:
Fixed dosing: For patients weighing ≥14 kg who are able to swallow tablets (using scored 150 mg tablets):
14 to <20 kg: Oral: 75 mg (1/2 tablet) twice daily.
20 to <25 kg: Oral: 75 mg (1/2 tablet) in the morning and 150 mg (1 tablet) in the evening.
≥25 kg: Oral: 150 mg (1 tablet) twice daily.
Oral solution:
Weight-directed dosing: Oral: 5 mg/kg/dose twice daily; maximum dose: 150 mg/dose.
Fixed dosing (HHS [pediatric] 2023):
3 to <6 kg: Oral: 30 mg twice daily.
6 to <10 kg: Oral: 40 mg twice daily.
10 to <14 kg: Oral: 60 mg twice daily.
Once-daily dosing: Note: Not recommended as initial therapy in children. Patients can be transitioned to once-daily treatment with the oral solution or tablet after they are stable on twice-daily treatment for ≥36 weeks with an undetectable viral load and stable CD4 count (HHS [pediatric] 2023).
Oral tablet: Weight-band dosing for patients ≥14 kg who are able to swallow tablets:
14 to <20 kg: Scored tablets: Oral: 150 mg (1 tablet) once daily.
20 to <25 kg: Scored tablets: Oral: 225 mg (1 plus 1/2 tablet) once daily.
≥25 kg: Scored tablets or nonscored tablets: Oral: 300 mg once daily.
Oral solution: Oral: 10 mg/kg/dose once daily; maximum dose: 300 mg/dose.
HIV-1 nonoccupational postexposure prophylaxis (nPEP): Limited data available: Note: Initiate therapy within 72 hours of exposure and continue for 28 days in combination with other retroviral agents (HHS [nPEP] 2016):
Infants, Children, and Adolescents <16 years:
Weight-directed dosing: Oral solution: Oral: 4 mg/kg/dose twice daily has been recommended (maximum dose: 150 mg/dose) (HHS [nPEP] 2016); however, based on newer pharmacokinetic data, a higher dose of 5 mg/kg/dose twice daily is recommended for HIV treatment in patients ≥3 months of age (HHS [pediatric] 2023).
Fixed dosing: Oral tablet: For patients ≥14 kg who are able to swallow tablets (scored 150 mg tablets):
14 to <20 kg: Oral: 75 mg (1/2 tablet) twice daily.
20 to <25 kg: Oral: 75 mg (1/2 tablet) in the morning and 150 mg (1 tablet) in the evening.
≥25 kg: Oral: 150 mg (1 tablet) twice daily.
Adolescents ≥16 years: Oral solution or tablet:
<50 kg: Oral: 4 mg/kg/dose twice daily; maximum dose: 150 mg/dose.
≥50 kg: Oral: 150 mg twice daily or 300 mg once daily.
Hepatitis B, treatment (alternative agent): Note: Patients coinfected with HIV should receive dosages according to HIV treatment recommendations (HHS [OI pediatric] 2022).
Epivir HBV: Children ≥2 years and Adolescents: Oral: 3 mg/kg/dose once daily; maximum dose: 100 mg/dose (manufacturer's labeling). In trials, oral antivirals were continued for 1 to 4 years; hepatitis B e antigen (HBeAg) seroconversion has been suggested as a therapeutic end point followed by an additional 12 months of consolidation (AASLD [Terrault 2018]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
HIV-1 infection:
Manufacturer's labeling: Epivir:
Infants, Children, and Adolescents <25 kg: There are no dosage adjustments provided in the manufacturer's labeling. Consider reducing the dose or increasing the dosing interval; use with caution; monitor closely. Note: Guidelines recommend dosage adjustment, though specific recommendations are not provided (HHS [pediatric] 2023).
Adolescents ≥25 kg:
CrCl ≥50 mL/minute: No adjustment necessary.
CrCl 30 to 49 mL/minute: Oral: 150 mg once daily.
CrCl 15 to 29 mL/minute: Oral: 150 mg first dose, then 100 mg once daily.
CrCl 5 to 14 mL/minute: Oral: 150 mg first dose, then 50 mg once daily.
