ceftazidime/avibactam (Rx)

Brand and Other Names:Avycaz

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

ceftazidime/avibactam

injection, powder of reconstitution

  • (2g/0.5g)/vial: 2.5g
  • Equivalent to 2.635 grams of ceftazidime pentahydrate/sodium carbonate powder and 0.551 grams of avibactam sodium

Intra-abdominal Infections

Indicated in combination with metronidazole for complicated intra-abdominal infections (cIAIs) caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa

2.5 g (2 g/0.5 g) IV q8hr infused over 2 hr for 5-14 days

Urinary Tract Infections

Indicated for complicated urinary tract infections (cUTIs) including pyelonephritis caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa

2.5 g (2 g/0.5 g) IV q8hr infused over 2 hr for 7-14 days

Bacterial Pneumonia

Indicated for hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by the following susceptible gram negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae

2.5 g (2 g/0.5 g) IV q8hr infused over 2 hr for 7-14 days

Dosage Modifications

Renal impairment

  • CrCl >50 mL/min: No dose adjustment required
  • CrCl 31-50 mL/min: 1.25 g (1 g/0.25 g) IV q8hr
  • CrCl 16-30 mL/min: 0.94 g (0.75 g/0.19 g) IV q12hr
  • CrCl 6-15 mL/min: 0.94 g (0.75 g/0.19 g) IV q24hr
  • CrCl <5 mL/min: 0.94 g (0.75 g/0.19 g) IV q48hr
  • Hemodialysis: Administer after hemodialysis on hemodialysis days

Dosing Considerations

To reduce the development of drug-resistant bacteria and maintain the effectiveness, use only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria

Dosage Forms & Strengths

ceftazidime/avibactam

injection, powder of reconstitution

  • (2g/0.5g)/vial: 2.5g
  • Equivalent to 2.635 grams of ceftazidime pentahydrate/sodium carbonate powder and 0.551 grams of avibactam sodium

Intra-abdominal Infections

Indicated in combination with metronidazole for complicated intra-abdominal infections (cIAIs) in adult and pediatric patients (aged ≥3 months) caused by the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa

<3 months: Safety and efficacy not established

3 months to <6 months: 50 mg/kg (ceftazidime 40 mg/kg and avibactam 10 mg/kg) IV q8hr for 5-14 days

6 months to <2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 5-14 days

2 years to <18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 5-14 days; not to exceed 2.5 grams/dose (ceftazidime 2 grams and avibactam 0.5 grams)

Urinary Tract Infections

Indicated for complicated urinary tract infections (cUTIs) including pyelonephritis in adult and pediatric patients (aged ≥3 months) caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, and Pseudomonas aeruginosa

<3 months: Safety and efficacy not established

3 months to <6 months: 50 mg/kg (ceftazidime 40 mg/kg and avibactam 10 mg/kg) IV q8hr for 7-14 days

6 months to <2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to <18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams/dose (ceftazidime 2 grams and avibactam 0.5 grams)

Bacterial Pneumonia

Indicated for treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adult and pediatric patients (aged ≥3 months) caused by the following susceptible Gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae

<3 months: Safety and efficacy not established

3 months to <6 months: 50 mg/kg (ceftazidime 40 mg/kg and avibactam 10 mg/kg) IV q8hr for 7-14 days

6 months to <2 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days

2 years to <18 years: 62.5 mg/kg (ceftazidime 50 mg/kg and avibactam 12.5 mg/kg) IV q8hr for 7-14 days; not to exceed 2.5 grams/dose (ceftazidime 2 grams and avibactam 0.5 grams)

