Brand name: Tygacil
Drug class: Glycylcyclines
VA class: AM250
Chemical name: (4S,4aS,5aR,12aS)-4,7-bis(dimethylamino)-9-[[[(1,1-dimethylethyl)amino]acetyl]amino]-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide
Molecular formula: C₂₉H₃₉N₅O₈
CAS number: 220620-09-7

Medically reviewed by Drugs.com on Jul 25, 2023. Written by ASHP.

Introduction

Antibacterial; glycylcycline antibiotic.

Uses for Tigecycline

Intra-abdominal Infections

Treatment of complicated intra-abdominal infections caused by susceptible Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, K. pneumoniae, Enterococcus faecalis (vancomycin-susceptible strains only), Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA; also known as oxacillin-resistant S. aureus or ORSA]), Streptococcus anginosus group (S. anginosus, S. intermedius, S. constellatus), Bacteroides fragilis, B. thetaiotaomicron, B. uniformis, B. vulgatus, Clostridium perfringens, or Peptostreptococcus micros.

For initial empiric treatment of mild to moderate community-acquired, extrabiliary, complicated intra-abdominal infections in adults (e.g., perforated or abscessed appendicitis), IDSA recommends either monotherapy with cefoxitin, ertapenem, moxifloxacin, tigecycline, or the fixed combination of ticarcillin and clavulanic acid, or a combination regimen that includes either a cephalosporin (cefazolin, ceftriaxone, cefotaxime, cefuroxime) or fluoroquinolone (ciprofloxacin, levofloxacin) in conjunction with metronidazole.

Consult current IDSA clinical practice guidelines at [Web] for additional information regarding management of intra-abdominal infections.

Respiratory Tract Infections

Treatment of community-acquired pneumonia caused by S. pneumoniae (penicillin-susceptible strains only), including cases with concurrent bacteremia, or caused by Haemophilus influenzae (β-lactamase-negative strains only) or Legionella pneumophila.

Do not use for treatment of hospital-acquired pneumonia^{† [off-label]}, including ventilator-associated pneumonia^{† [off-label]}. Efficacy not established and higher incidence of death reported in those receiving tigecycline than in those receiving comparator anti-infectives. (See Increased Mortality under Cautions.)

Skin and Skin Structure Infections

Treatment of complicated skin and skin structure infections caused by susceptible S. aureus (including MRSA), S. agalactiae (group B streptococci), S. anginosus group (S. anginosus, S. intermedius, S. constellatus), S. pyogenes (group A β-hemolytic streptococci), E. faecalis (vancomycin-susceptible strains only), E. cloacae, E. coli, K. pneumoniae, or B. fragilis.

Do not use for treatment of diabetic foot infections^{† [off-label]}. Efficacy not established and higher incidence of death reported in those receiving tigecycline than in those receiving comparator anti-infectives. (See Increased Mortality under Cautions.)

Tigecycline Dosage and Administration

Administration

Administer by IV infusion.

For solution and drug compatibility information, see Compatibility under Stability.

IV Infusion

Must be reconstituted and diluted prior to IV infusion. Final solution should have a maximum concentration of 1 mg/mL.

May be administered through a dedicated line or a Y-site. If same IV line is used for sequential infusion of several drugs, flush line before and after tigecycline infusion using 0.9% sodium chloride, 5% dextrose, or lactated Ringer's injection.

Reconstitution and Dilution

Reconstitute vial containing 50 mg of tigecycline by adding 5.3 mL of 0.9% sodium chloride, 5% dextrose, or lactated Ringer's injection to provide solution containing 10 mg/mL. Swirl gently until drug dissolves; reconstituted solution should be yellow to orange in color.

To prepare a 50-mg dose, withdraw 5 mL of reconstituted solution from the vial and dilute this in 100 mL of compatible IV solution. To prepare a 100-mg dose, reconstitute two 50-mg tigecycline vials and dilute 10 mL of reconstituted solution in 100 mL of compatible IV solution. (See Compatibility and see Storage under Stability.)

Rate of Administration

IV infusions should be given over 30–60 minutes.

Dosage

Pediatric Patients

General Pediatric Dosage

IV

Safety and efficacy not established; do not use unless no alternative anti-infectives available. Recommended dosage based on pharmacokinetic studies that included limited numbers of pediatric patients. (See Pediatric Use under Cautions.)

