Epivir

Nucleoside and Nucleotide Analog Antivirals for Hepatitis B
Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI)s

May be administered with or without food. Food decreases the rate, but not the extent, of oral absorption.
The scored tablet is the preferred dosage formulation in pediatric patients able to take a solid dosage form due to lower virologic suppression rates and increased risk of viral resistance with the oral solution as a result of an interaction with sorbitol-containing medicines. Consider increased monitoring of viral load when using the oral solution.

Administer using a calibrated oral syringe to give an accurate dosage.
Avoid chronic coadministration of lamivudine oral solution with sorbitol-containing medicines as decreased lamivudine concentrations may occur.

pancreatitis / Delayed / 0.3-18.0
rhabdomyolysis / Delayed / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
hepatitis B exacerbation / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
lactic acidosis / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 1.0-27.0
peripheral neuropathy / Delayed / 0-15.0
hepatomegaly / Delayed / 11.0-11.0
depression / Delayed / 9.0-9.0
lymphadenopathy / Delayed / 9.0-9.0
neutropenia / Delayed / 7.2-8.0
wheezing / Rapid / 7.0-7.0
stomatitis / Delayed / 6.0-6.0
splenomegaly / Delayed / 5.0-5.0
hyperamylasemia / Delayed / 3.0-4.2
thrombocytopenia / Delayed / 0.4-4.0
anemia / Delayed / 2.9-4.0
hyperglycemia / Delayed / 0-1.0
hyperbilirubinemia / Delayed / 0.8-0.8
jaundice / Delayed / Incidence not known
steatosis / Delayed / Incidence not known
lipodystrophy / Delayed / Incidence not known
hypoglycemia / Early / Incidence not known

headache / Early / 35.0-35.0
nausea / Early / 8.0-33.0
fatigue / Early / 27.0-27.0
malaise / Early / 27.0-27.0
infection / Delayed / 0-25.0
fever / Early / 10.0-25.0
nasal congestion / Early / 8.0-20.0
rhinorrhea / Early / 8.0-20.0
cough / Delayed / 15.0-18.0
diarrhea / Early / 8.0-18.0
paresthesias / Delayed / 0-15.0
vomiting / Early / 8.0-13.0
musculoskeletal pain / Early / 12.0-12.0
rash / Early / 9.0-12.0
insomnia / Early / 11.0-11.0
dizziness / Early / 10.0-10.0
chills / Rapid / 10.0-10.0
anorexia / Delayed / 10.0-10.0
abdominal pain / Early / 9.0-9.0
myalgia / Early / 8.0-8.0
otalgia / Early / 7.0-7.0
dyspepsia / Early / 5.0-5.0
arthralgia / Delayed / 5.0-5.0
weakness / Early / 0-1.0
alopecia / Delayed / 0-1.0
pruritus / Rapid / 0-1.0
urticaria / Rapid / 0-1.0
muscle cramps / Delayed / Incidence not known

Lamivudine is available in two formulations, Epivir and Epivir-HBV. Epivir is indicated for use as part of a fully suppressive antiretroviral regimen to treat patients with HIV, whereas Epivir-HBV is approved to treat patients with the hepatitis B virus (HBV). Prior to and during the use of the Epivir-HBV formulation, all patients should be offered HIV counseling and have their HIV serum status determined. If Epivir-HBV is administered to patients who have unrecognized or untreated HIV infection, or who acquire HIV infection during treatment, the virus may rapidly develop resistance to lamivudine, thereby limiting potential treatment options. Similarly, HBV screening is recommended for any patient who presents with HIV infection to assure appropriate treatment. Patients with hepatitis B and HIV coinfection should be started on a fully suppressive antiretroviral (ARV) regimen with activity against both viruses (regardless of CD4 counts and HBV DNA concentrations). HIV treatment guidelines recommend these patients receive an ARV regimen that contains a dual NRTI backbone of tenofovir alafenamide or tenofovir disoproxil fumarate with either emtricitabine or lamivudine (Epivir). If tenofovir cannot be used, entecavir should be used in combination with a fully suppressive ARV regimen (note: entecavir should not be considered part of the ARV regimen). Avoid using single-drug therapy to treat HBV (i.e., lamivudine, emtricitabine, tenofovir, or entecavir as the only active agent) due to the risk of developing HIV resistant strains. Further, HBV treatment regimens that include adefovir or telbivudine should also be avoided, as these regimens are associated with a higher incidence of toxicities and increased rates of HBV treatment failure. Most coinfected patients should continue treatment indefinitely with the goal of maximal HIV suppression and prevention of HBV relapse. If treatment must be discontinued, monitor transaminase concentrations every 6 weeks for the first 3 months, and every 3 to 6 months thereafter. Patients with hepatitis B and HIV coinfection have been reported to experience clinical or laboratory evidence of hepatitis B exacerbation upon discontinuation of lamivudine. For patients who refuse a fully suppressive ARV regimen, but still requires treatment for HBV, consider 48 weeks of peginterferon alfa; do not administer HIV-active medications in the absence of a fully suppressive ARV regimen. Instruct coinfected patients to avoid consuming alcohol, and offer vaccinations against hepatitis A and hepatitis B as appropriate. [29240] [46708] [46638] [34362]

