An increase in all-cause mortality has been observed in a meta-analysis of phase 3 and 4 clinical trials in tigecycline-treated patients versus comparator. The cause of this mortality risk difference of 0.6% (95% confidence interval [CI], 0.1 to 1.2) has not been established. Tigecycline should be reserved for use in situations when alternative treatments are not suitable.
Note: Given the increased mortality risk associated with tigecycline, reserve for use in situations when alternative treatments are not suitable (FDA 2013).
Intra-abdominal infection (alternative agent):
Note: Not recommended for routine empiric use. Reserve use for patients with or at risk for certain multidrug-resistant organisms (eg, K. pneumoniae carbapenemase-producing Enterobacteriaceae, Acinetobacter baumannii) (SIS [Mazuski 2017]).
IV: 100 mg once, then 50 mg every 12 hours; some experts suggest 200 mg once, then 100 mg every 12 hours for complicated infection (ie, with abscess or involving the peritoneum) (IDSA [Tamma 2020]). Some experts use as part of an appropriate combination regimen for certain resistant organisms (Quale 2021; SIS [Mazuski 2017]). Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Gomi 2018; Sawyer 2015; SIS [Mazuski 2017]).
Pneumonia, community-acquired (alternative agent for patients unable to tolerate beta-lactams or fluoroquinolones): Inpatients without risk factors for Pseudomonas aeruginosa; not recommended for routine empiric use (File 2021).
IV: 100 mg as a single dose, then 50 mg every 12 hours (Tanaseanu 2009). Total duration (which may include oral step-down therapy) is a minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued (ATS/IDSA [Metlay 2019]; File 2021).
Skin/skin structure infection, complicated: IV: Initial: 100 mg as a single dose; Maintenance dose: 50 mg every 12 hours for 5 to 14 days.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Korth-Bradley 2012; manufacturer's labeling).
Hemodialysis, intermittent (thrice weekly): Poorly dialyzed: No supplemental dose or dosage adjustment necessary (Korth-Bradley 2012; manufacturer's labeling).
Peritoneal dialysis: Unlikely to be dialyzed: No dosage adjustment necessary (expert opinion).
CRRT: No dosage adjustment necessary (Broeker 2018).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
Mild-to-moderate hepatic impairment (Child-Pugh class A or B): No dosage adjustment necessary.
Severe hepatic impairment (Child-Pugh class C): Initial: 100 mg single dose; Maintenance: 25 mg every 12 hours.
(For additional information see "Tigecycline: Pediatric drug information")
General dosing, susceptible infection: Limited data available: Note: Use should be reserved for situations when no effective alternative therapy is available; should not be used in pediatric patients <8 years due to adverse effects on tooth development, unless no alternatives are available (Red Book [AAP 2018]). Duration of therapy dependent on severity/site of infection and clinical status and response to therapy.
Infants and Children <8 years: Dosing based on small studies and case series in pediatric patients (age range: 36 days to 15 years); should only be used if potential benefits of use outweigh risks of uncertain dosing and impact on tooth development (Lin 2018; Ye 2018; Zeng 2017; Zhu 2016):
Loading dose (optional): IV: 1.5 to 3 mg/kg once
Maintenance dose: IV: 1 to 2 mg/kg/dose every 12 hours; maximum dose: 50 mg/dose; if no loading dose, a maintenance dose of 2 mg/kg every 12 hours has been used
Children ≥8 years and Adolescents: Dosing based on data from pharmacokinetic trials (Purdy 2012) and on small studies and case series in pediatric patients (age range: 36 days to 15 years) (Lin 2018; Ye 2018; Zeng 2017; Zhu 2016)
8 to 11 years: IV: 1.2 to 2 mg/kg/dose every 12 hours; maximum dose: 50 mg/dose
≥12 years: IV: 50 mg every 12 hours
There are no pediatric specific recommendations; data is insufficient. Based on experience in adult patients, no dosage adjustment may be necessary; end-stage renal disease (ESRD) on dialysis: Poorly dialyzed; no supplemental dose or dosage adjustment necessary, including patients on intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD).
There are no pediatric specific recommendations; data is insufficient. Based on experience in adult patients with mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment may be needed; for severe impairment, dosing adjustment suggested.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Tygacil: 50 mg (1 ea) [contains lactose]
Generic: 50 mg (1 ea)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Tygacil: 50 mg (1 ea) [contains lactose]
Generic: 50 mg (1 ea)
IV: Infuse over 30 to 60 minutes through dedicated line or via Y-site. If the same IV line is used for sequential infusion of several drugs, flush line with NS, D5W, or LR before and after tigecycline administration.
IV: Infuse over 30 to 60 minutes through dedicated line or via Y-site.
