4.8 Undesirable effects

 a. Summary of safety profile

The total number of patients treated with tigecycline in Phase 3 clinical studies was 1415. Adverse reactions were reported in approximately 41 % of patients treated with tigecycline. Treatment was discontinued due to adverse reactions in 5 % of patients.

In clinical trials, the most common drug-related treatment emergent adverse reactions were reversible nausea (20 %) and vomiting (14 %), which usually occurred early (on treatment days 1-2) and were generally mild or moderate in severity.

Adverse reactions reported with Tygacil, including clinical trials and post-marketing experience, are listed below:

Frequency categories are expressed as: Very common (1/10); Common (1/100 to <1/10); Uncommon (1/1,000 to <1/100); Rare (1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data)

For adverse reactions identified from post-marketing experience with Tygacil derived from spontaneous reports for which the frequency cannot be estimated, the frequency grouping is categorized as not known.

b. Tabulated summary of adverse reactions

Infections and infestations:

Common: Pneumonia, abscess, infections

Uncommon: Sepsis/septic shock

Blood and the lymphatic system disorders:

Common: Prolonged activated partial thromboplastin time (aPTT), Prolonged prothrombin time (PT)

Uncommon: Increased International Normalised Ratio (INR)

Not known: thrombocytopenia

Immune system disorders:

Not known: Anaphylaxis/anaphylactoid reactions (see sections 4.3 and 4.4)

Metabolism and nutrition disorders:

Common: Hypoglycaemia

Uncommon: Hypoproteinaemia

Nervous system disorders:

Common: Dizziness

Vascular disorders:

Common: Phlebitis

Uncommon: Thrombophlebitis

Gastrointestinal disorders:

Very common: Nausea, vomiting, diarrhoea

Common: Abdominal pain, dyspepsia, anorexia

Uncommon: Acute pancreatitis (see section 4.4)

Hepato-biliary disorders:

Common: Elevated aspartate aminotransferase (AST) in serum, and elevated alanine aminotransferase (ALT) in serum, hyperbilirubinaemia

Uncommon: Jaundice, liver injury, mostly cholestatic

Not known: Hepatic failure (see section 4.4)

Skin and subcutaneous tissue disorders:

Common: Pruritus, rash

Not known: Severe skin reactions, including Stevens-Johnson Syndrome

General disorders and administration site conditions:

Common: Headache

Uncommon: Injection site reaction, injection site inflammation, injection site pain, injection site oedema, injection site phlebitis

Investigations:

Common: Elevated amylase in serum, increased blood urea nitrogen (BUN)

c. Description of selected adverse reactions

Antibiotic Class Effects:

Pseudomembranous colitis which may range in severity from mild to life threatening (see section 4.4)

Overgrowth of non-susceptible organisms, including fungi (see section 4.4)

Tetracycline Class Effects:

Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Tetracycline class adverse reactions may include photosensitivity, pseudotumour cerebri, pancreatitis, and anti-anabolic actio