TIGECYCLINE (tigecycline)

There are 2 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Live Typhoid Vaccine/Antimicrobials 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)	VIVOTIF
Selected Retinoids (Systemic)/Tetracyclines 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: Both systemic tetracyclines(1-4,14) and systemic retinoids(5-14) have been independently associated with medication-induced intracranial hypertension. CLINICAL EFFECTS: The concurrent use of oral retinoids(5-12) with tetracyclines has been associated with pseudotumor cerebri (benign intracranial hypertension). Early signs of pseudotumor cerebri include papilledema (inflammation of the optic nerve), headache, nausea, vomiting, and visual disturbances such as blurred vision, double vision, and loss of vision.(15) PREDISPOSING FACTORS: Women of childbearing age who are overweight or have a previous history of intracranial hypertension are at a greater risk of developing intracranial hypertension.(15) PATIENT MANAGEMENT: The UK(5) and US(6) manufacturers of acitretin state state that concurrent use with tetracyclines is contraindicated. The UK manufacturer of isotretinoin states that concurrent use with tetracyclines is contraindicated.(7) The US manufacturer of isotretinoin states that the concurrent use of tetracyclines should be avoided.(8) The US manufacturer of minocycline states that the administration of isotretinoin should be avoided shortly before, during and shortly after minocycline therapy.(2) The UK manufacturers of oral tretinoin and alitretinoin states that concurrent use with tetracyclines is contraindicated.(9,11) The Canadian manufacturer of palovarotene states that coadministration of tetracycline derivatives should be avoided.(12) Patients who present with symptoms of pseudotumor cerebri should be screened for papilledema. If papilledema is present, they should discontinue the drug and be referred to a neurologist for further treatment.(5-13) DISCUSSION: The concurrent use of isotretinoin and tetracyclines has been associated with pseudotumor cerebri.(5-13) A review of ocular side effects from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, the Food and Drug Administration, and medical journals from 1979 to 2003 found 6 patients who developed intracranial hypertension while taking concurrent minocycline or tetracycline with tretinoin, acitretin, or etretinate.(13)	ABSORICA, ABSORICA LD, ACCUTANE, ACITRETIN, AMNESTEEM, CLARAVIS, ISOTRETINOIN, RETINOIC ACID, SOHONOS, TRETINOIN, TRETINOIN ACID, ZENATANE

Drug contraindication overview.

Known hypersensitivity to tigecycline or any ingredient in the formulation.

Adverse reaction overview.

Nausea, vomiting, and diarrhea are the most common adverse effects reported with tigecycline and have been reported in up to 35% of patients in clinical studies. Adverse effects reported in 2-8% of patients receiving tigecycline include abdominal pain, abnormal healing, abscess, anemia, asthenia, bilirubinemia, dizziness, dyspepsia, headache, hypoproteinemia, increased ALT or AST concentrations, increased alkaline phosphatase concentrations, increased amylase concentrations, increased BUN, infection, phlebitis, and rash.

Safety and efficacy of tigecycline have not been established in patients younger than 18 years of age and use in this age group is not recommended. Because of the increased mortality observed in adults receiving tigecycline, clinical trials evaluating safety and efficacy of tigecycline in pediatric patients have not been conducted. For circumstances when there are no alternative anti-infectives, pediatric dosage has been proposed based on data from pharmacokinetic studies that included limited numbers of pediatric patients.

For children 8-11 years of age, a pharmacokinetic simulation showed that a tigecycline dosage of 1.2 mg/kg in this age group would likely result in an area under the plasma concentration-time curve (AUC) similar to that reported in adults receiving the recommended adult dosage. For children and adolescents 12-16 years of age, a tigecycline dosage of 50 mg twice daily would likely result in exposures comparable to those observed in adults receiving the recommended adult dosage.

(See Pediatric Dosage under Dosage and Administration: Dosage.) Because use of tigecycline during tooth development (i.e., in infants and children younger than 8 years of age) may cause permanent discoloration (yellow-gray-brown) of the teeth, the drug should not be used in this age group unless other anti-infectives cannot be used. (See Cautions: Pediatric Precautions in the Tetracyclines General Statement 8:12.24.)

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None