Intra-abdominal infection: Treatment of complicated intra-abdominal infections in patients ≥18 years of age caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates), Staphylococcus aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus anginosus group (includes S. anginosus, Streptococcus intermedius, and Streptococcus constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.
Pneumonia, community acquired: Treatment of community-acquired bacterial pneumonia in patients ≥18 years of age caused by Streptococcus pneumoniae (penicillin-susceptible isolates), including cases with concurrent bacteremia, Haemophilus influenzae, and Legionella pneumophila.
Skin and skin structure infections, complicated: Treatment of complicated skin and skin structure infections in patients ≥18 years of age caused by E. coli, E. faecalis (vancomycin-susceptible isolates), S. aureus (methicillin-susceptible and methicillin-resistant isolates), Streptococcus agalactiae, S. anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes, E. cloacae, K. pneumoniae, and B. fragilis.
Limitations of use: Not indicated for treatment of diabetic foot infections; a clinical trial failed to demonstrate noninferiority of tigecycline for treatment of diabetic foot infections. Not indicated for treatment of hospital-acquired or ventilator-associated pneumonia; greater mortality and decreased efficacy were reported in tigecycline-treated patients in a comparative clinical trial.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Gastrointestinal: Diarrhea (12%), nausea (24% to 35%), vomiting (16% to 20%)
1% to 10%:
Cardiovascular: Phlebitis (3%), septic shock, thrombophlebitis
Dermatologic: Pruritus, skin rash (3%)
Endocrine & metabolic: Hypocalcemia, hypoglycemia, hyponatremia (2%), increased amylase (3%)
Gastrointestinal: Abdominal pain (6%), abnormal stools, anorexia, dysgeusia, dyspepsia (2%)
Genitourinary: Leukorrhea, vaginitis, vulvovaginal candidiasis
Hematologic & oncologic: Anemia (5%), eosinophilia, hypoproteinemia (5%), increased INR, prolonged partial thromboplastin time, prolonged prothrombin time, thrombocytopenia
Hepatic: Hyperbilirubinemia (2%), increased serum alanine aminotransferase (5%), increased serum alkaline phosphatase (3%), increased serum aspartate aminotransferase (4%), jaundice
Hypersensitivity: Hypersensitivity reaction
Infection: Abscess (2%), infection (7%), sepsis
Local: Inflammation at injection site, injection site phlebitis, injection site reaction, pain at injection site, swelling at injection site
Nervous system: Chills, dizziness (3%), headache (6%)
Neuromuscular & skeletal: Asthenia (3%)
Renal: Increased blood urea nitrogen (3%), increased serum creatinine
Respiratory: Pneumonia (2%)
Postmarketing:
Dermatologic: Severe dermatological reaction, Stevens-Johnson syndrome
Endocrine & metabolic: Hypoglycemia signs and symptoms (diabetic and nondiabetic patients)
Gastrointestinal: Acute pancreatitis, Clostridioides difficile associated diarrhea, enamel hypoplasia
Hematologic & oncologic: Hemorrhage (including rectal bleeding and ecchymoses [Ciu 2019]), hypofibrinogenemia
Hepatic: Hepatic failure, intrahepatic cholestasis
Hypersensitivity: Anaphylaxis, nonimmune anaphylaxis
Hypersensitivity to tigecycline or any component of the formulation
Documentation of allergenic cross-reactivity for tetracyclines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Canadian labeling: Additional contraindications (not in U.S. labeling): Hypersensitivity to tetracycline class of antibiotics
Concerns related to adverse effects:
• Anaphylactic/Hypersensitivity reactions: May cause life-threatening anaphylaxis. Due to structural similarity with tetracyclines, avoid use in patients with known hypersensitivity to tetracycline-class antibiotics.
• Antianabolic effects: May be associated with antianabolic effects observed with the tetracycline class (including increased BUN, azotemia, acidosis, and hyperphosphatemia).
• Coagulopathy: May be associated with abnormalities of blood coagulation parameters, including prolongation of PT and aPTT and decreased fibrinogen that may be dose- and/or time-dependent, in particular in patients with renal and hepatic impairment; discontinue use when suspected (Cui 2019).
• Hepatotoxicity: Abnormal liver function tests (increased total bilirubin, prothrombin time, transaminases) have been reported. Isolated cases of significant hepatic dysfunction and hepatic failure have occurred. Closely monitor for worsening hepatic function in patients who develop abnormal liver function tests during therapy. Adverse hepatic effects may occur after drug discontinuation.
• Pancreatitis: Acute pancreatitis (including fatalities) has been reported, including patients without known risk factors; discontinue use when suspected.
• Photosensitivity: May be associated with photosensitivity due to structural similarities with tetracyclines.