Dosage Modifications

Renal impairment

  • For patients (≥2 years) with eGFR ≤50 mL/min/1.73 m² dosage adjustments are recommended
  • eGFR 31-50 mL/min/1.73 m²: 31.25 mg/kg (ceftazidime 25 mg/kg and avibactam 6.25 mg/kg) IV q8hr; not to exceed 1.25 grams (ceftazidime 1 gram and avibactam 0.25 grams)
  • eGFR 16-30 mL/min/1.73 m²: 23.75 mg/kg (ceftazidime 19 mg/kg and avibactam 4.75 mg/kg) IV q12hr; not to exceed 0.94 grams (ceftazidime 0.75 gram and avibactam 0.19 grams)
  • eGFR 6-15 mL/min/1.73 m²: 23.75 mg/kg (ceftazidime 19 mg/kg and avibactam 4.75 mg/kg) IV q24hr; not to exceed 0.94 grams (ceftazidime 0.75 gram and avibactam 0.19 grams)
  • eGFR ≤5 mL/min/1.73 m²: 23.75 mg/kg (ceftazidime 19 mg/kg and avibactam 4.75 mg/kg) IV q48hr; not to exceed 0.94 grams (ceftazidime 0.75 gram and avibactam 0.19 grams)
  • Hemodialysis: Administer after hemodialysis on hemodialysis days

Carefully monitor renal function in patients aged >65 yr

Dosage adjustment for elderly patients should be based on renal function (see Dosage Modifications)

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Interactions

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              Serious - Use Alternative (2)

              • cholera vaccine

                ceftazidime/avibactam, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.

              • microbiota oral

                ceftazidime/avibactam decreases effects of microbiota oral by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Microbiota oral contains bacterial spores. Antibacterial agents may decrease efficacy if coadministered. Complete antibiotic regimens 2-4 days before initiating microbiota oral. .

              Monitor Closely (2)

              • probenecid

                probenecid increases levels of ceftazidime/avibactam by decreasing renal clearance. Use Caution/Monitor. Avoid, coadministration not recommended according to the prescribing information. In vitro, probenecid inhibits uptake of avibactam by OATP1 and OATP3 transporters in the kidney by 56-70%. This may result in decreased renal elimination of avibactam.

              • voclosporin

                voclosporin, ceftazidime/avibactam. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.

              Minor (0)

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                Adverse Effects

                1-10% (cIAI plus metronidazole)

                Diarrhea (8%)

                Nausea (7%)

                Vomiting (5%)

                Headache (3%)

                Dizziness (2%)

                Abdominal pain (1%)

                1-10% (cUTI in pediatric patients)

                Vomiting (>3%)

                Diarrhea (>3%)

                Rash (>3%)

                Infusion site phlebitis (>3%)

                1-10% (cUTI)

                Diarrhea (3%)

                Nausea (3%)

                Constipation (2%)

                Upper abdominal pain (1%)

                1-10% (HABP/VABP)

                Nausea (3%)

                Pruritus (2%)

                Frequency Not Reported

                Blood and lymphatic disorders: Thrombocytopenia, thrombocytosis, leukopenia

                General disorders and administration site conditions: Injection site phlebitis

                Infections and infestations: Candidiasis

                Investigations: Increased aspartate aminotransferase, increased alanine aminotransferase, increased gamma-glutamyltransferase

                Metabolism and nutrition disorders: Hypokalemia

                Nervous system disorders: Dysgeusia

                Renal and urinary disorders: Acute kidney injury, renal impairment, nephrolithiasis

                Skin and subcutaneous tissue disorders: Rash, rash maculopapular, urticaria

                Psychiatric disorders: Anxiety

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                Warnings

                Contraindications

                Known serious hypersensitivity to avibactam, ceftazidime, or other cephalosporins

                Cautions

                In clinical trials, cure rates were lower in patients with baseline moderate renal impairment (CrCl 30-50 mL/min) who were treated for cIAI with ceftazidime/avibactam plus metronidazole (45% cure rate) compared with meropenem (74% cure rate); during the clinical trial, the ceftazidime/avibactam dose was 33% lower than what is currently recommended for patients with moderate renal impairment (see Dosage Modifications); follow current dosage adjustment recommendations for renal impairment

