cefixime (Rx)

>10%

Diarrhea (16%)

Frequency Not Defined

Abdominal pain

Candidiasis

Dizziness

Dyspepsia

Elevated transaminases

Eosinophilia

Erythema multiforme

Fever

Flatulence

Headache

Increased blood urea nitrogen (BUN)

Increased creatinine

Leukopenia

Nausea

Prolonged prothrombin time (PT)

Pruritus

Pseudomembranous colitis

Rash

Serum sickness-like reaction

Stevens-Johnson syndrome

Thrombocytopenia

Urticaria

Vaginitis

Vomiting

Contraindications

Documented hypersensitivity

Cautions

Limited activity against anaerobes

Dosage must be adjusted in severe renal insufficiency (high doses may cause CNS toxicity, including seizures); superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy

Use with caution in patients with history of penicillin allergy

Bacterial or fungal overgrowth of nonsusceptible organisms may occur with prolonged or repeated therapy

Immune-mediated hemolytic anemia reported; monitor hematologic parameters during and for 2 to 3 weeks after therapy; discontinue therapy if hemolytic anemia occurs during treatment

Phenylalanine can be harmful to patients with phenylketonuria (PKU); chewable tablets contain aspartame, a source of phenylalanine; before prescribing, consider combined daily amount of phenylalanine from all sources, including chewable tablets

Use caution in patients with history of gastrointestinal disease

Clostridium difficile associated diarrhea (CDAD) reported with use of nearly all antibacterial agents, and may range in severity from mild diarrhea to fatal colitis; if CDAD is suspected or confirmed, discontinue ongoing antibacterial drug use not directed against C. difficile; institute appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile, and surgical evaluation as clinically indicated

Immune-mediated hemolytic anemia reported; monitor hematologic parameters during and for 2 to 3 weeks after therapy; discontinue therapy if hemolytic anemia occurs during treatment

Cephalosporins may be associated with a fall in prothrombin activity; patients with renal or hepatic impairment, or poor nutritional state, patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy; monitor prothrombin time in patients at risk and exogenous vitamin K administered as indicated

May cause acute renal failure including tubulointerstitial nephritis; discontinue therapy if renal failure occurs and initiate supportive therapy

Severe cutaneous reactions, including Stevens-Johnson syndrome, epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms (DRESS) reported; discontinue therapy and implement supportive therapy if reaction occurs

Drug interactions overview

• Concomitant use with cefixime and carbamazepine may elevate carbamazepine levels reported in postmarketing experience
• Administration of cefixime may result in a false-positive reaction for glucose in the urine using Clinitest®, Benedict’s solution, or Fehling’s solution; use glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix® or TesTape®) be used
• A false-positive direct Coombs test reported during treatment with other cephalosporins; therefore, it should be recognized that a positive Coombs test may be due to the drug

Pregnancy

Available data from published observational studies, case series, and case reports over several decades with cephalosporin use, including cefixime, in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Maternal gonorrhea may be associated with preterm birth, low neonatal birth weight, chorioamnionitis, intrauterine growth restriction, small for gestational age and premature rupture of membranes; perinatal transmission of gonorrhea to offspring can result in infant blindness, joint infections, and bloodstream infections

Animal data

• Reproduction studies have been performed in mice and rats at doses equivalent to 40 and 80 times, respectively, adult human recommended dose and have revealed no evidence of harm to the fetus due to cefixime

Lactation

There are no available data on presence of drug in human milk, effects on breastfed infant, or on milk production; drug is present in animal milk; when a drug is present in animal milk, it is likely the drug will be present in human milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from drug or from mother’s underlying condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Third-generation oral cephalosporin with broad activity against gram-negative bacteria; by binding to 1 or more penicillin-binding proteins, it arrests bacterial cell-wall synthesis and inhibits bacterial growth

Absorption

Bioavailability: 40-50%

Average peak plasma concentration: ~2 mcg/mL (single 200 mg-tablet); ~3.7 mcg/mL (single 400 mg-tablet)

Peak plasma time: 2-6 hr (single 200mg, 400 mg–tablet or 400mg suspension); 2-5 hr (single 200 mg-suspension); 3-8 hr (single 400 mg-capsule)

Food reduces absorption following administration of the capsule by ~15% based on AUC and 25% based on peak plasma concentrations

Distribution

Distributed widely throughout body and reaches therapeutic concentration in most tissues and body fluids, including synovial, pericardial, pleural, and peritoneal; bile, sputum, and urine; bone, myocardium, gallbladder, skin, and soft tissue

Protein bound: 65%

Elimination

Half-life: 3-4 hr

Excretion: Urine (50% as unchanged drug), feces (10%)

Oral Suspension Preparation

Tap bottle several times to loosen powder contents prior to reconstitution

Add ~1/2 of the total amount of water for reconstitution and shake well (refer to prescribing information for specific volumes)

Add remainder of water and shake well

Oral Administration

Administer orally once or twice daily depending on indication

Do not substitute tablet or capsule for the chewable tablets or suspension in the treatment of otitis media

Chewable tablets must be chewed or crushed before swallowing

Storage

Capsules, chewable tablets, or tablets: Store at 20-25°C (68-77°F)

Unused suspension: Store at 20-25°C (68-77°F)

Reconstituted suspension

• Store at room temperature, or under refrigeration, without significant loss of potency for up to 14 days
• Keep tightly closed
• Shake well before using
• Discard unused portion after 14 days