ADVERSE REACTIONS
Clinical Trials Experience
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 treatment-emergent adverse reactions through test of cure reported in ≥2% of patients in these trials.
Table 1. Incidence (%) of Adverse Reactions Through Test of Cure Reported in ≥2% of Patients Treated in Clinical Studies Body System Adverse Reactions | TYGACIL (N=2514) | Comparatorsa (N=2307) |
a Vancomycin/Aztreonam, Imipenem/Cilastatin, Levofloxacin, Linezolid. b LFT 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.
|
Body as a Whole | | |
Abdominal pain | 6 | 4 |
Abscess | 3 | 3 |
Asthenia | 3 | 2 |
Headache | 6 | 7 |
Infection | 8 | 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 | 4 | 5 |
Metabolic and Nutritional | | |
Alkaline Phosphatase Increased | 4 | 3 |
Amylase Increased | 3 | 2 |
Bilirubinemia | 2 | 1 |
BUN Increased | 3 | 1 |
Healing Abnormal | 4 | 3 |
Hypoproteinemia | 5 | 3 |
SGOT Increasedb | 4 | 5 |
SGPT Increasedb | 5 | 5 |
Nervous System | | |
Dizziness | 3 | 3 |
Skin and Appendages | | |
Rash | 3 | 4 |
In Phase 3 double-blind studies that included a comparator and employed a 1:1 randomization, death occurred in 4.7% (107/2274) of patients receiving TYGACIL and 3.8% (85/2264) of patients receiving comparator drugs. In a pooled analysis of these studies, the risk difference of all-cause mortality was 1.0% (95% CI -0.3, 2.2) between TYGACIL and comparator treated patients. No significant differences were observed between treatments by infection type (see Table 2). Generally, deaths represented complications of the underlying disease or progression of disease. A causal relationship to TYGACIL has not been established.
Table 2. Patients with Adverse Events with Outcome of Death by Infection Type | TYGACIL | Comparator | Risk Difference* |
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. * The difference between the percentage of patients who died in TYGACIL and comparator treatment groups. a These are subgroups of the HAP population. Note: The Phase 3 Studies include 300 and 305 (cSSSI), 301 and 306 (cIAI), 308 and 313 (CAP), and 311 (HAP). |
cSSSI | 6/566 | 1.1 | 1/550 | 0.2 | 0.9 (-0.3, 2.2) |
cIAI | 24/817 | 2.9 | 17/825 | 2.1 | 0.9 (-0.8, 2.6) |
CAP | 12/424 | 2.8 | 11/422 | 2.6 | 0.2 (-2.3, 2.7) |
HAP | 65/467 | 13.9 | 56/467 | 12.0 | 1.9 (-2.6, 6.4) |
Non-VAPa | 40/336 | 11.9 | 42/345 | 12.2 | -0.3 (-5.4, 4.9) |
VAPa | 25/131 | 19.1 | 14/122 | 11.5 | 7.6 (-2.0, 16.9) |
In comparative clinical studies, infection-related serious adverse events were more frequently reported for subjects treated with TYGACIL (7%) versus comparators (6%). Serious adverse events 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 [see Warnings and Precautions].
The most common treatment-emergent 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 tigecycline 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 infrequently (<2%) in patients receiving TYGACIL in 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 phlebitis
Cardiovascular System: thrombophlebitis
Digestive System: anorexia, jaundice, abnormal stools
Metabolic/Nutritional System: increased creatinine, hypocalcemia, hypoglycemia, hyponatremia
Special Senses: taste perversion
Hemic and Lymphatic System: partial thromboplastin time (aPTT), prolonged prothrombin time (PT), eosinophilia, increased international normalized ratio (INR), thrombocytopenia
Skin and Appendages: pruritus
Urogenital System: vaginal moniliasis, vaginitis, leukorrhea
Post-Marketing Experience
The following adverse reactions have been identified during postapproval use of TYGACIL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.
- anaphylaxis/anaphylactoid reactions
- acute pancreatitis
- hepatic cholestasis, and jaundice
|
REPORTS OF SUSPECTED TYGACIL SIDE EFFECTS / ADVERSE REACTIONS
Below is a sample of reports where side effects / adverse reactions may be related to Tygacil. The information is not vetted and should not be considered as verified clinical evidence.
Possible Tygacil side effects / adverse reactions in 31 year old female
Reported by a physician from United States on 2011-10-13
Patient: 31 year old female weighing 54.4 kg (119.7 pounds)
Reactions: Nasopharyngitis, Nausea, Anaemia, Adverse Drug Reaction, Rash, Hyperhidrosis, Middle Insomnia, Fatigue, Diarrhoea, Asthenia, White Blood Cell Count Increased
Suspect drug(s):
Tygacil
Indication: Infectious Peritonitis
Tygacil
Dosage: unk
Indication: Abdominal Infection
Start date: 2011-09-01
Tygacil
Indication: Appendix Disorder
Possible Tygacil side effects / adverse reactions in 31 year old female
Reported by a physician from United States on 2011-11-08
Patient: 31 year old female weighing 54.4 kg (119.7 pounds)
Reactions: Nasopharyngitis, Nausea, Anaemia, Rash, Hyperhidrosis, Fatigue, Middle Insomnia, Diarrhoea, Asthenia, White Blood Cell Count Increased
Suspect drug(s):
Tygacil
Other drugs received by patient: Motrin
Possible Tygacil side effects / adverse reactions in 75 year old male
Reported by a pharmacist from Australia on 2011-11-11
Patient: 75 year old male weighing 60.0 kg (132.0 pounds)
Reactions: Multi-Organ Failure, Thrombocytopenia, Blood Creatinine Increased, Cardiac Failure Congestive
Adverse event resulted in: death
Suspect drug(s):
Clarithromycin
Dosage: 500 mg, 2x/day
Administration route: Oral
Indication: Mycobacterium Chelonae Infection
Start date: 2011-10-03
Tobramycin
Dosage: 180 mg, 3x/day, every 8 hours
Indication: Mycobacterium Chelonae Infection
Start date: 2011-10-03
End date: 2011-10-10
Tygacil
Dosage: 100 mg, single
Indication: Mycobacterium Chelonae Infection
Start date: 2011-10-03
End date: 2011-10-03
Tygacil
Dosage: 50 mg, 2x/day
Start date: 2011-10-04
End date: 2011-10-10
Other drugs received by patient: Promethazine; Colchicine; Bisoprolol; Colchicine; Prednisolone; Acetaminophen; Mometasone; Thiamine; Ivabradine; Prednisolone; Digoxin; Salbutamol; Acetylsalicylic Acid; Fluticasone Propionate/salmeterol; Ceftriaxone; Amiodarone; Furosemide; Oxycontin; Spironolactone; Temazepam; Prednisolone
|