Brand names: Epivir, Epivir-HBV
Drug class: HIV Nucleoside and Nucleotide Reverse Transcriptase Inhibitors
- Reverse Transcriptase Inhibitors
VA class: AM800
Chemical name: (2R-cis) 4-Amino-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone
Molecular formula: C₈H₁₁N₃O₃S
CAS number: 134678-17-4

lamiVUDine is also contained as an ingredient in the following combinations:
Abacavir Sulfate, lamiVUDine, and Zidovudine
lamiVUDine and Zidovudine

Medically reviewed by Drugs.com on Mar 23, 2023. Written by ASHP.

Introduction

Antiretroviral; HIV nucleoside reverse transcriptase inhibitor (NRTI); also has antiviral activity against HBV.

Uses for Lamivudine

Treatment of HIV Infection

Treatment of HIV-1 infection in adults, adolescents, and pediatric patients; used in conjunction with other antiretrovirals.

Used with another NRTI (dual NRTIs) in conjunction with an HIV integrase strand transfer inhibitor (INSTI), HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), or HIV protease inhibitor (PI) in INSTI-, NNRTI-, or PI-based regimens.

For initial treatment in antiretroviral-naive HIV-infected adults and adolescents, experts state that a tenofovir prodrug (either tenofovir alafenamide or tenofovir disoproxil fumarate [tenofovir DF]) and emtricitabine (or lamivudine) is the preferred dual NRTI option for use in most INSTI-, NNRTI-, and PI-based regimens. Abacavir and lamivudine (or emtricitabine) also a recommended dual NRTI option for use in some initial treatment regimens, but use only in those negative for HLA-B*5701.

For initial treatment in antiretroviral-naive pediatric patients, experts state that zidovudine and lamivudine (or emtricitabine) is a preferred dual NRTI option for use in neonates, infants, and children <12 years of age and an alternative dual NRTI option in adolescents ≥12 years of age with sexual maturity rating (SMR) 3. These experts state that abacavir and lamivudine (or emtricitabine) is a preferred dual NRTI option in pediatric patients ≥3 months of age negative for HLA-B*5701, including adolescents ≥12 years of age with SMR 1–3. For adolescents with SMR 3, experts state that the dual NRTI option of tenofovir DF and lamivudine (or emtricitabine) is an alternative dual NRTI option. In special circumstances, tenofovir DF and lamivudine (or emtricitabine) can be used in conjunction with other antiretrovirals for initial treatment regimens in children ≥2 years of age and in adolescents with SMR 1 or 2.

A tenofovir prodrug (tenofovir alafenamide or tenofovir DF) and emtricitabine (or lamivudine) is the preferred dual NRTI option for antiretroviral regimens in HIV-infected patients coinfected with HBV. All 3 NRTIs (tenofovir, emtricitabine, lamivudine) have activity against both HIV and HBV; dual NRTI options that contain only 1 of these 3 NRTIs not recommended in coinfected patients.

Dual NRTI option of zidovudine and lamivudine no longer recommended for initial treatment regimens in nonpregnant antiretroviral-naive HIV-infected adults and adolescents (greater toxicity than currently recommended dual NRTI options), but is recommended as an alternative (not a preferred) dual NRTI option for initial treatment regimens in antiretroviral-naive pregnant women.

Dual NRTI option of didanosine and lamivudine not recommended for initial antiretroviral regimens in adults or adolescents (inferior virologic efficacy, limited clinical trial experience, didanosine-associated toxicities); can be considered in special circumstances for initial treatment regimens in children ≥2 years of age and adolescents with SMR 1 or 2.

Dual NRTI option of stavudine and lamivudine not recommended for initial antiretroviral regimens (toxicity).

Lamivudine/zidovudine fixed combination can be used in adults, adolescents, and pediatric patients weighing ≥30 kg when dual NRTI option of zidovudine and lamivudine indicated; used in conjunction with other antiretrovirals.

Abacavir/lamivudine fixed combination can be used in adults, adolescents, and pediatric patients weighing ≥25 kg when dual NRTI option of abacavir and lamivudine indicated; used in conjunction with other antiretrovirals.

Abacavir/lamivudine/zidovudine fixed combination can be used in adults, adolescents, and pediatric patients weighing ≥40 kg; used alone as a complete treatment regimen or in conjunction with other antiretrovirals. Data limited regarding use in patients with baseline viral loads >100,000 copies/mL.

Abacavir/dolutegravir/lamivudine fixed combination can be used alone as a complete treatment regimen or in conjunction with other antiretrovirals in adults, adolescents, and pediatric patients weighing ≥40 kg.

