DIPENTUM SIDE EFFECTS
- Generic Name: olsalazine sodium capsules
- Brand Name: Dipentum
- Drug Class: 5-Aminosalicylic Acid Derivatives
SIDE EFFECTS
Olsalazine has been evaluated in ulcerative colitis patients in remission, as well as those with acute disease. Both sulfasalazine-tolerant and intolerant patients have been studied in controlled clinical trials. Overall, 10.4% of patients discontinued olsalazine because of an adverse experience compared with 6.7% of placebo patients. The most commonly reported adverse reactions leading to treatment withdrawal were diarrhea or loose stools (olsalazine 5.9%; placebo 4.8%), abdominal pain, and rash or itching (slightly more than 1% of patients receiving olsalazine).
Diarrhea
Overall, approximately 17% of subjects receiving olsalazine in clinical studies reported diarrhea sometime during therapy. This diarrhea resulted in withdrawal of treatment in 6% of patients. This diarrhea appears to be dose related, although it may be difficult to distinguish from the underlying symptoms of the disease.
Other adverse reactions to olsalazine leading to withdrawal occurred in fewer than 1% of patients (Table 1).
Table 1 : Adverse Reactions Resulting In Withdrawal From Controlled Studies Total
Olsalazine (N = 441) |
Placebo (N = 208) |
|
Diarrhea/Loose Stools | 26 (5.9%) | 10 (4.8%) |
Nausea | 3 | 2 |
Abdominal Pain | 5 (1.1%) | 0 |
Rash/Itching | 5 (1.1%) | 0 |
Headache | 3 | 0 |
Heartburn | 2 | 0 |
Rectal Bleeding | 1 | 0 |
Insomnia | 1 | 0 |
Dizziness | 1 | 0 |
Anorexia | 1 | 0 |
Light Headedness | 1 | 0 |
Depression | 1 | 0 |
Miscellaneous | 4 (0.9%) | 3 (1.4%) |
Total Number of Patients Withdrawn | 46 (10.4%) | 14 (6.7%) |
For those controlled studies, the comparative incidences of adverse reactions reported in 1% or more patients treated with olsalazine or placebo are provided in Table 2.
Table 2 : Comparative Incidence (%) of Adverse Effects Reported By One Percent Or More of Ulcerative Colitis Patients Treated With Olsalazine Or Placebo in Double Blind Controlled Studies
Adverse Event | Olsalazine (N=441) % |
Placebo (N=208) % |
Gastrointestinal Disorders | ||
Diarrhea | 11.1 | 6.7 |
Abdominal Pain/Cramps | 10.1 | 7.2 |
Nausea | 5.0 | 3.9 |
Dyspepsia | 4.0 | 4.3 |
Bloating | 1.5 | 1.4 |
Vomiting | 1.0 | – |
Stomatitis | 1.0 | – |
Increased Blood in Stool | – | 3.4 |
Metabolism and Nutrition Disorders | ||
Anorexia | 1.3 | 1.9 |
Nervous System Disorders | ||
Headache | 5.0 | 4.8 |
Insomnia | – | 2.4 |
General Disorders and Administration Site Conditions | ||
Fatigue/Drowsiness/Lethargy | 1.8 | 2.9 |
Psychiatric Disorders | ||
Depression | 1.5 | – |
Ear and Labyrinth Disorders | ||
Vertigo/Dizziness | 1.0 | – |
Skin and Subcutaneous Tissue Disorders | ||
Rash | 2.3 | 1.4 |
Itching | 1.3 | – |
Musculoskeletal and Connective Tissue Disorders | ||
Arthralgia/Joint Pain | 4.0 | 2.9 |
Infections and Infestations | ||
Upper Respiratory Infection | 1.5 | – |
Over 2,500 patients have been treated with olsalazine in various controlled and uncontrolled clinical studies. In these as well as in post-marketing experience, olsalazine was administered mainly to patients intolerant to sulfasalazine. There have been rare reports of the following adverse effects in patients receiving olsalazine. These were often difficult to distinguish from possible symptoms of the underlying disease or from the effects of prior and/or concomitant therapy. A causal relationship to the drug has not been demonstrated for some of these reactions.
Blood And Lymphatic System Disorders
Anemia, Eosinophilia, Hemolytic anemia, Interstitial pulmonary disease, Leukopenia, Lymphopenia, Neutropenia, Reticulocytosis, Thrombocytopenia
Cardiac Disorders
Chest pains, Heart block second degree, Myocarditis, Palpitations, Pericarditis, Peripheral edema, Shortness of breath, Tachycardia
A patient who developed thyroid disease 9 days after starting DIPENTUM was given propranolol and radioactive iodine and subsequently developed shortness of breath and nausea. The patient died 5 days later with signs and symptoms of acute diffuse myocarditis.
Ear And Labyrinth Disorders
Tinnitus
Eye Disorders
Dry eyes, Vision blurred, Watery eyes
Gastrointestinal Disorders
Abdominal pain (upper), Diarrhea with dehydration, Dry mouth, Epigastric discomfort, Flare in symptoms, Flatulence, Increased blood in stool, Pancreatitis, Rectal bleeding, Rectal discomfort
In a double-blind, placebo-controlled study, increased frequency and severity of diarrhea were reported in patients randomized to olsalazine 500 mg B.I.D. with concomitant pelvic radiation.
Rare cases of granulomatous hepatitis and nonspecific, reactive hepatitis have been reported in patients receiving olsalazine. Additionally, a patient developed mild cholestatic hepatitis during treatment with sulfasalazine and experienced the same symptoms two weeks later after the treatment was changed to olsalazine. Withdrawal of olsalazine led to complete recovery in these cases.
General Disorders And Administration Site Conditions
Fever chills, Hot flashes, Irritability, Rigors
Immune System Disorders
Bronchospasm, Erythema nodosum
Laboratory
ALT (SGPT) or AST (SGOT) elevated beyond the normal range.
Musculoskeletal And Connective Tissue Disorders
Muscle cramps
Nervous System Disorders
Insomnia, Paraesthesia, Tremors
Psychiatric Disorders
Mood swings
Renal And Urinary Disorders
Dysuria, Hematuria, Interstitial nephritis, Nephrotic syndrome, Proteinuria, Urinary frequency
Reproductive System And Breast Disorders
Impotence, Menorrhagia
Skin And Subcutaneous Tissue Disorders
Alopecia, Erythema, Photosensitivity reaction
Vascular Disorders
Hypertension, Orthostatic hypotension
Postmarketing
The following events have been identified during post-approval use of products that contain (or are metabolized to) mesalamine in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of seriousness, frequency of reporting, or potential causal connection to mesalamine:
Blood And Lymphatic System Disorders
Aplastic anemia, Pancytopenia
General Disorders And Administration Site Conditions
Pyrexia
Hepatobiliary Disorders
Hepatic enzyme increased, Hepatitis, Increased bilirubin
Reports of hepatotoxicity, including elevated liver function tests (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, and possible hepatocellular damage including liver necrosis and liver failure. Some of these cases were fatal. One case of Kawasaki-like syndrome, which included hepatic function changes, was also reported.
Musculoskeletal And Connective Tissue Disorders
Myalgia
Respiratory, Thoracic And Mediastinal Disorders
Dyspnea, Interstitial lung disease, pleurisy/pleuritis
Skin And Subcutaneous Tissue Disorders
Angioneurotic edema, SJS/TEN, DRESS, and AGEP
Nervous System Disorders
Paresthesia, Peripheral neuropathy
Renal And Urinary Disorders
Interstitial nephritis, nephrolithiasis
SRC: NLM .