CrCl <5 mL/minute: Oral: 50 mg first dose, then 25 mg once daily.
Intermittent hemodialysis or peritoneal dialysis: No additional doses are required; negligible amounts are removed by 4-hour hemodialysis or peritoneal dialysis.
Chronic hepatitis B:
Epivir-HBV: Children ≥2 years and Adolescents: There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling (insufficient data). Based on recommendations in adults, dosage should be reduced.
Infants, Children, and Adolescents: No dosage adjustment necessary (HHS [pediatric] 2023). Safety and efficacy have not been established in patients with decompensated liver disease.
(For additional information see "Lamivudine: Drug information")
HIV-1 infection, treatment (Epivir, 3TC [Canadian product]): Oral (use in combination with other antiretroviral agents): 150 mg twice daily or 300 mg once daily
Note: Lamivudine, in combination with abacavir, and either efavirenz, raltegravir, boosted atazanavir, or boosted darunavir, is not recommended in patients with pretreatment HIV RNA ≥100,000 copies/mL (HHS [adult] 2019).
HIV-1 nonoccupational postexposure prophylaxis (nPEP) (Epivir) (off-label use) ( HHS [nPEP] 2016): Oral: Note: Initiate therapy within 72 hours of exposure and continue for 28 days; use in combination with other antiretroviral agents.
CrCl ≥60 mL/minute: Lamivudine is not a component of the recommended antiretroviral regimens for these patients.
CrCl <60 mL/minute: Dose should be adjusted based on renal function.
Hepatitis B, treatment (Epivir HBV, Heptovir [Canadian product]): Oral: 100 mg once daily
Treatment duration (AASLD practice guidelines): Treatment duration for nucleos(t)ide analog–based therapy (eg, lamivudine) is variable and influenced by HBeAg status, duration of HBV suppression, and presence of cirrhosis/decompensation (AASLD [Terrault 2016):
Patients without cirrhosis:
Hepatitis B e antigen (HBeAg) positive immune-active chronic hepatitis: Treat until HBeAg seroconversion; after seroconversion, prolonged duration of therapy is often required in patients treated with nucleos(t)ide analogues. Optimal duration is unknown; however, consolidation therapy is generally a minimum of 12 months of persistently normal ALT and undetectable serum HBV DNA levels after HBeAg seroconversion
HBeAg-negative immune-active chronic hepatitis: Indefinite antiviral therapy is suggested unless there is competing rationale for discontinuation (risk/benefit decision); treatment discontinuation may be considered in patients with loss of HBsAg; however, there is insufficient evidence to guide decisions in these patients.
Patients with cirrhosis:
HBeAg-positive immune-active chronic hepatitis: In patients who seroconvert on therapy, continue antiviral therapy indefinitely due to concerns with decompensation and death, unless there is a strong competing rationale for discontinuation.
HBeAg-negative immune-active chronic hepatitis: Treatment discontinuation is not recommended due to potential for decompensation and death (limited data).
Viral breakthrough ( AASLD practice guidelines) : Patients with confirmed viral breakthrough (HBV DNA ≥100 units/mL with previously undetectable levels [<10 units/mL] or >1 log increase in HBV DNA) should either be switched to an alternative antiviral monotherapy agent with a high genetic barrier to resistance or receive a second antiviral agent with a complementary resistance profile; consult current clinical practice guidelines for recommended agents (AASLD [Terrault 2016]).
Hepatitis B/HIV coinfection, treatment (in patients with both infections requiring treatment) (Epivir): Note: The formulation and dosage of Epivir HBV are not appropriate for patients infected with both HBV and HIV.
