Ultramox 500 500 mg Capsules

Infections caused by susceptible, non-penicillinase-producing organisms including:

• Upper respiratory tract infections
• Lower respiratory tract infections
• Otitis media
• Upper urinary tract infections
• Lower urinary tract infections
• Skin and soft tissue infections
• Gonorrhoea
• Non-specific urethritis
• Typhoid Fever
• Gastro-intestinal tract infections

Posology

The average adult dose for ULTRAMOX is 750 mg - 1,5 g per day, but in serious infections up to 6 g daily has been administered without harmful effects.

(a) General dosages: Adults: 250 mg (1 x 250 mg capsule) three times a day. In severe infections these dosages may safely be increased.

(b) Specific Dosages:

Indications

Daily Dosages

Duration

Adults

Children

4 u2013 5 days

Gastrointestinal tract infections

1 u2013 2 g

-

Acute Typhoid Fever

4 g

-

-

100 mg/kg

14 days

21 days

Gonorrhoea

2 u2013 3 g

-

stat

Hypersensitivity to the penicillins or any of the cephalosporins or to any of the excipients listed in section 6.1. Amoxicillin as contained in ULTRAMOX is penicillin and should not be given to patients with a history of hypersensitivity to u03b2-lactam antibiotics (e.g. carbapenem or monobactam). Potential cross allergy to other beta-lactams such as cephalosporins should be taken into account.

Hypersensitivity reactions:

• Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins.
• Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction (see section 4.8).
• Before commencing therapy with any penicillin as contained in ULTRAMOX, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergies (see section 4.3).
• If an allergic reaction occurs, appropriate therapy should be instituted and ULTRAMOX therapy discontinued.
• Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin (see section 4.8). DIES is an allergic reaction with the leading symptom of protracted vomiting (1-4 hours after medicine intake) 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.

Skin reactions:

• ULTRAMOX should be avoided if infectious mononucleosis and glandular fever is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of amoxicillin.
• ULTRAMOX should preferably not be used in patients with lymphatic leukaemia, since they are especially susceptible to ampicillin-induced skin rashes.
• The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AEGP). This reaction requires ULTRAMOX discontinuation and contraindicates any subsequent administration.
• Prolonged use may also occasionally result in overgrowth of non-susceptible organisms.
• Antibiotic associated Pseudomembranous colitis has been reported. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with ULTRAMOX use (this may occur up to several weeks after cessation of ULTRAMOX therapy). If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment with ULTRAMOX should be discontinued immediately.
• Anti-peristaltic medicines are contraindicated in this situation.
• Anticoagulants: Prolongation of prothrombin time has been reported rarely in patients receiving ULTRAMOX. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently.
• Hepatic impairment: ULTRAMOX should be used with caution in patients with evidence of hepatic dysfunction.
• Changes in liver function tests have been observed in some patients receiving ULTRAMOX.
• Transient hepatitis and cholestatic jaundice have been reported.
• Renal impairment: The dose should be reduced in patients with renal failure.
• Prolonged therapy: Periodic assessment of renal, hepatic, and haematopoietic functions should be made during prolonged therapy.
• The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur ULTRAMOX should be discontinued and/or appropriate therapy instituted.
• Jarisch-Herxheimer reaction: Caution is needed when administering ULTRAMOX to patients with syphilis, as the Jarisch-Herxheimer reaction may occur in these patients.
• Allopurinol: ULTRAMOX should preferably not be used in patients treated with allopurinol since they are especially susceptible to ampicillin-induced skin rashes (see section 4.5).
• Crystalluria: In patients with reduced urine output, crystalluria (including acute renal injury) has been observed. The presence of high urinary concentrations of ULTRAMOX can cause precipitation of the product in urinary catheters. Therefore, catheters should be visually inspected at intervals. When high doses are administered, adequate fluid intake and urinary output must be maintained (see section 4.8 and 4.9).
• Convulsions: Convulsions may occur in patients with impaired renal function, in those receiving high doses or in patients with predisposing factors (e.g. history of seizures, treated epilepsy or meningeal disorders) (see section 4.8).
• Non-susceptible microorganisms: The use of ULTRAMOX may lead to the appearance of resistant strains of organisms and sensitivity testing should therefore be carried out wherever possible, to ensure the appropriateness of the therapy.
• ULTRAMOX is not suitable for the treatment of some types of infection unless the pathogen is already documented and known to be susceptible or there is a very high likelihood that the pathogen would be suitable for treatment with ULTRAMOX. This particularly applies when considering the treatment of patients with urinary tract infections and severe infections of the ear, nose and throat.
• Amoxicillin, an aminopenicillin, 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, in the presence of which there is a high incidence of rash if amoxicillin is used (see sub-header u2018Skin reactionsu2019).
• There is insufficient evidence at present to show that ULTRAMOX penetrates into the cerebrospinal fluid in therapeutic quantities and it should, therefore, not be used in the treatment of cerebrospinal infections.
• Effects on laboratory tests: Since high urine concentrations of amoxicillin as contained in ULTRAMOX may result in false positive reactions when testing for the presence of glucose in urine, it is recommended that glucose tests based on enzyme-based glucose oxidase reactions be used (see section 4.5).