                Serious and occasionally fatal anaphylactic reactions and serious skin reactions have been reported with beta-lactam antibacterials; caution in patients with history of allergy to cephalosporins, penicillins, or carbapenems; exercise caution if this product is to be given to a penicillin or other beta-lactam-allergic patient; cross sensitivity among beta-lactam antibacterial drugs established; discontinue drug if allergic reaction occurs

                Seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with ceftazidime, especially in the setting of renal impairment; adjust dose according to CrCl (see Dosage Modifications)

                Confirm suspected bacterial infection when prescribing ceftazidime/avibactam to avoid the risk of developing drug-resistant bacteria; prescribing antibiotics in absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to patient and increases risk of development of drug-resistant bacteria

                Clostridium difficile-associated diarrhea

                • Clostridium difficile associated diarrhea (CDAD) has been associated with nearly all systemic antibacterials; severity may range from mild diarrhea to fatal colitis; may occur >2 months following antibacterial use; if CDAD suspected, manage fluid and electrolytes levels and monitor antibacterial treatment for CDAD
                • C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial use; careful medical history necessary because CDAD has been reported tooccur more than 2 months after administration of antibacterial drugs
                • If CDAD suspected or confirmed, antibacterial drugs not directed against C. difficile may need to be discontinued; manage fluid and electrolyte levels as appropriate, supplement protein intake, monitor antibacterial treatment of C. difficile, and institute surgical evaluation as clinically indicated

                Drug interactions overview

                • Avibactam is an OAT1/OAT3 substrate; probenecid, a potent OAT inhibitor, inhibits OAT uptake of avibactam by 56-70% and potentially decrease the elimination of avibactam when coadministered; therefore, coadministration of ceftazidime/avibactam with probenecid is not recommended
                • Ceftazidime administration may result in a false-positive reaction for glucose in the urine with certain methods; glucose tests based on enzymatic glucose oxidase reactions be used
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                Pregnancy & Lactation

                Pregnancy

                There are no adequate and well-controlled studies of ceftazidime/avibactam, ceftazidime, or avibactam in pregnant women

                Neither ceftazidime nor avibactam were teratogenic in rats at doses 40 and 9 times the recommended human clinical dose; in the rabbit, at twice the exposure as seen at the human clinical dose, there were no effects on embryofetal development with avibactam

                Because animal reproduction studies are not always predictive of human response, this drug should be used in pregnancy only if clearly needed

                Lactation

                Ceftazidime is excreted in human milk in low concentrations

                Unknown whether avibactam is excreted into human milk, although avibactam was shown to be excreted in the milk of rats

                No information is available on the effects of ceftazidime and avibactam on the breastfed child or on milk production

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Ceftazidime: Third-generation cephalosporin with broad-spectrum gram-negative activity, including Pseudomonas; arrests bacterial growth by binding to 1 or more penicillin-binding proteins, and thereby inhibiting final transpeptidation step of peptidoglycan synthesis in bacterial cell-wall synthesis and inhibiting cell-wall biosynthesis

                Avibactam: Diazabicyclooctanone, non-β-lactam, β-lactamase inhibitor; alone has no antibacterial activity at clinically relevant doses; when combined with ceftazidime, avibactam protects ceftazidime from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of ceftazidime to include many gram-negative bacteria normally not susceptible to ceftazidime

                Absorption

                Ceftazidime

                • Peak plasma concentration: 88.1 mg/L (single 2.5 g-dose); 90.4 mg/L (multiple 2.5 g-dose)
                • AUC: 289 mg·h/L (single 2.5 g-dose); 291 mg·h/L (multiple 2.5 g-dose)

                Avibactam

                • Peak plasma concentration: 15.2mg/L (single 2.5 g-dose); 14.6 mg/L (multiple 2.5 g-dose)
                • AUC: 42.1 mg·h/L (single 2.5 g-dose); 38.2 mg·h/L (multiple 2.5 g-dose)

