Tigecycline - Prescribing Guidance

Publication: 17/09/2007  --
Last review: 03/03/2017  
Next review: 03/03/2020  
Clinical Guideline
CURRENT 
ID: 1157 
Approved By: Trust DTC 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Tigecycline

Drug information
    Introduction
    Antimicrobial activity
    Dose/Routes of administration
    Therapeutic Drug Monitoring (checking levels)
    Pharmacokinetics
    Allergy advice
    Key interactions (include BNF black dot)
    Side effects and monitoring required
Drug indications
    Prophylaxis indications in LTHT
    Treatment indications in LTHT
    Prescribing restriction: Fully restricted outside of guidelines

This document provides guidelines for Microbiologists (including trainees) regarding the situations in which it would be appropriate to consider the use of Tigecycline electronic Medicines Compendium information on Tigecycline.  This document is supplementary to, and should be used in conjunction with, the summary of product characteristics.

The use of Tigecycline electronic Medicines Compendium information on Tigecycline can be considered within its currently approved LTHT Drugs and Therapeutics Group (DTG) application for complicated soft tissue and complicated intra-abdominal infections.

Please follow current LTHT guidelines for Management of Complicated Intra-abdominal Infection in Adults and soft tissue infections.

DRUG INFORMATION
Introduction

Tigecycline electronic Medicines Compendium information on Tigecycline is a glycylcycline, a class of antimicrobial derived from tetracyclines. Tetracycline allergic patients should not be prescribed tigecycline.  It should be used with caution in children under 18 years because of a lack of safety and efficacy data.

It should not normally be used in the under eights because of discoloration of the teeth.

Tigecycline electronic Medicines Compendium information on Tigecycline should not be used in pregnancy.

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Antimicrobial activity

Tigecycline electronic Medicines Compendium information on Tigecycline has in vitro activity against:
Staphylococcus aureus (including meticillin-resistant strains)
Coagulase negative staphylococci
Streptococci (including Group A and group B beta-haemolytic streptococci, Streptococcus anginosus group, Streptococcus pneumoniae)
Enterococci
Escherichia coli (including ESBL+ strains), Klebsiella, Enterobacter, Serratia, Citrobacter spp.
Acinetobacter calcoaceticus baumannii complex
Haemophilus spp.
Moraxella catarrhalis
Chlamydophila pneumoniae
Mycoplasma pneumoniae
Anaerobes (Clostridium perfringens, Prevotella, Peptostreptococcus sp.)
Mycobacterium abscessus, Mycobacterium chelonae and Mycobacterium fortuitum

Tigecycline electronic Medicines Compendium information on Tigecycline does not have in vitro activity against:

Pseudomonas aeruginosa
Mycobacterium avium complex

And may have reduced activity against Proteus, Providentia, Morganella spp., Stenotrophomonas maltophilia, Burkholderia cepacia complex.
Mycobacterium kansasii, Mycobacterium marinum

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Dose/Routes of administration

Twice-daily intravenous infusion over 30-60minutes with a loading dose of 100mg followed by 50mg every 12 hours.

No dosage adjustment is recommended for patients based on gender, ethnicity or renal impairment.

For Treating Infections caused by Carbapenemase Producing Organisms (CPOs) intermediate sensitivities 100mg BD (unlicensed).

Dose adjustment in renal impairment/failure
No dosage adjustment is recommended No dosage adjustment is necessary in patients with renal impairment or in patients undergoing haemodialysis.

Dose in obesity
No doses above the standard regimen could be found.

Dose in liver failure
No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child Pugh A and Child Pugh B). Dosage adjustment is recommended in patients with severe hepatic impairment (Child Pugh C) - the dose of Tigecycline electronic Medicines Compendium information on Tigecycline should be reduced to 25 mg every 12 hours following the 100 mg loading dose. Patients with severe hepatic impairment (Child Pugh C) should be treated with caution and monitored for treatment response.

Paediatric doses
Tigecycline electronic Medicines Compendium information on Tigecycline should not be used in children under 8 years of age because of teeth discolouration, and is not recommended in adolescents below 18 years due to the lack of data on safety and efficacy.