Epivir, Epivir HBV

Rx

Nucleoside reverse transcriptase inhibitor
Used for the treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents
Lower-dose formulation available for treatment of chronic hepatitis B in patients without HIV

NOTE: The scored tablet is the preferred dosage formulation in pediatric patients able to take a solid dosage form due to lower virologic suppression rates and increased risk of viral resistance with the oral solution.

300 mg PO once daily or 150 mg PO twice daily.

150 mg PO twice daily. May transition to 300 mg PO once daily for children 3 years or older who have been clinically stable for 36 weeks with undetectable viral loads and stable CD4 counts.

75 mg PO once daily in the morning and 150 mg PO once daily in the evening. May transition to 225 mg PO once daily for children 3 years or older who have been clinically stable for 36 weeks with undetectable viral loads and stable CD4 counts.

75 mg PO twice daily. May transition to 150 mg PO once daily for children 3 years or older who have been clinically stable for 36 weeks with undetectable viral loads and stable CD4 counts.

NOTE: The scored tablet is the preferred dosage formulation in pediatric patients able to take a solid dosage form due to lower virologic suppression rates and increased risk of viral resistance with the oral solution. Additionally, the tablet formulation is preferred when possible to avoid an interaction between lamivudine oral solution and sorbitol-containing medicines. Consider increased monitoring of viral load when using the oral solution.

300 mg PO once daily or 150 mg PO twice daily.

5 mg/kg/dose PO twice daily. May transition to 10 mg/kg/dose PO once daily for children 3 years or older who have been clinically stable for 36 weeks with undetectable viral loads and stable CD4 counts. Max: 300 mg/day. Guidelines recommend that adolescents in early puberty (i.e., Sexual Maturity Rating (SMR) Stages 1 to 3) be administered doses based on pediatric schedules, whereas those in late puberty (i.e., SMR Stage 4 or 5) use adult dosing schedules (i.e., 300 mg PO once daily or 150 mg PO twice daily).

5 mg/kg/dose PO twice daily. May transition to 10 mg/kg/dose PO once daily for children 3 years or older who have been clinically stable for 36 weeks with undetectable viral loads and stable CD4 counts. Max: 300 mg/day.

5 mg/kg/dose PO twice daily. The FDA-approved dose is 5 mg/kg/dose PO twice daily or 10 mg/kg/dose PO once daily with data regarding efficacy of once-daily dosing limited to patients who transitioned from twice-daily dosing after 36 weeks of treatment. Guidelines do not recommend once-daily dosing in infants and young children.

4 mg/kg/dose PO twice daily.

2 mg/kg/dose PO twice daily.

100 mg PO once daily. The optimum duration of treatment is not known. For HBeAg-positive chronic hepatitis, continue treatment until have achieved HBeAg seroconversion and undetectable serum HBV DNA and completed at least 6 months of additional treatment after the appearance of anti-HBe. For HBeAg-negative chronic hepatitis, continue treatment until have achieved HBsAg clearance. Persons not achieving a primary response (less than 2 log decrease in serum HBV DNA after at least 6 months of therapy) should be switched to alternative therapy or receive additional treatment.

3 mg/kg/dose PO once daily (Max: 100 mg/dose). The optimum duration of treatment is not known. Use of the oral solution is recommended for a required dose less than 100 mg or if unable to swallow tablets. For HBeAg-positive chronic hepatitis, continue treatment until have achieved HBeAg seroconversion and undetectable serum HBV DNA and completed at least 6 months of additional treatment after the appearance of anti-HBe. For HBeAg-negative chronic hepatitis, continue treatment until have achieved HBsAg clearance. Persons not achieving a primary response (less than 2 log decrease in serum HBV DNA after at least 6 months of therapy) should be switched to alternative therapy or receive additional treatment. Some experts suggest caution when initiating therapy and recommend considering treatment in children that are HBeAg-positive and immune active, that have reactivation, and that are HBeAg-negative and immune active if there is moderate or severe hepatic inflammation or fibrosis or a family history of hepatocellular carcinoma.

150 mg PO twice daily or 300 mg PO once daily as part of a fully suppressive antiretroviral regimen. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. Most persons on HAART should receive HBV therapy indefinitely.

150 mg PO twice daily or 300 mg PO once daily as part of a fully suppressive antiretroviral regimen. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. Most persons on HAART should receive HBV therapy indefinitely.

