Clavomax

Amoxicillin, clavulanic acid.

Each film-coated tablet contains: Amoxicillin (as amoxicilin trihydrate) 500 mg, Clavulanic acid (as potassium clavulanate) 125 mg.

Pharmacology: Pharmacodynamics: Clavomax is a registered product containing amoxicillin, a bactericidal broad spectrum penicillin, and potassium clavulanate, a progressive and irreversible inhibitor of β-lactamase enzymes.
The presence of potassium clavulanate protects amoxicillin from destruction and subsequent loss of antibacterial activity by the β-lactamase enzymes produced by many Gram-positive bacteria. The spectrum of amoxicillin is thus widened to include organisms normally resistant by virtue of their ability to produce β-lactamase.
Clavomax will not only eliminate primary pathogens but also will not be inactivated by non pathogenic β-lactamase producing organisms at the site of infection.
Pharmacokinetics: The pharmacokinetics of the two components of Clavomax are closely matched. Peak serum levels of both occur about 1 hour after oral administration. Absorption of Clavomax is optimized at start of a meal. Doubling the dosage of Clavomax approximately doubles the serum level achieved. Both clavulanate and amoxicillin have low levels of serum binding; about 70% remains free in serum.
Bacteriology: Clavomax is bactericidal to a wide range of Gram-positive and Gram-negative bacteria including many clinically important β-lactamase producing penicillin resistant organisms both in the hospital and general practice environment, including: Gram-Positive: Aerobes: Enterococcus faecalis*, Enterococcus faecium*, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Staphylococcus aureus*, Coagulase negative staphylococci* (including Staphylococcus epidermis*), Corynebacterium species, Bacillus anthracis*, Listeria monocytogenes.
Anaerobes: Clostridium species, Peptococcus species, Peptostreptococcus.
Gram-Negative: Aerobes: Haemophilus influenzae*, Moraxella catarrhalis* (Branhamella catarrhalis), Escherichia coli*, Proteus mirabilis*, Proteus vulgaris*, Klebsiella species*, Salmonella species*, Shigella species*, Bordetella pertussis, Brucella species, Neisseria gonorrhoeae*, Neisseria meningitidis*, Vibrio cholerae, Pasteurella multocida.
Anaerobes: Bacteroides species* including B. fragilis.
* Some members of these species of bacteria produce beta-lactamase, rendering them insensitive to amoxicillin alone.

Clavomax is indicated for the treatment of common bacterial infections where antibiotic therapy is indicated, including: Upper Respiratory Tract Infections (including ENT) e.g. Sinusitis, tonsillitis, otitis media.
Lower Respiratory Tract Infections e.g. Acute exacerbation of chronic bronchitis, lobar and bronchopneumonia.
Skin and Soft Tissue Infections e.g. Boils/abscesses, cellulitis and wound infections.
Genito-Urinary Tract Infections e.g. Cystitis, urethritis, pyelonephritis.
Bone and Joint Infections: e.g. osteomyelitis.
Other Infections: intra-abdominal sepsis.

Adult & children >12 years old: One Clavomax 625mg Tablet twice daily. Max duration: 14 days. Not suitable for children below 12 years old.
Dental infections: One Clavomax 625mg tablet twice daily for 5 days.
Clavomax is well absorbed and may be taken with or without food (May be given w/o regard to regard to meals. Best taken at the start of meals for better absorption & to reduce GI discomfort. Swallow whole, do not chew. Tab may be broken in half & swallowed w/o chewing).
Renal Impairment: (See table.)

Click on icon to see table/diagram/image

Hepatic Impairment: Dose with caution; monitor hepatic function at regular intervals.

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.
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.
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.

Patients with: Penicillin and cephalosporin hypersensitivity.
Patients with previous history of Clavomax associated jaundice/hepatic dysfunction.

Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents.
Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients receiving therapy with beta-lactams. Before initiating therapy with Clavomax, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, carbapenems or other beta-lactam agents. If an allergic reaction occurs, Clavomax must be discontinued immediately and appropriate alternative therapy instituted. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.
Amoxicillin/clavulanic acid should be avoided if infections mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.
Clavomax should be used with care in patients on anti-coagulation therapy.
Changes in liver function tests have been observed in some patients receiving Clavomax. The clinical significance of these changes is uncertain but Clavomax should be used with care in patients with evidence of severe hepatic dysfunction. Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Signs and symptoms may not become apparent for up to six weeks after treatment has ceased.
In patients with moderate or severe renal impairment Clavomax dosage should be adjusted as recommended in the "Dosage & Administration".
In patients with reduced urine output, crystalluria has been observed very rarely, 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.

Pregnancy: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development.
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. Use should be avoided during pregnancy, unless considered essential by the physician.
Lactation: Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued.
Amoxicillin/clavulanic acid should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

Clavomax is generally well tolerated. The majority of side effects reported are of mild to transient action and less than 3% of patients discontinued therapy because of drug related effects. Common adverse effects are as follows: Gastrointestinal: diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black hairy tongue, enterocolitis, mucco cutaneous candidiasis and pseudomembraneous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.
Hypersensitivity reactions: skin rashes, pruritis, urticaria, angioedema, serum sickness-like reactions, erytheme multiforme (rarely Stevens Johnson Syndrome) and an occasional case of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported. These reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur the drug should be discontinued. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions can occur with oral penicillin products.
Liver: a moderate rise in AST (SGOT) and/or ALT (SGTP) has been noted in patients with ampicillin class antibiotics, but the significance of these findings is unknown. Hepatic dysfunction, including increase in serum transaminases (AST and/or ALT), serum bilirubin and/or alkaline phosphatase, has been infrequently reported with amoxicillin. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic-hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. On rare occasions, death have been reported (less than 1 death reported per estimated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications.
Renal: Interstitial nephritis and heamaturia have rarely been reported.
Haemic and Lymphatic systems: anemia, thrombocytopenia, thrombocytopenic purpurea, eosinophilia, leucopenia and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensivity phenomena. A slight thrombocytosis was noted in less than 1% of patients treated with the combination of amoxicillin with clavulanic acid.
Central Nervous System: reversible hyperactivity, agitation, anxiety, insomnia, confusion, behavioral changes, and/or dizziness have been rarely reported.
Skin subcutaneous tissue disorders: Frequency 'very rare': Drug Reaction with Eosinophilia and System Symptoms (DRESS).

Oral anticoagulants: Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are cases of increased international normalised ration in patients maintained on acenocoumarol 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.
Probenecid: Concomitant use of probenecid is not recommended.
Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.
In common with other antibiotics, Clavomax may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.

Store below 30C. Protect form light and moisture.
Shelf-Life: 3 years.

Penicillins

J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

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