Tigilyn

5 mL transparent USP type I vial containing a light orange to orange coloured cake.
Each vial contains: Tigecycline 50 mg.

Pharmacotherapeutic group: Antibacterials for systemic use, tetracyclines.
Pharmacology: Pharmacodynamics: Mechanism of Action: Tigecycline (Tigilyn), a glycylcycline antibiotic, inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. In general, Tigecycline (Tigilyn) is considered bacteriostatic. At 4 times the minimum inhibitory concentration (MIC), a 2-log reduction in colony counts was observed with Tigecycline (Tigilyn) against Enterococcus spp., Staphylococcus aureus, and Escherichia coli.
Pharmacokinetics: Absorption: Tigecycline (Tigilyn) is administered intravenously and therefore has 100% bioavailability.
Distribution: The in vitro plasma protein binding of Tigecycline (Tigilyn) ranges from approximately 71% to 89% at concentrations observed in clinical studies (0.1 to 1.0 mcg/mL). Animal and human pharmacokinetic studies have demonstrated that Tigecycline (Tigilyn) readily distributes to tissues.
In rats, receiving single or multiple doses of C-tigecycline, radioactivity was well distributed to most tissues, with the highest overall exposure observed in bone marrow, salivary glands, thyroid gland, spleen, and kidney. In humans, the steady-state volume of distribution of Tigecycline (Tigilyn) averaged 500 to 700 L (7 to 9 L/kg), indicating that Tigecycline (Tigilyn) is extensively distributed beyond the plasma volume and concentrates into tissues.
No data are available on whether Tigecycline (Tigilyn) can cross the blood-brain barrier in humans.
Metabolism: Tigecycline is not extensively metabolized. In vitro studies with Tigecycline (Tigilyn) using human liver microsomes, liver slices, and hepatocytes led to the formation of only trace amounts of metabolites. In healthy male volunteers, receiving C-tigecycline, Tigecycline (Tigilyn) was the primary C-labeled material recovered in urine and feces, but a glucuronide, an N-acetyl metabolite and a Tigecycline (Tigilyn) epimer (each at no more than 10% of the administered dose) were also present.
Elimination: The recovery of the total radioactivity in feces and urine following administration of 14C-tigecycline indicates that 59% of the dose is eliminated by biliary/fecal excretion, and 33% is excreted in urine. Overall, the primary route of elimination for Tigecycline (Tigilyn) is biliary excretion of unchanged Tigecycline (Tigilyn). Glucuronidation and renal excretion of unchanged Tigecycline (Tigilyn) are secondary routes.
The total clearance of Tigecycline (Tigilyn) is 24 L/h after intravenous infusion. Renal clearance is approximately 13% of total clearance. Tigecycline (Tigilyn) shows a polyexponential elimination from serum with a mean terminal elimination half-life after multiple doses of 42 hours although high inter individual variability exists.

For the treatment of complicated skin and skin structure infections or complicated intra-abdominal infections caused by susceptible organisms.

The recommended dosage regimen for Tigecycline (Tigilyn) is an initial dose of 100 mg, followed by 50 mg every 12 hours. Intravenous infusions of Tigecycline (Tigilyn) should be administered over approximately 30 to 60 minutes every 12 hours.
The recommended dosage regimen for Tigecycline (Tigilyn) for complicated skin and skin structure infections or for complicated intra-abdominal infections is 5 to 14 days. The recommended duration of treatment with Tigecycline (Tigilyn) for community-acquired bacterial pneumonia is 7 to 14 days. The duration of therapy should be guided by the severity and site of the infection and the patient's clinical and bacteriological progress. Or as prescribed by the physician.

No specific information is available on the treatment of overdosage. Intravenous administration of Tigecycline (Tigilyn) at a single dose of 300 mg over 60 minutes in healthy volunteers resulted in an increased incidence of nausea and vomiting. Tigecycline (Tigilyn) is not removed in significant quantities by hemodialysis.

Hypersensitivity to the active substance or to any of the excipients. Patients hypersensitive to tetracycline class antibiotics may be hypersensitive to Tigecycline (Tigilyn).