4 mg/kg/dose (Max: 150 mg/dose) PO twice daily as part of a fully suppressive antiretroviral regimen. When treating both HIV and HBV in children 2 years and older, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. If tenofovir cannot be used, use another agent with anti-HBV activity in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection. Most persons on HAART should receive HBV therapy indefinitely.

150 mg PO twice daily or 300 mg PO once daily as part of a fully suppressive antiretroviral regimen. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. Most persons on HAART should receive HBV therapy indefinitely.

150 mg PO twice daily or 300 mg PO once daily as part of a fully suppressive antiretroviral regimen. When treating both HIV and HBV, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. Most persons on HAART should receive HBV therapy indefinitely.

150 mg PO twice daily or 300 mg PO once daily as part of a fully suppressive antiretroviral regimen. When treating both HIV and HBV in children 2 years and older, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. If tenofovir cannot be used, use another agent with anti-HBV activity in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection. Most persons on HAART should receive HBV therapy indefinitely.

75 mg PO in the morning and 150 mg PO in the evening or 225 mg PO once daily as part of a fully suppressive antiretroviral regimen. When treating both HIV and HBV in children 2 years and older, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. If tenofovir cannot be used, use another agent with anti-HBV activity in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection. Most persons on HAART should receive HBV therapy indefinitely.

75 mg PO twice daily or 150 PO as part of a fully suppressive antiretroviral regimen. When treating both HIV and HBV in children 2 years and older, tenofovir and lamivudine or tenofovir and emtricitabine (at appropriate HIV treatment doses and in combination with other antiretroviral agents) are appropriate first-line treatment options. If tenofovir cannot be used, use another agent with anti-HBV activity in combination with lamivudine or emtricitabine to assure adequate treatment of HBV infection. Most persons on HAART should receive HBV therapy indefinitely.

300 mg PO once daily plus tenofovir 300 mg PO once daily, in combination with a third antiretroviral agent, is a preferred regimen for HIV post-exposure prophylaxis (PEP). Alternative lamivudine dosing is 150 mg PO twice daily. According to PEP guidelines, individuals potentially exposed to HIV should receive a 3-drug regimen for a total of 28 days; however, if tolerability is a concern, use of a 2-drug regimen may be considered and is preferred to prophylaxis discontinuation. The recommended third antiretroviral agent to be administered in combination with lamivudine and tenofovir varies among published guidelines and includes one of the following: raltegravir, dolutegravir, lopinavir; ritonavir, or atazanavir boosted with ritonavir. Additionally, lamivudine plus tenofovir may be used as part of alternative regimens in combination with other antiretroviral agents. Begin prophylaxis as soon as possible, ideally within 2 hours of exposure. If initiation of prophylaxis is delayed (beyond 36 hours or 72 hours after exposure), efficacy of the antiretroviral regimen may be diminished and treatment should be determined on a case-by-case basis. Exposures for which PEP is indicated include: skin puncture by a sharp object that has been contaminated with blood, body fluid, or other infectious material; bite from a patient with visible bleeding in the mouth which causes bleeding by the exposed worker; splash of blood, body fluid, or other infectious material onto the workers mouth, nose, or eyes; exposure of blood, body fluid, or other infectious material on a workers non-intact skin (i.e., open wound, chapped skin, abrasion, dermatitis).

150 mg PO twice daily or 300 mg PO once daily in combination with zidovudine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adults with renal dysfunction (CrCl 59 mL/minute or less). Lamivudine and zidovudine doses should be adjusted to degree of renal impairment. Lamivudine in combination with zidovudine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

150 mg PO twice daily or 300 mg PO once daily in combination with zidovudine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents with renal dysfunction (CrCl 59 mL/minute or less). Lamivudine and zidovudine doses should be adjusted to degree of renal impairment. Lamivudine in combination with zidovudine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

150 mg PO twice daily or 300 mg PO once daily in combination with zidovudine and raltegravir or lopinavir/ritonavir for 28 days is an alternative HIV post-exposure prophylaxis (PEP) regimen in children 2 to 12 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

One-half tablet (75 mg) PO in the morning and 1 tablet (150 mg) PO in the evening or one and one-half tablets (225 mg) PO once daily in combination with zidovudine and raltegravir or lopinavir/ritonavir for 28 days is an alternative HIV post-exposure prophylaxis (PEP) regimen in children 2 to 12 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

One-half tablet (75 mg) PO twice daily or 1 tablet (150 mg) PO once daily in combination with zidovudine and raltegravir or lopinavir/ritonavir for 28 days is an alternative HIV post-exposure prophylaxis (PEP) regimen in children 2 to 12 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

150 mg PO twice daily or 300 mg PO once daily in combination with zidovudine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adults with renal dysfunction (CrCl 59 mL/minute or less). Lamivudine and zidovudine doses should be adjusted to degree of renal impairment. Lamivudine in combination with zidovudine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