Triple NRTI regimen of abacavir, lamivudine, and zidovudine not recommended in antiretroviral-naive or antiretroviral experienced patients (inferior antiretroviral activity).

Triple NRTI regimen of abacavir, lamivudine, and tenofovir DF not recommended at any time (high rate of virologic failure).

Prevention of Perinatal HIV Transmission

Empiric HIV therapy^{† [off-label]} in neonates born to HIV-infected women; used in 3-drug empiric regimen (zidovudine, lamivudine, and nevirapine) for prevention of perinatal HIV transmission^{† [off-label]} in neonates at highest risk of HIV acquisition.

Pregnant HIV-infected women: Multiple-drug antiretroviral regimens are standard of care in the US for treatment of HIV infection in pregnant women and for prevention of perinatal HIV transmission. In addition, to further decrease risk of perinatal HIV transmission, experts recommend that all pregnant HIV-infected women with plasma HIV-1 RNA levels >1000 copies/mL (or unknown HIV-1 RNA levels) near delivery receive an intrapartum IV zidovudine prophylaxis regimen initiated at the onset of labor (or 3 hours before scheduled cesarean delivery) and continued until delivery (unless contraindicated). Lamivudine and zidovudine is an alternative dual NRTI option for use in conjunction with other antiretrovirals for treatment of HIV-1 infection in pregnant women (see Pregnancy under Cautions), but is not a component of intrapartum or neonatal prophylaxis regimens recommended in the US for prevention of perinatal HIV transmission.

HIV-exposed neonates: Experts recommend that all neonates born to HIV-infected women (HIV-exposed neonates) receive an antiretroviral regimen (either prophylaxis or empiric HIV therapy) initiated as soon as possible after birth (preferably within 6–12 hours) and continued through 4–6 weeks of age. Select antiretroviral prophylaxis regimen or empiric HIV therapy regimen based on likelihood of perinatal HIV transmission. HIV-exposed neonates at low risk of HIV acquisition (i.e., infants born to mothers who were receiving a recommended multiple-drug antiretroviral regimen during pregnancy with sustained viral suppression near delivery and no concerns related to maternal adherence to the treatment regimen) may receive a 4-week zidovudine prophylaxis regimen used alone. HIV-exposed neonates at higher risk of HIV acquisition (e.g., those born to HIV-infected women who did not receive antepartum or intrapartum antiretrovirals, received only intrapartum antiretrovirals, or received antepartum and intrapartum antiretrovirals with suboptimal viral suppression near delivery) should receive a 2-drug prophylaxis regimen (6-week zidovudine prophylaxis and 3-dose nevirapine prophylaxis). Alternatively, those at highest risk can receive a 3-drug empiric HIV therapy regimen (zidovudine, lamivudine, and nevirapine).

Maternal and neonatal regimens recommended for prevention of perinatal HIV transmission in the US may differ from those used in other countries (e.g., resource-limited countries).

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding antiretroviral treatment of pregnant HIV-infected women and their infants and prevention of perinatal HIV transmission.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)

Postexposure prophylaxis of HIV infection following occupational exposure^{† [off-label]} (PEP) in health-care workers and others exposed via percutaneous injury (e.g., needlestick, cut with sharp object) or mucous membrane or nonintact skin (e.g., chapped, abraded, dermatitis) contact with blood, tissue, or other body fluids that might contain HIV.

USPHS recommends 3-drug regimen of raltegravir in conjunction with emtricitabine and tenofovir DF as the preferred regimen for PEP following occupational exposures to HIV. Several alternative regimens that include an INSTI, NNRTI, or PI and 2 NRTIs (dual NRTIs) also recommended. Preferred dual NRTI option for PEP regimens is emtricitabine and tenofovir DF (may be given as emtricitabine/tenofovir DF fixed combination); alternative dual NRTIs are tenofovir DF and lamivudine, lamivudine and zidovudine (may be given as lamivudine/zidovudine), or zidovudine and emtricitabine.

Management of occupational exposures to HIV is complex and evolving; consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) whenever possible. Do not delay initiation of PEP while waiting for expert consultation.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)

Postexposure prophylaxis of HIV infection following nonoccupational exposure^{† [off-label]} (nPEP) in individuals exposed to blood, genital secretions, or other potentially infectious body fluids that might contain HIV when that exposure represents a substantial risk for HIV transmission.

When nPEP indicated in adults and adolescents ≥13 years of age with normal renal function, CDC states preferred regimen is either raltegravir or dolutegravir used in conjunction with emtricitabine and tenofovir DF (given as emtricitabine/tenofovir DF fixed combination). These experts state preferred nPEP regimen in adults and adolescents ≥13 years of age with impaired renal function (Cl_cr ≤59 mL/minute) is either raltegravir or dolutegravir used in conjunction with zidovudine and lamivudine.

