Cefradine

Description : Cefradine is a semi-synthetic and first generation cephalosporin that can be given both by mouth and by injection. It is a broad-spectrum bactericidal antibiotic active against both gram-positive and gram-negative bacteria. It is also highly active against most strains of penicillinase pro ducting staphylococci. It has a high degree of stability to many beta-lactamases.

Mode of action : Cefradine works by inhibiting bacterial cell wall synthesis. The final stage of peptidoglycan  synthesis in the bacterial cell wall is a cross-linking reaction carried out by transpeptidase enzyme.Cefradine inhibits this transpeptidase enzyme. As aresult the cell wall of the bacterium is weekend, which then swells and ruptures.

Pharmacokinetics : The oral drug is well absorbed from the small intestine by cancer mediated active transport system. Plasma concentrations of 18-25 mg/l are achived after an oral dose of 500 mg and 24-35 mg/l after 1 gm, the peak plasma concentration being achieved around one hour after administration of the drug of the capsule. Serum concentrations after five minutes of intravenous administration were approximately 90 mg/l after 1 gm and 40 mg/l after 500 mg. The plasma half-life is 0.7 to 0.8 hour after oral administration and 0.3 hour after intravenous administration. Cefradine is not metabolized and has a large volume of distribution. Cefradine is excreted unchanged in urine.

Composition : Cefradine 250 mg capsules- Each capsule contains Cefradine USP 250 mg. Cefradine 500 mg capsules-Each capsule contains Cefradine USP 250 mg. Cefradine powder for paediatric drops- After reconstitution each 5 ml contains Cefradine BP 250 mg. Cefradine 250 mg injection- Each vial contains  Cefradine USP 250 mg. Cefradine 500 mg injection- Each vial contains Cefradine USP 500 mg and Cefradine 1 mg injection- Each vial contains Cefradine USP 1 mg.

Indication : Upper respiratory tract infections: Pharyngitis, tonsillitis, sinusitis, otitis media, laryngo-tracheo bronchitis. Lower respiratory tract infections: Acute and chronic bronchitis, lobar pneumonia, broncho pneumonia. Urinary tract infections: Cystitis, urethritis, pyelonephritis, Skin and soft tissue infections: Abscess, cellulitis, furunculosis, impetigo. Prophylaxis for surgical procedures associated with high risk of disastrous consequences of infection. Other serious infections caused by sensitive organisms in both adults and children.

Dosage and administration Cefradine: Cefradine may be given without regard to meals. 

Oral: Adults: For urinary tract infections the usual dose is 500 mg four times daily or 1 gm twice daily; severe or chronic infections may require larger doses. Prolonged intensive therapy is needed for complications such as prostatitis and epididymtitis. For respiratory tract infections and skin and soft tissue infections, the usual dose is 250 mg or 500 mg four times daily or 1 gm twice daily depending on the severity and site of infections.

Children : The usual dose is 25 to 50 mg/kg/day in two to four equally divided doses. For otitis media, the dose is 75 to 100 mg/kg/day in divided doses every 6 to 12 hours. Maximum dose is 4 gm per day. Deep IM/IV injection over 3-5 minutes or by IV infusion. Adults: 0.5 to 1 gm 6 hourly; increased to 8 gm daily in severe infections. Children: 50 to 100 mg/kg daily in 4 divided doses. For surgical prophylaxis, by deep IM/IV injection over 3 to 5 minutes, 1-2 gm immediately prior to surgery. Renal impairment dosage: Patients not on dialysis : The following dosage schedule is suggested as a guideline based on a dosage of 500 mg per 6 hours and on creatinine clearance. Further modification in the dosage schedule may be required because of the dosage selected and individual variation.

Creatinine clearance (ml/min)	Dose	Time interval
>20	500 mg	6 hrs
5-20	250 mg	6 hrs
<5	250 mg	50-70 hrs

    

Patients on chronic, intermittent haemodialysis:

250 mg at the start of haemodialysis; 250 mg 6-12 hours after start; 250 mg 36-48 hours after start; 250 mg at start of next haemodialysis if >30 hours after previous dose.

Direction for use: Cefradine DS powder for suspension: For the suspension, shake the bottle well before adding water. Then add 60 ml or 12 tea-spoonful of boiled and cooled water to the bottle. Continue shaking the bottle gently until the powder is mixed properly. Shake the bottle well before each use. Cefradine powder for suspension: For the suspension, shake the bottle well before adding water. Then add 75 ml or 15 tea-spoonful of boiled and cooled water to the bottle. Continue shaking the bottle gently until the powder is mixed properly. Shake the bottle well before each use. Cefradine powder for paediatric drops: Before adding water, shake the bottle well. Then add 10 ml or 2 tea-spoonful of boiled and cooled water to the bottle. Continue shaking the bottle gently until the powder is mixed properly. Shake the bottle well before each use. Cefradine 250 mg and 500 mg injection: Intramuscular. Add 2 ml of water for injection to 250 mg or 500 mg vial and shake. Intravenous: Add 5 ml of water for injection to 250 mg or 500 mg vial and shake. The solution should be slowly injected directly into the vein over a 3 to 5 minutes period. Cefradine 1 gm injection: Intramuscular: Add 4 ml of water for injection to 1 gm vial and shake. Intravenous: Add 10 ml of water for injection to 1gm and shake. The solution should be slowly injected directly into the vein over a 3 to 5 minutes period.

Contraindications: Patients with known hypersensitivity to cephalosporins and with caution to those known to be hypersensitive to penicillin, because cross-alergy can occur. Cefradine should not be administered intrathecally.

Side effects: Hypersensitivity phenomena are more likely in patients with a history of allergy, asthma, hay lever or urticaria. Most side effects have been encountered in about 7% of patients with oral cephalosporins, principally nausea and diarhoea, skin rashes and vaginitis.

Use to pregnancy and lactation: No teratogenicity has been demonstrated . Cefradine should be used during pregnancy when clearly needed. Cefradine is excreted in breast milk and should be used with caution in lactating mothers.

Precautions: In penicillin-sensitive patients. Cefradine should be used with great caution. Administer Cefradine with caution in the presence of markedly impaired renal tunction.

Drug Interactions : The cephalosporins are potentially nephrotoxic and may enhance the nephrotoxicity of aminoglycoside antibiotics, such as gentamicin and tobramycin. The nephrotoxicity of Cefradine is increased by furosemide and one should be cautious about the use of any cephalosporin with furosemide and ethacrynic and combinations with aminoglycosides may exert more potent bactericidal action against some organisms then used alone.

Overdosage: There are no well documented cases of overdose but severe nausea and diarhoea would be expected. Convulsions may occur in patients receiving large doses of some cephalosporins especially in patients with renal failure.

Storage : Store in a cool and dry place, protected from light.