150 mg PO twice daily or 300 mg PO once daily in combination with zidovudine and raltegravir or dolutegravir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in adolescents with renal dysfunction (CrCl 59 mL/minute or less). Lamivudine and zidovudine doses should be adjusted to degree of renal impairment. Lamivudine in combination with zidovudine and darunavir/ritonavir is an alternative regimen. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

4 mg/kg/dose (Max: 150 mg/dose) PO twice daily in combination with zidovudine and raltegravir or lopinavir/ritonavir for 28 days is an alternative HIV post-exposure prophylaxis (PEP) regimen in children 2 to 12 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

4 mg/kg/dose PO twice daily in combination with zidovudine and raltegravir or lopinavir/ritonavir for 28 days is a preferred HIV post-exposure prophylaxis (PEP) regimen in infants and children younger than 2 years. A 3-drug regimen is recommended for all cases when PEP is indicated; however, the use of a 2-drug regimen (2 NRTIs or a combination of a PI and a NNRTI) may be considered if tolerability or adherence is a concern. Begin prophylaxis as soon as possible after exposure; prophylaxis initiated more than 72 hours after exposure is unlikely to be effective.

4 mg/kg/dose PO twice daily. Optimal treatment duration has not been established. For low-risk infants, some recommend 2 to 6 weeks of treatment while others recommend continuing treatment throughout breastfeeding and 1 to 4 weeks after weaning. For high-risk infants, treatment is recommended throughout breastfeeding and for 1 to 4 weeks after weaning.

2 mg/kg/dose PO twice daily. Optimal treatment duration has not been established. For low-risk infants, some recommend 2 to 6 weeks of treatment while others recommend continuing treatment throughout breastfeeding and 1 to 4 weeks after weaning. For high-risk infants, treatment is recommended throughout breastfeeding and for 1 to 4 weeks after weaning.

4 mg/kg/dose PO twice daily in combination with zidovudine and either nevirapine or raltegravir. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For lamivudine, nevirapine, and raltegravir, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512] [42452]

2 mg/kg/dose PO twice daily in combination with zidovudine and either nevirapine or raltegravir. Initiate treatment as close to the time of birth as possible, preferably within 6 hours of delivery. The optimal duration of presumptive HIV therapy in high-risk infants is unknown. A 6-week course of zidovudine is recommended. For lamivudine, nevirapine, and raltegravir, a treatment duration of 2 to 6 weeks is recommended. The recommended duration for these drugs varies based on HIV nucleic acid test (NAT) results, maternal viral load at the time of delivery, and additional risk factors for HIV transmission, including breastfeeding. Consultation with an expert in pediatric HIV is recommended when selecting a therapy duration, as this decision should be based on patient-specific risk factors and interim HIV NAT results.[23512] [42452]

†Indicates off-label use

Pharmacokinetic parameters of lamivudine are not altered by diminishing hepatic function; therefore, no dosage adjustment is required with impaired hepatic function. Safety and efficacy have not been established in patients with decompensated hepatic disease. Treatment should be discontinued in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity.

FDA-labeled dosage adjustments in adults and adolescents weighing 25 kg or more when treating HIV (Epivir) :
CrCl 50 mL/minute or more: No dosage adjustment needed.
CrCl 30 to 49 mL/minute: 150 mg PO once daily.
CrCl 15 to 29 mL/minute: 150 mg PO first dose, then 100 mg PO once daily.
CrCl 5 to 14 mL/minute: 150 mg PO first dose, then 50 mg PO once daily.
CrCl less than 5 mL/minute: 50 mg PO first dose, then 25 mg PO once daily.
 
The following off-label pediatric dosage adjustments based on a twice daily dosage regimen in patients with normal renal function have been recommended when treating HIV :
GFR more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
GFR 30 to 50 mL/minute/1.73 m2: Extend the dosing interval to every 24 hours.
GFR 10 to 29 mL/minute/1.73 m2: Reduce dose to 50% of the normal dose and extend the dosing interval to every 24 hours.
GFR less than 10 mL/minute/1.73 m2: Reduce dose to 25% of the normal dose and extend the dosing interval to every 24 hours.
 
FDA-labeled dosage adjustments in adults being treated for hepatitis B (Epivir HBV) :
CrCl 50 mL/minute or more: No dosage adjustment needed.
CrCl 30 to 49 mL/minute: 100 mg PO once, then 50 mg PO once daily.
CrCl 15 to 29 mL/minute: 100 mg PO once, then 25 mg PO once daily.
CrCl 5 to 14 mL/minute: 35 mg PO once, then 15 mg PO once daily.
CrCl less than 5 mL/minute: 35 mg PO once, then 10 mg PO once daily.
 
