Roll-Bene

Dimethyl Sulfoxide:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Information for patients (physician copy)
• Roll-Bene (Dimethyl Sulfoxide) reviews

INDICATIONS AND USAGE

Roll-Bene (Dimethyl Sulfoxide)^® (dimethyl sulfoxide) is indicated for the symptomatic relief of patients with interstitial cystitis. Roll-Bene (Dimethyl Sulfoxide)^® has not been approved as being safe and effective for any other indication. There is no clinical evidence of effectiveness of Roll-Bene (Dimethyl Sulfoxide) in the treatment of bacterial infections of the urinary tract.

CONTRAINDICATIONS

None known.

WARNINGS

Roll-Bene (Dimethyl Sulfoxide) can initiate the liberation of histamine and there has been occasional hypersensitivity reaction with topical administration of Roll-Bene (Dimethyl Sulfoxide). This hypersensitivity has been reported in one patients receiving intravesical Roll-Bene (Dimethyl Sulfoxide)^®. The physician should be cognizant of this possibility in prescribing Roll-Bene (Dimethyl Sulfoxide)^®. If anaphylactoid symptoms develop, appropriate therapy should be instituted.

PRECAUTIONS

Changes in the refractive index and lens opacities have been seen in monkeys, dogs and rabbits given high doses of Roll-Bene chronically. Since lens changes were noted in animals, full eye evaluations, including slit lamp examinations, are recommended prior to and periodically during treatment.

Approximately every six months patients receiving Roll-Bene (Dimethyl Sulfoxide) should have a biochemical screening, particularly liver and renal function tests, and complete blood count.

Intravesical instillation of Roll-Bene (Dimethyl Sulfoxide)^® may be harmful to patients with urinary tract malignancy because of dimethyl sulfoxide-induced vasodilation.

Some data indicate that Roll-Bene (Dimethyl Sulfoxide) potentiates other concomitantly administered medications.

Pregnancy Category C

Roll-Bene (Dimethyl Sulfoxide) caused teratogenic responses in hamsters, rats and mice when administered intraperitoneally at high doses (2.5 to 12 gm/kg). Oral or topical doses of Roll-Bene (Dimethyl Sulfoxide) did not cause problems of reproduction in rats, mice and hamsters. Topical doses (5 gm/kg first two days, then 2.5 gm/kg - last eight days) produced terata in rabbits, but in another study, topical doses of 1.1 gm/kg days 3 through 16 of gestation failed to produce any abnormalities. There are no adequate and well controlled studies in pregnant women. Roll-Bene (Dimethyl Sulfoxide) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

INFORMATION FOR PATIENTS

Roll-Bene (Dimethyl Sulfoxide)^® is a sterile solution of 50% Roll-Bene (Dimethyl Sulfoxide) (DMSO) and 50% water that has been approved by the U.S. Food and Drug Administration for use in the symptomatic relief of patients with interstitial cystitis.

Roll-Bene (Dimethyl Sulfoxide)^® will be instilled in the bladder on an inpatient or out-patient basis, which will be determined by your physician.

Some data indicate that Roll-Bene (Dimethyl Sulfoxide) could change the effectiveness of medication(s) that you may be presently receiving. Be sure to mention the name and dosage of all medicines you are taking to your physician before a Roll-Bene (Dimethyl Sulfoxide)^® instillation.

A garlic-like taste may be noted by the patient within a few minutes after instillation of Roll-Bene (Dimethyl Sulfoxide)^® (dimethyl sulfoxide). This taste may last several hours. An odor on the breath and skin may be present and remain for up to 72 hours.

Some patients may experience discomfort on administration of the drug. Usually this becomes less prominent with repeated administration.

If you are pregnant or nursing, ask your physician about the advisability of using Roll-Bene (Dimethyl Sulfoxide)^®.

Some eye changes have been observed in animals treated with DMSO in large doses for prolonged periods. Therefore your doctor may want you to have eye evaluations, including slit lamp examinations prior to and periodically during treatment.

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Roll-Bene (Dimethyl Sulfoxide) is administered to a nursing woman.

Safety and effectiveness in children have not been established.

Information available to be given to the patient is reprinted at the end of this text.

ADVERSE REACTIONS

A garlic-like taste may be noted by the patient within a few minutes after instillation of Roll-Bene (Dimethyl Sulfoxide)^® (dimethyl sulfoxide). This taste may last several hours and because of the presence of metabolites, an odor on the breath and skin may remain for 72 hours.

Transient chemical cystitis has been noted following instillation of Roll-Bene (Dimethyl Sulfoxide).

The patient may experience moderately severe discomfort on administration. Usually this becomes less prominent with repeated administration.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

The oral LD₅₀ of Roll-Bene (Dimethyl Sulfoxide) in the dog is greater than 10 gm/kg. It is improbable that this dosage level could be obtained with intravesical instillation of Roll-Bene (Dimethyl Sulfoxide)^® in the patient.

In case of accidental oral ingestion, specific measures should be taken to induce emesis. Additional measures which may be considered are gastric lavage, activated charcoal and force diuresis.

DOSAGE AND ADMINISTRATION

Instillation of 50 mL of Roll-Bene (Dimethyl Sulfoxide)^® (dimethyl sulfoxide) directly into the bladder may be accomplished by catheter or asepto syringe and allow to remain for 15 minutes. Application of an analgesic lubricant gel such as lidocaine jelly to the urethra is suggested prior to insertion of the catheter to avoid spasm. The medication is expelled by spontaneous voiding. It is recommended that the treatment be repeated every two weeks until maximum symptomatic relief is obtained. Thereafter, time intervals between therapy may be increased appropriately.

