Sunday 15 April 2012

Sumatriptan Succinate



Class: Selective Serotonin Agonists
VA Class: CN105
Chemical Name: C14H21N3O2S
Molecular Formula: C14H21N3O2S•C4H6O4
CAS Number: 103628-46-2
Brands: Imitrex


REMS:


FDA approved a REMS for sumatriptan to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of sumatriptan and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().



Introduction

Selective serotonin (5-hydroxytryptamine; 5-HT) type 1-like receptor agonist (“triptan”).1 2 3 4 5 6 7 8 223 224 268


Uses for Sumatriptan Succinate


Vascular Headaches


Acute treatment of migraine attacks with or without aura.1 2 3 6 7 8 9 10 13 48 80 145 148 184 195 214 217 225 249


Sub-Q for acute treatment of cluster headache episodes.1 2 49 75 183 184 185 210 214 Safety and efficacy of oral or intranasal sumatriptan for this use not established.148 249


Not recommended for management of hemiplegic or basilar migraine or for prophylaxisof migraine or cluster headache.1 7 114 158


Sumatriptan Succinate Dosage and Administration


Administration


Administer orally, intranasally, or by sub-Q injection. Do not administer IM or IV; IV administration may induce coronary vasospasm.1 148 249


To achieve maximum relief, initiate therapy as soon as possible after onset of migraine attack.50 92 108 124 148 180 237


Oral Administration


Administer orally with fluids; swallow tablet whole.148


Intranasal Administration


Administer intranasally as a single spray into 1 nostril.249


Nasal solution unit contains only 1 spray; do not test before use.249


To administer, remove unit from package just before use.249 While sitting down, gently blow nose to clear nasal passages.249 Keep head in upright position and gently close 1 nostril with index finger; exhale gently through mouth.249 With other hand, hold unit with thumb supporting at bottom and index and middle fingers on either side of nozzle.249 Insert nozzle into open nostril about ½ inch.249 While gently inhaling through nose (with closed mouth), release spray by firmly pressing plunger.249 Remove nozzle from nostril while keeping head level for 10–20 seconds and gently inhaling through nose and exhaling through mouth; do not inhale deeply.249 Consult administration instructions provided by manufacturer before use.249


Sub-Q Administration


Administer only by sub-Q injection, preferably into lateral aspect of thigh or deltoid.1 12


Do not administer IM or IV; IV administration may induce coronary vasospasm.1


Autoinjection device available for use with prefilled syringes (each containing a 4- or 6-mg dose) to facilitate self-administration.1 273 Needles with this device penetrate approximately 5–6 mm (¼ inch); use injection sites with an adequate skin and subcutaneous thickness to accommodate needle length.1 273


Dosage


Available as sumatriptan (nasal solution) and sumatriptan succinate (tablets and injection); dosage expressed in terms of sumatriptan.1 148 249


Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.1 148 249


Adults


Vascular Headaches

Migraine

Oral

25, 50, or 100 mg as a single dose.148 274 Individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 50- or 100-mg dose; 100-mg dose may not provide substantially greater effect than 50-mg dose.148 274


If headache recurs or partial response occurs after initial dose, additional oral doses may be administered at intervals of ≥2 hours, up to a maximum oral dosage of 200 mg daily.274


If headache recurs after an initial sub-Q dose, additional oral doses may be administered at intervals ≥2 hours, up to a maximum oral dosage of 100 mg daily.274


Intranasal

5, 10, or 20 mg as a single dose; individualize dosage selection, weighing the possible benefit (greater effectiveness) and risks (increased adverse effects) of the 20-mg dose.249 Doses >20 mg provide no additional benefit.249


To achieve a 10-mg dose, administer a single 5-mg dose into each nostril.249


If headache recurs, dose may be repeated once after 2 hours, up to a maximum dosage of 40 mg daily.249


Sub-Q

≤6 mg as a single dose.1 If dose-limiting adverse effects occur with 6-mg dose, lower doses (e.g., 4 mg) may be given.1 273 In patients receiving doses other than 4 or 6 mg, only the single-dose vials containing 6 mg/0.5 mL should be used to provide the desired dose.1 273


If headache recurs, a 6-mg sub-Q dose may be repeated once after ≥1 hour or additional oral doses may be administered at intervals ≥2 hours, up to a maximum oral dosage of 100 mg daily.273


If patient does not respond to first 6-mg dose, additional doses are unlikely to provide benefit.1 2 3 6 7 8 9 174 176 181 236 237