Intermittent hemodialysis
The hemodialysis extraction ratio is approximately 53% to 65%. Dose after hemodialysis on dialysis days. After corrections for renal impairment, no additional dose modifications are required after routine (4-hour) hemodialysis. For pediatric patients, reducing the dose to 25% of the normal dose and extending the dosing interval to every 24 hours has been recommended based on a twice daily dosage regimen in patients with normal renal function being treated for HIV (Epivir).
 
Peritoneal dialysis
After corrections for renal impairment, no additional dose modifications are required after routine (4-hour) peritoneal dialysis (CAPD). Alternatively in adult patients, a dose of 50 mg PO once then 25 to 50 mg PO every 24 hours has been suggested. For pediatric patients, reducing the dose to 25% of the normal dose and extending the dosing interval to every 24 hours has been recommended based on a twice daily dosage regimen in patients with normal renal function being treated for HIV (Epivir).
 
Continuous renal replacement therapy (CRRT)
For adult patients, dose with 100 mg PO on day 1, then 50 mg PO every 24 hours. For pediatric patients, extending the dosing interval to every 24 hours has been recommended based on a twice daily dosage regimen in patients with normal renal function being treated for HIV (Epivir).

Adefovir: (Major) Patients who are concurrently taking adefovir with antiretrovirals (i.e., anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs)) are at risk of developing lactic acidosis and severe hepatomegaly with steatosis. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with antiretrovirals. A majority of these cases have been in women; obesity and prolonged nucleoside exposure may also be risk factors. Particular caution should be exercised when administering nucleoside analogs to any patient with known risk factors for hepatic disease; however, cases have also been reported in patients with no known risk factors. Suspend adefovir in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).
Alogliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Amiloride: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Drugs that are actively secreted via cationic tubular secretion, such as amiloride, should be co-administered with caution with lamivudine since they could increase lamivudine plasma concentrations, and therefore lamivudine associated adverse reactions, via potential competition for renal cationic secretion.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like lamivudine; the risk of peripheral neuropathy may be additive.
Cabozantinib: (Minor) Monitor for an increase in cabozantinib-related adverse reactions if coadministration with lamivudine is necessary. Cabozantinib is a Multidrug Resistance Protein 2 (MRP2) substrate and lamivudine is an MRP2 inhibitor. MRP2 inhibitors have the potential to increase plasma concentrations of cabozantinib; however, the clinical relevance of this interaction is unknown.
Canagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Dapagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Dofetilide: (Moderate) Drugs that are actively secreted via cationic secretion, such as lamivudine, should be co-administered with dofetilide with caution since they could increase dofetilide plasma concentrations via potential competition for renal tubular secretion.
Donepezil; Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as lamivudine, could result in elevated serum concentrations of one or both drugs.
Echinacea: (Moderate) Use Echinacea sp. with caution in patients taking medications for human immunodeficiency virus (HIV) infection. Some experts have suggested that Echinacea's effects on the immune system might cause problems for patients with HIV infection, particularly with long-term use. There may be less risk with short-term use (less than 2 weeks). A few pharmacokinetic studies have shown reductions in blood levels of some antiretroviral medications when Echinacea was given, presumably due to CYP induction. However, more study is needed for various HIV treatment regimens. Of the agents studied, the interactions do not appear to be significant or to require dose adjustments at the time of use. Although no dose adjustments are required, monitoring drug concentrations may give reassurance during co-administration. Monitor viral load and other parameters carefully during therapy.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Empagliflozin; Linagliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Empagliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Emtricitabine: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Tenofovir alafenamide: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Do not coadminister lamivudine, 3TC-containing products and emtricitabine-containing products due to similarities between emtricitabine and lamivudine.
Ertugliflozin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Glipizide; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Glyburide; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Interferons: (Moderate) Monitor for treatment-associated toxicities, especially hepatic decompensation, during coadministration of interferons (with or without ribavirin) and lamivudine. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh score greater than 6).
Linagliptin; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Memantine: (Moderate) Memantine is excreted in part by renal tubular secretion. Competition of memantine for excretion with other drugs that are also eliminated by tubular secretion, such as lamivudine, could result in elevated serum concentrations of one or both drugs.
Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Repaglinide: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Rosiglitazone: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Saxagliptin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Metformin; Sitagliptin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Orlistat: (Moderate) According to the manufacturer of orlistat, HIV RNA levels should be frequently monitored in patients receiving orlistat while being treated for HIV infection with anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs). Loss of virological control has been reported in HIV-infected patients taking orlistat with atazanavir, ritonavir, tenofovir disoproxil fumarate, emtricitabine, lopinavir; ritonavir, and emtricitabine; efavirenz; tenofovir disoproxil fumarate. The exact mechanism for this interaction is not known, but may involve inhibition of systemic absorption of the anti-retroviral agent. If an increased HIV viral load is confirmed, orlistat should be discontinued.
Pioglitazone; Metformin: (Moderate) Certain medications used concomitantly with metformin may increase the risk of lactic acidosis. Cationic drugs that are eliminated by renal tubular secretion, such as lamivudine, may decrease metformin elimination by competing for common renal tubular transport systems.
Procainamide: (Moderate) Cationic drugs that are eliminated by renal tubular secretion such as procainamide may compete with lamivudine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of the response to lamivudine and/or procainamide is recommended to individualize dosage. In selected individuals, procainamide serum concentration monitoring may be appropriate.
Ribavirin: (Moderate) Use lamivudine with ribavirin and interferon with caution and closely monitor for hepatic decompensation and anemia. Dose reduction or discontinuation of interferon, ribavirin, or both should be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Child-Pugh greater than 6). Hepatic decompensation (some fatal) has occurred in HCV/HIV coinfected patients who received both ribavirin/interferon and anti-retroviral nucleoside reverse transcriptase inhibitors (NRTIs) therapies. In addition, ribavirin has been shown in cell culture to inhibit phosphorylation of lamivudine, which could lead to decreased antiretroviral activity; however, while ribavirin inhibits the phosphorylation reactions required to activate lamivudine, no evidence of a pharmacokinetic or pharmacodynamic interaction has been observed.
Sorbitol: (Major) Avoid coadministration of lamivudine oral solution and sorbitol if possible due to sorbitol dose-dependent reduction in lamivudine exposure. An all-tablet regimen should be used when possible to avoid a potential interaction with sorbitol. Consider more frequent monitoring of viral load when treating with lamivudine oral solution. In a drug interaction study in 16 healthy adult patients, coadministration of a single 300 mg dose of lamivudine oral solution with sorbitol 3.2 g, 10.2 g, or 13.4 g resulted in dose-dependent decreases of 20%, 39%, and 44% in the AUC24 and 28%, 52%, and 55% in the Cmax of lamivudine.
Trospium: (Moderate) Trospium is eliminated by active tubular secretion and has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion including lamivudine. In theory, coadministration of trospium with lamivudine may increase the serum concentrations of trospium or lamivudine due to competition for the drug elimination pathway.

