Cefadroxil (cefadroxil)

In patients with creatinine clearances of 50 mL/minute per 1.73 m2 or lower, doses and/or frequency of administration of cefadroxil must be modified in response to the degree of renal impairment. The manufacturers recommend that adults receive an initial dose of 1 g followed by 500-mg maintenance doses at the following dosage intervals based on the patient's creatinine clearance: (See Table 1.)

Table 1. Adult Dosage of Cefadroxil in Renal Impairment

Clcr (mL/min per 1.73 Initial Dose Maintenance Dosage m2) 25-50 1 g 500 mg every 12 hours 10-25 1 g 500 mg every 24 hours 0-10 1 g 500 mg every 36 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)

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There are no contraindication contraindications for this drug.

• Clostridioides difficile infection

• Renal disease with mild to moderate renal function impairment

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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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