Excessive blood levels of Moldamin can be corrected by haemodialysis.
Excessive blood levels of Moldamin sodium can be corrected by haemodialysis.
Allergy to penicillins. Hypersensitivity to any ingredient of the preparation.
Cross allergy to other beta-lactams such as cephalosporins should be taken into account.
Moldamin and solutions that contain metal ions should be administered separately.
Moldamin 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
Moldamin sodium and solutions that contain metal ions should be administered separately.
Moldamin 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 Moldamin (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 Moldamin 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 Moldamin sodium (eg. Subacute bacterial endocarditis).
Immune System Disorders
Very Common (>10%)
Patients undergoing treatment for syphilis or neurosyphilis with Moldamin 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 Moldamin 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:
Moldamin 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 Moldamin 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 Moldamin 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:
Moldamin 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 Moldamin 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 Moldamin 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.
Moldamin 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 Moldamin accounts for only a minor fraction of the dose.
Moldamin 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 Moldamin sodium accounts for only a minor fraction of the dose.
600 mg benzylpenicillin contains 1.68 mmol of sodium. Massive doses of Moldamin 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.
600 mg Moldamin contains 1.68 mmol of sodium. Massive doses of Moldamin 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 Moldamin 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 Moldamin. In this situation, even if Clostridium difficile is only suspected, administration of Moldamin should be discontinued and appropriate treatment given.
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.