Epivir/Epivir HBV/Lamivudine Oral Tab: 100mg, 150mg, 300mg
Epivir/Lamivudine Oral Sol: 1mL, 10mg

300 mg/day PO for HIV and HIV/HBV coinfection; 100 mg/day PO for HBV alone.

300 mg/day PO for HIV and HIV/HBV coinfection; 100 mg/day PO for HBV alone.

300 mg/day PO for HIV and HIV/HBV coinfection; 3 mg/kg/day PO (Max: 100 mg/day) for HBV alone.

2 to 12 years: 10 mg/kg/day PO (Max: 300 mg/day) for HIV; doses up to 8 mg/kg/day PO (Max: 300 mg/day) have been recommended for HIV/HBV coinfection; 3 mg/kg/day PO (Max: 100 mg/day) for HBV alone.
1 year: 10 mg/kg/day PO for HIV; doses up to 8 mg/kg/day PO have been recommended for HIV/HBV coinfection.

3 to 11 months: 10 mg/kg/day PO for HIV; doses up to 8 mg/kg/day PO have been recommended for HIV/HBV coinfection.
1 to 2 months: Safety and efficacy have not been established; doses up to 8 mg/kg/day PO have been used off-label for HIV and HIV/HBV coinfection.

Safety and efficacy have not been established; doses up to 4 mg/kg/day PO have been used off-label for HIV.

Lamivudine is a potent reverse-transcriptase inhibitor. It has been shown to inhibit both type 1 and type 2 HIV reverse transcriptase. Lamivudine can also inhibit replication of hepatitis B virus (HBV) because this replication depends on reverse transcription of an intermediate RNA to a minus-stranded DNA, which then serves as the template for synthesis of the plus-stranded DNA. In vitro activity has been assessed in some cell lines where lamivudine showed anti-HIV activity in all virus-cell infections tested. Intracellular phosphorylation produces the 5'-triphosphate metabolite (L-TP) in vitro. This active metabolite inhibits reverse transcriptase and viral DNA synthesis. L-TP also inhibits cellular DNA polymerase. Combination therapy targets different points in the life cycle of HIV, reducing the ability of HIV to mutate to drug-resistant strains. In combination with zidovudine, lamivudine has been shown to increase CD4 cell counts and reduce HIV-1 RNA levels.[24710] [29240] [46708] [54476]
 
