ADVERSE REACTIONS
Experience in Adult Patients with COPD
Of the 1,456 COPD patients in the two 12-week, placebo-controlled trials, 288 were treated with BROVANA (arformoterol tartrate) Inhalation Solution 15 mcg twice daily and 293 were treated with placebo. Doses of 25 mcg twice daily and 50 mcg once daily were also evaluated. The numbers and percent of patients who reported adverse events were comparable in the 15 mcg twice daily and placebo groups.
The following table shows adverse events where the frequency was greater than or equal to 2% in the BROVANA 15 mcg twice daily group and where the rates of adverse events in the BROVANA 15 mcg twice daily group exceeded placebo. Ten adverse events demonstrated a dose relationship: asthenia, fever, bronchitis, COPD, headache, vomiting, hyperkalemia, leukocytosis, nervousness, and tremor.
Table 1: Number of Patients Experiencing Adverse Events from Two 12-Week, Double-Blind, Placebo Controlled Clinical Trials |
* Reported terms coded to “Lung Disorder” were predominantly pulmonary or chest congestion.
|
| BROVANA
15 mcg
twice daily | Placebo |
| n | (%) | n | (%) |
| Total Patients | 288 | (100) | 293 | (100) |
| Pain | 23 | (8) | 16 | (5) |
| Chest Pain | 19 | (7) | 19 | (6) |
| Back Pain | 16 | (6) | 6 | (2) |
| Diarrhea | 16 | (6) | 13 | (4) |
| Sinusitis | 13 | (5) | 11 | (4) |
| Leg Cramps | 12 | (4) | 6 | (2) |
| Dyspnea | 11 | (4) | 7 | (2) |
| Rash | 11 | (4) | 5 | (2) |
| Flu Syndrome | 10 | (3) | 4 | (1) |
| Peripheral Edema | 8 | (3) | 7 | (2) |
| Lung Disorder* | 7 | (2) | 2 | (1) |
Adverse events occurring in patients treated with BROVANA 15 mcg twice daily with a frequency of <2%, but greater than placebo were as follows:
- Body as a Whole: abscess, allergic reaction, digitalis intoxication, fever, hernia, injection site pain, neck rigidity, neoplasm, pelvic pain, retroperitoneal hemorrhage
- Cardiovascular: arteriosclerosis, atrial flutter, AV block, congestive heart failure, heart block, myocardial infarct, QT interval prolonged, supraventricular tachycardia, inverted T-wave
- Digestive: constipation, gastritis, melena, oral moniliasis, periodontal abscess, rectal hemorrhage
- Metabolic and Nutritional Disorders: dehydration, edema, glucose tolerance decreased, gout, hyperglycemia, hyperlipemia, hypoglycemia, hypokalemia
- Musculoskeletal: arthralgia, arthritis, bone disorder, rheumatoid arthritis, tendinous contracture
- Nervous: agitation, cerebral infarct, circumoral paresthesia, hypokinesia, paralysis, somnolence, tremor
- Respiratory: carcinoma of the lung, respiratory disorder, voice alteration
- Skin and Appendages: dry skin, herpes simplex, herpes zoster, skin discoloration, skin hypertrophy
- Special Senses: abnormal vision, glaucoma
- Urogenital: breast neoplasm, calcium crystalluria, cystitis, glycosuria, hematuria, kidney calculus, nocturia, PSA increase, pyuria, urinary tract disorder, urine abnormality.
Overall, the frequency of all cardiovascular adverse events for BROVANA in the two placebo controlled trials was low and comparable to placebo (6.9% in BROVANA 15 mcg twice daily and 13.3% in the placebo group). There were no frequently occurring specific cardiovascular adverse events for BROVANA (frequency ≥1% and greater than placebo). The rate of COPD exacerbations was also comparable between the BROVANA 15 mcg twice daily and placebo groups, 12.2% and 15.1%, respectively.
Other adverse reactions which may occur with selective beta2-adrenoceptor agonists such as BROVANA include: angina, hypertension or hypotension, tachycardia, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, metabolic acidosis and insomnia.
Drug Abuse and Dependence
There were no reported cases of abuse or evidence of drug dependence with the use of BROVANA in the clinical trials.
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