Tigecycline

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• 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 grp. (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 grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding

South African recommendations

Caution in the following patient groups

• Severe hepatic impairment (Child-Pugh C)

Special precautions for use

• In clinical studies for various infections, a numerically higher mortality rate among tigecycline treated patients has been reported as compared to the comparator treatment
• The causes of these findings remain unknown, but poorer efficacy and safety than the study comparators cannot be ruled out

Superinfection

• In reported clinical trials in cIAI patients, impaired healing of the surgical wound has been associated with superinfection
• A patient developing impaired healing should be monitored for the detection of superinfection
• Patients who develop superinfections, in particular nosocomial pneumonia, appear to be associated with poorer outcomes
• If a focus of infection other than cSSTI or cIAI is identified after initiation of tigecycline therapy, alternative antibacterial therapy should be considered

Anaphylaxis

• Anaphylaxis/anaphylactoid reactions, potentially life-threatening, have been reported with tigecycline

Hepatic failure

• Cases of liver injury with a predominantly cholestatic pattern have been reported in patients receiving tigecycline treatment, including some cases of hepatic failure with a fatal outcome
• Although hepatic failure may occur due to underlying conditions, a possible contribution of tigecycline should be considered

Tetracycline class antibiotics

• Tigecycline is structurally similar to tetracycline class antibiotics and may have similar adverse reactions
• Such reactions may include photosensitivity, pseudotumor cerebri, pancreatitis, and anti-anabolic action which has led to increased BUN, azotaemia, acidosis, and hyperphosphataemia
• Tigecycline should be administered with caution in patients with known hypersensitivity to tetracycline class antibiotics

Pancreatitis

• Acute pancreatitis, which can be serious, has been reported in association with tigecycline treatment
• The diagnosis should be considered in patients who develop clinical symptoms, signs, or laboratory abnormalities suggestive of acute pancreatitis
• Most cases developed after at least one week of treatment and improved after tigecycline discontinuation
• Consideration should be given to the cessation of treatment with tigecycline in cases suspected of having developed pancreatitis

Coagulopathy

• Tigecycline may prolong both prothrombin time (PT) and activated partial thromboplastin time (aPTT)
• Hypofibrinogenaemia has been reported with the use of tigecycline
• Blood coagulation parameters (PT or other tests, including blood fibrinogen) should be monitored prior to treatment initiation and regularly while on treatment
• Special care is recommended in seriously ill patients and in patients also using anticoagulants

Underlying diseases

• Reported experience in the use of tigecycline for treatment of infections in patients with severe underlying diseases is limited
• Tigecycline is not recommended for use in patients with diabetic foot infections as it was reported to be less effective than the comparator
• Caution is advised when treating patients with concurrent bacteraemia, immunocompromised patients, or those with APACHE II scores > 15
• Consideration should be given to the use of combination antibacterial therapy whenever tigecycline is to be administered to severely ill patients with cIAI secondary to intestinal perforation

Cholestasis

• The effect of cholestasis in the pharmacokinetics of tigecycline has not been properly established
• Biliary excretion accounts for approximately 50 % of the total tigecycline excretion; therefore, patients presenting with cholestasis should be closely monitored

Pseudomembranous colitis

• Pseudomembranous colitis has been reported with nearly all antibacterial medicines and may range in severity from mild to life-threatening
• It is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to administration

Overgrowth of non-susceptible organisms

• The use of tigecycline may result in overgrowth of non-susceptible organisms, including fungi

Tooth discolouration

• Tigecycline may be associated with permanent tooth discolouration in humans if used during tooth development

Hospital acquired pneumonia

• The sub-group of patients with ventilator-associated pneumonia who received tigecycline reported lower cure rates and greater mortality than the comparator

Paediatric population

• Safety and effectiveness in patients under 18 years of age have not been established; use is not recommended
• Nausea, vomiting, and abdominal pain are common reactions; abdominal pain may be indicative of pancreatitis
• Liver function tests, coagulation parameters, haematology, amylase, and lipase should be monitored prior to treatment and regularly while on treatment

Excipient information

• This medicine contains 71,77 mg sodium per 5mL of reconstituted solution, equivalent to 3.6 % of the WHO recommended maximum daily intake for an adult

