BLACK BOX WARNING
- increased all-cause mortality compared to other antibiotics — reserve for situations where alternative treatments are not suitable
tigecycline
Brand: Tygacil
⚠ BBW Prototype Drug
Drug Class: glycylcycline antibiotic
Drug Family: antibiotic
Subclass: expanded-spectrum tetracycline analog
Organ Systems: infectious-disease
Mechanism of Action
Binds 30S ribosomal subunit with higher affinity than tetracyclines due to the 9-glycylamido group; overcomes tetracycline resistance mechanisms including ribosomal protection and efflux pumps; bacteriostatic with extremely broad spectrum.
30S ribosomal subunit
Indications
- complicated skin/soft tissue infections (cSSSI)
- complicated intra-abdominal infections (cIAI)
- community-acquired bacterial pneumonia (CABP)
Contraindications
- tigecycline hypersensitivity
- pregnancy
- children <8 years
Adverse Effects
Common
- nausea (very frequent, ~30%)
- vomiting
- diarrhea
Serious
- anaphylaxis
- hepatotoxicity
- pancreatitis
- pseudotumor cerebri
- increased all-cause mortality in severe infections (pooled analysis)
Pharmacokinetics (ADME)
| Absorption | IV only |
| Distribution | very large volume of distribution (7–9 L/kg); excellent tissue penetration |
| Metabolism | minimal |
| Excretion | biliary/fecal (59%), renal (33%) |
| Half-life | 42 hours |
| Onset | immediate (IV) |
| Peak | end of infusion |
| Duration | 12 hours (twice-daily dosing) |
| Protein Binding | 71–89% |
| Vd | very large (7–9 L/kg) |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| warfarin | tigecycline increases INR via gut flora suppression; monitor INR | moderate |
| oral contraceptives | gut flora disruption may reduce enterohepatic recirculation of estrogens | minor |
Nursing Considerations
- Pre-medicate with an antiemetic before each tigecycline dose; nausea and vomiting occur in up to 30% of patients and are the primary tolerability issue.
- Administer IV over 30–60 minutes; infusion site reactions including phlebitis can occur.
- Given the FDA black box warning of increased mortality in severe infections, reserve tigecycline for infections without a superior alternative.
- Tigecycline does NOT achieve adequate blood concentrations for bacteremia; do not use as monotherapy when bacteremia is suspected.
Clinical Pearls
- Tigecycline overcomes the two main tetracycline resistance mechanisms (ribosomal protection and efflux), giving it activity against many drug-resistant organisms including MRSA, ESBL producers, and Acinetobacter baumannii.
- Its FDA black box warning notes higher all-cause mortality vs. comparators in pooled analyses of clinical trials; the mechanism is uncertain but may reflect inadequate serum concentrations in bacteremic patients due to its enormous Vd.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.