Ergotamine

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Ergotamine tartrate/

Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /Ergotamine tartrate/

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C. Hygroscopic. Light sensitive. Store under inert gas. /Ergotamine tartrate/

Preparations of ergotamine tartrate should be stored in light-resistant containers. Oral tablets containing ergotamine tartrate and caffeine should be stored at 15-30 °C. Ergotamine tartrate sublingual tablets should be stored at 20-25 °C but may be exposed to temperatures ranging from 15-30 °C. Suppositories containing ergotamine tartrate and caffeine should be stored at a temperature of 2-8 °C.

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Ergotamine tartrate/

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber; Contaminated packaging: Dispose of as unused product. /Ergotamine tartrate/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drains. /Ergotamine tartrate/

Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. /Ergotamine tartrate/

Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. /Ergotamine tartrate/

Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Ergotamine tartrate/

SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Ergotamine tartrate/

Skin protection: Handle with gloves. /Ergotamine tartrate/

Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Ergotamine tartrate/

Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Ergotamine tartrate/

Treatment consists of removal of the offending drug. Maintenance of adequate pulmonary ventilation, correction of hypotension, and control of convulsions and blood pressure are important considerations. Treatment of peripheral vasospasm should consist of warmth, but not heat, and protection of the ischemic limbs. Vasodilators may be beneficial but caution must be exercised to avoid aggravating an already existent hypotension. (L1733)

Coadministration of ergotamine with potent CYP 3A4 inhibitors such as protease inhibitors or macrolide antibiotics has been associated with serious adverse events; for this reason, these drugs should not be given concomitantly with ergotamine. While these reactions have not been reported with less potent CYP 3A4 inhibitors, there is a potential risk for serious toxicity including vasospasm when these drugs are used with ergotamine. Examples of less potent CYP 3A4 inhibitors include: saquinavir, nefazodone, fluconazole, fluoxetine, grapefruit juice, fluvoxamine, zileuton, metronidazole, and clotrimazole. These lists are not exhaustive, and the prescriber should consider the effects on CYP 3A4 of other agents being considered for concomitant use with ergotamine.

Ergomar Sublingual Tablets (Ergotamine Tartrate Sublingual Tablets USP) should not be administered with other vasoconstrictors. Use with sympathomimetics (pressor agents) may cause extreme elevation of blood pressure. The beta-blocker Inderal (propranolol) has been reported to potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine. Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy. The blood levels of ergotamine-containing drugs are reported to be elevated by the concomitant administration of macrolide antibiotics and vasospastic reactions have been reported with therapeutic doses of the ergotamine-containing drugs when coadministered with these antibiotics.

There have been a few reports of patients on ergotamine tartrate and caffeine therapy developing retroperitoneal and/or pleuropulmonary fibrosis. There have also been rare reports of fibrotic thickening of the aortic, mitral, tricuspid, and/or pulmonary valves with long-term continuous use of ergotamine tartrate and caffeine. Ergomar Sublingual Tablets should not be used for chronic daily administration.

The potential exists for excessive vasoconstriction to occur when ergotamine is used concomitantly with methysergide (no longer commercially available in the US). In patients who are receiving methysergide for prophylaxis, the dose of ergotamine tartrate may have to be decreased (by about 50%) and the frequency of ergotamine tartrate administration should be kept at a minimum.

For more Interactions (Complete) data for Ergotamine (25 total), please visit the HSDB record page.

Vasoconstrictive complications of a serious nature may occur at times. These include ischemia, cyanosis, absence of pulse, cold extremities, gangrene, precordial distress and pain, EKG changes and muscle pains. Although these effects occur most commonly with long-term therapy at relatively high doses, they have also been reported with short-term or normal doses. Other cardiovascular adverse effects include transient tachycardia or bradycardia and hypertension. Ingestion of ergoline alkaloids is also known to cause the disease ergotism. Ergotism occurs in two forms, gangrenous and convulsive, likely depending on the different kinds and amounts of ergoline alkaloids present. (A1497, L1452, A2913)

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 270,000(SRC), determined from a structure estimation method(2), indicates that ergotamine is expected to be immobile in soil(SRC). The estimated pKa of ergotamine is 8.75(3), indicating that this compound will exist almost entirely in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of the cation from moist soil is not expected because cations do not volatilize(SRC). Ergotamine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.6X10-24 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2017).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 270,000(SRC), determined from a structure estimation method(2), indicates that ergotamine is expected to adsorb to suspended solids and sediment(SRC). An estimated pKa of 8.75(3) indicates ergotamine will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). Ergotamine is not expected to undergo hydrolysis in the environment due to the absence of functional groups that hydrolyze under environmental conditions(4). According to a classification scheme(5), an estimated BCF of 23(SRC), from an estimated log Kow of 2.53(2) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low. Biodegradation data in water were not available(SRC, 2017).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ergotamine, which has an estimated vapor pressure of 1.6X10-24 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase ergotamine may be removed from the air by wet and dry deposition(SRC). Ergotamine contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

