Methysergide (Systemic)
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VA CLASSIFICATION
Primary: CN105
Commonly used brand name(s): Sansert.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Vascular headache prophylactic—
Indications
Accepted
Headache, vascular (prophylaxis)—Methysergide is indicated for prevention of vascular headaches such as migraine and cluster headaches in patients with frequent and/or disabling headaches not responsive to other treatment.
Unaccepted
Methysergide is not recommended for treatment of acute attacks or tension headaches.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
469.54
Mechanism of action/Effect:
Antiserotonin; actions on central nervous system (CNS); direct stimulation of smooth muscle leading to vasoconstriction. Little alpha-adrenergic blocking activity. The exact mechanism of action in preventing migraine is unknown, although it may be related to the antiserotonin effect.
Absorption:
Rapid after oral administration.
Biotransformation:
Probably hepatic.
Onset of action:
1 to 2 days.
Duration of action:
1 to 2 days.
Elimination:
Renal, 56%, as unchanged drug and metabolites.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to other ergot derivatives may be sensitive to this medication also.
Pregnancy/Reproduction
Problems in humans have not been documented. However, methysergide is not recommended during pregnancy due to its oxytocic properties.
FDA Pregnancy Category X.
Breast-feeding
Problems in humans have not been documented; however, ergot alkaloids are distributed into breast milk. Ergot alkaloids inhibit lactation and may cause ergotism (vomiting, diarrhea, weak pulse, unstable blood pressure, seizures) in the infant.
Pediatrics
Because of the hazards of long-term use of this medication, use in pediatric patients is not recommended.
Geriatrics
Caution is recommended in the elderly, who are more likely to have occlusive peripheral vascular disease, and are therefore more likely to be adversely affected by peripheral vasoconstriction, than are younger adults. This increases the risk of hypothermia and other ischemic complications. Elderly patients are also more likely to have age-related renal function impairment, which requires caution in patients receiving methysergide.
Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
Ergot alkaloids, other or
Sumatriptan or{04}{05}
Vasoconstrictors, systemic, other, such as:
Cocaine
Epinephrine, parenteral
Metaraminol
Methoxamine
Norepinephrine
Phenylephrine, parenteral or
Vasoconstrictor-containing local anesthetic solutions (concurrent use with methysergide may result in enhanced vasoconstriction; a reduced dosage of ergot alkaloids may be necessary when they are used to treat an acute attack)
Opioid (narcotic) analgesics{03} (concurrent use with methysergide may reverse the activity of the opioid)
Smoking, tobacco (administration of methysergide to patients who smoke heavily may increase the risk of peripheral vascular ischemia because nicotine also constricts blood vessels)
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With physiology/laboratory test values
Blood urea nitrogen (BUN) (may be increased, indicating renal failure, if retroperitoneal fibrosis occurs)
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
» Coronary artery disease, especially:
» Angina, unstable or vasospastic (vasospasm may aggravate existing angina, or cause angina or myocardial infarction)
» Hepatic function impairment (impaired metabolism may result in ergot poisoning)
» Hypertension, severe (may be aggravated)
Peptic ulcer (methysergide may elevate gastric hydrochloric acid concentrations)
» Peripheral vascular disease, occlusive or
» Pruritus, severe, especially when associated with hepatic disease or
» Sepsis or other severe infection (sensitivity to vascular effects may be increased)
» Pulmonary disease or
» Rheumatoid arthritis or other collagen diseases or
» Valvular heart disease (risk of retroperitoneal, pleuropulmonary, or cardiac fibrosis)
» Renal function impairment
Sensitivity to methysergide or other ergot alkaloids, history of
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
Retroperitoneal imaging (recommended prior to initiation of anticipated long-term therapy and at 6- to 12-month intervals during therapy to detect early signs of retroperitoneal fibrosis; may also be indicated if signs of urinary obstruction occur)
Side/Adverse Effects
Note: Most side effects are dose-related and are usually relieved by a reduction in dosage or withdrawal of the medication.
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent
Ischemia, peripheral vasospasm–induced (abdominal pain; chest pain; itching of skin; numbness and tingling of fingers, toes, or face; pain in arms, legs, or lower back; pale or cold hands or feet; weakness in legs)—specific symptoms are dependent on the blood vessel(s) involved, and may also rarely be caused by vascular insufficiency{01}
Incidence less frequent or rare
—dose-related
Changes in vision
clumsiness or unsteadiness{01}
CNS stimulation, mild (excitement or difficulty in thinking; feeling of being outside the body; hallucinations; nightmares)
convulsions
edema, peripheral{01} (swelling of hands, ankles, feet, or lower legs)
fast{01} or slow heartbeat
leukopenia{01} (rarely, fever or chills; cough or hoarseness; lower back or side pain; painful or difficult urination)—usually asymptomatic
mental depression
redness or flushing of face{01}
skin rash{01}
telangiectasia{01} (raised red spots on skin)
weight gain, unusual{03}
Note: Although methysergide is chemically related to the hallucinogen lysergic acid diethylamide (LSD), some of the listed CNS symptoms may be associated with vascular headaches rather than an effect of the medication {01}.