Oral: 150 mg twice daily or 300 mg once daily, in combination with tenofovir and other appropriate antiretrovirals (HHS [adult] 2019).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Oral:
HIV-1 infection:
|
CrCl |
Manufacturer's labelinga,b |
Alternative recommendationb |
|---|---|---|
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a Refers to the manufacturer's labeling of lamivudine as an individual component of an antiretroviral regimen. Lamivudine-containing combination products may have important differences (refer to combination product monographs for specific dosing recommendations). | ||
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b Lamivudine is primary eliminated by the kidney, and dose adjustments are generally recommended to prevent accumulation (Bouazza 2014; manufacturer's labeling). However, since lamivudine is usually well-tolerated, and the available strengths can make recommended dose adjustments difficult to achieve, the risks and benefits of the alternative recommendation (ie, no [or limited] dose adjustment) should be weighed on an individualized basis, with close monitoring for GI (eg, nausea) and hematologic (eg, anemia, neutropenia) side effects, as well as symptoms that could suggest more rare side effects (eg, lactic acidemia, pancreatitis, rhabdomyolysis) (Fischetti 2018; Mounzer 2021; Wood 2021). | ||
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c HHS [adult] 2021; Mounzer 2021. | ||
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d Very limited data; however, when potential benefits outweigh the risks, may consider using with close monitoring for side effects (Fischetti 2018; IDSA [Lucas 2014]; Wood 2021). | ||
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e Although lamivudine is removed by hemodialysis, its large Vd results in a minimal effect of hemodialysis on AUC (Bohjanen 2002). Supplemental dosing not needed (manufacturer's labeling); however, dosing after hemodialysis is recommended by some experts (HHS [adult] 2021). | ||
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f Asari 2007; Bohjanen 2002; IDSA [Lucas 2014]. | ||
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≥50 mL/minute |
No dose adjustment necessary |
No dose adjustment necessaryc |
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30 to <50 mL/minute |
150 mg once daily | |
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15 to <30 mL/minute |
150 mg on day 1, followed by 100 mg once daily |
150 mg on day 1, followed by 100 or 150 mg once daily (depending on available tablet strengths)d |
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5 to <15 mL/minute |
150 mg on day 1, followed by 50 mg once daily | |
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<5 mL/minute |
50 mg on day 1, followed by 25 mg once daily |
100 or 150 mg once daily (depending on available tablet strengths)d |
|
Hemodialysis, intermittent (thrice weekly)e |
50 mg on day 1, followed by 25 mg once dailyf | |
|
Peritoneal dialysis |
50 mg on day 1, followed by 25 mg once dailyf | |
Hepatitis B infection:
|
CrCl |
Manufacturer's labeling |
Alternative recommendationa |
|---|---|---|
|
a Lamivudine is primary eliminated by the kidney, and dose adjustments are generally recommended to prevent accumulation (Bouazza 2014; manufacturer's labeling). However, since lamivudine is usually well-tolerated, and the available strengths can make recommended dose adjustments difficult to achieve, the risks and benefits of the alternative recommendation (ie, no dose adjustment) should be weighed on an individualized basis, with close monitoring for GI (eg, nausea) and hematologic (eg, anemia, neutropenia) side effects, as well as symptoms that could suggest more rare side effects (eg, lactic acidemia, pancreatitis, rhabdomyolysis) (Fischetti 2018; Mounzer 2021; Wood 2021). | ||
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b Expert opinion extrapolated from studies in the HIV-1 population (Fischetti 2018; Mounzer 2021; Wood 2021). | ||
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c Although lamivudine is removed by hemodialysis, its large Vd results in a minimal effect of hemodialysis on AUC (Bohjanen 2002). Supplemental dosing not needed (manufacturer's labeling); however, dosing after hemodialysis is recommended by some experts (HHS [adult] 2021). | ||
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d Asari 2007; Bohjanen 2002; expert opinion. | ||
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≥50 mL/minute |
No dose adjustment necessary |
No dose adjustment necessaryb |
|
30 to <50 mL/minute |
100 mg on day 1, followed by 50 mg once daily | |
|
15 to <30 mL/minute |
100 mg on day 1, followed by 25 mg once daily | |
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5 to <15 mL/minute |
35 mg on day 1, followed by 15 mg once daily | |
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<5 mL/minute |
35 mg on day 1, followed by 10 mg once daily | |
|
Hemodialysis, intermittent (thrice weekly)c |
35 mg on day 1, followed by 10 mg once dailyd | |
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Peritoneal dialysis |
35 mg on day 1, followed by 10 mg once dailyd | |
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and side effects (eg, GI, hematologic) due to drug accumulation is important.
Oral:
HIV: No pharmacokinetic data available. May consider a dose of 150 mg once daily, as lamivudine is well-tolerated in subjects with impaired kidney function and some removal of lamivudine is expected with CRRT (expert opinion).
