Olsalazine

Olsalazine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rabin Bista, M.B.B.S. [2]

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Overview

Olsalazine is a Salicylate that is FDA approved for the treatment of ulcerative colitis. Common adverse reactions include Abdominal pain, Diarrhea, Indigestion, Nausea, Headache, Blurred vision.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Indications

• Olsalazine is indicated for the maintenance of remission of ulcerative colitis in patients who are intolerant of sulfasalazine.

Dosage

• The usual dosage in adults for maintenance of remission is 1.0 g/day in two divided doses.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Olsalazine in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Olsalazine in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Olsalazine in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Olsalazine in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Olsalazine in pediatric patients.

Contraindications

• Hypersensitivity to olsalazine, other salicylates, or any of the excipients.

Warnings

Precautions

General 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.

Exacerbation of the symptoms of colitis thought to have been caused by mesalamine or sulfasalazine has been noted.

Information for Patients Patients should be instructed to take olsalazine with food. The drug should be taken in evenly divided doses. Patients should be informed that about 17% of subjects receiving olsalazine during clinical studies reported diarrhea sometime during therapy. If diarrhea occurs, patients should contact their physician.

Adverse Reactions

Clinical Trials Experience

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). Other adverse reactions to olsalazine leading to withdrawal occurred in fewer than 1% of patients (TABLE 1).

This image is provided by the National Library of Medicine.

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.

This image is provided by the National Library of Medicine.

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 Experience

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 Dyspnoea, Interstitial lung disease

Skin and Subcutaneous Tissue Disorders Angioneurotic oedema

Nervous System Disorders Paraesthesia

Renal and Urinary Disorders Interstitial nephritis

Drug Interactions

• The co-administration of salicylates and low molecular weight heparins or heparinoids may result in an increased risk of bleeding (i.e., hematomas) following neuraxial anesthesia. Salicylates should be discontinued prior to the initiation of a low molecular weight heparin or heparinoid. If this is not possible, it is recommended to monitor patients closely for bleeding.

Increased prothrombin time in patients taking concomitant warfarin has been reported.

The co-administration of olsalazine and 6-mercaptopurine or thioguanine may result in an increased risk of myelosuppression. If co-administered with 6-mercaptopurine, it is recommended to use the lowest possible doses of each drug and to monitor the patient, especially for leukopenia. In case of co-administration with thioguanine, careful monitoring of blood counts is recommended.

It is recommended not to give salicylates for six weeks after the varicella vaccine to avoid a possible increased risk of developing Reye’s syndrome.

Drug/Laboratory Test Interactions None known.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

• Olsalazine has been shown to produce fetal developmental toxicity as indicated by reduced fetal weights, retarded ossifications, and immaturity of the fetal visceral organs when given during organogenesis to pregnant rats in doses 5 to 20 times the human dose (100 to 400 mg/kg).

There are no adequate and well-controlled studies in pregnant women. Olsalazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Olsalazine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Olsalazine during labor and delivery.

Nursing Mothers

• Small amounts of the active metabolite of olsalazine (5-ASA) may pass into breast milk. Harmful infant effects (diarrhea) have been reported when 5-ASA was used during breastfeeding. Unless the benefit of the treatment outweighs the risks, olsalazine should not be taken by breast-feeding women, or patients should be advised to discontinue breastfeeding if using olsalazine.

Oral administration of olsalazine to lactating rats in doses 5 to 20 times the human dose produced growth retardation in their pups.

Pediatric Use

• Safety and effectiveness in a pediatric population have not been established.

Geriatic Use

• Clinical studies of DIPENTUM did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, elderly patients should be treated with caution due to the greater frequency of decreased hepatic, renal, or cardiac function, co-existence of other disease, as well as concomitant drug therapy.

Gender

There is no FDA guidance on the use of Olsalazine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Olsalazine with respect to specific racial populations.

Renal Impairment

Patients with impaired renal function should be monitored.

