Search RXList.com© Drug Database

Zotrim
(sulfamethoxazole and trimethoprim) Tablets, USP and (phenazopyridine Hydrochloride) Tablets, USP

THE PRODUCTS ARE INTENDED ONLY FOR USE AS DESCRIBED. For use of the individual components when dispensed as medications outside this combination package for treating urinary tract infections (UTI), please see the package inserts for the individual products.

DESCRIPTION

This product consists of trimethoprim/sulfamethoxazole double strength (160 mg/800 mg) tablets and phenazopyridine hydrochloride 200 mg tablets for oral administration.

Trimethoprim/sulfamethoxazole double strength tablets. Trimethoprim/sulfamethoxazole double strength is a synthetic antibacterial combination product. Each trimethoprim/sulfamethoxazole double strength tablet contains 160 mg trimethoprim and 800 mg sulfamethoxazole.

Trimethoprim is 2,4-pyrimidinediamine, 5-[(3,4,5-trimethoxyphenyl)methyl]. It is a white to light yellow, odorless, bitter compound with a molecular weight of 290.32, the molecular formula C14H18N4O3. Its structual formula is:

Sulfamethoxazole is benzenesulfonamide, 4-amino-N-(5-methyl-3-isoxazolyl). It is an almost white, odorless, tasteless compound with a molecular weight of 253.28, the molecular formula C10H11N3O3S. Its structual formula is:

Inactive Ingredients: Each trimethoprim/sulfamethoxazole double strength tablet contains magnesium stearate, pregelatinized starch and sodium starch glycolate.

Phenazopyridine Hydrochloride tablets. Each round maroon tablet contains 200 mg phenazopyridine hydrochloride, USP for oral administration. Phenazopyridine Hydrochloride is chemically designated 2,6-pyridinediamine, 3-(phenylazo) monohydrochloride with a molecular weigth of 249.70, the molecular formula C11H11N5 ·HCl. Its structual formula is:

Inactive Ingredients: Each phenazopyridine hydrochloride tablet contains acacia, carnauba wax, confectioners sugar, corn starch powder, edible white ink, gelatin, hydrogenated vegetable oil, lactose, magnesium stearate, Opalux AS-3942 dark maroon, sodium starch glycolate, sucrose, talc powder and white bees wax.

INDICATIONS

The components of this product, trimethoprim/sulfamethoxazole/phenazopyridine hydrochloride, are indicated in the treatment of urinary tract infections as follows:

Trimethoprim/Sulfamethoxazole is indicated for the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis and Proteus vulgaris.

Phenazopyridine Hydrochloride is indicated for the symptomatic relief of pain, burning, urgency, frequency, and other discomforts arising from irritation of the lower urinary tract mucosa caused by infection. The use of phenazopyridine hydrochloride for relief of symptoms should not delay definitive diagnosis and treatment of causative conditions. Because it provides only symptomatic relief, prompt appropriate treatment of the cause of pain must be instituted and phenazopyridine hydrochloride should be discontinued when symptoms are controlled.

Phenazopyridine is compatible with antibacterial therapy and can help to relieve pain and discomfort during the interval before antibacterial therapy controls the infection. Treatment of a urinary tract infection with phenazopyridine hydrochloride should not exceed 2 days. (See DOSAGE AND ADMINISTRATION section.)

DOSAGE AND ADMINISTRATION

Adults

Trimethoprim/Sulfamethoxazole: One (1) double strength (160 mg/ 800 mg) tablet every 12 hours for 10 days.

Phenazopyridine Hydrochloride: One (1) 200 mg tablet 3 times a day after meals. The administration of phenazopyridine hydrochloride should not exceed 2 days.

For Patients with Impaired Renal Function: When renal function is impaired, a reduced dosage of trimethoprim/sulfamethoxazole should be employed using the following table:

HOW SUPPLIED

This product consists of a blister card containing trimethoprim/sulfamethoxazole double strength (160 mg/800 mg) tablets and phenazopyridine hydrochloride 200 mg tablets for oral administration as follows:

Twenty double strength (160 mg/800 mg) trimethoprim/sulfamethoxazole tablets, each a white capsule-shaped scored tablet with beveled edges, plain on one side, scored in half on the other, with "93" embossed on one side of the breakline and "089" embossed on the other side and six 200 mg phenazopyridine hydrochloride tablets, each a round, sugar coated, deep maroon tablet, imprinted "AP2" on one side.

NDC 53265-222-26

IN16027/01 05/01

VC8130

Store at controlled room temperature 15°C-25°C (59°F-77°F) in a dry place and protected from light.

REFERENCES

1. National Committee for Clinical Laboratory Standards. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically Fifth Edition. Approved Standard NCCLS Document M7-A5, Vol. 20, No. 2, NCCLS, Wayne, PA, January, 2000.

2. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing - Tenth Informational Supplement (Aerobic Dilution). NCCLS Document M100-S10 (M7), NCCLS, Wayne, PA, January, 2000.

3. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Disk Susceptibility Tests Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No. 1, NCCLS, Wayne, PA, January, 2000.

4. National Committee for Clinical Laboratory Standards. Performance Standards for Antimicrobial Susceptibility Testing - Tenth Informational Supplement (Disk Diffusion). NCCLS Document M100-S10 (M2), NCCLS, Wayne, PA, January, 2000.

5. Brumfitt W, Pursell R. Trimethoprim-sulfamethoxazole in the treatment of bacteriuria in women. J lnfect Dis. November 1973;128 (suppl):S657-S663.

Phenazopyridine Hydrochloride 200 mg tablets are manufactured by: Able Laboratories, Inc.

6 Hollywood Court,

South Plainfield, NJ 07080

Trimethoprim/sulfamethoxazole double strength tablets are manufactured by: TEVA Pharmaceutical Industries, Ltd. Kfar Sava Plant, 1 Hashikma Street Industrial Zone Kfar Sava, 44102 Israel for Able Laboratories, Inc.

This product is packaged by: Packaging Coordinators, Inc. , 3001 Red Lion Road Philadelphia, PA 19114 for Able Laboratories, Inc.

SIDE EFFECTS

Trimethoprim/Sulfamethoxazole: The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria).

FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA, OTHER BLOOD DYSCRASIAS AND HYPERSENSITIVITY OF THE RESPIRATORY TRACT (see WARNINGS section).

Phenazopyridine Hydrochloride: Headache, rash and occasional gastrointestinal disturbance. An anaphylactoid-like reaction has been described.

Methemoglobinemia, hemolytic anemia, renal and hepatic toxicity have been described, usually at overdosage levels (see OVERDOSAGE section).

Hematologic: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia.

Allergic: Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schonlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria and rash. In addition, periarteritis nodosa, and systemic lupus erythematosus have been reported.

Gastrointestinal: Hepatitis, including cholestatic jaundice and hepatic necrosis, elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia.

Genitourinary: Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, and crystalluria.

Metabolic: Hyperkalemia, hyponatremia.

Neurologic: Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache.

Psychiatric: Hallucinations, depression, apathy, nervousness.

Endocrine: The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides.

Musculoskeletal: Arthralgia and myalgia.

Respiratory System: Cough, shortness of breath, and pulmonary infiltrates (see WARNINGS section).

Miscellaneous: Weakness, fatigue, insomnia.

DRUG INTERACTIONS

In elderly patients concurrently receiving trimethoprim/sulfamethoxazole and certain diuretics, primarily thiazides, an increased incidence of thrombocytopenia with purpura has been reported. It has been reported that trimethoprim/sulfamethoxazole may prolong the prothrombin time in patients who are receiving the anticoagulant warfarin. This interaction should be kept in mind when trimethoprim/sulfamethoxazole is given to patients already on anticoagulant therapy, and the coagulation time should be reassessed.

Trimethoprim/sulfamethoxazole may inhibit the hepatic metabolism of phenytoin.

Sulfamethoxazole/trimethoprim, given at a common clinical dosage, increased the phenytoin half-life by 39% and decreased the phenytoin metabolic clearance rate by 27%. When administering these drugs concurrently, one should be alert for possible excessive phenytoin effect.

Sulfonamides can also displace methotrexate from plasma protein binding sites, thus increasing free methotrexate concentrations.

Interaction between Trimethoprim/sulfamethoxazole and Phenazopyridine Hydrochloride

In a prospective two-way crossover drug interaction study between trimethoprim/ sulfamethoxazole double strength and phenazopyridine hydrochloride (200 mg) administered first singly, then in combination to 12 healthy female subjects for three days, it was determined that plasma concentrations of trimethoprim, sulfamethoxazole, and phenazopyridine hydrochloride were significantly increased compared to when either drug product was administered alone (see CLINICAL PHARMACOLOGY section). Some laboratory values were altered when phenazopyridine hydrochloride was administered concomitantly with trimethoprim/sulfamethoxazole. No values fell outside the normal range. The clinical significance of these changes is unknown.

CHANGES* IN HEMATOLOGY AND CLINICAL CHEMISTRY PARAMETERS BETWEEN SINGLE TREATMENT TRIMETHOPRIM/SULFAMETHOXAZOLE OR PHENAZOPYRIDINE (TMP/SMX OR PZP) AND COMBINATION TREATMENT TMP/SMX AND PZP (N=12)

*Changes from baseline are statistically significant (p