CO-FLUAMPICIL ORAL SUSPENSION 125 MG / 125 MG IN 5 ML - summary of medicine characteristics

Co-Fluampicil 125/125 mg/5 ml Oral Suspension

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 5 ml reconstituted suspension contains Flucloxacillin Sodium equivalent to 125 mg Flucloxacillin and Ampicillin Trihydrate equivalent to 125 mg Ampicillin

Excipients with known effect

Sucrose 3.03 mg per 5 ml of Oral Suspension.

Sodium Content: 12.3 mg Sodium per 5 ml of Oral Suspension.

For the full list of excipients, see section 6.1.

Powder for Oral Suspension.

A free flowing powder in two layers the top layer being white, the bottom layer being off-white. Orange coloured suspension.

4.1 Therapeutic indications

Treatment of severe infections where the causative organism is unknown, and for mixed infections involving “Resistant” staphylococci.

In general practice the elixir can be used for chest infections, ENT infections, soft tissue infections and patients with an underlying pathology which makes them more susceptible to infections.

In hospital use, if laboratory tests are not yet available, it can be used for severe respiratory infections, post-operative chest and wound infections, septic abortion and puerperal fever. Septicaemia. Prophylaxis in major surgery and infections in patients receiving immunosuppressive therapy;

The products spectrum makes it suitable for the treatment of many mixed infections, particularly those where penicillinase-producing staphylococci are suspected or confirmed.

4.2 Posology and method of administration

Posology

Adults (including elderly patients)

10 ml four times a day;

Paediatric population

5 ml four times a day;

The above dosages may be doubled where necessary and should be administered half an hour to one hour before meals.

Method of administration

Oral

4.3 Contraindications

Ocular administration.

Co-fluampicil contains ampicillin and flucloxacillin which are penicillins, and should not be given to patients with a history of hypersensitivity to P-lactam antibiotics (e.g. penicillins, cephalosporins) or to any of the excipients listed in section 6.1.

Co-fluampicil is contraindicated in patients with a history of flucloxacillin-associated jaundice/hepatic dysfunction.

4.4 Special warnings and precautions for use

Caution is advised when flucloxacillin is administered concomitantly with paracetamol due to the increased risk of high anion gap metabolic acidosis (HAGMA). Patients at high risk for HAGMA are in particular those with severe renal impairment, sepsis or malnutrition especially if the maximum daily doses of paracetamol are used.

After co-administration of flucloxacillin and paracetamol, a close monitoring is recommended in order to detect the appearance of acid-base disorders, namely HAGMA, including the search of urinary 5-oxoproline.

If flucloxacillin is continued after cessation of paracetamol, it is advisable to ensure that there are no signals of HAGMA, as there is a possibility of flucloxacillin maintaining the clinical picture of HAGMA (see section 4.5).

Before initiating therapy with co-fluampicil careful enquiries should be made concerning previous hypersensitivity reactions to P—lactam antibiotics.

Serious and occasionally fatal hypersensitivity reactions (anaphylaxis) have been reported in patients receiving ß-lactam antibiotics. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral therapy.

These reactions are more likely to occur in individuals with a history of hypersensitivity to [Mactam antibiotics.

Co-fluampicil contains ampicillin and should be avoided if infectious mononucleosis and/or acute or chronic leukaemia of lymphoid origin are suspected. The occurrence of a skin rash has been associated with these conditions following the administration of ampicillin.

Co-fluampicil should be used with caution in patients with evidence of hepatic dysfunction (see section 4.8).

Special caution is essential in the newborn because of the risk of hyperbilirubinemia. Studies have shown that, at high dose following parenteral administration, flucloxacillin can displace bilirubin from plasma protein binding sites, and may therefore predispose to kernicterus in a jaundiced baby. In addition, special caution is essential in the newborn because of the potential for high serum levels of Flucloxacillin due to a reduced rate of renal excretion.

During prolonged treatments (e.g osteomyelitis, endocarditis), regular monitoring of hepatic and renal functions is recommended.

Prolonged use may occasionally result in the selection of resistant strains of organisms.

The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthematous pustulosis (AGEP) (see section 4.8). In case of AGEP diagnosis, flucloxacillin should be discontinued and any subsequent administration of flucloxacillin contra-indicated.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase insufficiency should not take this medicine.

Sodium Content: Co-Fluampicil Suspension contains 12.3mg Sodium per 5ml of Oral Suspension. This should be included in the daily allowance of patients on sodium restricted diets.

4.5 Interaction with other medicinal products and other forms of interaction

Caution should be taken when flucloxacillin is used concomitantly with paracetamol as concurrent intake has been associated with high anion gap metabolic acidosis, especially in patients with risk factors. (see section 4.4.)

Bacteriostatic drugs may interfere with the bactericidal action of ampicillin and flucloxacillin.

In common with other oral broad-spectrum antibiotics, co-fluampicil may reduce the efficacy of oral contraceptives and patients should be warned accordingly.

Probenecid decreases the renal tubular secretion of co-fluampicil. Concurrent use with co-fluampicil may result in increased and prolonged blood levels of both ampicillin and flucloxacillin.

Concurrent administration of all allopurinol during treatment with ampicillin can increase the likelihood of allergic skin reactions.

