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Tigecycline

Medically reviewed by Drugs.com. Last updated on Aug 20, 2020.

Pronunciation

(tye ge SYE kleen)

Index Terms

  • GAR-936

Dosage Forms

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)

Brand Names: U.S.

  • Tygacil

Pharmacologic Category

  • Antibiotic, Glycylcycline

Pharmacology

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

Metabolism

Hepatic, via glucuronidation, N-acetylation, and epimerization to several metabolites, each <10% of the dose

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.

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

Protein Binding

71% to 89%

Use: Labeled Indications

Intra-abdominal infections, complicated: 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.

Contraindications

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

Dosing: Adult

Pneumonia, community-acquired: IV: Initial: 100 mg as a single dose; Maintenance dose: 50 mg every 12 hours for 7 to 14 days.

Intra-abdominal infections, complicated (cIAI): IV: Initial: 100 mg as a single dose; Maintenance dose: 50 mg every 12 hours for 5 to 14 days; Note: 2010 Infectious Diseases Society of America guidelines recommend a treatment duration of 4 to 7 days (provided source controlled) for community-acquired, mild to moderate IAI (IDSA [Solomkin 2010]).

Skin/skin structure infections, complicated: IV: Initial: 100 mg as a single dose; Maintenance dose: 50 mg every 12 hours for 5 to 14 days.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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

Reconstitution

Add 5.3 mL NS, D5W, or LR to each 50 mg vial. Swirl gently to dissolve. Resulting solution is 10 mg/mL. Reconstituted solution must be further diluted to allow IV administration. Transfer to 100 mL IV bag for infusion (final concentration should not exceed 1 mg/mL). Reconstituted solution should be yellow-orange; discard if not this color.

Administration

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.

Storage

Store intact vials at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Reconstituted solution may be stored at room temperature (not to exceed 25°C [77°F]) for up to 6 hours in the vial or up to 24 hours if further diluted in NS, D5W, or LR. Alternatively, may be stored at 2°C to 8°C (36°F to 46°F) for up to 48 hours following immediate transfer of the reconstituted solution into NS or D5W.

Drug Interactions

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). 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. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lithium: Tetracyclines may increase the serum concentration of Lithium. Monitor therapy

Mecamylamine: Tetracyclines may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Methoxyflurane: Tetracyclines may enhance the nephrotoxic effect of Methoxyflurane. Avoid combination

Mipomersen: Tetracyclines may enhance the hepatotoxic effect of Mipomersen. Monitor therapy

Neuromuscular-Blocking Agents: Tetracyclines may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy

Penicillins: Tetracyclines may diminish the therapeutic effect of Penicillins. Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. 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. 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. Consider therapy modification

Tacrolimus (Systemic): Tigecycline may increase the serum concentration of Tacrolimus (Systemic). 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. Consider therapy modification

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Tetracyclines may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Warfarin: Tigecycline may increase the serum concentration of Warfarin. Monitor therapy

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Gastrointestinal: Nausea (24% to 35%), vomiting (16% to 20%), diarrhea (12%)

1% to 10%:

Cardiovascular: Localized phlebitis (≤3%), septic shock (<2%), thrombophlebitis (<2%)

Central nervous system: Headache (6%), dizziness (3%), chills (<2%)

Dermatologic: Skin rash (3%), pruritus (<2%)

Endocrine & metabolic: Increased amylase (3%), hyponatremia (2%), hypocalcemia (<2%), hypoglycemia (<2%)

Gastrointestinal: Abdominal pain (6%), dyspepsia (2%), abnormal stools (<2%), anorexia (<2%), dysgeusia (<2%)

Genitourinary: Leukorrhea (<2%), vaginitis (<2%), vulvovaginal candidiasis (<2%)

Hematologic & oncologic: Anemia (5%), hypoproteinemia (5%), eosinophilia (<2%), increased INR (<2%), prolonged partial thromboplastin time (<2%), prolonged prothrombin time (<2%), thrombocytopenia (<2%)

Hepatic: Increased serum ALT (5%), increased serum AST (4%), increased serum alkaline phosphatase (3%), hyperbilirubinemia (2%), jaundice (<2%)

Hypersensitivity: Hypersensitivity reaction (<2%)

Infection: Infection (7%), abscess (2%)

Local: Inflammation at injection site (<2%), injection site reaction (<2%), pain at injection site (<2%), swelling at injection site (<2%)

Neuromuscular & skeletal: Weakness (3%)

Renal: Increased blood urea nitrogen (3%), increased serum creatinine (<2%)

Respiratory: Pneumonia (2%)

<1%, postmarketing, and/or case reports: Acute pancreatitis, allergic skin reaction, anaphylactoid reaction, anaphylaxis, Clostridioides (formerly Clostridium) difficile-associated diarrhea, hepatic dysfunction, hepatic failure, hypersensitivity reaction, hypoglycemia signs and symptoms (diabetic and nondiabetic patients), intrahepatic cholestasis, Stevens-Johnson syndrome

ALERT: U.S. Boxed Warning

Mortality:

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.

Warnings/Precautions

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.

Monitoring Parameters

Hepatic function (periodically); coagulation parameters (including aPTT, PTT, fibrinogen) at baseline and regularly during therapy. Observe for signs and symptoms of anaphylaxis during administration.

Pregnancy Considerations

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.

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Diarrhea

• Abdominal pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes

• Acidosis like confusion, fast breathing, fast heartbeat, arrhythmia, severe abdominal pain, nausea, vomiting, fatigue, shortness of breath, or feeling very tired or weak

• Severe loss of strength and energy

• Headache

• Blurred vision

• Double vision

• Blindness

• Not able to pass urine

• Change in amount of urine passed

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.