Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/662
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Tygacil (Injection, Powder, Lyophilized, For Solution)
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The recommended dosage regimen
for TYGACIL is an initial dose of 100 mg, followed by 50 mg every
12 hours. Intravenous (IV) infusions of TYGACIL should be administered
over approximately 30 to 60 minutes every 12 hours. The recommended duration of treatment with TYGACIL
for complicated skin and skin structure infections or for complicated
intra-abdominal infections is 5 to 14 days. The duration of therapy
should be guided by the severity and site of the infection and the
patient's clinical and bacteriological progress. 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 initial dose of TYGACIL should be 100 mg followed by
a reduced maintenance dose of 25 mg every 12 hours. Patients
with severe hepatic impairment (Child Pugh C) should be treated with
caution and monitored for treatment response. (See CLINICAL PHARMACOLOGY, Special
Populations, Use in Patients with Hepatic Impairment and PRECAUTIONS,
Use in Patients with Hepatic Impairment.) No dosage adjustment
of TYGACIL is necessary in patients with renal impairment or in patients
undergoing hemodialysis. No dosage
adjustment of TYGACIL is necessary based on age, gender, or race.
(See CLINICAL
PHARMACOLOGY, Special Populations and PRECAUTIONS, Geriatric Use.)<br/>Preparation and Handling: Each vial of TYGACIL
should be reconstituted with 5.3 mL of 0.9% Sodium Chloride Injection,
USP, or 5% Dextrose Injection, USP, to achieve a concentration of
10 mg/mL of tigecycline. (Note: Each vial contains a 6% overage. Thus,
5 mL of reconstituted solution is equivalent to 50 mg of the
drug.) The vial should be gently swirled until the drug dissolves.
Withdraw 5 mL of the reconstituted solution from the vial and
add to a 100 mL IV bag for infusion (for a 100 mg dose, reconstitute
two vials; for a 50 mg dose, reconstitute one vial). The maximum concentration
in the IV bag should be 1 mg/mL. The reconstituted
solution should be yellow to orange in color; if not, the solution
should be discarded. Parenteral drug products should be
inspected visually for particulate matter and discoloration (e.g.,
green or black) prior to administration. Once reconstituted, TYGACIL
may be stored at room temperature for up to 24 hours (up to 6 hours
in the vial and the remaining time in the IV bag). Alternatively,
TYGACIL may be stored refrigerated at 2��to 8��C (36��to 46��F) for up to 45 hours following immediate transfer of the
reconstituted solution into the IV bag. TYGACIL may be administered intravenously through a dedicated line
or through a Y-site. If the same intravenous line is used for sequential
infusion of several drugs, the line should be flushed before and after
infusion of TYGACIL with either 0.9% Sodium Chloride Injection, USP,
or 5% Dextrose Injection, USP. Injection should be made with an infusion
solution compatible with tigecycline and with any other drug(s) administered
via this common line.<br/>Compatibilities/Incompatibilities: Compatible
intravenous solutions include 0.9% Sodium Chloride Injection, USP,
and 5% Dextrose Injection, USP. When administered through a Y-site,
TYGACIL is compatible with the following drugs or diluents: amikacin,
dobutamine, dopamine HCl, gentamicin, haloperidol, Lactated Ringer's,
lidocaine HCl, morphine, norepinephrine, piperacillin/tazobactam (EDTA
formulation), potassium chloride, propofol, ranitidine HCl, theophylline,
and tobramycin. The following drugs should not be administered simultaneously through
the same Y-site as TYGACIL: amphotericin B and diazepam.
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| dailymed-instance:descripti... |
TYGACIL (tigecycline) is
a glycylcycline antibacterial for intravenous infusion. The chemical
name of tigecycline is (4S,4aS,5aR,12aS)-9-[2-(tert-butylamino)acetamido]-4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide.
