Agents for Migraine include-

Almotriptan, Eletriptan, Frovatriptan, Naratripptan, Rizatriptan, Sumatriptan, Zolmitriptan

Interacting drugs- Summary

MAO inhibitors     +   Sumitriptan 
  MAOI increase sumiptriptan sytemic exposure and   elimination
                                                                      
Ergot containing drugs + Sumitriptan
 Avoid concurrent use within 24 hours of each other.                           .

Cimetidine + Zolmitriptan                                                                                       Following   coadministration with cimetidine half life and AUC of a  5mg dose of zolmitriptan and its active metabolite were approximately doubled

Potent CYP3A4  inhibitors e.g Ketoconazole,Itraconazole,Nefazodone, Troleandomycin,
Clarithromycin, Rrotonavir, Nelfinavir  +  Almotriptan ,Electriptam                     Coadmin. of almotriptan and ketoconazole (400mg/day for 3 days) resulted in an increase in AUC and maximal plasma concentration of almotriptan.                                                 The AUC and Cmax of eletriptan are increased with coadmin.Do not use electriptan within 72 hours of treatment with potent CYP3A4 inhibitors 

MAOIs + Almotriptan, Rizatriptan, Sumatriptan, Zolmitriptan-                                    Use of certain 5-HT1 agonists concurrently with or within 2 weeks following discontinuing an MAOI is contraindicated. If It is necessary to use such agents together, naratriptan, eletriptan, and fravotriptan appear to be  less likely to interact with MAOIs.

Almotriptan, Frovatriptan,Naratriptan, RizatriptanSumitriptan,Zolmitriptan 
 +  SSRIs Floxetine, Fluvoxetine,Paroxetine, Serataline-                                              Reports of weakness, hyperflexia, and incordination with  combined use of SSRIs. It is concomitant use is clinically warranted, observe the patient carefully. No interaction was observed when  Rizatriptan was coadministered with paroxetine. Fluoxetine had not effect   on almotriptan, but clearance, Cmax increased by 18%.

Ergot alkaloids, (dihydroergotamine, methysergide )  +  5-HT1 agonists-                   Risk of vasopatic recations may be increased . Use of 5-HT1 agonists  within 24 hours of treatment with an ergot containg medication is  contraindicated.           

Sibutramine + Naratriptan, Rizatriptan, Siumatriptan, Zolmitriptan-                              A (serotonin syndrome ) including CNS irritability , motor weakness,  shivering , myoclonus , and altered consciousness  may occur.Co-administration is not recommended. Monitor the patient for adverse effects if concurrent use cannot be avoided. 

Propranolol  + Rizatriptan-                                                                               Coadministration of 240mg/day propranolol and a single  dose of 10mg rizatriptan in healthy subjects, increased  plasma AUC  for rizatriptan  by 70% during propranolol     admin.                                           

Propranolol  +  Zolmitriptan-                                                                                   Propranal increased Cmax and AUC of zolmitriptan  but decreased  for the                       N-desmethyl metabolite. No effects on blood pressure or pulse rate were  observed 

Propranolol  +  Frovatriptan-                                                                                  Propranolol  increased the AUC of 2.5mg frovatripotan in males by 60%  and in            females by 29%.The Cmax  of frovatriptan was increased by  23% in males and            16% in females in the presence of propranolol.                                                    

Propranolol  + Eletriptan- 
Propranolol increased  Cmax and AUC  of eritriptan
 by 10% and 33% respy. No interactive increase
in blood pressure were observed   

Oral contraceptives + Frovatriptan -                                                                                   Mean Cmax and AUC of frovatriptan are 30% higher in persons  taking oral contraceptives  compared with those not taking oral  contraceptives

 INJECTIONS-
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CARDIOVASCULAR-
Hypertension, hypotension, bradycardia, tachycardia, palpitations, pulsating sensations, various transcient ECG changes, syncope,  1%  pallor, arrhythmia abnormal pulse, vasodilation, Reynauds syndrome  < 1%

METABOLIC  -
Thirst  1%  polydipsia, dehydration < 0.1%

GI-
Gastrointestinal reflux, diarrhea, disturbances of liver function tests 1%  peptic ulcer,
retching, flatulence /eructation, gallstones < 0.1%

MUSCULOSKELETAL  -
Various joint disturbances, ( pain, stiffness, swelling , ache 1% muscle stiffness, need
to flexcalf muscles.backache, muscle tiredness, swelling of the extremities < 0.1%