Consult infectious disease specialist, clinician with expertise in administration of antiretroviral agents, and/or the National Clinicians’ Postexposure Prophylaxis Hotline (PEPline at 888-448-4911) if nPEP indicated in certain exposed individuals (e.g., pregnant women, children, those with medical conditions such as renal impairment) or if considering a regimen not included in CDC guidelines, source virus is known or likely to be resistant to antiretrovirals, or healthcare provider is inexperienced in prescribing antiretrovirals. Do not delay initiation of nPEP while waiting for expert consultation.

Chronic HBV Infection

Treatment of chronic HBV infection associated with evidence of HBV replication and active liver inflammation in adults, adolescents, and pediatric patients ≥2 years of age.

Experts state that lamivudine is not a preferred antiviral for treatment of chronic HBV (high rate of lamivudine resistance). Manufacturer states consider lamivudine only when other antivirals with higher genetic barrier to resistance are unavailable or inappropriate.

Safety and efficacy not established in patients with decompensated liver disease.

Safety and efficacy not established for treatment of chronic HBV infection in patients coinfected with HIV. (See Considerations in Patients Coinfected with HIV and HBV under Cautions.)

Safety and efficacy not established for treatment of chronic HBV infection in patients coinfected with HCV or hepatitis D virus (HDV).

Safety and efficacy not established in liver transplant recipients. May reduce risk of HBV reinfection in orthotopic liver transplant recipients^{† [off-label]}.

Treatment of chronic HBV infection is complex and evolving; consult specialized references and experts. Information from the American Association for the Study of Liver Diseases (AASLD) regarding management of HBV infection, including recommendations for initial treatment, is available at [Web].

Lamivudine Dosage and Administration

Administration

Oral Administration

Administer lamivudine orally without regard to meals.

Lamivudine labeled by FDA for treatment of HIV-1 infection: Use oral solution containing 10 mg/mL or film-coated tablets containing 150 or 300 mg. The 150-mg scored tablets are the preferred preparation in pediatric patients weighing ≥14 kg if they can reliably swallow tablets. (See Pediatric Use under Cautions.) Use the 10-mg/mL oral solution in those unable to safely and reliably swallow tablets.

Lamivudine labeled by FDA for treatment of chronic HBV infection: Use oral solution containing 5 mg/mL or film-coated tablets containing 100 mg. Use the 5-mg/mL oral solution in patients requiring dose <100 mg and in pediatric patients unable to reliably swallow tablets.

Lamivudine/zidovudine: Administer orally twice daily without regard to meals. Do not use in pediatric patients weighing <30 kg, patients with renal impairment (i.e., Cl_cr <50 mL/minute), patients with hepatic impairment, or patients who experience dose-limiting adverse effects.

Abacavir/lamivudine: Administer orally once daily without regard to meals. Do not use in pediatric patients weighing <25 kg, patients with renal impairment (i.e., Cl_cr <50 mL/minute), or patients with hepatic impairment (contraindicated in those with moderate or severe hepatic impairment).

Abacavir/lamivudine/zidovudine: Administer orally twice daily without regard to meals. Do not use in pediatric patients weighing <40 kg, patients with impaired renal function (i.e., Cl_cr <50 mL/minute), or patients with hepatic impairment (contraindicated in those with moderate or severe hepatic impairment).

Abacavir/dolutegravir/lamivudine: Administer orally once daily without regard to meals. Do not use in pediatric patients weighing <40 kg, patients with renal impairment (i.e., Cl_cr <50 mL/minute), or patients with hepatic impairment (contraindicated in those with moderate or severe hepatic impairment).

Dosage

Pediatric Patients

Treatment of HIV Infection

Oral

Lamivudine in neonates and young infants^† (oral solution containing 10 mg/mL): Experts recommend 2 mg/kg twice daily in those <4 weeks of age and 4 mg/kg (up to 150 mg) twice daily in those ≥4 weeks of age.

Lamivudine in pediatric patients ≥3 months of age (oral solution containing 10 mg/mL): 5 mg/kg twice daily or 10 mg/kg once daily (up to 300 mg daily).

Lamivudine in pediatric patients ≥3 months of age weighing ≥14 kg (150-mg scored tablets): Recommended dosage is based on weight (see Table 1 and Table 2). Data regarding efficacy of once-daily regimen of lamivudine 150-mg scored tablets limited to those who transitioned from twice-daily regimen to once-daily regimen after 36 weeks of treatment.