                Distribution

                Protein bound: <10% (ceftazidime); 5.7-8.2% (avibactam)

                Ceftazidime

                • Vd (steady-state): 18.1 L (single 2.5 g-dose); 17 L (multiple 2.5 g-dose)

                Avibactam

                • Vd (steady-state): 23.2 L (single 2.5 g-dose); 22.2 L (multiple 2.5 g-dose)

                Metabolism

                80-90% of ceftazidime IV dose is eliminated unchanged via the urine

                Nearly 100% of avibactam IV dose is eliminated unchanged via the urine

                Elimination

                Ceftazidime

                • Half-life: 3.27 hr (single 2.5 g-dose); 2.76 hr (multiple 2.5 g-dose)
                • Clearance (L/h): 6.93 L/h (single 2.5 g-dose); 6.86 L/h (multiple 2.5 g-dose)
                • Excretion: Urine (~80- 90% as unchanged drug)

                Avibactam

                • Half-life: 2.22 hr (single 2.5 g-dose); 2.71hr (multiple 2.5 g-dose)
                • Clearance (L/h): 11.9 L/h (single 2.5 g-dose); 13.1 L/h (multiple 2.5 g-dose)
                • Excretion, single 0.5 g-dose: Urine (97%); feces (0.2%)
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                Administration

                IV Compatibilities

                0.9% NaCl

                D5W

                All combinations of dextrose and sodium chloride injection containing up to 2.5% dextrose and 0.45% NaCl

                Lactated Ringer injection

                Y-site compatibility

                • Compatible drugs for use with 0.9% NaCl, D5W or Lactated Ringer injection as diluents
                  • Daptomycin
                  • Dexmedetomidine HCl
                  • Dopamine HCl
                  • Furosemide
                  • Gentamicin sulfate
                  • Imipenem-cilastatin
                  • Magnesium sulfate
                  • Norepinephrine bitartrate
                  • Phenylephrine HCl
                  • Vasopressin
                  • Vecuronium bromide
                • Compatible drugs for use with 0.9% NaCl or D5W as diluents
                  • Ertapenem sodium
                  • Potassium phosphate
                  • Sodium glycerophosphate
                • Compatible drugs for use with D5W or Lactated Ringer injection as diluents
                  • Heparin sodium
                  • Linezolid
                  • Tobramycin sulfate
                • Compatible drugs for use with one compatible diluent only
                  • Meropenem (0.9% NaCl diluent only)
                  • Sodium bicarbonate (D5W diluent only)
                  • Tedizolid phosphate (D5W diluent only)
                  • Potassium chloride (Lactated Ringer injection diluent only)

                IV Preparation

                Reconstitute powder with 10 mL of one of the following solutions

                • Sterile water for injection
                • 0.9% NaCl
                • D5W
                • All combinations of dextrose and sodium chloride injection containing up to 2.5% dextrose and 0.45% NaCl
                • Lactated Ringer injection
                • Upon reconstitution, solution may be held for no longer than 30 minutes before transferring and further diluting in a suitable infusion bag

                Additional dilution required

                • Mix vial gently with 10 mL of a solution listed above
                • For adults and pediatric patient (≥40 kg), reconstituted solution results in 167 mg/mL of ceftazidime and 42 mg/mL of avibactam; final volume is ~12 mL
                • For pediatric patients (<40 kg), reconstitute solution with a final concentration of ceftazidime 167 mg/mL and avibactam 42 mg/mL
                • Further dilute with the same diluent used for reconstitution (except sterile water for injection), to achieve a total volume of 50-250 mL before infusion
                • Volume to withdraw from reconstituted vial for further dilution for patients (≥40 kg)
                  • 2.5 g (2 g/0.5 g): 12 mL (entire contents)
                  • 1.25 g (1 g/0.25 g): 6 mL
                  • 0.94 g (0.75 g/0.19 g): 4.5 mL
                • Mix gently and ensure contents are dissolved completely
                • Visually inspect for particulate matter and discoloration (color ranges from clear to light yellow)

