INDICATIONS

FDA

  • Treatment of HIV infection in combination with other antiretrovirals.
  • Treatment of HBV (Epivir HB)

NON-FDA APPROVED USES

  • Treatment of hepatitis in HIV-HBV co-infected pts.

FORMS

brand name

preparation

manufacturer

route

form

dosage^

cost*

Epivir

Lamivudine (3TC)

ViiV Healthcare

oral

tablet

150 mg, 300 mg

$7.63; $15.27

oral

solution

10 mg/mL (240 mL)

$122.14

Epivir HB (for HBV infection)

Lamivudine (3TC)Route

ViiV Healthcare

oral

tablet

100 mg

$13.66

oral

solution

5 mg/mL (240 mL)

$163.97

Combivir and generic AZT/3TC

Lamivudine (3TC)/Zidovudine (AZT)

ViiV Healthcare and generic manufacturer (Aurobindo Pharma Limited)

oral

tablet

150 mg 3TC/300 mg AZT

$16.55; generic price (TBA)

Trizivir

Lamivudine (3TC)/Zidovudine (AZT)/Abacavir (ABC)

ViiV Healthcare

oral

tablet

ABC 300 mg + AZT 300 mg + 3TC 150 mg

$26.81

Epzicom

Lamivudine (3TC)/Abacavir (ABC)

ViiV Healthcare

oral

tablet

ABC 600 mg + 3TC 300 mg

$35.78

Kivexa (brand name available in Europe)

ABC + 3TC

ViiV Healthcare

oral

tablet

ABC 600 mg + 3TC 300 mg

variable

*Prices represent cost per unit specified, are representative of "Average Wholesale Price" (AWP).
^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

  • Pill burden:
    • HIV: 1-2 tabs once-daily
    • HBV: 100 mg once-daily
  • As Epivir: 3TC 300 mg PO once-daily or 150 mg PO twice-daily
  • As Combivir or Trizivir: 1 tab PO twice-daily
  • As Epzicom: 1 tab PO once-daily

PEDIATRIC DOSING

USUAL PEDIATRIC DOSING

  • Neonate/Infant (< 4 weeks old):
    • For prevention of transmission or treatment of HIV: 2 mg/kg/dose twice daily
  • Pediatrics (≥4 weeks):
    • 4 mg/kg/dose (max 150mg/dose) twice daily
  • Pediatric dosing for scored 150-mg tablet (weight ≥14 kg):
    • 14 to 21 kg: 1/2 tablet (75mg) twice daily
    • >21 to < 30 kg: 1/2 tablet (75mg) in AM and 1 tablet (150mg) in PM
    • ≥ 30 kg: 1 tablet (150mg) twice daily
  • Adolescent (≥ 16 y/o):
    • < 50 kg: 4 mg/kg/dose (max 150 mg) twice daily
    • ≥50 kg: 150 mg twice daily OR 300 mg once daily
  • For combination tablets containing lamivudine for treatment of HIV: see adult dosing
  • For HBV:
    • Children ≥2 years and Adolescents: 3 mg/kg/dose (max 100 mg/dose) once daily

PEDIATRIC RENAL DOSING

  • Infants/Children: Requires renal dosage adjustment. Insufficient data exists to recommend specific dosing; however, the following has been suggested (Aronoff 2007):
    • CrCl 30-50 mL/min: 4 mg/kg/dose once daily
    • CrCl 10-29 mL/min: 2 mg/kg/dose once daily
    • CrCl < 10 mL/min: 1 mg/kg/dose once daily
    • HD: 1 mg/kg/dose once daily, dose after HD on HD days
  • Children and Adolescents ≥30 kg:
    • CrCl ≥50 mL/min: usual dose
    • CrCl 30-49 mL/min: 150 mg once daily
    • CrCl 15-29 mL/min: 150 mg x 1, then 100 mg once daily
    • CrCl 5-14 mL/min: 150 mg x 1, then 50 mg once daily
    • CrCl < 5 mL/min: 50 mg x 1, then 25 mg once daily
    • HD: 50 mg x 1, then 25 mg once daily, dose after HD on HD days

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

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

DOSING FOR GLOMERULAR FILTRATION OF 10-50

Cr Clearance 30-49 mL/min: 150 mg PO once-daily ; Cr Clearance 15-29 mL/min: 150 mg x1 then 100 mg once-daily.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

150 mg x1 then 25-50 mg once-daily.

DOSING IN HEMODIALYSIS

50 mg x1, then 25-50 mg once-daily (post HD).

DOSING IN PERITONEAL DIALYSIS

150 mg x1, then 25-50 mg once-daily (limited data).

DOSING IN HEMOFILTRATION

No data consider 150 mg PO once-daily.

ADVERSE DRUG REACTIONS

GENERAL

  • One of the best tolerated NRTIs with side effect profile comparable to placebo in hepatitis trials.

OCCASIONAL

  • Headache
  • GI: nausea, diarrhea, abdominal pain
  • Insomnia (association unclear; may be due to co-administered ARVs)
  • Hepatitis flare or fulminant hepatitis (in HBV co-infected pts if 3TC withdrawn or with development 3TC-resistant HBV)

RARE

  • Lactic acidosis: listed as NRTI class effect, but unlikely to be caused by 3TC.
    • In vitro, 3TC, along with TDF, FTC, and ABC, are not associated with mitochondrial toxicity.
  • Pancreatitis (reported in pediatric pts)

DRUG INTERACTIONS

No pertinent drug interactions since it is not a substrate, inhibitor, or inducer of CYP450 isoforms.

Drug-to-Drug Interactions

Drug

Effect of Interaction

Recommendations/Comments

Abacavir

3TC AUC decreased by 15%; Cmax decreased by 35%.

