Tigecycline

Usage

Tigecycline is prescribed for complicated skin and soft tissue infections (cSSTI) (excluding diabetic foot infections) and complicated intra-abdominal infections (cIAI). It is classified as a glycylcycline antibiotic, a subclass of tetracyclines. Tigecycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit, preventing aminoacyl-tRNA from entering the A site of the ribosome. This ultimately halts bacterial growth and replication.

Alternate Names

Tigecycline is also known by its international nonproprietary name (INN), tigecycline. A popular brand name for tigecycline is Tygacil®.

How It Works

Pharmacodynamics: Tigecycline exhibits bacteriostatic activity against a broad spectrum of Gram-positive, Gram-negative, and anaerobic bacteria, including multi-drug resistant organisms. Its mechanism of action involves binding to the 30S ribosomal subunit, inhibiting protein synthesis, and thereby preventing bacterial growth.

Pharmacokinetics: Tigecycline is administered intravenously. It has a large volume of distribution, suggesting extensive tissue penetration. It is primarily metabolized in the liver through glucuronidation and excreted mainly through the biliary route, with a small amount eliminated in the urine. Tigecycline is a substrate of P-glycoprotein (P-gp) transporters.

Mode of Action: Tigecycline binds to the 30S ribosomal subunit of bacteria with five times greater affinity than tetracycline, blocking the entry of aminoacyl-tRNA into the ribosome A site, which inhibits protein translation. Unlike other tetracyclines, tigecycline is not affected by the two major tetracycline resistance mechanisms: ribosomal protection proteins and efflux pumps.

Elimination: Tigecycline is primarily eliminated through biliary/fecal excretion (approximately 60%) after hepatic metabolism, with a smaller portion undergoing renal elimination (approximately 30%).

Dosage

Standard Dosage

Adults:

Initial dose: 100 mg IV followed by 50 mg IV every 12 hours. Infusion time: 30-60 minutes. Duration: 5-14 days based on infection severity and clinical response.

Children (8-17 years):

• 8 to <12 years: 1.2 mg/kg IV every 12 hours (maximum 50 mg every 12 hours).
• 12 to <18 years: 50 mg IV every 12 hours. Duration: 5-14 days based on infection severity and clinical response. Pediatric use is generally not recommended due to increased mortality risk observed in adult trials and the potential for tooth discoloration and bone growth inhibition. Tigecycline should only be used in children when no alternative antibacterial drugs are available.

Special Cases:

• Elderly Patients: No dosage adjustment is generally needed.
• Patients with Renal Impairment: No dosage adjustment is necessary.
• Patients with Hepatic Dysfunction:
  • Mild to moderate (Child-Pugh A and B): No dosage adjustment needed.
  • Severe (Child-Pugh C): 100 mg initial dose, followed by 25 mg every 12 hours.
• Patients with Comorbid Conditions: Close monitoring is recommended, especially in patients with diabetes or cardiovascular disease.

Clinical Use Cases

Dosing remains consistent with the standard adult dosage in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations.

Dosage Adjustments

Dose modifications are primarily required for patients with severe hepatic impairment.

Side Effects

Common Side Effects

Nausea, vomiting, diarrhea, abdominal pain, headache, and injection site reactions.

Rare but Serious Side Effects

Pancreatitis, anaphylaxis, jaundice, Stevens-Johnson syndrome, increased mortality (compared to other antibiotics), hepatotoxicity, significant coagulation abnormalities.

Long-Term Effects

Tooth discoloration (especially in children under 8) and potential for reversible bone growth inhibition.

Adverse Drug Reactions (ADR)

Anaphylaxis, severe skin reactions, pancreatitis, and hepatotoxicity.

Contraindications

Hypersensitivity to tigecycline or any tetracycline antibiotic.

Drug Interactions

Tigecycline may interact with warfarin (enhanced anticoagulant effect) and oral contraceptives (reduced efficacy). Co-administration with calcineurin inhibitors (tacrolimus, cyclosporine) may increase serum trough concentrations of the calcineurin inhibitor. Tigecycline is a P-gp substrate, so concomitant use with P-gp inhibitors (ketoconazole, cyclosporine) or inducers (rifampicin) may alter tigecycline levels. It is recommended to monitor serum concentrations of medications with narrow therapeutic indices when used with tigecycline.

