Professional Drug Information > Lamivudine

Lamivudine (Systemic)

VA CLASSIFICATION
Primary: AM840

Commonly used brand name(s): 3TC; Epivir; Epivir-HBV; Heptovir.

Another commonly used name is
3TC^{34}
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antiviral (systemic)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

General considerations
Lamivudine is the negative enantiomer of 2"-deoxy-3"-thiacytidine ^{{06} {11}}. Both the positive and negative enantiomers have in vitro activity against human immunodeficiency virus (HIV) ^{05}, but the negative enantiomer has greater activity ^{11} and less toxicity ^{{05} {11}}. In vitro inhibition of DNA polymerase gamma, which is thought to be associated with peripheral neuropathy, is minimal ^{{05} {06} {09} {11} {18}}.

Lamivudine has in vitro activity against HIV-1 and HIV-2, including zidovudine-resistant isolates ^{{05} {06} {09} {11}}, as well as hepatitis B virus ^{05}. Lamivudine is indicated in combination with other antiretroviral agents for the treatment of HIV infection ^{01}{28}. Lamivudine and zidovudine have been found to act synergistically in vitro ^{{12} {13}}. This is thought to produce better efficacy than either medication alone ^{17}. Resistance to lamivudine is associated with a mutation at codon 184 in HIV-1 reverse transcriptase ^{{01} {24}}; this can suppress the expression of pre-existing resistance to zidovudine in a number of different HIV isolates ^{24}. Strains of HIV-1 resistant to both lamivudine and zidovudine have been isolated ^{01}. Reduced sensitivity of hepatitis B virus (HBV) to lamivudine is related to mutations resulting in a methionine to valine or isoleucine substitution in the YMDD motif of the catalytic domain of HBV polymerase (position 552) and a leucine to methionine substitution at position 528 ^{27}.

Accepted

Hepatitis B, chronic (treatment)—Lamivudine is indicated in the treatment of chronic hepatitis B associated with evidence of hepatitis B viral replication and active liver inflammation. This use is based on 1–year histologic and serologic responses in patients with compensated chronic hepatitis B^{27}.

Human immunodeficiency virus (HIV) infection (treatment) or
Immunodeficiency syndrome, acquired (AIDS) (treatment)—Lamivudine is indicated, in combination with zidovudine^{30}or other antiretroviral agents, in the treatment of HIV infection or AIDS when therapy is warranted based on clinical and/or immunological evidence of disease progression ^{{01} {12} {18}{28}}.

[Human immunodeficiency virus (HIV) infection, occupational exposure (prophylaxis)]¹—Lamivudine may be used prophylactically in health care workers at risk of acquiring HIV infection after occupational exposure to the virus. It is being used in combination with zidovudine and, in some cases, a protease inhibitor. ^{20}

Note: Safety and efficacy of lamivudine in the treatment of chronic hepatitis B have not been established in patients with decompensated liver disease or organ transplants; pediatric patients; or patients dually infected with hepatitis B and hepatitis C, hepatitis delta, or HIV; or for a treatment period greater than 1 year.^{27}

¹ Not included in Canadian product labeling.

Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    229.26 ^{02}

Mechanism of action/Effect:

Lamivudine is metabolized intracellularly to its active 5"–triphosphate metabolite, lamivudine triphosphate (L-TP), which inhibits human immunodeficiency virus (HIV) reverse transcription and hepatitis B virus polymerase activity via viral DNA chain termination ^{{01} {06} {09} {18}{14}{15}{27}}.

Absorption:

Rapidly absorbed; bioavailability in adults and adolescents is 80 to 88% ^{{01} {05} {09} {10} {18}} and in children is approximately 66 ^{{01} {18}} to 68% ^{21}. Food delays the peak serum concentration and the time to peak serum concentration; however, there is no significant difference in bioavailability ^{{06} {18}}. Therefore, lamivudine may be administered with or without food ^{{01} {06} {18}}.

Distribution:

Lamivudine is widely distributed. Lamivudine crosses the blood-brain barrier and is distributed into the cerebrospinal fluid (CSF) to a limited extent ^{{01} {05}}. In children, CSF concentrations ranged from 10 to 17% of the corresponding, non–steady-state serum concentration ^{21}. Lamivudine crosses the placenta in rats, rabbits ^{01}, and humans ^{22}.

