Penicillin G Sodium injection
Benzylpenicillin Sodium Ph Eur, powder for injection, 1 million IU, 5
million IU and 10 million IU
Presentation
Penicillin G Sodium Injection is a white crystalline, water soluble powder
aseptically filled into glass vials. Reconstitution yields a clear solution of
Benzylpenicillin Injection BP.
The three presentations of Penicillin G Sodium Injection are: a 5 ml vial
containing 1 million IU (equivalent to approximately 0.6 g benzylpenicillin
sodium or penicillin G sodium); a 15 ml vial containing 5 million IU
(equivalent to approximately 3 g benzylpenicillin sodium or penicillin G
sodium); a 30 ml vial containing 10 million IU (equivalent to approximately 6
g benzylpenicillin sodium or penicillin G sodium).
Uses
Actions
Pharmacotherapeutic group
J01CE - Beta-lactamase sensitive penicillins.
Antibiotic class
Penicillin G Sodium is a water-soluble benzylpenicillin.
Antibiotic nature and mode of action
In adequate concentrations penicillin is bactericidal for sensitive,
proliferating micro-organisms by inhibiting cell wall biosynthesis.
Susceptibility data
The spectrum of action of benzylpenicillin covers group A, B, C, G, H, L
and M streptococci, Streptococcus viridans, enterococci, pneumococci,
non-penicillinase-producing staphylococci, meningococci, gonococci,
corynebacteria, Bacillus anthracis, Erysipelothrix rhusiopathiae,
Listeriae, Pasteurella multocida, streptobacilli, Spirillum minus,
actinomycetes and spirochaetal species (e.g. Leptospira, Treponema,
Borrelia, etc.) as well as numerous anaerobic organisms (e.g.
peptococci, pepto-streptococci, clostridia, fusobacteria, etc.). At high
concentrations benzylpenicillin is also active against other gram-negative
organisms such as Escherichia coli, Proteus mirabilis,
salmonellae, shigellae, Enterobacter aerogenes and Alcaligenes
faecalis.
In infections caused by staphylococci, enterococci, Escherichia coli
or Enterobacter aerogenes bacteriological studies including sensitivity
tests should be ordered.
Resistance
Penicillinase production (e.g. by staphylococci and in some countries by
gonococci) causes resistance.
Clinically relevant MIC ranges
The minimum inhibitory concentration (MIC) ranges from 0.006 to 2 mcg/ml.
Less sensitive micro-organisms require higher MIC values.
Pharmacokinetics
Absorption
Peak plasma levels of 150 to 200 IU/ml are reached 15 to 30 minutes after
intramuscular injections of 10 million IU of penicillin G sodium. Following
short infusions (30 minutes) levels may peak at up to 500 IU/ml. Approximately
55% of the dose applied is bound to plasma proteins.
Distribution
Even in poorly accessible tissues, e.g. cardiac valves, bone, CSF and
empyema, etc., high dose penicillin therapy produces therapeutically active
concentrations. It appears in pleural, pericardial, peritoneal, and synovial
fluids but diffuses less readily into the eye and only to a small extent into
abscess cavities and avascular areas. Inflamed tissue is more readily
penetrated. Benzylpenicillin diffuses across the placenta into the foetal
circulation, and very small amounts appear in the milk of nursing mothers, but
very little passes into the CSF unless the meninges are inflamed.
Elimination
In adults with normal kidney function plasma half-life is approximately 30
minutes. Most of the dose applied (50 to 80%) is eliminated along renal
pathways in an unchanged form (85 to 95%). Tubular excretion is inhibited by
probenecid which is sometimes given to increase plasma-penicillin
concentrations. Biliary elimination of the active medicine accounts for only a
minor fraction (about 5% of the dose).
Prematures and neonates
As kidney and liver functions are still immature in this age group, serum
half-life as long as 3 hours (and more). Therefore, the dosage interval should
not be less than 8 to 12 hours (depending on the degree of organ maturity).
Elderly patients
Elimination may also be delayed in patients of advanced age. Dosing should,
therefore be guided by the kidney function. Penicillin G Sodium may be used
alone or in combination with other antibiotics (for details, refer to
Interactions). To extend the dosage intervals
it may also be combined with depot preparations of penicillin.
Indications
Penicillin G Sodium is indicated in the following infections caused by
penicillin - sensitive pathogens: Septicaemia, skin and wound infections,
diphtheria (in addition to antitoxin), pneumonia, empyema, erysipela,
pericarditis, bacterial endocarditis, mediastinitis, peritonitis, meningitis,
brain abscesses, arthritis, osteomyelitis, infections of the genital tract
caused by fusobacteria.
Sensitivity should be tested wherever possible.
