Clavenir 1 g

/ BioAvenir

This product only be administered intravenously.
The dose selected to treat an individual infection should take into account:
• The expected pathogens and their likely susceptibility to antibacterial agents
• The severity and the site of the infection
• The age, weight and renal function of the patient.
This Clavenir powder for solution for injection/infusion provides a total daily dose of 3000 mg amoxicillin and 600 mg clavulanic acid. The duration of therapy should be determined by the response of the patient. Some infections (e.g. osteomyelitis) require longer periods of treatment. Treatment should not be extended beyond 14 days without review.
See prescribing information for full details.

For the treatment of the following infections in adults and children:
* Severe infections of the ear, nose and throat (such as mastoiditis, peritonsillar infections, epiglottitis)
* Sinusitis when accompanied by severe systemic signs and symptoms
* Acute exacerbations of chronic bronchitis (adequately diagnosed)
* Community acquired pneumonia
* Cystitis
* Pyelonephritis
* Skin and soft tissue infections in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis
* Bone and joint infections, in particular osteomyelitis
* Intra-abdominal infections
* Female genital infections
Prophylaxis against infections associated with major surgical procedures in adults, such as those involving the:
* Gastrointestinal tract
* Pelvic cavity
* Head and neck
* Biliary tract surgery

Hypersensitivity to the active substances or to any of the penicillins.
History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).
History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid.

* 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 on penicillin therapy. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction. If an allergic reaction occurs, amoxicillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.
* Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin/clavulanate. DIES is an allergic reaction with the leading symptom of protracted vomiting (1-4 hours after drug administration) in the absence of allergic skin or respiratory symptoms. Further symptoms could comprise abdominal pain, diarrhoea, hypotension or leucocytosis with neutrophilia. There have been severe cases including progression to shock.
* Convulsions may occur in patients with impaired renal function or in those receiving high doses.
* 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.
* Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.
* Prolonged use may occasionally result in overgrowth of non-susceptible organisms.
* The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP). This reaction requires discontinuation and contraindicates any subsequent administration of amoxicillin.
* Should be used with caution in patients with evidence of hepatic impairment.
* 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.
It’s reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely 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.

* Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening. 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. Anti-peristaltic medicinal products are contraindicated in this situation.
* Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
* Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin/clavulanic acid.
* In patients with reduced urine output crystalluria (including acute renal injury) 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.
* Enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods.
* The presence of clavulanic acid in this product may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.
* There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving amoxicillin/clavulanic acid who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving amoxicillin/clavulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.
See prescribing information for full details.

Common: Mucocutaneous candidosis, Diarrhoea
See prescribing information for full details.

Oral anticoagulants: In the literature there are cases of increased international normalised ratio 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. In practice without reports of interaction.
Methotrexate: Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.
Probenecid: 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.
Mycophenolate mofetil: In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. 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.
See prescribing information for full details.

Pregnancy: Limited data on the use of amoxicillin/clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. 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.

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.