Co-Amoxiclav S Unimed And Co-Amoxiclav Sf Unimed 10 mg/5 ml

CO-AMOXICLAV UNIMED formulations are indicated for the treatment of infections caused by amoxicillin-resistant organisms producing u03b2-lactamases sensitive to clavulanic acid:

• Upper respiratory tract infections, such as sinusitis, otitis media, recurrent tonsillitis.
• Lower respiratory tract infections, such as acute exacerbations of chronic bronchitis (caused by amoxicillin-resistant u03b2-lactamase producing Escherichia coli, Haemophilus influenzae and Haemophilus para-influenzae), bronchopneumonia.
• Genito-urinary tract infections, such as cystitis, urethritis, pyelonephritis.
• Skin and soft tissue infections.

CO-AMOXICLAV UNIMED formulations will also be effective in the treatment of infections caused by amoxicillin-sensitive organisms at the appropriate amoxicillin dosage since in this situation the clavulanic acid component does not contribute to the therapeutic effect.

Posology

General Information

For infections caused by amoxicillin-sensitive organisms the dosage is that approved for amoxicillin as the clavulanic acid component does not contribute to the therapeutic effect. Dosage depends on the age, weight and renal function of the patient and the severity of the infection. Duration of therapy should be appropriate to the indication and should not exceed 14 days without review.

Children 2-12 years

The dose of CO-AMOXICLAV UNIMED in children is 25-50 mg/kg/day of the 4 parts amoxicillin, 1 part clavulanic acid preparations (which corresponds to a daily dosage of the equivalent of 20-40 mg/kg of amoxicillin and 5-10 mg/kg of clavulanic acid) to be taken in divided doses every eight hours, at the start of a meal.

4:1 Formulation

Directions for use

In divided doses, three times per day (every 8 hours), at the start of a meal

Lower dose (mg/kg/day) 20/5-40/10

Higher dose (mg/kg/day) 40/10-60/15

The lower dose is recommended for infections such as skin and soft tissue and recurrent tonsillitis. The higher dose is recommended for infections such as otitis media, sinusitis, lower respiratory tract infections and urinary tract infections. Children weighing 40 kg and over should be dosed according to adult recommendations.

Dosage guide

Amoxicillin-sensitive organisms

Product Upper respiratory tract infections Lower respiratory tract infections Urinary tract infections Skin and soft tissue infections

CO-AMOXICLAV S UNIMED 13-21 kg (2-6 years) 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly

CO-AMOXICLAV SF UNIMED 22-40 kg (7-12 years) 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly

1 To correspond to a dosage of 25-50 mg/kg/day

Amoxicillin-resistant organisms

Product Upper respiratory tract infections (otitis media) H. influenzae, H. parainfluenzae Lower respiratory tract infections (bronchitis) H. influenzae, H. parainfluenzae Urinary tract infections E. coli. Klebsiella pneumomae Skin and soft tissue infections Staphylococcus aureus

CO-AMOXICLAV S UNIMED 13-21 kg (2-6 years) 5-10 ml 2 8 hourly 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly

CO-AMOXICLAV SF UNIMED 22-40 kg (7-12 years) 5-10 ml 2 8 hourly 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly 5-10 ml 1 8 hourly

1 To correspond to a dosage of 25-50 mg/kg/day

2 To correspond to a dosage of 50 mg/kg/day

Children aged 2 months to 2 years

Children under 2 years should be dosed according to body weight. CO-AMOXICLAV S UNIMED and CO-AMOXICLAV SF UNIMED may be used in this age group.

Special populations

Renal impairment

Both amoxicillin and clavulanic acid are excreted by the kidneys and the serum half-life of each, but particularly of amoxicillin, increases in patients with renal failure. Therefore, the dose may need to be reduced or the dosing interval extended. Dosage adjustments are based on the maximum recommended level of amoxicillin. The following schedule is proposed:

Mild impairment Moderate impairment Severe impairment

Creatinine clearance greater than 30 ml/minute Creatinine clearance 10 to 30 ml/minute Creatinine clearance less than 10 ml/minute

No change in dosage. 15/3,75 mg/kg given 12 hourly. 15/3,75 mg/kg given as a single daily dose. Maximum amoxicillin dose: 30 mg/kg/day. Maximum amoxicillin dose: 15 mg/kg/day. No dosage recommendations can be made for premature infants. Haemodialysis decreases serum concentrations of both amoxicillin and clavulanic acid and an additional dose should be administered at the end of dialysis.

Method of Administration

For oral administration only. CO-AMOXICLAV UNIMED formulations should be taken immediately before a meal to minimise potential gastrointestinal intolerances. For instructions of reconstitution of the medicine before administration, see section 6.6.

• Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients of CO-AMOXICLAV UNIMED (see section 6.1)
• History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam medicine (e.g. a cephalosporin, carbapenem or monobactam).
• Previous history of amoxicillin/clavulanic-associated jaundice/hepatic dysfunction (see section 4.8)
• Safety in children under 2 months of age has not been established.

Prescribers must adhere to the principles of antibiotic stewardship.

Hypersensitivity reactions

Before initiating therapy with CO-AMOXICLAV UNIMED, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents (see sections 4.3 and 4.8). There have been reports of individuals with a history of penicillin hypersensitivity, who have experienced severe reactions when treated with cephalosporins. Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic can result in myocardial infarction (see section 4.8). Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. If an allergic reaction occurs, CO-AMOXICLAV UNIMED therapy must be discontinued and appropriate alternative therapy instituted: adrenaline, corticosteroids and antihistamines.

Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin/clavulanate (see section 4.8). DIES is an allergic reaction with the leading symptom of protracted vomiting (1 u2013 4 hours after intake of amoxicillin/clavulanate) in the absence of allergic skin or respiratory symptoms. Further symptoms could compromise abdominal pain, diarrhoea, hypotension or leucocytosis with neutrophilia. There have been severe cases including progression to shock.

Skin reactions

CO-AMOXICLAV UNIMED should be given with caution to patients with lymphatic leukaemia since they are especially susceptible to amoxicillin induced skin rashes. Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions (see section 4.5). The occurrence at treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP) (see section 4.8). This reaction requires CO-AMOXICLAV UNIMED discontinuation and contraindicates any subsequent administration of amoxicillin.

Amoxicillin-susceptible organisms

In the case that an infection is proven to be due to an amoxicillin-susceptible organisms(s) then consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official guidance. CO-AMOXICLAV UNIMED is not suitable for use when there is a high risk that the presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This presentation should not be used to treat penicillin-resistant S. pneumoniae.

Infectious mononucleosis

Since CO-AMOXICLAV UNIMED contains amoxicillin, an aminopenicillin, it is not the treatment of choice in patients presenting with sore throat or pharyngitis because of the possibility that the underlying cause is infectious mononucleosis. Amoxicillin/clavulanic acid should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.

Antibiotic-associated colitis

Antibiotic-associated colitis has been reported with nearly all antibacterial agents including amoxicillin and may range in severity from mild to life threatening (see section 4.8). Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, amoxicillin/clavulanic acid should immediately be discontinued, a medical practitioner be consulted, and an appropriate therapy initiated. Antiperistaltic medicinal products are contraindicated in this situation.

Anticoagulants

Prolongation of prothrombin time has been reported in patients receiving CO-AMOXICLAV UNIMED. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see sections 4.5 and 4.8).

Overgrowth of non-susceptible microorganisms

Prolonged use may also occasionally result in overgrowth of non-susceptible organisms. The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Aerobacter, Pseudomonas or Candida), CO-AMOXICLAV UNIMED should be discontinued and/or appropriate therapy instituted.

Prolonged therapy

Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function, is advisable during prolonged therapy. The use of this antibiotic may lead to the selection of resistant strains of organisms and sensitivity testing should, therefore, be carried out whenever possible, to demonstrate the appropriateness of therapy (see section 5.1).

Hepatic impairment

CO-AMOXICLAV UNIMED should be used with caution in patients with evidence of hepatic impairment (see sections 4.2, 4.3 and 4.8). Changes in liver function tests have been observed in some patients receiving CO-AMOXICLAV UNIMED. Hepatic function should be monitored at regular intervals. Transient hepatitis and cholestatic jaundice have been reported (see section 4.8). Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been reported in children. In all populations, signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe, and, in extremely rare circumstances, deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects (see section 4.8).

Renal impairment

In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2).

Convulsions

Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.8).

Crystalluria

In patients with reduced urine output, crystalluria (including acute renal injury) has been observed, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained (see section 4.9).

