Aztreonam avibactam side effects can range from commonly reported reactions such as diarrhea, anemia, hypokalemia and fever to important safety concerns involving hypersensitivity, serious skin reactions, hepatic effects and Clostridioides difficile-associated diarrhea. Understanding the safety profile of aztreonam-avibactam is important when evaluating this antibacterial combination for serious Gram-negative infections.
Aztreonam-avibactam is a combination of aztreonam and avibactam. Like other antibacterial medicines, it can cause adverse reactions, and the reported safety profile may vary depending on the patient population, clinical setting and regulatory jurisdiction.
This article explains aztreonam avibactam side effects, important warnings, allergic reactions, liver effects, renal safety, neurological considerations and safety information from clinical studies.
Important: Safety information can differ between U.S. and European product information. Always refer to the current prescribing information applicable to the specific product and country.
Aztreonam Avibactam Side Effects at a Glance
The reported aztreonam avibactam side effects include both common adverse reactions and less frequent but potentially serious events.
According to current U.S. prescribing information, adverse reactions occurring in more than 5% of patients in the pivotal trial included:
| Adverse reaction | Aztreonam-avibactam ± metronidazole | Comparator |
|---|---|---|
| Hepatic adverse reactions | 14.5% | 11.7% |
| Anemia | 8.0% | 5.1% |
| Diarrhea | 5.8% | 3.6% |
| Hypokalemia | 5.8% | 2.9% |
| Pyrexia | 5.8% | 5.1% |
The term hepatic adverse reactions represents a broad category. It can include liver enzyme elevations and other hepatic laboratory or clinical findings. It should not automatically be interpreted as severe liver damage.
Other reported adverse effects can include nausea, vomiting, abdominal discomfort, headache, dizziness and infusion-related reactions.
Common Aztreonam Avibactam Adverse Effects
The most frequently reported aztreonam avibactam adverse effects involve several different body systems.
These may include:
- Diarrhea
- Nausea
- Vomiting
- Abdominal pain
- Anemia
- Hypokalemia
- Pyrexia
- Liver enzyme elevations
- Headache
- Dizziness
- Infusion-site or administration-related reactions
The frequency of individual adverse reactions can vary between studies and regulatory sources.
For example, European product information reports anemia, diarrhea, ALT elevation and AST elevation among commonly reported adverse reactions.
Therefore, an adverse reaction listed in product information should not automatically be interpreted as an event that will occur in every patient.
Serious Aztreonam Avibactam Side Effects and Warning Signs
Although many adverse reactions are manageable, some serious aztreonam avibactam side effects require prompt medical evaluation.
Important safety concerns include:
- Severe hypersensitivity or allergic reactions
- Serious skin reactions
- Significant hepatic reactions
- Severe or persistent diarrhea associated with C. difficile
- Neurological effects, particularly with renal impairment or excessive beta-lactam exposure
Patients receiving aztreonam-avibactam should be monitored according to the applicable prescribing information.
If symptoms suggest a severe allergic reaction, serious skin reaction or severe antibiotic-associated diarrhea, medical attention should be obtained promptly.
Aztreonam Avibactam Allergic Reactions
Hypersensitivity is an important consideration when discussing aztreonam avibactam side effects.
Current U.S. labeling contraindicates EMBLAVEO in patients with known hypersensitivity to aztreonam, avibactam or other components of the product.
Reported hypersensitivity manifestations include:
- Rash
- Flushing
- Bronchospasm
Serious allergic reactions can require discontinuation of treatment and appropriate medical management.
Aztreonam Avibactam and Beta-Lactam Allergy
Information concerning beta-lactam allergy differs between regulatory jurisdictions.
The U.S. product information specifically identifies known hypersensitivity to the components of EMBLAVEO as a contraindication.
European and UK product information additionally identifies severe hypersensitivity, including anaphylactic reactions or severe skin reactions, to other beta-lactam antibacterials such as:
- Penicillins
- Cephalosporins
- Carbapenems
Because of these differences, it is not appropriate to make a universal statement that aztreonam-avibactam is automatically safe for every patient with a previous beta-lactam allergy.
The applicable local prescribing information should be followed.
Anaphylaxis and Angioedema
Anaphylaxis and angioedema appear in U.S. labeling among reactions previously reported with aztreonam alone.
