AZACTAM

Posology Intramuscular or intravenous injection, or intravenous infusion. Azactam is given by deep injection into a large muscle mass, such as the upper quadrant of the gluteus maximus or the lateral part of the thigh.

Adults:

The dose range of Azactam is 1 to 8 g daily in equally divided doses. The usual dose is 3 to 4 g daily. The maximum recommended dose is 8 g daily. The dosage and route of administration should be determined by the susceptibility of the causative organisms, severity of infection and the condition of the patient.

Dosage Guide:

Adults (see table below) Type of Infection1 Dosage Frequency (hours) Route Urinary tract infections 500 mg or 1 g 8 or 12 IM or IV Gonorrhoea / cystitis 1 g single dose IM Cystic fibrosis 2 g 6 - 8 IV Moderately severe systemic infections 1 g or 2 g 8 or 12 IM or IV Severe systemic or life- threatening infections 2 g 6 or 8 IM or IV Other infections either or 1 g 2 g 8 12 IM or IV IV 1Because of the serious nature of infections due to Pseudomonas aeruginosa, a dose of 2 g every 6 or 8 hours is recommended, at least for initial therapy in systemic infections caused by this organism.

g. intra- abdominal abscess), peritonitis, meningitis or other severe systemic or life- threatening infections.

Elderly:

Renal status is a major determinant of dosage in the elderly; these patients in particular may have diminished renal function. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by the kidneys, estimates of creatinine clearance should be obtained, and appropriate dosage modifications made if necessary.

Elderly patients normally have a creatinine clearance in excess of 30 mL/min and therefore would receive the normal recommended dose. If renal function is below this level, the dosage schedule should be adjusted (see Renal Impairment).

Renal Impairment:

Prolonged serum levels of aztreonam may occur in patients with transient or persistent renal insufficiency. 73 m2. 73 m2), such as those supported by hemodialysis, the usual dose should be given initially. The maintenance dose should be one-fourth of the usual initial dose given at the usual fixed interval of 6, 8 or 12 hours.

For serious or life-threatening infections, in addition to the maintenance doses, one-eighth of the initial dose should be given after each hemodialysis session.

Hepatic impairment:

A dose reduction of 20-25% is recommended for long-term treatment of patients with chronic liver disease with cirrhosis, especially in cases of alcoholic cirrhosis and when renal function is also impaired.

Paediatric population:

The usual dosage for patients older than one week is 30 mg/kg/dose every 6 or 8 hours. For severe infections in patients 2 years of age or older, 50 mg/kg/dose every 6 or 8 hours is recommended. The recommended dose for all patients in the treatment of infections due to P.

aeruginosa is 50 mg/kg every six to eight hours. The maximum daily paediatric dose should not exceed the maximum recommended dose for adults. Dosage information is not yet available for new-borns less than 1 week old. 6.

The list of undesirable effects shown below is presented by system organ class, MedDRA preferred term, and frequency. Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (≥1/10,000); Not known (cannot be estimated from the available data).

System Organ Class Frequen cy MedDRA Term Blood and lymphatic system disorders Rare Pancytopeniaa, thrombocytopenia, thrombocythaemias, leukocytosis, neutropenia, eosinophilia, anaemia, prothrombin time prolonged, activated partial thromboplastin time prolonged, Coombs test positivea Ear and labyrinth disorders Rare Vertigo, tinnitus Eye disorders Rare Diplopia Gastrointestinal disorders Rare Not known Gastro intestinal haemorrhage, pseudomembranous colitisa, breath odour Abdominal pains, mouth ulceration, nausea, vomiting, diarrhoea, altered taste System Organ Class Frequen cy MedDRA Term General disorders and administration site conditions Rare Not known Chest pain, pyrexia, asthenia, malaise Injection site discomfort, weakness, sweating, muscle aches, fever, transient increases in serum creatinine Hepato-biliary disorders Rare Not known Hepatitis, jaundice Transaminases increased*, blood alkaline phosphatase increased* Infections and infestations Rare Vaginitis, vaginal candidiasis Immune system disorders Not known Anaphylactic reaction Investigations Rare Electrocardiogram change Musculoskeletal, connective tissue and bone disorders Rare Myalgia Nervous system disorders Rare Not known Convulsionsa, paraesthesia, dizziness, headache Dysgeusia Encephalopathy (confusional state, altered state of consciousness, epilepsy, movement disorder) Psychiatric disorders Rare Confusional state, insomnia Renal and urinary disorders Uncom mon Blood creatinine increased System Organ Class Frequen cy MedDRA Term Reproductive system and breast disorders Rare Breast tenderness Respiratory, thoracic and mediastinal disorders Rare Not known Wheezing, dyspnoea, sneezing, nasal congestion Bronchospasm Skin and subcutaneous tissue disorders Not known Toxic epidermal necrolysisa, angioedema, erythema multiforme, dermatitis exfoliative, hyperhidrosis, petechiae, purpura, urticaria, rash, pruritus Vascular disorders Rare Not known Hypotension, haemorrhage Phlebitis, thrombophlebitis, flushing *Usually reversing during therapy and without overt signs or symptoms of hepatobiliary dysfunction.

4. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard

Allergic reactions Antibiotics, like other drugs, should be given with caution to any patients with a history of allergic reaction to structurally related compounds. If an allergic reaction occurs, discontinue the drug and institute supportive treatments as appropriate.

Serious hypersensitivity reactions may require epinephrine and other emergency measures. Specific studies have not shown significant cross-reactivity between Azactam and antibodies to penicillins or cephalosporins. The incidence of hypersensitivity to Azactam in clinical trials has been low but caution should be exercised in patients with a history of hypersensitivity to beta-lactam antibiotics until further experience is gained.

g. confusion, impairment of consciousness, epilepsy, movement disorders); particularly in patients with renal impairment and in association with beta- lactam overdose. In patients with impaired hepatic or renal function, appropriate monitoring is recommended during therapy.

Serious blood/skin disorders Serious blood disorders (incl. pancytopenia) and skin disorders (incl. toxic epidermal necrolysis) have been reported with the use of aztreonam. In case of serious hemogram and skin changes, it is recommended to stop aztreonam.

8). Clostridium difficile associated diarrhoea Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including Azactam, and may range in severity from mild diarrhoea to fatal colitis.

CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Medication that inhibits intestinal peristalsis should not be given. Concurrent therapy with other antimicrobial agents and Azactam is recommended as initial therapy in patients who are at risk of having an infection due to pathogens that are not susceptible to aztreonam.

As with other antibiotics, in the treatment of acute pulmonary exacerbations in patients with cystic fibrosis, while clinical improvement is usually noted, lasting bacterial eradications may not be achieved. Overgrowth of non-susceptible organisms Therapy with Azactam may result in overgrowth of non-susceptible organisms, including gram-positive organisms and fungi.

Should superinfection occur during therapy, appropriate measures should be taken. In comparative studies, the number of patients treated for superinfections was similar to that of the control drugs used. Prolongation of prothrombin time / increased activity of oral anticoagulants Prolongation of prothrombin time has been reported rarely in patients receiving aztreonam.

Additionally, numerous cases of increased activity of oral anticoagulants have been reported in patients receiving antibiotics, including beta-lactams. Severe infection or inflammation, and the age and general condition of the patient appear to be risk factors.

Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. 8). Concomitant use with aminoglycosides If an aminoglycoside is used concurrently with aztreonam, especially if high dosages of the former are used or if therapy is prolonged, renal function should be monitored because of the potential nephrotoxicity and ototoxicity of aminoglycoside antibiotics.

Paediatric population Data on safety and effectiveness in neonates younger than one week are limited; use in this population needs to be carefully assessed. Arginine Aztreonam for injection contains arginine. Studies in low birth weight infants have demonstrated that arginine administered in the aztreonam formulation may result in increases in serum arginine, insulin, and indirect bilirubin.

The consequences of exposure to this amino acid during treatment of neonates have not been fully ascertained. Interference with serological testing A positive direct or indirect Coombs test may develop during treatment with aztreonam.

1. Aztreonam is contraindicated in pregnancy. Aztreonam crosses the placenta and enters the foetal circulation.