Lamivudine in adolescents (150-mg scored tablets or 300-mg tablets): Experts recommend 4 mg/kg (up to 150 mg) twice daily in those weighing <25 kg and 150 mg twice daily or 300 mg once daily in those weighing ≥25 kg.

Lamivudine/zidovudine in children and adolescents weighing ≥30 kg: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily.

Abacavir/lamivudine/zidovudine in children and adolescents weighing ≥40 kg: 1 tablet (abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg) twice daily.

Abacavir/dolutegravir/lamivudine in children and adolescents weighing ≥40 kg: 1 tablet (abacavir 600 mg, dolutegravir 50 mg, and lamivudine 300 mg) once daily. If used in those receiving concomitant therapy with efavirenz, ritonavir-boosted fosamprenavir, ritonavir-boosted tipranavir, carbamazepine, or rifampin, give 1 tablet of the fixed combination (abacavir 600 mg, dolutegravir 50 mg, and lamivudine 300 mg) once daily and give a 50-mg tablet of single-entity dolutegravir once daily 12 hours after the daily dose of the fixed combination.

Prevention of Perinatal HIV Transmission†

Empiric HIV Therapy in Neonates Born to HIV-infected Women†

Oral

Recommended empiric HIV therapy regimen consists of zidovudine, lamivudine, and nevirapine initiated as soon as possible after birth (within 6–12 hours); used in HIV-exposed neonates considered at highest risk of HIV acquisition. (See Prevention of Perinatal HIV Transmission under Uses.)

Lamivudine: 2 mg/kg twice daily from birth to 4 weeks of age and 4 mg/kg twice daily from 4–6 weeks of age.

Optimal duration of empiric HIV therapy in HIV-exposed neonates unknown. Many experts recommend that 3-drug empiric regimen be continued for 6 weeks; others discontinue nevirapine and/or lamivudine if results of neonate's HIV nucleic acid amplification test (NAAT) are negative, but recommend continuing zidovudine for 6 weeks.

Consult National Perinatal HIV Hotline at 888-448-8765 for information regarding selection of antiretrovirals, including dosage considerations, for prevention of perinatal HIV transmission.

Chronic HBV Infection

Oral

Lamivudine in children and adolescents ≥2 years of age (100-mg tablets or oral solution containing 5 mg/mL): 3 mg/kg (up to 100 mg) once daily.

Optimal duration of treatment unknown.

Adults

Treatment of HIV Infection

Oral

Lamivudine: 150 mg twice daily or 300 mg once daily.

Lamivudine/zidovudine in adults weighing ≥30 kg: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily.

Abacavir/lamivudine: 1 tablet (abacavir 600 mg and lamivudine 300 mg) once daily.

Abacavir/lamivudine/zidovudine in adults weighing ≥40 kg: 1 tablet (abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg) twice daily.

Abacavir/dolutegravir/lamivudine in adults weighing ≥40 kg: 1 tablet (600 mg of abacavir, 50 mg of dolutegravir, and 300 mg of lamivudine) once daily. If used in those receiving concomitant therapy with efavirenz, ritonavir-boosted fosamprenavir, ritonavir-boosted tipranavir, carbamazepine, or rifampin, give 1 tablet of the fixed combination (abacavir 600 mg, dolutegravir 50 mg, and lamivudine 300 mg) once daily and give a 50-mg tablet of single-entity dolutegravir once daily 12 hours after the daily dose of the fixed combination.

Postexposure Prophylaxis following Occupational Exposure to HIV (PEP)†

Oral

Lamivudine: 300 mg once daily. Alternatively, 150 mg twice daily. Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Occupational Exposure to HIV under Uses).

Lamivudine/zidovudine: 1 tablet (lamivudine 150 mg and zidovudine 300 mg) twice daily. Use in conjunction with a recommended INSTI, NNRTI, or PI (see Postexposure Prophylaxis following Occupational Exposure to HIV [PEP] under Uses).

Initiate PEP as soon as possible following occupational exposure to HIV (preferably within hours); continue for 4 weeks, if tolerated.

Postexposure Prophylaxis following Nonoccupational Exposure to HIV (nPEP)†

Oral

Lamivudine: Adjust dosage based on renal impairment. Use in conjunction with other antiretrovirals (see Postexposure Prophylaxis following Nonoccupational Exposure to HIV [nPEP] under Uses).

Initiate nPEP as soon as possible (within 72 hours) following nonoccupational exposure to HIV that represents a substantial risk for HIV transmission and continue for 28 days.

nPEP not recommended if exposed individual seeks care >72 hours after exposure.