Apparent Vol _D= Approximately 1.3 liters per kg ^{{01} {09} {18}}.

Protein binding:

Low (36%) ^{{01} {18}}.

Biotransformation:

Trans-sulfoxide is the only known metabolite of lamivudine; serum concentrations of this metabolite have not been determined ^{01}{27}.

Half-life:


Intracellular lamivudine triphosphate:

11 to 15 hours ^{{01} {06} {09} {18}}.



Lamivudine (serum):

Adults: 2.6 ± 0.5 hours ^{{31} {01} {05} {09} {10} {11} {18} {19}}.

Children (4 months to 14 years of age): 1.7 to 2 hours ^{{01} {21}}.



Renal function impairment:

Creatinine clearance, 10 to 40 mL per min (mL/min) (0.17 to 0.67 mL per sec [mL/sec])—Approximately 13.6 hours ^{19}.

Creatinine clearance, less than 10 mL/min (0.17 mL/sec)—Approximately 19.4 hours ^{19}.


Time to peak concentration:

Approximately 0.5 to 2 hours after a single 100–milligram dose^{27}.


With food:

Approximately 3.2 hours ^{{01} {06}}.



Fasting:

Approximately 1 hour ^{{01} {05} {06} {09}}.


Peak serum concentration:


Adults and adolescents:

2 mg per kg of body weight (mg/kg): 1.5 micrograms per mL (mcg/mL) (6.5 micromoles per liter) ^{{01} {18}}.



Children:

8 mg/kg: 1.1 mcg/mL (4.8 micromoles per liter) ^{01}.


Elimination:
    Renal; the majority of lamivudine is eliminated unchanged in the urine (68 to 71%) ^{{01} {06} {09} {18}}; approximately 5.2% of the trans-sulfoxide metabolite is excreted in the urine within 12 hours ^{01}. The renal clearance of lamivudine is greater than the glomerular filtration rate, implying active secretion into the renal tubules ^{09}.


In dialysis—
        Hemodialysis increases lamivudine clearance by a mean of 24 mL/min, however, the length of dialysis treatment (i.e., 4 hours) may not be long enough to alter mean lamivudine exposure. Thus, dose modification beyond correction for creatinine clearance is not required after routine dialysis.^{27}
        It is not known whether lamivudine is removed by peritoneal dialysis or continuous (24 hour) hemodialysis ^{01}.



Precautions to Consider

Carcinogenicity

Studies in mice and rats given lamivudine doses 10 times and 58 times the human therapeutic HIV dose, respectively, have shown no evidence of carcinogenic potential.^{28} Studies in mice and rats given 34 times and 200 times the human therapeutic hepatitis B dose, respectively, have shown no evidence of carcinogenic potential.^{27}{29}

Mutagenicity

Lamivudine was not active in a microbial mutagenicity screen or in an in vitro cell transformation assay. It showed weak in vitro mutagenic activity in a cytogenic assay using cultured human lymphocytes and in the mouse lymphoma assay. However, lamivudine showed no evidence of in vivo genotoxic activity in rats at oral doses of up to 2000 mg per kg of body weight (mg/kg), which is approximately 65 times the recommended human dose based on body surface area ^{01}{27}{28}.

Pregnancy/Reproduction
Fertility—
Rats given doses of lamivudine up to 130 times the usual adult dose based on body surface area revealed no evidence of impaired fertility ^{01}{28} No evidence of impaired fertility or adverse effects on offspring were noted in rats given doses up to 4000 mg per kg daily (plasma levels 80 to 120 times those in humans).^{27}.

Pregnancy—
Adequate and well-controlled studies have not been done in humans ^{{01} {18}}. However, lamivudine has been found to cross the placenta in humans ^{22}.

Lamivudine crosses the placenta in rats and rabbits ^{{01} {18}}. Studies have been done in rats and rabbits administered doses up to approximately 130 and 60 times the usual adult dose, respectively. Some evidence of embryo lethality in rabbits, but not in rats, at doses similar to the usual adult dose or higher has been seen ^{01}.

FDA Pregnancy Category C ^{01}.