Treatment-emergent lamivudine resistance in HIV is believed to be caused by a single mutation at codon 184 of the HIV reverse transcriptase gene (M184V or M184I). However, this mutation inhibits the appearance of the mutation at codon 215 that is associated with resistance to zidovudine. Apart from the benefits of combination therapy in antiretroviral-naive patients, it has been found that lamivudine can restore zidovudine sensitivity for patients already carrying HIV by reversing an existing mutation at codon 215. For HBV, resistance to lamivudine develops with rtM204V/I substitutions in the YMDD motif of the catalytic domain of HBV reverse transcriptase. Other substitutions reported in lamivudine-resistant HBV isolates include rtV173L, rtL180M, rtH55R, rtL80I/V, rtV173M, rtA181T/V, rtT184S, rtF219Y, rtL229F/M/V/W, and rtQ267H. In clinical trials, the prevalence of YMDD substitutions in recipients of lamivudine (100 mg daily) was 10% and 24% at treatment weeks 24 and 52, respectively. A long-term follow up of patients with HBV receiving 100 mg of lamivudine daily found the prevalence of treatment-emergent YMDD substitutions to be 23% at year 1, 46% at year 2, 55% at year 3, 71% at year 4, and 65% at year 5.[25078] [29240] [46708]

Lamivudine is administered orally. It distributes into extravascular spaces. When administered to pregnant women, drug concentrations in cord blood are similar to those observed in maternal blood at delivery. The volume of distribution is independent of dose and does not correlate with body weight. Plasma protein binding is less than 36%. Hepatic metabolism is a minor route of elimination; most of an oral dose (71%) is excreted unchanged in the urine by active organic cationic secretion. The only known metabolite in humans is the trans-sulfoxide metabolite, which accounts for approximately 5% of a dose appearing in the urine. The mean elimination half-life after a single dose ranged from 13 to 19 hours with plasma sampling for up to 48 or 72 hours after dosing.
 
Affected cytochrome P450 isoenzymes: none
Based on in vitro study results, lamivudine at therapeutic drug exposures is not expected to affect the pharmacokinetics of drugs that are substrates of the following transporters: organic anion transporter polypeptide 1B1/3 (OATP1B1/3), breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), multidrug and toxin extrusion protein 1 (MATE1), MATE2-K, organic cation transporter 1 (OCT1), OCT2, or OCT3.
 
Lamivudine is a substrate of MATE1, MATE2-K, and OCT2 in vitro. Trimethoprim, an inhibitor of these transporters, has been shown to increase lamivudine plasma concentrations; however, the interaction is not considered clinically significant as no dose adjustments are necessary. Lamivudine is also a substrate of P-gp and BCRP; however, considering its absolute bioavailability (87%), it is unlikely that these transporters play a significant role in the absorption of lamivudine and coadministration of drugs that affect these transporters is unlikely to affect the disposition and elimination of lamivudine.

Lamivudine absorption is rapid, with a mean absolute bioavailability of 86% for the tablet and 87% for the oral solution. The bioavailability in children is about 66%. Food has no significant effect on systemic exposure. Food decreases Cmax and increases time to Cmax, but does not affect the bioavailability. AUC and Cmax increase in proportion to oral dose over the range from 0.25 to 10 mg/kg.

