Bepen

Benzylpenicillin sodium.

BEPEN INJECTION 1.0 MU: Each vial contains Benzylpenicillin Sodium BP 600 mg.
BEPEN INJECTION 5.0 MU: Each vial contains Benzylpenicillin Sodium BP 3 g.

Pharmacology: Pharmacodynamics: General Properties: Benzylpenicillin sodium BP is a beta-lactam antibiotic. It is bactericidal by inhibiting bacterial cell wall biosynthesis.
Breakpoints: The tentative breakpoints (British Society for Antimicrobial Chemotherapy, BSAC) for Benzylpenicillin sodium BP are as follows: (See Table 1.)

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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 BP or not. (See Tables 2 and 3.)

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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.
Pharmacokinetics: Benzylpenicillin sodium BP 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 BP accounts for only a minor fraction of the dose.

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.

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 1.2 g (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 BP 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 BP should be adjusted in accordance with the following schedule: (See Table 4.)

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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: Benzylpenicillin may be given by intramuscular or intravenous injection. The intravenous route is preferred in cases of shock as blood levels following intramuscular injection are unreliable in shocked patients.
Preparation of solution: Pharmaceutical preparation: BEPEN Injection should be reconstituted with Water for Injections BP. To achieve a particular concentration, Water for Injections BP should be added to the vial according to the table as follows. (See Table 5.)

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When BEPEN is reconstituted with Water for Injections, it must be used immediately to reduce microbiological hazard. BEPEN is for one dose in one patient only. Discard any remaining contents.
Intramuscular Injection: 600 mg vial: Dissolve 600 mg (1 mega unit) in 1.6 to 2.0 mL of Water for Injections BP.
3 g vial: Dissolve 3 g (5 mega unit) in 8.0 to 10.0 mL of Water for Injections BP as indicated in the previously mentioned Table 5 to give 300 mg/mL.
Intravenous Administration: Intravenous administration may be by intermittent injections or by injection into an infusion line. It should not be added to an intravenous infusion bottle as benzylpenicillin is unstable at room temperature and may form highly allergenic derivatives.
Reconstitute and dilute each 600 mg of BEPEN in a sufficient volume of Water for Injection to achieve a final concentration of 600 mg per 10 mL. This quantitative ratio produces an approximately isotonic solution with the recommended osmolarity for I.V. injection/infusion.
Sodium overload and/or heart failure may occur if benzylpenicillin sodium is administered in sodium-containing solvents to patients who suffer from renal failure and/or heart failure. Therefore, for such patients, benzylpenicillin sodium should not be reconstituted in sodium-containing liquids such as Sodium Chloride Injection BP or Ringer's solution due to their additional electrolytic content.

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.

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.

BEPEN 1.0 MU INJECTION contains 41.6 mg of sodium/vial.
BEPEN 5.0 MU INJECTION contains 208 mg of sodium/vial.
Massive doses of Benzylpenicillin Sodium BP can cause hypokalaemia and sometimes hypernatremia. 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 sensitization may occur in persons handling the antibiotic and care should be taken to avoid contact with the substance.
It should be recognized 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.
Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients receiving therapy with beta-lactams. Before initiating therapy with BEPEN, careful inquiry should be made concerning previous hypersensitivity reactions to penicillin, cephalosporins, carbapenems or other beta-lactam agents. If an allergic reaction occurs, BEPEN must be discontinued immediately and appropriate alternative therapy instituted.
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.

Benzylpenicillin sodium BP 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 BP 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.

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 BP (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 BP at doses of more than 12 g per day.

The efficacy of oral contraceptives may be impaired under concomitant administration of Benzylpenicillin sodium BP, 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 BP.
Probenecid inhibits tubular secretion of Benzylpenicillin sodium BP 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.

Incompatibility: Benzylpenicillin sodium BP 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.

Store below 30°C.
Shelf Life: Unopened vials: 36 months from the date of manufacture if kept as recommended.
Reconstituted solution: Freshly prepared solutions should be used immediately.

Penicillins

J01CE01 - benzylpenicillin ; Belongs to the class of beta-lactamase sensitive penicillins. Used in the systemic treatment of infections.

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