Tigecycline (Tigilyn) is not approved for clinical indications other than complicated skin and soft tissue infections, and complicated intra-abdominal infections. The use of Tigecycline (Tigilyn) in non-approved indications is not recommended.
Anaphylaxis/anaphylactoid reactions, potentially life-threatening, have been reported with Tigecycline (Tigilyn).
Use in Pregnancy: Tigecycline (Tigilyn) may cause fetal harm when administered to a pregnant woman.
The use of Tigecycline (Tigilyn) during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent discoloration of the teeth.

Pregnancy: There are no or limited amount of data from the use of Tigecycline (Tigilyn) in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. As it is known for tetracycline class antibiotics, Tigecycline (Tigilyn) may also induce permanent dental defects (discolouration and enamel defects) and a delay in ossification processes in fetuses, exposed in utero during the last half of gestation, and in children under eight years of age due to the enrichment in tissues with a high calcium turnover and formation of calcium chelate complexes. Tigecycline (Tigilyn) should not be used during pregnancy unless the clinical condition of the woman requires treatment with Tigecycline (Tigilyn).
Breastfeeding: It is unknown whether Tigecycline (Tigilyn) metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of Tigecycline (Tigilyn) metabolites in milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Tigecycline (Tigilyn) therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility: Tigecycline (Tigilyn) did not affect mating or fertility in rats at exposures up to 4.7 times the human daily dose based on AUC. In female rats, there were no compound-related effects on ovaries or oestrus cycles at exposures up to 4.7 times the human daily dose based on AUC.

The most common side effects with Tigecycline (Tigilyn) are nausea, vomiting, diarrhea, hypoglycaemia, dizziness, abdominal pain, dyspepsia, anorexia, pruritus, rash and headache.

Interaction studies have only been performed in adults.
Concomitant administration of Tigecycline (Tigilyn) and warfarin (25 mg single-dose) to healthy subjects resulted in a decrease in clearance of R-warfarin and S-warfarin by 40% and 23%, and an increase in AUC by 68% and 29%, respectively. The mechanism of this interaction is still not elucidated. Available data does not suggest that this interaction may result in significant INR changes. However, since Tigecycline (Tigilyn) may prolong both prothrombin time (PT) and activated partial thromboplastin time (aPTT), the relevant coagulation tests should be closely monitored when Tigecycline (Tigilyn) is co-administered with anticoagulants. Warfarin did not affect the pharmacokinetic profile of Tigecycline (Tigilyn).
Tigecycline (Tigilyn) is not extensively metabolised. Therefore, clearance of Tigecycline (Tigilyn) is not expected to be affected by active substances that inhibit or induce the activity of the CYP450 isoforms. In vitro, Tigecycline (Tigilyn) is neither a competitive inhibitor nor an irreversible inhibitor of CYP450 enzymes.
Tigecycline (Tigilyn) in recommended dosage did not affect the rate or extent of absorption, or clearance of digoxin (0.5 mg followed by 0.25 mg daily) when administered in healthy adults. Digoxin did not affect the pharmacokinetic profile of Tigecycline (Tigilyn). Therefore, no dosage adjustment is necessary when Tigecycline (Tigilyn) is administered with digoxin.
In in vitro studies, no antagonism has been observed between Tigecycline (Tigilyn) and other commonly used antibiotic classes.
Concurrent use of antibiotics with oral contraceptives may render oral contraceptives less effective.

Directions for Reconstitution: Each vial of Tigecycline (Tigilyn) should be reconstituted with 5.2 mL of 0.9% Sodium Chloride Injection BP or 5.2 mL of 5% Dextrose Injection BP to achieve a concentration of 10 mg/mL of Tigecycline (Tigilyn).
The vial should be gently swirled until the drug dissolves. Immediately withdraw 5 mL of the reconstituted solution from the vial and add to a 100 mL IV bag for infusion for a 100 mg dose, reconstitute two vials, for a 50 mg dose, reconstitution solution should be yellow to orange in colour, if not, the solution should be discarded.

Store at temperatures not exceeding 30°C.
Store reconstituted solution in the IV bag at room temperature for up to 6 hours and between 2°C-8°C for up to 24 hours.

Tetracyclines

J01AA12 - tigecycline ; Belongs to the class of tetracyclines. Used in the systemic treatment of infections.

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