Tygacil (tigecycline)

No dosing information is available for this tab.

Tigecycline is administered by IV infusion.

Tigecycline may be administered through a dedicated line or through a Y-site. If the same IV line is used for sequential infusion of several drugs, the line should be flushed before and after infusion of tigecycline with 0.9% sodium chloride, 5% dextrose, or lactated Ringer's injection. Tigecycline should not be administered simultaneously through the same Y-site with amphotericin B, amphotericin B lipid complex, diazepam, esomeprazole, or omeprazole.

There is no enhanced messaging for this drug.

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)

Tetracyclines/Selected Retinoids (SYSTEMIC)

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)

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

Misc Antibiotics/Neuromuscular Blocking Agents

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

MECHANISM OF ACTION: Aminoglycosides, bacitracin, clindamycin, lincomycin, and polymyxins may enhance the pharmacologic effects of neuromuscular blocking agents.

CLINICAL EFFECTS: May see an increase in the pharmacologic effects of neuromuscular blocking agents, including prolonged respiratory depression and apnea.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If it is necessary to administer these drugs concurrently, do so with extreme caution. Monitor neuromuscular function and adjust the dose of the neuromuscular blocking agent accordingly.

DISCUSSION: Concomitant administration of aminoglycosides, bacitracin, clindamycin, lincomycin, and polymixins with neuromuscular blocking agents has been shown to produce synergism of the effects on skeletal muscles. Concurrent administration of these drugs has been associated with prolonged respiratory depression, respiratory paralysis, and fatal apnea. The interaction usually occurs when the antibiotic is given prior to or concurrently with the neuromuscular blocking drug, but it may also occur when given after administration. Any antibiotic dosage or route of administration may produce respiratory depression.

Myelosuppressives; Immunomodulators/Sodium Iodide I 131

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

MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)

CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)

DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)

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

Tetracyclines; Tigecycline/Contraceptives

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

MECHANISM OF ACTION: Not established.

CLINICAL EFFECTS: Reduced pharmacologic effects of oral contraceptives with resultant breakthrough bleeding and pregnancy may occur.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Current guidelines suggest that additional precautions are not necessary when non-enzyme inducing antibiotics are used concurrently with hormonal contraceptives; however, some patients may still prefer to use an additional method of contraception.

DISCUSSION: Evidence for this interaction is limited and conflicting; however, the CDC and the Faculty of Sexual and Reproductive Healthcare Clinical Effectiveness Unit no longer recommend use of a backup contraceptive method during use of a non-enzyme inducing antibiotic. Pregnancy has been reported following the addition of tetracycline to oral contraceptive therapy.(1) In contrast, a study in 7 healthy women found no effect of tetracycline on ethinyl estradiol or norethindrone levels.(2) A study in 24 healthy women found no significant effects of doxycycline on ethinyl estradiol, norethindrone, or progesterone levels. However, the authors noted that there large inter-patient and inter-patient variability in these levels and that the interaction may just manifest itself in a small proportion of women.(3)

Tigecycline/Cyclosporine

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

MECHANISM OF ACTION: The mechanism of the interaction is unknown but may be related to competitive inhibition of P-glycoprotein-mediated biliary excretion of tigecycline and cyclosporine.(1)

CLINICAL EFFECTS: Concurrent use of tigecycline may result in elevated levels of and toxicity from cyclosporine, including nephrotoxicity.(2,3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Monitor cyclosporine levels during and after therapy with tigecycline. The dosage of cyclosporine may need to be adjusted.(2,3)

DISCUSSION: A 61-year-old renal transplant recipient on cyclosporine 120 mg daily was started on intravenous tigecycline for a urinary tract infection. Cyclosporine levels and serum creatinine rose markedly and the dose of cyclosporine was reduced by 50%. After tigecycline was discontinued for 3 days, the dose of cyclosporine had to be increased back to 120 mg daily to maintain therapeutic levels.(4)

Tigecycline/Tacrolimus

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

MECHANISM OF ACTION: The mechanism of the interaction is unknown but may be related to competitive inhibition of P-glycoprotein-mediated biliary excretion of tigecycline and tacrolimus.(1)