Due to amoxicillinu2019s effect on intestinal flora, the absorption of other medicines may be affected.

Allopurinol: The concomitant administration of allopurinol and ampicillin substantially increases the incidence of skin rashes in patients receiving both medicines as compared to patients receiving ampicillin alone (see section 4.4). It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricaemia present in these patients.

Digoxin: The absorption of concurrently administered digoxin may be increased during treatment with ULTRAMOX.

Anticoagulants: Concomitant administration of ULTRAMOX and anticoagulants e.g. coumarin may prolong the bleeding time. A dose adjustment of anticoagulants may be necessary (see section 4.4). If coadministration is necessary, the prothrombin time or internationally normalised ratio should be carefully monitored with the addition or withdrawal of ULTRAMOX.

Probenecid: Probenecid decreases the renal tubular secretion of ULTRAMOX. Concurrent use with ULTRAMOX may result in increased and prolonged blood concentrations of ULTRAMOX.

Tetracyclines: Tetracyclines and other bacteriostatic medicines may interfere with the bactericidal effects of ULTRAMOX.

Interaction with Laboratory tests: It is recommended that when testing for the presence of glucose in urine during ULTRAMOX treatment, enzymatic glucose oxidase methods should be used. Due to the high urinary concentrations of ULTRAMOX, false positive readings are common with chemical methods (see section 4.4).

Methotrexate: Interaction between ULTRAMOX and methotrexate leading to methotrexate toxicity has been reported. Serum methotrexate levels should be closely monitored in patients who receive ULTRAMOX and methotrexate simultaneously (see section 4.4). ULTRAMOX decreases the renal clearance of methotrexate, probably by competition at the common tubular secretion system.

Women of childbearing potential/ Contraception in males and females: ULTRAMOX may reduce the efficacy of oral contraceptives and patients should be warned accordingly (see section 4.5).

Pregnancy: Safety in pregnancy has not been established.

Breastfeeding: ULTRAMOX is excreted in breast milk and should be used with caution when administered to lactating women.

ULTRAMOX may cause allergic reactions, dizziness or convulsions and may thus have an effect on mental and/or physical abilities to perform or execute tasks or activities requiring mental alertness, judgment and/or sound coordination and vision (see section 4.8).

Summary of the safety profile: The most frequently reported adverse side effects are diarrhoea, nausea, vomiting, indigestion, abdominal pain, skin rashes, urticaria and erythema multiforme, vaginitis, abnormal taste, headache, dizziness, tiredness and hot flushes.

Tabulated list of adverse reactions:

System Organ Class Undesirable effects

Less frequent Frequency not known

Infections and Infestations: Mucocutaneous candidosis

Blood and lymphatic system disorders: Haemolytic anaemia, Reversible thrombocytopenia, Thrombocytopenic purpura, Eosinophilia, Reversible leucopenia, Agranulocytosis, Leucopenia (including severe neutropenia or agranulocytosis), Prolongation of bleeding time and prothrombin time (see section 4.4)

Immune system disorders: Serum sickness-like syndrome, Hypersensitivity vasculitis, Anaphylaxis, Angioneurotic oedema

Nervous system disorders: Dizziness, Headache, Reversible hyperactivity, Convulsions (see section 4.4)

Cardiac disorders: Kounis syndrome (see section 4.4)

Gastrointestinal disorders: Diarrhoea, Nausea, Vomiting, Gastritis, Stomatitis, Glossitis, Enterocolitis, Black hairy tongue, Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) (see section 4.4), Drug-induced enterocolitis syndrome (see section 4.4)

Hepatobiliary disorders: Hepatitis and cholestatic jaundice. Rises in AST and/or ALT

Skin and subcutaneous tissue disorders: Skin rash, Erythematous maculopapular rash, Pruritis, Urticaria, Erythema multiforme, Bullous exfoliative dermatitis, Toxic epidermal necrolysis, Stevens-Johnson syndrome, Acute generalised pustulosis, Lyellu2019s syndrome, Acute generalised exanthemous pustulosis (AGEP) (see section 4.4), Drug reaction with eosinophilia and systemic symptoms (DRESS), Jarisch-Herxheimer reaction (see section 4.4)

Renal and urinary tract disorders: Interstitial nephritis, Crystalluria (including acute renal injury) (see section 4.9)

In overdose, side effects can be precipitated and/or be of increased severity (see section 4.8).

Symptoms: Oral administration can cause gastro-intestinal symptoms such as transient diarrhoea, nausea and colic which are dose-related and a result of local irritation and not toxicity.

Treatment: If encountered, gastro-intestinal symptoms and disturbances of the fluid and electrolyte balance may be evident. They may be treated symptomatically and supportive with attention to the water/electrolyte balance. In the absence of an adequate fluid intake and urinary output, crystalluria, in some cases leading to renal failure, is a possibility.

Amoxicillin may be removed from the circulation by haemodialysis.