Cluster Headache

Sub-Q

≤6 mg as a single dose.1 If dose-limiting adverse effects occur with 6-mg dose, lower doses may be administered using only single-dose vials; use autoinjection device only with prefilled, unit-of-use syringes containing 6 mg.1


If headache recurs, 6-mg dose may be repeated once after ≥1 hour, up to a maximum dosage of 12 mg in any 24-hour period.1


If patient does not respond to first 6-mg dose, additional doses are unlikely to provide benefit.1 2 3 6 7 8 9 174 176 181 236 237


Prescribing Limits


Adults


Vascular Headaches

Migraine

Oral

Maximum 200 mg daily; do not exceed 100 mg daily if following an initial sub-Q dose.273


Safety of treating an average of >4 headaches per 30-day period has not been established.148


Intranasal

Maximum 40 mg daily.249


Safety of treating an average of >4 headaches per 30-day period has not been established.249


Sub-Q

Maximum 6 mg as a single dose; do not exceed 12 mg (i.e., two 6-mg doses given ≥1 hour apart) in any 24-hour period.1


Cluster Headache

Sub-Q

Maximum 6 mg as a single dose; do not exceed 12 mg (i.e., two 6-mg doses given ≥1 hour apart) in any 24-hour period.1


Special Populations


Hepatic Impairment


Contraindicated in patients with severe hepatic impairment.1 148 249 Unpredictable increases in bioavailability following oraladministration in patients with hepatic impairment.148 If oral therapy is deemed advisable in these patients, do not exceed 50 mg as a single dose.148


Patients Receiving MAO-A Inhibitors


Concurrent or recent (within 2 weeks) use of MAO-A inhibitor and oral or intranasal sumatriptan is contraindicated;148 249 sub-Qsumatriptan is not generally recommended, but if concomitant use is clinically warranted, decrease sumatriptan sub-Q dosage and administer under careful medical supervision.1 237


Cautions for Sumatriptan Succinate


Contraindications



  • Known or suspected ischemic heart disease (e.g., angina pectoris, MI, silent ischemia).1 148 249




  • Coronary artery vasospasm (e.g., Prinzmetal variant angina).1 148 249




  • Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).1 148 249




  • Cerebrovascular syndromes (e.g., stroke syndrome, TIAs).1 148 249




  • Peripheral vascular ischemia (e.g., ischemic bowel disease).1 148 249




  • Hemiplegic or basilar migraine.1 148 249




  • Treatment within previous 24 hours with another 5-HT1 receptor agonist or an ergot alkaloid.1 148 249 (See Specific Drugs under Interactions.)




  • Concurrent or recent (within 2 weeks) treatment with an MAO-A inhibitor (oral and nasal sumatriptan formulations).1 148 249




  • Severe hepatic impairment.1 148 249




  • Known hypersensitivity to sumatriptan or any ingredient in the formulation.1 148 249



Warnings/Precautions


Warnings


Use oral or intranasal sumatriptan only in patients in whom a clear diagnosis of migraine has been established.148 249 Use sub-Q sumatriptan only in patients in whom a clear diagnosis of migraine or cluster headache has been established.1


Exclude other potentially serious neurologic disorders before administering sumatriptan to patients not previously diagnosed with migraine or cluster headache or to those with atypical symptoms.1 61 148 236 237


Cardiac Effects

Risk of myocardial ischemia and/or infarction, coronary vasospasm, life-threatening cardiac rhythm disturbances, and death.1 148 249


Use not recommended in patients with known or suspected ischemic or vasospastic heart disease or in patients in whom unrecognized CAD is likely (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, or family history of CAD) unless there is satisfactory evidence from prior cardiovascular evaluation that patient does not have CAD, ischemic heart disease, or other underlying cardiovascular disease.1 148 249


Administer initial dose to patients with risk factors for CAD who have completed satisfactory cardiovascular evaluation under medical supervision (e.g., in clinician’s office, possibly followed by ECG) unless patient previously received the drug.1 148 249


Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy, including patients with cluster headache (predominantly males >40 years of age).1 148 249


Patients with symptoms suggestive of angina after receiving sumatriptan should be evaluated for presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses; if administration resumed and such signs or symptoms recur, ECG evaluation recommended.1 148 249


Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage, stroke, and other cerebrovascular events, sometimes fatal.1 148 249


Risk of certain cerebrovascular events (e.g., stroke, TIA) may be increased in patients with migraine.1 148 249


Other Cardiovascular or Vasospastic Effects

Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported.1 148 249 Further evaluation recommended if signs or symptoms of decreased arterial flow (e.g., ischemic bowel syndrome, Raynaud’s syndrome) occur following administration.1 6 8


Substantial increases in BP, including hypertensive crises, reported rarely in patients with or without history of hypertension; administer with caution in patients with controlled hypertension as transient increases in BP and peripheral vascular resistance are possible.1 148 249 (See Contraindications under Cautions.)


Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported during concurrent therapy with 5-HT1 receptor agonists (“triptans”) and SSRIs or selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs).272 273 274 275 Symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).272 273 274 275


Local Effects

Possible transient irritation in nose and throat (e.g., burning, numbness, paresthesia, discharge, pain/soreness), sometimes severe, after intranasal administration; symptoms usually resolve in <2 hours.249 Effects of extended and repeated use on nasal and/or respiratory mucosa not systematically evaluated.249


Sensitivity Reactions


Hypersensitivity

Hypersensitivity reactions (e.g., anaphylaxis/anaphylactoid reactions), possibly life-threatening or fatal, reported rarely; increased risk in patients with history of sensitivity to multiple allergens.1 148 249


General Precautions


Seizures

Seizures reported rarely; use with caution in patients with a history of seizures or with conditions associated with a lowered seizure threshold.273 274 275


Ocular Effects

Possible accumulation of sumatriptan and/or its metabolites in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.1 148 249


Corneal opacities and corneal epithelial defects reported in dogs. No specific recommendations for monitoring.


Specific Populations


Pregnancy

Category C.1 148 249 Sumatriptan Pregnancy Registry at 800-336-2176.1 148 249


Lactation

Distributed into human milk.1 148 249 The manufacturer recommends avoiding breast-feeding for 12 hours after receiving sumatriptan oral tablets, sub-Q injection, or nasal spray.273 274 275


Pediatric Use

Safety and efficacy not established in children <18 years of age; use not recommended.1 148 249


Geriatric Use

Use not recommended due to possible decreased hepatic function, potential for more pronounced increases in BP, and increased risk for CAD in geriatric patients.1 148 249


Hepatic Impairment

Contraindicated in patients with severe hepatic impairment.1 148 249 Due to important role of the liver in presystemic clearance of oral sumatriptan, dosage adjustment recommended if oral therapy is deemed advisable in patients with hepatic impairment.148 (See Special Populations under Dosage and Administration.)


Common Adverse Effects


With oral therapy, pain/pressure sensations in chest/neck/throat/jaw, paresthesia, warm or cold sensation, malaise/fatigue, vertigo.148


With intranasal therapy, taste disturbances, nausea, vomiting, disorder/discomfort of nasal cavity or sinuses.249


With sub-Q therapy, injection site reaction, atypical sensations (e.g., tingling, warm/hot sensation, burning, feeling of heaviness, pressure, tightness, numbness), dizziness/vertigo, flushing, mouth/tongue discomfort, weakness, neck pain/stiffness, chest discomfort.1


Interactions for Sumatriptan Succinate


Metabolized principally by MAO-A isoenzyme in vitro.148


Protein-bound Drugs


Effect on protein binding of other drugs has not been evaluated,1 but expected to be minor due to low-level protein binding of sumatriptan.148 249


Specific Drugs




































Drug



Interaction



Comments



Acetaminophen



Pretreatment with oral sumatriptan followed by acetaminophen affected rate, but not extent of acetaminophen absorption over 8 hours187



Alcohol



Administration of alcohol 30 minutes prior to oral sumatriptan did not affect sumatriptan pharmacokinetics44 45 148 236



Amitriptyline



Concomitant use did not affect sumatriptan efficacy1 40 62



Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g., duloxetine, venlafaxine)



Potentially life-threatening serotonin syndrome272 273 274 275



Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated272 273 274 275



Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide)



Additive vasospastic effects1 148 249



Use within 24 hours contraindicated1 148 249



5-HT1receptor agonists



Additive vasospastic effects1 148 249



Use within 24 hours contraindicated1 148 249



MAO inhibitors



MAO-A inhibitors decrease sumatriptan clearance, resulting in substantially increased systemic exposure; no substantial effect on sumatriptan metabolism seen with an MAO-B inhibitor1 148 249



Use of nasal or oralsumatriptan within 2 weeks of MAO-A inhibitor contraindicated; although not generally recommended, if clinically warranted, sub-Q sumatriptan may be used concurrently with MAO-A inhibitors with appropriate dosage adjustment and careful monitoring1 237



Propranolol



Concomitant use did not affect sumatriptan efficacy;1 40 62 pretreatment with propranolol did not alter pharmacokinetics or pharmacodynamics of oral sumatriptan62



