Suprax

Generic Name: Cefixime
Class: Third Generation Cephalosporins
Chemical Name: [6R - [6α,7β(Z)]] - 7 - [[(2 - Amino - 4 - thiazoyl)[(carboxymethoxy)imino]acetyl]amino] - 3 - ethenyl - 8 - oxo - 5 - thia - 1 - azabicyclo[4.2.0]oct - 2 - ene - 2 - carboxylic acid
CAS Number: 79350-37-1

Introduction

Antibacterial; β-lactam antibiotic; third generation cephalosporin.^{1 2 3 4 6 7 13 23 42 57 60 75 83}

Uses for Suprax

Respiratory Tract Infections

Treatment of acute bronchitis caused by Streptococcus pneumoniae,^{1 2 23 44 70 72 103 187 188} Haemophilus influenzae (including β-lactamase-producing strains),^{1 2 23 44 70 72 103 187 188} or Moraxella catarrhalis†.^{2 44 70 72 103 187}

Treatment of acute exacerbations of chronic bronchitis caused by S. pneumoniae,^{1 2 23 44 70 72 103 187 188} H. influenzae (including β-lactamase-producing strains),^{1 2 23 44 70 72 103 187 188} or M. catarrhalis†.^{2 44 70 72 103}

Treatment of mild to moderate community-acquired pneumonia† (CAP) caused by S. pneumoniae,^{2 23 44 70 72 103} H. influenzae,^{1 2 23 44 70 72 103} M. catarrhalis,^{2 44 70 72 103 137 166} E. coli, H. parahaemolyticus, or H. parainfluenzae.^{2 3 44 64 75}

Treatment of mild to moderate sinusitis† caused by S. pneumoniae,^{2 23 44 70 72 103} H. influenzae,^{1 2 23 44 70 72 103} M. catarrhalis,^{2 44 70 72 103 137 166} E. coli, H. parahaemolyticus, or H. parainfluenzae.^{2 3 44 64 75}

Acute Otitis Media (AOM)

Treatment of AOM^{1 2 3 5 23 43 49 56 61 62 63 75 138 164 165 187} caused by H. influenzae (including β-lactamase-producing strains),^{1 2 23 61 62 63 187} M. catarrhalis (including β-lactamase-producing strains),^{1 2 23 61 62 63 187} or S. pyogenes (group A β-hemolytic streptococci).^{1 2 23 62 63 187}

Pharyngitis and Tonsillitis

Treatment of pharyngitis and tonsillitis caused by susceptible S. pyogenes (group A β-hemolytic streptococci).^{1 2 3 5 23 44 56 64 75 187 188} Generally effective in eradicating S. pyogenes from the nasopharynx, but efficacy in prevention of subsequent rheumatic fever has not been established to date.^{1 187 188}

CDC, AAP, IDSA, AHA, and others recommend oral penicillin V or IM penicillin G benzathine as treatments of choice;^{5 82 86 104 151 152} oral cephalosporins and oral macrolides considered alternatives.^{5 82 152} Amoxicillin sometimes used instead of penicillin V, especially for young children.¹⁵²

Urinary Tract Infections (UTIs)

Treatment of uncomplicated UTIs^{1 2 5 40 42 51 64 74 75 182 187 188} caused by susceptible Escherichia coli^{1 2 40 51 64 74 75 182 187 188} or Proteus mirabilis;^{1 2 40 51 74 75 182 187 188} also has been used for treatment of uncomplicated UTIs caused by susceptible Citrobacter spp.†,^{2 51 64 74} C. diversus†,^{2 74} C. freundii†,^{2 74} Enterobacter spp.†,^{2 40 51} E. aerogenes†,^{2 40 74} E. agglomerans†,^{2 64} Klebsiella spp.†,^{2 40 51 182} K. pneumoniae†,^{2 64 74} Morganella morganii†,² Proteus spp.†,^{2 51 64} or Serratia†^{2 51 74} .