CNS -
Mental confusion, euphoria, agitation, relaxation, chills, sensation of lightness, tremor, shivering,taste disturbances,  paresthsia, stinging sensation, headache, facial pain,
photophobia  1%

sleep disturbances, difficulties incocenration, smell disturbances, hot and cold sensation,
yawning, reduced appitite < 0.1%

RESPIRATORY -
Dyspnea, 1% influenza, diseases of lower respiratory tract, hiccoughs   < 0.1%

DERMATITIS -
Erythema, pruritus, skin rashes, eruptions  1%  skin tenderness  < 0.1%

MISCELLANEOUS -
hypersensitivity to various agents ,eye irritation to 1%  fever  0.1%

ORAL-
--------
Most reactions are mild and transcient-

ATYPICAL SENSATIONS-
Feeling of heaviness(<  1% , feeling of tightness,  < 1%  pressure sensation  < 1%
tingling  8%  warm/hot  sensation  2%

CARDIOVASCULAR  -
Chest discomfort/pressure/heaviness/tightness  > 1% , arrhyhthmias, ECG changes ,hypertension,pallor, tachycardia  0.1% angina, bradycardia, cerebral ischema, transcient myocardial ischema,vasoldilation  < 0.1%

SPECIAL SENSES-
Nasal discomfort, throat symptoms,  > 1%  hearing disturbances,  1% ,
feeling of fullness in ear , mydriasis  0.1%

 NEUROLOGICAL  -
 Dizziness/vertigo, drowsiness/sedation, headache, anxiety, malaise/fatigue  < 0.1%

GI-
Diarrhea, gastric symptoms  > 1% , constipation .dysphagia, gastrointestinal reflux 1%
Gi bleeding, melena, peptic ulcer  < 0.1% ,abdominal discomfort, , taste disturbances, nausea, vomiting  < 0.1%

MUSCULOSKELETAL -
Myalgia  > 1%  muscle cramps. 1%

CNS-
Confusion, depression, difficulty in concentration, facial pain sleep disturbances  1%
anxiety, migraine, headache, drowsiness/sedation, dizziness, vertigo  < 0.1%

RESPIRATORY -
Dyspnea,  > 1% asthma  1%  hicoughs  < 0.1%

DERMATOLOGIC -
Sweating  > 1% , erythema , pruritus, rash, skin tenderness 1%  dry skin, tightness/
wrinkling of skin  < 0.1%

GU-
Breast tendernes, dysmenorrhoea, increased urination, intermenstrual bleeding 1%
nipple discharge, abortion, hematuria < 0.1%

MISCELLANEOUS-
Hypersensitivity includes rash, urticaria, prutitus, shortness of breathness, burning sensation , numbness parathesia  > 1%  fever, fluid retentionoverdose 1%  hot and cold sensation, hematoma, speech/voice disturbance  < 0.1%

IV use(because of its potential to cause coronary vasospasm),SC use in patients with ischemic heart disease (angina pectoris,history of myocardial infarction or documenented silent ischemia. Hypersensitivity to sumatriptan,management of hemiplegic or basilar migraine.

Special precautions:

Cluster headache- safety and efficacy not established, cluster headache predominantly present in older male population.

Chest, jaw or neck tightness- is relatively common after sumatriptan injection, but has only rarely been associated with ischemic ECG changes.

Blood pressure changes- sumatriptan injection may cause mild transceint elevation of blood pressure and peripheral vascular resistence.

Seizures- there have been rare reports of seizures following sumitriptan use.

Building to melanin-containing tissues- because sumitriptan binds to melanin , it could accumulate in melanin-rich tissues (such as the eye) over time, raising the possiblilty that toxicity in these tissues could occur after extended use.

Be aware of the possibility of long-term ophthmologic changes

Corneal opacities- sumitriptan causes corneal opacities and defects in the dog , raising the possibility that these changes may occur in humans. Be aware of the possibility of these changes.

Warnings-

Migraine diagnosis- use oral sumitriptan where a clear diagnosis of migraine has been established.

Cardiac events- serious coronary events including some that have been fatal following sumitriptan have occured but are extremely rare.

Fatalities- in extensive worldwide postmarketing experience, deaths have been reported following the use of sumitriptan. In most cases, these have occured well after sumitriptan use (ie > 3 hours post dose) and probalbly reflect underlying disease and spontaneous events.

Hypersentivity- hypersentivity reactions have occured on rare occassions and severe anaphylaxis/anaphylactoid reactions have occured. Such can be life-threatening or fatal.

