Aztreonam avibactam drug interactions are an important consideration when this intravenous antibacterial combination is used with other medicines. Current prescribing information identifies particular concern with organic anion transporter (OAT) 1 and OAT 3 inhibitors such as probenecid, while available data suggest that aztreonam-avibactam has relatively low interaction potential through major CYP enzymes and several hepatic or renal transporters.
Because aztreonam-avibactam is primarily eliminated through the kidneys, medicines that affect renal transport or renal function may be clinically relevant. The interaction profile should therefore be considered together with the patient’s renal function, concomitant medicines and applicable product information.
Important: This article is for educational purposes. Drug-interaction information may differ between regulatory jurisdictions and individual products. Always check the current prescribing information and consult a qualified healthcare professional before combining medicines.
Aztreonam Avibactam Drug Interactions at a Glance
The current U.S. prescribing information has a specific drug-interaction section covering OAT1/OAT3 transport inhibitors.
The key points are:
- Concomitant use of OAT1/OAT3 inhibitors such as probenecid is not recommended with EMBLAVEO.
- There is insufficient information to fully characterize the effect of OAT1/OAT3 inhibitors on aztreonam-avibactam.
- Avibactam is a substrate of OAT1 and OAT3 transporters.
- Aztreonam is also associated with OAT1/OAT3 renal transport.
- Aztreonam is not metabolized by CYP enzymes.
- Avibactam has not shown significant CYP inhibition or induction at clinically relevant concentrations.
- No drug-drug interaction was observed between aztreonam, avibactam and metronidazole in clinical studies.
European product information similarly states that co-dosing with probenecid is not recommended because a clinical interaction study has not been conducted.
Probenecid and Aztreonam Avibactam
Probenecid is the most specifically identified medicine in the current interaction information for aztreonam-avibactam.
Probenecid is a potent inhibitor of OAT transporters. In vitro data showed that probenecid inhibited uptake of avibactam through these transport pathways by approximately 56% to 70%. This creates the potential to alter avibactam elimination.
However, an important distinction is that this interaction has not been adequately characterized in a dedicated clinical interaction study with aztreonam-avibactam.
For this reason, current U.S. labeling does not recommend concomitant use of OAT1/OAT3 inhibitors such as probenecid with EMBLAVEO.
Why Does Probenecid Matter?
Avibactam is eliminated predominantly through the kidneys and is a substrate of OAT1 and OAT3.
When these transport pathways are inhibited, the elimination of avibactam could potentially be altered.
This is different from saying that a clinically significant interaction has definitely been demonstrated in patients.
The more accurate statement is:
Probenecid may affect avibactam elimination, and concomitant use is not recommended because the clinical effect has not been adequately characterized.
Aztreonam Avibactam and OAT1/OAT3 Inhibitors
OAT1 and OAT3 are renal organic anion transporters involved in the active uptake of certain substances from the blood into renal tubular cells.
Both aztreonam and avibactam are associated with these transport pathways.
Current U.S. labeling specifically identifies OAT1/OAT3 inhibitors as an interaction category.
The important clinical point is that the interaction information is not simply about one particular drug.
Healthcare professionals should consider whether a patient’s medication list contains an OAT1/OAT3 inhibitor, especially when evaluating medicines such as probenecid.
The current label states that there is insufficient information to characterize the effect of concomitant OAT1/OAT3 transporter inhibitors with EMBLAVEO.
Does Aztreonam Avibactam Interact with CYP Enzymes?
Available evidence suggests that CYP-mediated drug interactions are unlikely to be a major interaction pathway for aztreonam-avibactam.
Aztreonam is not metabolized by cytochrome P450 enzymes.
In vitro studies also found that avibactam did not significantly inhibit the major CYP enzymes and did not induce CYP enzymes at clinically relevant exposure levels.
This means that aztreonam-avibactam does not have the same type of CYP-based interaction profile seen with some medicines that strongly inhibit or induce CYP3A4, CYP2C9 or other CYP enzymes.
However, this should not be interpreted as meaning that aztreonam-avibactam cannot interact with any other medicine.