Specific infections
Penicillin G Sodium is effective in infections such as anthrax, clostridial
infections including tetanus, listeriosis, pasteurellosis, rat bite fever,
fusospirochaetosis, actinomycosis. In addition, it has a place in the
treatment of complications secondary to gonorrhoea and syphilis (e.g.
gonorrhoeal endocarditis or arthritis, and congenital syphilis).
If uncomplicated, gonorrhoea and syphilis should preferably be treated with
long-acting penicillins.
Penicillin G sodium is also beneficial in patients with Lyme borreliosis
after the first stage of the disease (meningopolyneuritis
Garin-Bujadoux-Bannwarth, acrodermatitis chronica atrophicans, Lyme arthritis,
Lyme carditis), if oral penicillin is no longer indicated. During pregnancy
parenteral penicillin G at high doses is recommended after the first stage of
Lyme disease to prevent diaplacental infections.
Dosage and administration
Penicillin G Sodium Injection may be administered intravenously both by
injection or short infusion and intramuscularly. In general, 30,000 IU/kg body
weight daily, divided into 2 to 3 doses, are administered. In general, the
following dosage schedule should be followed:
Average benzylpenicillin doses
Adults
High dose
10 to 40 million IU daily i.v.
Normal dose
1 to 5 million IU daily i.m. or i.v.
Infants
Body weight, up to 10 kg and children up to age 12 years.
High dose
0.1 to 0.5 (to 1.0) million IU/kg daily i.v.
Normal dose
0.03 to 0.1 million IU/kg daily i.m. or i.v.
Neonates and premature infants
Body weight approximately 3.5 kg.
High dose
0.2 to 0.5 million IU/kg daily i.v.
Normal dose
0.03 to 0.1 million IU/kg daily i.m. or i.v.
Special dosage recommendations
Sepsis
Sepsis induced by Gram-negative bacilli (E. coli, E. aerogenes,
A. faecalis, salmonellae, shigellae and P. mirabilis): In the
presence of sensitive organisms adults receive 20 to 80 million units daily.
Bacterial endocarditis
Adults are given 10 to 80 million IU daily i.v. in combination with
aminoglycosides.
Meningitis
To prevent convulsions and Jarisch-Herxheimer reactions, daily doses should
not exceed 20 to 30 million IU in adults and 12 million IU in children. In
extremely severe clinical conditions the first dose should be protracted,
starting with 1 quarter of the individual single dose level, and administered
slowly under careful observation of the patient.
Death cap (Amanita phalloides) poisoning
In general, 0.5 to 1.0 million IU/kg daily.
Lyme borreliosis
20 to 30 million IU daily i.v. in 2 to 3 doses for 14 days in adults and
0.5 million IU/kg i.v. in 2 to 3 doses for 14 days in children.
According to WHO recommendations, treatment of streptococcal infections
should be continued for at least 10 days.
If necessitated by the patient's clinical condition, penicillin G sodium
may also be administered by intrapleural instillation at a dose of up to 0.2
million IU (5,000 IU/ml), by intra-articular injection at a dose of up to 0.1
million IU (25,000 IU/ml) or by intrathecal instillation. Intrathecal dosing
rapidly produces reliable bactericidal CSF concentrations. Doses should not
exceed 10,000 to 20,000 IU for adults, 8,000 IU for children between age 6 and
12 years, 5,000 IU for children between age 1 and 6 years and 2,500 IU for
infants. After withdrawing a corresponding amount of CSF, the sterile solution
(no more than 1,000 IU/ml) should be injected slowly (1 ml/min) at body
temperature. Local dosing should invariably be adjuvant to systemic treatment.
For intrathecal instillations the dosage level designed for systemic treatment
(i.v., i.m.) should be reduced accordingly.
Dosage guidelines for patients with renal insufficiency
In patients with severely reduced renal function, single doses and dosage
intervals of Penicillin G Sodium should be adjusted to the clearance levels.
| Penicillin G doses by creatinine clearances (adults) |
||||
|---|---|---|---|---|
| Creatinine clearance (ml/min) | 100 to 60 | 50 to 40 | 30 to 10 | <10 |
| Serum creatinine (mg %) | 0.8 to 1.5 | 1.5 to 2.0 | 2 to 8 | 15 |
| Daily dose of Penicillin G Sodium | adults < 60 yrs: 40 (to 60) million IU adults > 60 yrs: 10 to 40 million IU divided into 3 to 6 doses |
10 to 20 million IU divided into 3 doses | 5 to 10 million IU divided into 2 to 3 doses | 2 to 5 million IU divided into 1 to 2 doses |
In children with renal insufficiency the dose should be adjusted accordingly
relative to the patient's body weight.
Extremely severe renal and hepatic functional impairment may delay
penicillin metabolism and elimination. This should be remembered for dosing.