A recent study by Purdy et al. concluded that a Tigecycline electronic Medicines Compendium information on Tigecycline dosage of ∼1.2 mg/kg every 12 hours may represent the most appropriate dosage for subsequent evaluation in Phase III clinical trials in children aged 8 to 11 years with selected serious bacterial infections.

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Therapeutic Drug Monitoring (checking levels)

Not required.

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Pharmacokinetics

AbsorptionTigecycline electronic Medicines Compendium information on Tigecycline must be given by intravenous infusion (100% bioavailability)
 
Distribution: Tigecycline electronic Medicines Compendium information on Tigecycline distributes beyond plasma volume and concentrates into tissues.  Blood-brain barrier penetration – not known.
 
Excretion/metabolism: <20% metabolised. Mostly excreted unchanged in urine and faeces, but urinary excretion is much less than faecal and Tigecycline electronic Medicines Compendium information on Tigecycline is unsuitable for treatment of urinary tract infections.

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Allergy advice

Hypersensitivity to the active substance or to any of the excipients. Patients hypersensitive to tetracycline class antibiotics may be hypersensitive to Tigecycline electronic Medicines Compendium information on Tigecycline.

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Key interactions (include BNF black dot)

Tigecycline electronic Medicines Compendium information on Tigecycline possibly enhances anticoagulant effect of coumarins.
[THIS LIST IS NOT EXHAUSTIVE]

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Side effects and monitoring required

Nausea (29.5%) vomiting (19.7%) and diarrhoea (12.7%).

The drug induced nausea may be controlled by antiemetics.

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DRUG INDICATIONS
Prophylaxis indications in LTHT

Tigecycline electronic Medicines Compendium information on Tigecycline has not been assessed as a prophylactic agent and should not be recommended for this purpose.

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Treatment indications in LTHT

'Consideration should be given to the use of combination antibacterial therapy whenever Tigecycline electronic Medicines Compendium information on Tigecycline is to be administered to severely ill patients with complicated intra-abdominal infections (cIAI) secondary to clinically apparent intestinal perforation or patients with incipient sepsis or septic shock.'

The following LTH antimicrobial guidelines have recommendations for Tigecycline electronic Medicines Compendium information on Tigecycline:

Acute Cholecystitis and Cholangitis
Appendicitis in Adults
Breast abscesses and Mastitis, (breast cellulitis) in adults
Intra-abdominal Infection of Unknown Cause in Adults
Spontaneous bacterial peritonitis (SBP) in adults
Spontaneous bacterial peritonitis prophylaxis including acute variceal bleeding

Tigecycline electronic Medicines Compendium information on Tigecycline can be used in patients:

1. With a surgical wound infection (Breedt et al., 2005; Sacchidanand et al., 2005) (purulent exudate and/or >1cm erythema and pain), in a patient without severe sepsis* or septic shock*

  1. When the wound is potentially infected with mixed organisms including MRSA and/or ESBL-positive Enterobacteriaceae that are Tigecycline electronic Medicines Compendium information on Tigecycline susceptible.
  2. When the wound has not improved with 72 hours treatment with either a suitable penicillin or cephalosporin or vancomycin.
  3. When the patient is allergic to or intolerant of penicillins, cephalosporins and vancomycin.
    * using standard definitions (Bone et al., 1992),

NB.  If the wound may be infected by Pseudomonas aeruginosa, alternative therapies are more appropriate.

2. Who have suffered a perforated abdominal viscus and require post-operative antimicrobials for peritoneal contamination but are allergic to penicillins and cephalosporins and have no evidence of septic shock or severe sepsis (Oliva et al., 2005).

NB. Note that ciprofloxacin plus metronidazole is the current recommendation for this situation and Tigecycline electronic Medicines Compendium information on Tigecycline should be used as second line, or when susceptibility testing of the causative organism indicates Tigecycline electronic Medicines Compendium information on Tigecycline would be appropriate.

Unlicensed indication:

3. With cystic fibrosis as second line therapy (when first line has failed or if first line is excluded by allergy/toxicity concerns) for infections caused by non-Pseudomonas aeruginosa non-fermenters (e.g. Burkholderia cepacia complex, Alcaligenes xylosoxidans, Pandoraea apista).