Although renal abnormalities were not reported in clinical trials with olsalazine, there have been rare reports from post-marketing experience (see ADVERSE REACTIONS, POSTMARKETING). Therefore, the possibility of renal tubular damage due to absorbed mesalamine or its n-acetylated metabolite, as noted in the ANIMAL TOXICOLOGY section must be kept in mind, particularly for patients with pre-existing renal disease. In these patients, monitoring with urinalysis, BUN, and creatinine determinations is advised.

Hepatic Impairment

Patients with impaired hepatic function should be monitored

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Olsalazine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Olsalazine in patients who are immunocompromised.

Severe Allergies and/or Asthma

• Patients with severe allergies or asthma should be monitored for signs of worsening symptoms.

Administration and Monitoring

Administration

• Oral

Monitoring

• If co-administered with 6-mercaptopurine, it is recommended to use the lowest possible doses of each drug and to monitor the patient, especially for leukopenia. In case of co-administration with thioguanine, careful monitoring of blood counts is recommended.
• Patients with severe allergies or asthma should be monitored for signs of worsening symptoms
• Patients with impaired renal function should be monitored.
• For patients with pre-existing renal disease monitoring with urinalysis, BUN, and creatinine determinations is advised.
• Patients with impaired hepatic function should be monitored

IV Compatibility

There is limited information regarding IV Compatibility of Olsalazine in the drug label.

Overdosage

No overdosage has been reported in humans. The knowledge of overdosage is limited. Possible overdose symptoms include nausea, vomiting and diarrhea. It is recommended to check hematology, acid-base, electrolyte, liver and kidney status, and to provide supportive treatment. There is no specific antidote to DIPENTUM.

Maximum single oral doses of 5g/kg in mice and rats and 2 g/kg in dogs were not lethal. Symptoms of acute toxicity were decreased motor activity and diarrhea in all species tested. In addition, vomiting was reported in dogs.

DRUG ABUSE AND DEPENDENCY Abuse None reported.

Dependence Drug dependence has not been reported with chronic administration of olsalazine.

Pharmacology

There is limited information regarding Olsalazine Pharmacology in the drug label.

Mechanism of Action

Structure

File:Olsalazine01.png

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Olsalazine in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Olsalazine in the drug label.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility In a two year oral rat carcinogenicity study, olsalazine was tested in male and female Wistar rats at daily doses of 200, 400, and 800 mg/kg/day (approximately 10 to 40 times the human maintenance dose, based on a patient weight of 50 kg and a human dose of 1 g). Urinary bladder transitional cell carcinomas were found in three male rats (6%, p=0.022, exact trend test) receiving 40 times the human dose and were not found in untreated male controls. In the same study, urinary bladder transitional cell carcinoma and papilloma occurred in 2 untreated control female rats (2%). No such tumors were found in any of the female rats treated at doses up to 40 times the human dose.

In an eighteen month oral mouse carcinogenicity study, olsalazine was tested in male and female CD-1 mice at daily doses of 500, 1000, and 2000 mg/kg/day (approximately 25 to 100 times the human maintenance dose). Liver hemangiosarcomata were found in two male mice (4%) receiving olsalazine at 100 times the human dose, while no such tumor occurred in the other treated male mice groups or any of the treated female mice. The observed incidence of this tumor is within the 4% incidence in historical controls.

Olsalazine was not mutagenic in in vitro Ames tests, mouse lymphoma cell mutation assays, human lymphocyte chromosomal aberration tests, or the in vivo rat bone marrow cell chromosomal aberration test.

Olsalazine in a dose range of 100 to 400 mg/kg/day (approximately 5 to 20 times the human maintenance dose) did not influence the fertility of male or female rats. The oligospermia and infertility in men associated with sulfasalazine have not been reported with olsalazine.

Clinical Studies

There is limited information regarding Clinical Studies of Olsalazine in the drug label.

How Supplied

Storage

There is limited information regarding Olsalazine Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

File:Olsalazine01.png

This image is provided by the National Library of Medicine.

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This image is provided by the National Library of Medicine.

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Olsalazine in the drug label.

Precautions with Alcohol

• Alcohol-Olsalazine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• ®

Look-Alike Drug Names

• A® — B®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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