trimethoprim/sulfamethoxazole

REMS

Treatment of:
- Bronchitis,
- Shigella enteritis,
- Otitis media,
- Pneumocystis jiroveciipneumonia (PCP),
- Urinary tract infections,
- Traveler’s diarrhea.
Prevention of PCP in HIV-positive patients.

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. Crosses the blood-brain barrier and placenta and enters breast milk.

Protein Binding: Trimethoprim — 45%; Sulfamethoxazole — 68%.

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

Half-life: Trimethoprim — 6–11 hr; sulfamethoxazole — 9–12 hr, both prolonged in renal failure.

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 hepatic or renal impairment
Concurrent use with dofetilide
Lactation: Avoid breastfeeding infants who have glucose-6–phosphate dehydrogenase (G6PD) deficiency or hyperbilirubinemia
Pedi: Children <2 mo (can cause kernicterus).

Use Cautiously in:

Mild to moderate hepatic or renal impairment (dose ↓ required if CCr <30 mL/min)
G6PD deficiency (↑ risk hemolysis)
HIV-positive patients (↑ 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.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension.

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

Endo: hypoglycemia.

F and E: hyperkalemia, hyponatremia.

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

GU: crystalluria.

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

Local: phlebitis at IV site.

Neuro: fatigue, hallucinations, headache, insomnia, mental depression, kernicterus in neonates.

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

Interactions ⬆ ⬇

Drug-Drug:

May ↑dofetilidelevels and the risk of QT interval prolongation with arrhythmias; concurrent use contraindicated.
May ↑ levels of phenytoin; closely monitor phenytoin levels.
May ↑ levels of and risk of bleeding from warfarin; closely monitor INR.
May ↑ hypoglycemic effects of sulfonylureas, pioglitazone, rosiglitazone, 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 ↑ digoxin levels, especially in older adults; closely monitor digoxin levels.
Indomethacin may ↑ levels and risk of toxicity; avoid concurrent use.
Concurrent use with 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 ⬆ ⬇

(TMP = trimethoprim; SMX = sulfamethoxazole).
Dosing based on TMP content.

Bacterial Infections

PO, IV (Adults and Children >2 mo): Mild-moderate infections — 6–12 mg TMP/kg/day divided every 12 hr; Serious infection/Pneumocystis — 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).

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:
Rate: Infuse over 60–90 min.
Y-Site Compatibility:
- acyclovir
- aldesleukin
- alemtuzumab
- allopurinol
- amifostine
- aminocaproic acid
- amphotericin B liposome
- anidulafungin
- argatroban
- arsenic trioxide
- azithromycin
- bivalirudin
- bleomycin
- cangrelor
- carboplatin
- carmustine
- cefepime
- ceftaroline
- cisplatin
- cyclophosphamide
- cytarabine
- dactinomycin
- daptomycin
- defibrotide
- dexmedetomidine
- diltiazem
- docetaxel
- doxorubicin liposome
- eptifibatide
- ertapenem
- etoposide
- etoposide phosphate
- fenoldopam
- filgrastim
- fludarabine
- fluorouracil
- fosphenytoin
- gemcitabine
- gemtuzumab ozogamicin
- granisetron
- hetastarch
- hydromorphone
- ifosfamide
- irinotecan
- leucovorin calcium
- levofloxacin
- linezolid
- lorazepam
- melphalan
- meropenem
- mesna
- methotrexate
- metronidazole
- milrinone
- mitoxantrone
- octreotide
- oxaliplatin
- paclitaxel
- palonosetron
- pamidronate
- pancuronium
- pemetrexed
- perphenazine
- piperacillin/tazobactam
- potassium acetate
- remifentanil
- rituximab
- sargramostim
- sodium acetate
- thiotepa
- tigecycline
- tirofiban
- trastuzumab
- vecuronium
- vinblastine
- vincristine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- alfentanil
- amikacin
- aminophylline
- amphotericin B lipid complex
- ampicillin
- ampicillin/sulbactam
- ascorbic acid
- atropine
- azathioprine
- benztropine
- blinatumomab
- bumetanide
- buprenorphine
- butorphanol
- calcium chloride
- calcium gluconate
- caspofungin
- cefazolin
- cefotaxime
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- chlorpromazine
- clindamycin
- cyanocobalamin
- cyclosporine
- dantrolene
- daunorubicin hydrochloride
- dexamethasone
- dexrazoxane
- diazepam
- diazoxide
- digoxin
- diphenhydramine
- dobutamine
- dopamine
- doxorubicin hydrochloride
- doxycycline
- ephedrine
- epinephrine
- epirubicin
- epoetin alfa
- erythromycin
- famotidine
- fentanyl
- fluconazole
- folic acid
- furosemide
- ganciclovir
- gentamicin
- glycopyrrolate
- heparin
- hydralazine
- hydrocortisone
- hydroxyzine
- idarubicin
- imipenem/cilastatin
- indomethacin
- insulin, regular
- isoproterenol
- ketamine
- ketorolac
- lactated Ringer's
- lidocaine
- mannitol
- methadone
- methylprednisolone
- metoclopramide
- metoprolol
- midazolam
- minocycline
- multivitamins
- mycophenolate
- nafcillin
- nalbuphine
- naloxone
- nitroglycerin
- nitroprusside
- norepinephrine
- ondansetron
- oritavancin
- oxacillin
- oxytocin
- papaverine
- penicillin G
- pentamidine
- pentobarbital
- phenobarbital
- phentolamine
- phenylephrine
- phenytoin
- phytonadione
- potassium chloride
- procainamide
- prochlorperazine
- promethazine
- propranolol
- protamine
- pyridoxine
- quinupristin/dalfopristin
- sodium bicarbonate
- succinylcholine
- sufentanil
- theophylline
- thiamine
- tobramycin
- topotecan
- vancomycin
- verapamil
- vinorelbine

US Brand Names ⬆ ⬇

Bactrim, Bactrim DS, Septra, Septra DS, Sulfatrim Pediatric

Canadian Brand Names ⬆ ⬇

Sulfatrim, Sulfatrim DS

Classifications ⬆ ⬇

Therapeutic Classification: anti-infectives, antiprotozoals

Pharmacologic Classification: folate antagonists, sulfonamides

Availability ⬆ ⬇

(Generic available)

Oral suspension (cherry, grape flavors): 40 mg TMP/200 mg SMX per 5 mL;
- Cost: Generic— $58.10/473 mL.
Solution for injection: 16 mg TMP/80 mg SMX per mL (contains 40% propylene glycol);
Tablets: 20 mg TMP/100 mg SMX; 80 mg TMP/400 mg SMX; 160 mg TMP/800 mg SMX (double-strength);
- Cost: Generic— 80 mg TMP/400 mg SMX; $6.99/30 160 mg TMP/800 mg SMX; $6.70/30.

Time/Action Profile ⬆ ⬇

(blood levels)

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

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.

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.
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 breast feeding.
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 ⬇

Indications ⬆ ⬇