These should not be presented as though they occurred at a specific frequency in the EMBLAVEO pivotal combination trial.
If a severe hypersensitivity reaction develops, treatment should be discontinued and appropriate medical management provided.
Serious Skin Reactions with Aztreonam Avibactam
Serious skin reactions are another important part of the aztreonam avibactam safety profile.
The U.S. prescribing information contains a warning concerning serious skin disorders and describes toxic epidermal necrolysis associated with aztreonam in patients with additional risk factors.
European product information also lists serious dermatological reactions, including:
- Toxic epidermal necrolysis
- Exfoliative dermatitis
- Erythema multiforme
- Angioedema
- Urticaria
- Purpura
- Petechiae
- Pruritus
These reactions are not typical everyday side effects. Some are uncommon or rare but potentially serious.
A new severe rash, blistering, skin peeling or other concerning skin reaction should receive prompt medical assessment.
Aztreonam Avibactam Liver Side Effects
Hepatic adverse reactions are among the more frequently reported adverse-reaction categories in current U.S. labeling.
Reported hepatic findings include:
- ALT elevation
- AST elevation
- Increased transaminases
- Increased hepatic enzymes
- Abnormal hepatic function
- Other hepatic adverse reactions
In the U.S. pivotal trial, hepatic adverse reactions occurred in 40 of 275 patients receiving EMBLAVEO.
ALT elevations of at least five times the upper limit of normal occurred in 10 of 275 patients.
No Hy’s Law cases were observed across the reported Trials 1–3. Four patients discontinued treatment because of hepatic enzyme elevations across those trials, and the elevations resolved after discontinuation.
Does Aztreonam Avibactam Cause Liver Damage?
It is more accurate to say that hepatic adverse reactions and liver enzyme elevations have been reported.
The phrase “liver damage” can imply that every hepatic adverse reaction represents clinically significant liver injury, which is not supported by the broader adverse-reaction category.
Patients with existing liver conditions or those receiving other potentially hepatotoxic medicines may require appropriate monitoring.
Aztreonam Avibactam and Diarrhea
Diarrhea is one of the reported aztreonam avibactam side effects.
In the U.S. pivotal trial, diarrhea occurred in 5.8% of patients receiving EMBLAVEO compared with 3.6% in the comparator group.
However, ordinary diarrhea should be distinguished from Clostridioides difficile-associated diarrhea.
Aztreonam Avibactam and C. difficile
Systemic antibacterial treatment can be associated with C. difficile-associated diarrhea.
Symptoms can range from diarrhea to severe or potentially life-threatening colitis.
Importantly, C. difficile-associated diarrhea can develop during treatment or after antibacterial treatment has ended.
Severe, persistent or bloody diarrhea should therefore be evaluated by a healthcare professional rather than automatically being considered a routine medication side effect.
Aztreonam Avibactam Kidney Safety
Renal function is an important consideration when evaluating aztreonam avibactam safety.
Both aztreonam and avibactam are substantially eliminated through the kidneys. When renal function decreases, exposure to the medicines can increase.
This can affect:
- Drug exposure
- Dose requirements
- Safety monitoring
- Risk of excessive beta-lactam exposure
The current U.S. prescribing information recommends monitoring creatinine clearance when renal function changes and adjusting treatment accordingly.
Aztreonam Avibactam Side Effects and Renal Impairment
Renal impairment is important not only because of dose adjustment but also because increased drug exposure can influence safety.
Neurological adverse effects associated with beta-lactam exposure are particularly relevant when renal function is significantly impaired.
For detailed CrCl-based dosing, hemodialysis and renal dose adjustment, see our dedicated aztreonam avibactam renal dosing guide.
Neurological Aztreonam Avibactam Adverse Effects
Neurological safety information requires careful interpretation.
European product information discusses neurological sequelae associated with aztreonam in situations such as renal impairment and beta-lactam overdose.
Reported neurological events include:
- Encephalopathy
- Confusion
- Seizures
- Impaired consciousness
- Movement disorders
- Dizziness
- Headache
- Paresthesia
The U.S. product information distinguishes some neurological reactions reported historically with aztreonam alone from adverse reactions observed in the pivotal EMBLAVEO Trial 1.
Therefore, these events should not automatically be described as common adverse effects of the aztreonam-avibactam combination.
