The active ingredient in DIPENTUM Capsules (olsalazine sodium) is the sodium salt of a salicylate, disodium 3,3'-azobis (6-hydroxybenzoate) a compound that is effectively bioconverted to 5-aminosalicylic acid (5- ASA), which has anti-inflammatory activity in ulcerative colitis. 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 hard gelatin capsules for oral administration. The inert ingredient in each 250 mg capsule of olsalazine sodium is magnesium stearate. The capsule shell has the following inactive ingredients: black iron oxide, caramel, gelatin, and titanium dioxide.

Olsalazine is indicated for the maintenance of remission of ulcerativecolitis in patients who are intolerant of sulfasalazine.

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

Beige colored capsules, containing 250 mg olsalazine sodium imprinted with "DIPENTUM® 250 mg" on the capsule shell. Packaged in bottles of 100 (NDC 0013-0105-01) and 300 (NDC 0013-0105-20).

Storage

Store at 25°C (77°F). Excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Manufactured for: Pharmacia & Upjohn Company, A subsidiary of Pharmacia Corporation, Kalamazoo, MI 49001, USA. by: Pharmacia AB Stockholm, Sweden. FDA Rev date: 7/10/2007

In the course of treatment with preparations containing the prothrombin complex, thromboembolic events may occur particularly after high doses and/or in patients with thrombotic risk factors.

After application of high doses (single infusion of 100 units per kg of body weight, and daily doses of 200 units per kg of body weight) of FEIBA VH (AICC), laboratory and/or clinical signs of DIC have occasionally been observed.

In individual instances myocardial infarction was found to occur after high doses and/or prolonged administration and/or in the presence of risk factors predisposing to myocardial infarction.

As with all human plasma products, any kind of allergic reaction may be seen ranging from mild, short-term urticarial rashes to severe anaphylactoid reactions. Administration of FEIBA VH (AICC), Vapor Heated should be discontinued immediately, if such signs appear. Allergic reactions should be treated with antihistamines and glucocorticoids. Shock should be treated in the usual way.

No information provided.

FEIBA VH (AICC), Vapor Heated, is made from human plasma. Products made from plasma may contain infectious agents, such as viruses, that can cause disease. The risk that such products will transmit an infectious agent has been reduced by effective donor screening, testing for the presence of certain current virus infections, by inactivating and/or removing certain viruses. Despite these measures, such products can still potentially transmit disease. Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g. viruses, and theoretically the Creutzfeldt-Jacob disease (CJD) agent. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other health care provider to Baxter Healthcare Corporation, at 1-800-423-2862 (in the U.S.). The physician should discuss the risks and benefits of this product with the patient.

FEIBA VH (AICC), Vapor Heated must be used only in patients with circulating inhibitors to one or more coagulation factors and should not be used for the treatment of bleeding episodes resulting from coagulation factor deficiencies. It should not be given to patients with significant signs of disseminated intravascular coagulation (DIC) or fibrinolysis.

Thromboembolic events may occur in the course of treatment with preparations containing the prothrombin complex, particularly following the administration of high doses and/or in patients with thrombotic risk factors.

Infusion of FEIBA VH (AICC) should not exceed single dosage of 100 units per kg of body weight and daily doses of 200 units per kg of body weight. Patients receiving more than 100 units per kg of body weight of FEIBA VH (AICC) must be monitored for the development of DIC and/or symptoms of acute coronary ischemia (see ADVERSE REACTIONS section).

High doses of FEIBA VH (AICC) should be given only as long as absolutely necessary to stop bleeding.

It has been reported that FEIBA VH (AICC) and antifibrinolytics have been given simultaneously without complications. It is recommended not to use antifibrinolytics until 12 hours after the administration of FEIBA VH (AICC).

Anamnestic responses with rise in Factor VIII inhibitor titer have been observed in 20% of the cases (see CLINICAL PHARMACOLOGY section).

Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly non A, non B hepatitis.

Monitoring of Therapy

If clinical signs of intravascular coagulation occur, which include changes in blood pressure, changes in pulse rate, respiratory distress, chest pain and/or cough, the infusion should be stopped promptly and appropriate diagnostic and therapeutic measures are to be initiated.

