Tygacil Prescribing Information
TYGACIL is not indicated for the treatment of diabetic foot infections. A clinical trial failed to demonstrate non-inferiority of TYGACIL for treatment of diabetic foot infections.
TYGACIL is not indicated for the treatment of hospital-acquired or ventilator-associated pneumonia. In a comparative clinical trial, greater mortality and decreased efficacy were reported in TYGACIL-treated patients
An increase in all-cause mortality has been observed in a meta-analysis of Phase 3 and 4 clinical trials in TYGACIL-treated patients versus comparator-treated patients. In all 13 Phase 3 and 4 trials that included a comparator, death occurred in 4.0% (150/3788) of patients receiving TYGACIL and 3.0% (110/3646) of patients receiving comparator drugs. In a pooled analysis of these trials, based on a random effects model by trial weight, the adjusted risk difference of all-cause mortality was 0.6% (95% CI 0.1, 1.2) between TYGACIL and comparator-treated patients. An analysis of mortality in all trials conducted for approved indications (cSSSI, cIAI, and CABP), including post-market trials showed an adjusted mortality rate of 2.5% (66/2640) for tigecycline and 1.8% (48/2628) for comparator, respectively. The adjusted risk difference for mortality stratified by trial weight was 0.6% (95% CI 0.0, 1.2).
The cause of this mortality difference has not been established. Generally, deaths were the result of worsening infection, complications of infection or underlying co-morbidities. TYGACIL should be reserved for use in situations when alternative treatments are not suitable
A trial of patients with hospital acquired, including ventilator-associated, pneumonia failed to demonstrate the efficacy of TYGACIL. In this trial, 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).
In this trial, greater mortality was seen in patients with ventilator-associated pneumonia who received TYGACIL (25/131 [19.1%] versus 15/122 [12.3%] in comparator-treated patients)
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In clinical trials, 2514 patients were treated with TYGACIL. TYGACIL was discontinued due to adverse reactions in 7% of patients compared to 6% for all comparators. Table 1 shows the incidence of adverse reactions through test of cure reported in ≥2% of patients in these trials.
Body System Adverse Reactions | TYGACIL (N=2514) | Comparators Vancomycin/Aztreonam, Imipenem/Cilastatin, Levofloxacin, Linezolid.(N=2307) |
|---|---|---|
Body as a Whole | ||
Abdominal pain | 6 | 4 |
Abscess | 2 | 2 |
Asthenia | 3 | 2 |
Headache | 6 | 7 |
Infection | 7 | 5 |
Cardiovascular System | ||
Phlebitis | 3 | 4 |
Digestive System | ||
Diarrhea | 12 | 11 |
Dyspepsia | 2 | 2 |
Nausea | 26 | 13 |
Vomiting | 18 | 9 |
Hemic and Lymphatic System | ||
Anemia | 5 | 6 |
Metabolic and Nutritional | ||
Alkaline Phosphatase Increased | 3 | 3 |
Amylase Increased | 3 | 2 |
Bilirubinemia | 2 | 1 |
BUN Increased | 3 | 1 |
Healing Abnormal | 3 | 2 |
Hyponatremia | 2 | 1 |
Hypoproteinemia | 5 | 3 |
SGOT IncreasedLFT abnormalities in TYGACIL-treated patients were reported more frequently in the post therapy period than those in comparator-treated patients, which occurred more often on therapy. | 4 | 5 |
SGPT Increased | 5 | 5 |
Respiratory System | ||
Pneumonia | 2 | 2 |
Nervous System | ||
Dizziness | 3 | 3 |
Skin and Appendages | ||
Rash | 3 | 4 |
In all 13 Phase 3 and 4 trials that included a comparator, death occurred in 4.0% (150/3788) of patients receiving TYGACIL and 3.0% (110/3646) of patients receiving comparator drugs. In a pooled analysis of these trials, based on a random effects model by trial weight, an adjusted risk difference of all-cause mortality was 0.6% (95% CI 0.1, 1.2) between TYGACIL and comparator-treated patients (see Table 2). The cause of the imbalance has not been established. Generally, deaths were the result of worsening infection, complications of infection or underlying co-morbidities.