In finished products purchased from local markets and online stores in the US from Aug 2011 to Jan 2012, ergotamine was not detected (detection limit 0.2-0.3 ug/kg) in 6 rice, 18 corn, 11 peanut, 10 pistachio or 9 almond samples; but was detected in 2 of 16 wheat samples at 8.3 and 10.7 ug/kg(1). Ergotamine was not detected (LOQ 5, 10, 50 ug/kg, respectively) in plant based supplements intended for treatment of liver diseases (32), reduction of menopause effects (9) and general health support (28) collected from Czech and US retail markets(2). In samples collected from German markets, ergotamine was detected in nine rye flour samples at 2.0-23.0 ug/kg, but not in seven wheat germ oil samples (detection limit 0.3 ug/kg)(3). The mean concentration of ergotamine in rye and whole wheat flour was 8.04-84.7 and 5.01-19.7 ug/kg, respectively(4). Ergotamine was detected in 4 of 43 barley malt samples collected in 2013 across the Umbria region of Italy at an average of 239.7 ug/kg(5).

Ergotamine concentrations in rye flour products from Germany were as follows(1):[Table#4800]

IDENTIFICATION AND USE: Ergotamine tartrate is used to prevent or abort vascular headaches, including migraine and cluster headaches. It is also used in veterinary medicine. HUMAN STUDIES: There have been reports of drug abuse and psychological dependence in patients on ergotamine tartrate therapy. In addition to the adverse effects which may occur with usual doses or prolonged administration of high doses (especially adverse vasospastic effects, nausea, and vomiting), acute overdosage of ergotamine may cause lassitude, impaired mental function, confusion, depression, drowsiness, delirium, severe dyspnea, hypotension, hypertension, rapid and weak pulse, unconsciousness, spasms of the limbs, seizures (rarely), shock, and death. Ergotism is manifested by intense arterial vasoconstriction, producing signs and symptoms of peripheral vascular ischemia. Ergotamine induces vasoconstriction by a direct action on vascular smooth muscle. In chronic intoxication with ergot derivatives, headache, intermittent claudication, muscle pains, numbness, coldness, and pallor of the digits may occur. If the condition is allowed to progress untreated, gangrene can result. Nausea and vomiting, due to a direct effect on CNS emetic centers, occur in approximately 10% of patients after oral administration of ergotamine, and in about twice that number after parenteral administration. Leg weakness is common, and muscle pains that occasionally are severe may occur in the extremities. Numbness and tingling of the fingers and toes are other reminders of the ergotism that this alkaloid may cause. Precordial distress and pain suggestive of angina pectoris, as well as transient tachycardia or bradycardia, also have been noted, presumably as a result of coronary vasospasm induced by ergotamine. Ergotamine has been tested for its ability to induce chromosomal damage in human lymphocyte cells. Treatment with 0.1, 0.25 and 0.5 ug/mL significantly increased frequency of aberrations. Ergotamine is contraindicated in pregnant women. ANIMAL STUDIES: It is suggested that dietary ergotamine is atherogenic in the rabbit. Daily oral doses of 1.0 mg/kg of ergotamine tartrate resulted in death of 4 of 6 sheep in 10 days. Postmortem exam revealed intestinal inflammation. 0.5 mg/day over a period of 10 days was not fatal. Extended exposure of bulls to ergotamine appeared to reduce fertilization potential of sperm. Single-day oral treatment of rats with ergotamine (10 mg/kg) causes fetal deaths. In early pregnancy, from days 4-10, mortality was only 0-11%, and on days 14 and 15, 62% and 59% respectively. Typical anomalies resulting from "edema syndrome" were seen only on days 13-16. Male mice were injected with 25, 50 and 100 mg/kg ergotamine, and significant number of chromosome aberrations were observed with higher doses. Almost all damage was in form of chromatid aberrations. Dominant lethal test with mice using ergotamine was negative in doses up to 100 mg/kg. Several accidental poisonings in cows were described in the literature.

