Is there an intravenous form of trimethoprim (TMP)-sulfamethoxazole (SMX) available?

Intravenous TMP-SMX Availability and Clinical Use

Yes, intravenous (IV) trimethoprim-sulfamethoxazole (TMP-SMX) is available and is used for treating various serious infections, particularly when oral administration is not feasible or appropriate. 1

Dosing and Administration

• IV TMP-SMX is administered with the following dosages:

  • For HIV-infected children >2 months: 15-20 mg/kg/day of TMP component (75-100 mg/kg of SMX component) in 3-4 divided doses, infused over 1 hour 1
  • For adults with severe infections: typically 150 mg TMP and 750 mg SMX/m² body surface area every 8 hours 2
  • For hemodialysis patients: 20 mg/kg loading dose infused during the last hour of dialysis session 1

• After clinical improvement with IV therapy, patients with mild to moderate disease who don't have malabsorption or diarrhea can be switched to oral treatment with the same dose to complete the treatment course 1

Clinical Indications

• Pneumocystis jiroveci pneumonia (PCP) in HIV-infected patients 1
• Serious bacterial infections including:
  • Soft tissue and skeletal infections 3
  • Severe skin and soft tissue infections (SSTIs) including MRSA infections 1
  • CSF shunt infections 3
  • Severe urinary tract infections 4
  • Severe respiratory tract infections 4

Pharmacokinetics

• Half-life of IV TMP is approximately 9.6 hours and SMX is 10.7 hours 2
• Both TMP and SMX have good penetration into cerebrospinal fluid with CSF/blood ratios of approximately 0.6 and 0.5, respectively 3
• Dosage adjustment is required in patients with renal impairment (creatinine clearance <30 mL/min) 5, 2
• In renal failure, the dosage interval should be increased according to serum creatinine levels 2

Adverse Effects

• Common adverse reactions include:

  • Rash (including erythema multiforme and rarely Stevens-Johnson syndrome) 1
  • Hematologic abnormalities (neutropenia, thrombocytopenia, megaloblastic or aplastic anemia) 1, 3
  • Gastrointestinal complaints (usually mild) 1
  • Hepatitis and renal disorders (interstitial nephritis) 1
  • Hyperkalemia, especially in patients with reduced kidney function 6

• The frequency of adverse reactions appears to be lower in HIV-infected children than adults, with approximately 15% experiencing substantial adverse reactions 1

Monitoring Recommendations

• Regular monitoring of complete blood counts with differential and platelet count is recommended to assess hematologic toxicity 1, 6
• Renal function and electrolytes should be monitored, particularly in patients with pre-existing renal impairment 6, 2
• For mild or moderate skin rash, TMP-SMX can be temporarily discontinued and restarted when the rash resolves 1
• If urticarial rash or Stevens-Johnson syndrome occurs, TMP-SMX should be discontinued permanently 1

Alternative Agents

• For patients intolerant of TMP-SMX or who demonstrate clinical treatment failure, alternatives include:
  • Pentamidine isothionate (4 mg/kg/day IV over 60-90 minutes) for PCP 1
  • Atovaquone for mild to moderately severe PCP 1
  • Daptomycin, linezolid, ceftaroline, dalbavancin, vancomycin, tigecycline, or tedizolid for MRSA skin infections 1

Clinical Considerations

• IV TMP-SMX achieves more reliable and higher peak drug concentrations compared to oral administration 2
• The combination of TMP-SMX with other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, or vancomycin) should be used with caution 1
• Care should be taken when coadministering with agents associated with pancreatitis (e.g., didanosine) 1