Quality of Generic Clarithromycin Products
Quality of Generic Clarithromycin Products
Objective: This study evaluated the quality of 40 generic clarithromycin products from Latin America and Asia.
Materials and Methods: The generic products were examined visually, assayed by high pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories.
Results: This survey found that many generic clarithromycin products are not equivalent to the innovator product, falling short of the approved, registered specifications for the innovator product. Overall, 20% (8 of 40) of all generic tablets tested, and 33% (6 of 18) of tablets from Latin America, failed to contain between 95 and 105% of the clarithromycin claimed in the label, thus falling short of the approved registered specification for the innovator product. Atotal of 70% (28 of 40) of products tested released less drug in 30 minutes than did the innovator tablets, although they still met the dissolution specification requiring that 80% of the drug must dissolve in 30 minutes; one generic product failed to meet the specification. A total of 60% (24 of 40) of the generic products tested exceeded the Abbott Laboratories' 3% limit for total impurities in bulk drug, and 70% (28 of 40) exceeded the Abbott Laboratories' 0.8% limit for 6,11 di-O-methyl erythromycin A.
Conclusions: These results suggest that generic tablets are not equivalent to the innovator product, raising concerns that clinical trial results achieved with branded clarithromycin (Abbott Laboratories) should not be extrapolated to generic products.
Clarithromycin is a broad-spectrum antibiotic with activity against a range of Gram-positive and Gram-negative organisms, atypical pathogens, and some anaerobes. Clarithromycin acts by binding reversibly to the 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis. In multiple clinical trials clarithromycin has proven to be an effective treatment for a variety of upper and lower respiratory tract infections including sinusitis, pharyngitis, otitis media, pneumonia, community-acquired pneumonia, and acute bronchitis. The drug has been widely prescribed because it provides rapid symptomatic relief and is well tolerated.
Clarithromycin (Biaxin®, Biclar®, Klacid®, Klaricid®, Zeclar®) is marketed worldwide by Abbott Laboratories. In addition to the innovator product, generic products and bulk drugs are manufactured by a variety of companies. To date, no comparative studies of the relative quality of branded and generic clarithromycin have been undertaken. Such studies are needed because clinical trials evaluating efficacy and tolerability have been conducted solely with the Abbott product.
The primary goal of the present survey was to determine if generic clarithromycin products were of the same quality as the Abbott Laboratories' reference product. To assess relative quality, the clarithromycin content, dissolution properties, and purity of branded and generic clarithromycin tablets were evaluated. In addition to each generic product being evaluated against the innovator product, each product was measured against United States Pharmacopoeial (USP) and Abbott Laboratories' specifications, the only registered specifications for clarithromycin tablets.
Objective: This study evaluated the quality of 40 generic clarithromycin products from Latin America and Asia.
Materials and Methods: The generic products were examined visually, assayed by high pressure liquid chromatography for clarithromycin content and impurities, tested for dissolution properties, and compared with the innovator product manufactured by Abbott Laboratories.
Results: This survey found that many generic clarithromycin products are not equivalent to the innovator product, falling short of the approved, registered specifications for the innovator product. Overall, 20% (8 of 40) of all generic tablets tested, and 33% (6 of 18) of tablets from Latin America, failed to contain between 95 and 105% of the clarithromycin claimed in the label, thus falling short of the approved registered specification for the innovator product. Atotal of 70% (28 of 40) of products tested released less drug in 30 minutes than did the innovator tablets, although they still met the dissolution specification requiring that 80% of the drug must dissolve in 30 minutes; one generic product failed to meet the specification. A total of 60% (24 of 40) of the generic products tested exceeded the Abbott Laboratories' 3% limit for total impurities in bulk drug, and 70% (28 of 40) exceeded the Abbott Laboratories' 0.8% limit for 6,11 di-O-methyl erythromycin A.
Conclusions: These results suggest that generic tablets are not equivalent to the innovator product, raising concerns that clinical trial results achieved with branded clarithromycin (Abbott Laboratories) should not be extrapolated to generic products.
Clarithromycin is a broad-spectrum antibiotic with activity against a range of Gram-positive and Gram-negative organisms, atypical pathogens, and some anaerobes. Clarithromycin acts by binding reversibly to the 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis. In multiple clinical trials clarithromycin has proven to be an effective treatment for a variety of upper and lower respiratory tract infections including sinusitis, pharyngitis, otitis media, pneumonia, community-acquired pneumonia, and acute bronchitis. The drug has been widely prescribed because it provides rapid symptomatic relief and is well tolerated.
Clarithromycin (Biaxin®, Biclar®, Klacid®, Klaricid®, Zeclar®) is marketed worldwide by Abbott Laboratories. In addition to the innovator product, generic products and bulk drugs are manufactured by a variety of companies. To date, no comparative studies of the relative quality of branded and generic clarithromycin have been undertaken. Such studies are needed because clinical trials evaluating efficacy and tolerability have been conducted solely with the Abbott product.
The primary goal of the present survey was to determine if generic clarithromycin products were of the same quality as the Abbott Laboratories' reference product. To assess relative quality, the clarithromycin content, dissolution properties, and purity of branded and generic clarithromycin tablets were evaluated. In addition to each generic product being evaluated against the innovator product, each product was measured against United States Pharmacopoeial (USP) and Abbott Laboratories' specifications, the only registered specifications for clarithromycin tablets.
