General: Caution should be exercised when considering Tygacil monotherapy in patients with complicated intra-abdominal infections (cIAI) secondary to clinically apparent intestinal perforation. In Phase 3 cIAI studies (n=1642), 6 patients treated with tigecycline and 2 patients treated with imipenem/cilastatin presented with intestinal perforations and developed sepsis/septic shock. The 6 patients treated with tigecycline had higher APACHE II scores (median=13) vs the 2 patients treated with imipenem/cilastatin (APACHE II scores: 4 and 6). Due to differences in baseline APACHE II scores between treatment groups and small overall numbers, the relationship of this outcome to treatment can not be established.
Isolated cases of significant hepatic dysfunction and hepatic failure have been reported in patients being treated with tigecycline.
Acute pancreatitis, which can be fatal, has occurred (frequency: uncommon) in association with tigecycline treatment (see Adverse Reactions). The diagnosis of acute pancreatitis should be considered in patients taking tigecycline who develop clinical symptoms, signs, or laboratory abnormalities suggestive of acute pancreatitis. 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.
The safety and efficacy of tigecycline in patients with hospital-acquired pneumonia have not been established. In a study of patients with hospital-acquired pneumonia, patients were randomized to receive tigecycline (100 mg initially, then 50 mg every 12 hrs) or a comparator. In addition, patients were allowed to receive specified adjunctive therapies. The subgroup of patients with ventilator-associated pneumonia who received tigecycline had lower cure rates (47.9% vs 70.1% for the clinically evaluable population) and greater mortality [25/131 (19.1%) vs 14/122 (11.5%)] than the comparator. Of those patients with ventilator-associated pneumonia and bacteremia at baseline, those who received tigecycline had greater mortality [9/18 (50%) vs 1/13 (7.7%)] than the comparator.
As with other antibiotic preparations, use of Tygacil may result in overgrowth of nonsusceptible organisms, including fungi. Patients should be carefully monitored during therapy. If superinfection occurs, appropriate measures should be taken.
Prescribing Tygacil in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
Information for Patients: Patients should be counseled that antibacterial drugs including Tygacil should only be used to treat bacterial infections. They do not treat viral infections (eg, common cold). When Tygacil is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, Tygacil should be taken exactly as directed. Skipping doses or not completing the full course of therapy may decrease the effectiveness of the immediate treatment and increase the likelihood that bacteria will develop resistance and will not be treatable by Tygacil or other antibacterial drugs in the future.
Use in Patients with Hepatic Impairment: No dosage adjustment is warranted in patients with mild to moderate hepatic impairment (Child-Pugh A and Child-Pugh B). In patients with severe hepatic impairment (Child-Pugh C), the dose of tigecycline should be reduced to 100 mg followed by 25 mg every 12 hrs. Patients with severe hepatic impairment (Child-Pugh C) should be treated with caution and monitored for treatment response. (See Pharmacokinetics: Special Populations under Actions and Dosage & Administration.)
Effects on the Ability to Drive or Operate Machinery: Tigecycline can cause dizziness (see Adverse Reactions), which may impair the ability to drive and/or operate machinery.
Carcinogenicity, Mutagenicity & Impairment of Fertility: Lifetime studies in animals have not been performed to evaluate the carcinogenic potential of tigecycline. No mutagenic or clastogenic potential was found in a battery of tests, including in vitro chromosome aberration assay in Chinese hamster ovary (CHO) cells, in vitro forward mutation assay in CHO cells (HGRPT locus), in vitro forward mutation assays in mouse lymphoma cells, and in vivo micronucleus assay. 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 estrous cycles at exposures up to 4.7 times the human daily dose based on AUC.
Use in pregnancy: Pregnancy Category C: Tigecycline may cause fetal harm when administered to a pregnant woman. Results of animal studies indicate that tigecycline crosses the placenta and is found in fetal tissues. Decreased fetal weights in rats and rabbits (with associated delays in ossification) and fetal loss in rabbits have been observed with tigecycline.
Tigecycline was not teratogenic in the rat or rabbit. In preclinical safety studies, 14C-labeled tigecycline crossed the placenta and was found in fetal tissues, including fetal bony structures. The administration of tigecycline was associated with slight reductions in fetal weights and an increased incidence of minor skeletal anomalies (delays in bone ossification) at exposures of 4.7 and 1.1 times the human daily dose based on AUC in rats and rabbits, respectively. An increased incidence of fetal loss was observed at exposures of 1.1 times the human daily dose based on AUC in rabbits, at dosages producing minimal maternal toxicity.
There are no adequate and well-controlled studies of tigecycline in pregnant women. Tygacil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (see Warnings).
Labor and Delivery: Tygacil has not been studied for use during labor and delivery.
Use in lactation: Results from animal studies using 14C-labeled tigecycline indicate that tigecycline is excreted readily via the milk of lactating rats. Consistent with the limited oral bioavailability of tigecycline, there is little or no systemic exposure to tigecycline in nursing pups as a result of exposure via maternal milk.
It is not known whether Tygacil is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Tygacil is administered to a nursing woman. (See Warnings.)
Use in children: Safety and effectiveness in pediatric patients <18 years have not been established (see Warnings). Therefore, use in patients <18 years is not recommended.
Use in the elderly: Of the total number of subjects who received Tygacil in phase 3 clinical studies (n=2514), 664 were ≥65, while 288 were ≥75. No unexpected overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity to adverse events of some older individuals cannot be ruled out.