Renal impairment and excessive beta-lactam exposure are important considerations when evaluating neurological symptoms.
Blood and Laboratory Abnormalities
Some aztreonam avibactam adverse effects involve blood counts or laboratory findings.
Reported abnormalities include:
- Anemia
- Thrombocytopenia
- Thrombocytosis
- Leukocytosis
- Eosinophilia
- Coagulation abnormalities
European product information additionally reports:
- Neutropenia
- Pancytopenia
- Prolonged prothrombin time
- Prolonged activated partial thromboplastin time
- Positive direct or indirect Coombs tests
These findings should be understood as reported laboratory or hematologic abnormalities rather than assuming that every abnormality represents a common clinical symptom.
Infusion-Related Aztreonam Avibactam Side Effects
Aztreonam-avibactam is administered intravenously, so local or infusion-related reactions can occur.
Reported events include:
- Phlebitis
- Thrombophlebitis
- Injection-site pain
- Extravasation
- Flushing
- Hypotension
- Chest discomfort
The frequency and terminology of these reactions can differ between clinical trials and regulatory product information.
For detailed information about preparation, dilution, administration and infusion, see the dedicated aztreonam avibactam dosage and administration article.
Aztreonam Avibactam Safety in Older Adults
Age alone does not automatically determine the dose of aztreonam-avibactam.
However, older adults may have reduced renal function, which can increase exposure to medicines that are primarily eliminated through the kidneys.
Clinical trials included patients aged 65 years and older, but the available data were not sufficient to establish meaningful age-related differences for every safety outcome.
Therefore, renal function remains particularly important when evaluating treatment in older adults.
Aztreonam Avibactam Side Effects in Hepatic Impairment
The U.S. labeling states that EMBLAVEO has not been specifically studied in patients with hepatic impairment.
Significant hepatic metabolism is not expected to be a major route of elimination.
European product information states that dose adjustment is not required for hepatic impairment but recommends appropriate monitoring because liver enzyme elevations have been reported.
This is another area where regulatory information should be interpreted according to the applicable jurisdiction.
Aztreonam Avibactam During Pregnancy
Human pregnancy data for aztreonam-avibactam are limited.
Current product information does not provide sufficient evidence to establish the risk profile of the combination during pregnancy.
European information similarly describes limited human data and recommends considering treatment when clinically indicated after evaluating potential benefits and risks.
Pregnancy-related treatment decisions should be made with a qualified healthcare professional.
Aztreonam Avibactam and Breastfeeding
Aztreonam has been detected in human milk, while human milk data for avibactam are limited.
There is insufficient information to fully determine the potential effects of avibactam exposure on a breastfed infant.
Patients who are breastfeeding should discuss treatment with their healthcare professional before starting or continuing therapy.
Aztreonam Avibactam Safety in Children
Safety and effectiveness in patients younger than 18 years have not been established in the cited U.S. and European product information.
Adult safety and dosing information should therefore not automatically be applied to pediatric patients.
What Clinical Trials Show About Aztreonam Avibactam Safety
Clinical trials provide useful information about the safety profile of aztreonam-avibactam.
The FDA safety database reviewed for the combination included approximately 305 patients receiving aztreonam-avibactam across relevant Phase 2 and Phase 3 studies.
However, uncommon adverse events can be difficult to characterize when the overall number of exposed patients is limited.
REVISIT Phase 3 Safety Findings
The REVISIT Phase 3 study included 422 adults, with 282 patients receiving aztreonam-avibactam and 140 receiving a meropenem-based comparator.
The study evaluated serious infections caused by Gram-negative bacteria.
Aztreonam-avibactam was generally well tolerated in the study population, and no treatment-related serious adverse events were reported in the aztreonam-avibactam group.
This does not mean serious adverse events can never occur. It describes the findings observed in that particular clinical trial.
ASSEMBLE Phase 3 Safety Findings
The ASSEMBLE Phase 3 study evaluated aztreonam-avibactam in serious infections involving metallo-beta-lactamase-producing Gram-negative pathogens.
Only 12 patients received aztreonam-avibactam in the relevant treatment arm.
All-cause adverse events were reported in 11 of 12 patients, while treatment-related adverse events occurred in 2 patients. Serious adverse events occurred in 5 patients, with no treatment-related serious adverse events reported.
