Tygacil 50mg / 5ml Infusion

TYGACIL is indicated for treatment of the following severe life-threatening infections in adults:

• Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus group (includes S.anginosus, S.intermedius, and S. constellatus), Streptococcus pyogenes and Bacteroides fragilis.
• Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus anginosus group (includes S.anginosus, S.intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros.

The recommended dosage regimen for TYGACIL is an initial dose of 100 mg, followed by 50 mg every 12 hours. Intravenous (IV) infusions of TYGACIL should be administered over approximately 30 to 60 minutes every 12 hours. The recommended duration of treatment with TYGACIL for complicated skin and skin structure infections or for complicated intra-abdominal infections is 5 to 14 days. The duration of therapy should be guided by the severity and site of the infection and the patientu2019s clinical and bacteriological progress.

TYGACIL is contra-indicated for use in patients who have known hypersensitivity to TYGACIL.

Anaphylaxis/anaphylactoid reactions have been reported with nearly all antibacterial agents, including TYGACIL, and may be life-threatening. Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Therefore, TYGACIL should be administered with caution in patients with known hypersensitivity to tetracycline class antibiotics. Results of studies in rats with TYGACIL have shown bone discolouration. TYGACIL may be associated with permanent tooth discolouration in the teeth in humans during tooth development. Pseudomembranous colitis has been reported with TYGACIL. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of TYGACIL.

Effects on Activities Requiring Concentration and Performance: TYGACIL can cause dizziness (see SIDE EFFECTS AND SPECIAL PRECAUTIONS), which may impair the ability to drive and/or operate machinery.

TYGACIL (100 mg followed by 50 mg every 12 hours) and digoxin (0.5 mg followed by 0.25 mg every 24 hours) were co-administered to healthy subjects in a drug interaction study. TYGACIL slightly decreased the C max of digoxin by 13%, but did not affect the AUC or clearance of digoxin. This small change in C max did not affect the steady-state pharmacodynamic effects of digoxin as measured by changes in ECG intervals. In addition, digoxin did not affect the pharmacokinetic profile of TYGACIL. Therefore, no dosage adjustment is necessary when TYGACIL is administered with digoxin.

Concomitant administration of TYGACIL (100 mg followed by 50 mg every 12 hours) 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. TYGACIL did not significantly alter the effects of warfarin on increased international normalized ratio (INR). In addition, warfarin did not affect the pharmacokinetic profile of TYGACIL. However, prothrombin time or other suitable anticoagulation test should be monitored if TYGACIL is administered with warfarin.

In vitro studies in human liver microsomes indicate that TYGACIL does not inhibit metabolism mediated by any of the following 6 cytochrome CYP450 isoforms: 1A2, 2C8, 2C9, 2C19, 2D6, and 3A4. Therefore, TYGACIL is not expected to alter the metabolism of drugs metabolized by these enzymes. In addition, because TYGACIL is not extensively metabolized, clearance of TYGACIL is not expected to be affected by drugs that inhibit or induce the activity of these CYP450 isoforms.

Concurrent use of antibiotics with oral contraceptives may render oral contraceptives less effective.

Pregnancy: TYGACIL may cause foetal harm when administered to a pregnant woman. Results of animal studies indicate that TYGACIL crosses the placenta and is found in foetal tissues. There are no adequate and well-controlled studies of TYGACIL in pregnant women. TYGACIL should not be used during pregnancy. TYGACIL has not been studied for use during labour and delivery.

Lactation: Results from animal studies using 14C-labeled TYGACIL indicate that TYGACIL is excreted readily via the milk of lactating rats. It is not known whether this drug is excreted in human milk.

TYGACIL can cause dizziness (see SIDE EFFECTS AND SPECIAL PRECAUTIONS), which may impair the ability to drive and/or operate machinery.

Expected frequency of adverse reactions is presented in CIOMS frequency categories: Very Common u2265 10%, Common: u2265 1% and < 10%, Uncommon: u2265 0.1% and < 1%, Rare: u2265 0.01% and < 0.1%, Very rare: < 0.01%.

For patients who received TYGACIL, the following adverse reactions were reported:

• Blood and lymphatic system disorders: Common - Prolonged activated partial thromboplastin time (aPTT), Prolonged prothrombin time (PT); Uncommon - Increased international normalized ratio (INR).
• Immune system disorders: Frequency undetermined - Anaphylaxis/anaphylactoid reactions.
• Metabolism and nutrition disorders: Common - Bilirubinaemia, increased Blood Urea Nitrogen (BUN); Uncommon - Hypoproteinaemia.
• Nervous system disorders: Common - Dizziness.
• Cardiac disorders: Common - Phlebitis; Uncommon - Thrombophlebitis.
• Gastrointestinal disorders: Very common - Nausea, vomiting, diarrhoea; Common - Anorexia, abdominal pain, dyspepsia; Uncommon - Acute pancreatitis.
• Hepato-biliary disorders: Common - Frequency undetermined - Elevated aspartate aminotransferase (AST) in serum, elevated alanine aminotransferase (ALT) in serum; Hepatic cholestasis.
• Skin and subcutaneous tissue disorders: Common - Pruritus, rash.
• General disorders and administration site conditions: Common - Headache; Uncommon - Injection site inflammation, injection site pain, injection site reaction, injection site oedema, injection site phlebitis.
• Investigations: Common - Elevated amylase in serum.

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