• Pseudotumor cerebri: May be associated with pseudotumor cerebri due to structural similarities with tetracyclines.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Treatment-related mortality: [US Boxed Warning]: In a meta analysis of Phase 3 and 4 clinical trials, an increase in all-cause mortality has been observed in tigecycline-treated patients versus comparator-treated patients. The cause of the mortality risk difference (0.6% [95% CI 0.1, 1.2]) has not been established. Use should be reserved for situations in which alternative treatments are not suitable. In general, deaths were the result of worsening infection, complications of infection, or underlying comorbidity.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage adjustment recommended in severe hepatic impairment.
• Intra-abdominal infections: Avoid use as monotherapy for patients with intestinal perforation (in the small sample of available cases, sepsis/septic shock occurred more frequently than patients treated with imipenem/cilastatin comparator).
Special populations:
• Pediatric: Safety and efficacy in children and adolescents <18 years of age have not been established due to increased mortality observed in trials of adult patients. Use only if no alternative antibiotics are available. Because of effects on tooth development (yellow-gray-brown discoloration), use in patients <8 years of age is not recommended.
Other warnings/precautions:
• Appropriate use: Do not use for diabetic foot infections; non-inferiority was not demonstrated in studies. Do not use for healthcare-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP); increased mortality and decreased efficacy have been reported in HAP and VAP trials.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Lithium: Tetracyclines may increase the serum concentration of Lithium. Risk C: Monitor therapy
Mecamylamine: Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine. Risk X: Avoid combination
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Methoxyflurane: Tetracyclines may enhance the nephrotoxic effect of Methoxyflurane. Risk X: Avoid combination
Mipomersen: Tetracyclines may enhance the hepatotoxic effect of Mipomersen. Risk C: Monitor therapy
Neuromuscular-Blocking Agents: Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Penicillins: Tetracyclines may diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Retinoic Acid Derivatives: Tetracyclines may enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Risk X: Avoid combination
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Sulfonylureas: Tetracyclines may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Tacrolimus (Systemic): Tigecycline may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Tetracyclines may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Warfarin: Tigecycline may increase the serum concentration of Warfarin. Risk C: Monitor therapy
Tigecycline crosses the placenta.
Tetracyclines accumulate in developing teeth and long tubular bones (Mylonas 2011). Permanent discoloration of teeth (yellow, gray, brown) can occur following in utero exposure and is more likely to occur following long-term use or short-term repeated exposure. In addition, tetracycline use has been associated with reversible retardation of skeletal development and reduced bone growth.
It is not known if tigecycline is found in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Although oral bioavailability is low and exposure to the breastfed infant is expected to be limited, the manufacturer does not recommend breastfeeding if maternal therapy is required for >3 weeks due to the potential risk of tooth discoloration and inhibition of bone growth in the infant. The manufacturer suggests temporarily pumping and discarding breast milk during therapy and for 9 days after the last maternal tigecycline dose to minimize exposure to the breastfed infant. In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea. Use of medications other than tetracyclines should be used when possible (WHO 2002).
Hepatic function (periodically); coagulation parameters (including aPTT, PTT, fibrinogen) at baseline and regularly during therapy. Observe for signs and symptoms of anaphylaxis during administration.
A glycylcycline antibiotic that binds to the 30S ribosomal subunit of susceptible bacteria, thereby, inhibiting protein synthesis. Generally considered bacteriostatic; however, bactericidal activity has been demonstrated against isolates of S. pneumoniae and L. pneumophila. Tigecycline is a derivative of minocycline (9-t-butylglycylamido minocycline), and while not classified as a tetracycline, it may share some class-associated adverse effects. Tigecycline has demonstrated activity against a variety of gram-positive and -negative bacterial pathogens including methicillin-resistant staphylococci.
Distribution: Vd: Children (8 to 11 years): 2.84 L/kg (range: 0.397 to 11.2 L/kg) (Purdy 2012); Adults: 7 to 9 L/kg; extensive tissue distribution; distributes into gallbladder, lung, and colon
Protein binding: 71% to 89%
Metabolism: Hepatic, via glucuronidation, N-acetylation, and epimerization to several metabolites, each <10% of the dose
Half-life elimination: Single dose: 27 hours; following multiple doses: 42 hours; increased by 23% in moderate hepatic impairment and 43% in severe hepatic impairment
Excretion: Feces (59%, primarily as unchanged drug); urine (33%, with 22% of the total dose as unchanged drug)
Clearance: Reduced by 25% in patient with moderate hepatic impairment and 55% in severe hepatic impairment.
Solution (reconstituted) (Tigecycline Intravenous)
50 mg (per each): $124.80 - $187.20
Solution (reconstituted) (Tygacil Intravenous)
50 mg (per each): $142.87
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