Administration
Preparation of solutions for i.v. injection or infusion
Reconstitute each 1 million IU (600 mg) of Penicillin G Sodium Injection in
a sufficient volume of a suitable diluent to give a final concentration of 1
million IU per 10 ml. This quantitative ratio produces an approximately
isotonic solution with the recommended osmolarity for iv injection/infusion.
To avoid electrolyte imbalances, do not use Ringer's lactate or other
solutions containing sodium ions.
Notes on i.m. injections
Administer up to, but no more than 10 million IU (= approximately 6 g) of
penicillin G sodium dissolved in 5 to 10 ml of water for injections up to
twice daily by deep intramuscular injection into the upper, outer quadrant of
the buttock or Hochstetter's ventrogluteal field.
Up to 5 ml of injectable solution/injection site will be tolerated.
Alternate injection sites for repeated injections. Higher doses may be
administered by i.v. infusion.
To prevent hypersensitivity reactions caused by degradation products,
solutions should be injected immediately after their preparation.
Contraindications
History of penicillin hypersensitivity. In patients known to be
hypersensitive to cephalosporins potential cross allergenicity should be kept
in mind (reported incidence, 5 to 10%).
Warnings and precautions
Warnings
1 million IU (= 600 mg) of penicillin G sodium contains 1.68 mmol of
sodium. 10 million IU are, therefore, equivalent to the sodium load produced
by 100 ml of isotonic saline solution.
Patients should be alerted to the potential occurrence of allergic
reactions and instructed to report them. They should be watched for 30 minutes
after medicine administration and adrenalin should be kept ready for
injection. If allergic reactions occur, the medicine should be withdrawn and
the usual treatment with adrenalin, antihistamines and corticosteroids should
be initiated.
In diabetics delayed absorption from the intramuscular depot should be kept
in mind.
If high-dose penicillin treatment is continued for more than 5 days,
electrolyte balance, blood counts and renal function should be monitored.
The potential overgrowth of resistant organisms should be considered during
long-term treatment. Patients developing secondary infections should be
treated accordingly.
As infants have been found to develop severe local reactions to
intramuscular injections, treatment should preferably be intravenous.
In patients receiving very high intravenous doses (more than 10 million IU
daily) injection sites should be alternated every 2 days to prevent
superinfections and thrombophlebitis.
Local penicillin G sodium application to the skin or mucous membranes or by
aerosol is contraindicated.
In patients treated for venereal diseases who are suspected of having
co-existent syphilis dark-field examinations should be ordered prior to
treatment and serologic tests should be obtained for at least 4 months. To
suppress or mitigate Jarisch-Herxheimer reactions (refer to
Adverse effects) prednisolone 50 mg, or an
equivalent steroid may be administered at the time of the first antibiotic
dose. In patients with cardiovascular or meningovascular syphilis
Jarisch-Herxheimer reactions can be prevented by prednisolone, 50 mg daily, or
an equivalent steroid, for 1 to 2 weeks.
Sustained severe diarrhoea should prompt suspicion of antibiotic-related
pseudomembranous colitis (blood-streaked, mucoid, watery diarrhoea; dull,
diffuse to colicky abdominal pain; fever and occasionally also tenesms). As
this condition may be life-threatening, penicillin G sodium should immediately
be withdrawn and treatment guided by bacteriological studies (e.g. with oral
vancomycin, 250 mg q.i.d) should be instituted. Antiperistaltics are
contraindicated.
Precautions
Particular caution should be exercised in patients with an allergic
diathesis or with bronchial asthma.
Caution should also be exercised in newborns, patients with severe
cardiopathies, hypovolaemia, epilepsy and renal or hepatic damage.
Pregnancy and lactation
Use in pregnancy
Assigned Category A by the Australian Drug Evaluation Committee. This
category includes medicines which have been taken by a large number of
pregnant women and women of childbearing age without any proven increase in
the frequency of malformations or other direct or indirect harmful effects on
the foetus having been observed. There is currently no evidence suggesting
that penicillins, if administered during pregnancy, have an embryotoxic,
teratogenic or mutagenic effect.
Use in lactation
Penicillins may be present in breast milk.
Effects on ability to drive and use machines
This medicine is presumed to be safe or unlikely to produce an effect.
Adverse effects
Systemic adverse effects
Hypersensitivity
Allergic reactions are uncommon. Potential allergic reactions include
urticaria, angioneurotic oedema, erythema multiforme, exfoliative dermatitis,
fever, joint pain, anaphylaxis or anaphylactoid reactions (asthma, purpura,
gastrointestinal symptoms).
Gastrointestinal
Stomatitis and glossitis are, at times, seen. In patients developing
diarrhoea during treatment pseudomembranous colitis should be excluded (refer
to Warnings and precautions).