Note: Physicians are encouraged to register patients in the Lamivudine Pregnancy Registry, a registry set up to monitor maternal-fetal outcomes of exposure to lamivudine during pregnancy, by calling 800–258–4263.^{27}


Breast-feeding

Lamivudine is distributed into human breast milk .^{31}

The manufacturer recommends that patients not breast-feed while taking lamivudine.^{27}{28}

Pediatrics

In one study, pancreatitis was reported in 14 of 97 (14%) and paresthesias and peripheral neuropathies were seen in 13 of 97 (13%) of pediatric patients receiving lamivudine monotherapy ^{{01} {18}}. However, the patients who developed these complications had advanced HIV disease and a prior history of pancreatitis, most commonly associated with the use of didanosine ^{{21} {26}}. The combination of lamivudine and zidovudine should be used with caution in children with advanced HIV disease and/or a history of pancreatitis. In addition, an increase in serum transaminases (greater than 10 times the upper limits of normal) was observed in 3 of 89 (3%) of pediatric patients receiving lamivudine monotherapy ^{21}.

The pharmacokinetics of lamivudine have not been studied in combination with zidovudine in children ^{{01} {18}}. Pharmacokinetic properties of lamivudine monotherapy were assessed in 57 children (ages 4.8 months to 16 years). The absolute bioavailability was 66 to 68%, which is less than the 86% seen in adults and adolescents ^{{01} {21}}. The mechanism for this diminished bioavailability in infants and children is unknown ^{01}. The area under the serum concentration–time curve (AUC) was comparable for pediatric patients receiving a dose of 8 mg/kg per day and adults receiving a dose of 4 mg/kg per day ^{01}.


Geriatrics


Although appropriate studies on the relationship of age to the effects of lamivudine have not been performed in the geriatric population, no geriatrics-specific problems have been documented to date. However, elderly patients are more likely to have age-related renal function impairment, which may require a dosage adjustment in patients receiving lamivudine.

Lamivudine pharmacokinetics have not been studied in patients over 65 years of age ^{01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Lamivudine tablets and oral solution for treatment of human immunodeficiency virus (HIV) contain a higher dose than lamivudine tablets and oral solution for treatment of hepatitis B; the two formulations of lamivudine (higher- and lower-dose tablets/oral solution) should not be used concurrently ^{27}. Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Drugs associated with pancreatitis, such as alcohol, didanosine, intravenous pentamidineor sulfonamides    (pancreatitis was seen in 14% (14 of 97) of pediatric patients receiving lamivudine monotherapy; this population had advanced HIV disease and a history of pancreatitis ^{21}; although no interactions have been documented to date, concurrent use of lamivudine with medications associated with the development of pancreatitis should be avoided or, if concurrent use is necessary, used with caution ^{{01} {18}})


Drugs associated with peripheral neuropathy, such as dapsone, didanosine, isoniazid or stavudine    (paresthesias and peripheral neuropathy were seen in 13% (13 of 97) of pediatric patients with advanced HIV disease receiving lamivudine monotherapy ^{21}; although no interactions have been documented to date, other medications associated with the development of neuropathy should be avoided or, if concurrent use is necessary, used with caution ^{{01} {18}})


Indinavir ^{23}    (concurrent administration of lamivudine 150 mg twice a day, indinavir 800 mg every eight hours, and zidovudine 200 mg every eight hours resulted in a 6% decrease in the AUC of lamivudine, no change in AUC of indinavir, and a 36% increase in the AUC of zidovudine; no adjustment in dose is necessary )


Lamivudine and zidovudine    (lamivudine and zidovudine fixed dose combination tablet should not be administered concomitantly with lamivudine tablets or lamivudine oral solution.)