Verapamil



Concomitant use did not affect sumatriptan efficacy1 40 62



Xylometazoline



Topical application of xylometazoline to nasal mucosa 15 minutes prior to intranasal sumatriptan did not affect sumatriptan pharmacokinetics249


Sumatriptan Succinate Pharmacokinetics


Absorption


Bioavailability


Absorbed rapidly after oral, intranasal, or sub-Q administration, with peak plasma concentrations attained within approximately 0.5–5 hours, 0.8–1.8 hours, or 5–20 minutes, respectively.1 2 3 13 45 61 78 79 89 96 123 146 148 166 168 236 Bioavailability after sub-Q administration averages 97% of that obtained with IV administration1 44 ; bioavailability after oral or intranasal administration averages only about 15 or 17%, respectively, principally due to presystemic metabolism and in part due to incomplete absorption.2 13 14 44 45 61 89 146 148 166 168 249


Oral absorption is not appreciably affected by gastric stasis that may occur during migraine attack,3 13 45 146 but time to peak concentration is prolonged by about 30 minutes;3 13 45 96 146 148 pharmacokinetics after sub-Q injection appear to be similar during migraine attacks and pain-free periods.1


Special Populations


In patients with hepatic impairment, bioavailability after oral administration may be markedly increased.148 In a small study, AUC and peak plasma concentrations increased approximately 70% and time to peak plasma concentrations occurred 40 minutes earlier after oral administration compared with such values in healthy adults.148


Onset


After oral administration, onset of relief of migraine symptoms generally occurs within 1–3 hours after single doses (25–100 mg),92 148 162 178 191 with maximum pain relief attained within 3–6 hours.148 178 191


After intranasal administration, onset of headache relief occurs within 30 minutes following a 10-, 20-, or 40-mg dose.123 243


After sub-Q administration, onset of pain relief usually occurs within 10–34 minutes in patients with moderate to severe migraine headache pain, with maximum relief attained within 1–2 hours;1 8 9 13 47 56 162 176 181 onset of pain relief generally occurs within 4–7 minutes in patients with cluster headache, with headache resolution shortly thereafter.40 49 75 184


Food


Food does not appreciably affect oral bioavailability, but prolongs time to peak concentration.2 13 44 148


Distribution


Extent


Rapidly and widely distributed into body tissues after sub-Q administration.1 14 146 148 168


Distributed into human milk;1 148 only small amounts cross placenta by passive transport in vitro.235


Plasma Protein Binding


Approximately 14–21%.1 14 45 148


Elimination


Metabolism


Metabolized in the liver and possibly in the GI tract principally to inactive indole acetic acid metabolite and other minor metabolites;1 2 3 13 14 104 148 166 metabolized principally by MAO-A isoenzyme in vitro.1 37 48 148


Elimination Route


After oral administration, excreted in urine (57–60%) and feces (37–40%); only 3 and 9% of dose is excreted as unchanged drug in urine and feces, respectively.14 45 148 13 45 148 166 168 After sub-Q administration, approximately 22 or 38–53% of dose is excreted in urine unchanged or as indole acetic acid metabolite, respectively;1 45 168 0.6 and 3.3% of dose is excreted in feces as unchanged drug and indole acetic acid metabolite, respectively.2 13 14 45


Half-life


1.5–2.6 hours.1 6 44 45 78 79 89 91 148 166 168 249


Special Populations


In patients with renal impairment, pharmacokinetics not evaluated, but little clinical effect expected since drug is largely metabolized to an inactive metabolite.1 148 249


Stability


Storage


Oral


Tablets

2–30°C.148


Intranasal


Solution

2–30°C; protect from light.249


Parenteral


Injection

2–30°C; protect from light.1


Actions



  • Binds with high affinity to 5-HT type 1-like receptors, probably 5-HT1B and 5-HT1D subtypes.1 2 3 4 5 6 7 8 223 224




  • Precise mechanism of action not established;4 6 9 13 77 87 may ameliorate migraine and cluster headache through selective constriction of certain large cranial blood vessels and/or inhibition of neurogenic inflammatory processes in the CNS.1 2 3 6 7 9 10 13 47 66 73 77 88 110 119 131 177 184 186 217 236 237



Advice to Patients



  • Importance of immediately informing a clinician of any tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck, as well as sudden and/or severe abdominal pain, shortness of breath, wheezing, heart throbbing, facial swelling (e.g., eyelids, face, lips), rash, or hives after taking sumatriptan and of not taking sumatriptan again until evaluated by a clinician.1




  • Importance of taking sumatriptan exactly as prescribed.1 148 249




  • Importance of providing patient a copy of manufacturer’s patient information.1 148 249 Importance of clinician providing adequate instructions, as well as the written administration instructions supplied with the autoinjection device or nasal spray, before first use.1 171 249




  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).1 148 249




  • Importance of informing patients of risk of serotonin syndrome with concurrent use of sumatriptan and an SSRI or SNRI.272 273 274 275 Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.272 273 274 275




  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 148 249




  • Importance of informing patients of other important precautionary information.1 148 249 (See Cautions.)