Has been used for treatment of uncomplicated UTIs^{1 2 5 40 42 51 64 74 75 182} caused by susceptible gram-positive bacteria, including Staphylococcus epidermidis†,² Staphylococcus spp.†,^{2 51} Streptococcus agalactiae†,^{2 40} nonhemolytic streptococci†,^{2 40 51} or Enterococcus faecalis†.^{2 40} Consider that treatment failures have been reported and gram-positive bacteria (e.g., staphylococci, S. agalactiae, enterococci) have been isolated in urine during or after cefixime treatment and usually are resistant to cefixime.^{2 51 74}

Treatment of pyelonephritis† and other complicated UTIs†^{2 23 40 75} caused by susceptible Enterobacteriaceae, including E. coli.^{2 23}

Gonorrhea and Associated Infections

Treatment of uncomplicated urethral, endocervical, or rectal infections† caused by susceptible Neisseria gonorrhoeae.^{1 2 23 48 71 105 106 108 109 110 111 130 186 187 188} CDC recommends ceftriaxone or cefixime as drug of choice for uncomplicated cervical, urethral, or rectal gonorrhea in adults and adolescents;^{130 186} ceftriaxone is recommended for pharyngeal gonorrhea.^{130 186}

Follow-up treatment of disseminated gonococcal infections† after an initial parenteral regimen (ceftriaxone or, alternatively, cefotaxime, or spectinomycin [not currently commercially available in the US]); CDC recommends cefixime or cefpodoxime as drug of choice for follow-up treatment.^{130 186}

Salmonella and Shigella Infections

Has been used for treatment of typhoid fever (enteric fever) or septicemia caused by multidrug-resistant Salmonella typhi†.^{141 142 189 190 191}

Has been used for treatment of shigellosis† caused by susceptible Shigella.^{139 148}

Lyme Disease

Has been used for treatment of disseminated Lyme disease†.¹⁸¹ Other cephalosporins (cefotaxime, ceftriaxone, cefuroxime axetil) usually recommended by IDSA and others when a cephalosporin is used in the treatment of Lyme disease.^{104 185}

Suprax Dosage and Administration

Administration

Oral Administration

Administer orally.^{1 187 188}

Reconstitution

Reconstitute oral suspension at the time of dispensing by adding the amount of water specified on the container in 2 portions; invert bottle and shake after each addition.^{1 187} The reconstituted suspension contains 100 or 200 mg/5 mL.^{1 187}

Shake oral suspension well just prior to administration of each dose.^{1 187}

Dosage

Available as cefixime trihydrate; dosage expressed in terms of cefixime.^{1 187 188}

Pediatric Patients

Respiratory Tract Infections

Acute Bronchitis

Oral

Oral suspension in children 6 months to 12 years of age: 8 mg/kg once daily or 4 mg/kg every 12 hours^{1 187 188} for 10–14 days.^{44 64 72}

Oral suspension or tablet in children >12 years of age or weighing >50 kg: 400 mg once daily or 200 mg every 12 hours^{1 187 188} for 10–14 days.^{44 64 72}

Acute Exacerbations of Chronic Bronchitis

Oral

Oral suspension in children 6 months to 12 years of age: 8 mg/kg once daily or 4 mg/kg every 12 hours^{1 187 188} for 10–14 days.^{44 64 72}

Oral suspension or tablet in children >12 years of age or weighing >50 kg: 400 mg once daily or 200 mg every 12 hours^{1 187 188} for 10–14 days.^{44 64 72}

Acute Otitis Media (AOM)

Oral

Oral suspension in children 6 months to 12 years of age: 8 mg/kg once daily or 4 mg/kg every 12 hours^{1 187} for 10–14 days.^{23 47 49 55 56 62 63}

Oral suspension in children >12 years of age or weighing >50 kg: 400 mg daily^{1 187} for 10–14 days.^{44 64 72}

Do not use tablets for treatment of AOM.^{1 187 188}

Pharyngitis and Tonsillitis

Oral

Oral suspension in children 6 months to 12 years of age: 8 mg/kg once daily^{1 5 23 43 49 56 61 62 63 64 75 187} or 4 mg/kg every 12 hours^{1 5 23 61 62 187} for ≥10 days.¹

Oral suspension or tablet in children >12 years of age or weighing >50 kg: 400 mg once daily or 200 mg every 12 hours^{1 187 188} for ≥10 days.^{44 64 72 188}

Urinary Tract Infections (UTIs)

Uncomplicated UTIs

Oral

Oral suspension in children 6 months to 12 years of age: 8 mg/kg once daily^{1 5 23 43 49 56 61 62 63 64 75 187} or 4 mg/kg every 12 hours^{1 5 23 61 62 187} for 5–10 days.^{2 40 51 74}

Oral suspension or tablet in children >12 years of age or weighing >50 kg: 400 mg once daily or 200 mg every 12 hours^{1 187 188} for 5–10 days.^{2 40 51 74}

Gonorrhea and Associated Infections

Uncomplicated Urethral, Endocervical, or Rectal† Gonorrhea

Oral

Oral suspension (200 mg/5 mL) or tablet in adolescents: 400 mg as a single dose.^{130 186 187 188}