Chronic HBV Infection

Oral

Lamivudine (100-mg tablets or oral solution containing 5 mg/mL): 100 mg once daily.

Optimal duration of treatment unknown.

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Lamivudine in children ≥3 months of age: Maximum 300 mg daily.

Chronic HBV Infection

Oral

Lamivudine in children ≥2 years of age: Maximum 100 mg daily.

Special Populations

Hepatic Impairment

Treatment of HIV Infection

Oral

Lamivudine: Dosage adjustments not needed. Safety and efficacy not established in those with decompensated liver disease.

Lamivudine/zidovudine: Do not use in patients with hepatic impairment.

Abacavir/lamivudine, abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine: Do not use in patients with hepatic impairment; contraindicated in those with moderate or severe hepatic impairment.

Chronic HBV Infection

Oral

Lamivudine: Dosage adjustments not needed. Safety and efficacy not established in those with decompensated liver disease.

Renal Impairment

Treatment of HIV Infection

Oral

Lamivudine in pediatric patients with renal impairment: Consider reducing dose and/or increasing dosing interval; data insufficient to make specific recommendations.

Lamivudine in adults and adolescents with renal impairment: Decrease dosage in those with Cl_cr <50 mL/minute (see Table 3).

Lamivudine/zidovudine, abacavir/lamivudine, abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine: Do not use in patients with Cl_cr <50 mL/minute.

Chronic HBV Infection

Oral

Lamivudine in pediatric patients with renal impairment: Manufacturer states data insufficient to make specific recommendations.

Lamivudine in adults with renal impairment: Decrease dosage in those with Cl_cr <50 mL/minute (see Table 4).

Geriatric Patients

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Lamivudine

Contraindications

• Lamivudine: History of hypersensitivity to the drug.

• Lamivudine/zidovudine: History of hypersensitivity to lamivudine or zidovudine.

• Abacavir/lamivudine: Positive for HLA-B*5701 allele; history of hypersensitivity to abacavir or lamivudine; moderate or severe hepatic impairment.

• Abacavir/lamivudine/zidovudine: Positive for HLA-B*5701 allele; history of hypersensitivity to abacavir, lamivudine, or zidovudine; moderate or severe hepatic impairment.

• Abacavir/dolutegravir/lamivudine: Positive for HLA-B*5701 allele; history of hypersensitivity to abacavir, dolutegravir, or lamivudine; concurrent dofetilide; moderate or severe hepatic impairment.

Warnings/Precautions

Warnings

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving nucleoside analogs, including lamivudine, and other antiretrovirals. Reported most frequently in women; obesity also may be a risk factor. Has been reported in patients with no known risk factors.

Use with caution in patients with known risk factors for liver disease.

Discontinue lamivudine or fixed combination containing lamivudine if there are clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., hepatomegaly and steatosis even in the absence of markedly increased serum aminotransferase concentrations).

Exacerbations of HBV Infection

Posttreatment exacerbations of HBV infection and emergence of resistant strains of HBV reported following discontinuance of lamivudine therapy for HBV in non-HIV-infected patients.

Exacerbations of HBV infection also reported when lamivudine discontinued from antiretroviral regimens in HIV-infected patients coinfected with HBV.

Such exacerbations of HBV infection detected principally by increases in serum ALT in addition to re-emergence of serum HBV DNA. Most events appear to have been self-limited and causal relationship to lamivudine discontinuance unknown; some fatalities reported.

After discontinuing lamivudine, closely monitor patients with both clinical and laboratory follow-up for at least several months. If appropriate, initiation or resumption of anti-HBV therapy may be warranted. Insufficient evidence to determine whether reinitiation of therapy alters the course of posttreatment exacerbations of hepatitis.

Considerations in Patients Coinfected with HIV and HBV

Lamivudine preparations labeled for treatment of chronic HBV infection (100-mg tablets or oral solution containing 5 mg/mL) are not appropriate for patients coinfected with HBV and HIV since these preparations contain a lower dose of lamivudine than those labeled for treatment of HIV-1 infection (150-mg scored tablets, 300-mg tablets, or oral solution containing 10 mg/mL).

Use of lamivudine for treatment of HBV infection (100-mg tablets or oral solution containing 5 mg/mL) in patients with unrecognized or untreated HIV infection may result in rapid emergence of lamivudine-resistant HIV and limit antiretroviral treatment options.

Prior to and periodically during lamivudine treatment of chronic HBV infection, offer HIV counseling and testing to all patients.

If a decision is made to use lamivudine in patients coinfected with HBV and HIV, lamivudine should be used in dosages appropriate for the treatment of HIV infection and used in conjunction with other antiretrovirals.