^{33}
Sulfamethoxazole and trimethoprim combination    (in one small study, concurrent administration of sulfamethoxazole and trimethoprim combination resulted in a 44% increase in lamivudine AUC, and a decrease of 29% in lamivudine oral clearance and a 30% decrease in lamivudine renal clearance ^{{01} {07}{33}}; the pharmacokinetic properties of sulfamethoxazole and trimethoprim were not altered by concurrent administration of lamivudine ^{{01} {07}}; no adjustment in dose is necessary unless the patient has renal function impairment ^{18})


Zalcitabine    (Lamivudine and zalcitabine may inhibit the phosphorylation of one another and concurrent administration is not recommended)

^{33}
Zidovudine    (in one small study, concurrent administration of lamivudine resulted in a 39% increase in the peak plasma concentration of zidovudine ^{01}; although statistically significant, this increase is not thought to be significant to patient safety ^{18}; no significant changes were observed in the AUC or total clearance of lamivudine or zidovudine ^{{01} {08}})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and ^{{21} {25}}
Aspartate aminotransferase (AST [SGOT]) ^{{21} {25}}    (an increase in serum transaminases [greater than 10 times the upper limits of normal] was observed in 3 of 89 (3%) of pediatric patients receiving lamivudine monotherapy ^{21})


Amylase, serum ^{{01} {18}}    (values may be increased)


Hemoglobin concentration ^{01} and
Neutrophil count ^{{01} {05} {11}}    (values may be decreased)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Human immunodeficiency virus (HIV) ^{27}    (HIV counseling and testing should be offered to patients with hepatitis B before they initiate lamivudine. Lamivudine tablets and oral solution for treatment of hepatitis B contain a lower dose than lamivudine tablets and oral solution for treatment of HIV. If lamivudine treatment for chronic hepatitis B is prescribed for a patient with unrecognized or untreated HIV, rapid emergence of HIV resistance to lamivudine is likely to occur because of the subtherapeutic dose and inappropriate monotherapy ^{27}.)


Hypersensitivity to lamivudine ^{01}
Pancreatitis, or history of ^{{01} {18}}    (pancreatitis occurred in 14% (14 of 97) of pediatric patients receiving lamivudine monotherapy; these patients had advanced HIV disease and a history of pancreatitis ^{21}; pancreatitis has been reported rarely in adults ^{01}; lamivudine should be used with extreme caution in patients who have pancreatitis or a history of pancreatitis)


Peripheral neuropathy, or history of    (peripheral neuropathy occurred in approximately 13% (13 of 97) of pediatric patients receiving lamivudine monotherapy ^{01}; these patients had advanced HIV disease ^{21}; it has also been reported rarely in adults ^{{04} {11}}; lamivudine should be used with caution in patients who have peripheral neuropathy or a history of peripheral neuropathy)


» Renal function impairment ^{{01} {18} {19}}    (decreased renal function has been found to result in an increase in the peak plasma concentration and elimination half-life of lamivudine; dosage modification is recommended in patients with a creatinine clearance of < 50 mL/min [0.83 mL/sec])



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Alanine aminotransferase (ALT [SGPT]) and ^{{21} {25}}
Aspartate aminotransferase (AST [SGOT]) ^{{21} {25}}    (an increase in serum transaminases [greater than 10 times the upper limits of normal] was observed in 3 of 89 (3%) of pediatric patients receiving lamivudine monotherapy ^{21})

    (exacerbation of hepatitis has occurred following discontinuation of lamivudine; post-treatment clinical and laboratory follow-up should be maintained^{27} for at least 4 months^{29})


» Amylase, serum, and ^{{01} {18} {21}}
» Lipase, serum, and ^{21}
Triglycerides, serum ^{{01} {18}}    (lamivudine administration has been associated with pancreatitis in approximately 14% of pediatric patients; patients should be monitored for laboratory changes consistent with pancreatitis, such as elevated amylase, lipase, and triglyceride concentrations)


» Blood urea nitrogen (BUN) and
» Creatinine, serum ^{01}    (blood urea nitrogen and serum creatinine concentrations should be monitored in patients with renal function impairment; an adjustment in dosage or dosage interval may be required)






