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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

Drugs>Antimicrobial Agents>
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Trimethoprim + Sulfamethoxazole

Paul A. Pham, Pharm.D. and John G. Bartlett, M.D.
01-11-2010

Zambia Specific Information

  • Available formulation in Zambia: Injection: SMX 80 mg + TMP16 mg/ml in 5 ml and 10 ml ampoules. Oral liquid: SMX 200 mg/5 ml + TMP 40 mg/5 ml. Tablet: SMX/TMP 100 + 20 mg; 400 + 80 mg.
  • PCP treatment: 5 mg/kg (TMP component) q6h: <60kg three 400/80 mg tabs q6h x 21 days; >60 kg four 400/80 mg tabs q6h x 21 days.
  • PCP prophylaxis: 1-2 tabs (400/80 mg) once daily. If Toxo IgG+, SMX/TMP 800/160 mg once daily.
  • Toxoplasmosis: 1600/320 mg q12h (5 mg/kg q12h TMP component) x 4weeks, then 800/160 mg q12h x 12 weeks. Consider induction for 6 weeks, then ½ dose for maintenance.
  • UTI prophylaxis: SMX/TMP 400/80 mg qhs
  • High level of SMX/TMP resistance observed in strains of non-typhoidal Salmonellae, S. flexneri, and S. dysenteriae in tertiary hospital in Zambia.

REFERENCES

Zambia Information Author: Paul A. Pham Pharm.D.

INDICATIONS

FDA

  • Acute exacerbation of chronic bronchitis
  • Otitis media (in S. pneumoniae sensitive cases only) 
  • PCP prophylaxis
  • PCP treatment
  • Traveler's diarrhea, shigellosis
  • Urinary tract infections
NON-FDA APPROVED USES

  • Nocardia infection
  • Toxoplasmosis treatment and prophylaxis
  • Bacterial cystitis prophylaxis
  • Isospora infections
  • Salmonella infections
  • MSSA and community-acquired MRSA soft tissue infections
  • Legionellosis treatment (2nd line)
  • Listeriosis treatment (2nd line for PCN allergic pts)

FORMS

brand 
name
 
generic 
Mfg 
brand 
forms
 
cost* 
 Bactrim or Septra Trimethoprim-sulfamethoxazole (TMP-SMX) Generic manufacturersoral
tablet
400 mg/80 mg (SS)
$0.66
      oral
tablet
800 mg/160 mg (DS)
$1.14
      IV
vial
80 mg/16 mg per ml (30ml)
$19.49 /30 ml
      oral
suspension
200-40 mg/5 ml (473 ml bottle)
$58.10/473 ml bottle

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

USUAL ADULT DOSING

PCP

  • PCP treatment: 5 mg/kg (TMP component) IV or PO q8h x 21d (usually 5-6 DS/d but must dose based on weight using TMP component).
  • PCP prophylaxis: 1 DS or 1 SS PO once-daily or 1 DS 3x/wk (alternative).
  • Toxoplasmosis prophylaxis: 1 DS PO once-daily.
  • Toxoplasmosis treatment: 5 mg/kg (TMP component) PO or IV q12h x 6 wks, then 1/2 dose for maintenance (sulfadiazine + pyrimethamine preferred).
  • UTI: 1 DS PO twice-daily x 3-14 d, (3d recommended for uncomplicated cystitis in women).
  • Traveler's diarrhea, Salmonella, Shigella, E. coli, and Cyclospora: 1 DS PO twice-daily x 5-7 d.
  • Skin and soft tissue infections (including CA-MRSA): 1-2 DS PO q12h.
  • Nocardia: 2-3 DS PO twice-daily x >6 mos.
  • Isospora: 1 DS PO twice-daily x 7-10 d, then 1 DS 3x/wk.
  • Gradual dose escalation over 6 d may improves long-term tolerability of TMP/SMX compared to direct rechallenge, but dosing may be impractical for some pts. Start with 12.5% of SS TMP/SMX (10 mg TMP component), then increase by 12.5%/d until target dose of 1 SS TMP/SMX on day 6 (J Infect Dis. 2001;184:992-7).
  • Acute exacerbations of chronic bronchitis (bacterial): 1 DS twice-daily x 14 d

RENAL DOSING

DOSING FOR GLOMERULAR FILTRATION OF 50-80

Usual dose.

DOSING FOR GLOMERULAR FILTRATION OF 10-50

GFR 10-30 ml/min: 5 mg/kg IV q12h; oral 50% of dose.