Haematological
Eosinophilia, positivity of the direct Coombs' test, haemolytic anaemia,
leucopenia, thrombocytopenia and agranulocytosis have been reported, but are
extremely rare.
Patients undergoing treatment for syphilis may show Jarisch - Herxheimer
reactions secondary to bacteriolysis.
Other adverse effects
As infants have been found to develop severe local reactions to
intramuscular injections, treatment should preferably be intravenous.
To prevent potential electrolyte imbalances intravenous penicillin G sodium
doses of more than 10 million IU should be administered slowly. Patients
receiving high doses by infusion (more than 20 million IU in adults) may
become convulsive, particularly in the presence of severely reduced renal
function, epilepsy, meningitis or cerebral oedema or during cardiopulmonary
bypass procedures.
Nephropathy has been reported to occur sporadically after i.v. penicillin G
sodium doses of more than 10 million IU. Rarely patients with pre-existent
kidney disease may develop albuminuria, cylindruria and haematuria. Oliguria
and anuria are uncommon during high-dose penicillin treatment and usually
disappear within 48 hours after discontinuing treatment. Diuresis may be
stimulated with 10% mannitol solutions.
There have been rare reports of paraesthesia following long term
administration.
Penicillin can simulate falsely positive results on performing diagnostic
urinary sugar determinations.
Interactions
As penicillins are only active against proliferating micro-organisms,
penicillin G sodium should not be combined with bacteriostatic antibiotics.
Combinations with other antibiotics should only be considered if their effects
can be expected to be synergistic or at least additive. In general, the
combination partners should be fully dosed. (Exception: In combinations with
proven synergistic action, the dose of the more toxic combination partner may
be reduced.)
If indicated, bactericidal antibiotic candidates for combination with
penicillin G sodium include isoxazolyl penicillins like flucloxacillin and
other narrow-spectrum beta-lactam antibiotics, aminopenicillins,
aminoglycosides. These should be administered by slow i.v. injection prior to
penicillin G sodium infusions. Wherever possible, amino-glycosides should be
applied by separate intramuscular injection.
Competitive inhibition of medicine elimination should be remembered,
whenever antiinflammatories, antirheumatics, antipyretics (particularly
indomethacin, phenylbutazone and salicylates in high doses) or probenecid are
concomitantly used.
Like other antibiotics, penicillin G sodium may occasionally reduce the
efficacy of oral contraceptives.
To preclude undesirable chemical reactions, mixed-content injections or
infusions as well as solutions containing glucose should be avoided (refer
also Pharmaceutical precautions).
Overdosage
Signs and symptoms
Overdosage by the intrathecal route can cause convulsions, paralysis and
may be fatal.
Management
Excessive blood levels of penicillin G can be corrected by haemodialysis.
In the event of overdosage by the intrathecal route, CSF lavage to reduce
the toxic concentration of penicillin G may be considered.
Pharmaceutical precautions
Instructions for use/handling
If properly stored, non-reconstituted Penicillin G Sodium Injection retains
its full potency to the date of expiration shown on the pack.
Freshly prepared solutions for injection or infusion should be used
immediately, because even at refrigerator temperatures aqueous solutions of
penicillin G rapidly disintegrate to form degradation and conversion products.
Incompatibilities
Penicillin G sodium is incompatible with metal ions, particularly those of
copper, zinc, mercury and zinc compounds that may be present in rubber
stoppers of infusion bottles. Oxidising and reducing substances, alcohol,
glycerol, macrogols and other hydroxy compounds may also inactivate it. In
slightly alkaline solutions penicillin G sodium is rapidly inactivated by
cysteine and other aminothiol compounds.
Sympathomimetic amines are equally incompatible with penicillin. Penicillin
G sodium should not be administered in dextrose injections. Incompatibilities
may occur on concomitant administration of tetracycline hydrochloride and some
other antibiotics.
Shelf life
Unopened container:
60 months.
After container first opened:
Not applicable. For immediate use only.
After dilution or reconstitution:
24 hours only when reconstituted in sterile water for injections or
dextrose 5% w/v solution and stored between 2 to 8°C. For immediate use only
at temperatures outside the 2 to 8°C range.
Special precautions for storage
Store at or below 25°C.
Medicine classification
Prescription Medicine.
Package quantities
1 million IU (5 ml vials): packs of 10 and 100 vials.
5 million IU (15 ml vials): packs of single, 5 and 10 vials.
10 million IU (30 ml vials): packs of single, 5 and 10 vials.
Further information
List of excipients
Nil.
Displacement volume
Penicillin G Sodium 1 million IU (600 mg) is packaged in a 5 ml vial and
has a target filling mass of 599 mg. Reconstitution with diluent yields a
displacement volume of approximately 0.4 ml.