drug-information.ru

|Trimethoprim/Sulfamethoxazole

Trimethoprim/Sulfamethoxazole

Trade Names:
Bactrim
- Tablets 80 mg trimethoprim and 400 mg sulfamethoxazole

Trade Names:
Bactrim D.S.
- Tablets, double-strength 160 mg trimethoprim and 800 mg sulfamethoxazole

Trade Names:
Bactrim IV
- Injection 80 mg trimethoprim and 400 mg sulfamethoxazole/5 mL

Trade Names:
Bactrim Pediatric
- Oral suspension 40 mg trimethoprim and 200 mg sulfamethoxazole/5 mL

Trade Names:
Cotrim
- Tablets 80 mg trimethoprim and 400 mg sulfamethoxazole

Trade Names:
Cotrim D.S.
- Tablets, double-strength 160 mg trimethoprim and 800 mg sulfamethoxazole

Trade Names:
Cotrim Pediatric
- Oral suspension 40 mg trimethoprim and 200 mg sulfamethoxazole/5 mL

Trade Names:
Septra
- Tablets 80 mg trimethoprim and 400 mg sulfamethoxazole

Trade Names:
Septra DS
- Tablets, double-strength 160 mg trimethoprim and 800 mg sulfamethoxazole

Trade Names:
Septra IV
- Injection 80 mg trimethoprim and 400 mg sulfamethoxazole/5 mL

Trade Names:
Sulfatrim
- Oral suspension 40 mg trimethoprim and 200 mg sulfamethoxazole/5 mL

Trade Names:
Uroplus DS
- Tablets 160 mg trimethoprim and 800 mg sulfamethoxazole

Trade Names:
Uroplus SS
- Tablets 80 mg trimethoprim and 400 mg sulfamethoxazole

Mechanism of Action

Pharmacology

Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with PABA. Trimethoprim blocks production of tetrahydrofolic acid by inhibiting the enzyme dihydrofolate reductase. This combination blocks 2 consecutive steps in bacterial biosynthesis of essential nucleic acids and proteins and is usually bactericidal.

Pharmacokinetics

Absorption

Trimethoprim/sulfamethoxazole is rapidly absorbed following PO administration. T _max is 1 to 4 hr. Steady state is achieved after 3 days.

Distribution

70% of sulfamethoxazole and 44% of trimethoprim is protein bound. Trimethoprim/sulfamethoxazole is distributed to sputum, vaginal fluid, and middle ear fluid. Trimethoprim/sulfamethoxazole passes the placental barrier and is excreted in human milk.

Metabolism

Metabolism of sulfamethoxazole is primarily by N ₄ -acetylation. The principal metabolites of trimethoprim are the 1- and 3-oxides and the 3- and 4-hydroxy derivatives. The free forms are considered therapeutically active.

Elimination

Serum t _½ of sulfamethoxazole and trimethoprim is 10 hr and 8 to 10 hr, respectively. Trimethoprim/sulfamethoxazole is primarily eliminated by kidneys through glomerular filtration and tubular secretion. Urine concentrations are higher than blood concentrations.

Onset

Onset of action is 24 hr after administration.

Special Populations

Patients with severely impaired renal function exhibit an increase in the half lives of both components, requiring dosage adjustments.

Indications and Usage

Treatment of UTIs caused by susceptible strains of bacteria, shigellosis enteritis, and Pneumocystis carinii pneumonitis.

Treatment of acute otitis media and acute exacerbations of chronic bronchitis; treatment of traveler"s diarrhea.

Unlabeled Uses

Treatment of cholera, salmonella-type infections and nocardiosis; prevention of recurrent UTIs in women; prophylaxis of bacterial infections in susceptible patients; treatment of prostatitis; prophylaxis of Pneumocystis carinii pneumonitis.

Contraindications

Hypersensitivity to sulfonamides; megaloblastic anemia caused by folate deficiency; pregnancy at term; lactation; infants less than 2 mo.

Dosage and Administration

PO 160 mg trimethoprim/800 mg sulfamethoxazole q 12 hr for 10 to 14 days and 5 days for shigellosis. IV 8 to 10 mg/kg/day (based on trimethoprim) in 2 to 4 divided doses q 6 to 12 hr for up to 14 days for severe UTIs and 5 days for shigellosis.

