Amaryl - Indications & Dosage

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HOW SUPPLIED

AMARYL tablets are available in the following strengths and package sizes:

1 mg (pink, flat-faced, oblong with notched sides at double bisect, either imprinted with "AMA RYL" on one side, or imprinted with "AMA RYL" on one side and the Hoechst logo on both sides of the bisect on the other side)Bottles of 100 (NDC 0039-0221-10)

2 mg (green, flat-faced, oblong with notched sides at double bisect, either imprinted with "AMA RYL" on one side, or imprinted with "AMA RYL" on one side and the Hoechst logo on both sides of the bisect on the other side)Bottles of 100 (NDC 0039-0222-10)

Unit Dose Cartons (100) (NDC 0039-0222-11)

4 mg (blue, flat-faced, oblong with notched sides at double bisect, either imprinted with "AMA RYL" on one side, or imprinted with "AMA RYL" on one side and the Hoechst logo on both sides of the bisect on the other side)Bottles of 100 (NDC 0039-0223-10)

Unit Dose Cartons (100) (NDC 0039-0223-11)

Store between 59 and 86° F (15 and 30° C). Dispense in well-closed containers with safety closures.

ANIMAL TOXICOLOGY

Reduced serum glucose values and degranulation of the pancreatic beta cells were observed in beagle dogs exposed to 320 mg glimepiride/kg/day for 12 months (approximately 1,000 times the recommended human dose based on surface area). No evidence of tumor formation was observed in any organ.

One female and one male dog developed bilateral subcapsular cataracts. Non-GLP studies indicated that glimepiride was unlikely to exacerbate cataract formation. Evaluation of the co-cataractogenic potential of glimepiride in several diabetic and cataract rat models was negative and there was no adverse effect of glimepiride on bovine ocular lens metabolism in organ culture.

HUMAN OPHTHALMOLOGY DATA

Ophthalmic examinations were carried out in over 500 subjects during long-term studies using the methodology of Taylor and West and Laties et al.

No significant differences were seen between AMARYL and glyburide in the number of subjects with clinically important changes in visual acuity, intra-ocular tension, or in any of the five lens-related variables examined. Ophthalmic examinations were carried out during long-term studies using the method of Chylack et al.

No significant or clinically meaningful differences were seen between AMARYL and glipizide with respect to cataract progression by subjective LOCS II grading and objective image analysis systems, visual acuity, intraocular pressure, and general ophthalmic examination.

Rev. February 2003Aventis Pharmaceuticals NJBridgewater, NJ 08807 USAwww.aventis-us.comUS Patent 4,379,785©2003 Aventis Pharmaceuticals Inc.