Ergotamine derivatives include-
Dihydrergotamine mesylate, Ergotamine tartarate, Methysergide maleate

Drug interactions- Summary
--------------------------------------
Betablockers              +      Ergot alkaloids    incr    increased cold extremities

CYP3A4 inhibitors      +      Ergot alkaloids     incr    increased risk of ergot toxicity
eg.protease inhibitors
macrolides,ketoconazole
itraconazole, nefazodone,
fluconazole, fluvoxamine,
delavirdine, erfavirenz

Nicotine                     +      Ergot alkaloids      incr     provoke vasoconstriction and response

Siburamine                +      Ergot alkaloids      incr      Co-admin. is not recommended.    

Dihydrogotamine      +      Nitrates                   decr      decreased effects

Ergot alkaloids          +     5-HT1 receptor      incr       Admin of 5-HT1 receptor agonists or ergot
                                            agonists                              alkaloids within 24 hours of each other is
                                                                                         contraindicated
Ergot alkaloids           +    vasoconstrictors   incr       concurrent use can combine to cause dangerous
                                                                                        hypertension.

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Betablocker with
----------------------
Ergot alkaloids     incr     peripheral ischemia manifested by cold extremities, possible peripheral
                                           gangrene

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CYP3A4 inhibitors
eg.protease inhibitors
macrolides,ketoconazole
itraconazole, nefazodone,
fluconazole, fluvoxamine,
delavirdine, erfavirenz
with
-----------------------------------
Ergot alkaloids        incr      the risk of ergot toxicity (ie, peripheral vasospasm) may be increased
                                               Co-admin. with potent CYP3A4 inhibitor is contraindicated. Use with
                                               caution with less than potent CYP3A4  inhibitors

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Nicotine  with
------------------
Ergot alkaloids        incr       nicotine may provoke vasoconstriction in some patients, predisposing
                                                them to greater ischemic response to ergot therapy

-------------------------------------------------------------------------------------------------------------------------------------
Siburamine with
----------------------
Ergot alkaloids       incr        a serotonin syndrome may occur. Co-admin. is not recommended.       
                                                Carefully monitor patients if concorent use can not be avoided.

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Dihydrogotamine with
-------------------------------
Nitrates                 decr        functional antagonism between these agents, decreasing effects
                                              may occur
------------------------------------------------------------------------------------------------------------------------
Ergot alkaloids with
---------------------------
5-HT1 receptor      incr      risk of vasopastic recations may be increased. Admin. 5-HT1 agonists
agonists                              or ergot alkaloids within 24hrs hours of each other is contraindicated
eg. sumatriptan,
frovatriptan,
naratriptan
rizatriptan, zolmitriptan
----------------------------------------------------------------------------------------------------------------------------
Ergot alkaloids with
---------------------------
vasoconstrictors    incr   the pressor effects of concurrent use can combine to cause dangerous
                                          hypertension.
------------------------------------------------------------------------------------------------------------------------------

To abort or prevent vascular headaches such as migraine, migraine variant.

Ergotamine derivatives include-
Dihydrergotamine mesylate, Ergotamine tartarate, Methysergide maleate

Drug interactions- Summary
---------------------------------------
Betablockers              +      Ergot alkaloids    incr    increased cold extremities

CYP3A4 inhibitors      +      Ergot alkaloids     incr    increased risk of ergot toxicity
eg.protease inhibitors
macrolides,ketoconazole
itraconazole, nefazodone,
fluconazole, fluvoxamine,
delavirdine, erfavirenz

Nicotine                     +      Ergot alkaloids      incr     provoke vasoconstriction and response

Siburamine                +      Ergot alkaloids      incr      Co-admin. is not recommended.    

Dihydrogotamine      +      Nitrates                   decr      decreased effects

Ergot alkaloids          +     5-HT1 receptor      incr       Admin of 5-HT1 receptor agonists or ergot
                                            agonists                              alkaloids within 24 hours of each other is
                                                                                         contraindicated
Ergot alkaloids           +    vasoconstrictors   incr       concurrent use can combine to cause dangerous
                                                                                        hypertension.