Laboratory indications of DIC are decreased fibrinogen, decreased platelet count, and/or presence of fibrin-fibrinogen degradation products (FDP). Other indications of DIC include significantly prolonged thrombin time, prothrombin time, or partial thromboplastin time.

Non-Hemophilic Patients

Non-hemophilic patients with acquired inhibitors against Factors VIII, IX or XII may have both a bleeding tendency and an increased risk of thrombosis at the same time.

Laboratory Tests and Clinical Efficacy

Tests used to control efficacy such as APTT, WBCT, and TEG do not correlate with clinical improvement. For this reason, attempts at normalizing these values by increasing the dose of FEIBA VH (AICC), Vapor Heated may not be successful and are strongly discouraged because of the potential hazard of producing DIC by overdose.

Pregnancy Category C

Animal reproduction studies have not been conducted with FEIBA VH (AICC). It is also not known whether FEIBA VH (AICC) can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. FEIBA VH (AICC) should be given to a pregnant woman only if clearly needed.

Pediatric Use

No data are available regarding the use of FEIBA VH (AICC) in newborns.

No information provided.

The use of FEIBA VH (AICC) is contraindicated in patients who are known to have a normal coagulation mechanism.

In a preclinical study to determine the virus inactivating efficacy of vapor heating, samples of bulk FEIBA IMMUNO (AICC) were spiked with 2 x 106/mL infectious units of HIV and subjected to vapor heat treatment. The residual virus titer was found to be less than 1 infectious unit/0.5 mL. A clinical study⁴ testing Antihemophilic Factor treated by a similar vapor heating procedure has shown none of 4 lots used in the study to produce non A, non B hepatitis in intensively followed patients naive to blood product administration.

The safety and efficacy of FEIBA IMMUNO (AICC) has been demonstrated by two prospective clinical trials^5–7. The first, conducted by Sixma and collaborators during 1979 and early 1980, was a randomized double-blind study comparing the effect of FEIBA IMMUNO (AICC) and PROTHROMPLEX IMMUNO (a non-activated prothrombin complex concentrate) in 15 patients with hemophilia A and inhibitors to Factor VIII. A total of 150 bleeding episodes (primarily joint and musculoskeletal plus a few mucocutaneous) were treated. A single dose of 88 Units per kg of body weight was used uniformly for treatments with FEIBA IMMUNO (AICC). The study showed that, based on subjective patient evaluation, FEIBA IMMUNO (AICC) was fully effective in 41.0% and partly effective in 24.6% of episodes (i.e. combined effectiveness of 65.6%), while PROTHROMPLEX IMMUNO was rated fully effective in 25.0% and partly effective in 21.4% of episodes (i.e. combined effectiveness of 46.4%).

The second study with FEIBA IMMUNO (AICC) was a multiclinic study conducted by Hilgartner et al. It was designed to evaluate the efficacy of FEIBA IMMUNO (AICC) in the treatment of joint, mucous membrane, musculocutaneous and emergency bleeding episodes such as central nervous system hemorrhages and surgical bleedings. In 49 patients with inhibitor titers of greater than 5 Bethesda Units (from nine co-operating hemophilia centers), 489 single doses were given for the treatment of 165 bleeding episodes. The usual dosage was 50 Units per kg of body weight, repeated at 12-hour intervals (6-hour intervals in mucous membrane bleedings), if necessary. Bleeding was controlled in 153 episodes (93%). In 130 (78%) of the episodes, hemostasis was achieved with one or more infusions within 36 hours. Of these, 36% were controlled with one infusion within 12 hours. An additional 14% of episodes responded after more than 36 hours.

Of the 489 single doses, only 18 (3.7%) caused minor transient reactions in recipients. 10 out of 49 patients (20%) showed a rise in their inhibitor titers. In 5 of these patients (10%), the rise was tenfold or more. However, of these 10 patients, 3 had received Factor VIII or Factor IX concentrates within 2 weeks prior to treatment with FEIBA IMMUNO (AICC). These anamnestic rises have not been observed to interfere with the efficacy of FEIBA IMMUNO (AICC).

