Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: Novartis New Zealand Limited, PO Box 99102, Newmarket, Auckland 1149 Telephone: 0800 354 335
Hypersensitivity to one of the constituents of the medicine.
In patients with a history of hypersensitivity to other beta-lactams such as penicillins, cephalosporins, carbapenems or monobactams.
Curam and Curam Duo are contraindicated in patients with a previous history of amoxicillin/clavulanic acid – associated jaundice or hepatic dysfunction.
Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens.
Serious and occasionally fatal hypersensitivity reactions (anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction. Presenting symptoms of such reactions can include chest pain occurring in association with an allergic reaction to amoxicillin/clavulanic acid (see section 4.8 Undesirable effects). If an allergic reaction occurs, amoxicillin/clavulanic acid therapy should be discontinued and appropriate alternative therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline or epinephrine. Oxygen, intravenous steroids and airway management, including intubation may also be required.
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.
Prolonged use may also occasionally 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. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further.
In general, amoxicillin/clavulanic acid is well tolerated and possesses the characteristic low toxicity of the penicillin group of antibiotics. Periodic assessment of organ system functions; including renal, hepatic and haematopoietic function is advisable during prolonged therapy.
Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving amoxicillin/clavulanic acid and oral anticoagulants. 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.
Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepatic dysfunction.
Hepatic effects have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These side effects are very rarely 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 a serious underlying disease, or taking concomitant medications know to have the potential for hepatic effects.
In patients with renal impairment, dosage should be adjusted according to the degree of impairment (see section 4.2 Dose and method of administration).
Convulsions may occur in patients with impaired renal function or in those receiving high doses.
The occurrence at treatment initiation of a feverish generalised erythema associated with pustule may be a symptom of acute generalised exanthemous pustulosis (AGEP). This reaction requires Curam discontinuation and is a contraindication to subsequent administration of amoxicillin.
The presence of clavulanic acid may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.
Amoxicillin/clavulanic acid suspensions contain aspartame, which is a source of phenylalanine and should be used with caution in patients with phenylketonuria.
In patients with reduced urine output crystalluria has been observed very rarely, predominantly with parenteral therapy. During 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 (refer to Section 4.9 Overdose).
Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepatic dysfunction.
In patients with renal impairment, dosage should be adjusted according to the degree of impairment (refer to Section 4.2 Dose and method of administration).
See Section 4.2 Dose and method of administration.
See Section 4.2 Dose and method of administration.
No data available.
Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with amoxicillin/clavulanic acid may result in increased and prolonged blood levels of amoxicillin, but not of clavulanic acid.
Concomitant use of allopurinol during treatment with amoxicillin can increase the risk of allergic skin reactions. There are no data on the concomitant use of amoxicillin/clavulanic acid and allopurinol.
In common with other antibiotics, amoxicillin/clavulanic acid may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives.
In the literature, there are rare cases of increased international normalised ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If coadministration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin.
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.
There are no data on the effects of amoxicillin trihydrate/potassium clavulanate on fertility in humans. Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and parenterally administered amoxicillin/clavulanic acid have shown no teratogenic effects.
Category B1.
Assigned Category B1 by the Australian Drug Evaluation Committee. This category includes medicines, which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human foetus having been observed. Studies in animals have not shown evidence of an increased occurrence of foetal damage.
In a single study in women presenting preterm, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, unless considered essential by the physician.
Amoxicillin/clavulanic acid may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breastfed infant.
This medicine is presumed to be safe or unlikely to produce an effect. Adverse effects on the ability to drive or operate machinery have not been observed.
Data from large clinical trials were used to determine the frequency of very common to rare adverse effects. The incidences of all other adverse effects occurring below 1 in 10,000 were mainly determined from post-marketing data and reflect the reporting rate rather than the true incidence.
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.
Common: Mucocutaneous candidiasis
Unknown: Overgrowth of non-susceptible organism
Rare: Reversible leucopenia (including neutropenia) and thrombocytopenia
Very rare: Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and prothrombin time
Very rare: Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis
Uncommon: Dizziness, headache
Very rare: Aseptic meningitis, reversible hyperactivity and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses (refer to Section 4.4 Special warnings and precautions for use).
Very rare: Kounis syndrome (see section 4.4 Special warnings and precautions for use).
Very common: Diarrhoea
Common: Nausea, vomiting
Uncommon: Indigestion
Very rare: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) (see Section 4.4 Special warnings and precautions for use). Black hairy tongue. Superficial tooth discolouration has been reported very rarely in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.
Common: Diarrhoea, nausea, vomiting
Uncommon: Indigestion
Very rare: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) (see Section 4.4 Special warnings and precautions for use). Black hairy tongue. Superficial tooth discolouration has been reported very rarely in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.
In all populations, nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking amoxicillin/clavulanic acid at the start of a meal. Lower gastro-intestinal irritation reactions such as diarrhoea and pruritus have been observed. These side effects are generally of a mild and transitory nature.
Uncommon: A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown.
Very rare: Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and other beta-lactam antibiotics (see Section 4.4 Special warnings and precautions for use).
Common: Allergic skin reactions occur significantly more often than with other penicillins and generally are maculopapular in nature. In a small majority of cases, “fifth day rash” (a morbilliform exanthema) is reported. This is dependent on the size of the dose and the patient’s condition.
Uncommon: Skin rash, pruritus, urticaria and purpura; angio-oedema and anaphylaxis can occur less frequently
Rare: Erythema multiforme
Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliativedermatitis, acute generalised exanthemous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS) If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.
Very rare: Interstitial nephritis, crystalluria (see Section 4.9 Overdose)
Rare: Allergies, which result in anaphylactic shock
Non-enzymatic methods for glucose determination in urine may give false-positive results.
Clavulanic acid may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test (refer to Section 4.4 Special warnings and precautions for use).
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/.
None known.
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