Tigecycline (Tygacil) is a bacteriostatic antibiotic that inhibits protein synthesis by attaching to the 30S ribosomal subunit of sensitive bacteria.

In 2019, it was removed from the WHO's list of essential medicine

It is used to treat the following infections:

• Patients older than 18 with community-acquired bacterial pneumonia caused by:
  • Penicillin-susceptible isolates of Streptococcus pneumoniae including cases with concurrent bacteremia,
  • Haemophilus influenzae,
  • Legionella pneumophila &  
  • Chlamydia pneumoniae
• Severe intra-abdominal infections in people over the age of 18 brought on by:
  • Methicillin-susceptible and methicillin-resistant isolates of Staphylococcus aureus,
  • Citrobacter freundii,
  • Enterobacter cloacae,
  • Escherichia coli,
  • Klebsiella oxytoca,
  • Klebsiella pneumoniae,
  • Vancomycin-susceptible isolates of Enterococcus faecalis,
  • Streptococcus anginosus group including S. anginosus, Streptococcus intermedius, and Streptococcus constellatus,
  • Bacteroides fragilis,
  • Bacteroides thetaiotaomicron,
  • Bacteroides uniformis,
  • Bacteroides vulgatus,
  • Clostridium perfringens, and
  • Peptostreptococcus micros.

• Infections of the skin and soft tissues that are complicated in people over the age of 18 brought on by:

  • E. coli,
  • Vancomycin susceptible isolates of E. faecalis,
  • Streptococcus agalactiae,
  • S. anginosus group including S. anginosus, S. intermedius, and S. constellatus,
  • S. anginosus ,
  • Streptococcus pyogenes,
  • E. cloacae,
  • K. pneumoniae,
  • B. fragilis &
  • Methicillin-susceptible and methicillin-resistant isolates of Staphylococcus aureus.

Tigecycline (Tygacil) Dose in Adults

Tigecycline (Tygacil) dosage in the treatment of  community-acquired Pneumonia:

• Initially, a single intravenous injection of 100 mg;
• For 7 to 14 days, the maintenance dose is 50 mg every 12 hours.

Tigecycline (Tygacil) dosage in the treatment of complicated Intra-abdominal infections:

• 100 mg intravenously as a single dosage at first
• For 5 to 14 days, the maintenance dose is 50 mg every 12 hours.

Tigecycline (Tygacil) dosage in the treatment of complicated skin/skin structure infections:

• First, one dose of 100 mg intravenously;
• For 5 to 14 days, the maintenance dose is 50 mg every 12 hours.

Tigecycline (Tygacil) Dose in Children

Tigecycline (Tygacil) dosing in susceptible infection:

1 It should not be used in pediatric patients  younger than 8 years due to adverse effects on tooth development unless no alternatives are available

• Infants and Children <8 years:

  • Loading dose (optional):

    • 1.5 to 3 mg/kg intravenously once

  • Maintenance dose: 

    • Every 12 hours, 1 to 2 mg/kg/dose is administered.
    • 50 mg is the maximum dose per dose.
    • A maintenance dose of 2 mg/kg every 12 hours has been utilised if no loading dose is administered.

• Children ≥8 years and Adolescents

  • 8 to 11 years:

    • Every 12 hours, an intravenous dose of 1.2 to 2 mg/kg is administered.
    • 50 mg is the maximum dose per dose.

  • ≥12 years:

    • 50 mg IV every 12 hours is given

Tigecycline (Tygacil) Pregnancy Risk Factor D

• Tigecycline is classified in pregnancy category D because of its potential to cause permanent tooth discoloration and adverse effects on animals.
• Tigecycline can cause nausea and vomiting, so it is not recommended for pregnant women.

Tigecycline (Tygacil) use during breastfeeding:

• If tigecycline is found in breast milk is unknown.
• Tigecycline should not be given to a woman who is nursing.
• Modification of the bowel flora is an example of non-dose-related effects.

Tigecycline (Tygacil) Dose in Renal disease:

• No dosage adjustment is required

End-stage renal disease (ESRD) on dialysis:

• It is poorly dialyzed
• Patients undergoing intermittent hemodialysis, peritoneal dialysis, or continuous renal replacement treatment do not require the addition of a dose or a dosage change (eg, CVVHD).

Tigecycline (Tygacil) Dose in Liver disease:

• Mild-to-moderate hepatic impairment (Child-Pugh class A or B):

  • dosage adjustment not required.

• Severe hepatic impairment (Child-Pugh class C):

  • 100 mg single dose is given initially;
  • Every 12 hours, a dose of 25 mg is used for maintenance.

Common Side Effects of Tigecycline (Tygacil):

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Diarrhea

Less Common Side Effects of Tigecycline (Tygacil):

• Cardiovascular:

  • Localized Phlebitis
  • Septic Shock
  • Thrombophlebitis

• Central Nervous System:

  • Headache
  • Dizziness
  • Chills

• Dermatologic:

  • Skin Rash
  • Pruritus

• Endocrine & Metabolic:

  • Increased Amylase
  • Hyponatremia
  • Hypocalcemia
  • Hypoglycemia

• Gastrointestinal:

  • Abdominal Pain
  • Dyspepsia
  • Abnormal Stools
  • Anorexia
  • Dysgeusia

• Genitourinary:

  • Leukorrhea
  • Vaginitis
  • Vulvovaginal Candidiasis

• Hematologic & Oncologic:

  • Anemia
  • Hypoproteinemia
  • Eosinophilia
  • Increased INR
  • Prolonged Partial Thromboplastin Time
  • Prolonged Prothrombin Time
  • Thrombocytopenia

• Hepatic:

  • Increased Serum ALT
  • Increased Serum AST
  • Increased Serum Alkaline Phosphatase
  • Hyperbilirubinemia
  • Jaundice

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Infection
  • Abscess

• Local:

  • Inflammation At Injection Site
  • Injection Site Reaction
  • Pain At Injection Site
  • Swelling At Injection Site

• Neuromuscular & Skeletal:

  • Weakness

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine

• Respiratory:

  • Pneumonia

Contraindications to Tigecycline (Tygacil):

• Allergy to tigcycline or any component of the formulation
• Very few studies have documented allergenic cross-reactivity with tetracyclines.
• Hypersensitivity to the tetracycline antibiotic class.

Warnings and precautions

• Anaphylactic and hypersensitivity reactions
  • Can lead to life-threatening anaphylaxis.
  • Patients with hypersensitivity to tetracyclines-class antibiotics should not be given this medication due to their structural similarities.
• Antianabolic effects
  • It may be associated with the antianabolic effects of the tetracycline tetracycline classes (e.g., increased BUN, azotemia and acidosis and hyperphosphatemia).
• Hepatotoxicity:
  • A few abnormal liver function tests have been observed (increased total and prothrombin times, transaminases, etc.
  • There have been reports of liver dysfunction and liver failure.
  • Patients with abnormal liver function tests need to be carefully watched for any symptoms of hepatic dysfunction.
  • After discontinuation of a drug, adverse hepatic effects may occur.
• Pancreatitis
  • Patients without known risk factors have been diagnosed with acute pancreatitis, which can lead to fatalities.
  • If you suspect that your treatment is not working, discontinue it.
• Photosensitivity
  • Photosensitivity can be linked to tetracyclines' structural similarities.
• Pseudotumor cerebri:
  • Due to structural similarities with Tetracyclines, can be mistaken for pseudotumor cerebri.
• Superinfection
  • Long-term use may lead to fungal or bacterial superinfection, including pseudomembranous colitis and C.difficile-associated diarrhoea (CDAD).
• Treatment-related Mortality: [US Boxed Warning]
  • A meta-analysis of Phase 3, 4 and 5 clinical trials showed an increase in all-cause death in patients treated with tigecycline compared to patients who were not.
  • You should not use it if other treatments are unavailable.
  • Deaths were generally the result of a worsening infection, complications, or an underlying condition.
• Hepatic impairment
  • Hepatic patients need to exercise caution.
  • It is advised to alter the dosage in cases of severe hepatic impairment.
• Intestinal infections
  • It is best to avoid its monotherapy in patients with intestinal perforation.
  • In a small number of cases, sepsis/septichock occurred more often than patients who were treated with imipenem/cilastatin comparator.

Tigecycline: Drug Interaction

Monitor:

• Monitor hepatic function periodically.
• Anaphylaxis symptoms and signs should be watched while administering

How to administer Tigecycline (Tygacil)?

• It should be administered intravenously over 30 to 60 minutes through a dedicated line or via Y-site.
• If the same intravenous line is used for sequential infusion of several drugs, then flush the line with NS, D5W, or LR before and after tigecycline administration.

Mechanism of action of Tigecycline (Tygacil):

• It is a glycylcycline antibacterial that binds with the 30S subunit of susceptible bacteria and inhibits its protein synthesis.
• They are generally considered to be bacteriostatic.
• However, the bactericidal properties of L. pneumophila and S. pneumoniae have been shown to be effective.
• Tigecycline, although not classified as a tetracycline, it is a derivative of minocycline (9-t-butylglycylamido minocycline) and shares some class-associated adverse effects.
• Methicillin-resistant staphylococci and other gram-positive and gram-negative bacterial pathogens have been successfully combatted by it.

Distribution:

• It has extensive tissue distribution including the gallbladder, lungs, and colon.

Protein binding: 71% - 89%

Metabolism:

• Mainly hepatic, via glucuronidation, N-acetylation, and epimerization to several metabolites, each <10% of the dose

Half-life elimination:

• Single dose is 27 hours & following multiple doses is 42 hours; It is increased by 23% in moderate hepatic impairment and 43% in severe hepatic impairment

Excretion:

• Via feces (59%, primarily as unchanged drug); urine (33%, with 22% of unchanged drug)
• Clearance: 25% less in individuals with mild hepatic impairment, and 55% less in those with severe hepatic impairment.

International Brands of Tigecycline:

• Bacticil
• Capessa
• Linicetil
• Standiga
• Tagix
• Treprex
• Tygacil
• Tylin
• Widebac IV

Tigecycline brands in Pakistan:

• B Tig (Inj. 50 mg - 2940 per vial) - Bosch
• Tagagy (Inj. 50 mg - 2940 per vial) - MTI
• TigaBio (Inj. 50 mg - 2940 per vial) - Bio-Labs
• Tigatec (Inj. 50 mg - 2940 per vial) - Laderly
• Tigelin (Inj. 50 mg - 2500 per vial) - Global/ Vision
• Tilane (Inj. 50 mg - 2500 per vial) - Continental Pharma
• Tygacil (Inj. 50 mg - 4200 per vial)  - Pfizer [/bg_collapse]