CLINICAL EFFECTS: Concurrent use of tigecycline may result in elevated levels of and toxicity from tacrolimus, including nephrotoxicity, neurotoxicity, and prolongation of the QTc interval and life-threatening cardiac arrhythmias, including torsades de pointes.(2,3)

PREDISPOSING FACTORS: The risk of QT prolongation or torsade de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsade de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(4) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsade de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, and/or renal/hepatic dysfunction).(4)

PATIENT MANAGEMENT: Monitor tacrolimus levels during and after therapy with tigecycline. The dosage of tacrolimus may need to be adjusted.(2,3) When concurrent therapy of tigecycline and tacrolimus is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting.

DISCUSSION: A 43-year-old kidney transplant recipient on tacrolimus 7 mg daily with a trough level of 11.5 mcg/L was started on intravenous tigecycline for a urinary tract infection. Concomitant medications included mycophenolate, prednisolone, insulin, amlodipine, cotrimoxazole, acyclovir and diltiazem. Tacrolimus trough level rose to 28.2 mcg/L after 6 days of tigecycline and 43.6 mcg/L after 10 days, and potassium increased to 5.7 mmol/L.(5) A 51-year-old kidney transplant recipient on a stable dose of tacrolimus was started on intravenous tigecycline for sepsis. Her tacrolimus trough level rose, and she required a reduction in tacrolimus dose. After tigecycline was discontinued, her tacrolimus levels became subtherapeutic within one day and she resumed her previous dose of tacrolimus.(6) A 58-year-old kidney transplant recipient on tacrolimus 1.5 mg daily received 2 weeks of intravenous tigecycline for Brucellosis. His tacrolimus levels and serum creatinine remain stable during concomitant therapy.(7)

Known hypersensitivity to tigecycline or any ingredient in the formulation.

• Pancreatitis

• Child-pugh class C hepatic impairment
• Clostridioides difficile infection
• Disease of liver
• Gastrointestinal perforation
• Pregnancy

There are no moderate contraindications for this drug.

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.

More Frequent

• Abnormal hepatic function tests
• Increased alanine transaminase
• Infection

Less Frequent

• Abscess
• Anemia
• Increased aspartate transaminase
• Thrombocytopenic disorder

Rare or Very Rare

• Acute eruptions of skin
• Acute pancreatitis
• Anaphylaxis
• Cholestasis
• Cholestatic hepatitis
• Clostridioides difficile infection
• Eosinophilia
• Hemorrhage
• Hepatic failure
• Hyperbilirubinemia
• Hypocalcemia
• Hypofibrinogenemia
• Hypoglycemic disorder
• Hyponatremia
• Idiopathic intracranial hypertension
• Injection site sequelae
• Jaundice
• Phlebitis after infusion
• Prolonged activated partial thromboplastin time
• Septic shock
• Stevens-johnson syndrome
• Thrombophlebitis
• Tooth enamel hypoplasia

More Frequent

• Acute abdominal pain
• Diarrhea
• Headache disorder
• Nausea
• Vomiting

Less Frequent

• Dizziness
• Dyspepsia
• Pruritus of skin
• Skin rash

Rare or Very Rare

• Anorexia
• Chills
• Dysgeusia
• General weakness
• Skin photosensitivity
• Vaginal discharge
• Vaginitis
• Vulvovaginal candidiasis

No enhanced messaging available.

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.)

Category D. (See Users Guide.) Tigecycline crosses the placenta and is found in fetal tissues. (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Other Warnings/Precautions, in Cautions.)

Use of tigecycline during tooth development (last half of pregnancy) may cause permanent discoloration (yellow-gray-brown) of the teeth. (See Cautions: Pediatric Precautions in the Tetracyclines General Statement 8:12.24.)

Tigecycline is distributed into milk in rats. It is not known whether tigecycline is distributed into human milk; caution is advised if the drug is administered in nursing women.

There are no substantial differences in safety and efficacy in patients 65 years of age or older relative to younger adults, but increased sensitivity cannot be ruled out.