N.B this is an off-license use of Tigecycline electronic Medicines Compendium information on Tigecycline that has been approved by the LTHT DTG and requires Microbiology Consultant approval.

4. Tigecycline electronic Medicines Compendium information on Tigecycline can also be used for treatment of infections caused by rapid growing non-tuberculous mycobacteria according to LTHT guidelines.

N.B this is an off-license use of Tigecycline electronic Medicines Compendium information on Tigecycline that has been approved by the LTHT DTG and requires Microbiology Consultant approval.

Tigecycline electronic Medicines Compendium information on Tigecycline is also used for Treating Infections caused by Carbapenemase Producing Organisms (CPOs)

It is a good practice point to arrange a follow-up bed-side visit(s) since Tigecycline electronic Medicines Compendium information on Tigecycline is still relatively new and its effectiveness should be monitored. 

It is prudent to ask the prescribing clinician to contact Microbiology for advice should there be any clinical deterioration attributable to infection or side effects of Tigecycline electronic Medicines Compendium information on Tigecycline.

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Prescribing restriction: FULLY RESTRICTED OUTSIDE OF GUIDELINES

Tigecycline electronic Medicines Compendium information on Tigecycline can only be prescribed with approval from a consultant medical microbiologist/infectious disease outside recommended LTH antimicrobial guidelines.  The prescribing clinician will be required to complete a generic restricted antimicrobial request form which will be used to audit use.

Microbiology trainees can recommend Tigecycline electronic Medicines Compendium information on Tigecycline in categories 1-3 but should discuss the recommendation with the on-call Consultant at the earliest opportunity.

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Provenance

Record: 1157
Objective:
Clinical condition:

Situations in which it would be appropriate to consider the use of tigecycline

Target patient group:
Target professional group(s): Secondary Care Doctors
Pharmacists
Adapted from:

Evidence base

  1. BNF Link
  2. EMC Link: Summary of Product Characteristics. Tygacil® powder for solution for infusion. Date of revision of text August 2013. Pfizer Limited http://www.medicines.org.uk/emc/medicine/17779/spc Assessed 6th December 2013.
  3. Bone, R. C., Sprung, C. L. & Sibbald, W. J. (1992). Definitions for sepsis and organ failure. Critical care medicine 20, 724-726.
  4. Breedt, J., Teras, J., Gardovskis, J. & other authors (2005). Safety and efficacy of tigecycline in treatment of skin and skin structure infections: results of a double-blind phase 3 comparison study with vancomycin-aztreonam. Antimicrobial agents and chemotherapy 49, 4658-4666.
  5. Oliva, M. E., Rekha, A., Yellin, A., Pasternak, J., Campos, M., Rose, G. M., Babinchak, T., Ellis-Grosse, E. J. & Loh, E. (2005). A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections [Study ID Numbers: 3074A1-301-WW; ClinicalTrials.gov Identifier: NCT00081744]. BMC Infect Dis 5, 88.
  6. Sacchidanand, S., Penn, R. L., Embil, J. M., Campos, M. E., Curcio, D., Ellis-Grosse, E., Loh, E. & Rose, G. (2005). Efficacy and safety of tigecycline monotherapy compared with vancomycin plus aztreonam in patients with complicated skin and skin structure infections: Results from a phase 3, randomized, double-blind trial. Int J Infect Dis 9, 251-261.
  7. Janson, B. and Thursky, K. (2012). Dosing of antibiotics in obesity. Curr Opin Infect Dis 25:634-649
  8. MHRA - Tigecycline (Tygacil▼): increased mortality in clinical trials – use only when other antibiotics are unsuitable
  9. See letter for healthcare professionals sent March 2011
  10. Purdy J, Jouve S, Yan JL, Balter I, Dartois N, Cooper CA, Korth-Bradley J. (2012). Pharmacokinetics and safety profile of tigecycline in children aged 8 to 11 years with selected serious infections: a multicenter, open-label, ascending-dose study. Clin Ther. Feb;34(2):496-507

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Approved By

Trust DTC

Document history

LHP version 1.0

Related information

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