Side/Adverse Effects

Note: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including lamivudine, alone or in combination. A majority of these cases have been in women.^{33}
Lamivudine is given in combination with other antiretroviral agents ^{{01} {18}{28}}. Some side effects, such as pancreatitis, peripheral neuropathy and hematologic abnormalities may be seen with other antiretroviral agents, such as zidovudine, and/or severe human immunodeficiency virus (HIV) disease; therefore, differentiation between the side effects of lamivudine and other medications or the complications of HIV disease may be difficult.
In one study, 14 of 97 pediatric patients (14%) being treated with lamivudine monotherapy developed pancreatitis; in a second pediatric study, 7 of 47 patients (15%) receiving lamivudine in combination therapy with other antiretroviral agents developed pancreatitis ^{01}. Pancreatitis was most commonly seen in patients who had advanced HIV disease, as well as a prior history of pancreatitis, most commonly associated with the use of didanosine ^{{21} {26}}. The combination of lamivudine and zidovudine therapy should be used with caution in pediatric patients with a history of pancreatitis or other risk factors for pancreatitis ^{01}. Pancreatitis was seen in only 3 of 656 adult patients (< 0.5%) who received lamivudine ^{{01} {18}}. Lamivudine should be discontinued immediately if any signs or symptoms of pancreatitis occur ^{18}. In addition, an increase in serum transaminases (greater than 10 times the upper limits of normal) was observed in 3 of 89 (3%) of pediatric patients receiving lamivudine monotherapy. ^{21}
Paresthesias and peripheral neuropathy were reported in 13% of pediatric patients ^{01} and have been reported rarely in adults ^{{04} {11}}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Pancreatitis (nausea ; vomiting; severe abdominal or stomach pain)^{01}— more frequent in children
    
paresthesias and peripheral neuropathy ( tingling, burning, numbness, or pain in the hands, arms, feet, or legs)^{01}{04}{11}—more frequent in children
    
splenomegaly ( abdominal pain; feeling of fullness)—more frequent in children
^{31}
Incidence rare
    
Anemia (unusual tiredness or weakness)^{01}{25}
    
severe hepatomegaly with steatosis ^{27}(abdominal discomfort; feeling of fullness)
    
lactic acidosis ^{27}(abdominal discomfort ; decreased appetite ; diarrhea ; fast, shallow breathing ; general feeling of discomfort ; muscle pain or cramping ; nausea ; shortness of breath ; sleepiness ; unusual tiredness or weakness )
    
neutropenia (fever, chills, or sore throat)^{01}{25}
    
skin rash ^{{01}{11}{15}{18}}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Ear erythema ( redness of skin; unusually warm skin)—more frequent in children^{31}
    
ear discharge —more frequent in children ^{31}
    
ear pain —more frequent in children^{31}
    
ear swelling — more frequent in children^{31}
    
lymphadenopathy (swollen, painful, or tender lymph glands in neck, armpit, or groin )—more frequent in children ^{31}
    
nasal discharge or congestion — more frequent in children^{31}
    
stomatitis (canker sores ; sores, ulcers, or white spots on lips or tongue or inside the mouth)— more frequent in children^{31}
    
wheezing — more frequent in children^{31}

Incidence less frequent
    
Cough ^{01}{05}{18}
    
dizziness ^{01}{15}{18}
    
fatigue (unusual tiredness or weakness)^{{01}{05}{09}{12}{15}{18}{25}}
    
gastrointestinal distress ^{{01}{05}{11}{12}{18}{25}}(abdominal or stomach pain ^{{05} {09} {11}}; diarrhea ^{{05} {11} {15}}; nausea; vomiting ^{{05} {25}})
    
headache ^{{01}{05}{09}{11}{12}{15}{18}{25}}
    
insomnia (trouble sleeping )^{{01}{05}{11}{18}}

Incidence rare
    
Hair loss ^{03}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing ).

Clinical effects of overdose
There is one reported case in which an adult ingested 6 grams of lamivudine; no clinical signs and symptoms were noted and hematologic tests remained normal ^{{01} {18}}

Two cases of pediatric overdose were reported in study ACTG300. One case was a single dose of 7 mg/kg of lamivudine; the second case involved administration of 5 mg/kg of lamivudine twice daily for 30 days. There were no clinical signs or symptoms noted in either case.^{28}

Treatment of overdose
There is no known antidote for lamivudine. ^{{01} {18}{27}{28}}

Lamivudine is not removed by hemodialysis. It is not known whether lamivudine is removed by peritoneal dialysis or continuous (24 hour) hemodialysis. ^{27}

Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Lamivudine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Hypersensitivity to lamivudine

Pregnancy—Lamivudine crosses the placenta. Lamivudine has caused embryo lethality in rabbits at doses similar to the usual adult dose or higher; physicians are encouraged to register pregnant patients





Breast-feeding—Lamivudine is distributed in human breast milk





Use in children—Lamivudine monotherapy has resulted in the development of pancreatitis in 14% (14 of 97) of children with advanced HIV disease and a prior history of pancreatitis, and paresthesias and peripheral neuropathies in 13% (13 of 97) of pediatric patients with advanced HIV disease; in addition, an increase in serum transaminases (greater than 10 times the upper limits of normal) was observed in 3 of 89 (3%) of pediatric patients receiving lamivudine monotherapy ^{21}; the absolute bioavailability is 66 to 68% in children, less than the 86% seen in adults and adolescents

Other medical problems, especially renal function impairment or untreated or potentially unrecognized human immunodeficiency virus ^{27}.