Hepatitis B: No pharmacokinetic data available. May consider a dose of 100 mg on day 1, followed by 50 mg once daily, as lamivudine is well-tolerated in subjects with impaired kidney function and some removal of lamivudine is expected with CRRT (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and side effects (eg, GI, hematologic) due to drug accumulation is important.
Oral:
HIV: No pharmacokinetic data available. May consider a dose of 150 mg once daily, as lamivudine is well-tolerated in subjects with impaired kidney function and some removal of lamivudine is expected with PIRRT. When scheduled dose falls on a PIRRT day, administer after PIRRT session (expert opinion).
Hepatitis B: No pharmacokinetic data available. May consider a dose of 100 mg on day 1, followed by 50 mg once daily, as lamivudine is well-tolerated in subjects with impaired kidney function and some removal of lamivudine is expected with PIRRT. When scheduled dose falls on a PIRRT day, administer after PIRRT session (expert opinion).
No dosage adjustment necessary. However, has not been studied in the setting of decompensated liver disease.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence data include patients on combination therapy with other antiretroviral agents.
>10%:
Central nervous system: Headache (35%), fatigue (≤27%), malaise (≤27%), paresthesia (≤15%), peripheral neuropathy (≤15%), neuropathy (12%), insomnia (≤11%), sleep disorder (≤11%)
Dermatologic: Skin rash (9% to 12%)
Gastrointestinal: Nausea (≤33%), diarrhea (adults: 14% to 18%, children: 8%), pancreatitis (≤18%; higher percentage in pediatric patients), sore throat (13%), vomiting (≤13%)
Hematologic & oncologic: Neutropenia (7% to 15%)
Hepatic: Increased serum alanine aminotransferase (adults: 4% to 27%, children: 1%), hepatomegaly (children: 11%, adults: <1%)
Infection: infection (25%; includes ear, nose, and throat)
Neuromuscular & skeletal: Musculoskeletal pain (12%)
Respiratory: Nasal signs and symptoms (8% to 20%), cough (15% to 18%)
Miscellaneous: Fever (children: 25%, adults: ≤10%)
1% to 10%:
Central nervous system: Dizziness (10%), chills (≤10%), depression (9%)
Endocrine & metabolic: Increased amylase (2% to 4%)
Gastrointestinal: Increased serum lipase (adults: 10%, children: 3%), anorexia (≤10%), decreased appetite (≤10%), abdominal pain (9%), abdominal cramps (6%), stomatitis (children: 6%, adults: <1%), dyspepsia (5%)
Hematologic & oncologic: Lymphadenopathy (children: 9%), splenomegaly (children 5%, adults <1%), thrombocytopenia (adults: 4%, children: 1%), decreased hemoglobin (2% to 4%)
Hepatic: Increased serum aspartate aminotransferase (2% to 4%)
Neuromuscular & skeletal: Increased creatine phosphokinase (9%), myalgia (8%), arthralgia (5%)
Otic: Ear disease (children: 7%)
Respiratory: Abnormal breath sounds (children: ≤7%; adults: <1%), wheezing (children: ≤7%, adults: <1%)
<1%, postmarketing, and/or case reports: Alopecia, anaphylaxis, anemia, asthenia, cramps, exacerbation of hepatitis B, hyperbilirubinemia, hyperglycemia, immune reconstitution syndrome, lactic acidosis, liver steatosis, muscle cramps, myasthenia, pruritus, pure red cell aplasia, redistribution of body fat, rhabdomyolysis, urticaria
Hypersensitivity to lamivudine or any component of the formulation
Concerns related to adverse effects:
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues, including fatal cases; suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. Use with caution in patients with risk factors for liver disease (risk may be increased with female gender or obesity) and discontinue in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Pancreatitis: Has been reported, particularly in HIV-infected pediatric patients with a history of nucleoside use. Discontinue treatment if signs of symptoms of pancreatitis occur.
Disease-related concerns:
• Chronic hepatitis B: [US Boxed Warning]: Severe acute exacerbations of hepatitis B (some fatal) have been reported in patients with HBV or HIV/HBV coinfection who have discontinued lamivudine; hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuation. Initiate antihepatitis B (HBV) medications if clinically appropriate.
• Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended.
• Resistance:
- HIV: [US Boxed Warning]: HIV-1 resistance may emerge in chronic hepatitis B-infection patients with unrecognized or untreated HIV-1 infection. Counseling and HIV testing should be offered to all patients before beginning treatment with lamivudine for hepatitis B and then periodically during treatment. Lamivudine dosing for hepatitis B is subtherapeutic if used for HIV-1 infection treatment. Lamivudine monotherapy is not appropriate for HIV-1 infection treatment. Lamivudine resistant HIV-1 can develop rapidly and limit treatment options if used in unrecognized or untreated HIV-1 infection or if a patient becomes coinfected during HBV treatment. Lamivudine dosing for hepatitis B is also subtherapeutic if used for HIV-1/HBV coinfection treatment. If lamivudine is chosen as part of a HIV-1 treatment regimen in coinfected patients, the higher lamivudine dosage indicated for HIV-1 therapy should be used, with other drugs, in an appropriate combination regimen.
- HBV: Patients treated with lamivudine-HBV with YMDD-mutant HBV showed diminished treatment response (lower rates of HBeAg seroconversion and HBeAg loss, more frequent return of positive HBV DNA, more frequent ALT elevations) compared to patients without evidence of YMDD substitutions. Emergence of lamivudine resistant HBV variants has also been reported in HIV-1/HBV coinfected patients who have received lamivudine-containing antiretroviral regimens.
Dosage form specific issues:
• Appropriate product selection: Epivir HBV: [US Boxed Warning]: Do not use Epivir HBV tablets or Epivir HBV oral solution for the treatment of HIV.
• Oral solution: Use of lamivudine oral solution has been associated with lower rates of virologic suppression, lower plasma lamivudine exposure, and increased rates of resistance when compared to lamivudine tablets in pediatric clinical trials. Lamivudine scored tablet is the preferred formulation for HIV-1 infected pediatric patients weighing ≥14 kg and for whom a solid dosage form is appropriate; consider more frequent monitoring of HIV-1 viral load if oral solution is used.
• Sucrose: Lamivudine oral solutions contains 3 g of sucrose/15 mL; advise diabetic patients of sucrose content.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007).
Other warnings/precautions:
• Appropriate use:
-HIV: Do not use as monotherapy in treatment of HIV. Treatment of HIV in patients with unrecognized/untreated HBV may lead to rapid HBV resistance; HIV-infected patients should be screened for hepatitis B prior to starting lamivudine HIV therapy. Lamivudine combined with emtricitabine is not recommended as a dual-nucleoside reverse transcriptase inhibitor (NRTI) combination due to similar resistance patterns and negligible additive antiviral activity (HHS [adult] 2019).
- HBV: Current clinical hepatitis B practice guidelines do not recommend lamivudine for initial use in the management of chronic HBV due to low barrier to resistance; other antiviral agents with a high genetic barrier to drug resistance are preferred (eg, tenofovir or entecavir) (AASLD [Terrault 2016]).
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis, which occurred in 14% of patients in one open-label, dose-escalation trial; discontinue lamivudine therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. Use with extreme caution and only if there is no satisfactory alternative therapy in pediatric patients with a history of pancreatitis or other significant risk factors for the development of pancreatitis. Infants receiving lamivudine in combination with nelfinavir (powder no longer available in the United States) and zidovudine for prevention of perinatal transmission experienced a higher rate of neutropenia compared to zidovudine/nevirapine combination or zidovudine alone (27.5% vs 14.9% vs 16.4%). Other studies in infants also reported significantly higher rates of anemia and neutropenia when lamivudine was administered in combination with zidovudine (HHS [perinatal] 2023).
In pediatric subjects, the bioavailability of the oral solution is lower than that of the tablets, whereas there is no difference in adults. The exact cause has not been fully defined; however, concurrent use of medications with sorbitol-containing dosage forms has been reported as a possible explanation; decreases in lamivudine absorption in the presence of sorbitol has been observed in pharmacokinetic trials; expert dosing recommendations have been adjusted to account for this possible alteration (HHS [pediatric] 2023). If possible, avoid concomitant use of lamivudine solution with sorbitol-containing dosage forms (eg, abacavir, some OTC medication preparations); if necessary, patients should be closely monitored for efficacy.
Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults, including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Oral:
Epivir: 10 mg/mL (240 mL) [contains methylparaben, propylene glycol, propylparaben; strawberry-banana flavor]
Epivir HBV: 5 mg/mL (240 mL [DSC]) [contains methylparaben, propylene glycol, propylparaben; strawberry-banana flavor]
Generic: 10 mg/mL (240 mL)
Tablet, Oral:
Epivir: 150 mg [scored]
Epivir: 300 mg
Epivir HBV: 100 mg [DSC]
Generic: 100 mg, 150 mg, 300 mg
Yes
Solution (Epivir Oral)
10 mg/mL (per mL): $0.55
Solution (lamiVUDine Oral)
10 mg/mL (per mL): $0.50 - $2.25
Tablets (Epivir Oral)
150 mg (per each): $8.31
300 mg (per each): $16.63
Tablets (lamiVUDine Oral)
100 mg (per each): $16.09 - $16.11
150 mg (per each): $7.15 - $7.16
300 mg (per each): $14.31 - $14.32
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Oral:
Heptovir: 5 mg/mL ([DSC]) [contains methylparaben, propylene glycol, propylparaben]
3TC: 10 mg/mL (240 mL) [contains methylparaben, propylene glycol, propylparaben]
Tablet, Oral:
Heptovir: 100 mg [DSC] [contains polysorbate 80]
3TC: 150 mg, 300 mg [contains polysorbate 80]
Generic: 100 mg, 150 mg, 300 mg
Oral: May be administered without regard to meals.
Oral: May be administered without regard to meals.
Oral solution:
Epivir: Store at 25°C (77°F) tightly closed.
Epivir HBV: Store at 20°C to 25°C (68°F to 77°F) tightly closed.
Tablet: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).
Epivir: Treatment of HIV-1 infection in combination with other antiretroviral agents (FDA approved in ages ≥3 months and adults). Note: HIV regimens consisting of three active antiretroviral agents from at least two classes are recommended. Has also been used for nonoccupational HIV postexposure prophylaxis (nPEP) and prevention of perinatal of HIV infection.
Epivir-HBV: Treatment of chronic hepatitis B infection associated with evidence of hepatitis B viral replication and active liver inflammation (FDA approved in ages ≥2 years and adults).
LamiVUDine may be confused with lamoTRIgine
Epivir may be confused with Combivir
Substrate of OCT1, OCT2; Inhibits MRP2
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
Erdafitinib: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Consider alternatives to this combination when possible. If combined, monitor for increased effects/toxicities of OCT2 substrates and consider OCT2 substrate dose reductions when appropriate. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with MATE1/2-K substrates when possible. If combined, monitor for increased MATE1/2-K substrate toxicities. Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of fexinidazole with OCT2 substrates when possible. If combined, monitor for increased OCT2 substrate toxicities. Risk D: Consider therapy modification
Foslevodopa: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Risdiplam: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of risdiplam with MATE substrates if possible. If the combination cannot be avoided, monitor closely for adverse effects. Consider a reduced dose of the MATE substrate according to that substrate's labeling if appropriate. Risk D: Consider therapy modification
Sorbitol: May decrease the serum concentration of LamiVUDine. Management: When possible, avoid chronic coadministration of sorbitol-containing solutions with lamivudine, but if this combination cannot be avoided, monitor patients more closely for possible therapeutic failure associated with decreased lamivudine exposure. Risk D: Consider therapy modification
Tafenoquine: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling. Risk D: Consider therapy modification
Tafenoquine: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Risk D: Consider therapy modification
Trimethoprim: May increase the serum concentration of LamiVUDine. Risk C: Monitor therapy
Food decreases the rate of absorption and Cmax; however, there is no change in the systemic AUC. Management: Administer with or without food.
Some products may contain sucrose.
Contraception is not required to initiate or continue antiretroviral therapy.