Disseminated Gonococcal Infections†

Oral

Oral suspension (200 mg/5 mL) or tablet in adolescents: 400 mg twice daily recommended by CDC; given to complete ≥1 week of treatment after an initial parenteral regimen of ceftriaxone or, alternatively, cefotaxime or spectinomycin (not currently commercially available in the US).^{130 186}

Salmonella and Shigella Infections†

Typhoid Fever†

Oral

Children 6 months to 16 years of age: 5–10 mg/kg twice daily.^{141 142 189 190 191} Usually given for 14 days;^{141 142 189} high rate of treatment failure occurred when given for only 7 days.¹⁹⁰

Shigellosis†

Oral

8 mg/kg daily for 5 days.^{139 148}

Adults

Respiratory Tract Infections

Acute Bronchitis

Oral

Oral suspension or tablet: 400 mg once daily^{1 3 5 23 40 44 51 70 72 74 75 187 188} or 200 mg every 12 hours^{1 2 3 23 44 187 188} for 10–14 days.^{44 64 72}

Acute Exacerbations of Chronic Bronchitis

Oral

Oral suspension or tablet: 400 mg once daily^{1 3 5 23 40 44 51 70 72 74 75 187 188} or 200 mg every 12 hours^{1 3 5 23 44 51 187 188} for 10–14 days.^{44 64 72}

Acute Otitis Media (AOM)

Oral

Oral suspension: 400 mg once daily^{1 2 3 5 23 40 44 51 70 72 74 75 187} or 200 mg every 12 hours^{1 2 3 23 187} for 10–14 days.^{23 47 49 55 56 62 63}

Do not use tablets for treatment of AOM.^{1 187 188}

Pharyngitis and Tonsillitis

Oral

Oral suspension or tablet: 400 mg once daily^{1 3 5 23 40 44 51 70 72 74 75 187 188} or 200 mg every 12 hours^{1 3 5 23 44 187 188} for ≥10 days.^{1 187 188}

Urinary Tract Infections (UTIs)

Uncomplicated UTIs

Oral

Oral suspension or tablet: 400 mg once daily^{1 3 5 23 40 44 51 70 72 74 75 187 188} or 200 mg every 12 hours^{1 3 5 23 51 187 188} for 5–10 days.^{40 51 74}

Gonorrhea and Associated Infections

Uncomplicated Urethral, Endocervical, or Rectal† Gonorrhea

Oral

Oral suspension (200 mg/5 mL) or tablet: 400 mg as a single dose.^{1 100 105 106 108 130 186 187}

Disseminated Gonococcal Infections†

Oral

Oral suspension (200 mg/5 mL) or tablet: 400 mg twice daily recommended by CDC; given to complete ≥1 week of treatment after an initial parenteral regimen of ceftriaxone or, alternatively, cefotaxime or spectinomycin (not currently commercially available in the US).^{130 186}

Lyme Disease†

Oral

200 mg daily for 100 days (administered with oral probenecid).¹⁸¹

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with Cl_cr <60 mL/minute.^{1 2 187 188}

Dosage in Adults with Renal Impairment

Clcr (mL/min)	Dosage
21–60	75% of the usual dose given at usual intervals1 187 188
<20	50% of the usual dose given at the usual intervals1 187 188
Hemodialysis Patients	75% of the usual dose given at usual intervals;1 187 188 supplemental doses not necessary during or after hemodialysis33 75
CAPD Patients	50% of the usual dose given at the usual intervals1 23 37 75 187 188 or the usual dose given at twice the usual dosing interval;33 supplemental doses not necessary during or after CAPD33 75

Geriatric Patients

No dosage adjustments except those related to renal impairment.^{2 35 37} (See Renal Impairment under Dosage and Administration.)

Cautions for Suprax

Contraindications

• 
  

  Known hypersensitivity to cefixime or other cephalosporins.^{1 187 188}

  
  

Warnings/Precautions

Warnings

Superinfection/Clostridium difficile-associated Diarrhea and Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi, especially Enterobacter, Pseudomonas, enterococci, staphylococci, or Candida.^{1 5 187 188} Careful observation of the patient is essential.^{1 187 188} Institute appropriate therapy if superinfection occurs.^{1 187 188}

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.^{1 175 176 177 178 179 187 188} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including cefixime, and may range in severity from mild diarrhea to fatal colitis.^{1 175 176 177 178 179 187 188} Hyper toxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{1 175 176 177 178 179 187 188} Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.