DOSING FOR GLOMERULAR FILTRATION OF <10 ML/MIN

Manufacturer recommends avoiding. For severe PCP or serious infections, authors recommend 5-7.5 mg/kg/d in 2-3 divided doses (1/2-1/3 standard dose) for GFR <10ml/min. HD: 5-7.5 mg/kg/d (1/2-1/3 standard dose). PCP prophylaxis: consider 1 SS po once-daily.

DOSING IN HEMODIALYSIS

Dialyzed out, consider 5-7.5mg/kg/d in 2-3 divided doses (dose post-HD on days of dialysis). PCP prophylaxis: consider 1 SS PO qday.

DOSING IN PERITONEAL DIALYSIS

Not dialyzed out. PCP prophylaxis: consider 1 DS PO q48h. PCP treatment: consider 5 mg/kg/d.

DOSING IN HEMOFILTRATION

CVVH and CVVHD: limited data. Consider 5 mg/kg IV q 8h-12h.

ADVERSE DRUG REACTIONS

Generally well tolerated in the immunocompetent host. HIV+ pts at increased risk for developing SMX-TMP-associated ADRs.

COMMON

  • GI intolerance with nausea and vomiting (in 20-50% receiving high dose >15 mg/kg).
  • Rash and pruritus (usually 7-14 d after starting SMX/TMP).
  • Continue treatment if Sx not disabling.
  • Pseudo elevation in serum creatinine (an average increase of18%) [Kainer et al. Chemotherapy. 1981;27:229-32].
OCCASIONAL

  • Reversible hyperkalemia (with higher TMP doses +/- chronic renal insufficiency ).
  • Bone marrow suppression (anemia with folate deficiency, thrombocytopenia, and leukopenia; more common with higher doses).
  • Serum sickness and drug fever.
  • Hepatitis (may be cholestatic).
  • Photosensitivity.
  • Methemoglobinemia (with severe G6PD deficiency). African-American pts with mild to moderate G6PD deficiency can tolerate TMP-SMX.
RARE

  • Crystalluria with azotemia, urolithiasis and oliguria (more common with sulfadiazine).
  • Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN)
  • Aseptic meningitis
  • Pancreatitis
  • Neurologic toxicity (tremor, ataxia, apathy, and ankle clonus)
  • Interstitial nephritis

DRUG INTERACTIONS

  • Cyclosporine: may decrease cyclosporine serum levels. Monitor cyclosporine serum levels.
  • Folinic acid: possible antagonism. Avoid co-administration.
  • Para-aminobenzoic acid (PABA) and derivatives (such as benzocaine, procaine, tetracaine): theoretical antagonism.
  • Phenytoin: may increase phenytoin serum levels. Monitor free phenytoin levels with co-administration.
  • Porfimer: may increase the risk of photosensitivity reaction. Avoid co-administration.
  • Sulfonylurea: may increase hypoglycemia. Monitor closely with co-administration.
  • Warfarin: may increase INR. Monitor closely.

SPECTRUM

T. gondii, P. jiroveci , CA-MRSA, Gram-negative bacilli

Detailed Spectrum of Activity

RESISTANCE

  • E. coli: (urine isolates) certain regions in US and world-wide >20% resistance
  • S. pneumoniae: 15-30% resistance
  • P. jiroveci: increasing rates of mutations in the dihydropteroate synthase (DHPS) gene of P. jiroveci associated with resistance to sulfonamide and dapsone but not clinically significant since clinical outcome was not worse with DHPS mutation in a prospective trial (Lancet 2001;358:545-9).
  • CA-MRSA: low resistance rates to TMP-SMX

PHARMACOLOGY

Pharmacology

COMMENTS

First line agent for PCP prophylaxis and treatment. Active against other pathogens (T. gondii, Listeria, Legionella, 70% of S. pneumoniae, many S. aureus including CA-MRSA, and H. influenzae) which may protect patients against CAP and soft tissue infections. Although generally well tolerated in immunocompetent host, there is higher incidence of intolerance requiring discontinuation in HIV+ pts.

Basis for Recommendations

  •  National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the HIV Medicine Association of the Infectious Diseases Society of America (HIVMA/IDSA); Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents ; http://AIDSinfo.nih.gov/ ; 2008 ; Vol.
    Rating: Basis for recommendation
    Comments:TMP-SMX usage recommendations in HIV patients. TMP-SMX is the preferred agent for PCP prophylaxis and treatment.

REFERENCES

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