TYGACIL | Comparator | Risk Difference The difference between the percentage of patients who died in TYGACIL and comparator treatment groups. The 95% CI for each infection type was calculated using the normal approximation method without continuity correction. | |||
|---|---|---|---|---|---|
Infection Type | n/N | % | n/N | % | % (95% CI) |
| CAP = Community-acquired pneumonia; cIAI = Complicated intra-abdominal infections; cSSSI = Complicated skin and skin structure infections; HAP = Hospital-acquired pneumonia; VAP = Ventilator-associated pneumonia; RP = Resistant pathogens; DFI = Diabetic foot infections. Note: The studies include 300, 305, 900 (cSSSI), 301, 306, 315, 316, 400 (cIAI), 308 and 313 (CAP), 311 (HAP), 307 [Resistant gram-positive pathogen study in patients with MRSA or Vancomycin-Resistant Enterococcus (VRE)], and 319 (DFI with and without osteomyelitis). | |||||
cSSSI | 12/834 | 1.4 | 6/813 | 0.7 | 0.7 (-0.3, 1.7) |
cIAI | 42/1382 | 3.0 | 31/1393 | 2.2 | 0.8 (-0.4, 2.0) |
CAP | 12/424 | 2.8 | 11/422 | 2.6 | 0.2 (-2.0, 2.4) |
HAP | 66/467 | 14.1 | 57/467 | 12.2 | 1.9 (-2.4, 6.3) |
Non-VAPThese are subgroups of the HAP population. | 41/336 | 12.2 | 42/345 | 12.2 | 0.0 (-4.9, 4.9) |
VAP | 25/131 | 19.1 | 15/122 | 12.3 | 6.8 (-2.1, 15.7) |
RP | 11/128 | 8.6 | 2/43 | 4.7 | 3.9 (-4.0, 11.9) |
DFI | 7/553 | 1.3 | 3/508 | 0.6 | 0.7 (-0.5, 1.8) |
Overall Adjusted | 150/3788 | 4.0 | 110/3646 | 3.0 | 0.6 (0.1, 1.2)Overall adjusted (random effects model by trial weight) risk difference estimate and 95% CI. |
An analysis of mortality in all trials conducted for approved indications - cSSSI, cIAI, and CABP, including post-market trials (one in cSSSI and two in cIAI) - showed an adjusted mortality rate of 2.5% (66/2640) for tigecycline and 1.8% (48/2628) for comparator, respectively. The adjusted risk difference for mortality stratified by trial weight was 0.6% (95% CI 0.0, 1.2).
In comparative clinical studies, infection-related serious adverse reactions were more frequently reported for subjects treated with TYGACIL (7%) versus comparators (6%). Serious adverse reactions of sepsis/septic shock were more frequently reported for subjects treated with TYGACIL (2%) versus comparators (1%). Due to baseline differences between treatment groups in this subset of patients, the relationship of this outcome to treatment cannot be established
The most common adverse reactions 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 26% (17% mild, 8% moderate, 1% severe) and vomiting incidence was 18% (11% mild, 6% moderate, 1% severe).
In patients treated for complicated skin and skin structure infections (cSSSI), nausea incidence was 35% for TYGACIL and 9% for vancomycin/aztreonam; vomiting incidence was 20% for TYGACIL and 4% for vancomycin/aztreonam. In patients treated for complicated intra-abdominal infections (cIAI), nausea incidence was 25% for TYGACIL and 21% for imipenem/cilastatin; vomiting incidence was 20% for TYGACIL and 15% for imipenem/cilastatin. In patients treated for community-acquired bacterial pneumonia (CABP), nausea incidence was 24% for TYGACIL and 8% for levofloxacin; vomiting incidence was 16% for TYGACIL and 6% for levofloxacin.
Discontinuation from TYGACIL was most frequently associated with nausea (1%) and vomiting (1%). For comparators, discontinuation was most frequently associated with nausea (<1%).
The following adverse reactions were reported (<2%) in patients receiving TYGACIL in clinical studies:
Contraindications ( TYGACIL is contraindicated for use in patients who have known hypersensitivity to tigecycline or to any of the excipients. Reactions have included anaphylactic reactions[see Warnings and Precautions (5.3)and Adverse Reactions (6.2)].
| 3/2025 |
Warnings and precautions, Tetracycline-Class Adverse Effects ( TYGACIL is structurally similar to tetracycline-class antibacterial drugs and may have similar adverse effects. Such effects may include: photosensitivity, fixed drug eruption, pseudotumor cerebri, and anti-anabolic action (which has led to increased BUN, azotemia, acidosis, and hyperphosphatemia).Discontinue TYGACIL if any of these adverse reactions are suspected. | 3/2025 |
TYGACIL is a tetracycline class antibacterial indicated in patients 18 years of age and older for:
• Complicated skin and skin structure infections ()1.1 Complicated Skin and Skin Structure InfectionsTYGACIL is indicated in patients 18 years of age and older for the treatment of complicated skin and skin structure infections caused by susceptible isolates of
Escherichia coli, Enterococcus faecalis(vancomycin-susceptible isolates),Staphylococcus aureus(methicillin-susceptible and -resistant isolates),Streptococcus agalactiae, Streptococcus anginosusgrp. (includesS. anginosus, S. intermedius,andS. constellatus),Streptococcus pyogenes, Enterobacter cloacae, Klebsiella pneumoniae,andBacteroides fragilis.• Complicated intra-abdominal infections ()1.2 Complicated Intra-abdominal InfectionsTYGACIL is indicated in patients 18 years of age and older for the treatment of complicated intra-abdominal infections caused by susceptible isolates of
Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis(vancomycin-susceptible isolates),Staphylococcus aureus(methicillin-susceptible and -resistant isolates),Streptococcus anginosusgrp. (includesS. anginosus, S. intermedius,andS. constellatus),Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens,andPeptostreptococcus micros.• Community-acquired bacterial pneumonia ()1.3 Community-Acquired Bacterial PneumoniaTYGACIL is indicated in patients 18 years of age and older for the treatment of community-acquired bacterial pneumonia caused by susceptible isolates of
Streptococcus pneumoniae(penicillin-susceptible isolates), including cases with concurrent bacteremia,Haemophilus influenzae, andLegionella pneumophila.