There have been no studies of Epivir-HBV in pregnant patients with hepatitis B virus (HBV), and there are no data regarding the effects on vertical transmission; appropriate infant immunizations should be used to prevent neonatal acquisition of HBV. For HIV, antiretroviral therapy should be provided to all patients during pregnancy, regardless of HIV RNA concentrations or CD4 cell count. Using highly active antiretroviral combination therapy (HAART) to maximally suppress viral replication is the most effective strategy to prevent the development of resistance and to minimize the risk of perinatal transmission. Begin HAART as soon as pregnancy is recognized, or HIV is diagnosed. HIV guidelines recommend lamivudine as part of a preferred 2-NRTI backbone in patients who are pregnant or trying to conceive. Available data from the Antiretroviral Pregnancy Registry, which includes more than 5,500 first trimester exposures to lamivudine, have shown no difference in the risk of overall major birth defects when compared to the 2.7% background rate among pregnant women in the US. When exposure occurred in the first trimester, prevalence of defects was 3.1% (95% CI: 2.6% to 3.6%). Nucleoside reverse transcriptase inhibitors (NRTIs) are known to induce mitochondrial dysfunction. An association of mitochondrial dysfunction in infants and in-utero antiretroviral exposure has been suggested, but not established. While the development of severe or fatal mitochondrial disease in exposed infants appears to be extremely rare, more intensive monitoring of hematologic and electrolyte parameters during the first few weeks of life is advised. Nucleoside analogs have been associated with the development of lactic acidosis, especially during pregnancy. It is unclear if pregnancy augments the incidence of lactic acidosis/hepatic steatosis in patients receiving nucleoside analogs. However, because pregnancy itself can mimic some early symptoms of the lactic acid/hepatic steatosis syndrome or be associated with other significant disorders of liver metabolism, clinicians need to be alert for early diagnosis of this syndrome. Pregnant patients receiving nucleoside analogs should have LFTs and serum electrolytes assessed more frequently during the last trimester of pregnancy, and any new symptoms should be evaluated thoroughly. Regular laboratory monitoring is recommended to determine antiretroviral efficacy. Monitor CD4 counts at the initial visit. Patients who have been on HAART for at least 2 years and have consistent viral suppression and CD4 counts consistently greater than 300 cells/mm3 do not need CD4 counts monitored after the initial visit during the pregnancy. However, CD4 counts should be monitored every 3 months during pregnancy for patients on HAART less than 2 years, patients with CD4 count less than 300 cells/mm3, or patients with inconsistent adherence or detectable viral loads. Monitor plasma HIV RNA at the initial visit (with review of prior levels), 2 to 4 weeks after initiating or changing therapy, monthly until undetectable, and then at least every 3 months during pregnancy. Viral load should also be assessed at approximately 36 weeks gestation, or within 4 weeks of delivery, to inform decisions regarding mode of delivery and optimal treatment for newborns. Patients whose HIV RNA levels are above the threshold for resistance testing (usually greater than 500 copies/mL but may be possible for levels greater than 200 copies/mL in some laboratories) should undergo antiretroviral resistance testing (genotypic testing, and if indicated, phenotypic testing). Resistance testing should be conducted before starting therapy in treatment-naive patients who have not been previously tested, starting therapy in treatment-experienced patients (including those who have received pre-exposure prophylaxis), modifying therapy in patients who become pregnant while receiving treatment, or modifying therapy in patients who have suboptimal virologic response to treatment that was started during pregnancy. DO NOT delay initiation of antiretroviral therapy while waiting on the results of resistance testing; treatment regimens can be modified, if necessary, once the testing results are known. First trimester ultrasound is recommended to confirm gestational age and provide an accurate estimation of gestational age at delivery. A second trimester ultrasound can be used for both anatomical survey and determination of gestational age in those patients not seen until later in gestation. Perform standard glucose screening in patients receiving antiretroviral therapy at 24 to 28 weeks gestation, although it should be noted that some experts would perform earlier screening with ongoing chronic protease inhibitor-based therapy initiated prior to pregnancy, similar to recommendations for patients with high-risk factors for glucose intolerance. Liver function testing is recommended within 2 to 4 weeks after initiating or changing antiretroviral therapy, and approximately every 3 months thereafter during pregnancy (or as needed). All pregnant patients should be counseled about the importance of adherence to their antiretroviral regimen to reduce the potential for development of resistance and perinatal transmission. It is strongly recommended that antiretroviral therapy, once initiated, not be discontinued. If a patient decides to discontinue therapy, a consultation with an HIV specialist is recommended. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to lamivudine; information about the registry can be obtained at www.apregistry.com or by calling 1-800-258-4263.

HIV treatment guidelines recommend clinicians provide mothers with evidence-based, patient-centered counseling to support shared decision-making regarding infant feeding. Inform patients that use of replacement feeding (i.e., formula or banked pasteurized donor human milk) eliminates the risk of HIV transmission; thus, replacement feeding is recommended for use when mothers with HIV are not on antiretroviral therapy (ART) or do not have suppressed viral load during pregnancy, as well as at delivery. For patients on ART who have achieved and maintained viral suppression during pregnancy (at minimum throughout the third trimester) and postpartum, the transmission risk from breast-feeding is less than 1%, but not zero. Virologically suppressed mothers who choose to breast-feed should be supported in this decision. If breast-feeding is chosen, counsel the patient about the importance of adherence to therapy and recommend that the infant be exclusively breast-fed for up to 6 months of age, as exclusive breast-feeding has been associated with a lower rate of HIV transmission as compared to mixed feeding (i.e., breast milk and formula). Promptly identify and treat mastitis, thrush, and cracked or bleeding nipples, as these conditions may increase the risk of HIV transmission through breast-feeding. Breast-fed infants should undergo immediate diagnostic and virologic HIV testing. Testing should continue throughout breast-feeding and up to 6 months after cessation of breast-feeding. For expert consultation, healthcare workers may contact the Perinatal HIV Hotline (888-448-8765). Lamivudine was found to be secreted in human breast milk during a study involving 20 breast-feeding mothers with HIV who were administered either 300 mg of lamivudine twice daily as a single agent (n = 10) or lamivudine 150 mg twice daily in combination with zidovudine (n = 10). The mean breast milk concentrations of lamivudine in the respective groups were similar at 1.22 mg/L (range less than 0.5 to 6.09 mg/L) and 0.9 mg/L (range less than 0.5 to 8.2 mg/L). Use of lamivudine in HIV-negative breast-feeding mothers being treated for hepatitis B infection has not been studied; a consensus among health-care providers regarding the use of lamivudine in this population has not been established. Other antiretroviral mediations whose passage into human breast milk have been evaluated include tenofovir, nevirapine, zidovudine, and nelfinavir.