Class: Anti-infective, Glycylcycline
- Injection, lyophilized powder for solution 50 mg
Inhibits protein transportation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains.
C max and AUC 0-24h for 50 mg every 12 h as a 30-min infusion are 0.87 mcg/mL and 4.7 mcg•h/mL, respectively.
Plasma protein binding ranges from 71% to 89%. Vd is 7 to 9 L/kg.
Not extensively metabolized.
The half-life is approximately 42 h and Cl is approximately 23.8 L/h (multiple dosing). Primary route of elimination is biliary/fecal excretion (59% of dose); glucuronidation and renal excretion are secondary routes (33% of dose excreted in urine, 22% as unchanged tigecycline).
Special PopulationsRenal Function Impairment
Pharmacokinetics not significantly altered.Hepatic Function Impairment
Systemic Cl reduced 25% and half-life prolonged 23% in patients with moderate hepatic impairment (Child-Pugh class B); systemic Cl reduced 55% and half-life prolonged 43% in patients with severe hepatic impairment (Child-Pugh class C).Elderly
No significant differences in pharmacokinetics were observed between healthy elderly subjects and younger subjects.Gender
There was no significant difference in tigecycline clearance between women and men.Race
There was no significant difference in tigecycline clearance among Asian, black, Hispanic, or white subjects, or subjects of other races.
Indications and Usage
Treatment of community-acquired bacterial pneumonia, complicated skin and skin structure infections, and complicated intra-abdominal infections caused by susceptible strains of specific microorganisms in patients 18 y of age and older.
Known hypersensitivity to tigecycline.
Dosage and AdministrationAdults
IV Initial dose of 100 mg followed by 50 mg every 12 h for 5 to 14 days (complicated skin and skin structure infections and intra-abdominal infections) or 7 to 14 days (community-acquired bacterial pneumonia).Hepatic Function Impairment
Severe hepatic impairment (Child-Pugh class C)
Initial dose of 100 mg followed by maintenance dosage of 25 mg every 12 h.
- For IV infusion only. Not for intradermal, subcutaneous, IM, IV bolus, or intra-arterial administration.
- Reconstitute each vial of tigecycline 50 mg with 5.3 mL of sodium chloride 0.9% injection, dextrose 5% injection, or Ringer's lactate injection (2 vials for 100 mg dose, 1 vial for 50 mg dose). Gently swirl until drug dissolves. Reconstituted solution contains tigecycline 10 mg/mL. Prepare infusion solution by immediately withdrawing 5 mL of reconstituted solution from the vial and adding to 100 mL IV bag for infusion. Max concentration in IV bag should be 1 mg/mL.
- Reconstituted solution should be yellow to orange in color; if not, the solution should be discarded. Do not administer if particulate matter, cloudiness, or discoloration (eg, black, green) is noted.
- Administer prescribed dose over 30 to 60 min through a dedicated IV line or through a Y-site. If IV line is used for sequential infusion of other drugs, flush IV line with sodium chloride 0.9% injection, dextrose 5% injection, or Ringer's lactate injection before and after infusion of tigecycline.
- The following drugs or diluents are compatible with tigecycline when administered through a Y-site: amikacin, dobutamine, dopamine, gentamicin, haloperidol, lidocaine, metoclopramide, morphine, norepinephrine, piperacillin/tazobactam (EDTA formulation), potassium chloride, propofol, ranitidine, Ringer's lactate, theophylline, and tobramycin.
- The following drugs should not be administered simultaneously through the same Y-site as tigecycline: amphotericin B, amphotericin B lipid complex, diazepam, esomeprazole, and omeprazole.
Store unopened vials at 59° to 86°F. Once reconstituted, tigecycline may be stored at room temperature for up to 24 hours (up to 6 hours in the vial and the remaining time in the IV bag). Diluted solution may be stored at room temperature for up to 24 h (up to 6 h in the vial and the remaining time in the IV bag), or refrigerated (36° to 46°F) for up to 48 h after immediate transfer of the reconstituted solution to the IV bag.