Preparations


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.


















Sumatriptan

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Nasal



Solution



5 mg/0.1 mL



Imitrex Nasal Spray



GlaxoSmithKline



20 mg/0.1 mL



Imitrex Nasal Spray



GlaxoSmithKline

































Sumatriptan Succinate

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Oral



Tablets, film-coated



25 mg (of sumatriptan)



Imitrex



GlaxoSmithKline



50 mg (of sumatriptan)



Imitrex



GlaxoSmithKline



100 mg (of sumatriptan)



Imitrex



GlaxoSmithKline



Parenteral



Injection, for sub-Q use only



4 mg/0.5 mL (of sumatriptan)



Imitrex (available in 0.5-mL [4-mg] unit-of-use syringes)



GlaxoSmithKline



6 mg/0.5 mL (of sumatriptan)



Imitrex (available in 0.5-mL [6-mg] unit-of-use syringes and as 0.5 mL [6-mg] single-dose vials)



GlaxoSmithKline


Comparative Pricing


This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.


Imitrex 100MG Tablets (GLAXO SMITH KLINE): 9/$250.99 or 27/$743.93


Imitrex 20MG/ACT Solution (GLAXO SMITH KLINE): 6/$270.98 or 18/$790.96


Imitrex 25MG Tablets (GLAXO SMITH KLINE): 9/$272.65 or 27/$791.50


Imitrex 5MG/ACT Solution (GLAXO SMITH KLINE): 1/$55.49 or 3/$136.30


Imitrex 50MG Tablets (GLAXO SMITH KLINE): 9/$266.99 or 27/$774.99


Imitrex STATdose Refill 6MG/0.5ML Solution (GLAXO SMITH KLINE): 1/$217.16 or 3/$603.25


Imitrex STATdose System 6MG/0.5ML Solution (GLAXO SMITH KLINE): 1/$217.16 or 3/$628.59


SUMAtriptan 20MG/ACT Solution (SANDOZ): 1/$45.99 or 3/$119.96


SUMAtriptan 5MG/ACT Solution (SANDOZ): 1/$45.99 or 3/$125.97


SUMAtriptan Succinate 100MG Tablets (SUN PHARMACEUTICAL): 9/$199.97 or 27/$569.98


SUMAtriptan Succinate 25MG Tablets (SUN PHARMACEUTICAL): 9/$219.99 or 27/$619.95


SUMAtriptan Succinate 50MG Tablets (SUN PHARMACEUTICAL): 9/$199.99 or 27/$569.97


Sumavel DosePro 6MG/0.5ML Device (ZOGENIX): 1/$101.99 or 2/$291.97


Treximet 85-500MG Tablets (GLAXO SMITH KLINE): 9/$216.99 or 27/$607.99



Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.


The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.




References



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7. Anon. Sumatriptan for migraine. Med Lett Drugs Ther. 1992; 34:91-3. [PubMed 1326077]



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12. Glaxo, Research Triangle Park, NC: Personal communication.



13. Plosker GL, McTavish D. Sumatriptan: a reappraisal of its pharmacology and therapeutic efficacy in the acute treatment of migraine and cluster headache. Drugs. 1994; 47:622-51. [PubMed 7516861]



14. Dixon CM, Saynor DA, Andrew PD et al. Disposition of sumatriptan in laboratory animals and humans. Drug Metabol Disp. 1993; 21:761-9.



15. Dechant KL, Clissold SP. Sumatriptan: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the acute treatment of migraine and cluster headache. Drugs. 1992; 43:776-98. [PubMed 1379152]



16. D’Arcy PF. Adverse drug reaction (ADR) problems with sumatriptan. Intl Pharm J. 1992; 6:264-5.



17. D’Arcy PF. Warnings from the UK committee on safety of medicines: chest pain with sumatriptan. Intl Pharm J. 1992; 6:217-8.



18. Willett F, Curzen N, Adams J et al. Coronary vasospasm induced by subcutaneous sumatriptan. BMJ. 1992; 304:1415. [IDIS 297248] [PubMed 1320974]



19. Price LH, Charney DS, Delgado PL et al. Lithium treatment and serotoninergic function. Arch Gen Psych. 1989; 46:13-9.



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