PO 8 mg/kg trimethoprim/40 mg/kg sulfamethoxazole daily in 2 divided doses q 12 hr for 10 days and 5 days for shigellosis.

PO 20 mg/kg trimethoprim/100 mg/kg sulfamethoxazole daily in divided doses q 6 hr for 14 days. IV 15 to 20 mg/kg/day (based on trimethoprim) in 3 to 4 divided doses for up to 14 days.

PO 160 mg trimethoprim/800 mg sulfamethoxazole q 12 hr for 5 days.

PO 160 mg trimethoprim/800 mg sulfamethoxazole q 12 hr for 14 days.

General Advice

• For IV infusion, must dilute in 75 or 125 mL of D5W only. Administer each dose over 60 to 90 min. Flush IV line after infusion. Do not use IV solution if cloudy or precipitates are noted.
• If local irritation or inflammation because of extravascular infiltration occurs, discontinue infusion and restart at another site.
• Avoid rapid or direct IV injection. Do not inject IM.

Storage/Stability

Store IV solution at room temperature. Do not refrigerate. Discard prepared IV solution if not used within 2 hr (75 mL) or 6 hr (125 mL). Store tablets or suspension at room temperature in a tight, light-resistant container.

Drug Interactions

May cause decrease in therapeutic effect of cyclosporine and increased risk of nephrotoxicity.

May displace methotrexate from protein-binding sites, thus increasing free methotrexate levels.

Trimethoprim may inhibit metabolism of phenytoin or other hydantoins.

Trimethoprim may inhibit renal elimination of procainamide and its metabolites.

May increase hypoglycemic response to sulfonylureas because of displacement from protein-binding sites or inhibition of hepatic metabolism.

May cause prolonged PT.

Incompatibility

Do not mix with other drugs or solutions other than D5W.

Laboratory Test Interactions

Can interfere with serum methotrexate assay as determined by competitive binding protein technique when bacterial dihydrofolate reductase is used as binding protein. May interfere with Jaffe alkaline picrate reaction assay for creatinine, resulting in overestimations.

Precautions

Pregnancy

Category C . Do not use at term because of risk of neonatal kernicterus.

Lactation

Undetermined. Not recommended during nursing because sulfonamides are excreted in breast milk and may cause kernicterus. Premature infants and infants with hyperbilirubinemia or G-6-PD deficiency are also at risk for adverse effects.

Children

Not recommended for infants less than 2 mo.

Elderly

Are at increased risk of severe adverse reactions.

Renal Function

Use drug with caution. Dosage adjustment may be required.

Hepatic Function

Use drug with caution. Dosage adjustment may be required.

Special Risk Patients

Use drug with caution in patients with possible folate deficiency (eg, elderly patients, chronic alcoholics, patients undergoing anticonvulsant therapy, patients with malabsorption syndromes or malnutrition), patients with severe allergy or bronchial asthma, patients who have sulfite sensitivity and G-6-PD-deficient individuals.

Ulceration

Take tablets with water or food to prevent lodging in esophagus and subsequent ulceration.

Hematologic effects

Sulfonamide-associated deaths, although rare, have occurred from hypersensitivity of respiratory tract, Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Both components can interfere with hematopoiesis. IV use at high doses for extended periods of time may cause bone marrow depression.

Patients with AIDS

Incidence of side effects, especially rash, fever, and leukopenia, is greatly increased.

Streptococcal pharyngitis

Do not use for streptococcal pharyngitis.

Sulfonamides

Are chemically similar to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Goiter production, diuresis, and hypoglycemia occur rarely in patients receiving sulfonamides. Cross-sensitivity may occur.

Overdosage

Symptoms

Anorexia, colic, nausea, vomiting, dizziness, headache, drowsiness, depression, confusion, altered mental status, fever, hematuria, crystalluria, blood dyscrasias, jaundice, bone marrow depression.

Patient Information

• Advise patient to complete full course of therapy.
• Encourage patient to maintain adequate fluid intake.
• Advise patient to take tablet with full glass of water.
• Educate patient and family to report any signs of superinfection such as fever, vaginitis, oral candidiasis, and fatigue.
• Instruct patient to report these symptoms to health care provider: skin rash, sore throat, fever, unusual bruising or bleeding.
• Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.