Olsalazine Sodium

FDA Drug Information • Also known as: Dipentum

Brand Names: Dipentum
Route: ORAL
Dosage Form: CAPSULE, GELATIN COATED
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION The active ingredient in DIPENTUM (olsalazine sodium) is the sodium salt of a salicylate, disodium 3,3'-azobis (6-hydroxybenzoate) a compound that is effectively bioconverted to mesalamine (5-aminosalicylic acid,5-ASA), an aminosalicylate. Its empirical formula is C14H8N2Na2O6 with a molecular weight of 346.21. The structural formula is: Olsalazine sodium is a yellow crystalline powder, which melts with decomposition at 240°C. It is the sodium salt of a weak acid, soluble in water and DMSO, and practically insoluble in ethanol, chloroform, and ether. Olsalazine sodium has acceptable stability under acidic or basic conditions. DIPENTUM is supplied in capsules for oral administration. Each DIPENTUM hard gelatin capsule contains 250 mg olsalazine sodium (equivalent to 233.4 mg of olsalazine). The inert ingredient in each capsule is magnesium stearate. The capsule shell contains the following inactive ingredients: black iron oxide, caramel, gelatin, and titanium dioxide. Olsalazine Sodium Structural Formula

What Is Olsalazine Sodium Used For?

1 INDICATIONS AND USAGE DIPENTUM is indicated for the maintenance of remission of ulcerative colitis in adult patients who are intolerant of sulfasalazine. DIPENTUM is an aminosalicylate indicated for the maintenance of remission of ulcerative colitis in adult patients who are intolerant of sulfasalazine. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Evaluate renal function before initiating therapy with DIPENTUM [see Warnings and Precautions (5.1) ]. The recommended dosage is 500 mg orally twice daily. Drink an adequate amount of fluids during treatment [see Warnings and Precautions (5.7) ] .

Evaluate renal function prior to initiation of DIPENTUM and periodically while on therapy. ( 2 , 5.1 )

The recommended dosage is 500 mg orally twice daily. ( 2 )

Drink an adequate amount of fluids. ( 2 , 5.7 )

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling:

Renal impairment [see Warnings and Precautions (5.1) ]

Mesalamine-induced acute intolerance syndrome [see Warnings and Precautions (5.2) ]

Hypersensitivity reactions [see Warnings and Precautions (5.3) ]

Hepatic failure [see Warnings and Precautions (5.4) ]

Severe cutaneous adverse reactions [see Warnings and Precautions (5.5) ]

Photosensitivity [see Warnings and Precautions (5.6) ]

Nephrolithiasis [see Warnings and Precautions (5.7) ] The following adverse reactions have been identified from clinical studies or postmarketing reports of olsalazine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In double-blind, placebo- and active-controlled clinical trials of ulcerative colitis, discontinuations due to adverse reactions were reported in 10% of DIPENTUM-treated patients (N=441) and 7% of placebo-treated patients (N=208). Both sulfasalazine-tolerant and intolerant patients were included. The most common adverse reactions leading to discontinuation in DIPENTUM-treated patients were diarrhea/loose stools (6%), abdominal pain (1%), and rash/itching (1%). In these controlled trials, adverse reactions reported in 1% or more of patients treated with DIPENTUM and greater than placebo are provided in Table 1. Table 1 Adverse Reactions reported in at least 1% of patients in the DIPENTUM group and greater than placebo in Patients with Ulcerative Colitis in Double-Blind, Controlled Clinical Trials Adverse Reaction DIPENTUM (N=441) % Placebo (N=208) % Diarrhea 11 7 Abdominal pain/cramps 10 7 Nausea 5 4 Arthralgia/Joint Pain 4 3 Rash 2 1 Upper Respiratory Infection 2 0 Depression 2 0 Vomiting 1 0 Stomatitis 1 0 Vertigo/Dizziness 1 0 Itching 1 0 Other adverse reactions reported in clinical trials or post-marketing experience: Blood and Lymphatic System Disorders aplastic anemia, anemia, eosinophilia, hemolytic anemia, leukopenia, lymphopenia, neutropenia, pancytopenia, 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 General Disorders and Administration Site Conditions fever chills, hot flashes, irritability, pyrexia, rigors Hepatobiliary Disorders hepatic enzyme increased, hepatitis (including cholestasis, granulomatous, and non-specific, reactive), 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. Immune System Disorders bronchospasm, erythema nodosum Musculoskeletal and Connective Tissue Disorders myalgia, muscle cramps Nervous System Disorders insomnia, paraesthesia, peripheral neuropathy, tremors Psychiatric Disorders mood swings Renal and Urinary Disorders dysuria, hematuria, interstitial nephritis, nephrolithiasis, nephrotic syndrome, proteinuria, urinary frequency

Urine discoloration occurring ex-vivo caused by contact...

