Zambian HIV Guidelines:: Lamivudine

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Drugs>Antiretrovirals>

Lamivudine

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
03-25-2008

Available formulation in Zambia: Oral liquid: 50 mg/5 ml; Tablet: 150 mg. AZT 300 mg/3TC 150 mg combination tab. AZT 300 mg/3TC 150 mg/NVP 200 mg combination tab
Co-formulations with 3TC: AZT+3TC (300 mg+150 mg); AZT+3TC+NVP (300 mg+150 mg+200 mg); d4T+3TC+NVP (30 mg+150 mg+200 mg). Dose: 1 tablet twice daily.
Active against HBV, but should be co-administered with TDF in HBV co-infected patients to prevent emergence of 3TC resistance.
AZT /3TC plus NVP no longer first-line ARV regimen in ARV-naïve patients. TDF/FTC/EFV now preferred due to long-term efficacy, favorable mutation pathway, and lower incidence of anemia.
After TDF/FTC/EFV failure, AZT/3TC plus LPV/r is recommended second line regimen.

Zambia Information Author: Paul A. Pham, Pharm.D.

INDICATIONS

FDA

Treatment of HIV infection in combination with other antiretrovirals.
Treatment of hepatitis in HIV-HBV co-infected pts.

FORMS

brand name	generic	Mfg	brand forms	cost*
Epivir	Lamivudine (3TC)	GlaxoSmithKline	oral tablet 150 mg, 300 mg	$6.10; $12.10
			oral solution 10mg/mL (240mL)	$102.92
Epivir HB (for HBV infection)	Lamivudine (3TC)	GlaxoSmithKline	oral tablet 100 mg	$9.51
			oral solution 5 mg/mL (240 mL)	$114.23
Combivir	Lamivudine (3TC)/Zidovudine (AZT)	GlaxoSmithKline	oral tablet 150 mg 3TC/300 mg AZT	$13.22

Trizivir	Lamivudine (3TC)/Zidovudine (AZT)/Abacavir (ABC)	GlaxoSmithKline	oral tablet ABC 300 mg + AZT 300 mg + 3TC 150 mg	$20.90per tab
Epzicom	Lamivudine (3TC)/Abacavir (ABC)	GlaxoSmithKline	oral tablet ABC 600 mg + 3TC 300 mg	$28.59 per tab
Kivexa (brand name available in Europe)	ABC + 3TC	GlaxoSmithKline	oral tablet ABC 600 mg + 3TC 300 mg	variable

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

Pill burden: 1-2 tabs qd

As Epivir: 3TC 300 mg PO qd or 150 mg PO bid. As Combivir or Trizivir: 1 tab PO bid. As Epzicom: 1 tab PO qd.

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

300 mg qd or 150 mg PO bid

DOSING FOR GLOMERULAR FILTRATION OF 10-50

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

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

150 mg x1 then 25-50 mg qd.

DOSING IN HEMODIALYSIS

25-50 mg qd (post HD).

DOSING IN PERITONEAL DIALYSIS

25-50 mg qd (limited data).

DOSING IN HEMOFILTRATION

No data consider 150 mg PO qd.

ADVERSE DRUG REACTIONS

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

OCCASIONAL

Headache, nausea, diarrhea, abdominal pain, and insomnia (association unclear; may be due to co-administered ARTs).
Fulminant hepatitis (in HBV co-infected pts if lamivudine is withdrawn or with the development lamivudine-resistant HBV)

RARE

LACTIC ACIDOSIS: listed as NRTI class effect, but not clear that it is caused by 3TC. In vitro, 3TC, along with TDF, FTC, and ABC, are not clearly 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-to-Drug Interaction

Drug	Effect of Interaction	Recommendations/Comments
ABC	3TC AUC decreased by 15%; Cmax decreased by 35%.	Not clinically significant. Use standard dose.
NFV	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.
Methadone	3TC: No reported interaction. Methadone: No change.	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): with multiple TAMs, resistance likely.
T69S: high-level resistance.
Q151M complex: high-level resistance.
K65R: intermediate resistance.
44D and 119I: increase 3TC resistance in combination with TAMs.

PHARMACOLOGY

Pharmacology

COMMENTS

Pros: very well tolerated; active against HBV; convenient coformulations available; qd dosing with low pill burden (1 tab qd); longer-term safety data than FTC; increases susceptibility to AZT, d4T, and TDF; 3TC or FTC are essential components of all recommended initial regimens; coformulated with AZT (Combivir), ABC (Epzicom), and AZT + ABC (Trizivir).
Cons: high level resistance with single point mutation (184V); risk of fulminant hepatitis if 3TC is withdrawn in co-infected pts; high rate of HBV resistance with prolonged therapy of HBV.

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