Tall fescue (Festuca arundinacea Schreb.) infected by the endophytic fungus (Neotyphoidium coenophialum) did not contain ergotamine(1). In 23 Canada western amber durum and 42 Canada western red spring grain samples harvested in 2011, ergotamine comprised 14% of the total alkaloids found; from shipment samples (117 wheat, 46 durum, 25 barley, 1 rye) from 2010-2012, ergotamine was 10% of total alkaloids detected(2).

The concentration of ergotamine measured in rye harvested in 2005-2009 from Germany was as follows(1):[Table#4804]

Signs of ergotamine overexposure include irritation, nausea, vomiting, headache, diarrhea, thirst, coldness of skin, pruritus, weak pulse, numbness, tingling of extremities, and confusion. Convulsive ergotism can cause painful seizures and spasms, diarrhea, paresthesias, itching, headaches, nausea and vomiting. Usually the gastrointestinal effects precede the central nervous system effects. As well as seizures there can be hallucinations and mental effects including mania or psychosis. Gangrenous ergotism causes dry gangrene as a result of vasoconstriction induced in the more poorly vascularized distal structures, such as the fingers and toes. Symptoms include desquamation, weak periphery pulse, loss of peripheral sensation, edema and ultimately the death and loss of affected tissues. (A1497, L1733, L1920)

The following link will take the user to the National Toxicology Program (NTP) Test Status of Agents Search page, which tabulates the results and current status of tests such as "Short-Term Toxicity Studies", "Long-term Carcinogenicity Studies", "Developmental Studies", "Genetic Toxicology Studies", etc., performed with this chemical. Testing status for ergotamine tartrate is available. /Ergotamine tartrate/[Available from, as of May 8, 2017: https://ntpsearch.niehs.nih.gov/?e=True&ContentType=Testing+Status]

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ergotamine can be estimated to be 270,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that ergotamine is expected to be immobile in soil. The pKa of ergotamine is estimated to be 8.75(3), indicating that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ergotamine tartrate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Ergotamine tartrate/

Releases of CERCLA hazardous substances are subject to the release reporting requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the requirements of 40 CFR part 355. Ergotamine tartrate is an extremely hazardous substance (EHS) subject to reporting requirements when stored in amounts in excess of its threshold planning quantity (TPQ) of 500 or 10,000 lbs. Extremely hazardous substances that are solids are subject to either of two threshold planning quantities ... The lower quantity applies only if the solid exists in powdered form and has a particle size less than 100 microns; or is handled in solution or in molten form; or meets the criteria for a National Fire Protection Association (NFPA) rating of 2, 3 or 4 for reactivity. If the solid does not meet any of these criteria, it is subject to the upper ... threshold planning quantity ... . /Ergotamine tartrate/

Ergot lysergic acid alkaloid produced by Claviceps species (fungal pathogens) commonly found on various grasses; Used to treat migraines (in pure form); [Reference #1] An alkaloid produced by fungi growing on rye; [Hawley]

Oxytocics; Vasoconstrictor Agents; Serotonin Receptor Agonists; Analgesics, Non-Narcotic; Adrenergic alpha-1 Receptor Agonists

MEDICATION

MEDICATION (VET)

For use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called "histaminic cephalalgia". Ergotamine is a secondary metabolite (natural product) and principal alkaloid of the ergot fungus, Claviceps purpurea, and related fungi in the family Clavicipitaceae. It is used medicinally for treatment of acute migraine attacks (sometimes in combination with caffeine), and to induce childbirth and prevent post-partum haemorrhage. (L1927)

Commercial production involves generation parasitically on rye in the field or production in culture because a commercially useful synthesis is unavailable. The common technique today is to grow the fungus in submerged culture. Claviceps paspali (Stevens and Hall) is said to be more productive than C. purpurea (Fries). In this way, ergotamine and ergonovine are produced. Ergotamine is obtained from crude extract by formation of an aluminum complex. Destruction of the aluminum complex with ammonia then permits hydrocarbon extraction of the alkaloid. The alkaloid is subsequently both isolated and used as its tartrate salt.

Table: Ergotamine Tartrate Preparations [Table#4801]

Table: Ergotamine Tartrate Combination Preparations [Table#4802]

Ergotamine and its salts

A chemical specified by regulation that, in addition to legitimate uses, is used in manufacturing a controlled substance in violation of the Act and is important to the manufacture of a controlled substance. (21 eCFR 1310.02)

Among individual alkaloids only levo-isomers (names ending in "ine" versus "inine" for dextro forms) are highly active. /Ergot alkaloids/

Cultivation of ergot on triticale using strain of Claviceps purpurea, isolated from ergot sclerotia produced on infected rye is described. Yield (ergotamine 0.434%) was higher than prodn from rye ergot (0.23%).