Other mechanisms, especially renal transport, renal function and product compatibility, remain relevant.
Aztreonam Avibactam and Metronidazole
Metronidazole is relevant because it may be administered alongside aztreonam-avibactam in certain treatment settings.
Current U.S. prescribing information reports that no drug-drug interaction was observed between aztreonam, avibactam and metronidazole in clinical studies.
European assessment information also describes the available interaction data for avibactam and metronidazole without identifying a clinically significant interaction.
Therefore, metronidazole is not identified as the principal drug-interaction concern in current aztreonam-avibactam labeling.
Aztreonam Avibactam and Other Antibiotics
Aztreonam-avibactam can be used in clinical settings where other antibacterial medicines may also be involved.
Current U.S. information reports that in vitro studies did not demonstrate antagonism between EMBLAVEO and several antibacterial agents, including:
- Amikacin
- Ciprofloxacin
- Colistin
- Daptomycin
- Gentamicin
- Levofloxacin
- Linezolid
- Metronidazole
- Tigecycline
- Tobramycin
- Vancomycin
These findings are in vitro data and should not be interpreted as a blanket clinical recommendation to combine aztreonam-avibactam with every listed antibiotic.
The appropriate antibacterial regimen depends on the infection, susceptibility results, patient factors and current clinical guidance.
Aztreonam Avibactam and Nephrotoxic Medicines
Renal function is important when considering the overall safety of aztreonam-avibactam.
European product information specifically notes that concomitant treatment with nephrotoxic products, such as aminoglycosides, may adversely affect renal function. It recommends monitoring creatinine clearance in patients with changing renal function and adjusting Emblaveo accordingly.
This is an important distinction:
A medicine does not necessarily have to directly interact with aztreonam or avibactam pharmacokinetically to be clinically relevant.
A concomitant medicine that affects kidney function may indirectly affect the exposure and dosing requirements of renally eliminated medicines.
Examples of medicines requiring clinical consideration can include certain nephrotoxic antibacterial agents.
The exact combination and patient’s renal status should be assessed by the treating healthcare professional.
Aztreonam Avibactam and Oral Anticoagulants
European product information includes an additional precaution concerning coagulation.
Prolongation of prothrombin time has been reported with aztreonam. Therefore, appropriate monitoring is recommended when oral anticoagulants are prescribed concomitantly, and anticoagulant dose adjustment may be necessary to maintain the desired level of anticoagulation.
This information should be distinguished from the specific OAT1/OAT3 interaction described in U.S. labeling.
In other words, the interaction profile can involve different mechanisms:
- Renal transporter interactions
- Renal-function-related effects
- Laboratory or coagulation considerations
- Product compatibility issues
Aztreonam Avibactam and Other Renal Transporters
Available in vitro data indicate that avibactam does not significantly inhibit several major renal or hepatic transporters at clinically relevant concentrations.
These include transporters such as:
- OAT1
- OAT3
- OATP1B1
- OATP1B3
- BSEP
- MRP4
- OCT1
- OCT2
Avibactam was identified as a substrate of human OAT1 and OAT3 in transporter studies.
These findings support the conclusion that the overall transporter-mediated interaction potential is relatively limited, while OAT1/OAT3 inhibition remains the specifically identified concern.
Aztreonam Avibactam Drug Compatibility During IV Administration
Drug interactions and drug compatibility are related but are not the same thing.
Current U.S. product information states that EMBLAVEO is compatible with specific diluents used for preparation and administration, including:
- Sterile Water for Injection for reconstitution
- 0.9% Sodium Chloride Injection
- 5% Dextrose Injection
- Lactated Ringer’s Injection
However, compatibility with other medicinal products has not been established.
The U.S. label states that EMBLAVEO should not be mixed with or physically added to solutions containing other medicinal products.
This is a physical/administration compatibility issue, rather than evidence of a systemic drug-drug interaction.
For detailed reconstitution and infusion instructions, refer to the dedicated aztreonam avibactam dosage and administration resource.
Aztreonam Avibactam and Renal Impairment
Renal impairment deserves separate consideration when reviewing potential interactions.
