Tigecycline

BRAND NAMES

• Tygacil –
  The most widely known and original brand name, manufactured by Pfizer.
  Approved in many countries including the USA, UK, Canada, and EU.

• Tigecyl –
  A generic version available in some countries such as India.

MECHANISM OF ACTION

Tigecycline, a member of the glycylcycline class, works by inhibiting bacterial protein synthesis. It binds to the 30S ribosomal subunit, blocking the entry of aminoacyl-tRNA into the A site of the ribosome. This action prevents the addition of amino acids to the growing peptide chain, effectively halting protein production in bacteria.

Structurally, tigecycline is derived from minocycline, with a unique glycylamido group attached at the 9-position. This specific chemical modification is not found in any naturally occurring or semisynthetic tetracycline and gives tigecycline distinctive microbiological properties.

PHARMACOKINETICS

Absorption:

Tigecycline is administered exclusively by intravenous injection because it is poorly absorbed through the gastrointestinal tract. Its low oral bioavailability makes it unsuitable for oral use, as it would not achieve effective concentrations in the bloodstream to treat systemic infections.

Distribution

Tigecycline is administered intravenously and has a large volume of distribution (greater than 12 L/kg), allowing it to penetrate effectively into various tissues, including the bone, lungs, liver, and kidneys.

Metabolism:

Tigecycline undergoes minimal metabolism. In vitro studies using human liver microsomes, liver slices, and hepatocytes have shown that only trace amounts of metabolites are formed. The main metabolites identified include a glucuronide conjugate, an N-acetyl derivative, and a tigecycline epimer—each accounting for no more than 10% of the administered dose.

Excretion:

Tigecycline is mainly excreted through the bile into the feces, with a lesser amount eliminated by the kidneys. Because of this elimination pattern, dose adjustments may be necessary in patients with severe hepatic impairment, whereas no adjustment is usually needed for those with renal impairment.

PHARMACODYNAMICS

Tigecycline is the first clinically available antibiotic from the newly developed glycylcycline class. Glycylcyclines are tetracycline derivatives specifically engineered to overcome common resistance mechanisms associated with traditional tetracyclines. These include resistance due to acquired efflux pumps and ribosomal protection proteins, which often limit the effectiveness of older tetracycline antibiotics.

ADMINISTRATION

Tigecycline is an intravenous antibiotic used for treating severe bacterial infections, including complicated skin and intra-abdominal infections. Because studies have shown a higher risk of mortality compared to other antibiotics, its use is generally limited to situations where no suitable alternatives are available. Tigecycline is given only through IV infusion, typically over 30 to 60 minutes. In paediatric patients, it is recommended to administer the infusion over 60 minutes for safety (refer to sections 4.4 and 6.6).

DOSAGE AND STRENGTH

Tigecycline (Tygacil) is available as a 50 mg powder intended for intravenous infusion. In adults aged 18 and over, it is used to treat serious infections such as complicated skin and soft tissue infections, complicated intra-abdominal infections, and community-acquired bacterial pneumonia. Treatment typically begins with an initial IV loading dose, followed by regular maintenance doses, with a treatment duration of 5 to 14 days, depending on the clinical condition. For patients with severe liver impairment (Child-Pugh Class C), a reduction in the maintenance dose is usually recommended after the initial dose. In contrast, no dose adjustment is generally required for patients with renal impairment.

DRUG INTERACTIONS 

• Acenocoumarol: Co-administration with tigecycline may increase the serum concentration of acenocoumarin, potentially enhancing its anticoagulant effect.

• Acitretin: When used together with tigecycline, there is an increased risk or severity of pseudotumor cerebri (a condition resembling increased intracranial pressure).

• Alitretinoin: Combining alitretinoin with tigecycline may raise the risk or worsen symptoms of pseudotumor cerebri.

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FOOD INTERACTIONS

• Since tigecycline is not taken orally, no significant food interactions have been reported.

• Unlike oral tetracyclines, which can be affected by dairy products or antacids, tigecycline does not interact with calcium, magnesium, or other food components.

• Nausea and vomiting are common side effects of tigecycline; taking the infusion with a light meal beforehand (if medically appropriate) may help reduce gastrointestinal discomfort, although this is a supportive measure and not related to drug absorption.

CONTRAINDICATIONS

Tigecycline is not recommended for use in patients with a known allergy to the drug and in children under 8 years old. It carries a boxed warning due to an increased risk of death, so its use should be limited to cases where no appropriate alternative treatments are available.

SIDE EFFECTS

• Persistent cough or hoarseness

  • Feeling dizzy or lightheaded

  • Experiencing fever or chills

  • Headaches

  • Pain in the lower back or sides

  • Sensations of pain, warmth, or burning in fingers, toes, or legs

  • Painful or difficult urination

  • Issues with vision or hearing

OVER DOSE

Overdosing on tigecycline can increase the severity of its most common side effects, such as nausea and vomiting. Tigecycline is an intravenous-only antibiotic, so a healthcare professional will typically administer it. There is no specific treatment for an overdose other than supportive care, and the drug is not effectively removed by hemodialysis

TOXICITY

The most common side effects of tigecycline include nausea, vomiting, and diarrhea. It may also cause liver-related issues, such as elevated liver enzymes and, in rare cases, serious liver dysfunction or jaundice. Additional potential adverse effects include photosensitivity, anaphylaxis (a severe allergic reaction), serious skin conditions like toxic epidermal necrolysis, and pancreatitis.