Excessive blood levels of Depocillin can be corrected by haemodialysis.
Excessive blood levels of Depocillin sodium can be corrected by haemodialysis.
Depocillin and solutions that contain metal ions should be administered separately.
Depocillin 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.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products
Depocillin sodium and solutions that contain metal ions should be administered separately.
Depocillin 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.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products
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 Depocillin (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%-.01%)
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 Depocillin at doses of more than 12 g per day.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
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 Depocillin sodium (eg. Subacute bacterial endocarditis).
Immune System Disorders
Very Common (>10%)
Patients undergoing treatment for syphilis or neurosyphilis with Depocillin 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%-.01%)
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 Depocillin sodium at doses of more than 12 g per day.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.
Pharmacotherapeutic group: Beta-lactamase sensitive penicillins.
ATC code: J01 CE01.
General Properties:
Depocillin 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 Depocillin are as follows:
| Organism | S ≤ (mg/L) | I (mg/L) | R > (mg/L) |
| Streptococcus pneumoniae Neisseria gonorrhoeae | 0.06 | 0.12-1.0 | 2.0 |
| Neisseria meningitides | 0.06 | 0.12 | |
| Haemolytic streptococci Staphylococci Moraxella catarrhalis Haemophilus influenzae | 0.12 | 0.25 | |
| Rapidly growing anaerobes | 1.0 | 2.0 |
S = Susceptible, I = Intermediate susceptibility, R = Resistant
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 Depocillin or not.
| Susceptible and intermediately susceptible microorganisms | ||
| Type of Microorganism | Microorganism | Range of acquired resistance |
| Aerobic Gram-positive microorganisms | - Bacillus anthracis | 0%** |
| - Corynebacterium diphtheriae | 0%* | |
| - Haemolytic streptococci (including Streptococcus pyogenes) | 0%*-3%** | |
| - Listeria monocytogenes | 0%** | |
| - Streptococcus pneumoniae | 4%*-40%** | |
| - Streptococcus viridans | 3-32%* | |
| Aerobic Gram-negative microorganisms | - Neisseria gonorrhoeae | 9-10%* |
| - Neisseria meningitidis | 18%* | |
| - Pasteurella multocida | 0%*** | |
| Anaerobic microorganisms | - Actinomyces israelii | 8%** |
| - Fusobacterium nucleatum and Fusobacterium necrophorum | Usually sensitive | |
| - Gram-positive sporing bacilli (including Clostridium tetani and Clostridium perfringens (welchii)) | 14%** | |
| - Gram-positive cocci (including peptostreptococcus) | 7%* | |
| Other microorganisms | - Borrelia bugdorferi | Usually sensitive |
| - Capnocytophaga canimorosus | Usually sensitive | |
| - Leptospirae | Usually sensitive | |
| - Streptobacillus moniliformis and spirrillum minus | Usually sensitive | |
| - Treponema pallidum | 0%*** | |
* UK data; ** European data, ***Global data
| Insusceptible microorganisms | ||
| Type of Microorganism | Microorganism | Range of acquired resistance |
| Aerobic Gram-positive microorganisms | - Coagulase negative Staphylococcus | 71-81%* |
| - Enterococcus Spp | Resistant | |
| - Staphylococcus aureus | 79-87%* | |
| Aerobic Gram-negative microorganisms | - Acinetobacter | Resistant |
| - Bordetella pertussis | Generally resistant | |
| - Brucella spp. | Resistant | |
| - Enterobacteriaceae (including Escherichia coli, Salmonella, Shigella, Enterobacter, Klebsiella, Proteus, Citrobacter). | Generally resistant | |
| - Haemophilus influenzae | Resistant | |
| - Pseudomonas | Resistant | |
| Anaerobic microorganisms | - Bacteroides fragilis | 100%*** |
* UK data; ** European data, *** Global data
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.
Pharmacotherapeutic group: Beta-lactamase sensitive penicillins.
ATC code: J01 CE01.
General Properties:
Depocillin 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 Depocillin sodium are as follows:
| Organism | S ≤ (mg/L) | I (mg/L) | R > (mg/L) |
| Streptococcus pneumoniae Neisseria gonorrhoeae | 0.06 | 0.12-1.0 | 2.0 |
| Neisseria meningitides | 0.06 | 0.12 | |
| Haemolytic streptococci Staphylococci Moraxella catarrhalis Haemophilus influenzae | 0.12 | 0.25 | |
| Rapidly growing anaerobes | 1.0 | 2.0 |
S = Susceptible, I = Intermediate susceptibility, R = Resistant
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 Depocillin sodium or not.
| Susceptible and intermediately susceptible microorganisms | ||
| Type of Microorganism | Microorganism | Range of acquired resistance |
| Aerobic Gram-positive microorganisms | - Bacillus anthracis | 0%** |
| - Corynebacterium diphtheriae | 0%* | |
| - Haemolytic streptococci (including Streptococcus pyogenes) | 0%*-3%** | |
| - Listeria monocytogenes | 0%** | |
| - Streptococcus pneumoniae | 4%*-40%** | |
| - Streptococcus viridans | 3-32%* | |
| Aerobic Gram-negative microorganisms | - Neisseria gonorrhoeae | 9-10%* |
| - Neisseria meningitidis | 18%* | |
| - Pasteurella multocida | 0%*** | |
| Anaerobic microorganisms | - Actinomyces israelii | 8%** |
| - Fusobacterium nucleatum and Fusobacterium necrophorum | Usually sensitive | |
| - Gram-positive sporing bacilli (including Clostridium tetani and Clostridium perfringens (welchii)) | 14%** | |
| - Gram-positive cocci (including peptostreptococcus) | 7%* | |
| Other microorganisms | - Borrelia bugdorferi | Usually sensitive |
| - Capnocytophaga canimorosus | Usually sensitive | |
| - Leptospirae | Usually sensitive | |
| - Streptobacillus moniliformis and spirrillum minus | Usually sensitive | |
| - Treponema pallidum | 0%*** | |
* UK data; ** European data, ***Global data
| Insusceptible microorganisms | ||
| Type of Microorganism | Microorganism | Range of acquired resistance |
| Aerobic Gram-positive microorganisms | - Coagulase negative Staphylococcus | 71-81%* |
| - Enterococcus Spp | Resistant | |
| - Staphylococcus aureus | 79-87%* | |
| Aerobic Gram-negative microorganisms | - Acinetobacter | Resistant |
| - Bordetella pertussis | Generally resistant | |
| - Brucella spp. | Resistant | |
| - Enterobacteriaceae (including Escherichia coli, Salmonella, Shigella, Enterobacter, Klebsiella, Proteus, Citrobacter). | Generally resistant | |
| - Haemophilus influenzae | Resistant | |
| - Pseudomonas | Resistant | |
| Anaerobic microorganisms | - Bacteroides fragilis | 100%*** |
* UK data; ** European data, *** Global data
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.
Depocillin 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 Depocillin accounts for only a minor fraction of the dose.
Depocillin 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 Depocillin sodium accounts for only a minor fraction of the dose.
None
After contact with skin, wash immediately with water. In case of contact with eyes, rinse immediately with plenty of water and seek medical advice if discomfort persists.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