Other Warnings and Precautions

HBV Resistance

Lamivudine-resistant HBV detected in patients receiving the drug for treatment of HBV; diminished treatment response reported. Lamivudine-resistant HBV also detected in HIV-infected patients coinfected with HBV who received a lamivudine-containing antiretroviral regimen.

Monitoring ALT and HBV DNA levels during lamivudine treatment may assist in treatment decisions if emergence of resistant HBV is suspected.

HIV-infected Patients Coinfected with HCV

Hepatic decompensation, sometimes fatal, reported in patients coinfected with HIV and HCV receiving antiretroviral therapy concomitantly with interferon alfa with or without ribavirin. (See Specific Drugs under Interactions.)

Use of Fixed Combinations

Lamivudine/zidovudine, abacavir/lamivudine, abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine: Consider cautions, precautions, contraindications, and interactions associated with each drug in the fixed combination. Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, pediatric patients, geriatric patients) for each drug.

Do not use lamivudine or fixed combinations containing lamivudine concomitantly with any preparation containing emtricitabine.

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance. Mechanisms and long-term consequences of adipogenic effects unknown; causal relationship not established.

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome) also reported in the setting of immune reconstitution; however, time to onset is more variable and can occur many months after initiation of antiretroviral therapy.

Diabetes Mellitus

Lamivudine oral solution containing 5 or 10 mg/mL: Each mL contains 200 mg of sucrose.

Possible Prescribing and Dispensing Errors

Ensure accuracy of the prescription; similarity of spelling lamotrigine (Lamictal) and lamivudine may result in errors.

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].

Available data from the pregnancy registry indicate no difference in risk of overall major birth defects among infants born to women who received lamivudine during pregnancy compared with US background rate for major birth defects.

Experts state that preferred dual NRTI options for initial regimens used for treatment of HIV-1 in antiretroviral-naive pregnant women are abacavir and lamivudine (use only in those negative for HLA-B*5701) or tenofovir DF and emtricitabine (or lamivudine). Tenofovir DF and emtricitabine (or lamivudine) is the preferred dual NRTI option in pregnant women coinfected with HBV.

Experts state that zidovudine and lamivudine is an alternative dual NRTI option for initial treatment regimens in antiretroviral-naive pregnant women.

Routine screening for HBV infection recommended for all pregnant women. AASLD suggests that hepatitis B surface antigen (HBsAg)-positive pregnant women with HBV DNA levels >200,000 IU/mL should receive antiviral therapy since this may reduce the risk of perinatal transmission of HBV; however, preferred antiviral agents, exact viral load threshold, and optimal gestational week during the third trimester to initiate such therapy not clearly identified. For prevention of perinatal transmission of HBV, US Public Health Service Advisory Committee on Immunization Practices (ACIP), AAP, and others state that infants born to HBsAg-positive women should receive first dose of hepatitis B vaccine and a dose of hepatitis B immune globulin (HBIG) within 12 hours of birth.

Lactation

Lamivudine is distributed into human milk. Not known whether the drug affects human milk production or affects the breast-fed infant.

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.

In HBV-infected women, consider benefits of breast-feeding and importance of the drug to the woman; also consider potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Lamivudine (150-mg scored tablets, 300-mg tablets, oral solution containing 10 mg/mL): Safety and efficacy established for treatment of HIV infection in pediatric patients ≥3 months of age. Because there is some evidence that use of the oral solution in pediatric patients is associated with lower rates of virologic suppression, lower plasma lamivudine exposures, and more frequent emergence of lamivudine-resistant HIV-1, the 150-mg tablets are preferred in pediatric patients weighing ≥14 kg if they can swallow tablets.

Lamivudine (100-mg tablets, oral solution containing 5 mg/mL): Safety and efficacy established for management of chronic HBV infection in pediatric patients ≥2 years of age. Safety and efficacy for this indication not established in children <2 years of age.

Pancreatitis, sometimes fatal, reported in antiretroviral nucleoside-experienced HIV-infected pediatric patients. Use with caution in pediatric patients with prior antiretroviral nucleoside exposure, history of pancreatitis, or other risk factors for pancreatitis. Immediately discontinue if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur.

Lamivudine/zidovudine: Do not use in pediatric patients weighing <30 kg.

Abacavir/lamivudine: Do not use in pediatric patients weighing <25 kg.

Abacavir/lamivudine/zidovudine: Do not use in pediatric patients weighing <40 kg.

Abacavir/dolutegravir/lamivudine: Do not use in pediatric patients weighing <40 kg.