Children 8–11 years of age: 1.2 mg/kg every 12 hours (up to 50 mg every 12 hours).

Children and adolescents 12–17 years of age: 50 mg every 12 hours.

Adults

Complicated Intra-abdominal Infections

IV

Initial dose of 100 mg, followed by 50 mg every 12 hours.

Recommended duration of treatment is 5–14 days. Duration should be guided by severity and site of infection and patient's clinical and bacteriological progress.

Community-acquired Pneumonia

IV

Initial dose of 100 mg, followed by 50 mg every 12 hours.

Recommended duration of treatment is 7–14 days. Duration should be guided by severity and site of infection and patient's clinical and bacteriological progress.

Complicated Skin and Skin Structure Infections

IV

Initial dose of 100 mg, followed by 50 mg every 12 hours.

Recommended duration of treatment is 5–14 days. Duration should be guided by severity and site of infection and patient's clinical and bacteriological progress.

Prescribing Limits

Pediatric Patients

IV

Children 8–11 years of age: Maximum 50 mg every 12 hours.

Adults

IV

Maximum 100 mg daily.

Special Populations

Hepatic Impairment

Mild to moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not necessary.

Severe hepatic impairment (Child-Pugh class C): Initial dose of 100 mg in adults, followed by 25 mg every 12 hours. (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustments not necessary in patients with renal impairment or undergoing hemodialysis.

Geriatric Patients

Routine dosage adjustments based on age not necessary.

Cautions for Tigecycline

Contraindications

Known hypersensitivity to tigecycline or any ingredient in the formulation.

Warnings/Precautions

Warnings

Increased Mortality

Meta-analyses of phase 3 and 4 clinical trials indicate all-cause mortality higher in patients treated with tigecycline than in those treated with comparator anti-infectives. Reserve tigecycline for situations when alternative treatments not suitable.

Increased risk of death observed when tigecycline was used for FDA-labeled or unlabeled uses. Reason for increased mortality risk not established. Deaths generally resulted from worsening infections, complications of infection, or other underlying medical conditions.

Pooled analysis of data from 13 phase 3 and 4, active-controlled clinical trials evaluating tigecycline for treatment of serious infections indicate 4% mortality in tigecycline-treated patients versus 3% in patients treated with comparator anti-infectives. Overall adjusted risk difference in all-cause mortality between patients receiving tigecycline and those receiving comparators was 0.6%.

Data from 10 clinical trials evaluating tigecycline for FDA-labeled indications (i.e., complicated skin and skin structure infections, complicated intra-abdominal infections, community-acquired pneumonia) indicate an adjusted mortality rate of 2.5% for tigecycline-treated patients versus 1.8% for those treated with comparator anti-infectives. Adjusted risk difference in mortality stratified by trial weight was 0.6%.

Mortality risk was greatest when tigecycline was used for treatment of hospital-acquired pneumonia^{† [off-label]}, particularly ventilator-associated pneumonia^{† [off-label]}, a use not included in FDA-approved labeling. (See Patients with Hospital-acquired Pneumonia under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Potentially life-threatening anaphylaxis/anaphylactoid reactions reported.

Postmarketing reports of severe skin reactions, including Stevens-Johnson syndrome.

Use with caution in patients with known hypersensitivity to tetracyclines.

Other Warnings/Precautions

Hepatic Effects

Elevated total bilirubin and aminotransferase concentrations and prolonged prothrombin time reported. Clinically important hepatic dysfunction and hepatic failure reported rarely; postmarketing reports of hepatic cholestasis and jaundice. Adverse hepatic effects may occur after the drug is discontinued.

If abnormal liver function tests develop during tigecycline therapy, monitor for worsening hepatic function; consider risks and benefits of continuing the drug.

Patients with Hospital-acquired Pneumonia

Not effective and not labeled for treatment of hospital-acquired pneumonia^†, including ventilator-associated pneumonia^†.

Increased mortality in patients with ventilator-associated pneumonia^† who received tigecycline (19.1%) versus a comparator anti-infective (12.3%). Mortality was particularly high in tigecycline-treated patients who had bacteremia at baseline (50%). (See Increased Mortality under Cautions.)

Pancreatitis

Acute pancreatitis reported; sometimes fatal. Risk factors for pancreatitis not always present; improvement usually occurs after tigecycline is discontinued.