                IV Administration

                Infuse IV over 2 hr

                Storage

                Unopened vials

                • Store at 25°C (77°F); excursion permitted between 15-30°C (59-86°F)
                • Protect from light

                Diluted solution

                • Stored at room temperature, 25°C (77°F) for up to 12 hr
                • Refrigerate at 2-8°C (36- 46°F) up to 24 hr following dilution and used within 12 hr of subsequent storage at room temperature
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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                Avycaz intravenous
                -
                2.5 gram vial
                Avycaz intravenous
                -
                2.5 gram vial

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

                Patient Education
                ceftazidime-avibactam intravenous

                CEFTAZIDIME/AVIBACTAM - INJECTION

                (sef-TAZ-i-deem/a-vi-BAK-tam)

                COMMON BRAND NAME(S): Avycaz

                USES: This medication is used to treat a wide variety of bacterial infections. This product contains 2 different medications: ceftazidime and avibactam. Ceftazidime is a cephalosporin antibiotic that works by stopping the growth of bacteria. Avibactam is an enzyme inhibitor (beta-lactamase inhibitor) that helps ceftazidime work better.This antibiotic treats only bacterial infections. It will not work for viral infections (such as common cold, flu). Using any antibiotic when it is not needed can cause it to not work for future infections.

                HOW TO USE: This medication is given by injection into a vein, as directed by your doctor, usually every 8 hours over 2 hours. The dosage and length of treatment are based on your medical condition and response to treatment. Children's dosage is also based on age and weight.If you are using this medication at home, learn all preparation and usage instructions from your health care professional. The solution is normally clear and light yellow. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.For the best effect, use this antibiotic at evenly spaced times. To help you remember, use this medication at the same time(s) every day.Continue to use this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may result in a return of the infection.Tell your doctor if your condition lasts or gets worse.

                SIDE EFFECTS: Nausea, vomiting, constipation, or anxiety may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: mental/mood changes (such as confusion, hallucinations), loss of consciousness, seizures, shaking (tremors), muscle spasms, jerking movements, easy bruising/bleeding, yellowing eyes/skin.This medication may rarely cause a severe intestinal condition due to a bacteria called C. difficile. This condition may occur during treatment or weeks to months after treatment has stopped. Tell your doctor right away if you develop: diarrhea that doesn't stop, abdominal or stomach pain/cramping, blood/mucus in your stool.If you have these symptoms, do not use anti-diarrhea or opioid products because they may make symptoms worse.Use of this medication for prolonged or repeated periods may result in oral thrush or a new yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

                PRECAUTIONS: Before using this medication, tell your doctor or pharmacist if you are allergic to ceftazidime or avibactam; or to penicillins, beta-lactam antibiotics, or other cephalosporins; or to other beta-lactamase inhibitors (such as sulbactam); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease.Ceftazidime/avibactam may cause live bacterial vaccines (such as typhoid vaccine) to not work well. Tell your health care professional that you are using ceftazidime/avibactam before having any immunizations/vaccinations.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.Ceftazidime passes into breast milk. It is unknown if avibactam passes into breast milk. Consult your doctor before breast-feeding.

                DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.One product that may interact with this drug is: probenecid.This medication may interfere with certain lab tests (such as Coombs' test, urine glucose tests), possibly causing false test results. Make sure lab personnel and all your doctors know you use this drug.

                OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

                NOTES: Do not share this medication with others.This medication has been prescribed for your current condition only. Do not use it later for another infection unless your doctor tells you to.Lab and/or medical tests (such as kidney function) should be done while you are using this medication. Keep all medical and lab appointments. Consult your doctor for more details.

                MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule. Do not double the dose to catch up.

                STORAGE: Consult the product instructions and your pharmacist for storage details. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

                Information last revised July 2023. Copyright(c) 2023 First Databank, Inc.

                IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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                Formulary

                FormularyPatient Discounts

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                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.