Drug Interactions

7 DRUG INTERACTIONS

Nephrotoxic Agents including Non-Steroidal Anti-inflammatory Drugs (NSAIDs) : Increased risk of nephrotoxicity; monitor for changes in renal function and mesalamine-related adverse reactions. ( 7.1 )

Azathioprine or 6-Mercaptopurine : Increased risk of blood dyscrasias; monitor complete blood cell counts and platelet counts. ( 7.2 )

Low Molecular Weight Heparins or Heparinoids : Increased risk of bleeding following neuraxial anesthesia; if possible, discontinue DIPENTUM or closely monitor for bleeding. ( 7.1 )

Varicella Vaccine : Avoid use for 6 weeks after vaccination. ( 7.4 ) 7.1 Nephrotoxic Agents, Including Non-Steroidal Anti-Inflammatory Drugs The concurrent use of mesalamine with known nephrotoxic agents, including non‑steroidal anti‑inflammatory drugs (NSAIDs), may increase the risk of nephrotoxicity. Monitor patients taking nephrotoxic drugs for changes in renal function and mesalamine-related adverse reactions [see Warnings and Precautions (5.1) ] . 7.2 Azathioprine or 6-Mercaptopurine The concurrent use of mesalamine with azathioprine or 6‑mercaptopurine and/or any other drugs known to cause myelotoxicity (e.g., thioguanine) may increase the risk for blood disorders, bone marrow failure, and associated complications. If concomitant use of DIPENTUM and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts. 7.3 Low Molecular Weight Heparins or Heparinoids 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. Discontinue DIPENTUM 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. 7.4 Varicella Vaccine Avoid DIPENTUM, and other salicylates, for six weeks after the varicella vaccine to avoid a possible increased risk of developing Reye’s syndrome. 7.5 Interference With Urinary Normetanephrine Measurements Use of DIPENTUM, which is converted to mesalamine, may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection [see Warnings and Precautions (5.8) ] . Consider an alternative, selective assay for normetanephrine.

Contraindications

4 CONTRAINDICATIONS DIPENTUM is contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or to any of the excipients in DIPENTUM [see Warnings and Precautions (5.3) , Description (11) ] . Known or suspected hypersensitivity to salicylates or aminosalicylates or to any of the ingredients of DIPENTUM. ( 4 , 5.3 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Published data from meta-analyses, cohort studies and case series on the use of mesalamine, the active moiety in DIPENTUM, during pregnancy have not reliably informed an association with mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data ) . There are adverse effects on maternal and fetal outcomes associated with ulcerative colitis in pregnancy (see Clinical Considerations ) . In animal reproduction studies, there were adverse developmental effects observed after oral administration of olsalazine sodium in pregnant rats during organogenesis at doses of 5 to 20 times the maximum recommended human dose (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo/fetal risk Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. Data Human Data Published data from meta-analyses, cohort studies and case series on the use of mesalamine, the active moiety in DIPENTUM, during early pregnancy (first trimester) and throughout pregnancy have not reliably informed an association of mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes. There is no clear evidence that mesalamine exposure in early pregnancy is associated with an increased risk in major congenital malformations, including cardiac malformations. Published...

Overdosage

10 OVERDOSAGE DIPENTUM is an aminosalicylate, and symptoms of salicylate toxicity include: nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe salicylate intoxication may lead to electrolyte and blood pH imbalance and potentially to other organ (e.g., renal and liver) damage. There is no specific antidote for olsalazine overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage and may include gastrointestinal tract decontamination to prevent of further absorption. Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING DIPENTUM is supplied as beige colored capsules, containing 250 mg olsalazine sodium imprinted with “DIPENTUM ® 250 mg” on the capsule shell, available as: Bottles of 100’s NDC 0037-6860-10 Store at 20°C to 25°C (68°F to 77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.