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Category Antibacterial; antiprotozoal.

      Sulfamethoxazole and Trimethoprim Tablets contain not less than 93.0 per cent and not more than 107.0 per cent of the labelled amounts of C₁₀H₁₁N₃O₃S and C₁₄H₁₈N₄O₃.

Strengths available 100 mg and 20 mg; 400 and 80 mg; and 800 and 160 mg of sulfamethoxazole and trimethoprim.

Dose Adults and children 40 kg of body weight and over----Antibacterial (systemic): 800 mg of sulfamethoxazole and 160 mg of trimethoprim every 12 hours.

      Antiprotozoal----Pneumocystis carinii pneumonia (PCP)----

      Treatment: 18.75 to 25 mg of sulfamethoxazole and 3.75 to 5 mg of trimethoprim per kg of body weight every 6 hours for 14 to 21 days.

      Prophylaxis: 800 mg of sulfamethoxazole and 160 mg of trimethoprim once a day.

      Acceptable alternative dosing schedules include: 800 mg of sulfamethoxazole and 160 mg of trimethoprim three times a week (e.g., Monday, Wednesday, Friday); or 400 mg of sulfamethoxazole and 80 mg of trimethoprim once a day.

      Children up to 40 kg of body weight and infants 2 months of age and over----Antibacterial (systemic): 20 to 30 mg of sulfamethoxazole and 4 to 6 mg of trimethoprim per kg of body weight every 12 hours.

      Antiprotozoal----(PCP)----

         Treatment: 18.75 to 25 mg of sulfamethoxazole and 3.75 to 5 mg of trimethoprim per kg of body weight every 6 hours for 14 to 21 days.

         Prophylaxis----Children 4 weeks of age and over: 375 mg of sulfamethoxazole per m2 of body surface area (Appendix 1.17) and 75 mg of trimethoprim per m2 of body surface area twice a day, three times a week on consecutive days (e.g., Monday, Tuesday, Wednesday).

         Acceptable alternative dosing schedules include: 750 mg of sulfamethoxazole per m2 of body surface area and 150 mg of trimethoprim per m2 of body surface area as a single daily dose three times a week on consecutive days (e.g., Monday, Tuesday, Wednesday); or 375 mg of sulfamethoxazole per m2 of body surface area and 75 mg of trimethoprim per m2 of body surface area twice a day, 7 days a week; or 375 mg of sulfamethoxazole per m2 of body surface area and 75 mg of trimethoprim per m2 of body surface area twice a day, three times a week on alternate days (e.g., Monday, Wednesday, Friday).

(Note PCP prophylaxis is recommended for all infants born to HIV-infected mothers starting at 4 weeks of age, regardless of their CD4 lymphocyte counts. However, if the infant is receiving zidovudine during the first 6 weeks of life for the prevention of perinatal HIV transmission, sulfamethoxazole and trimethoprim combination prophylaxis should be delayed until zidovudine is discontinued at 6 weeks of age, to reduce the chance of anemia that may occur if these two medications are given concurrently.)

Contra-indication; Warning; Precaution; Additional information See under Sulfamethoxazole, p. 152 and Trimethoprim, p. 166.

Packaging and storage Sulfamethoxazole and Trimethoprim Tablets shall be protected from light.

Identification

      A. Carry out the test as described in the “Thin-layer Chromatography” (Appendix 3.1), using silica gel GF254  as the coating substance and a mixture of 6 volumes of chloroform, 5 volumes of 2-propanol, and 1 volume of diethylamine as the mobile phase. Apply separately to the plate, 5 μl of each of the following solutions. For solution (A), transfer a portion of the powdered tablets, containing 4 mg of trimethoprim, to a 10-ml volumetric flask. Add 8 ml of methanol, warm for several minutes on a water-bath with frequent shaking and cool. Dilute with methanol to volume, mix and centrifuge briefly. Solution (B) contains 400 μg per ml of Trimethoprim RS in methanol. Solution (C) contains 2 mg per ml of Sulfamethoxazole RS in methanol. After removal of the plate, allow it to dry in air and examine under ultraviolet light (254 nm): the principal spots in the chromatogram obtained from solution (A) correspond to those obtained from solution (B) and solution (C).

      B. The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.

Dissolution Carry out the test as described in the “Dissolution Test” (Appendix 4.24).

      Dissolution medium: 0.1 M hydrochloric acid; 900 ml.

      Apparatus 2: 75 rpm.

      Time: 60 minutes.

      Procedure Determine the amounts of C₁₀H₁₁N₃O₃S and C₁₄H₁₈N₄O₃ dissolved, employing the procedure set forth in the Assay, making any necessary volumetric adjustments. Calculate the percentage of each active component dissolved by comparison of the peak responses obtained from filtered portions of the test solution with the peak responses from the corresponding component obtained from the Standard preparation.

      Tolerances Not less than 70 per cent (Q) of the labelled amounts of C₁₀H₁₁N₃O₃S and C₁₄H₁₈N₄O₃ are dissolved in 60 minutes.

Assay Carry out the determination as described in the “High-pressure Liquid Chromatography” (Appendix 3.5).

      Mobile phase, Standard preparation, Chromatographic system, and Procedure Proceed as directed in the Assay under Sulfamethoxazole and Trimethoprim Oral Suspension, p. 155.

Assay preparation Weigh and finely powder not less than 20 Sulfamethoxazole and Trimethoprim Tablets. Transfer an accurately weighed portion of the powdered tablets, containing about 160 mg of sulfamethoxazole, to a 100-ml volumetric flask. Add about 50 ml of methanol and sonicate, with intermittent shaking, for 5 minutes. Allow to equilibrate to room temperature, dilute with methanol to volume, mix, and filter. Transfer 5.0 ml of the clear filtrate to a 50-ml volumetric flask, dilute with Mobile phase to volume and mix.

      Calculation Calculate the content of C₁₀H₁₁N₃O₃S and C₁₄H₁₈N₄O₃ in the Tablets using the declared content of C₁₀H₁₁N₃O₃S in Sulfamethoxazole RS and C₁₄H₁₈N₄O₃ in Trimethoprim RS, respectively. Other requirements Comply with the requirements described under “Tablets” (Appendix 1.16).

Other requirements Comply with the requirements described under “Tablets” (Appendix 1.16).