Pregnancy and Breastfeeding

Pregnancy: Tigecycline is Pregnancy Category D. It can cause permanent tooth discoloration and reversible bone growth inhibition in the fetus if used during the second and third trimesters. Use only if the potential benefit outweighs the risk.

Breastfeeding: It is unknown whether tigecycline is excreted in human milk. However, animal studies show excretion in rat milk. Due to the potential risk to the newborn/infant, a decision should be made to discontinue breastfeeding or discontinue/abstain from tigecycline therapy, considering the benefits of both. If continued, minimize infant exposure by temporarily withholding breastfeeding for five half-lives of tigecycline after the last dose.

Drug Profile Summary

• Mechanism of Action: Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.
• Side Effects: Nausea, vomiting, diarrhea, pancreatitis, anaphylaxis, increased all-cause mortality.
• Contraindications: Hypersensitivity to tigecycline or tetracyclines.
• Drug Interactions: Warfarin, oral contraceptives, calcineurin inhibitors, P-gp inhibitors/inducers.
• Pregnancy & Breastfeeding: Category D; potential for tooth discoloration and bone growth inhibition in the fetus; unknown effects on breastfeeding infants, but present in rat milk.
• Dosage: Adults: 100 mg initial dose, followed by 50 mg every 12 hours IV. Children (8-17 years): refer to the dosage section. Special adjustments for severe hepatic impairment.
• Monitoring Parameters: Liver function tests, signs of pancreatitis, signs of hypersensitivity reactions, prothrombin time (if co-administered with warfarin), serum concentrations of calcineurin inhibitors (if co-administered), complete blood count (CBC).

Popular Combinations

Not commonly used in combination therapy due to its broad-spectrum activity and risk of increased mortality.

Precautions

Screen for hypersensitivity to tigecycline and tetracyclines. Monitor liver function and for signs of pancreatitis. Assess renal and hepatic function before and during therapy. Use cautiously in pregnant and breastfeeding women. Children under 8 should not receive tigecycline due to potential effects on tooth development and bone growth. Photosensitivity can occur; advise patients to use sun protection.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Tigecycline?

A: Adults: 100 mg initial dose, followed by 50 mg IV every 12 hours. Children (8-17 years): Refer to the dosage section. Adjust for severe hepatic impairment (Child-Pugh C).

Q2: What are the most common side effects of Tigecycline?

A: Nausea, vomiting, diarrhea, and injection site reactions.

Q3: Is Tigecycline safe to use in pregnancy?

A: No. Tigecycline is Pregnancy Category D and should only be used during pregnancy if the potential benefit outweighs the potential risk to the fetus. It may cause permanent tooth discoloration and reversible bone growth inhibition.

Q4: How is Tigecycline administered?

A: Intravenously over 30-60 minutes.

Q5: What are the contraindications for using Tigecycline?

A: Hypersensitivity to tigecycline or any tetracycline antibiotics.

Q6: What are the clinically significant drug interactions with Tigecycline?

A: Warfarin, oral contraceptives, calcineurin inhibitors (e.g., tacrolimus, cyclosporine), and P-gp inhibitors/inducers (e.g., ketoconazole, rifampicin).

Q7: What is the mechanism of action of Tigecycline?

A: Tigecycline binds to the bacterial 30S ribosomal subunit, inhibiting protein synthesis and thus bacterial growth.

Q8: What is the primary route of elimination for Tigecycline?

A: Primarily biliary/fecal excretion after hepatic metabolism (about 60%), with some renal elimination (about 30%).

Q9: Why is Tigecycline use not generally recommended in children?

A: Due to the increased mortality risk observed in clinical trials with adults and the potential for permanent tooth discoloration and reversible bone growth inhibition in children under 8 years of age. Tigecycline should only be used in children if no other suitable antibacterial options are available.

Q10: What monitoring parameters are important when administering Tigecycline?

A: Liver function tests, signs of pancreatitis, hypersensitivity reactions, coagulation parameters if using concomitantly with warfarin, serum concentrations of calcineurin inhibitors if used together, and complete blood count (CBC).