Proper use of this medication
» Importance of not taking more medication than prescribed; importance of not discontinuing lamivudine or zidovudine without checking with physician

» Compliance with full course of therapy

» Importance of not missing doses and of taking at evenly spaced times

Proper administration technique for oral liquids

Not sharing medication with others

» Proper dosing
Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Regular visits to physician for blood tests

» Importance of not taking other medications concurrently without checking with physician


Side/adverse effects
Signs of potential side effects, especially hepatomegaly with steatosis, lactic acidosis, pancreatitis, paresthesias, peripheral neuropathy, splenomegaly, anemia, neutropenia, or skin rash


General Dosing Information
Lamivudine may be taken on a full or empty stomach ^{{01} {06}{29}}.

Lamivudine tablets and lamivudine oral solution for HIV patients (Epivir)contain a higher dose of the same active ingredient that is found in lamivudine tablets and oral solution for hepatitis B patients(Epivir-HBV ). The formulation and dosage of lamivudine in Epivir-HBV is not appropriate for patients who are infected with both HIV and HBV.^{33}

If treatment with lamivudine Epivir-HBVis prescribed for a patient with unrecognized or untreated HIV infection, rapid emergence of HIV resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV treatment. ^{33}

If a decision is made to administer lamivudine to patients dually infected with HIV and HBV, an appropriate combination regimen should be used. ^{33}

Before beginning treatment of hepatitis B infection, patients should be assessed by a physician experienced in the management of chronic hepatitis B ^{27}.

Hepatitis B virus—Adults and adolescents with renal function impairment require a reduction in dose as follows^{27}:

Creatinine Clearance (mL/min)/(mL/sec)	Dose
³50/0.83	100 mg once a day
30–49/0.50–0.82	100 mg first dose, then 50 mg once a day
15–29/0.25–0.48	100 mg first dose, then 25 mg once a day
5–14/0.08–0.23	35 mg first dose, then 15 mg once a day
<5/<0.08	35 mg first dose, then 10 mg once a day

Human immunodeficiency virus—Adults and adolescents with renal function impairment require a reduction in dose as follows ^{{01} {18}}:

Creatinine Clearance (mL/min)/(mL/sec)	Dose
³50/0.83	150 mg twice a day
30–49/0.50–0.82	150 mg once a day
15–29/0.25–0.48	150 mg first dose, then 100 mg once a day
5–14/0.08–0.23	150 mg first dose, then 50 mg once a day
<5/<0.08	50 mg first dose, then 25 mg once a day

Oral Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

LAMIVUDINE ORAL SOLUTION

Usual adult and adolescent dose
Hepatitis B, chronic (treatment)
Oral, 100 mg of lamivudine once a day. The optimum duration of treatment is unknown ^{27}{29}

Human immunodeficiency virus (HIV) infection (treatment) or
Immunodeficiency syndrome, acquired (AIDS) (treatment)
Adults and adolescents weighing 50 kg (110 pounds) or more: Oral, 150 mg of lamivudine twice a day ^{{01} {18}} in combination with other antiretroviral agents^{31}{28}.

Adults weighing less than 50 kg (110 pounds): Oral, 2 mg per kg of body weight of lamivudine twice a day in combination with other antiretroviral agents ^{28}{31}.

[Human immunodeficiency virus (HIV) infection, occupational exposure (prophylaxis)]¹
Oral, 150 mg of lamivudine twice a day, in combination with zidovudine 200 mg three times a day, for four weeks. In certain cases, a protease inhibitor may also be added to the regimen. ^{20}


Note: Lamivudine doses should be adjusted in accordance with renal function^{31}


Note: Patients that require treatment for both hepatitis B and either HIV or AIDS should follow the HIV/AIDS dosing regimen^{32}.