TYGACIL is not indicated for the treatment of diabetic foot infections. A clinical trial failed to demonstrate non-inferiority of TYGACIL for treatment of diabetic foot infections.
TYGACIL is not indicated for the treatment of hospital-acquired or ventilator-associated pneumonia. In a comparative clinical trial, greater mortality and decreased efficacy were reported in TYGACIL-treated patients
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 bacteria (
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.
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.
• Initial dose of 100 mg followed by 50 mg every 12 hours administered intravenously over approximately 30 to 60 minutes. ()2.1 Recommended Adult DosageThe recommended dosage regimen for TYGACIL is an initial dose of 100 mg, followed by 50 mg every 12 hours. Intravenous 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 recommended duration of treatment with TYGACIL for community-acquired bacterial pneumonia is 7 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.
• Severe hepatic impairment (Child Pugh C): Initial dose of 100 mg followed by 25 mg every 12 hours. ()2.2 Dosage in Patients With Hepatic ImpairmentNo 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 (12.3)and Use in Specific Populations (8.6)].• Obtain baseline blood coagulation parameters, including fibrinogen, and continue to monitor regularly during treatment with TYGACIL. (,2.4 Monitoring of Blood Coagulation ParametersObtain baseline blood coagulation parameters, including fibrinogen, and continue to monitor regularly during treatment with TYGACIL
[see Warnings and Precautions (5.6)].)5.6 Monitoring of Blood Coagulation ParametersHypofibrinogenemia has been reported in patients treated with TYGACIL
[see Adverse Reactions (6.2)]. Obtain baseline blood coagulation parameters, including fibrinogen, and continue to monitor regularly during treatment with TYGACIL.
For Injection: Each single-dose 10 mL glass vial contain 50 mg of tigecycline as an orange lyophilized powder for reconstitution.
• Lactation: Avoid breastfeeding for longer than 3 weeks while taking TYGACIL. A lactating woman may also pump and discard breast milk during treatment and for 9 days after the last dose of TYGACIL ()8.2 LactationRisk SummaryThere are no data on the presence of tigecycline in human milk; however, tetracycline-class antibacterial drugs are present in breast milk. It is not known whether tigecycline has an effect on the breastfed infant or on milk production. Tigecycline has low oral bioavailability; therefore, infant exposure is expected to be low. Tigecycline is present in rat milk with little or no systemic exposure to tigecycline in nursing pups as a result of exposure via maternal milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TYGACIL and any potential adverse effects on the breastfed child from TYGACIL or from the underlying maternal condition
(see Clinical Considerations).Clinical ConsiderationsBecause of the theoretical risk of dental discoloration and inhibition of bone growth, avoid breastfeeding if taking TYGACIL for longer than three weeks. A lactating woman may also consider interrupting breastfeeding and pumping and discarding breastmilk during administration of TYGACIL and for 9 days (approximately 5 half-lives) after the last dose in order to minimize drug exposure to a breastfed infant.
• Pediatrics: Use in patients under 18 years of age is not recommended. Pediatric trials were not conducted because of the higher risk of mortality seen in adult trials ()8.4 Pediatric UseUse in patients under 18 years of age is not recommended. Safety and effectiveness in pediatric patients below the age of 18 years have not been established. Because of the increased mortality observed in TYGACIL-treated adult patients in clinical trials, pediatric trials of TYGACIL to evaluate the safety and efficacy of TYGACIL were not conducted.
In situations where there are no other alternative antibacterial drugs, dosing has been proposed for pediatric patients 8 to 17 years of age based on data from pediatric pharmacokinetic studies
[see Dosage and Administration (2.3)and Clinical Pharmacology (12.3)].Because of effects on tooth development, use in patients under 8 years of age is not recommended
[see Warnings and Precautions (5.7)].