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Basic Drug Info

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Drug Name:	Sansert
Manufacturer:	Novartis Pharmaceuticals Corporation
Other Info:	Considering structure/effect relationships, it has been demonstrated that methylation of the indole nitrogen in the lysergic acid ring of the alkanolamides fundamentally alters their pharmacologic behavior and is associated with inhibition or blockade of a great variety of serotonin-induced effects: 1. Methysergide maleate is 6 times more active than methylergonovine maleate in antagonizing the effect of serotonin on the rat uterus in vitro. 2. Greater inhibition of the serotonin-induced edema in the rat’s paw is revealed by the ED50 of 12.9 µg/kg for methysergide maleate as against 37.4 µg/kg for methylergonovine maleate (see following graph). 3. The more complex effects of serotonin on the cardiovascular system are equally subject to inhibition by methysergide maleate as is evident from the subsequent record of various circulatory parameters in the dog before and after administration of 10 µg/kg. Acute Toxicity LD 50 in mg/kg Mice Rabbits Rats Compound i.v. oral i.v. i.v. oral Methysergide maleate 185 581 28 125 2100 methylergonovine maleate 85 187 2.6 23 93 Chronic Toxicity Rats Daily Oral Doses mg/kg No. of Weeks Animals Tested Mortality 5 50 4/16 20 50 2/16 50 50 2/16 150 17 8/30 450 17 17/30 Control 50 1/16 Dogs Oral administration of 1, 2, and 5 mg/kg/day of methysergide maleate failed to produce any major signs of toxicity over a period of 6 months. *Trademark of Medical Economics Company, Inc. Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936 REV: NOVEMBER 2000 T2000-69

Clinical Trials:	NIH - Clinical Trials

Indications and Usage

For the prevention or reduction of intensity and frequency of vascular headaches in the following kinds of patients: Patients suffering from one or more severe vascular headaches per week. Patients suffering from vascular headaches that are uncontrollable or so severe that preventive therapy is indicated regardless of the frequency of the attack.

Vascular Headache -- Secondary headache disorders attributed to a variety of cranial or cervical vascular disorders, such as BRAIN ISCHEMIA; INTRACRANIAL HEMORRHAGES; and CENTRAL NERVOUS SYSTEM VASCULAR MALFORMATIONS.

Contraindications

Hypersensitivity to the drug or to tartrazine (FD&C Yellow #5) or any other components of the formulation, pregnancy, lactation, peripheral vascular disease, severe arteriosclerosis, severe hypertension, coronary artery disease, phlebitis or cellulitis of the lower limbs, pulmonary disease, collagen diseases or fibrotic processes, impaired liver or renal function, valvular heart disease, debilitated states and serious infections.

Hypersensitivity -- Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.

Peripheral Vascular Diseases -- Pathological processes involving any one of the BLOOD VESSELS in the vasculature outside the HEART.

Arteriosclerosis -- Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.

Hypertensive disease -- Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.

Coronary Artery Disease -- Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.

Phlebitis -- Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (THROMBOPHLEBITIS).

Cellulitis -- An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions.

Lung diseases -- Pathological processes involving any part of the LUNG.

Collagen Diseases -- Historically, a heterogeneous group of acute and chronic diseases, including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, dermatomyositis, etc. This classification was based on the notion that "collagen" was equivalent to "connective tissue", but with the present recognition of the different types of collagen and the aggregates derived from them as distinct entities, the term "collagen diseases" now pertains exclusively to those inherited conditions in which the primary defect is at the gene level and affects collagen biosynthesis, post-translational modification, or extracellular processing directly. (From Cecil Textbook of Medicine, 19th ed, p1494)

Heart valve disease -- Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).

Infection -- Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.

Warnings

With long-term, uninterrupted administration, retroperitoneal fibrosis or related conditions — pleuropulmonary fibrosis and cardiovascular disorders with murmurs or vascular bruits have been reported.

Patients must be warned to report immediately the following symptoms and to discontinue the drug: cold, numb, and painful hands and feet; leg cramps on walking; any type of girdle, flank, or chest pain, shortness of breath, or any associated symptomatology.

Should any of these symptoms develop, methysergide should be discontinued.

Continuous administration should not exceed 6 months.

There must be a drug-free interval of 3-4 weeks after each 6-month course of treatment.

The dosage should be reduced gradually during the last 2-3 weeks of each treatment course to avoid “headache rebound.” The drug is not recommended for use in children.