The US Department of Health and Human Services (HHS) perinatal HIV guidelines consider lamivudine a preferred nucleoside reverse transcriptase inhibitor for patients with HIV who are not yet pregnant but are trying to conceive.
Maximum viral suppression sustained below the limits of detection prior to conception is recommended for all persons with HIV who are planning a pregnancy. Optimization of the health of the person who will become pregnant is recommended. Selection of or changes to a specific antiretroviral regimen prior to pregnancy should be done as part of a shared decision-making process. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender-diverse people assigned female sex at birth.
Health care providers caring for couples planning a pregnancy when one or both partners are diagnosed with HIV may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).
Lamivudine has a high level of transfer across the human placenta.
No increased risk of overall teratogenic effects has been observed following first trimester exposure according to data collected by the antiretroviral pregnancy registry. Maternal antiretroviral therapy (ART) may be associated with adverse pregnancy outcomes, including preterm birth, low birth weight, and small-for-gestational-age infants. Actual risks may be influenced by maternal factors such as disease severity, GA at initiation of therapy, and specific ART regimen; therefore, close fetal monitoring is recommended. Based on data collected by the antiretroviral pregnancy registry, the risk of spontaneous abortions, induced abortions, and preterm birth is less in lamivudine-containing regimens compared with regimens without lamivudine. Because there is clear benefit to appropriate treatment, maternal ART should not be withheld due to concerns for adverse neonatal outcomes. Long-term follow-up is recommended for all infants exposed to antiretroviral medications; children not diagnosed with HIV but who were exposed to ART in utero or as a neonate and develop significant organ system abnormalities of unknown etiology (particularly of the CNS or heart) should be evaluated for potential metabolic dysfunction.
The US Department of Health and Human Services (HHS) perinatal HIV guidelines consider lamivudine a preferred nucleoside reverse transcriptase inhibitor (NRTI) for pregnant patients with HIV who are antiretroviral-naive, who have had ART therapy in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). In addition, patients who become pregnant while taking lamivudine may continue if viral suppression is effective and the regimen is well tolerated.
The HHS perinatal HIV guidelines consider lamivudine in combination with either abacavir, tenofovir alafenamide, or tenofovir disoproxil fumarate to be a preferred NRTI backbone for initial therapy in antiretroviral-naive pregnant patients. The lamivudine/abacavir backbone is not recommended with atazanavir/ritonavir or efavirenz if pretreatment HIV RNA is >100,000 copies/mL. In addition, the HHS perinatal HIV guidelines consider lamivudine in combination with abacavir and dolutegravir to be a preferred integrase strand transfer inhibitor regimen for initial therapy in antiretroviral-naive patients who are pregnant. The guidelines consider lamivudine with zidovudine to be an alternative NRTI backbone for initial therapy in antiretroviral-naive pregnant patients. The guidelines also consider lamivudine plus tenofovir disoproxil fumarate or tenofovir alafenamide a recommended dual NRTI backbone in regimens for HIV/hepatitis B virus (HBV)-coinfected patients who are pregnant.
Lamivudine is also a preferred component of an initial regimen when early (acute/recent) HIV infection is detected during pregnancy; genotyping may be required if the person had prior use of long-acting cabotegravir for preexposure prophylaxis.
The pharmacokinetics of lamivudine during pregnancy are not significantly altered, and dose adjustment is not required.
ART is recommended for all pregnant people with HIV infection to maximize their health, maintain the viral load below the limit of detection, and reduce the risk of perinatal transmission. Selection of or changes to a specific antiretroviral regimen during pregnancy should be done as part of a shared decision-making process. Patients on fully suppressive regimens prior to pregnancy generally may continue the same regimen considering known pregnancy outcomes and pharmacokinetic data. Monitoring of patients who are pregnant is more frequent than in patients who are not pregnant. ART initiated during pregnancy can be modified after delivery. In most cases, recommendations from the HHS perinatal HIV guidelines (based on data obtained from cisgender women) can be applied to transgender and gender-diverse people assigned female sex at birth.