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Hepatic Impairment

Lamivudine: Safety and efficacy not established in patients with decompensated liver disease.

Lamivudine/zidovudine: Do not use in patients with impaired hepatic function.

Abacavir/lamivudine, abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine: Do not use in patients with hepatic impairment; contraindicated in those with moderate or severe hepatic impairment.

Renal Impairment

Lamivudine: Dosage adjustments recommended based on degree of renal impairment. (See Renal Impairment under Dosage and Administration.)

Lamivudine/zidovudine, abacavir/lamivudine, abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine: Do not use in patients with Cl_cr <50 mL/minute.

Common Adverse Effects

Nausea, fatigue and/or malaise, headache, nasal symptoms, diarrhea, cough.

Interactions for Lamivudine

The following drug interactions are based on studies using lamivudine. When lamivudine/zidovudine, abacavir/lamivudine, abacavir/lamivudine/zidovudine, or abacavir/dolutegravir/lamivudine is used, consider interactions associated with each drug in the fixed combination.

Drugs Affecting or Affected by Membrane Transporters

Lamivudine is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). However, concomitant use of drugs that are inhibitors of these efflux transporters unlikely to affect disposition and elimination of lamivudine.

Lamivudine is a substrate of multidrug and toxin extrusion protein (MATE) 1, MATE2-K, and organic cation transporter (OCT) 2 in vitro.

At clinically important concentrations, lamivudine not expected to affect pharmacokinetics of drugs that are substrates of organic anion transporter polypeptide 1B1/3 (OATP1B1/3), BCRP, P-gp, MATE1, MATE2-K, OCT1, OCT2, or OCT3.

Specific Drugs

Lamivudine Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract; peak plasma concentrations achieved within 0.5–2 hours.

Absolute bioavailability of 150-mg scored tablets and oral solution is similar (86 and 87%, respectively) in adults. Comparison of steady-state pharmacokinetics of once-daily lamivudine regimen (300-mg tablet once daily) or twice-daily lamivudine regimen (150-mg tablet twice daily) in healthy adults indicates AUC is similar with both regimens; peak plasma concentrations are 66% higher and trough concentrations 53% lower with once-daily regimen.

Fixed-combination tablet containing lamivudine 150 mg and zidovudine 300 (lamivudine/zidovudine) is bioequivalent to one 150-mg tablet of lamivudine and one 300-mg tablet of zidovudine given simultaneously.

Fixed-combination tablet containing abacavir 600 mg and lamivudine 300 (abacavir/lamivudine) is bioequivalent to two 300-mg tablets of abacavir and two 150-mg tablets of lamivudine given simultaneously.

Fixed-combination tablet containing abacavir 300 mg, lamivudine 150 mg, and zidovudine 300 mg (abacavir/lamivudine/zidovudine) is bioequivalent to a 300-mg abacavir tablet, 150-mg lamivudine tablet, and 300-mg zidovudine tablet given simultaneously.

Fixed-combination tablet containing abacavir 600 mg, dolutegravir 50 mg, and lamivudine 300 mg (abacavir/dolutegravir/lamivudine) is bioequivalent to one 50-mg tablet of dolutegravir administered simultaneously with one fixed-combination tablet containing abacavir 600 mg and lamivudine 300 mg (abacavir/lamivudine).

Food

Food does not appear to affect AUC.

Special Populations

Pediatric patients: Absolute bioavailability (lamivudine tablets or oral solution) is lower in children than in adults; relative bioavailability of the oral solution is approximately 40% lower than tablets. Lower exposures reported in pediatric patients receiving the oral solution are likely due to an interaction between lamivudine and concomitant solutions containing sorbitol (e.g., abacavir oral solution). (See Specific Drugs under Interactions.) In HIV-1-infected pediatric patients 3 months through 12 years of age, AUCs attained with once-daily lamivudine regimens were similar to those attained with twice-daily lamivudine regimens when comparison made within same formulation (i.e., either tablets or oral solution). However, mean peak plasma concentrations were approximately 80–90% higher with once-daily regimens compared with twice-daily regimens.

Pregnant women: Pharmacokinetics similar to that reported in nonpregnant adults and postpartum women.

Hepatic impairment: Peak plasma concentration and AUC similar to those in patients with normal hepatic function.

Renal impairment: Peak plasma concentration and AUC increased depending on degree of renal impairment.

Distribution

Extent

Not well characterized; distributes into extravascular spaces.

Distributed into CSF; concentrations in CSF may be 5.6–30.9% of concurrent serum concentrations in HIV-infected children.

Crosses the placenta and is distributed into cord blood and amniotic fluid. Concentrations in amniotic fluid typically twofold higher than maternal serum concentrations.