The empirical formula is CHNOand the molecular weight is 585.65. The following represents the chemical structure of tigecycline: TYGACIL is an orange lyophilized
powder or cake. Each TYGACIL vial contains 50 mg tigecycline lyophilized
powder for intravenous infusion and 100 mg of lactose monohydrate.
The pH is adjusted with hydrochloric acid, and if necessary sodium
hydroxide. The product does not contain preservatives.
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Pharmacokinetics: The mean pharmacokinetic
parameters of tigecycline after single and multiple intravenous doses
based on pooled data from clinical pharmacology studies are summarized
in Table 1. Intravenous infusions
of tigecycline were administered over approximately 30 to 60 minutes.<br/>Distribution: The in vitro
plasma protein binding of tigecycline ranges from approximately 71%
to 89% at concentrations observed in clinical studies (0.1 to 1.0��g/mL). The steady-state volume of distribution of tigecycline
averaged 500 to 700 L (7 to 9 L/kg), indicating tigecycline is extensively
distributed beyond the plasma volume and into the tissues. Following the administration
of tigecycline 100 mg followed by 50 mg every 12 hours to 33 healthy
volunteers, the tigecycline AUC(134��g��h/mL)
in alveolar cells was approximately 78-fold higher than the AUCin the serum, and the AUC(2.28��g��h/mL)
in epithelial lining fluid was approximately 32% higher than the AUCin serum. The AUC(1.61��g��h/mL)
of tigecycline in skin blister fluid was approximately 26% lower than
the AUCin the serum of 10 healthy subjects. In a single-dose
study, tigecycline 100 mg was administered to subjects prior to undergoing
elective surgery or medical procedure for tissue extraction. Concentrations
at 4 hours after tigecycline administration were higher in gallbladder
(38-fold, n=6), lung (8.6-fold, n=1), and colon (2.1-fold, n=5), and
lower in synovial fluid (0.58-fold, n=5), and bone (0.35-fold, n=6)
relative to serum. The concentration of tigecycline in these tissues
after multiple doses has not been studied.<br/>Metabolism: Tigecycline
is not extensively metabolized. In vitro studies with tigecycline
using human liver microsomes, liver slices, and hepatocytes led to
the formation of only trace amounts of metabolites. In healthy malevolunteers receivingC-tigecycline, tigecycline was the
primaryC-labeled material recovered in urine and feces,
but a glucuronide, an N-acetyl metabolite, and a tigecycline epimer
(each at no more than 10% of the administered dose) were also present.<br/>Elimination: The recovery
of total radioactivity in feces and urine following administration
ofC-tigecycline indicates that 59% of the dose is eliminated
by biliary/fecal excretion, and 33% is excreted in urine. Approximately
22% of the total dose is excreted as unchanged tigecycline in urine.
Overall, the primary route of elimination for tigecycline is biliary
excretion of unchanged tigecycline and its metabolites. Glucuronidation
and renal excretion of unchanged tigecycline are secondary routes.<br/>Special Populations:<br/>Use in Patients with Hepatic Impairment: In a study
comparing 10 patients with mild hepatic impairment (Child Pugh A),
10 patients with moderate hepatic impairment (Child Pugh B), and 5
patients with severe hepatic impairment (Child Pugh C) to 23 age and
weight matched healthy control subjects, the single-dose pharmacokinetic
disposition of tigecycline was not altered in patients with mild hepatic
impairment. However, systemic clearance of tigecycline was reduced
by 25% and the half-life of tigecycline was prolonged by 23% in patients
with moderate hepatic impairment (Child Pugh B). Systemic clearance
of tigecycline was reduced by 55%, and the half-life of tigecycline
was prolonged by 43% in patients with severe hepatic impairment (Child
Pugh C). Based on the pharmacokinetic profile of tigecycline, no dosage
adjustment is warranted in patients with mild to moderate hepatic
impairment (Child Pugh A and Child Pugh B). However, in patients with
severe hepatic impairment (Child Pugh C), the initial dose of TYGACIL
