ADVERSE REACTIONS
In Phase III clinical trials, 4,780 patients (n=2702 in controlled trials) received daily oral doses of KETEK 800 mg once daily for 5 days or 7 to 10 days. Most adverse events were mild to moderate in severity. In the combined Phase III studies, discontinuation due to treatment-emergent adverse events occurred in 4.4% of KETEK-treated patients and 4.3% of combined comparator-treated patients. Most discontinuations in the KETEK group were due to treatment-emergent adverse events in the gastrointestinal body system, primarily diarrhea (0.9% for KETEK vs. 0.7% for comparators), nausea (0.7% for KETEK vs. 0.5% for comparators).
All and possibly related treatment-emergent adverse events (TEAEs) occurring in controlled clinical studies in ≥ 2.0% of all patients are included below:
Table 5 | All and Possibly Related Treatment-Emergent Adverse Events Reported in Controlled Phase III Clinical Studies (Percent Incidence) |
|---|
| Adverse Event
| All TEAEs | Possibly-Related TEAEs |
|---|
| KETEK
n= 2702 | Comparator
n= 2139 | KETEK
n= 2702 | Comparator
n= 2139 |
|---|
| Diarrhea | 10.8% | 8.6% | 10.0% | 8.0% |
| Nausea | 7.9% | 4.6% | 7.0% | 4.1% |
| Headache | 5.5% | 5.8% | 2.0% | 2.5% |
| Dizziness (excl. vertigo) | 3.7% | 2.7% | 2.8% | 1.5% |
| Vomiting | 2.9% | 2.2% | 2.4% | 1.4% |
| Loose Stools | 2.3% | 1.5% | 2.1% | 1.4% |
| Dysgeusia | 1.6% | 3.6% | 1.5% | 3.6% |
The following events judged by investigators to be at least possibly drug related were observed infrequently (≥ 0.2% and < 2%), in KETEK-treated patients in the controlled Phase III studies.
Gastrointestinal system: abdominal distension, dyspepsia, gastrointestinal upset, flatulence, constipation, gastroenteritis, gastritis, anorexia, oral candidiasis, glossitis, stomatitis, watery stools.
Liver and biliary system: abnormal liver function tests: increased transaminases, increased liver enzymes (e.g., ALT, AST) were usually asymptomatic and reversible. ALT elevations above 3 times the upper limit of normal were observed in 1.6%, and 1.7% of patients treated with KETEK and comparators, respectively. Hepatitis, with or without jaundice, occurred in 0.07% of patients treated with KETEK, and was reversible. (See PRECAUTIONS, General.)
Nervous system: dry mouth, somnolence, insomnia, vertigo, increased sweating
Body as a whole: abdominal pain, upper abdominal pain, fatigue
Special senses: Visual adverse events most often included blurred vision, diplopia, or difficulty focusing. Most events were mild to moderate; however, severe cases have been reported. Some patients discontinued therapy due to these adverse events. Visual adverse events were reported as having occurred after any dose during treatment, but most visual adverse events (65%) occurred following the first or second dose. Visual events lasted several hours and recurred upon subsequent dosing in some patients. For patients who continued treatment, some resolved on therapy while others continued to have symptoms until they completed the full course of treatment. (See WARNINGS and PRECAUTIONS, Information for patients.)
Females and patients under 40 years old experienced a higher incidence of telithromycin-associated visual adverse events. (See CLINICAL STUDIES.)
Urogenital system: vaginal candidiasis, vaginitis, vaginosis fungal
Skin: rash
Hematologic: increased platelet count
Other possibly related clinically-relevant events occurring in <0.2% of patients treated with KETEK from the controlled Phase III studies included: anxiety, bradycardia, eczema, elevated blood bilirubin, erythema multiforme, flushing, hypotension, increased blood alkaline phosphatase, increased eosinophil count, paresthesia, pruritus, urticaria.
Post-Marketing Adverse Event Reports
In addition to adverse events reported from clinical trials, the following events have been reported from worldwide post-marketing experience with KETEK.
Allergic: face edema, rare reports of severe allergic reactions, including angioedema and anaphylaxis.
Cardiovascular: atrial arrhythmias, palpitations
Gastrointestinal system: pancreatitis
Liver and biliary system: Hepatic dysfunction has been reported.
Severe and in some cases fatal hepatotoxicity, including fulminant hepatitis, hepatic necrosis and hepatic failure have been reported in patients treated with KETEK. These hepatic reactions were observed during or immediately after treatment. In some of these cases, liver injury progressed rapidly and occurred after administration of only a few doses of KETEK. (See CONTRAINDICATIONS and WARNINGS.) Severe reactions, in some but not all cases, have been associated with serious underlying diseases or concomitant medications.
Data from post-marketing reports and clinical trials show that most cases of hepatic dysfunction were mild to moderate. (See PRECAUTIONS, General.)
Musculoskeletal: muscle cramps, rare reports of exacerbation of myasthenia gravis. (See CONTRAINDICATIONS.)
Nervous system: loss of consciousness, in some cases associated with vagal syndrome.
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