• Probenecid: Concomitant use decreases the renal tubular secretion of amoxicillin, but does not affect clavulanic acid excretion, which may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
• Allopurinol: Concomitant administration of allopurinol and ampicillin could substantially increase the incidence of skin rashes in patients receiving both agents as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricaemia present in these patients. There is no data on CO-AMOXICLAV UNIMED and allopurinol administered concomitantly.
• Oral anticoagulants: Use with penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are cases of increased international normalised ratio in patients maintained on acenocoumarin or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see section 4.4 and 4.8).
• Methotrexate: Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.
• Mycophenolate mofetil: In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) of approximately 50% has been reported following commencement of oral CO-AMOXICLAV UNIMED. The change in pre-dose level may not accurately represent changes in overall MPA exposure. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.
• Oral contraceptives: CO-AMOXICLAV UNIMED may reduce the efficacy of oral contraceptives and patients should be warned accordingly (see section 4.6).
• Alcohol: No information is available about the concurrent use of CO-AMOXICLAV UNIMED and alcohol. However, the ingestion of alcohol whilst being treated with some other u03b2-lactam antibiotics has precipitated a disulfiram (Antabuse) like reaction in some patients. Therefore, the ingestion of alcohol should be avoided during and for several days after treatment with CO-AMOXICLAV UNIMED.

Women of childbearing potential / Contraception in males and females

Concurrent use of CO-AMOXICLAV UNIMED and oral contraceptives decreases the efficacy of the oral contraceptive. Patients should be strongly advised to use an alternative or additional method of contraception while taking this medicine (see section 4.5).

Pregnancy

Safety in pregnancy has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). Limited data on the use of amoxicillin/clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. There is limited information on the use of CO-AMOXICLAV UNIMED in pregnancy and its use should be avoided.

Breastfeeding

Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). CO-AMOXICLAV UNIMED may be administered during the period of lactation. The possibility of sensitisation should be taken into account. Diarrhoea and fungal infection of the mucous membranes is possible in the breast-fed infant, so breast-feeding might have to be discontinued. With the exception of the associated risk of sensitisation, there are no known detrimental effects for the breastfed infant.

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see section 4.8).

The most commonly reported adverse drug reactions are diarrhoea, nausea, vomiting, abdominal pain, skin rashes, urticaria and erythema multiforme, vaginitis, abnormal taste, headache, dizziness, tiredness and hot flushes. The incidence and severity of adverse effects, particularly nausea and diarrhoea is more often associated with higher oral dosages. In addition, as these symptoms are especially related to the potassium clavulanate component, where these gastro-intestinal symptoms occur and a higher concentration of amoxicillin is required, consideration should be given to administering the additional amoxicillin separately.

The following undesirable effects have been observed and reported during treatment with amoxicillin/clavulanic acid:

Infections and infestations

Frequent: Mucocutaneous candidiasis (including vaginitis).

Frequency unknown: Overgrowth of non-susceptible organisms.

Blood and lymphatic system disorders

Frequent: Thrombocytopenic purpura, Eosinophilia

Less frequent: Reversible leukopenia (including neutropenia) and thrombocytopenia, Frequency not known: Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and prothrombin time (Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. See sections 4.4 and 4.5).

Immune system disorders

Less frequent: Angioedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis (see section 4.3 and 4.4).

Nervous system disorders

Less frequent: Dizziness, headache

Frequency unknown: Reversible hyperactivity and convulsions (Convulsions may occur in patients with impaired renal function or in those receiving high doses, see section 4.4), Aseptic meningitis

Cardiac disorders

Frequency unknown: Kounis syndrome (see section 4.4)

Gastrointestinal disorders

Frequent: Diarrhoea, Nausea, Vomiting (Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking CO-AMOXICLAV UNIMED at the start of a meal.), Gastritis, Stomatitis, Glossitis, Enterocolitis

Less frequent: Indigestion, Frequency unknown: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis, see section 4.4). Superficial tooth discolouration has been reported which can usually be removed by brushing. Abdominal pain, black u201chairyu201d tongue, abnormal taste, drug-induced enterocolitis syndrome, pancreatitis acute tiredness and hot flushes have been reported.

Hepato-biliary disorders

Less frequent: A moderate rise in AST and/or ALT has been noted in patients treated with u03b2-lactam class antibiotics, but the significance of these findings is unknown. Frequency unknown: Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins (see section 4.4).

Skin and subcutaneous tissue disorders

Less frequent: Skin rash, pruritus, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP) (see section 4.4)

Frequency unknown: Drug reaction with eosinophilia and systemic symptoms (DRESS), Linear IgA

Renal and urinary disorders

Frequency unknown: Interstitial nephritis, Crystalluria (including acute renal injury - see sections 4.4 and 4.9)

Description of selected adverse reactions

Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been reported in children. Signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe and in extremely rare circumstances deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications known to have the potential for hepatic effects.

Symptoms and signs of overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed. (see section 4.4). Convulsions may occur in patients with impaired renal function or in those receiving high doses. Amoxicillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of large doses. A regular check of patency should be maintained (see section 4.4).

Treatment of intoxication

Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance. Amoxicillin/clavulanic acid can be removed from the circulation by haemodialysis.