should be 100 mg followed by a reduced maintenance dose of 25 mg every
12 hours. Patients with severe hepatic impairment (Child Pugh C) should
be treated with caution and monitored for treatment response. (See PRECAUTIONS, Use in Patients
with Hepatic Impairment and DOSAGE AND ADMINISTRATION.)<br/>Use in Patients with Renal Impairment: A single
dose study compared 6 subjects with severe renal impairment (creatinine
clearance<30 mL/min), 4 end stage renal disease (ESRD) patients
receiving tigecycline 2 hours before hemodialysis, 4 ESRD patients
receiving tigecycline 1 hour after hemodialysis, and 6 healthy control
subjects. The pharmacokinetic profile of tigecycline was not significantly
altered in any of the renally impaired patient groups, nor was tigecycline
removed by hemodialysis. No dosage adjustment of TYGACIL is necessary
in patientswith renal impairment or in patients undergoing hemodialysis.<br/>Pediatric Use: The pharmacokinetics
of tigecycline in patients less than 18 years of age have not been
established.<br/>Geriatric Use: No significant
differences in pharmacokinetics were observed between healthy elderly
subjects (n=15, age 65-75; n=13, age>75) and younger subjects (n=18)
receiving a single 100-mg dose of TYGACIL. Therefore, no dosage adjustment
is necessary based on age.<br/>Gender: In a pooled
analysis of 38 women and 298 men participating in clinical pharmacology
studies, there was no significant difference in the mean (��SD)
tigecycline clearance between women (20.7��6.5 L/h) and men (22.8��8.7
L/h). Therefore, no dosage adjustment is necessary based on gender.<br/>Race: In a pooled
analysis of 73 Asian subjects, 53 black subjects, 15 Hispanic subjects,
190 white subjects, and 3 subjects classified as���other���participating in clinical pharmacology studies, there was no significant
difference in the mean (��SD) tigecycline clearance among the
Asian subjects (28.8��8.8 L/h), black subjects (23.0��7.8
L/h), Hispanic subjects (24.3��6.5 L/h), white subjects (22.1��8.9
L/h), and���other���subjects (25.0��4.8 L/h). Therefore,
no dosage adjustment is necessary based on race.<br/>Drug-drug Interactions: TYGACIL (100 mg
followed by 50 mg every 12 hours) and digoxin (0.5 mg followed
by 0.25 mg, orally, every 24 hours) were coadministered to healthy
subjects in a drug interaction study. Tigecycline slightly decreased
the Cof digoxin by 13%, but did not affect the AUC
or clearance of digoxin. This small change in Cdid
not affect the steady-state pharmacodynamic effects of digoxin as
measured by changes in ECG intervals. In addition, digoxin did not
affect the pharmacokinetic profile of tigecycline. Therefore, no dosage
adjustment of either drug is necessary when TYGACIL is administered
with digoxin. Concomitant administration of TYGACIL (100 mg followed by 50 mg every
12 hours) 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%, an increase in Cby 38% and 43% and an
increase in AUC by 68% and 29%, respectively. Tigecycline did not
significantly alter the effects of warfarin on INR. In addition, warfarin
did not affect the pharmacokinetic profile of tigecycline. However,
prothrombin time or other suitable anticoagulation test should be
monitored if tigecycline is administered with warfarin. In vitro studies in human
liver microsomes indicate that tigecycline does not inhibit metabolism
mediated by any of the following 6 cytochrome P450 (CYP) isoforms:
1A2, 2C8, 2C9, 2C19, 2D6, and 3A4. Therefore, TYGACIL is not expected
to alter the metabolism of drugs metabolized by these enzymes. In
addition, because tigecycline is not extensively metabolized, clearance
of tigecycline is not expected to be affected by drugs that inhibit
or induce the activity of these CYP450 isoforms.<br/>Microbiology: Tigecycline, a glycylcycline,
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. Tigecycline carries a glycylamido
moiety attached to the 9-position of minocycline. The substitution
pattern is not present in any naturally occurring or semisynthetic
tetracycline and imparts certain microbiologic properties to tigecycline.
