Symptoms:
There is currently limited experience with overdosage of Paldar Cream.
Management:
There is no specific treatment for an overdose of Paldar Cream. In the event of overdose, the patient should be treated supportively with appropriate monitoring as necessary. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
Symptoms and signs
There is currently limited experience with overdosage of mupirocin.
Treatment
There is no specific treatment for an overdose of mupirocin. In the event of overdose, the patient should be treated supportively with appropriate monitoring as necessary. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.
Hypersensitivity to mupirocin or any of the excipients.
None known
None known.
Data from clinical trials was used to determine the frequency of very common to rare undesirable effects. Very rare adverse reactions were primarily determined from post-marketing experience data and therefore refer to reporting rate rather than true frequency.
The following convention has been used for the classification of frequency:-
very common >1/10, common >1/100 and <1/10 , uncommon >1/1000 and <1/100, rare >1/10,000 and <1/1000 , very rare <1/10,000.
Immune system disorders: | |
Very rare: | Systemic allergic reactions including anaphylaxis, generalised rash, urticaria and angioedema |
Skin and subcutaneous tissue disorders: | |
Common: | Application site hypersensitivity reactions including urticaria, pruritus, erythema, burning sensation, contact dermatitis, rash |
Skin dryness and erythema have been reported in irritancy studies in volunteers.
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
Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000), including isolated reports.
Uncommon adverse reactions were determined from pooled safety data from a clinical trial population of 422 treated patients encompassing 12 clinical studies. Very rare adverse reactions were primarily determined from post-marketing experience data and therefore refer to reporting rate rather than true frequency.
| Immune system disorders | |
| Very rare: | Cutaneous hypersensitivity reactions. Systemic allergic reactions including anaphylaxis, generalised rash, urticaria and angioedema. |
| Respiratory, thoracic and mediastinal disorders | |
| Uncommon: | Nasal mucosa reactions. |
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
Pre-clinical effects were seen only at exposures which are extremely unlikely to cause concern for humans under normal conditions of clinical use. Mutagenicity studies revealed no risks to man.
Paldar Cream is indicated for the topical treatment of secondarily infected traumatic lesions such as small lacerations, sutured wounds or abrasions (up to 10 cm in length or 100 cm2 in area), due to susceptible strains of Staphylococcus aureus and Streptococcus pyogenes.
The elimination of nasal carriage of staphylococci, including methicillin resistant Staphylococcus aureus (MRSA).
Pharmacotherapeutic group: Dermatologicals ATC code: D06AX09, Antibiotics and chemotherapeutics for dermatological use
Mode of Action
Mupirocin is a novel antibiotic produced through fermentation by Pseudomonas fluorescens. Mupirocin inhibits isoleucyl transfer-RNA synthetase, thereby arresting bacterial protein synthesis.
Mupirocin has bacteriostatic properties at minimum inhibitory concentrations and bactericidal properties at the higher concentrations reached when applied locally.
Mechanism of Resistance
Low-level resistance in staphylococci is thought to result from point mutations within the usual staphylococcal chromosomal gene (ileS) for the target isoleucyl tRNA synthetase enzyme. High-level resistance in staphylococci has been shown to be due to a distinct, plasmid encoded isoleucyl tRNA synthetase enzyme.
Intrinsic resistance in Gram negative organisms such as the Enterobacteriaceae could be due to poor penetration of the outer membrane of the Gram-negative bacterial cell wall.
Due to its particular mode of action, and its unique chemical structure, mupirocin does not show any cross-resistance with other clinically available antibiotics.
Microbiological Susceptibility
The prevalence of acquired resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infection is questionable.
| Commonly susceptible species |
| Staphylococcus aureus* |
| Streptococcus pyogenes* |
| Streptococcus spp. (β-haemolytic, other than S. pyogenes) |
| Species for which acquired resistance may be a problem |
| Staphylococcus spp., coagulase negative |
| Inherently resistant organisms |
| Corynebacterium spp. |
| Micrococcus spp. |
* Activity has been satisfactorily demonstrated in clinical studies
Pharmacotherapeutic group: Antibiotics and chemotherapeutics for dermatological use.
ATC code: D06AX09
Mode of Action
Mupirocin is a novel antibiotic produced through fermentation by Pseudomonas fluorescens. Mupirocin inhibits isoleucyl transfer-RNA synthetase, thereby arresting bacterial protein synthesis.
Mupirocin has bacteriostatic properties at minimum inhibitory concentrations and bactericidal properties at the higher concentrations reached when applied locally.
