Comparison of Generic Zidovudine + Lamivudine (Cipla, Duovir) and GlaxoSmithKline Brand (Combivir) Tablets

Approximately 25 million people have died from AIDS over the past two decades and estimates of current HIV infection rates worldwide exceed 40 million persons. Extensive use of HAART regimens in developed countries has demonstrated that death rates can decline significantly and quality of life can improve dramatically when HIV positive individuals use HAART.

Following is the text of a Letter to the Editor, published in the April 15, 2004 issue of JAIDS regarding the purity of generic zidovudine (AZT)/lamivudine (3TC) tablets (Duovir from Cipla) versus Combivir tablets (GlaxoSmithKline).

Because few data have been published regarding the purity of generic antiretroviral medications, an evaluation of the chemical purity of Duovir compared to Combivir (GlaxoSmithKline) was performed at the University of Minnesota Antiviral Pharmacology Laboratory. Generic antiretroviral medications are available at a cost as low as 97% less than brand name drugs.

One tablet each of Combivir (AZT 300 mg + 3TC 150 mg/capsule; Glaxo-Smith-Kline lot #1ZP2346) and Duovir (AZT 300 mg + 3TC 150 mg/capsule; Cipla lot #C10237) were analyzed for AZT and 3TC content using a procedure derived from United States Pharmacopeia (USP) guidelines for AZT tablets (USP 24-NF19).

Solutions from analytical standards and each drug product were independently prepared to achieve final concentrations of 1.25 μg/mL for 3TC and 2.50 μg/mL for AZT. High-performance liquid chromatographic analysis was performed using a validated method for nucleoside analogues. The mean peak areas of the triplicate injections were used for comparison.

The tolerance allowed by the USP protocol is 90-110% of the analytical standard target. Combivir was 109 and 95.7%, respectively, and Duovir was 112 and 95.5%, respectively, of target concentrations for 3TC and AZT.

Cipla generic antiretroviral medications are on the World Health Organization list of vital medications. Cipla has offered to sell generic antiretroviral medications to resource poor-countries.

The Combivir tablet was within the allowed USP tolerances for both AZT and 3TC. The Duovir tablet was within specification for AZT but slightly beyond the upper tolerance at 112% for 3TC. The difference in results between AZT and 3TC could be due to the preparation of the analytical standard for 3TC or some unknown factor.

The cost of a 30-day supply of Duovir is 95% less than the cost of a 30-day supply of Combivir ($34.25 according to the Web site: http://www.cipla.com ) vs. $675.69 (at the University-Fairview Pharmacy, respectively).

The authors conclude, “Further studies comparing the purity and pharmacokinetics of generic vs. branded antiretrovirals are important to optimize use of antiretrovirals in resource-poor countries.”

04/05/04

Reference
K Henry and others. Comparison of Generic Zidovudine + Lamivudine (Cipla, Duovir) and the GlaxoSmithKline Brand (Combivir) Tablets (Letter to the Editor). Journal of Acquired Immune Deficiency Syndromes 35(5): 537. April 15, 2004.