Tigecycline is not affected by the two major tetracycline resistance
mechanisms, ribosomal protection and efflux. Accordingly, tigecycline
has demonstrated in vitro and in vivo activity against a broad spectrum
of bacterial pathogens. There has been no cross resistance observed
between tigecycline and other antibiotics. Tigecycline is not affected
by resistance mechanisms such as beta-lactamases (including extended
spectrum beta-lactamases), target site modifications, macrolide efflux
pumps or enzyme target changes (e.g. gyrase/topoisomerase). In vitro
studies have not demonstrated antagonism between tigecycline and other
commonly used antibacterial drugs. In general, tigecycline is considered
bacteriostatic. Tigecycline has been shown to be active against most strains of the
following microorganisms, both in vitro and in clinical infections
as described in the INDICATIONS AND USAGE section.<br/>Aerobic and facultative Gram-positive microorganisms: Enterococcus faecalis (vancomycin-susceptible isolates only)Staphylococcus aureus (methicillin-susceptible and -resistant
isolates)Streptococcus agalactiaeStreptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus)Streptococcus pyogenes<br/>Aerobic and facultative Gram-negative microorganisms: Citrobacter freundiiEnterobacter cloacaeEscherichia coliKlebsiella oxytocaKlebsiella pneumoniae<br/>Anaerobic microorganisms: Bacteroides fragilisBacteroides thetaiotaomicronBacteroides uniformisBacteroides vulgatusClostridium perfringensPeptostreptococcus micros The following in vitro data are available, but their clinical significance is unknown. At least 90% of these microorganisms exhibit in vitro minimum inhibitory
concentrations (MICs) less than or equal to the susceptible breakpoint
for tigecycline. However, the safety and effectiveness of tigecycline
in treatingclinical infections due to these microorganisms have not
been established in adequate and well-controlled clinical trials.<br/>Aerobic and facultative Gram-positive microorganisms: Enterococcus aviumEnterococcus casseliflavusEnterococcus faecalis (vancomycin-resistant isolates)Enterococcus faecium (vancomycin-susceptible and -resistant
isolates)Enterococcus gallinarumListeria monocytogenesStaphylococcus epidermidis (methicillin-susceptible and -resistant isolates)Staphylococcus haemolyticus<br/>Aerobic and facultative Gram-negative microorganisms: Acinetobacter baumanniiAeromonas hydrophilaCitrobacter koseriEnterobacter aerogenesPasteurella multocidaSerratia marcescensStenotrophomonas maltophilia<br/>Anaerobic microorganisms: Bacteroides distasonisBacteroides ovatusPeptostreptococcus spp.Porphyromonas spp.Prevotella spp.<br/>Other microorganisms: Mycobacterium abscessusMycobacterium chelonaeMycobacterium fortuitum<br/>Susceptibility Test Methods: When available,
the clinical microbiology laboratory should provide cumulative results
of the in vitro susceptibility test results for antimicrobial drugs
used in local hospitals and practice areas to the physician as periodic
reports that describe the susceptibility profile of nosocomial and
community-acquired pathogens. These reports should aid the physician
in selecting the most effective antimicrobial.
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TYGACIL is contraindicated
for use in patients who have known hypersensitivity to tigecycline.
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| dailymed-instance:supply |
TYGACIL (tigecycline) for
injection is supplied in a single-dose 5 mL glass vial containing
50 mg tigecycline lyophilized powder for reconstitution. Supplied 10 vials/box. NDC: 0008-4990-02<br/>Storage: Prior to reconstitution,
TYGACIL should be stored at 20��to 25��C (68��to 77��F);
excursions permitted to 15��to 30��C (59��to 86��F).
[See USP Controlled Room Temperature.] Once reconstituted, TYGACIL
may be stored at room temperature for up to 24 hours (up to 6 hours
in the vial and the remaining time in the IV bag). Alternatively,
TYGACIL may be stored refrigerated at 2��to 8��C (36��to 46��F) for up to 45 hours following immediate transfer of the
reconstituted solution into the IV bag. Reconstituted solution must
be transferred and further diluted for I.V. infusion.