Because of the small sample size, these figures should not be used to estimate the general frequency of aztreonam-avibactam side effects.
REJUVENATE Phase 2 Safety Findings
The earlier REJUVENATE Phase 2a study included 34 adults with complicated intra-abdominal infections.
Reported adverse events included:
- Hepatic enzyme increases: 26.5%
- Diarrhea: 14.7%
The study did not identify new safety concerns, but its smaller sample size and earlier development stage mean that current regulatory product information remains the more appropriate source for approved-product safety information.
U.S. and European Aztreonam Avibactam Safety Information
Safety information is not identical across all regulatory jurisdictions.
| Safety area | U.S. information | European/UK information |
|---|---|---|
| Component hypersensitivity | Contraindication | Contraindication |
| Other severe beta-lactam allergy | Focuses on product-component hypersensitivity | Explicit severe beta-lactam hypersensitivity wording |
| Hepatic effects | Hepatic adverse reactions and monitoring emphasized | Liver enzyme elevations and monitoring emphasized |
| C. difficile | Explicit warning | Explicit warning |
| Serious skin reactions | TEN warning | TEN and other serious skin reactions listed |
| Renal function | CrCl monitoring and dose adjustment important | Renal considerations plus neurological warning |
| Neurological effects | Historical aztreonam reactions distinguished from Trial 1 | Neurological effects discussed with renal impairment/overdose |
| Pediatric use | Not established under 18 | Not established under 18 |
For this reason, the current local prescribing information should be consulted before making clinical decisions.
Frequently Asked Questions About Aztreonam Avibactam Side Effects
What are the most common aztreonam avibactam side effects?
Current U.S. labeling identifies hepatic adverse reactions, anemia, diarrhea, hypokalemia and pyrexia among adverse reactions occurring in more than 5% of patients in the pivotal trial.
Can aztreonam-avibactam cause an allergic reaction?
Yes. Hypersensitivity reactions have been reported, including rash, flushing and bronchospasm. Severe allergic reactions are an important safety consideration.
Can aztreonam-avibactam affect the liver?
Yes. Hepatic adverse reactions and liver enzyme elevations have been reported. Not every hepatic adverse reaction represents severe liver injury.
Can aztreonam-avibactam cause diarrhea?
Yes. Diarrhea is a reported adverse reaction. Antibiotic-associated C. difficile diarrhea is also an important warning.
Does aztreonam-avibactam affect kidney function?
Renal function is important because both components are substantially renally eliminated. Reduced renal function can increase exposure and may require dose adjustment.
Can aztreonam-avibactam cause neurological problems?
Neurological events are included in European product information, particularly in the context of renal impairment or excessive beta-lactam exposure. Some events in U.S. labeling relate to historical aztreonam experience.
Is aztreonam-avibactam safe during pregnancy?
Pregnancy data for the combination are limited. Treatment decisions should be based on the applicable product information and clinical assessment.
Can children receive aztreonam-avibactam?
Safety and effectiveness in patients younger than 18 years have not been established in the cited U.S. and European product information.
Are aztreonam avibactam side effects the same in every country?
Not necessarily. Regulatory product information can differ between the U.S., Europe and other regions, including differences in contraindications, warnings and adverse-reaction terminology.
Where can I find aztreonam-avibactam dosage information?
For detailed dosing, administration and infusion information, refer to the dedicated aztreonam avibactam dosage and administration guide. Renal dose adjustment is covered separately in the aztreonam avibactam renal dosing article.
Conclusion
Understanding aztreonam avibactam side effects is important when evaluating the safety of this antibacterial combination.
Commonly reported adverse reactions include hepatic adverse reactions, anemia, diarrhea, hypokalemia and pyrexia. Important warnings include hypersensitivity reactions, serious skin reactions, hepatic effects and C. difficile-associated diarrhea.
Renal function is also an important safety consideration because both components are substantially renally eliminated. Reduced renal function can increase drug exposure and may require appropriate dose adjustment.
Safety information can vary between regulatory jurisdictions, so the current prescribing information for the specific product and country should always be consulted.
Medical Disclaimer: This article is intended for educational and informational purposes only. It does not replace current prescribing information or advice from a qualified healthcare professional. Safety information may vary by product and regulatory jurisdiction.