Cyclosporine concentrations and risk of adverse reactions may be increased. Closely monitor cyclosporine trough whole blood concentrations when tigecycline is started or stopped. Adjust the cyclosporine dose as needed.Hormonal contraceptives
Coadministration may decrease the effectiveness of the oral contraceptive. Consider an additional nonhormonal method of contraception.Warfarin
Warfarin Cl may be reduced and plasma levels may be increased. Monitor PTT or other suitable anticoagulant tests if tigecycline and warfarin are given concurrently. Adjust the warfarin dose as needed.
Phlebitis (3%); thrombophlebitis (less than 2%).
Headache (6%); asthenia, dizziness (3%).
Rash (3%); pruritus (less than 2%).
Taste perversion (less than 2%).
Nausea (26%); vomiting (20%); diarrhea (12%); abdominal pain (6%); dyspepsia (2%); abnormal stools, anorexia (less than 2%).
Leukorrhea, vaginal moniliasis, vaginitis (less than 2%).
Anemia (4%); eosinophilia, increased INR, prolonged APTT, prolonged PTT, thrombocytopenia (less than 2%).
Jaundice (less than 2%); ALT increased (5%); alkaline phosphatase increased, AST increased (4%); bilirubinemia (2%); acute pancreatitis, hepatic cholestasis (postmarketing).
Injection-site edema, inflammation, pain, phlebitis, or reaction (less than 2%).
Hypoproteinemia (5%); increased amylase, increased BUN (3%); hypocalcemia, hypoglycemia, hyponatremia, increased creatinine (less than 2%).
Infection (8%); death (5%); abnormal healing (4%); abscess (3%); septic shock (2%); allergic reactions, chills (less than 2%); anaphylaxis/anaphylactoid reactions (postmarketing).
Monitor patient for superinfection. Monitor PT/INR if used with warfarin. Monitor for worsening hepatic function in patients who develop abnormal LFTs and evaluate for risk/benefit of continuing tigecycline therapy.
Category D . May cause fetal harm.
Safety and efficacy in children younger than 18 y of age have not been established. Use in patients younger than 8 y of age is not recommended because of effects on tooth development.
Anaphylaxis/anaphylactoid reactions have been reported. Use with caution in patients with known hypersensitivity to tetracycline-class antibiotics.
Treat patients with severe hepatic function with caution; reduce dose and monitor for treatment response.
May result in overgrowth of nonsusceptible organisms.
Clostridium difficile –associated diarrhea
Has been reported and may range in severity from mild diarrhea to fatal colitis.
Increases in total bilirubin, PTT, and transaminases have been seen. Isolated cases of significant hepatic dysfunction and hepatic failure have also been reported.
Use caution when considering tigecycline monotherapy in patients with complicated intra-abdominal infections secondary to intestinal perforation.
An increase in all-cause mortality has been observed.
Acute pancreatitis, including fatal cases, has occurred in association with tigecycline.
Prescribing tigecycline in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Tigecycline is structurally similar to tetracycline-class antibiotics and may have similar adverse effects (eg, anti-anabolic action, pancreatitis, photosensitivity, pseudotumor cerebri).
May cause permanent discoloration of teeth (yellow-gray-brown) if used during tooth development (last half of pregnancy, infancy, and children younger than 8 y of age). Do not use during tooth development unless other drugs are not likely to be effective or are contraindicated.
Efficacy not demonstrated in patients with hospital-acquired pneumonia. Lower cure rates and greater mortality were observed in the subgroup of patients with ventilator-associated pneumonia.
Nausea and vomiting.
- Advise patient or caregiver that medication will be prepared and administered by a health care provider in a health care setting.
- Advise patient to take medication exactly as directed. Skipping doses or not completing therapy may decrease the effectiveness of the treatment.
- Review dosing schedule and prescribed length of therapy with patient. Advise patient that duration of therapy is dependent on site, severity of infection, and response to treatment.
- Advise patient or caregiver to immediately inform health care provider if hives, injection-site pain or redness, itching, shortness of breath, or skin rash occur during treatment.
- Advise patient or caregiver to report signs of superinfection to health care provider: black, furry tongue; foul-smelling stools; vaginal itching or discharge; white patches in mouth.
- Warn patient or caregiver that diarrhea containing blood or pus may be a sign of a serious disorder and, if noted after discharge, to seek medical care and not to treat at home.
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