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General: Abnormalities in total bilirubin concentration,
prothrombin time and transaminases have been seen in patients treated
with tigecycline. Isolated cases of significant hepatic dysfunction
and hepatic failure have been reported in patients being treated with
tigecycline. Some of these patients were receiving multiple concomitant
medications. Patients who develop abnormal liver function tests during
tigecycline therapy should be monitored for evidence of worsening
hepatic function and evaluated for risk/benefit of continuing tigecycline
therapy. Adverse events may occur after the drug has been discontinued. 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 TYGACIL and 2 patients treated
with imipenem/cilastatin presented with intestinal perforations and
developed sepsis/septic shock. The 6 patients treated with TYGACIL
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 cannot be established. Glycylcycline class antibiotics
are structurally similar to tetracycline class antibiotics and may
have similar adverse effects. Such effects may include: photosensitivity,
pseudotumor cerebri, and anti-anabolic action (which has led to increased
BUN, azotemia, acidosis, and hyperphosphatemia). As with tetracyclines,
pancreatitis has been reported with the use of TYGACIL. The safety and efficacy
of Tygacil in patients with hospital acquired pneumonia have not been
established. In a study of patients with hospital acquired pneumonia,
patients were randomized to receive Tygacil (100 mg initially, then
50 mg every 12 hours) or a comparator. In addition, patients were
allowed to receive specified adjunctive therapies. The sub-group of
patients with ventilator-associated pneumonia who received Tygacil
had lower cure rates (47.9% versus 70.1% for the clinically evaluable
population) and greater mortality (25/131 [19.1%] versus 15/122 [12.3%])
than the comparator. As with other antibacterial
drugs, use of TYGACIL may result in overgrowth of non-susceptible
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 is unlikely to provide benefit to the patient and increases
the risk of the development of drug-resistant bacteria.<br/>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
(e.g., the 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, the medication should be taken
exactly as directed. Skipping doses or not completing the full course
of therapy may (1) decrease the effectiveness of the immediate treatment
and (2)increase the likelihood that bacteria will develop resistance
and will not be treatable by TYGACIL or other antibacterial drugs
in the future. Diarrhea is a common problem
caused by antibiotics which usually ends when the antibiotic is discontinued.
Sometimes after starting treatment with antibiotics, patients can
develop watery and bloody stools (with or without stomach cramps and
fever) even as late as two or more months after having taken the last
dose of the antibiotic. If this occurs, patients should contact their
physician as soon as possible.<br/>Drug Interactions: Prothrombin time
or other suitable anticoagulation test should be monitored if tigecycline
is administered with warfarin. Concurrent use of antibacterial drugs with oral contraceptives may
render oral contraceptives less effective.<br/>Drug/Laboratory Test Interactions: There are
no reported drug-laboratory test interactions.<br/>Carcinogenesis, Mutagenesis, 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 mouse micronucleus assay. Tigecycline
did not affect mating or fertility in rats at exposures up to 5 times
the human daily dose based on AUC. In female rats, there were no compound-related
effects on ovaries or estrous cycles atexposures up to 5 times the
human daily dose based on AUC.<br/>Pregnancy:<br/>Teratogenic Effects���Pregnancy Category D: Tigecycline
was not teratogenic in the rat or rabbit. In preclinical safety studies,C-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 5 times and 1 times the human daily
dose based on AUC in rats and rabbits, respectively. An increased
incidence of fetal loss was observed at maternotoxic doses in the
rabbits with exposure equivalent to human dose. 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.<br/>Labor and Delivery: TYGACIL has not
been studied for use during labor and delivery.<br/>Nursing Mothers: Results from animal
studies usingC-labeled tigecycline indicate that tigecyclineis 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 this drug 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.<br/>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 initial dose of tigecycline should
be 100 mg followed by a reduced maintenance dose of 25 mg every 12
hours. Patients with severe hepatic impairment (Child Pugh C) should
be treated with caution and monitored for treatment response. (See CLINICAL PHARMACOLOGY, Special
Populations, Use in Patients with Hepatic Impairment and DOSAGE AND ADMINISTRATION.)<br/>Pediatric Use: Safety and effectiveness
in pediatric patients below the age of 18 years have not been established.
