cephradine
Velosef

Pharmacologic classification: first-generation cephalosporin
Therapeutic classification: antibiotic
Pregnancy risk category B


Available forms
Available by prescription only
Capsules: 250 mg, 500 mg
Suspension: 125 mg/5 ml, 250 mg/5 ml

Indications and dosages
 Serious respiratory tract, skin and skin-structure infections. Adults: 250 P.O. q 6 hours or 500 mg P.O. q 12 hours. Severe or chronic infections may require larger or more frequent doses (up to 1 g P.O. q 6 hours).
Children older than age 9 months: 25 to 50 mg/kg P.O. daily in equally divided doses q 6 to 12 hours.
 Otitis media. Children older than age 9 months: 75 to 100 mg/kg/day P.O. in equally divided doses q 6 to 12 hours. Maximum dose is 4 g/day.
 Uncomplicated urinary tract infections, lobar pneumonia. Adults: 500 mg P.O. q 12 hours. For more serious infections and prostatitis, 500 mg q 6 hours or 1 g q 12 hours.
  Larger doses (up to 1 g q.i.d.) may be given for severe or chronic infections in all patients regardless of age and weight.
≡ Dosage adjustment. To prevent toxic accumulation, reduced dosage may be required if patient has reduced creatinine clearance. For patients with creatinine clearance of 5 to 20 ml/minute, give 250 mg q 6 hours. For those with creatinine clearance below 5 ml/minute, give 250 mg q 12 hours.
  For patients receiving long-term intermittent dialysis, give 250 mg initially; repeat in 12 hours and after 36 to 48 hours. Children may need dose modifications proportional to weight and severity of infection.

Pharmacodynamics
Antibacterial action: Primarily bactericidal; it also may be bacteriostatic. Activity depends on the organism, tissue penetration, dosage, and rate of organism multiplication. It acts by adhering to bacterial penicillin-binding proteins, inhibiting cell wall synthesis.
  Like other first-generation cephalosporins, cephradine is active against many gram-positive organisms and some gram-negative organisms. Susceptible organisms include Escherichia coli and other coliform bacteria, group A beta-hemolytic streptococci, Haemophilus influenzae, Klebsiella, Proteus mirabilis,Staphylococcus aureus, Streptococcus pneumoniae, staphylococci, and Streptococcus viridans.

Pharmacokinetics
Absorption: Well absorbed from the GI tract.
Distribution: Distributed widely into most body tissues and fluids, including the gallbladder, liver, kidneys, bone, sputum, bile, and pleural and synovial fluids; CSF penetration is poor. Cephradine crosses the placental barrier and is 6% to 20% protein-bound.
Metabolism: Not metabolized.
Excretion: Excreted primarily in urine by renal tubular and glomerular filtration; small amounts of drug appear in breast milk. Elimination half-life is about 1/2 to 2 hours in normal renal function; end-stage renal disease prolongs half-life to 8 to 15 hours. Hemodialysis or peritoneal dialysis removes drug.

Route Onset Peak Duration
P.O. Unknown 1 hr Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drug and other cephalosporins. Use cautiously in breast-feeding women and patients with impaired renal function or penicillin allergy.

Interactions
Drug-drug. Bacteriostatic drugs (chloramphenicol, erythromycin, tetracyclines): May interfere with bactericidal activity. Avoid use together.
Loop diuretics, nephrotoxic drugs (aminoglycosides, colistin, polymyxin B, or vancomycin): May increase risk of nephrotoxicity. Monitor patient closely.
Probenecid: Competitively inhibits renal tubular secretion of cephalosporins, resulting in higher, prolonged serum levels of these drugs. Sometimes used for this effect.

Adverse reactions
CNS: dizziness, headache, malaise, paresthesia.
GI: pseudomembranous colitis,nausea, anorexia, vomiting, heartburn, abdominal cramps, diarrhea, oral candidiasis.
GU: genital pruritus and candidiasis, vaginitis.
Hematologic: transient neutropenia, eosinophilia, thrombocytopenia.
Skin: maculopapular and erythematous rash, urticaria.
Other: hypersensitivity reactions (serum sickness, anaphylaxis).

Effects on lab test results
• May increase ALT, AST, alkaline phosphatase, bilirubin, and LDH levels.
• May increase eosinophil count. May decrease neutrophil and platelet counts.

Overdose and treatment
Overdose may cause neuromuscular hypersensitivity; seizures may follow high CNS levels.
 Remove cephradine by hemodialysis.

Special considerations
 ALERT Names of some cephalosporins are similar. Use caution when prescribing.
• Reconstituted oral suspension may be stored for 7 days at room temperature or for 14 days in the refrigerator.
• Because drug is dialyzable, patients undergoing treatment with hemodialysis may require dosage adjustments.
• Drug causes false-positive results in urine glucose tests using cupric sulfate (Benedict’s reagent or Clinitest); use glucose oxidase tests (Chemstrip uG, Diastix, or glucose enzymatic test strip) instead. Cephradine also causes false elevations in serum or urine creatinine levels in tests using Jaffe reaction. Cephradine may cause positive Coombs’ test results.
• With large doses or prolonged therapy, watch for superinfection, especially in high-risk patients.
• If patient has renal impairment, monitor renal function before and during therapy.
Breast-feeding patients
• Drug appears in breast milk; use cautiously in breast-feeding women. Safety hasn’t been established.
Pediatric patients
• Serum half-life is prolonged in neonates and infants younger than age 12 months. Safety hasn’t been established.
Geriatric patients
• Reduced dosage may be required in patients with reduced renal function. Use cautiously.

Patient education
• Inform patient of potential adverse reactions.
• Advise patient to take drug with food to lessen GI upset.
• Caution patient to take all medication as prescribed, even if he feels better.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use