TIGECYCLINE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Tigecycline is a glycylcycline antibiotic that inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit, blocking entry of amino-acyl tRNA into the A site, thereby preventing peptide chain elongation.
| Metabolism | Tigecycline is not extensively metabolized. It undergoes minimal hepatic metabolism, primarily via glucuronidation and possibly by amide hydrolysis, but specific CYP450 enzymes are not significantly involved. |
| Excretion | Approximately 59% of the dose is excreted via bile/feces, with 22% eliminated unchanged in urine. The remainder undergoes hepatic metabolism. |
| Half-life | Terminal elimination half-life is approximately 27-42 hours in patients with normal renal function, supporting twice-daily dosing. Half-life may be prolonged in severe hepatic impairment. |
| Protein binding | Tigecycline is primarily bound to plasma proteins, with a binding rate of approximately 71-89% (mainly to albumin and lipoproteins). |
| Volume of Distribution | Volume of distribution is large, ranging from 7-10 L/kg, indicating extensive tissue penetration and distribution beyond plasma volume. |
| Bioavailability | Tigecycline is administered only intravenously; oral bioavailability is negligible due to poor absorption. Absolute IV bioavailability is 100%. |
| Onset of Action | Intravenous administration: Onset of action is rapid, with therapeutic plasma levels achieved within 60 minutes following a 30-60 minute infusion. |
| Duration of Action | Duration of action is approximately 12 hours post-dose, aligning with the recommended dosing interval of every 12 hours. Clinical effect persists for the dosing interval. |
Loading dose: 100 mg IV once, then 50 mg IV every 12 hours.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for renal impairment, including hemodialysis. Tigecycline is not removed by hemodialysis. |
| Liver impairment | Child-Pugh A and B: No adjustment. Child-Pugh C: Loading dose 100 mg IV once, then 25 mg IV every 12 hours. |
| Pediatric use | For patients aged 8 to 11 years: 1.2 mg/kg IV every 12 hours (maximum dose 50 mg per infusion). For patients aged 12 to 17 years: 50 mg IV every 12 hours. |
| Geriatric use | No specific dose adjustment; monitor for adverse effects, as elderly patients may have increased risk of mortality and gastrointestinal effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Warfarin metabolism may be affected increasing INR Can increase all-cause mortality and is reserved for use when alternatives are not suitable.
| Breastfeeding | It is unknown whether tigecycline is excreted in human breast milk. A risk to the breastfeeding infant cannot be excluded. The M/P ratio is not available. Tigecycline should be used with caution during breastfeeding only if clearly needed. |
| Teratogenic Risk | Tigecycline is classified as FDA Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience. In animal studies, tigecycline caused reduced fetal weights and minor skeletal abnormalities. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Avoid use in the first trimester if possible. |
■ FDA Black Box Warning
An increase in all-cause mortality was observed in clinical trials with tigecycline compared to comparators. The cause of this increase has not been established. Tigecycline should be reserved for use in patients with limited or no alternative treatment options.
| Common Effects | Nausea |
| Serious Effects |
["Hypersensitivity to tigecycline or any component of the formulation","Use in patients with known hypersensitivity to tetracyclines"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis","Hepatic effects: increased liver enzymes, hepatic dysfunction","Pancreatitis","Fetal harm if used in pregnancy; avoid in pregnant women unless benefit outweighs risk","Tooth discoloration in children <8 years","Use in patients with intestinal perforation: risk of sepsis","Photosensitivity","Superinfection: prolonged use may result in bacterial or fungal overgrowth"] |
Loading safety data…
| Fetal Monitoring | Monitor for signs of hepatotoxicity and pancreatitis in both mother and fetus. Monitor liver function tests (AST, ALT, bilirubin) and pancreatic enzymes (amylase, lipase) periodically. Assess for fetal growth and well-being via ultrasound if clinical concerns arise. |
| Fertility Effects | Tigecycline has not been studied for effects on fertility in humans. In animal studies, there were no effects on mating or fertility at clinically relevant doses. However, theoretical risks from its anti-anaerobic activity on gut flora may indirectly affect fertility. |