Therefore, use in patients under 18 years of age is
not recommended.<br/>Geriatric Use: Of the total number
of subjects who received TYGACIL in Phase 3 clinical studies (n=1415),
278 were 65 and over, while 110 were 75 and over. 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.
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No specific information
is available on the treatment of overdosage with tigecycline. Intravenous
administration of TYGACIL at a single dose of 300 mg over 60 minutes
in healthy volunteers resulted in an increased incidence of nausea
and vomiting. In single-dose IV toxicity studies conducted with tigecycline
in mice, the estimated median lethal dose (LD) was 124
mg/kg in males and 98 mg/kg in females. In rats, the estimated LDwas 106 mg/kg for both sexes. Tigecycline is not removed
in significant quantities by hemodialysis.
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Tigecycline
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Tygacil (Injection, Powder, Lyophilized, For Solution)
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Because clinical studies
are conducted under varying conditions, adverse reaction rates observed
in the clinical studies of a drug cannot be directly compared to rates
in the clinical studies of another drug and may not reflect the rates
observed in practice. The adverse reaction information from clinical
studies does, however, provide a basis for identifying the adverse
events that appear to be related to drug use and for approximating
rates. Phase 3 clinical
studies enrolled 1415 patients treated with TYGACIL. TYGACIL was discontinued
due to treatment-emergent adverse events in 5.0% of patients compared
to 4.7% for all comparators (5.3% for vancomycin/aztreonam
and 4.4% for imipenem/cilastatin). Table 4 shows the incidence of treatment-emergent adverse events through
test of cure reported in���2% of patients in these studies regardless
of causality. In Phase 3 cSSSI and cIAI
studies, death occurred in 2.3% (32/1383) of patients receiving TYGACIL
and 1.6% (22/1375) of patients receiving comparator drugs; this difference
is not statistically significant and relationship to treatment cannot
be established. In all treatment groups, mortality was associated
with higher baseline co-morbidity and/or greater severity of baseline
infections. In Phase 3
clinical studies, infection-related serious adverse events were more
frequently reported for subjects treated with TYGACIL (6.7%) vs comparators
(4.6%). Significant differences in sepsis/septic shock with TYGACIL
(1.5%) vs comparators (0.5%) were observed. Due to baseline differences
between treatment groups in this subset of patients, the relationship
of this outcome to treatment cannot be established. Other events included nonsignificant differences in abscess (1.8%
vs 1.6%) and infections, including wound infections (1.7% vs 1.1%)
for TYGACIL vs comparators, respectively. The most common treatment-emergent adverse events, were nausea and
vomiting which generally occurred during the first 1���2 days
of therapy. The majority of cases of nausea and vomiting associated
with TYGACIL and comparators were either mild or moderate in severity.
In patients treated with TYGACIL, nausea incidence was 29.5% (19.6%
mild, 8.5% moderate, 1.4% severe) and vomiting incidence was 19.7%
(12.3% mild, 6.3% moderate, 1.1% severe). In patients treated for
complicated skin and skin structure infections (cSSSI), nausea incidence
was 35.0% for TYGACIL and 8.9% for vancomycin/aztreonam; vomiting
incidence was 20.0% for TYGACIL and 4.2% for vancomycin/aztreonam.
In patients treated for complicated intra-abdominal infections (cIAI),
nausea incidence was 25.3% for TYGACIL and 20.5% for imipenem/cilastatin;
vomiting incidence was 19.5% for TYGACIL and 15.3% for imipenem/cilastatin. Discontinuation from tigecycline
was most frequently associated with nausea (1.3%) and vomiting (1.0%).