If CDAD is suspected or confirmed, the anti-infective may need to be discontinued.^{175 176 177 178 179} Some mild cases may respond to discontinuance alone.^{1 175 176 177 178 179 187 188} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin); and surgical evaluation when clinically indicated.^{1 175 176 177 178 179}

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions such as anaphylaxis (including shock and fatalities), angioedema, serum sickness-like reactions, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported.^{1 5 40 41 43 56 64 75 187 188}

If an allergic reaction occurs, discontinue cefixime and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, and maintenance of an adequate airway and oxygen).^{1 187 188}

Cross-hypersensitivity

Partial cross-allergenicity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.^{1 172 173 187 188} Use caution.^{1 187 188}

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, or other drugs.^{1 187 188} Cefixime is contraindicated in individuals hypersensitive to cephalosporins.^{1 187 188} Avoid use in those who have had an immediate-type (anaphylactic) hypersensitivity reaction and administer with caution in those who have had a delayed-type (e.g., rash, fever, eosinophilia) reaction.¹⁷³

General Precautions

History of GI Disease

Use cefixime with caution in patients with a history of GI disease, particularly colitis.^{1 187 188} (See Superinfection/Clostridium difficile-associated Diarrhea and Colitis under Cautions.)

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of cefixime and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.^{1 187 188}

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.^{1 187 188} In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.^{1 187 188}

Coombs' Test Results

Positive direct Coombs’ test results reported with cephalosporins.^{1 187 188 b} This may interfere with certain hematologic studies or transfusion cross-matching procedures.^b

Decreased Prothrombin Activity

Prolonged PT^{1 2 187 188} and prolonged partial thromboplastin time^{2 33 41} reported rarely.^{1 2 41 187 188}

Patients with renal or hepatic impairment, poor nutritional status, prolonged anti-infective therapy, and previous anticoagulant therapy (stabilized) appear to be at risk.^{1 187 188} Monitor PT in such patients and administer exogenous vitamin K as indicated.^{1 187 188}

Specific Populations

Pregnancy

Category B.^{1 187 188}

Lactation

Discontinue nursing or the drug.^{1 187 188}

Pediatric Use

Safety and efficacy not established in children <6 months of age.^{1 187 188} Frequency of adverse GI effects (e.g., diarrhea, loose stools) similar to that in adults.^{1 187 188}

Geriatric Use

Possible increased oral bioavailability;^{1 35 37 187 188} not considered clinically important.^{35 37}

Consider age-related decreases in renal function when selecting dosage and adjust dosage if necessary.^{2 35 37} (See Renal Impairment under Dosage and Administration.)

Renal Impairment

Increased serum half-life.^{1 2 23 33 37 75 187 188} Dosage adjustments necessary if Cl_cr <60 mL/minute.^{1 2 33 35 37 187 188} (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea,^{1 2 33 40 41 43 44 51 56 63 64 67 75 103 187 188} loose or frequent stools,^{1 187 188} abdominal pain,^{1 2 23 40 41 44 51 56 64 67 75 187 188} nausea,^{1 2 23 40 41 44 51 63 64 74 75 187 188} dyspepsia,^{1 2 23 40 41 44 51 75 187 188} flatulence).^{1 2 40 41 75 187 188}

Interactions for Suprax

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Antacids (aluminum- or magnesium-containing)	No clinically important effect on cefixime pharmacokinetics 32
Anticoagulants, oral (warfarin)	Possible increased PT (with or without bleeding)1 187 188
Carbamazepine	Increased carbamazepine concentrations1 187 188	Monitor carbamazepine concentrations1 187 188
Nifedipine	Possible increased plasma concentrations and AUC of cefixime143
Probenecid	Increased cefixime plasma concentrations and AUC2
Salicylates	Possible decreased plasma concentrations and AUC of cefixime2 25	Clinical importance unclear2 102
Tests for glucose	Possible false-positive reactions in urine glucose tests using Clinitest, Benedict’s solution, or Fehling’s solution1 187 188	Use glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)1 187 188
Tests for ketones	Possible false-positive reaction for ketones in urine if nitroprusside tests used; not reported with tests using nitroferricyanide1 187 188

Suprax Pharmacokinetics

Absorption

Bioavailability

30–50% of a single oral dose absorbed;^{1 2 5 75 100 188} peak serum concentrations attained within 2–6 hours.^{1 2 26 30 31 35 37 100 188}

Tablets and oral suspension are not bioequivalent;^{1 188} oral suspension results in peak plasma