Ceftazidime and Avibactam

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Probenecid (Probalan)

This is not a complete list of ceftazidime/avibactam drug interactions. Ask your doctor or pharmacist for more information.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X - are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Ceftazidime/avibactam falls into category B. In animal studies, pregnant animals were given ceftazidime and avibactam, and some babies had minor problems. There are no well-done studies that have been done in humans with ceftazidime/avibactam.

Use ceftazidime/avibactam exactly as prescribed.

This medication is available in injectable form to be given directly into a vein (IV) by a healthcare professional.

If you miss a dose,the missed dose should be administered as soon as possible. If it is almost time for the next dose, skip the missed dose and administer the next dose at the regular time. Do not take 2 doses of ceftazidime/avibactam at the same time.

• It is used to treat bacterial infections.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Anxiety.
• Hard stools (constipation).
• Dizziness.
• Upset stomach or throwing up.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Aminoglycosides: Cephalosporins (3rd Generation) may enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Chloramphenicol: May diminish the therapeutic effect of CefTAZidime. Management: Consider using a different combination of antimicrobials, especially if bactericidal activity is desired. If these agents are combined, monitor for reduced antimicrobial effectiveness and/or therapeutic failure. Consider therapy modification

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Probenecid: May increase the serum concentration of Avibactam. Avoid combination

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Teriflunomide: May increase the serum concentration of OAT3 Substrates. Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Concerns related to adverse effects:

• Hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam drugs. Before initiating therapy, carefully investigate previous penicillin, cephalosporin, or carbapenem hypersensitivity. Use caution if given to a patient with a penicillin or other beta-lactam allergy; cross sensitivity has been established. If an allergic reaction occurs, discontinue and institute appropriate management.

• Neurotoxicity: Severe neurological reactions have been reported with ceftazidime, including asterixis, coma, encephalopathy, myoclonus, neuromuscular excitability, seizures, and nonconvulsive status epilepticus. Risk may be increased in the presence of renal impairment; ensure dose adjusted for renal function. Discontinue therapy if patient develops neurotoxicity.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: In a complicated intra-abdominal infection clinical trial, patients with a creatinine clearance (CrCl) of 30 to 50 mL/minute had lower clinical cure rates than those with CrCl >50 mL/minute; however, these patients received a daily dose that was 33% lower than what is currently recommended for patients with this degree of renal impairment. Decreased clinical response was not seen in patients with a baseline CrCl of 30 to 50 mL/minute in complicated UTI clinical trials. Monitor renal function at baseline and at least daily in patients with changing renal function. Adjust the dose accordingly.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitor for signs of anaphylaxis during first dose. Monitor renal function at baseline in all patients, and at least daily in patients with changing renal function.

Adverse events have not been observed in animal reproduction studies conducted with ceftazidime; adverse events have been observed in some animal reproduction studies conducted with avibactam.