Tigecycline
🧬 Cross-allergy: Tetracyclines
JFDA label: Tagix 50mg
- Mortality:
Mechanism of Action
Inhibitor of Bacterial 70S ribosome — Bacterial 70S ribosome inhibitor
| Target | Action | Gene / class |
|---|---|---|
| Bacterial 70S ribosome efficacy | INHIBITOR |
Indications
Approved
- Canadian labeling
- Intra-abdominal infections, complicated
- Pneumonia, community-acquired bacterial
- Skin and skin structure infections, complicated
- US labeling
Antimicrobial Spectrum
Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.
Bacteria
| Organism | Activity | MIC |
|---|---|---|
| Acinetobacter baumannii | Susceptible | 1.0 mg/L |
| Acinetobacter calcoaceticus | Active | — |
| Bacteroides distasonis | Active | — |
| Bacteroides fragilis | Active | — |
| Bacteroides fragilis group | Susceptible | 2.0 mg/L |
| Bacteroides ovatus | Active | — |
| Bacteroides thetaiotaomicron | Active | — |
| Bacteroides uniformis | Active | — |
| Bacteroides vulgatus | Active | — |
| Citrobacter freundii | Active | — |
| Citrobacter koseri | Active | — |
| Clostridium perfringens | Active | — |
| Enterobacter aerogenes | Active | — |
| Enterobacter cloacae | Active | — |
| Enterococcus avium | Active | — |
| Enterococcus casseliflavus | Active | — |
| Enterococcus faecalis | Susceptible | 0.25 mg/L |
| Enterococcus faecium | Susceptible | 0.25 mg/L |
| Enterococcus gallinarum | Active | — |
| Enterococcus spp. | Susceptible | 0.52 mg/L |
| Escherichia coli | Susceptible | 1.0 mg/L |
| Haemophilus influenzae | Active | — |
| Haemophilus parainfluenzae | Active | — |
| Klebsiella oxytoca | Active | — |
| Klebsiella pneumoniae | Susceptible | 1.0 mg/L |
| Legionella pneumophila | Active | — |
| Listeria monocytogenes | Active | — |
| Mycobacterium abscessus | Active | — |
| Mycobacterium fortuitum | Active | — |
| Pasteurella multocida | Active | — |
| Peptostreptococcus micros | Active | — |
| Serratia marcescens | Active | — |
| Staphylococcus aureus | Susceptible | 0.5 mg/L |
| Staphylococcus epidermidis | Active | — |
| Staphylococcus haemolyticus | Active | — |
| Staphylococcus spp. | Susceptible | 0.53 mg/L |
| Streptococcus A/B/C/G | Susceptible | 0.1253 mg/L |
| Streptococcus agalactiae | Active | — |
| Streptococcus anginosus | Active | — |
| Streptococcus pneumoniae | Active | — |
| Streptococcus pyogenes | Active | — |
Class profile
| gramStatus | Both |
|---|---|
| spectrumBreadth | Extended |
| atypicalCoverage | Yes |
| isBactericidal | 0 |
| moaCategory | Protein synthesis inhibitor (30S ribosomal, glycylcycline) |
| pdIndex | Time-dependent |
| postAntibioticEffect | Short |
| mrsaCoverage | 1 |
| resistanceMechanisms | Overexpression of AcrAB efflux pump,Target site mutations |
Contraindications
Source: Lexicomp
- Additional contraindications (not in U.S. labeling): Hypersensitivity to tetracycline class of antibiotics Absolute
- 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 Absolute
Adverse Reactions
Cardiac disorders (2)
Common Localized phlebitis · septic shock, dizziness, chills, pruritus, hyponatremia, hypocalcemia, dyspepsia, abnormal stools, hypoproteinemia, eosinophilia, increased serum AST, increased serum alkaline phosphatase, hyperbiliru
Renal and urinary disorders (2)
Common Increased blood urea nitrogen · increased serum creatinine
General disorders and administration site conditions (2)
Common Abnormal healing · Inflammation at injection site
Other (3)
Very Common diarrhea · Gastrointestinal: Nausea · vomiting
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
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 (Canadian labeling contraindicates use in patients with hypersensitivity to tetracyclines).
Antianabolic effects
May be associated with antianabolic effects observed with the tetracycline class (including increased BUN, azotemia, acidosis, and hyperphosphatemia).
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
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 (Canadian labeling recommends using with caution) 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 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.
Pregnancy & Lactation
Pregnancy
Because adverse effects were observed in animals and because of the potential for permanent tooth discoloration, tigecycline is classified pregnancy category D. Tigecycline frequently causes nausea and vomiting and, therefore, may not be ideal for use in a patient with pregnancy-related nausea.
Lactation
It is not known if tigecycline is found in breast milk. The manufacturer recommends caution if giving tigecycline to a nursing woman. Nondose-related effects could include modification of bowel flora.
LactMed: monitor the infant.
Monitoring
| Efficacy | Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin) |
|---|---|
| Toxicity | Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea) |
| Clinical pearl | Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship). |
| Counseling | Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h. |
Chemistry & Properties
| Formula | C29H39N5O8 |
|---|---|
| Molecular weight | 585.66 g/mol |
| IUPAC name | (4S,4aS,5aR,12aR)-9-[[2-(tert-butylamino)acetyl]amino]-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide |
| CAS | 220620-09-7 |
| PubChem CID | 54686904 |
| InChIKey | FPZLLRFZJZRHSY-HJYUBDRYSA-N |
| logP | 0.51 (XLogP 1.1) |
| Polar surface area | 205.76 Ų |
| H-bond acceptors / donors | 11 / 7 |
| Drug-likeness (QED) | 0.18 |
| Lipinski violations | 3 |
SMILES
CN(C)c1cc(NC(=O)CNC(C)(C)C)c(O)c2c1C[C@H]1C[C@H]3[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]3(O)C(O)=C1C2=OBiology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 70.0% |
|---|---|
| Half-life | 2.437 h |
| Volume of distribution | 12.48 L/kg |
| Protein binding | 80.7% |
| BBB penetrant | No |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)
Drug–drug interactions (13, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Aminolevulinic acid | major | |
| Bexarotene | major | |
| Aminolevulinic acid (topical) | moderate | |
| Cyclosporine | moderate | |
| Dicoumarol | moderate | |
| Ethinylestradiol | moderate | |
| Methoxsalen | moderate | |
| Methyl aminolevulinate (topical) | moderate | |
| Mycophenolic acid | moderate | |
| Picosulfuric acid | moderate | |
| Porfimer sodium | moderate | |
| Tacrolimus | moderate | |
| Warfarin | moderate |
Registered Products (5)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Tagix | Vial 50 mg | 1 vial | Hikma Pharmaceuticals Co.Ltd/Jordan | — |
| Tegavi | Vial 50 mg | 1 vial | Pharma International Company | — |
| Tegecen 50mg/vial Powder for Solution for Injection | Powder for Injection 50 mg | One Vial pack varies | MS PHARMA/JORDAN | — |
| Tegecen 50mg/vial Powder for Solution for Injection | Powder for Injection 50 mg | 10 vial pack varies | MS PHARMA/JORDAN | — |
| Tygacil 50mg/Vial ( Lyophilized Powder for IV Infusion) | Infusion 50 mg | 10 | Khoury Drug Store | — |