Incidence rare
—dependent on duration of therapy
Fibrosis (chest pain; difficult or painful urination; fever; large increase or decrease in amount of urine; leg cramps; loss of appetite; lower back, side, or groin pain; shortness of breath or difficult breathing; swelling of hands, ankles, feet, or lower legs; tightness in chest; weight loss)—fibrosis may occur in cardiac, penile, pleuropulmonary, and/or retroperitoneal tissues; specific symptoms depend on the site involved and the occurrence of associated complications, such as ureteral obstruction and vascular insufficiency{01}
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
CNS effects or hypotension, orthostatic{01} (dizziness or lightheadedness, especially when getting up from a lying or sitting position)
diarrhea{01}
drowsiness{01}
nausea, vomiting, or stomach pain{01}
Incidence less frequent or rare
Alopecia{03} (hair loss)
constipation{01}
heartburn{01}
trouble in sleeping{01}
Those indicating possible withdrawal and the need for medical attention if they occur after medication is discontinued
Headache{01}
Overdose
For specific information on the agents used in the management of methysergide overdose, see:
• Anesthetics, Barbiturate (Systemic) monograph;
• Diazepam in Benzodiazepines (Systemic) monograph; and/or
• Neuromuscular Blocking Agents (Systemic).
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).
Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and chronic
Cold and pale hands or feet
dizziness, severe
excitement
Treatment of overdose
Discontinuing methysergide administration.
To decrease absorption—Gastric lavage.
Specific treatment—
For treatment of convulsions:
If convulsions do not respond to respiratory support, administration of a benzodiazepine such as diazepam or an ultrashort-acting barbiturate such as thiopental or thiamylal is recommended. The fact that these agents, especially the barbiturates, may cause circulatory depression when administered intravenously must be kept in mind. Administration of a neuromuscular blocking agent has also been recommended to decrease the muscular manifestations of persistent convulsions; artificial respiration is mandatory if such an agent is used. See the package inserts or Diazepam in Benzodiazepines (Systemic) , Anesthetics, Barbiturate (Systemic) , or Neuromuscular Blocking Agents (Systemic) for specific dosing guidelines for use of these products.
For treatment of peripheral vasospasm:
Treat by applying warmth (but avoiding excessive heat) to ischemic extremities and, in some cases, by use of prazosin or sodium nitroprusside (the risk of hypotension being kept in mind). Also, careful nursing technique designed to prevent tissue damage should be instituted.
Monitoring—Prolonged and careful monitoring is recommended.
Supportive care—Support of respiration is recommended. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Methysergide (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to ergot derivatives
Pregnancy—Not recommended during pregnancy because of oxytocic properties
Breast-feeding—Ergot alkaloids inhibit lactation; also, they are distributed into breast milk and may cause ergotism in the infant
Use in children—Use is not recommended, because of the hazards associated with long-term use of methysergide
Use in the elderly—Increased risk of hypothermia and other adverse effects associated with peripheral vasoconstriction
Other medical problems, especially cardiovascular disease, hepatic function impairment, hypertension, peripheral vascular disease, severe pruritus (especially when associated with hepatic disease), severe infection, pulmonary disease, rheumatoid arthritis, valvular heart disease, and renal function impairment
Proper use of this medication
» Importance of not using more medication than the amount prescribed; risk of ergotism and gangrene with overdosage
» Taking with meals or milk to reduce gastrointestinal irritation
Missed dose: Not taking at all; not doubling doses
» Proper dosing
» Proper storage
Precautions while using this medication
» Checking with physician before discontinuing medication; withdrawal headache may occur
» Not taking for longer than 6 months at a time
» Caution in driving or doing jobs requiring alertness because of possible dizziness, lightheadedness, or drowsiness
Caution when getting up suddenly from a lying or sitting position
Avoiding alcohol, which aggravates headache
Avoiding smoking, since nicotine constricts blood vessels
Avoiding exposure to excessive cold, which may aggravate peripheral vasoconstriction
Notifying physician if infection develops, since infection may cause increased sensitivity to medication
Side/adverse effects
Signs of potential side effects, especially changes in vision, clumsiness or unsteadiness, CNS stimulation, convulsions, fast or slow heartbeat, fibrosis, ischemia, leukopenia, mental depression, peripheral edema, peripheral ischemia, redness or flushing of face, skin rash, telangiectasia, and unusual weight gain
General Dosing Information
Methysergide is not as potent a vasoconstrictor as ergotamine.
Because of the risk of fibrosis, methysergide should be administered for no longer than 6 months, with a drug-free interval of 3 to 4 weeks between each course.
Incidence and severity of some of the side effects may be minimized if the dosage is increased slowly to its therapeutic concentration and methysergide is given with meals.
If a response has not occurred after 3 weeks of treatment, further treatment is unlikely to produce an effect.
Gradual withdrawal of methysergide over 2 to 3 weeks is recommended to prevent rebound headache.
It is recommended that methysergide be withdrawn immediately and diagnostic tests performed if signs of retroperitoneal, pleuropulmonary, or cardiac fibrosis occur. Partial to complete regression may occur after the medication is discontinued, although surgery may be necessary in some patients.
Methysergide should be withdrawn at the first sign of vascular insufficiency.
Oral Dosage Forms
METHYSERGIDE MALEATE TABLETS USP
Usual adult dose
Oral, 4 to 8 mg a day in divided doses.
Strength(s) usually available
U.S.—
2 mg (Rx) [Sansert (lactose) (tartrazine)]{01}
Canada—
2 mg (Rx) [Sansert (lactose) (tartrazine)]{01}
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.
Auxiliary labeling:
• Take with meals or milk.
Revised: 07/07/1997
References
Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.
- Sansert package insert (Sandoz—US), Rev 7/86, Rec 10/88.
- Sansert (Sandoz). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association; 1988. p. 831.
- Sansert package insert (Sandoz—US), Rev 6/95, Rec 1/96.
- Imitrex tablets package insert (Glaxo—US), Rev 6/96, Rec 6/96.
- Imitrex injection package insert (Glaxo—US), Rev 5/96, Rec 6/96.
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