trimethoprim/sulfamethoxazole

BEERS REMS

Treatment of:
- Bronchitis,
- Shigella
  enteritis,
- Otitis media,
- Pneumocystis jirovecii
  pneumonia (PJP),
- Urinary tract infections,
- Traveler’s diarrhea.
Prevention of PJP in patients with HIV.

Unlabeled Use:

Biliary tract infections, osteomyelitis, burn and wound infections, chlamydial infections, endocarditis, gonorrhea, intra-abdominal infections, nocardiosis, rheumatic fever prophylaxis, sinusitis, eradication of meningococcal carriers, prophylaxis of urinary tract infections, and an alternative agent in the treatment of chancroid.
Prevention of bacterial infections in immunosuppressed patients.

Action ⬆ ⬇

Combination inhibits the metabolism of folic acid in bacteria at two different points.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Active against many strains of gram-positive aerobic pathogens including:
- Streptococcus pneumoniae,
- Staphylococcus aureus.
Has activity against many aerobic gram-negative pathogens, such as:
- Enterobacter,
- Klebsiella,
- Morganella morganii,
- Escherichia coli,
- Proteus mirabilis,
- Proteus vulgaris,
- Shigella,
- Haemophilus influenzae.
Pneumocystis jirovecii.
Not active against Pseudomonas aeruginosa.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed from the GI tract.

Distribution: Widely distributed to tissues. Crosses the blood-brain barrier.

Metabolism/Excretion: Some metabolism by the liver (20%); remainder excreted unchanged by the kidneys.

Half-Life: Trimethoprim (TMP): 6–11 hr; sulfamethoxazole (SMX): 9–12 hr, both prolonged in renal failure.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	rapid	2–4 hr	6–12 hr
IV	rapid	end of infusion	6–12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to sulfonamides or trimethoprim;
History of drug-induced immune thrombocytopenia due to sulfonamides or trimethoprim;
Megaloblastic anemia secondary to folate deficiency;
Severe renal impairment;
Severe hepatic impairment;
Concurrent use with dofetilide;
Lactation: Avoid breastfeeding in infants who have glucose-6–phosphate dehydrogenase (G6PD) deficiency or hyperbilirubinemia;
Pedi: Children 2 mo (can cause kernicterus).

Use Cautiously in:

Mild or moderate renal impairment (dose ↓ required if CCr <30 mL/min);
Mild or moderate hepatic impairment;
G6PD deficiency (↑ risk hemolysis);
HIV (↑ incidence of adverse reactions);
Concurrent use with other products containing propylene glycol (IV only) (↑ risk of lactic acidosis);
OB: risk of neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, and club foot in fetus when used during pregnancy; use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Geri: Appears on Beers list. Use with caution in older adults taking an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, or angiotensin receptor/neprilysin inhibitor, and in those with a reduced CCr because of risk of hyperkalemia.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension

Derm: rash, ACUTE FEBRILE NEUTROPHILIC DERMATOSIS, ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, FEBRILE NEUTROPHILIC DERMATOSIS, photosensitivity, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS

Endo: hypoglycemia

F and E: hyperkalemia, hyponatremia

GI: nausea, vomiting, cholestatic jaundice, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), diarrhea, HEPATIC NECROSIS, hepatitis, pancreatitis, stomatitis

GU: crystalluria

Hemat: AGRANULOCYTOSIS, APLASTIC ANEMIA, hemolytic anemia, leukopenia, megaloblastic anemia, thrombocytopenia

Local: phlebitis at IV site

Neuro: fatigue, hallucinations, headache, insomnia, kernicterus (neonates), mental depression

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND RESPIRATORY FAILURE)

Interactions ⬆ ⬇

Drug-drug:

May ↑dofetilide levels and the risk of QT interval prolongation with arrhythmias; concurrent use contraindicated.
May ↑ levels and the risk of toxicity of phenytoin; closely monitor phenytoin levels.
May ↑ levels of and the risk of bleeding from warfarin; closely monitor INR.
May ↑ hypoglycemic effects of sulfonylureas, pioglitazone, repaglinide, and metformin.
May ↑ toxicity of methotrexate; avoid concurrent use.
↑risk of thrombocytopenia from thiazidediuretics, especially in older adults.
May ↑ risk of nephrotoxicity associated with cyclosporine; avoid concurrent use.
May ↑ levels and the risk of toxicity of digoxin, especially in older adults; closely monitor digoxin levels.
Indomethacin may ↑ levels and the risk of toxicity; avoid concurrent use.
ACE inhibitors may ↑ risk of hyperkalemia; avoid concurrent use.
May ↓ the effects of tricyclic antidepressants.
May ↑ risk of myelosuppression with zidovudine.
May ↑ procainamide levels and the risk of QT interval prolongation with arrhythmias; closely monitor procainamide levels.