REFERENCE

4. Mannucci P. M.: Personal communication

5. Sjamsoedin L. J. M., Heijnen L., Mauser-Bunschoten E. P., van Geijlswijk J. L., van Houwelingen H., van Asten P., Sixma J. J.: The Effect of Activated Prothrombin-Complex Concentrate (FEIBA) on Joint and Muscle Bleeding in Patients with Hemophilia A and Antibodies to Factor VIII. The New Engl. J. of Med. 305: 717, 1981.

6. Roberts H. R.: Hemophiliacs with Inhibitors: Therapeutic Options. The New Engl. J. of Med. 305:757, 1981.

7. Hilgartner M. W., Knatterud G. AND THE FEIBA STUDY GROUP: The Use of Factor-Eight-Inhibitor-ByPassing-Activity (FEIBA IMMUNO) Product for Treatment of Bleeding Episodes in Hemophiliacs with Inhibitors. Blood 61: 36, 1983.

Some viruses, such as parvovirus B19 or hepatitis A, are particularly difficult to remove or inactivate at this time. Parvovirus B19 most seriously affects pregnant women or immune-compromised individuals. Symptoms of parvovirus B19 infection include fever, drowsiness, chills, and runny nose followed about two weeks later by a rash, and joint pain. Evidence of hepatitis A may include several days to weeks of poor appetite, tiredness, and low-grade fever followed by nausea, vomiting, and pain in the belly. Dark urine and a yellowed complexion are also common symptoms. Patients should be encouraged to consult their physician if such symptoms appear.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

OLSALAZINE - ORAL

(ohl-SAL-uh-zeen)

COMMON BRAND NAME(S): Dipentum

USES: Olsalazine is used to treat a certain type of bowel disease called ulcerative colitis. It does not cure ulcerative colitis, but it may decrease symptoms such as stomach pain, diarrhea, and rectal bleeding caused by irritation/swelling of the colon/rectum. After an attack is treated, olsalazine is used to increase the amount of time between attacks.

Olsalazine is a salicylate anti-inflammatory drug. It is believed to work by blocking the production of certain natural substances (e.g., prostaglandins) that may cause pain and swelling.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This medication may also be used to treat another type of bowel disease called Crohn's disease.

HOW TO USE: Take this medication by mouth, usually twice a day about 12 hours apart or as directed by your doctor. Take with food or after meals to prevent stomach upset. Dosage is based on your medical condition and response to treatment.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same times each day.

Tell your doctor if your condition persists or worsens.

SIDE EFFECTS: Headache, nausea, vomiting, or loss of appetite may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if diarrhea occurs. Your doctor may need to lower your dose or prescribe another medication to treat the diarrhea.

Tell your doctor immediately if any of these rare but very serious side effects occur: severe stomach/abdominal pain, pale stools, unusual tiredness, persistent nausea/vomiting, change in the amount of urine, dark urine, yellowing eyes/skin, signs of infection (e.g., fever, persistent sore throat), easy bruising/bleeding.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking olsalazine, tell your doctor or pharmacist if you are allergic to it; or to aspirin or related drugs (salicylates such as mesalamine, NSAIDs such as ibuprofen); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: asthma, growths in the nose (nasal polyps), kidney problems, liver problems, radiation treatment in the pelvic area.

This medicine may cause stomach bleeding. Daily use of alcohol may increase your risk for stomach bleeding, especially when combined with this medicine. Check with your doctor or pharmacist for more information.

This medication is similar to aspirin. Children and teenagers should not take aspirin or aspirin-related medications (e.g., salicylates) if they have chickenpox, flu, or any undiagnosed illness, or if they have just been given a live virus vaccine (e.g., varicella vaccine), without first consulting a doctor about Reye's syndrome, a rare but serious illness.

During pregnancy, this drug should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This drug may pass into breast milk and could have undesirable effects on a nursing infant. Therefore, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: mercaptopurine, thioguanine, warfarin.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., kidney/liver function tests) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.