trimethoprim/sulfamethoxazole

BEERS REMS

Treatment of:
- Bronchitis,
- Shigella enteritis,
- Otitis media,
- Pneumocystis jiroveciipneumonia (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: 6–11 hr; sulfamethoxazole: 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 if CCr <30 mL/min);
Mild or moderate hepatic impairment;
G6PD deficiency (↑ risk hemolysis);
HIV (↑ risk 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 ↓ CCr because of ↑ risk of hyperkalemia.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension

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

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, HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, hemolytic anemia, leukopenia, megaloblastic anemia, thrombocytopenia

Local: phlebitis

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

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

Route/Dosage ⬆ ⬇

Dosing based on trimethoprim content.

Bacterial Infections

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

Urinary Tract Infection Prophylaxis

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

P. jirovecii Pneumonia Prevention

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

Availability ⬆ ⬇

(Generic available)

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

Assessment ⬆ ⬇

Assess for sulfonamide allergy prior to initiation.
Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
Inspect IV site frequently for infusion reaction, including phlebitis.
Monitor for signs/symptoms of hypersensitivity reaction and anaphylaxis. If symptoms occur, immediately discontinue therapy and treat as indicated. Keep emergency medication and equipment nearby during therapy.
Assess for signs/symptoms of hemophagocytic lymphohistiocytosis (fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, ↑ ferritin, hypertriglyceridemia, liver enzyme and coagulation abnormalities). If hemophagocytic lymphohistiocytosis suspected, discontinue trimethoprim/sulfamethoxazole immediately and treat as indicated.
Monitor intake and output. Fluid intake should be sufficient to maintain a urine output of ≥1200–1500 mL daily to prevent crystalluria and stone formation.
Monitor for signs/ symptoms of CDAD (diarrhea, abdominal cramping, fever, bloody stools). If CDAD occurs, discontinue trimethoprim/sulfamethoxazole and treat as indicated. May begin up to several weeks following cessation of therapy.
Assess for rash periodically during therapy. May cause SJS, TEN, EM, and AGEP. If severe skin reaction occurs or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, or eosinophilia, discontinue trimethoprim/sulfamethoxazole.

Lab Test Considerations:

Obtain specimens for culture and sensitivity before initiating therapy. 1st dose may be given before receiving results.
- Monitor CBC, including platelets, and urinalysis periodically during therapy.
- May ↑ serum bilirubin, 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: 1.06 mg/mL.
Rate: Infuse over 60–90 min.
Y-Site Compatibility:
- acyclovir
- aldesleukin
- alemtuzumab
- allopurinol
- aminocaproic acid
- amphotericin B liposomal
- anidulafungin
- argatroban
- arsenic trioxide
- azithromycin
- bivalirudin
- bleomycin
- cangrelor
- carboplatin
- carmustine
- cefepime
- cefiderocol
- ceftaroline
- ceftobiprole
- cisplatin
- cyclophosphamide
- cytarabine
- dactinomycin
- daptomycin
- defibrotide
- dexmedetomidine
- diltiazem
- dimenhydrinate
- docetaxel
- doxorubicin liposomal
- edetate disodium
- eptifibatide
- ertapenem
- etoposide
- etoposide phosphate
- filgrastim
- fludarabine
- fluorouracil
- fosphenytoin
- gemcitabine
- gemtuzumab ozogamicin
- granisetron
- hydromorphone
- ifosfamide
- irinotecan
- leucovorin
- levofloxacin
- linezolid
- lorazepam
- melphalan
- meropenem
- mesna
- methotrexate
- metronidazole
- milrinone
- mitomycin
- mitoxantrone
- octreotide
- oxaliplatin
- paclitaxel
- palonosetron
- pamidronate
- pemetrexed
- piperacillin/tazobactam
- potassium acetate
- remifentanil
- rituximab
- sargramostim
- sodium acetate
- thiotepa
- tigecycline
- tirofiban
- trastuzumab
- vecuronium
- vinblastine
- vincristine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- amikacin
- aminophylline
- amphotericin B deoxycholate
- ampicillin
- ampicillin/sulbactam
- ascorbic acid
- atropine
- azathioprine
- benztropine
- blinatumomab
- bumetanide
- buprenorphine
- butorphanol
- calcium chloride
- calcium gluconate
- caspofungin
- cefazolin
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- chlorpromazine
- clindamycin
- cyanocobalamin
- cyclosporine
- dacarbazine
- dantrolene
- daunorubicin
- 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
- haloperidol
- hydralazine
- hydrocortisone
- idarubicin
- imipenem/cilastatin
- indomethacin
- insulin regular
- isoproterenol
- ketamine
- ketorolac
- 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
- sodium bicarbonate
- succinylcholine
- sufentanil
- theophylline
- thiamine
- tobramycin
- topotecan
- vancomycin
- verapamil
- vinorelbine

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient to take full course of therapy, even if feeling better, and to take missed dose as soon as remembered unless almost time for next dose. Skipping doses or not completing full course may result in ↓ effectiveness and ↑ risk of bacterial resistance.
Instruct patient to notify health care provider 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 provider.
Emphasize importance of regular follow-up exams to monitor blood counts in patients on prolonged therapy.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reaction.
Advise patient to notify health care provider if rash, sore throat, fever, mouth sores, or unusual bleeding or bruising occurs.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Instruct patient to notify health care provider if signs/symptoms of infection do not improve within a few days.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Fetal exposure during pregnancy may lead to congenital malformations, neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, and club foot.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