Demadex (Torsemide) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

At the time of approval, DEMADEX had been evaluated for safety in approximately 4000 subjects: over 800 of these subjects received DEMADEX for at least 6 months, and over 380 were treated for more than 1 year. Among these subjects were 564 who received DEMADEX during United States-based trials in which 274 other subjects received placebo.

The reported side effects of DEMADEX were generally transient, and there was no relationship between side effects and age, sex, race, or duration of therapy. Discontinuation of therapy due to side effects occurred in 3.5% of United States patients treated with DEMADEX and in 4.4% of patients treated with placebo. In studies conducted in the United States and Europe, discontinuation rates due to side effects were 3.0% (38/1250) with DEMADEX and 3.4% (13/380) with furosemide in patients with congestive heart failure, 2.0% (8/409) with DEMADEX and 4.8% (11/230) with furosemide in patients with renal insufficiency, and 7.6% (13/170) with DEMADEX and 0% (0/33) with furosemide in patients with cirrhosis.

The most common reasons for discontinuation of therapy with DEMADEX were (in descending order of frequency) dizziness, headache, nausea, weakness, vomiting, hyperglycemia, excessive urination, hyperuricemia, hypokalemia, excessive thirst, hypovolemia, impotence, esophageal hemorrhage, and dyspepsia. Dropout rates for these adverse events ranged from 0.1% to 0.5%.

The side effects considered possibly or probably related to study drug that occurred in United States placebo-controlled trials in more than 1% of patients treated with DEMADEX are shown in Table 1.

Table 1 Reactions Possibly or Probably Drug-Related United States Placebo-Controlled Studies Incidence (Percentages of Patients)

	DEMADEX (N=564)	Placebo (N=274)
Headache	7.3	9.1
Excessive Urination	6.7	2.2
Dizziness	3.2	4.0
Rhinitis	2.8	2.2
Asthenia	2.0	1.5
Diarrhea	2.0	1.1
ECG Abnormality	2.0	0.4
Cough Increase	2.0	1.5
Constipation	1.8	0.7
Nausea	1.8	0.4
Arthralgia	1.8	0.7
Dyspepsia	1.6	0.7
Sore Throat	1.6	0.7
Myalgia	1.6	1.5
Chest Pain	1.2	0.4
Insomnia	1.2	1.8
Edema	1.1	1.1
Nervousness	1.1	0.4

The daily doses of DEMADEX used in these trials ranged from 1.25 mg to 20 mg, with most patients receiving 5 mg to 10 mg; the duration of treatment ranged from 1 to 52 days, with a median of 41 days. Of the side effects listed in the table, only "excessive urination" occurred significantly more frequently in patients treated with DEMADEX than in patients treated with placebo. In the placebo-controlled hypertension studies whose design allowed side-effect rates to be attributed to dose, excessive urination was reported by 1% of patients receiving placebo, 4% of those treated with 5 mg of daily DEMADEX, and 15% of those treated with 10 mg. The complaint of excessive urination was generally not reported as an adverse event among patients who received DEMADEX for cardiac, renal, or hepatic failure.

Serious adverse events reported in the clinical studies for which a drug relationship could not be excluded were atrial fibrillation, chest pain, diarrhea, digitalis intoxication, gastrointestinal hemorrhage, hyperglycemia, hyperuricemia, hypokalemia, hypotension, hypovolemia, shunt thrombosis, rash, rectal bleeding, syncope, and ventricular tachycardia.

Angioedema has been reported in a patient exposed to DEMADEX who was later found to be allergic to sulfa drugs.

Of the adverse reactions during placebo-controlled trials listed without taking into account assessment of relatedness to drug therapy, arthritis and various other nonspecific musculoskeletal problems were more frequently reported in association with DEMADEX than with placebo, even though gout was somewhat more frequently associated with placebo. These reactions did not increase in frequency or severity with the dose of DEMADEX. One patient in the group treated with DEMADEX withdrew due to myalgia, and one in the placebo group withdrew due to gout.

Hypokalemia

See WARNINGS.

REPORTS OF SUSPECTED DEMADEX SIDE EFFECTS / ADVERSE REACTIONS

Possible Demadex side effects / adverse reactions in 93 year old female

Reported by a pharmacist from United States on 2012-04-04

Patient: 93 year old female weighing 46.0 kg (101.2 pounds)

Reactions: Large Intestinal Ulcer, International Normalised Ratio Increased, Coagulopathy, Upper Gastrointestinal Haemorrhage, Haemorrhagic Anaemia, Renal Failure Acute

Adverse event resulted in: hospitalization

Suspect drug(s):
Aspirin
    Dosage: 81mg daily po chronic
    Administration route: Oral
    Indication: Coronary Artery Disease

Coumadin
    Dosage: 2mg / 1.5mg mf/twthss po recent
    Administration route: Oral
    Indication: Atrial Fibrillation

Coumadin
    Dosage: 2mg / 1.5mg mf/twthss po recent
    Administration route: Oral
    Indication: Coronary Artery Disease

Demadex
    Dosage: 10mg q daily

Other drugs received by patient: Omeprazole; Amiodarone HCL; Lipitor; Atenolol; Ferrous Sulfate TAB; Ascorbic Acid; Multi-Vitamins

Possible Demadex side effects / adverse reactions in 63 year old female

Reported by a individual with unspecified qualification from United States on 2012-06-29

Patient: 63 year old female

Reactions: Pneumonia, Dehydration, Helicobacter Gastritis

Adverse event resulted in: hospitalization

Suspect drug(s):
Demadex

Other drugs received by patient: Vitamin D (Vitamin); Metoprolol Tartrate; Klonopin; Chantix; Singulair; Zoloft; Symbicort (Budesonide, Formoterol Fumrate)