The American Association for the Study of Liver Diseases chronic hepatitis B treatment guidelines provide recommendations for the management of hepatitis B-infected patients who are pregnant (not coinfected with HIV). Patients meeting standard indications for HBV therapy should be treated; patients without standard indications but with an HBV DNA >200,000 units/mL in the second trimester should consider treatment to reduce the risk of perinatal transmission. Lamivudine is one of the antivirals that has been studied in pregnancy, with most studies initiating antiviral therapy at 28 to 32 weeks gestation and discontinuing antiviral therapy between birth to 3 months postpartum (monitor for ALT flares every 3 months for 6 months following discontinuation). There are insufficient long-term safety data in infants born to mothers who took antiviral agents during pregnancy (AASLD [Terrault 2018]).
Data collection to monitor pregnancy and infant outcomes following exposure to ART are ongoing. Health care providers should enroll all patients exposed to antiretroviral medications during pregnancy in the Antiretroviral Pregnancy Registry (1-800-258-4263). Enrollment should be done as early in pregnancy as possible.
Health care providers caring for pregnant patients with HIV infection and their infants may contact the National Perinatal HIV Hotline (1-888-448-8765) for clinical consultation (HHS [perinatal] 2023).
HIV: General recommendations: Management of HIV infection requires extensive monitoring; refer to current guidelines (https://clinicalinfo.hiv.gov/en/guidelines) for additional guidance. Antiretroviral (ARV) drug-resistance testing is recommended before initiation of therapy in treatment-naive patients and before changing regimens in patients for whom treatment has failed. After initiation of or change in ARV therapy regimen, pediatric patients should be evaluated for clinical adverse effects and treatment adherence at 1 to 2 weeks, and laboratory testing for drug toxicity should occur at 2 to 4 weeks; monitor for therapy adherence, effectiveness, and toxicities every 3 to 4 months.
Drug-specific monitoring: Frequency may vary based on several factors including age, concomitant therapy, and clinical response; refer to current guidelines for additional information.
Screen for hepatitis B prior to starting therapy (in patients who previously demonstrated no immunity to hepatitis B). For patients with hepatitis B coinfection, monitor hepatic function and hepatitis B viral load for several months after therapy with lamivudine is stopped.
Serum electrolytes (including anion gap), SCr, lipid profiles (baseline and periodically with therapy or if clinical presentation indicates need); serum lactate (if clinical presentation indicates need). For neonates and infants receiving lamivudine in combination with zidovudine as presumptive HIV therapy, monitor Hgb and neutrophils (at baseline and, if therapy continues, 4 weeks after initiation) (HHS [perinatal] 2023).
Lamivudine is a cytosine analog. In vitro, lamivudine is triphosphorylated, the principle mode of action is inhibition of HIV reverse transcription via viral DNA chain termination; inhibits RNA- and DNA-dependent DNA polymerase activities of reverse transcriptase. In hepatitis B, the monophosphate form of lamivudine is incorporated into the viral DNA by hepatitis B virus polymerase, resulting in DNA chain termination.
Absorption: Rapid.
Distribution: Into extravascular spaces.
Children (n=38): CSF concentrations were 14.2% ± 7.9% of the serum concentration.
Vd: 1.3 ± 0.4 L/kg.
Protein binding: Plasma: <36%.
Metabolism: Minor; only known metabolite is trans-sulfoxide metabolite.
Bioavailability: Absolute; Cpmax decreased with food although AUC not significantly affected.
Children: Oral solution: 66% ± 26%; relative bioavailability is 40% lower than with tablets.
Adolescents and Adults: Oral solution: 87% ± 13%; Tablet 150 mg: 86% ± 16%.
Half-life:
Intracellular: 10 to 15 hours.
Elimination:
Pediatric patients 4 months to 14 years: 2 ± 0.6 hours.
Adults: 5 to 7 hours; increased with renal impairment.
Time to peak, plasma:
Pediatric patients 0.5 to 17 years: Median: 1.5 hours (range: 0.5 to 4 hours) (Lewis 1996).
Adolescents 13 to 17 years: 0.5 to 1 hour.
Adults: Fed: 3.2 hours; Fasted: 0.9 hours.
Excretion: Primarily urine (majority as unchanged drug); weight-corrected oral clearance is highest at age 2 years, then declines from age 2 to 12 years, where values then remain comparable to adult values.
Altered kidney function: AUC and Cmax are increased.
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