Route/Dosage ⬆ ⬇

Dosing based on TMP content.

Bacterial Infections

PO IV (Adults and Children >2 mo): Mild to moderate infections: 6–12 mg TMP/kg/day divided every 12 hr; Serious infection/PJP: 15–20 mg TMP/kg /day divided every 6–8 hr.
PO (Adults ): Urinary tract infection/chronic bronchitis: 1 double-strength tablet (160 mg TMP/800 mg SMX) every 12 hr for 10–14 days.

Urinary Tract Infection Prophylaxis

PO IV (Adults and Children >2 mo): 2 mg TMP/kg/dose once daily or 5 mg TMP/kg/dose twice weekly.

P. jirovecii Pneumonia Prevention

PO (Adults ): 1 double-strength tablet (160 mg TMP/800 mg SMX) once daily (may also be given 3 times weekly).
PO (Children >1 mo): 150 mg TMP/m²/day divided every 12 hr or given as a single dose on 3 consecutive days/wk (not to exceed 320 mg TMP/1600 mg SMX per day).

Availability ⬆ ⬇

(Generic available)

Tablets: 20 mg TMP/100 mg SMX; 80 mg TMP/400 mg SMX; 160 mg TMP/800 mg SMX (double-strength)
Oral suspensioncherry, grape flavors: 40 mg TMP/200 mg SMX per 5 mL
Solution for injection: 16 mg TMP/80 mg SMX per mL (contains 40% propylene glycol)

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
Obtain specimens for culture and sensitivity before initiating therapy. First dose may be given before receiving results.
Inspect IV site frequently. Phlebitis is common.
Assess patient for allergy to sulfonamides.
Monitor intake and output ratios. Fluid intake should be sufficient to maintain a urine output of at least 1200–1500 mL daily to prevent crystalluria and stone formation.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
Assess for rash periodically during therapy. May cause SJS. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.

Lab Test Considerations:

Monitor CBC and urinalysis periodically during therapy.
- May produce ↑ serum bilirubin, serum potassium, serum creatinine, and alkaline phosphatase.
- May cause hypoglycemia.

Implementation ⬆ ⬇

Do not confuse DS (double-strength) formulations with single-strength formulations.
- Do not administer medication IM.
PO: Administer around the clock with a full glass of water. Use calibrated measuring device for liquid preparations.

IV Administration:

Intermittent Infusion: Diluent: Dilute each 5 mL of trimethoprim/sulfamethoxazole with 125 mL of D5W (stable for 24 hr at room temperature). May also dilute each 5 mL of drug with 75 mL of D5W if fluid restriction is required (stable for 6 hr at room temperature). Do not refrigerate.Concentration: Should not exceed 1.06 mg/mL.
Rate: Infuse over 60–90 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication around the clock and to finish drug completely as directed, even if feeling well. Take missed doses as soon as remembered unless almost time for next dose. Advise patient that sharing of this medication may be dangerous.
Instruct patient to notify health care professional if rash or fever and diarrhea develop, especially if diarrhea contains blood, mucus, or pus. Advise patient not to treat diarrhea without consulting health care professional.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Advise patient to notify health care professional if skin rash, sore throat, fever, mouth sores, or unusual bleeding or bruising occurs.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Instruct patient to notify health care professional if symptoms do not improve within a few days.
Rep: May cause fetal harm. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, or if breastfeeding. Fetal exposure during pregnancy may lead to increased risk of congenital malformations, neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, and club foot.
Emphasize importance of regular follow-up exams to monitor blood counts in patients on prolonged therapy.
Home Care Issues: Instruct family or caregiver on dilution, rate, and administration of drug and proper care of IV equipment.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