Dosing and uses of Tygacil (tigecycline)
Adult dosage forms and strengths
powder for injection
- 50mg/vial
Complicated Intra-abdominal Infections
Initial: 100 mg IV infusion, THEn
50 mg IV infusion q12hr for 5-14 days
Complicated Skin Infections
Initial: 100 mg IV infusion, THEn
50 mg IV infusion q12hr for 5-14 days
Community-Acquired Pneumonia
Initial: 100 mg IV infusion, THEn
50 mg IV infusion q12hr for 7-14 days
Acute Myeloid Leukemia (Orphan)
Orphan designation for treatment of acute myeloid leukemia
Tigecycline selectively targets leukemia cells and leukemic stem cells by inhibiting mitochondrial protein synthesis
Orphan sponsor
- Stem Cell Therapeutics Corporation; 96 Skyway Avenue; Toronto, ON M9W 4Y9, Canada
Dosing Modifications
Renal impairment: Dose adjustment not necessary (minimum dialyzed through hemodialysis or peritoneal dialysis)
Hepatic impairment
- Severe (Child-Pugh C): Maintenance 25 mg IV q12hr (following initial 100 mg)
Dosing Considerations
Not indicated for the treatment of diabetic foot infections; a clinical trial failed to demonstrate noninferiority
Not indicated for the treatment of hospital-acquired or ventilator-associated pneumonia; in a comparative clinical trial, greater mortality and decreased efficacy were reported in tigecycline-treated patients
Susceptible organisms
- Complicated skin infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible only), Staphylococcus aureus (MRSA and methicillin-susceptible), Streptococcus pyogenes, Streptococcus anginosus grp, Streptococcus agalactiae, or Bacteroides fragilis
- Complicated intra-abdominal infections caused by E coli, Enterococcus faecalis (vancomycin-susceptible only), S aureus (methicillin-susceptible only), Citrobacter freundii, Enterobacter cloacae, Klebsiella pneumoniae, K oxytoca, B thetaiotaomicron, B uniformis, B vulgatus, Clostridium perfringens, Peptostreptococcus micros
- Community-acquired pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Tygacil (tigecycline) adverse (side) effects
>10%
Nausea (29.5%)
Vomiting (19.7%)
Diarrhea (12.7%)
1-10%
Infection (8.3%)
Fever (7.1%)
Abd pain (6.8%)
Headache (5.9%
HTN (4.9%)
Anemia (4.2%)
Dizziness (3.5%)
Dyspnea (2.9%)
Pruritus (2.6%)
Rash (2.4%)
Hypotension (2.3%)
Insomnia (2.3%)
Postmarketing Reports
Anaphylaxis/anaphylactoid reactions
Acute pancreatitis
Hepatic cholestasis and jaundice
Severe skin reactions, including Stevens-Johnson Syndrome
Symptomatic hypoglycemia in patients with or without diabetes mellitus
Prolonged activated partial thromboplastin time (aPTT), prolonged prothrombin time (PT), eosinophilia, increased international normalized ratio (INR), thrombocytopenia
Warnings
Black box warnings
Increased mortality with use of tigecycline for FDA-approved indications, as well as for nonapproved indications, compared with other antibiotics
FDA approved to treat complicated skin and skin structure infections (cSSSI), complicated intra-abdominal infections (cIAI), and community-acquired bacterial pneumonia (CABP); it is not approved for treatment of diabetic foot infection or for hospital-acquired or ventilator-associated pneumonia
Analysis from 10 clinical trials for FDA-approved uses (cSSSI, cIAI, CABP), including trials conducted after the drug was approved, showed a higher risk of death among patients receiving tigecycline, compared with other antibacterial drugs: 2.5% (66/2640) vs. 1.8% (48/2628), respectively; the adjusted risk difference for death was 0.6%, with a corresponding 95% confidence interval (0.0%, 1.2%)
Contraindications
Documented hypersensitivity
Cautions
Severe hepatic impairment
Pregnancy
Caution in severe hepatic impairment (reduce dose); patients who develop abnormal liver function tests during therapy should be monitored for evidence of worsening hepatic function and evaluated for risk/benefit of continuing tigecycline therapy
Use during tooth development may cause permanent discoloration of teeth
May permit clostridia overgrowth, resulting in antibiotic-associated colitis; evaluate for Clostridium difficile if diarrhea occurs
Avoid use in patients with known hypersensitivity to tetracyclines
May have adverse effects similar to those of tetracyclines (eg, photosensitivity, pseudotumor cerebri, antianabolic action)
Pancreatitis, including fatalities, reported; if pancreatitis suspected, consider stopping treatment
Increased mortality risk with use of IV tigecycline (see Black box warnings)
May cause fetal harm when administered to a pregnant woman
Pregnancy and lactation
Pregnancy category: d
Lactation: Not known whether distributed in breast milk; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tygacil (tigecycline)
Mechanism of action
A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics; inhibits bacterial protein translation by binding to 30S ribosomal subunit, and blocks entry of amino-acyl tRNA molecules in ribosome A site.
Distribution
Protein bound: 71-89%
Vdss: 500-700 L
Metabolism
Not extensive
Elimination
Half-life: (single dose) 27 hr; (multiple dose) 42 hr
Excretion: urine (33%); feces (59%)
Administration
IV Incompatibilities
Y-site: amphotericin B, chlorpromazine, methylprednisolone, voriconazole
IV Compatibilities
Solution: NS, D5W
Y-site: dobutamine, dopamine, LR, KCl, theophylline, ranitidine, lidocaine
IV Preparation
Reconstitute each vial with 5.3 mL NS or D5W to achieve a conc of 10 mg/mL
Gently swirl to dissolve
Immediately withdraw 5 mL and add to a 100-mL infusion bag
IV Administration
Infuse over 30-60 min
Through dedicated line or Y-site
Storage
Store vials at 20-25°C (68-77°F)
May be stored in IV bag at room temp for up to 6 hr or refrigerated at 2-8°C for up to 24 hr