Effects on ability to drive and use machines

• Dizziness may occur and this may have an effect on driving and use of machines

Forms avail. in SA and covered in this monograph: inj 

Infections caused by Gram positive cocci (including methicillin-resistant Staphylococcus aureus); Gram negative bacilli (including E. coli, Klebsiella spp.); Anaerobic organisms (including Bacteroides spp., Clostridium perfringens, Peptostreptococcus micros)

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Complicated skin and skin structure infections, excluding diabetic foot infections
Complicated intra-abdominal infections

• IV: Initial: 100mg, as a single dose; Maintenance: 50mg, 12hrly; Treatment duration: 5-14 days

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Administered by intravenous infusion over 30-60min

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See additional prescribing points for administration guidelines

Not established for use in children below 18 years in South Africa

Pregnancy

South African recommendations

• Contraindicated
• Tigecycline may cause foetal harm when administered to a pregnant woman. Results of animal studies reported that tigecycline crosses the placenta and is found in foetal tissues. There are no reported studies of tigecycline in pregnant women
• Tigecycline should not be used during pregnancy and has not been studied for use during labour and delivery

Breastfeeding

South African recommendations

• Contraindicated
• It is unknown whether tigecycline/metabolites are excreted in human milk
• Available pharmacodynamic/toxicological data in animals have reported excretion of tigecycline/metabolites in milk. A risk to the newborns/infants cannot be excluded

Fertility

South African recommendations

• The effects of tigecycline on fertility in humans have not been studied. Tigecycline reported to not affect mating or fertility in rats. In female rats, no compound-related effects on ovaries or oestrus cycles were reported at exposures up to 4.7 times the human daily dose based on AUC

South African recommendations

• No dose adjustment recommended
  No dosage adjustment of tigecycline is necessary in patients with renal impairment or in patients undergoing haemodialysis

South African recommendations

• Mild to moderate (Child-Pugh A or B): No dose adjustment recommended
• Severe (Child-Pugh C): Caution; dose adjustment recommended
  Initial: 100mg, as a single dose; Maintenance: 25mg, 12hrly
  Patients with severe hepatic impairment (Child Pugh C) should be treated with caution and monitored for treatment response

South African recommendations

• No dose adjustment recommended

Central Nervous System Disorders

• Dizziness
• Headache

Cardiovascular Disorders

• Phlebitis
• Thrombophlebitis

Respiratory Disorders

• Pneumonia  

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Abdominal pain
• Dyspepsia

Hepatobiliary disorders

• Increased aspartate aminotransferase 
• Increased alanine aminotransferase
• Increased amylase
• Hyperbilirubinaemia
• Jaundice
• Hepatic injury
• Hepatic failure
• Acute pancreatitis

Genitourinary Disorders

• Increased blood urea nitrogen 

Endocrine and Metabolic Disorders

• Hypoglycaemia
• Hypoproteinaemia 
• Anorexia 

Skin and Subcutaneous Tissue Disorders

• Pruritus
• Rash
• Severe skin reactions (including Stevens-Johnson Syndrome)
• Injection site inflammation
• Injection site pain
• Injection site oedema
• Abscess formation 

Immune, Blood and Lymphatic System Disorders

• Prolonged activated partial thromboplastin time
• Prolonged prothrombin time
• Thrombocytopenia
• Increased international normalised ratio 
• Anaphylaxis
• Anaphylactoid reactions
• Impaired healing
• Sepsis
• Septic shock

• Warfarin 
• Oral contraceptives 
• P-glycoprotein inducers
• P-glycoprotein inhibitors

None routine. Specific cases may require

• Prothrombin time
• Hepatic function

• To achieve a concentration of 10 mg/ml of tigecycline, the powder from one vial should be reconstituted with 5.3ml of either sodium chloride, 5% dextrose or ringers lactate
• 5ml of the reconstituted solution should be withdrawn and added to a 100ml intravenous bag for infusion

Tigecycline is a glycylcycline antibiotic. It 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.

Spectrum of activity: Gram positive cocci (including methicillin-resistant Staphylococcus aureus); Gram negative bacilli (including E. coli, Klebsiella spp.); Anaerobic organisms (including Bacteroides spp., Clostridium perfringens, Peptostreptococcus micros)

Injection (per 5ml) 50mg

• Rubicil (Ruby Pharmaceuticals)
• Tigebax (Glenmark Pharmaceuticals SA)
• Tigecycline Accord ( Accord Healthcare)
• Tygacil (Pfizer) originator