Mechanism of Resistance
Low-level resistance in staphylococci is thought to result from point mutations within the usual staphylococcal chromosomal gene (ileS) for the target isoleucyl tRNA synthetase enzyme. High-level resistance in staphylococci has been shown to be due to a distinct, plasmid encoded isoleucyl tRNA synthetase enzyme.
Intrinsic resistance in Gram negative organisms such as the Enterobacteriaceae could be due to poor penetration of the outer membrane of the Gram-negative bacterial cell wall.
Due to its particular mode of action, and its unique chemical structure, mupirocin does not show any cross-resistance with other clinically available antibiotics.
Microbiological Susceptibility
The prevalence of acquired resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infection is questionable.
| Commonly susceptible species: |
| Staphylococcus aureus* |
| Streptococcus spp. |
| Species for which acquired resistance may be a problem: |
| Methicillin-Resistant-Staphylococcus aureus (MRSA) |
| Methicillin-resistant coagulase-negative Staphylococci (MRCoNS) |
| Inherently resistant organisms: |
| Corynebacterium spp. |
| Micrococcus spp. |
*Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications.
Mupirocin susceptibility (MIC) breakpoints for Staphylococcus aureus:
Susceptible: less than or equal to 1mg/L
Resistant: greater than 256 mg/L
Absorption
Systemic absorption of mupirocin through intact human skin is low although it may occur through broken/diseased skin. However, clinical trials have shown that when given systemically, it is metabolised to the microbiologically inactive metabolite monic acid and rapidly excreted.
Excretion
Mupirocin is rapidly eliminated from the body by metabolism to its inactive metabolite monic acid which is rapidly excreted by the kidney.
Studies have shown that following topical application of mupirocin there is very little systemic absorption of drug-related material. To mimic possible enhanced systemic penetration of mupirocin by application to damaged skin or a vascular site such as the mucous membrane, intravenous studies have been performed. Mupirocin was rapidly eliminated from the plasma by metabolism to monic acid, which in turn was excreted mainly in the urine.
Should a possible sensitisation reaction or severe local irritation occur with the use of Paldar Cream, treatment should be discontinued, the product should be washed off and appropriate therapy instituted.
As with other antibacterial products, prolonged use may result in overgrowth of non-susceptible organisms.
Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. Although this is less likely to occur with topically applied mupirocin, if prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.
Paldar Cream formulation is not suitable for ophthalmic use and intranasal use.
Avoid contact with the eyes. If contaminated, the eyes should be thoroughly irrigated with water until the cream residues have been removed.
Paldar Cream contains cetyl alcohol and stearyl alcohol. These inactive ingredients may cause local skin reactions (e.g. contact dermatitis).
Should a possible sensitisation reaction or severe local irritation occur with the use of Paldar, treatment should be discontinued, the product should be wiped away and appropriate therapy instituted.
As with other antibacterial products, prolonged use may result in overgrowth of non-susceptible organisms.
Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. Although this is less likely to occur with topically applied mupirocin, if prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.
This mupirocin nasal ointment formulation is not suitable for ophthalmic use.
Avoid contact with the eyes. If contaminated, the eyes should be thoroughly irrigated with water until the ointment residues have been removed.
No adverse effects on the ability to drive or operate machinery have been identified.
Dosage
Adults/children > 1 year/elderly
3 times a day for up to 10 days, depending on the response.
Patients not showing a clinical response within 3 to 5 days should be re-evaluated.
The duration of treatment should not exceed 10 days.
Children < 1 year
Paldar Cream has not been studied in infants under 1 year old and therefore it should not be used in these patients until further data become available.
Patients with hepatic impairment: No dosage adjustment is necessary.
Patients with renal impairment: No dosage adjustment is necessary.
Method of administration
A thin layer of cream should be applied to the affected area with a piece of clean cotton wool or gauze swab.
The treated area may be covered by a dressing.
Do not mix with other preparations, as there is a risk of dilution, resulting in a reduction in the antibacterial activity and potential loss of stability of the mupirocin in the cream.
Posology
Adults (including the elderly) and children:
Paldar should be applied to the anterior nares two to three times a day as follows:
A small amount of the ointment about the size of a match head is placed on the little finger and applied to the inside of each nostril. The nostrils are closed by pressing the sides of the nose together; this will spread the ointment throughout the nares. A cotton bud may be used instead of the little finger for the application in particular to infants or patients who are very ill.
Nasal carriage should normally clear within 5-7 days of commencing treatment.
Method of administration
Topical.
Any product remaining at the end of treatment should be discarded.
Wash your hands after application.
Any product remaining at the end of treatment should be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Wash your hands after application.