For comparators, discontinuations were most frequently associated
with rash (1.1%, vancomycin/aztreonam) and nausea (1.0%, imipenem/cilastatin). The following drug-related adverse
events were reported infrequently (���0.2% and<2%) in patients
receiving TYGACIL in Phase 3 clinical studies: Body as a Whole: injection
site inflammation, injection site pain, injection site reaction, septic
shock, allergic reaction, chills, injection site edema, injection
site phlebitisCardiovascular System: thrombophlebitis, bradycardia, tachycardia, vasodilatationDigestive System: anorexia, dry mouth,
jaundice, abnormal stoolsMetabolic/Nutritional
System: increased creatinine, hypocalcemia, hypoglycemia,
hyponatremiaNervous System: somnolenceSpecial Senses: taste perversionHemic and Lymphatic
System: prolonged activated partial thromboplastin time
(aPTT), prolonged prothrombin time (PT), eosinophilia, increased international
normalized ratio (INR), thrombocytopeniaUrogenital System: vaginal moniliasis, vaginitis, leukorrhea<br/>Post-Marketing Experience: Worldwide post-marketing adverse events not previously
listed in the product label include: anaphylaxis/anaphylactoid reactions,
acute pancreatitis, hyperbilirubinemia, hepatic cholestasis, increases
in liver enzymes, and jaundice.
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| dailymed-instance:warning |
Anaphylaxis/anaphylactoid
reactions have been reported with nearly all antibacterial agents,
including tigecycline, and may be life-threatening. Glycylcycline class antibiotics are structurally similar to tetracycline
class antibiotics and may have similar adverse effects. TYGACIL should
be administered with caution in patients with known hypersensitivity
to tetracycline class antibiotics. TYGACIL may cause fetal harm when administered
to a pregnant woman. If the patient becomes pregnant while
taking tigecycline, the patient should be apprised of the potential
hazard to the fetus. 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. The use of TYGACIL during tooth development (last
half of pregnancy, infancy, and childhood to the age of 8 years) may
cause permanent discoloration of the teeth (yellow-gray-brown).
Results of studies in rats with TYGACIL have shown bone discoloration.
TYGACIL should not be used during tooth development unless other drugs
are not likely to be effective or are contraindicated. Clostridium difficile associated diarrhea
(CDAD) has been reported with use of nearly all antibacterial agents,
including TYGACIL, and may range in severity from mild diarrhea to
fatal colitis. Treatment with antibacterial agents alters the normal
flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B
which contribute to the development of CDAD. Hypertoxin producing
strains of C. difficile cause
increased morbidity and mortality, as these infections can be refractory
to antimicrobial therapy and may require colectomy. CDAD must be considered
in all patients who present with diarrhea following antibiotic use.
Careful medical history is necessary since CDAD has been reported
to occur overtwo months after the administration of antibacterial
agents. If CDAD is suspected or confirmed,
ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid
and electrolyte management, protein supplementation, antibiotic treatment
of C. difficile, and surgical
evaluation should be instituted as clinically indicated.
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| dailymed-instance:indicatio... |
TYGACIL is indicated for
the treatment of infections caused by susceptible strains of the designated
microorganisms in the conditions listed below for patients 18 years
of age and older: 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. Appropriate specimens for bacteriological
examination should be obtained in order to isolate and identify the
causative organisms and to determine their susceptibility to tigecycline.
TYGACIL may be initiated as empiric monotherapy before results of
these tests are known. To reduce the development of drug-resistant bacteria and maintain
the effectiveness of TYGACIL and other antibacterial drugs, TYGACIL
should be used only to treat infections that are proven or strongly
suspected to be caused by susceptible bacteria. When culture and susceptibility
information are available, they should be considered in selecting
or modifying antibacterial therapy. In the absence of such data, local
epidemiology and susceptibility patterns may contribute to the empiric
selection of therapy.
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| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Tygacil
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