Consider diagnosis of pancreatitis in any patient receiving tigecycline who develops symptoms, signs, or laboratory abnormalities suggestive of acute pancreatitis. If pancreatitis is suspected, consider discontinuing tigecycline.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.

Pregnancy should be avoided. If patient becomes pregnant while receiving tigecycline, patient should be apprised of the potential hazard to the fetus. (See Pregnancy under Cautions.)

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible bacteria and fungi. Monitor carefully; institute appropriate therapy if superinfection occurs.

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile. C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including tigecycline, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contribute to development of CDAD; hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.

Consider CDAD if diarrhea develops during or after therapy and manage accordingly. Obtain careful medical history since CDAD may occur as late as ≥2 months after anti-infective therapy is discontinued.

If CDAD suspected or confirmed, discontinue anti-infectives not directed against C. difficile whenever possible. Initiate appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), anti-infective therapy directed against C. difficile (e.g., metronidazole, vancomycin), and surgical evaluation as clinically indicated.

Patients with Intestinal Perforation

Use with caution in complicated intra-abdominal infections secondary to clinically apparent intestinal perforation. Although causal relationship not established, sepsis or septic shock reported in several patients who received tigecycline for treatment of complicated intra-abdominal infections secondary to intestinal perforation.

Tetracycline-class Effects

Adverse effects reported with tetracyclines (e.g., photosensitivity, pseudotumor cerebri, pancreatitis, antianabolic activity that may result in increased BUN, azotemia, acidosis, and hypophosphatemia) possible. (See Pancreatitis under Cautions.)

Endocrine Effects

Postmarketing reports of symptomatic hypoglycemia in patients with and without diabetes.

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of tigecycline and other antibacterials, use only for treatment of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing. In absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.

Specific Populations

Pregnancy

Category D. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Crosses placenta and distributed into fetal tissues in animals.

Use during tooth development (last half of pregnancy) may cause permanent discoloration (yellow-gray-brown) of teeth.

Use during pregnancy only if potential benefits outweigh risks to the fetus.

Lactation

Distributed into milk in rats; not known if distributed into milk in humans.

Use with caution in nursing women.

Pediatric Use

Safety and efficacy not established in patients <18 years of age; use in this age group not recommended. Clinical trials not conducted in pediatric patients because of increased mortality observed in adults. (See Increased Mortality under Cautions.)

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, 1.2 mg/kg would likely result in AUCs comparable to those observed in adults receiving the recommended adult dosage. For children and adolescents 12–16 years of age, 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.)

Use during tooth development (i.e., in infants and children <8 years of age) may cause permanent discoloration (yellow-gray-brown) of teeth; do not use in this age group unless other anti-infectives cannot be used.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Mild hepatic impairment (Child-Pugh class A): Pharmacokinetics similar to those in healthy adults. Dosage adjustments not necessary.

Moderate hepatic impairment (Child-Pugh class B): Systemic clearance reduced, AUC increased, and half-life prolonged. Dosage adjustments not necessary.

Severe hepatic impairment (Child-Pugh class C): Use with caution and at a reduced dosage. (See Hepatic Impairment under Dosage and Administration.) Monitor for treatment response. Systemic clearance reduced, AUC increased, and half-life prolonged.

Renal Impairment

Pharmacokinetics not substantially altered. Dosage adjustments not necessary in patients with renal impairment or undergoing hemodialysis.

Common Adverse Effects

GI effects (nausea, vomiting, diarrhea).

Drug Interactions

Not metabolized by and does not inhibit CYP isoenzymes 1A2, 2C8, 2C9, 2C19, 2D6, or 3A4.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely with drugs metabolized by or affecting CYP1A2, 2C8, 2C9, 2C19, 2D6, or 3A4.

Specific Drugs

Tigecycline Pharmacokinetics

Distribution

Extent

Following IV administration, widely distributed into body tissues and fluids, including epithelial lining fluid, skin blister fluid, synovial fluid, bone, colon, gallbladder, and lung. Concentrations in certain tissues (i.e., alveolar cells, gallbladder, lung, colon, epithelial fluid) higher than serum concentrations.

Animal studies indicate tigecycline crosses the placenta and is distributed into fetal tissues.

Distributed into milk in animals.

Plasma Protein Binding

71–89%.

Elimination

Metabolism

Not extensively metabolized. Each recovered metabolite (a glucuronide, an N-acetyl metabolite, a tigecycline epimer) constitutes <10% of administered dose.