Distributed into milk.

Plasma Protein Binding

<36%.

Elimination

Metabolism

Metabolism is a minor route of elimination; only known metabolite is the trans-sulfoxide metabolite.

Not substantially metabolized by CYP isoenzymes.

Intracellularly, lamivudine is phosphorylated and converted by cellular enzymes to the active 5′-triphosphate metabolite.

Elimination Route

Majority of dose eliminated unchanged in urine by active organic cationic secretion. Within 24 hours, approximately 5% of an oral dose excreted in urine as the trans-sulfoxide metabolite.

Half-life

5–7 hours.

HIV-infected children 4 months to 14 years of age: 2 hours.

Special Populations

Hepatic impairment: Pharmacokinetics not altered.

Renal impairment: Half-life increased with diminishing renal function.

Hemodialysis increases clearance; length of time of hemodialysis (4 hours) insufficient to substantially alter mean lamivudine exposure after single-dose administration. Continuous ambulatory peritoneal dialysis and automated peritoneal dialysis have negligible effects on lamivudine clearance.

Stability

Storage

Oral

Solution

Lamivudine (oral solution containing 10 mg/mL): 25°C in tightly closed bottles.

Lamivudine (oral solution containing 5 mg/mL): 20–25°C in tightly closed bottles.

Tablets

Lamivudine: 25°C (may be exposed to 15–30°C).

Lamivudine/zidovudine: 2–30°C.

Abacavir/lamivudine: 25°C (may be exposed to 15–30°C).

Abacavir/lamivudine/zidovudine: 25°C (may be exposed to 15–30°C).

Abacavir/dolutegravir/lamivudine: 25°C (may be exposed to 15–30°C).

Actions and Spectrum

• Lamivudine is a dideoxy analogue of cytidine.

• Pharmacologically related to, but structurally different from, other NRTIs and other currently available antiretrovirals.

• A prodrug that is inactive until converted intracellularly to lamivudine triphosphate.

• Active in vitro against HIV-1 and HIV-2. Also active against HBV.

• Inhibits replication of HIV by interfering with viral RNA-directed DNA polymerase (reverse transcriptase).

• Inhibits replication of HBV by interfering with HBV polymerase.

• HIV-1 with reduced susceptibility to lamivudine have been produced in vitro and have emerged during therapy with the drug.

• Lamivudine-resistant HIV may be cross-resistant to some other NRTIs (e.g., abacavir, didanosine, emtricitabine, tenofovir, stavudine).

• HBV with reduced susceptibility to lamivudine have emerged during therapy, including YMDD-mutant HBV associated with diminished treatment response. Prevalence of YMDD-mutants increases with long-term lamivudine therapy.

• Some lamivudine-resistant HBV remain susceptible to adefovir, but have reduced susceptibility to entecavir and telbivudine. Other lamivudine-resistant HBV have reduced susceptibility to telbivudine and/or tenofovir.

Advice to Patients

• Importance of reading the patient package insert for lamivudine (Epivir-HBV) provided by the manufacturer.

• Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician. Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.

• Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others. Importance of continuing to practice safer sex (e.g., consistent use of condoms).

• Inform HIV-infected patients coinfected with HCV that hepatic decompensation (sometimes fatal) has been reported when antiretrovirals were used concomitantly with interferon alfa with or without ribavirin.

• When used for treatment of chronic HBV infection, advise patients that the long-term benefits of the drug are unknown and that the relationship between treatment response and outcomes such as hepatocellular carcinoma and decompensated cirrhosis is unknown. Importance of reporting any new symptoms to a clinician. Advise patients that deterioration of liver disease has occurred when treatment is discontinued, and that any change in treatment should be discussed with a clinician.

  Importance of testing for HIV prior to and periodically during lamivudine therapy used for treatment of chronic HBV infection.

• Advise patients that lactic acidosis and severe hepatomegaly with steatosis have been reported with use of nucleoside analogs and other antiretrovirals. Importance of discontinuing lamivudine and notifying a clinician if symptoms suggestive of lactic acidosis or pronounced hepatotoxicity develop.

• Advise diabetic patients receiving lamivudine oral solutions that each mL contains 200 mg of sucrose.

• Advise patients to immediately contact a clinician if they have any signs or symptoms of infection since inflammation from previous infections may occur soon after antiretroviral therapy is initiated.

• Redistribution/accumulation of body fat may occur, with as yet unknown long-term health effects.

• Possibility of pancreatitis in pediatric patients; advise parents or guardians to monitor pediatric patients for signs and symptoms.

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise HIV-infected women not to breast-feed.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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