Renal/hepatic function impairment- administer with caution to patients with diseases that may alter after absorption.

Elderly- pharmacokinetic disposition of sumitriptan in the elderly is similar to that seen in younger adults.

Pregnancy- use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation- excercise caution when administering to a nursing woman

Children- safety and efficay have not been established

Acute treatment of migraine attacks.

Dosage: 6 mg injected SC.Maximum recommended dose to be given in 24 hours is 2 to 6 mg injections.

Overdosage- Symptoms

Overdoses would cause convulsions, tremor, inactivity, erythema of the extremities,reduced respiratory rate, cyanosis, ataxia, mydraisis, injection site reactions, (desquamation, hair loss and scab formation) and paralysis.

Treatment

1. Eliminationn half-life of sumatriptatan is about 2 hours, while symptoms or signs persist, and for at least 10 hours

2. It is unknown what effect hemodialysis or peritoneal dialysis has on serum concentrations of sumatriptan

 Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

SUMATRIPTAN - AGENTS FOR MIGRAINE 

1.Sumatriptan tablets are to be swallowed whole. Do not break, crush, or chew the tablets before swallowing them.

2.Patient information leaflets,normally come along with the medicines. Read it carefully.

3.Check with the doctor if you have used sumatriptan for 3 headaches,and have not had good relief. Check with your doctor if your migraine headaches are worse,or if they are occuring more often,than before you started using sumatriptan.

4. Drinking alcoholic beverages can make headaches worse or cause new headaches to occur.

5. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to sumatriptan. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

6.Pregnancy- in some animal studies sumatriptan caused harmful efects on the fetus,

7.Breast feeding- breast-feeding mothers should discuss the risks and benefits of this medicine with their doctors.

8.Children- no specific information comparing the use of sumatriptan with use in other age groups

9. Elderly- no specific information comparing use of sumatriptan in patients older than 65 years of age with use in younger groups.

9. Other medicines - Tell your doctor if you taking Any non prescription or OTC drugs or if you smoke tobacco Your doctor may want to change the dose or other prescriptions may be necessary

10. Other medical problems - Angina or Fast or irregular beat or Heart or blood vessel disease High blood pressure or Kidney disease or Liver disease or Stroke - chance of side effects may be increased

11. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

12. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

13. Date expired medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Injection- sumitriptan-

Instruct patients who are advised to self administer sumatriptan in medically unsupervised situations, on the proper use of the product prior to doing so for the first time, including loading the auto-injector and discarding empty syringes

For adults the usual dose is a single injection given just below the skin.

Administer as soon as migraine symptoms appear, but it may given at any time during the attack. A second injection can be given if symptoms of migraine return.

Do not use more than 2 injections/24 hours and allow at least 1 hour between each dose. The patient may experience pain or redness at the site of injection, but this usually lasts less than 1 hour.

Intranasal- for adults,

Usual dose is a single nasal spray into 1 nostril. If headache returns, a second nasal spray may be given 2 hours after the first spray.

For any attack where the patient has no response to the first nasal spray, do not use a second nasal spray without consulting a physician

Do not administer more than 40mg sumatriptan or more than 10mg zolmitriptan nasal spray in any 24 hour period.

Oral- Take a single dose with fluids as soon as symptoms of migraine appear.

A second dose may be taken if symptoms return, but no sooner than 2 hours ( sumatriptan, zolmitriptan, eletriptan ) or 4 hours ( naratriptan, ) following the first dose.

For a given attack if there is no response to the first dose do not take a second dose without first consulting a physician.

Do not take more than 200mg sumatriptan, more than 5mg naratriptan, more than 10mg zolmitriptan or more than 80mg eletriptan in any 24 hours period.

Photosensitization ( photoallergy or photoxicity ) may occur.

Therefore, caution patients to take protective measures (ie. sunscreens, protective clothing ) against exposure to sunlight or ultraviolet light until tolerance is determined

Food has significant effect on oral 5-HT1 agonists bioavailability, but delays sumatriptans Tmax by aaproximately 30 minutes and rizatriptans time to reach peak concentration by 1 hour.

AUC and Cmax of eletriptan are increased approximately 20% to 30% following oral admin. of a high fat meal.

Pregnancy:

Use during only if needed.

Lactation:

Sumatriptan is excreted in breast mlik. Excercise caution when administering to a nursing woman.

Children-

Safety and efficay have not been established