Elimination Route

Eliminated by renal and nonrenal mechanisms; approximately 59% of a dose eliminated by biliary/fecal excretion and 33% eliminated in urine (22% as unchanged drug).

Not substantially removed by hemodialysis.

Half-life

Adults: 27.1 or 42.4 hours following single or multiple doses, respectively.

Special Populations

Children 8–11 years of age: Based on pharmacokinetic simulation, 1.2 mg/kg will likely result in AUCs similar to those reported in adults receiving 50 mg every 12 hours.

Children and adolescents 12–16 years of age: 50 mg twice daily will likely result in exposures similar to those reported in adults.

Geriatric patients ≥65 years of age: Pharmacokinetics similar to younger adults.

Mild hepatic impairment (Child-Pugh class A): Pharmacokinetics not substantially altered compared with normal hepatic function.

Moderate hepatic impairment (Child-Pugh class B): Systemic clearance reduced by 25%, AUC increased by 50%, and half-life prolonged by 23%.

Severe hepatic impairment (Child-Pugh class C): Systemic clearance reduced by 55%, AUC increased by 105%, and half-life prolonged by 43%.

Renal impairment, including severe renal impairment Cl_cr <30 mL/minute): Pharmacokinetics not substantially altered compared with normal renal function.

Obese patients: After single 100-mg dose, serum and urine concentrations in otherwise healthy adults with class III obesity (body mass index [BMI] ≥40 kg/m²) were similar to concentrations reported in healthy normal-weight adults (BMI 18.5–24.99 kg/m²).

Stability

Storage

Parenteral

Powder for Infusion

20–25°C (may be exposed to 15–30°C).

Following reconstitution with 0.9% sodium chloride injection, 5% dextrose injection, or lactated Ringer's injection, may be stored at room temperature (≤25ºC) for up to a total of 24 hours (up to 6 hours in original vial, remaining time after dose is diluted in IV bag containing 0.9% sodium chloride or 5% dextrose injection). If storage conditions exceed 25ºC after reconstitution, use immediately.

Alternatively, may be stored at 2–8°C for up to 48 hours if dose of reconstituted tigecycline is immediately diluted in IV bag containing 0.9% sodium chloride or 5% dextrose.

Compatibility

Parenteral

Solution CompatibilityHID

Y-Site Compatibility

Actions and Spectrum

• Glycylcycline antibiotic; synthetic derivative of minocycline.

• Inhibits protein synthesis in susceptible organisms mainly by reversibly binding to 30S ribosomal subunits, thereby inhibiting binding of aminoacyl transfer-RNA to those ribosomes.

• Broad spectrum of antibacterial activity; usually bacteriostatic.

• Spectrum of activity includes various gram-positive aerobic and facultatively aerobic bacteria, including Staphylococcus aureus (including methicillin-resistant [oxacillin-resistant] strains), Streptococcus agalactiae (group B streptococci), S. anginosusgroup (S. anginosus, S. intermedius, S. constellatus), S. pneumoniae (penicillin-susceptible strains), S. pyogenes (group A β–hemolytic streptococci), and Enterococcus faecalis (vancomycin-susceptible strains only).

• Also active against various gram-negative aerobic and facultatively aerobic bacteria, including Citrobacter freundii, Enterobacter cloacae, Escherichia coli, H. influenzae (β-lactamase-negative strains), Klebsiella oxytoca, and K. pneumoniae, L. pneumophila, and some anaerobic bacteria, including Bacteroides fragilis, B. thetaiotaomicron, B. uniformis, B. vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

• May be active against some bacteria resistant to conventional tetracyclines since tigecycline susceptibility not affected by the 2 major tetracycline resistance mechanisms (i.e., ribosomal protection, efflux). Susceptibility to tigecycline also not affected by many other common resistance mechanisms, including β-lactamases (e.g., extended-spectrum β-lactamases [ESBLs]), target site modifications, macrolide efflux pumps, or enzyme target (e.g., gyrase, topoisomerase) changes.

• Resistance to tigecycline in some bacteria (e.g., Acinetobacter calcoaceticus-baumannii complex) is attributed to multidrug-resistant (MDR) efflux pumps.

Advice to Patients

• Advise patients that antibacterials (including tigecycline) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).

• Importance of completing full course of therapy, even if feeling better after a few days.

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with tigecycline or other antibacterials in the future.

• Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued. Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise pregnant women of risk to the fetus.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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