Chemical formula: C₂₉H₃₉N₅O₈ Molecular mass: 585.649 g/mol PubChem compound: 54686904
Tigecycline interacts in the following cases:
Based on an in-vitro study tigecycline is a P-gp substrate. Co-administration of P-gp inhibitors (e.g. ketoconazole or cyclosporine) or P-gp inducers (e.g. rifampicin) could affect the pharmacokinetics of tigecycline.
In patients (including paediatrics) with severe hepatic impairment (Child Pugh C), the dose of tigecycline should be reduced by 50%. Adult dose 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.
Concomitant administration of tigecycline 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 may prolong both prothrombin time (PT) and activated partial thromboplastin time (aPTT), the relevant coagulation tests should be closely monitored when tigecycline is co-administered with anticoagulants. Warfarin did not affect the pharmacokinetic profile of tigecycline.
Concurrent use of antibiotics with oral contraceptives may render oral contraceptives less effective.
Results of studies in rats with tigecycline have shown bone discolouration. Tigecycline may be associated with permanent tooth discolouration in humans if used during tooth development.
Acute pancreatitis, which can be serious, has occurred (frequency: uncommon) in association with tigecycline treatment. The diagnosis of acute pancreatitis should be considered in patients taking tigecycline who develop clinical symptoms, signs, or laboratory abnormalities suggestive of acute pancreatitis. Most of the reported cases developed after at least one week of treatment. Cases have been reported in patients without known risk factors for pancreatitis. Patients usually improve after tigecycline discontinuation. Consideration should be given to the cessation of the treatment with tigecycline in cases suspected of having developed pancreatitis.
Anaphylaxis/anaphylactoid reactions, potentially life-threatening, have been reported with tigecycline.
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 has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibacterial agent.
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 in patients treated with tigecycline due to the underlying conditions or concomitant medicinal products, a possible contribution of tigecycline should be considered.
There are no or limited amount of data from the use of tigecycline 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 may also induce permanent dental defects (discolouration and enamel defects) and a delay in ossification processes in foetuses, 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 should not be used during pregnancy unless the clinical condition of the woman requires treatment with tigecycline.
It is unknown whether tigecycline/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of tigecycline/metabolites in milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from tigecycline therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Tigecycline 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.
Dizziness may occur and this may have an effect on driving and use of machines.
The total number of cSSTI and cIAI patients treated with tigecycline in Phase 3 and 4 clinical studies was 2,393.
In clinical trials, the most common medicinal product-related treatment emergent adverse reactions were reversible nausea (21%) and vomiting (13%), which usually occurred early (on treatment days 1-2) and were generally mild or moderate in severity.
Adverse reactions reported with tigecycline, including clinical trials and post-marketing experience, are tabulated below. Very Common ≥1/10, common ≥1/100 to <1/10, uncommon ≥1/1,000 to <1/100, frequency not known (cannot be estimated from the available data).
Common: sepsis/septic shock, pneumonia, abscess, infections
Common: prolonged activated partial thromboplastin time (aPTT), prolonged prothrombin time (PT)
Uncommon: thrombocytopenia, increased international normalised ratio (INR)
Frequency not known: hypofibrinogenaemia
Frequency not known: anaphylaxis/anaphylactoid reactions*
Common: hypoglycaemia, hypoproteinaemia
Common: dizziness
Common: phlebitis
Uncommon: thrombophlebitis
Very Common: nausea, vomiting, diarrhoea
Common: abdominal pain, dyspepsia, anorexia
Uncommon: acute pancreatitis
Common: elevated aspartate aminotransferase (AST) in serum, and elevated alanine aminotransferase (ALT) in serum, hyperbilirubinaemia
Uncommon: jaundice, liver injury, mostly cholestatic
Frequency not known: hepatic failure*
Common: pruritus, rash
Frequency not known: severe skin reactions, including Stevens-Johnson Syndrome*
Common: impaired healing, injection site reaction, headache
Uncommon: injection site inflammation, injection site pain, injection site oedema, injection site phlebitis
Common: elevated amylase in serum, increased blood urea nitrogen (BUN)
* ADR identified post-marketing
Pseudomembranous colitis which may range in severity from mild to life threatening.
Overgrowth of non-susceptible organisms, including fungi.
Glycylcycline class antibiotics are structurally similar to tetracycline class antibiotics. Tetracycline class adverse reactions may include photosensitivity, pseudotumour cerebri, pancreatitis, and anti- anabolic action which has led to increased BUN, azotaemia, acidosis, and hyperphosphataemia.
Tigecycline may be associated with permanent tooth discolouration if used during tooth development.
In Phase 3 and 4 cSSTI and cIAI clinical studies, infection-related serious adverse reactions were more frequently reported for subjects treated with tigecycline (7.1%) vs comparators (5.3%). Significant differences in sepsis/septic shock with tigecycline (2.2%) vs comparators (1.1%) were observed.
AST and ALT abnormalities in tigecycline-treated patients were reported more frequently in the post therapy period than in those in comparator-treated patients, which occurred more often on therapy.
In all Phase 3 and 4 (cSSTI and cIAI) studies, death occurred in 2.4% (54/2216) of patients receiving tigecycline and 1.7% (37/2206) of patients receiving active comparators.
Very limited safety data were available from two PK studies. No new or unexpected safety concerns were observed with tigecycline in these studies.
In an open-label, single ascending dose PK study, the safety of tigecycline was investigated in 25 children aged 8 to 16 years who recently recovered from infections. The adverse reaction profile of tigecycline in these 25 subjects was generally consistent with that in adults.
The safety of tigecycline was also investigated in an open-label, ascending multi-dose PK study in 58 children aged 8 to 11 years with cSSTI (n=15), cIAI (n=24) or community-acquired pneumonia (n=19). The adverse reaction profile of tigecycline in these 58 subjects was generally consistent with that in adults, with the exception of nausea (48.3%), vomiting (46.6%) and elevated lipase in serum (6.9%) which were seen at greater frequencies in children than in adults.
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