Bepen

Bepen

benzylpenicillin

Manufacturer:

KAPL

Distributor:

Averroes Pharma
Full Prescribing Info
Contents
Benzylpenicillin sodium.
Description
Bepen Injection 1 MU: Each vial contains Benzylpenicillin Sodium 600 mg.
Bepen Injection 5 MU: Each vial contains Benzylpenicillin Sodium 3 g.
Action
Pharmacology: Pharmacodynamics: General Properties: Benzylpenicillin sodium is a beta-lactam antibiotic. It is bacteriocidal by inhibiting bacterial cell wall biosynthesis.
Breakpoints: The tentative breakpoints (British Society for Antimicrobial Chemotherapy, BSAC) for Benzylpenicillin sodium are as follows: (See Table 1.)

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Pharmacokinetics: Benzylpenicillin sodium rapidly appears in the blood following intramuscular injection of water-soluble salts and maximum concentrations are usually reached in 15-30 minutes. Peak plasma concentrations of about 12 mcg/ml have been reported after doses of 600 mg with therapeutic plasma concentrations for most susceptible organisms detectable for about 5 hours. Approximately 60% of the dose injected is reversibly bound to plasma protein.
In adults with normal renal function, the plasma half-life is about 30 minutes. Most of the dose (60-90%) undergoes renal elimination, 10% by glomerular filtration and 90% by tubular secretion. Tubular secretion is inhibited by probenecid, which is sometimes given to increase plasma penicillin concentrations. Biliary elimination of Benzylpenicillin sodium accounts for only a minor fraction of the dose.
Microbiology: Susceptibility: The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. The following table gives only approximate guidance on probabilities whether microorganisms will be susceptible to Benzylpenicillin sodium or not. (See Tables 2 and 3.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Other Information: Known Resistance Mechanisms and Cross-resistance: Penicillin resistance can be mediated by alteration of penicillin binding proteins or development of beta-lactamases.
Resistance to penicillin may be associated with cross-resistance to a variety of other beta lactam antibiotics either due to a shared target site that is altered, or due to a beta-lactamase with a broad range of substrate molecules. In addition to this, cross resistance to unrelated antibiotics can develop due to more than one resistance gene being present on a mobile section of DNA (e.g. plasmid, transposon etc) resulting in two or more resistance mechanisms being transferred to a new organism at the same time.
Indications/Uses
Benzylpenicillin is indicated for most wound infections, pyogenic infections of the skin, soft tissue infections and infections of the respiratory tract.
It is also indicated for the following infections caused by penicillin-sensitive microorganisms: Generalised infections and septicaemia from susceptible bacteria.
Acute and chronic osteomyelitis, sub-acute bacterial endocarditis and meningitis caused by susceptible organisms. Tetanus, actinomycosis, anthrax, rat-bite fever, listeriosis and severe Lyme disease.
Complications secondary to gonorrhoea and syphilis (e.g. gonococcal arthritis or endocarditis, congenital syphilis and neurosyphilis).
Diphtheria, brain abscesses and pasteurellosis.
Consideration should be given to official local guidance (e.g. national recommendations) on the appropriate use of antibacterial agents.
Susceptibility of the causative organism to the treatment should be tested (if possible), although therapy may be initiated before the results are available.
Dosage/Direction for Use
Preparation of solution: Reconstituted solutions of Benzylpenicillin sodium are intended for immediate administration.
600mg vial: Dissolve the contents in 2ml or more of Sterilised Water for Injections immediately before use.
3g vial: Dissolve the contents in 10ml or more of Sterilised Water for Injections immediately before use.
Adults: 600 to 3,600 mg (1 to 6 mega units) daily, divided into 4 to 6 doses, depending on the indication. Higher doses [up to 14.4 g/day (24 mega units) in divided doses] may be given in serious infections such as adult meningitis by the intravenous route.
In bacterial endocarditis, 7.2 to 12 g (12 to 20 mega units) or more may be given daily in divided doses by the intravenous route, often by infusion.
High doses should be administered by intravenous injection or infusion, with intravenous doses in excess of 1.2g (2 mega units) being given slowly, taking at least one minute for each 300 mg (0.5 mega unit) to avoid high levels causing irritation of the central nervous system and/or electrolyte imbalance.
High dosage of Benzylpenicillin sodium may result in hypernatraemia and hypokalaemia unless the sodium content is taken into account.
Children aged 1 month to 12 years: 100 mg/kg/day in 4 divided doses; not exceeding 4 g/day.
Infants 1-4 weeks: 75 mg/kg/day in 3 divided doses.
Newborn Infants: 50 mg/kg/day in 2 divided doses.
Meningococcal disease: Children 1 month to 12 years: 180-300 mg/kg/day in 4-6 divided doses, not exceeding 12 g/day.
Infants 1-4 weeks: 150 mg/kg/day in 3 divided doses.
Newborn infants: 100 mg/kg/day in 2 divided doses.
Adults and children over 12 years: 2.4 g every 4 hours.
Premature babies and neonates: Dosing should not be more frequent than every 8 or 12 hours in this age group, since renal clearance is reduced at this age and the mean half-life of Benzylpenicillin may be as long as 3 hours.
Since infants have been found to develop severe local reactions to intramuscular injections, intravenous treatment should preferably be used.
Patients with renal insufficiency: For doses of 0.6-1.2 g (1-2 mega units), the dosing interval should be no more frequent than every 8-10 hours.
For high doses e.g. 14.4 g (24 mega units) required for the treatment of serious infections such as meningitis, the dosage and dose interval of Benzylpenicillin sodium should be adjusted in accordance with the following schedule: (See Table 4.)
Click on icon to see table/diagram/image