Not clinically significant. Use standard dose.

Methadone

3TC: No reported interaction. Methadone: No change.

Not clinically significant. Use standard dose.

Nelfinavir

No effect on 3TC AUC.

Not clinically significant. Use standard doses of both.

Trimethoprim/Sulfamethoxazole

3TC AUC increased by 44%.

Not clinically significant. Use standard dose.

SPECTRUM

HIV and HBV

RESISTANCE

  • 184V: selected by 3TC, resulting in high-level resistance to 3TC and FTC, slight decrease in susceptibility to ddI and ABC, and enhanced susceptibility to AZT, d4T, and TDF.
  • TAMs (41L, 210W, 215Y/F, 219Q/E, 67N, 70R): resistance likely with multiple TAMs.
  • T69S: high-level resistance.
  • Q151M complex: high-level resistance.
  • K65R: intermediate resistance.
  • 44D and 119I: increase 3TC resistance in combination with TAMs.

PHARMACOLOGY

MECHANISM

Intracellular phosphorylation to active lamivudine triphosphate, which competitively inhibits HIV DNA polymerase.

PHARMACOKINETIC PARAMETERS

Absorption

86%

Metabolism and Excretion

Renal excretion accounts for 71%.

Protein Binding

36%

Cmax, Cmin, and AUC

Cmax = 3mcg/mL; Intracellular carbovir triphosphate 100 FM/million cells.

T1/2

Serum: 5-7 hrs; Intracellular:12 hrs.

Distribution

Widely distributed. Vd = 1.3 L/kg.

DOSING FOR DECREASED HEPATIC FUNCTION

Usual dose.

PREGNANCY RISK

Category C: Negative carcinogenicity and teratogenicity studies in rodents. Placental passage ratio of 1.0 (newborn:mother). Well tolerated in pregnant pts.

BREAST FEEDING COMPATIBILITY

No human data, breast milk excretion in animal studies. Breast feeding is not recommended in the U.S. in order to avoid post-natal transmission of HIV to the child, who may not yet be infected.

COMMENTS

  • Pros: very well tolerated; active against HBV.
    • Convenient coformulations available; once-daily dosing with low pill burden (1 tab once-daily).
    • Resistance (184V mutation) increases susceptibility to AZT, d4T, and TDF, and delays accumulation of TAMs.
    • 3TC or FTC are essential components of all recommended initial regimens; coformulated with AZT (Combivir), ABC (Epzicom), and AZT + ABC (Trizivir).
    • Decreased fitness with 184V mutation, which may result in partial antiviral activity.
  • Cons: high-level resistance with single point mutation (184V).
    • Risk of hepatitis flare or fulminant hepatitis if 3TC withdrawn or if resistance develops in co-infected pts.
    • High rate of HBV resistance with prolonged therapy if not used in combination with other anti-HBV agent (typically TDF).
    • Shorter intracellular half-life compared to FTC.
    • More frequent emergence of 184V with AZT/3TC than TDF/FTC in GS934 study.

References

  1. Castagna A et al: Lamivudine monotherapy in HIV-1-infected patients harbouring a lamivudine-resistant virus: a randomized pilot study (E-184V study). AIDS 20:795, 2006  [PMID:16549962]

    Comment: This open-label pilot study determined whether there was clinical or immunological benefit to continuing 3TC in pts harboring M184V mutation. Pts randomly assigned to monotherapy with 3TC 300 mg once -daily or discontinuation of all ARV drugs (TI group). By wk 48, 20 of 29 (69%) pts in TI group (69%) and 12 of 29 (41%) in the 3TC group had discontinued study because of immunological (CD4 <350) or clinical failure, which was significantly delayed in 3TC group (p = 0.018).

  2. Fox Z et al: A randomized trial to evaluate continuation versus discontinuation of lamivudine in individuals failing a lamivudine-containing regimen: the COLATE trial. Antivir Ther 11:761, 2006  [PMID:17310820]

    Comment: In vitro data suggest benefit of continuing 3TC after virological failure due to a decrease in viral fitness. This prospective randomized trial did not support this theory. At wk 48 the average decline in VL (AAUCMB) was comparable between the 2 groups (p=0.65). However, continuing 3TC despite M184V mutation may be beneficial for resistance reasons, especially in pts taking AZT, d4T, or TDF. In pts who continued 3TC, 10.7 (95% CI: 7.5, 14.0) fewer nucleotide changes in viruses containing M184V (p<0.0001) were observed.

  3. Dienstag JL et al: Lamivudine as initial treatment for chronic hepatitis B in the United States. N Engl J Med 341:1256, 1999  [PMID:10528035]

    Comment: Randomized, placebo-controlled trial in 34 centers in U.S. with 66 untreated pts with HBV given 3TC 100 mg/day for 52 wks. Statistically significant histologic improvement with 3TC treatment (52% vs. 23%), decreased levels of HBeAg(undetectable in 32% vs. 11%), and suppression of HBV DNA (44% vs. 16%). Rate of AEs same in both groups. Limitation of 3TC monotherapy is development of resistance, which occurred at rate of 15-20% per yr.

  4. Perry CM, Faulds D: Lamivudine. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in the management of HIV infection. Drugs 53:657, 1997  [PMID:9098665]

    Comment: Review article outlining therapeutic efficacy, pharmacokinetic properties, and antiviral activity.

  5. Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Available at
    http://aidsinfo.nih.gov/contentfiles/lvguidelines/pediatricguidelines.pdf. Accessed (04/23/14) [pages O-16 to O-21]

    Comment: DHHS dosing recommendations for lamivudine in pediatric patients.

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Last updated: July 11, 2014