Cefotan (cefotetan disodium)

Dosage of cefotetan disodium is expressed in terms of cefotetan.

In patients with renal impairment, doses and/or frequency of administration of cefotetan should be modified in response to the degree of renal impairment, type and severity of the infection, and susceptibility of the causative organisms.

The manufacturers and some clinicians recommend that adults with impaired renal function receive the following dosage of cefotetan given at dosage intervals based on the patient's creatinine clearance. (See Table 1.)

Table 1. Dosage of Cefotetan for Adults with Renal Impairment

Creatinine Clearance (mL/minute) Dosage >30 Usual dose every 12 hours 10-30 Usual dose every 24 hours or 50% of usual dose every 12 hours <10 Usual dose every 48 hours or 25% of usual dose every 12 hours Hemodialysis patients 25% of usual dose every 24 hours on days between dialysis and 50% of usual dose on the day of dialysis

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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)

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Selected Cephalosporins/Ethyl Alcohol

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Certain cephalosporins have a methyltetrazolethiol side chain that resembles part of the disulfiram molecule. It has been suggested that the cephalosporins with this side chain interfere with the activity of the alcohol-metabolizing enzyme, aldehyde dehydrogenase, resulting in elevated concentrations of acetaldehyde and a "disulfiram-like" reaction.(1)

CLINICAL EFFECTS: A disulfiram-like reaction may occur in patients who ingest alcohol during and after taking some cephalosporins. Symptoms include throbbing in the head and neck, palpitations, tachycardia, hypotension, sweating, nausea, and vomiting.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients receiving cephalosporins with a methyltetrazolethiol side chain should be cautioned about consuming alcohol during and for several days after therapy. Patients should be informed about unsuspected sources of alcohol such as elixirs and topical preparations. Alcohol is used to improve docetaxel and paclitaxel solubility. - The quantity of alcohol in paclitaxel injection formulations (0.385-0.396 grams/mL) is similar across manufacturers. A paclitaxel 200 mg dose contains approximately 13 grams of alcohol. - The quantity of alcohol in docetaxel formulations varies approximately 3-fold depending upon the manufacturer. FDA data on alcohol content (17) : Product Manufacturer Alcohol/200 mg dose Docetaxel Inj. Pfizer 6.4 grams Docetaxel Inj. Sandoz 5.5 grams Docetaxel Inj. Accord 4.0 grams Taxotere-one vial Sanofi 4.0 grams formulation Docetaxel Inj. Hospira 3.7 grams Docefrez Sun Pharma 2.9 grams Taxotere-two vial Sanofi 2.0 grams formulation

DISCUSSION: A disulfiram-like reaction has been reported following the ingestion of alcohol by patients receiving cefamandole,(2-4) cefoperazone, (5-7) cefotetan,(8) and moxalactam.(9-11) The reaction has been reported in patients who had been receiving the antibiotic periodically or continuously before alcohol consumption. The reaction occurred within 30 minutes of alcohol consumption.(5-7) In one patient, the reaction occurred after an injection of 15 ml of a 67% alcohol into the paraaortic space for celiac plexus alcohol block.(11) Cefonicid and ceforanide have exhibited these effects in animal studies. (12) However, another study showed that cefonicid did not interact with alcohol.(13) No interaction was found with cefazolin, cefotaxime, cefoxitin, cephalothin, or cephradine in animal studies.(14-15) A study in humans found no interaction with ceftizoxime.(1) These cephalosporins do not have a methyltetrazolethiol side chain. A single case reported a disulfiram-like reaction in a patient taking cefonicid therapy on two separate occasions.(16)

Slt Cephalosporins/Slt Anticoagulants (Vit K Antagonists)

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The exact mechanism is unknown, but may involve a combination of the cephalosporin's N-methylthiotetrazole (NMTT) side chain antagonizing vitamin K, 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 (INR) 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. 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: Cephalosporins with a NMTT side chain have been reported to significantly prolong bleeding time and cause hypoprothrombinemia; therefore, the risk of serious bleeding may be increased in patients taking concurrent anticoagulants. 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).

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.

• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Clostridioides difficile infection
• Hemolytic anemia

• Colitis
• Hypoprothrombinemia
• Kidney disease with likely reduction in glomerular filtration rate (GFr)

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More Frequent

• Hypoprothrombinemia

Less Frequent

• Abnormal hepatic function tests
• Hypersensitivity drug reaction

Rare or Very Rare

• Agranulocytosis
• Anaphylaxis
• Angioedema
• Autoimmune hemolytic anemia
• Clostridioides difficile infection
• Eosinophilia
• Erythema multiforme
• Leukopenia
• Nephrotoxicity
• Seizure disorder
• Serum sickness
• Stevens-johnson syndrome
• Thrombocytopenic disorder
• Thrombocytosis

More Frequent

• Vulvovaginal candidiasis

Less Frequent

• Abdominal pain with cramps
• Diarrhea
• Nausea
• Oral candidiasis
• Vomiting

Rare or Very Rare

• Drug fever
• Erythema
• Injection site sequelae
• Phlebitis after infusion
• Pruritus of skin
• Skin rash
• Urticaria

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