The dose in the previous table should be further reduced to 300 mg (0.5 mega units) 8 hourly if advanced liver disease is associated with severe renal failure.
If haemodialysis is required, an additional dose of 300 mg (0.5 mega units) should be given 6 hourly during the procedure.
Elderly patients: Elimination may be delayed in elderly patients and dose reduction may be necessary.
Route of administration: The following dosages apply to both intramuscular and intravenous injection.
Alternate sites should be used for repeated injections.
Overdosage
Symptoms of overdosage includes convulsion and neurological adverse reactions. In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures as required. In patients with renal function impairment, ampicillin-class antibiotics can be removed by haemodialysis but not by peritoneal dialysis.
Contraindications
Benzylpenicillin is contraindicated in individuals with a history of allergy to penicillins.
Hypersensitivity to any ingredient of the preparation.
Cross allergy to other beta-lactams such as cephalosporins should be taken into account.
Special Precautions
600 mg Benzylpenicillin contains 1.68 mmol of sodium. Massive doses of Benzylpenicillin Sodium can cause hypokalaemia and sometimes hypernatraemia. Use of a potassium-sparing diuretic may be helpful. In patients undergoing high-dose treatment for more than 5 days, electrolyte balance, blood counts and renal functions should be monitored.
In the presence of impaired renal function, large doses of penicillin can cause cerebral irritation, convulsions and coma.
Skin sensitisation may occur in persons handling the antibiotic and care should be taken to avoid contact with the substance.
It should be recognised that any patient with a history of allergy, especially to drugs, is more likely to develop a hypersensitivity reaction to penicillin. Patients should be observed for 30 minutes after administration and if an allergic reaction occurs, the drug should be withdrawn and appropriate treatment given.
Delayed absorption from the intramuscular depot may occur in diabetics.
Prolonged use of Benzylpenicillin may occasionally result in an overgrowth of non-susceptible organisms or yeast and patients should be observed carefully for superinfections.
Pseudomembranous colitis should be considered in patients who develop severe and persistent diarrhoea during or after receiving Benzylpenicillin. In this situation, even if Clostridium difficile is only suspected, administration of Benzylpenicillin should be discontinued and appropriate treatment given.
Use In Pregnancy & Lactation
Benzylpenicillin sodium has been taken by a large number of pregnant women and women of childbearing age without an increase in malformations or other direct or indirect harmful effects on the foetus having been observed.
Although it is not known if Benzylpenicillin sodium may be excreted into the breast milk of nursing mothers, it is actively transported from the blood to milk in animals and trace amounts of other penicillins in human milk have been detected.
Side Effects
Blood and Lymphatic System Disorders: Rare (0.01% - 0.1%): Haemolytic anaemia and granulocytopenia (neutropenia), agranulocytosis, leucopenia and thrombocytopenia, have been reported in patients receiving prolonged high doses of benzylpenicillin sodium (eg. Subacute bacterial endocarditis).
Immune System Disorders: Very Common (>10%): Patients undergoing treatment for syphilis or neurosyphilis with Benzylpenicillin may develop a Jarisch-Herxheimer reaction. Common (1-10%): Hypersensitivity to penicillin in the form of rashes (all types), fever, and serum sickness may occur (1-10% treated patients). These may be treated with antihistamine drugs. Rare (0.01%-0.1%): More rarely, anaphylactic reactions have been reported (<0.05% treated patients).
Nervous System Disorders: Rare (0.01%-0.1%): Central nervous system toxicity, including convulsions, has been reported with massive doses over 60 g per day and in patients with severe renal impairment.
Renal and Urinary Disorders: Rare (0.01%-0.1%): Interstitial nephritis has been reported after intravenous Benzylpenicillin sodium at doses of more than 12 g per day.
Drug Interactions
The efficacy of oral contraceptives may be impaired under concomitant administration of Benzylpenicillin sodium, which may result in unwanted pregnancy. Women taking oral contraceptives should be aware of this and should be informed about alternative methods of contraception.
There is reduced excretion of methotrexate (and therefore increased risk of methotrexate toxicity) when used with Benzylpenicillin sodium.
Probenecid inhibits tubular secretion of Benzylpenicillin sodium and so may be given to increase the plasma concentrations.
Penicillins may interfere with: Urinary glucose tests; Coomb's tests; Tests for urinary or serum proteins; Tests which use bacteria e.g. Guthrie test.
Caution For Usage
Incompatibilities: Benzylpenicillin sodium and solutions that contain metal ions should be administered separately.
Benzylpenicillin sodium should not be administered in the same syringe / giving set as amphotericin B, cimetidine, cytarabine, flucloxacillin, hydroxyzine, methylprednisolone, or promethazine since it is incompatible with these drugs.
Storage
Store below 30°C.
This product is stable for 2 days when stored at temperature 30°C ± 2°C, Relative Humidity 70 ± 5% and 6 days when stored at refrigeration temperature (2°C to 8°C) after reconstitution.
Shelf-Life: The injection can be used within 36 months from the date of manufactured if kept as recommended.
This product is stable for 2 days when stored at temperature 30°C ± 2°C, Relative Humidity 70 ± 5% and 6 days when stored at refrigeration temperature (2°C to 8°C) after reconstitution.
MIMS Class
ATC Classification
J01CE01 - benzylpenicillin ; Belongs to the class of beta-lactamase sensitive penicillins. Used in the systemic treatment of infections.
Presentation/Packing
Powd for inj (white crystalline powder in vial, pale yellow solution after reconstitution) 600 mg x 10's, 50's. 3 g x 10's, 50's.
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