Usual pediatric dose
Hepatitis B, chronic (treatment)
Children 16 years of age and older: See Adult and adolescent dose.^{29}

Children up to 16 years of age: Safety and efficacy have not been established.^{27}{29}

Human immunodeficiency virus (HIV) infection (treatment) or
Immunodeficiency syndrome, acquired (AIDS) (treatment)
Children 16 years of age and older: See Adult and adolescent dose .^{28}

Children 3 months to 16 years of age: Oral, 4 mg per kg of body weight of lamivudine, up to a 150-mg dose, twice a day^{18}{28} in combination with other antiretroviral agents^{28}.

Children up to 3 months of age: Safety and efficacy have not been established.^{28}Reduce dose in children with renal impairment.


Note: Patients that require treatment for both hepatitis B and either HIV or AIDS should follow the HIV/AIDS dosing regimen^{32}.


Strength(s) usually available
U.S.—


10 mg per mL (Rx) [Epivir (ethanol 6% v/v ) (methylparaben) (propylparaben ) (sucrose)]


5 mg per mL (Rx) [Epivir-HBV (methylparaben ) (propylene glycol) ( propylparaben) (sodium citrate) ( sucrose)]

Canada—


10 mg per mL (Rx) [3TC (ethanol 6% v/v) (methylparaben) (propylparaben) (sucrose)]


5 mg per mL (Rx) [Heptovir (methylparaben ) (propylparaben) (propylene glycol) (sodium citrate) ( sucrose)]

Packaging and storage:
Store between 2 and 25 ºC (36 and 77 ºF) in a tight container ^{{01} {18}}.

Auxiliary labeling:
   • Continue medicine for full time of treatment.

Note: When dispensing, include a calibrated liquid-measuring device.



LAMIVUDINE TABLETS

Usual adult and adolescent dose
See Lamivudine Oral Solution .

Usual pediatric dose
See Lamivudine Oral Solution .

Strength(s) usually available
U.S.—


150 mg (Rx) [Epivir]


100 mg (Rx) [Epivir-HBV]

Canada—


150 mg (Rx) [3TC]


100 mg (Rx) [Heptovir]

Packaging and storage:
Store between 2 and 30 ºC (36 and 86 ºF) in a tight container ^{{01} {18}}.

Auxiliary labeling:
   • Continue medicine for full time of treatment.

Developed: 08/08/1996
Revised: 02/10/2003

References

1. Epivir package insert (Glaxo Wellcome—US), New 11/95, Rec 1/96.
   

2. Fleeger CA, editor. USP dictionary of USAN and international drug names 1996. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1995: 390.
   

3. Fong IW. Hair loss associated with lamivudine. Lancet 1994; 344: 1702.
   

4. Cupler EJ, Dalakas MC. Exacerbation of peripheral neuropathy by lamivudine. Lancet 1995; 345: 460-1.
   

5. van Leeuwen R, Katlama C, Kitchen V, et al. Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study. J Infect Dis 1995; 171: 1166-71.
   

6. Angel JB, Hussey EK, Hall ST, et al. Pharmacokinetics of 3TC (GR109714X) administered with and without food to HIV-infected patients. Drug Invest 1993; 6(2): 70-4.
   

7. Moore K, Raasch R, Yuen G, et al. Pharmacokinetics (PK) of lamivudine (3TC) administered alone and with oral trimethoprim (TMP) plus sulfamethoxazole (SMX) in patients with human immunodeficiency virus (HIV) infection [abstract PI–32]. Clin Pharmacol Ther 1995; 57(2): 143.
   

8. Horton CM, Yuen G, Mikolich DM, et al. Pharmacokinetics (PK) of oral lamivudine administered alone and with oral zidovudine (ZDV) in asymptomatic patients with human immuno-deficiency virus (HIV) infection [abstract PIII–64]. Clin Pharmacol Ther 1994; 55(2): 198.
   

9. van Leeuwen R, Lange JMA, Hussey EK, et al. The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study. AIDS 1992; 6: 1471-5.
   