Co-fluampicil contains ampicillin. It is recommended that when testing for the presence of glucose in urine during ampicillin treatment, enzymatic glucose oxidase methods should be used because false positive readings are common with chemical methods due to the high urinary concentrations of ampicillin.

4.6 Fertility, pregnancy and lactation

Pregnancy

Animal studies with co-fluampicil have shown no teratogenic effects. The product has been in clinical use since 1971 and the limited number of reported cases of use in human pregnancy have shown no evidence of untoward effects. The decision to administer any drug during pregnancy should be taken with the utmost care. Therefore co-fluampicil should only be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.

Breast-feeding

Trace quantities of penicillin, ampicillin and flucloxacillin can be detected in breast milk. The possibility of hypersensitivity reactions must be considered in breast-fed infants. Therefore co-fluampicil should only be administered to a breast-feeding mother when the potential benefit outweigh the potential risks associated with treatment.

4.7 Effects on ability to drive and use machines

No known adverse effects on the ability to drive or operate machinery have been observed.

4.8 Undesirable effects

Side effects, as with other penicillins, are uncommon and mainly of a mild and transitory nature. An urticarial rash suggests penicillin hypersensitivity; an erythematous rash may arise in patients receiving ampicillin who have glandular fever

Metabolism and nutrition disorders

Post marketing experience: very rare cases of high anion gap metabolic acidosis, when flucloxacillin is used concomitantly with paracetamol, generally in the presence of risk factors (see section 4.4.)

Renal effects

Interstitial nephritis can occur rarely but it is reversible when treatment is discontinued.

Haematological effects

As with other P-iactam antibiotics, haematological effects including reversible leucopenia, reversible thrombocytopenia and haemolytic anaemia have been report rarely.

Hypersensitivity reactions

If any hypersensitivity reaction (e.g skin rash) occurs, the treatment should be discontinued.

Skin rash, puritis and urticaria have been reported occasionally. The incidence of rash is higher in patients suffering from infectious mononucleosis and acute or chronic leukaemia of lymphoid origin. Purpura, fever, eosinophilia and sometimes angioneurotic oedema have also been reported. Rarely, skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported. Reactions such as fever, arthralgia and myalgia can develop more than 48 hours after the start of the treatment.

Anaphylaxis (see section 4.4) has been reported rarely.

Gastrointestinal reactions

Minor gastrointestinal disturbances, including occasionally nausea, vomiting and diarrhoea may occur during treatment. Pseudomembranous colitis has been reported rarely.

Hepatic effects

Hepatitis and cholestatic jaundice have been reported rarely. These may be delayed for up to two months after withdrawal of treatment. In some cases the course of these conditions has been protracted and lasted for several months. Very rarely deaths have been reported from hepatic effects but are mostly limited to patients with serious underlying disease.

A moderate transient increase in transaminases has been reported.

Skin and subcutaneous tissue disorders

Frequency not known: AGEP – acute generalized exanthematous pustulosis (see section 4.4)

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.

4.9 Overdose

Problems of over dosage with co-fluampicil are unlikely to occur; if encountered they may be treated symptomatically.

Gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and should be treated symptomatically.

Co-fluampicil contains flucloxacillin. Haemodialysis does not lower the serum levels of flucloxacillin.

Co-fluampicil contains ampicillin, which may be removed from the circulation by haemodialysis.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other Beta-Lactam Antibacterials, ATC code: J01D

Fluclaxacillin is used for the treatment of infections due to staphylococci resistant to benzylpenicillin. It is also used for the mixed streptococcal infections when the staphylococci are penicillin-resistant.

Ampicillin is a broad spectrum antibiotic which is bactericidal for both gram positive and gram negative bacteria.

5.2 Pharmacokinetic properties

Flucloxacillin after an oral dose of 250 to 500 mg in fasting subjects shows peak serum concentrations at one hour ranging from 3–27 mcg/ml with a mean peak 11–15 mcg/ml. Therapeutic concentrations persist for about four hours. Doubling the dose can double the plasma concentrations. About 95% of flucoxacillin is metabolised to a limited extent and the unchanged drug and metabolites are excreted in the urine.

Ampicillin is relatively stable in gastric secretion and is well absorbed from the gastro-intestinal tract producing peak concentrations in about two hours. Doubling the dose can produce double the concentration. Ampicillin diffuses across the placenta and the foetal circulation and concentrations can persist in amniotic fluid. Concentrations can be detected in the milk of nursing mothers. There is little diffusion into the cerebro-spinal fluid except when the meninges are infected, when high concentrations are achieved. Concentrations of ampicillin are found in ascetic, pleural, joint and ocular fluids. 30% of the orally administered dose is excreted unchanged in the urine in about six hours.

5.3 Preclinical safety data

Not applicable

6.1

Sodium benzoate

Disodium edetate

Saccharin sodium

Mono-ammonium glycyrrhizinate

Sodium citrate (dried)

Flavour apricot

Flavour menthol

Yellow F.D. & C.No:6 (E110)

Sucrose (Caster)

6.2

None known

6.3

2 years unopened.

7 days after reconstitution.

6.4 Special precautions for storage

Store in a cool dry place. Store below 25°C.

6.5 Nature and contents of container

High density polyethylene bottles with tamper-evident and child-resistant cap or Amber Beatson Clark Winchester with polypropylene screw cap. Each pack contains 100ml when reconstituted.

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.