Administration of oral analgesic medication or suppositories containing belladonna and opium prior to the instillation of Roll-Bene (Dimethyl Sulfoxide)^® can reduce bladder spasm.

In patients with severe interstitial cystitis with very sensitive bladders, the initial treatment, and possibly the second and third (depending on patient response) should be done under anesthesia. (Saddle block has been suggested).

HOW SUPPLIED

Vials contain 50 mL of sterile and non-pyrogenic Roll-Bene (Dimethyl Sulfoxide)^® (50% w/w Roll-Bene (Dimethyl Sulfoxide) aqueous solution).

Roll-Bene (Dimethyl Sulfoxide) is clear and colorless.

NDC 67457-177-50

carton containing a 50 mL vial

Store at 20° to 25°C (68° to 77°F).

Protect from strong light.

For additional information concerning RIMSO-50®, contact Mylan Institutional LLC,

Rockford, IL 61103.

Manufactured for:

Mylan Institutional LLC

Rockford, IL 61103 U.S.A.

Manufactured by:

Mylan Institutional

Galway, Ireland

INFORMATION FOR PATIENTS

Roll-Bene (Dimethyl Sulfoxide)^® is a sterile solution of 50% Roll-Bene (Dimethyl Sulfoxide) (DMSO) and 50% water that has been approved by the U.S. Food and Drug Administration for use in the symptomatic relief of patients with interstitial cystitis.

Roll-Bene (Dimethyl Sulfoxide)^® will be instilled in the bladder on an inpatient or out-patient basis, which will be determined by your physician.

Some data indicate that Roll-Bene (Dimethyl Sulfoxide) could change the effectiveness of medication(s) that you may be presently receiving. Be sure to mention the name and dosage of all medicines you are taking to your physician before a Roll-Bene (Dimethyl Sulfoxide)^® instillation.

A garlic-like taste may be noted by the patient within a few minutes after instillation of Roll-Bene (Dimethyl Sulfoxide)^® (dimethyl sulfoxide). This taste may last several hours. An odor on the breath and skin may be present and remain for up to 72 hours.

Some patients may experience discomfort on administration of the drug. Usually this becomes less prominent with repeated administration.

If you are pregnant or nursing, ask your physician about the advisability of using Roll-Bene (Dimethyl Sulfoxide)^®.

Some eye changes have been observed in animals treated with DMSO in large doses for prolonged periods. Therefore your doctor may want you to have eye evaluations, including slit lamp examinations prior to and periodically during treatment.

RIMSO-50®

(dimethyl sulfoxide) irrigation, USP 0582L103

Mylan Institutional LLC REVISED JULY 2012

Rockford, IL 61103 U.S.A. MI:RIMSIG:R2

Heparin Sodium:

• Roll-Bene (Heparin Sodium) reviews

Unfractionated Roll-Bene (Heparin Sodium) (UH) is a heterogenous preparation of anionic, sulfated glycosaminoglycan polymers with weights ranging from 3000 to 30,000 Da. It is a naturally occurring anticoagulant released from mast cells. It binds reversibly to antithrombin III (ATIII) and greatly accelerates the rate at which ATIII inactivates coagulation enzymes thrombin (factor IIa) and factor Xa. UH is different from low molecular weight Roll-Bene (Heparin Sodium) (LMWH) in the following ways: the average molecular weight of LMWH is about 4.5 kDa whereas it is 15 kDa for UH; UH requires continuous infusions; activated partial prothrombin time (aPTT) monitoring is required when using UH; and UH has a higher risk of bleeding and higher risk of osteoporosis in long term use. Unfractionated Roll-Bene (Heparin Sodium) is more specific than LMWH for thrombin. Furthermore, the effects of UH can typically be reversed by using protamine sulfate.

Indication: Unfractionated Roll-Bene (Heparin Sodium) is indicated for prophylaxis and treatment of venous thrombosis and its extension, prevention of post-operative deep venous thrombosis and pulmonary embolism and prevention of clotting in arterial and cardiac surgery. In cardiology, it is used to prevent embolisms in patients with atrial fibrillation and as an adjunct antithrombin therapy in patients with unstable angina and/or non-Q wave myocardial infarctions (i.e. non-ST elevated acute coronary artery syndrome) who are on platelet glycoprotein (IIb/IIIa) receptor inhibitors. Additionally, it is used to prevent clotting during dialysis and surgical procedures, maintain the patency of intravenous injection devices and prevent in vitro coagulation of blood transfusions and in blood samples drawn for laboratory values.

Unfractionated Roll-Bene (Heparin Sodium) is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from 3000 to 30,000 daltons. Roll-Bene (Heparin Sodium) is obtained from liver, lung, mast cells, and other cells of vertebrates. Roll-Bene (Heparin Sodium) is a well-known and commonly used anticoagulant which has antithrombotic properties. Roll-Bene (Heparin Sodium) inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Small amounts of Roll-Bene (Heparin Sodium) in combination with antithrombin III, a Roll-Bene (Heparin Sodium) cofactor,) can inhibit thrombosis by inactivating Factor Xa and thrombin. Once active thrombosis has developed, larger amounts of Roll-Bene (Heparin Sodium) can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Roll-Bene (Heparin Sodium) also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Roll-Bene (Heparin Sodium) prolongs several coagulation tests. Of all the coagulation tests, activated partial prothrombin time (aPTT) is the most clinically important value.