Aztreonam and Avibactam interacts in the following cases:
Elevated liver enzymes have been observed with aztreonam/avibactam. In patients with hepatic impairment, close monitoring is recommended during treatment with aztreonam/avibactam.
No dosage adjustment is required in patients with mild renal impairment (estimated CrCL >50 to ≤80 mL/min).
The table below shows the recommended dose adjustments for patients with estimated creatinine clearance ≤50 mL/min. A single loading dose is followed by maintenance doses beginning at the next dosing interval.
Recommended doses for patients with estimated CrCL ≤50 mL/min:
| Estimated CrCL (mL/min)a | Dose of aztreonam-avibactamb | Infusion time | Dosing interval | |
|---|---|---|---|---|
| Loading | Maintenance | |||
| >30 to ≤50 | 2 g/0.67 g | 0.75 g/0.25 g | 3 hours | Every 6 hours |
| >15 to ≤30 | 1.35 g/0.45 g | 0.675 g/0.225 g | 3 hours | Every 8 hours |
| ≤15 mL/min, on intermittent haemodialysisc,d | 1 g/0.33 g | 0.675 g/0.225 g | 3 hours | Every 12 hours |
a Calculated using the Cockcroft-Gault formula.
b Dose recommendations are based on PK modelling and simulation.
c Both aztreonam and avibactam are removed by haemodialysis; on haemodialysis days aztreonam/avibactam should be administered after the haemodialysis session.
d Aztreonam-avibactam should not be used in patients with CrCl ≤15 mL/min unless haemodialysis or another form of renal replacement therapy is initiated.
In patients with renal impairment, close monitoring of estimated creatinine clearance is advised.
There are insufficient data to make dosing adjustment recommendations for patients undergoing renal replacement therapy other than haemodialysis (e.g. continuous veno-venous hemofiltration or peritoneal dialysis). Patients receiving continuous renal replacement therapy (CRRT) need a higher dose than patients on haemodialysis. For patients receiving continuous renal replacement therapy, the dose should be adjusted guided by the CRRT clearance (CLCRRT in mL/min).
In vitro, aztreonam and avibactam are substrates of organic anion transporters OAT1 and OAT3 which might contribute to the active uptake from the blood compartment and, thereby, renal excretion. Probenecid (a potent OAT inhibitor) inhibits uptake of avibactam by 56% to 70% in vitro and, therefore, has the potential to alter the elimination of avibactam when co-administered. Since a clinical interaction study of aztreonam-avibactam and probenecid has not been conducted, co-dosing with probenecid is not recommended.
There are no or limited amount of data from the use of aztreonam or avibactam in pregnant women. Animal studies with aztreonam do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Animal studies with avibactam have shown reproductive toxicity without evidence of teratogenic effects.
Aztreonam/avibactam should only be used during pregnancy when clearly indicated and only if the benefit for the mother outweighs the risk for the child.
Aztreonam is excreted in human milk in concentrations that are less than 1% of those in simultaneously obtained maternal serum. It is unknown whether avibactam is excreted in human milk. A risk to the breastfed child cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from aztreonam/avibactam therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
No human data on the effect of aztreonam/avibactam on fertility are available. Animal studies with aztreonam or avibactam do not indicate harmful effects with respect to fertility.
Undesirable effects may occur (e.g. dizziness) which may have a minor influence on the ability to drive or use machines.
The most common adverse drug reactions (ADRs) in patients treated with aztreonam/avibactam (ATM-AVI) were anaemia (6.9%), diarrhoea (6.2%), alanine aminotransferase (ALT) increased (6.2%), and aspartate aminotransferase (AST) increased (5.2%).
The following ADRs have been reported with aztreonam alone and/or identified during Phase 2 and Phase 3 clinical trials with aztreonam/avibactam (N=305).
The ADRs listed in the table below are presented by System Organ Class (SOC) and frequency categories, defined using the following convention: very common (≥1/10); common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100), rare (≥1/10 000 to <1/1 000), very rare (<1/10 000), or frequency not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Frequency of adverse drug reactions presented by system organ class:
| System Organ Class | Common ≥1/100 to <1/10 | Uncommon ≥1/1 000 to <1/100 | Rare ≥1/10 000 to <1/1 000 | Frequency not known (cannot be estimated from the available data) |
|---|---|---|---|---|
| Infections and infestations | Vulvovaginal candidiasis Vaginal infection | Superinfection | ||
| Blood and lymphatic system disorders | Anaemia Thrombocytosis Thrombocytopenia | Eosinophil count increased Leukocytosis | Pancytopenia Neutropenia Prothrombin time prolonged Activated partial thromboplastin time prolonged Coombs test positive Coombs direct test positive Coombs indirect test positive | |
| Immune system disorders | Anaphylactic reaction Drug hypersensitivity | |||
| Psychiatric disorders | Confusional state | Insomnia | ||
| Nervous system disorders | Dizziness | Encephalopathy Headache Hypoaesthesia oral Dysgeusia | Seizure Paraesthesia | |
| Eye disorders | Diplopia | |||
| Ear and labyrinth disorders | Vertigo Tinnitus | |||
| Cardiac disorders | Extrasystoles | |||
| Vascular disorders | Haemorrhage Hypotension Flushing | |||
| Respiratory, thoracic and mediastinal disorders | Bronchospasm | Dyspnoea Wheezing Sneezing Nasal congestion | ||
| Gastrointestinal disorders | Diarrhoea Nausea Vomiting Abdominal pain | Clostridium difficile colitis Gastrointestinal haemorrhage Mouth ulceration | Pseudomembranous colitis Breath odour | |
| Hepatobiliary disorders | Aspartate aminotransferase increased Alanine aminotransferase increased Transaminases increased | Gamma- glutamyltransferase increased Blood alkaline phosphatase increased | Hepatitis Jaundice | |
| Skin and subcutaneous tissue disorders | Rash | Angioedema Toxic epidermal necrolysis Dermatitis exfoliative Erythema multiforme Purpura Urticaria Petechiae Pruritus Hyperhidrosis | ||
| Musculoskeletal and connective tissue disorders | Myalgia | |||
| Renal and urinary disorders | Blood creatinine increased | |||
| Reproductive system and breast disorders | Breast tenderness | |||
| General disorders and administration site conditions | Phlebitis Thrombophlebitis Infusion site extravasation Injection site pain Pyrexia | Chest discomfort Asthenia | Malaise |
Acute coronary syndrome associated with an allergic reaction (Kounis syndrome) has been reported with other beta-lactam antibiotics.
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