Cefazolin In 0.9% Sod Chloride (cefazolin sodium in 0.9 % sodium chloride)

Dosage of cefazolin sodium is expressed in terms of cefazolin and is identical for IM or IV administration.

To avoid unintentional overdosage, the commercially available Duplex(R) drug delivery system containing cefazolin and dextrose injection and the commercially available frozen premixed cefazolin injection in dextrose should not be used in patients who require less than the entire 1- or 2-g dose in the container.

In patients with impaired renal function, doses and/or frequency of administration of cefazolin must be modified in response to the degree of impairment, severity of the infection, susceptibility of the causative organism, and serum concentrations of the drug.

The manufacturers recommend an initial loading dose appropriate for the severity of the infection followed by dosage based on the degree of renal impairment. (See Table 1 and Table 2.)

Table 1. Dosage for Adults with Renal Impairment

Creatinine Clearance (mL/minute) Dosage After Initial Loading Dose 35-54 Full doses at intervals >=8 hours 11-34 50% of usual dose every 12 hours <=10 50% of usual dose every 18-24 hours

Table 2. Dosage for Children Older than 1 Month of Age with Renal Impairment

Creatinine Clearance (mL/minute) Dosage After Initial Loading Dose 40-70 60% of usual daily dosage in divided doses every 12 hours 20-40 25% of usual daily dosage in divided doses every 12 hours 5-20 10% of usual daily dosage once every 24 hours

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Selected Cephalosporins & Penicillins/Probenecid

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Probenecid impairs the clearance of some cephalosporins and penicillins via inhibition of renal anion transporters in the proximal tubule.(49) It has also been hypothesized that probenecid may affect tissue distribution of cephalosporins.(1-5)

CLINICAL EFFECTS: The concurrent administration of probenecid may result in increased maximum concentration (Cmax), area-under-curve (AUC), and half-life of the cephalosporin or penicillin.(49) While this may improve antibiotic efficacy,(46-48) increased levels may also increase the risk for antibiotic-associated nephrotoxicity.(4)

PREDISPOSING FACTORS: Underlying renal dysfunction may increase the risk for nephrotoxicity.

PATIENT MANAGEMENT: In patients receiving the combination to improve antibiotic efficacy, monitor for antibiotic adverse effects and consider monitoring renal function. In patients receiving probenecid therapy to prevent or treat hyperuricemia, exposure to the antibiotic will be increased. A decrease in antibiotic dose or frequency may be required. The US manufacturer of piperacillin-tazobactam states probenecid should not be coadministered with piperacillin-tazobactam unless the benefit outweighs the risk.(50)

DISCUSSION: Concurrent use of probenecid with a cephalosporin or penicillin may cause an increase in the Cmax, AUC, and an increased elimination half life of the antibiotic.(6-8,49) This may be beneficial or necessary in difficult to treat infections,(46-48) but an increased risk for adverse effects should be expected. Antibiotics not dose adjusted for concurrent use with probenecid may be associated with an increased risk for adverse effects, such as nephrotoxicity. Probenecid administered concurrently with piperacillin-tazobactam prolongs the half-life of piperacillin by 21% and tazobactam by 71%. In a study in 8 healthy males, concurrent administration of probenecid (1 g) with piperacillin (1 g IM) increased piperacillin's Cmax and AUC by 30% and 60%. Renal clearance was reduced by 40%.(51) The cephalosporins affected by probenecid include cefazolin,(9-11) cephacetrile,(12,13) cephaloglycin,(14,15) cephalexin,(16-21) cephradine, (22-23) cefoxitin,(24-28) cefadroxil(29), cefaclor,(23) cefamandole,(30) ceftizoxime,(31,32) cefuroxime,(33,34) cefprozil,(35) cefonicid,(36) cefmetazole,(37) cefmenoxime,(38) and cefditoren.(39) Probenecid has been shown not to affect moxalactam,(4,40,41) ceforanide, (4,42), cefoperazone, ceftazidime(4,34,43) or ceftriaxone.(4)

Slt Cephalosporins/Slt Anticoagulants (VIT K ANTAGONISTS)

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown, but may involve a combination of cephalosporin induced platelet inhibition and alteration of gut flora.

CLINICAL EFFECTS: Concurrent use of some cephalosporins may increase the hypoprothrombinemic effect of the anticoagulant with possible bleeding.

PREDISPOSING FACTORS: High doses, hepatic and/or renal impairment, and poor nutrition may increase the risk of bleeding. The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs).

PATIENT MANAGEMENT: Monitor prothrombin activity and adjust the anticoagulant dosage accordingly. Consider using an alternative antibiotic. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug.

DISCUSSION: Although the majority of cephalosporins that have been documented to interact with anticoagulants have a NMTT side chain, there are reports of interactions with cefazolin, cefoxitin, ceftaroline, and ceftriaxone as well. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. A large systematic review was performed on 72 warfarin drug-drug interactions studies that reported on bleeding, thromboembolic events, or death. Most studies were retrospective cohorts. A meta-analysis of 11 of those studies found a higher rate of clinically significant bleeding in patients on warfarin and antimicrobials (OR=1.63; 95% CI 1.45-1.83). Increased bleeding risk was also seen in subgroup analyses with cephalosporins (OR=1.50; 95% CI 1.21-1.86).

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There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 2 (mild) GFR 60-89 ml/min
• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Clostridioides difficile infection

• Hypoprothrombinemia

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Rare or Very Rare

• Abnormal hepatic function tests
• Acute generalized exanthematous pustulosis
• Agranulocytosis
• Anaphylaxis
• Angioedema
• Aplastic anemia
• Candidiasis
• Cholestasis
• Clostridioides difficile infection
• Colitis
• DRESS syndrome
• Eosinophilia
• Erythema multiforme
• Hallucinations
• Hemolytic anemia
• Hemorrhage
• Hepatitis
• Hyperbilirubinemia
• Hypersensitivity drug reaction
• Hypoprothrombinemia
• Interstitial nephritis
• Jaundice
• Kidney disease with reduction in glomerular filtration rate (GFr)
• Myocardial ischemia
• Myoclonus
• Obstructive hyperbilirubinemia
• Pancytopenia
• Pemphigus
• Pruritus of skin
• Renal failure
• Seizure disorder
• Serum sickness
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Toxic epidermal necrolysis
• Urticaria

More Frequent

• Acute abdominal pain
• Diarrhea
• Dyspepsia
• Nausea
• Vomiting

Less Frequent

• Gastritis
• Vulvovaginal candidiasis

Rare or Very Rare

• Acute cognitive impairment
• Agitation
• Arthralgia
• Dizziness
• Drug fever
• Fatigue
• Genital organ pruritus
• Headache disorder
• Paresthesia
• Phlebitis after infusion
• Prolonged prothrombin time
• Pruritus ani
• Skin rash
• Vaginitis

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