10. Yuen GJ, Morris DM, Mydlow PK, et al. Pharmacokinetics, absolute bioavailability, and absorption characteristics of lamivudine. J Clin Pharmacol 1995; 35: 1174-80.
    

11. Pluda JM, Cooley TP, Montaner JSG, et al. A phase I/II study of 2"-deoxy-3"-thiacytidine (lamivudine) in patients with advanced human immunodeficiency virus infection. J Infect Dis 1995; 171: 1438-47.
    

12. Eron JJ, Benoit SL, Jemsek J, et al. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. N Engl J Med 1995; 333(25): 1662-9.
    

13. Mathez D, Schinazi RF, Liotta DC, Leibowitch J. Infectious amplification of wild-type human immunodeficiency virus from patients" lymphocytes and modulation by reverse transcriptase inhibitors in vitro. Antimicrob Agents Chemother 1993; 37(10): 2206-11.
    

14. Benhamou Y, Dohin E, Lunel-Fabiani, et al. Efficacy of lamivudine on replication of hepatitis B virus in HIV-infected patients. Lancet 1995; 345: 396-7.
    

15. Dienstag JL, Perrillo RP, Schiff ER, et al. A preliminary trial of lamivudine for chronic hepatitis B infection. N Engl J Med 1995; 333(25): 1657-61.
    

16. Honkoop P, de Man RA, Heijtink RA, Schalm SW. Hepatitis B reactivation after lamivudine. Lancet 1995; 346: 1156-7.
    

17. Caliendo AM, Hirsch MS. Combination therapy for infection due to human immunodeficiency virus type 1. Clin Infect Dis 1994; 18: 516-24.
    

18. 3TC product monograph (Glaxo Wellcome—Canada), New 12/95, Rec 4/96.
    

19. Heald AE, Hsyu PH, Yuen GJ, et al. Pharmacokinetics of lamivudine in human immunodeficiency virus-infected patients with renal dysfunction. Antimicrob Agents Chemother 1996; 40(6): 1514-9.
    

20. Centers for Disease Control and Prevention. Update: Provisional public health service recommendations for chemoprophylaxis after occupational exposure to HIV. MMWR 1996; 45(22): 468-72.
    

21. Lewis LL, Venzon D, Church J, et al. Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. J Infect Dis 1996; 174: 16-25.
    

22. Panel comment, 7/96.
    

23. Crixivan package insert (Merck—US), Rev 3/96, Rec 7/96.
    

24. Staszewski S, Loveday C, Picazo JJ, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients. JAMA 1996; 276: 111-7.
    

25. Katlama C, Ingrand D, Loveday C, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. JAMA 1996; 276: 118-25.
    

26. Panel comment, 6/96.
    

27. Product Information: Epivir®-HBV™, lamivudine tablets and oral solution. Physicians' Desk Reference (electronic version), MICROMEDEX, Inc, Englewood, CO (PI revised 12/1998) reviewed 3/2000.
    

28. Product Information: Epivir®, lamivudine tablets and oral solution. Physicians' Desk Reference (electronic version), MICROMEDEX, Inc, Englewood, CO (PI revised 3/1999) reviewed 3/2000.
    

29. Product Information: Heptovir®, lamivudine tablets and oral solution. Glaxo Wellcome BioChem, Mississauga, Ontario, Canada (PI revised 4/1999) reviewed 3/2000.
    

30. Product Information: 3TC®, lamivudine tablets and oral solution. Glaxo Wellcome BioChem, Mississauga, Ontario, Canada (PI revised 8/1998) reviewed 3/2000.
    

31. Product Information: 3TC®, lamivudine tablets and oral solution. Glaxo Wellcome BioChem, Mississauga, Ontario, Canada (PI revised 05/2000) reviewed 01/2001.
    

32. Product Information: 3TC®, lamivudine tablets and oral solution. Glaxo Wellcome Research Triangle Park, NC, (PI revised 01/2001) reviewed 01/2001.
    

33. Product Information: Epivir®, lamivudine tablets and oral solution. Glaxo Wellcome Research Triangle Park, NC, (PI revised 06/2001) reviewed 07/2001.
    

34. Feinberg, William, R.Ph.,M.B.A., 2002 Update Pharmacy Perspective: Acquired Immune Deficiency Disease. CE PRN^®2002; 13-18.
    

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