Both aztreonam and avibactam are substantially dependent on renal elimination.
When renal function changes, exposure can change even if no direct drug-drug interaction occurs.
This is why medicines that:
- Alter renal function
- Affect renal transport
- Are themselves nephrotoxic
- Require renal dose adjustment
may be particularly relevant in a patient receiving aztreonam-avibactam.
For detailed creatinine-clearance-based dosing, see:
Aztreonam Avibactam Renal Dosing: Dose Adjustment by Creatinine Clearance
Important Points About Aztreonam Avibactam Interactions
The current interaction evidence can be summarized as follows:
| Medicine / interaction category | What current information indicates |
|---|---|
| Probenecid | Concomitant use not recommended |
| OAT1/OAT3 inhibitors | Concomitant use not recommended due to insufficient characterization |
| Metronidazole | No drug-drug interaction observed in clinical studies |
| CYP inhibitors/inducers | Major CYP-mediated interaction not expected |
| Nephrotoxic medicines | May adversely affect renal function; monitor renal function |
| Oral anticoagulants | European information recommends appropriate coagulation monitoring |
| Other IV medicines | Compatibility may not be established; do not mix unless compatibility is documented |
How to Check for Aztreonam Avibactam Drug Interactions
Before aztreonam-avibactam treatment, the healthcare professional should review the patient’s complete medication list.
This can include:
- Prescription medicines
- Over-the-counter medicines
- Antibiotics
- Anticoagulants
- Medicines affecting kidney function
- Probenecid or other relevant transporter inhibitors
- Supplements and other products
A medication review is particularly important in patients with renal impairment, multiple chronic medicines or changing kidney function.
Patients should not stop a prescribed medicine simply because a potential interaction is mentioned online. The treating healthcare professional should determine whether the medicine should be continued, changed, monitored or avoided.
Frequently Asked Questions About Aztreonam Avibactam Drug Interactions
Does aztreonam-avibactam interact with probenecid?
Yes. Current U.S. and European product information identifies probenecid as a concern because it inhibits OAT transporters involved in avibactam uptake and renal elimination. Concomitant use is not recommended.
Can aztreonam-avibactam be given with metronidazole?
Current U.S. information reports no drug-drug interaction between aztreonam, avibactam and metronidazole in clinical studies.
Does aztreonam-avibactam interact with CYP3A4?
Aztreonam is not metabolized by CYP enzymes, and avibactam has not shown significant CYP inhibition or induction at clinically relevant concentrations.
Can aztreonam-avibactam affect kidney function?
Renal function is clinically important because both components are substantially renally eliminated. Some concomitant nephrotoxic medicines may adversely affect renal function.
Can aztreonam-avibactam be given with aminoglycosides?
European product information notes that concomitant nephrotoxic products such as aminoglycosides may adversely affect renal function. The appropriateness of a combination should therefore be assessed clinically, with renal monitoring when indicated.
Does aztreonam-avibactam interact with blood thinners?
European product information recommends appropriate monitoring when oral anticoagulants are used concomitantly because prolongation of prothrombin time has been reported with aztreonam.
Can aztreonam-avibactam be mixed with other IV medicines?
Not unless compatibility has been established. Current U.S. labeling states that compatibility with other medicinal products has not been established and the product should not be mixed with solutions containing other medicines.
Conclusion
Aztreonam avibactam drug interactions are primarily relevant through renal transport, renal function and certain medication-specific safety considerations.
The most clearly identified interaction concern is with OAT1/OAT3 inhibitors such as probenecid, for which concomitant use is not recommended in current U.S. labeling. Available evidence does not suggest a major CYP-mediated interaction pathway, and no drug-drug interaction was observed between aztreonam, avibactam and metronidazole in clinical studies.
Other medicines can still be clinically relevant because of their effects on kidney function, coagulation or IV compatibility.
For that reason, a complete medication review and the current product-specific prescribing information should be used when evaluating potential interactions.
Medical Disclaimer: This article is for educational and informational purposes only. It does not replace current prescribing information or individualized advice from a qualified healthcare professional. Drug-interaction information can vary by product and regulatory jurisdiction.