 

Ergotamine tartrate -
nausea and vomiting occur.
Numbness and tingling of fingers and toes, muscle pain, in the extremities,
pulse lessness, weakness in the legs
precordial pain
transcient tachycardia
localized edema and itching

Dihydroergotamine injection-
serious cardiac events, including some have been fatal following use of dihyroergotamine injection.
but extremely rare.
Events reported- coronary artery vasospasm, transient myocardial ischemia, MI ,
ventricular tachycardiaventricular fibrillation,

Pregnancy, women who may become pregnant (powerful uterine stimulant actions of ergotamine and
dihydroergotamine may cause fetasl harm
Hypersensitivity to ergot alkaloids or component of formulation
peripheral vascular disease, severe arteriosclerosis, thrombophebitis, hepatic or renal impairment
severe pruritus, coronary artery disease, hypertension , sepsis.

Do not give dihydroergotamine to patients with ischemic heart disease, angina pectoris,
history of MI

Serious adverse effects associated with coadministration of dihydroergotamine with potent
CYP3A4  inhibitors ( eg. protease inhibitors, macrolide antibiotics  resulting in vasospasm that led to
cerbral ischemia and /or ischemia of extremities.
Use of potent CYP3A4  ( ritonavir, indiavir, erythromycin, clarithromycin, troleandomycin, ketoconazole,
itraconazole ) is therfore contraindicated

Dihydroergotamine may increase blood pressre, do not give to patients with uncontrolled
hypertension

Do not use dihydroergotamine , 5-HT1 agonists eg.sumiatriptan , ergotamine containg or
ergor medication or methysergide within 24 of each other.

Do not administer dihydroergotamine to patients with hemiplegic or basilar migraine

Do not administer dihyroergotamine to nursing mothers.


Special precautions:
Risk of myocardial ischemia and or MI and other cardiac events-
Do not use dihydroergotamine in patients with documented ischemic or vasopastic coronary artery
disease

Cardiac events and fatalities-
No deaths have been reported in patients using dihydroergotamine. The potential for adverse
reactions exits.

Drug-associated cerebrovascular events and fatalities-
Cerbral haemorrhage ,subarchnoid , stroke, and other cerebrovascular events have been
reported in patients treated with dihydroergotamine, some have resulted in fatalities. it should
be noted that patients with migraine may be at risk of certain cerbrovascular events eg. stroke,
hemorrhage, transcient ischemic attack.

Elevation in blood pressure-
Significant increase in blood pressure has been reported in rare occassions in patients with or
without history of hypertension treated with dihydroergotamine.

Coronary artery vasospasm-
Dihydroergotamine may cause coronary artery vasospasm. Patients who experience signs or
symptoms suggestive of angina should be evaluted.

Drug abuse and dependence-
Patients who take ergotamine for extended periods of time may become dependent upon and
require progressively increasing doses for relief of vascular headache and prevention of
dysporic effects that follow withdrawal.

To abort or prevent vascular headaches such as migraine, migraine variant.

Ergotamine sublingal-
Initiate therapy as soon as possible after the first symptoms of attack.
Place one 2mg tablet under the the tongue, take another tablet at 30 minutes intervals thereafter.
do not exceed 3 tablets in any 24 hour period
 

Dosage is individualized. Take exactly as prescribed

Do not exceed the dosing guidelines. Do not use for chronic daily administratin.
 Do not stop taking or change the dose unless directed by your physician
Take at the first sign of a migraine attack.

Stop taking the drug and notify physician if you experience the following-
numbness, tingling, coldness, or paleness in fingers or toes, muscle pain in arms or legs,  weakness
in legs, chest pain, heart rate changes, sudden worsening of headache, swelling, itching.
 

Ergotamine derivatives include-
Dihydrergotamine mesylate, Ergotamine tartarate, Methysergide maleate
---------------------------------------------------------------------------------------------------------------------------

Pharmacology-
Ergotamine has partial antagonist activity against trytaminergic , dopaminergic and alpha-adrenergic
receptors, depending upon their site. It is highly active uterine stimulant.

Pharmacokinetics-
Ergotamine is metabolised by the liver, 90% of the metabolites are excreted in the bile. Although
plasma half life is about 2 hours, ergotamine has long lasting effects that may caused by tisue
storage.

 

Administration with grape friut juice may increase the serum levels of ergotamine derivatives. Use with caution.

Although no specific teratogenic effects have been found the fetus suffers if erogotamine is
given to mother.  

If this is used during pregnancy or if the patient becomes pregnant while taking the drug, appraise
the patient about the potential hazard to the fetus.

Lactation-
Ergotamine is secreted into breast milk and has caused symptomatic ergotism eg. vomiting,diarrhea
in the infant. Because of the potential for serious adverse reactions, nursing should not be undertaken
while on this medication.  

Children-
Safety for use in children have not been established