DOSAGE FORMS AND STRENGTHS. Injection: 6 mg single-dose vial. (3)

Transcription

1 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use SUMATRIPTAN SUCCINATE INJECTION sfely nd effectively. See full prescribing informtion for SUMATRIPTAN SUCCINATE INJECTION. SUMATRIPTAN SUCCINATE INJECTION, for subcutneous use Initil U.S. Approvl: 199 INDICATIONS AND USAGE succinte injection is serotonin (-HT 1B/1D ) receptor gonist (triptn) indicted for: Acute tretment of migrine with or without ur in dults (1) Acute tretment of cluster hedche in dults (1) Limittions of Use: Use only if cler dignosis of migrine or cluster hedche hs been estblished. (1) Not indicted for the prevention of migrine ttcks. (1) DOSAGE AND ADMINISTRATION For subcutneous use only. (.1) Acute tretment of migrine: 1 to Single dose. (.1) Acute tretment of cluster hedche: Single dose. (.1) Mximum dose in 4-hour period: 1 mg, Seprte doses by t lest 1 hour. (.1) Ptients receiving doses other thn : Use the singledose vil. (.) DOSAGE FORMS AND STRENGTHS Injection: single-dose vil. (3) CONTRAINDICATIONS Coronry rtery disese or coronry vsospsm (4) Wolff-Prkinson-White syndrome or other crdic ccessory conduction pthwy disorders (4) History of stroke, trnsient ischemic ttck, or hemiplegic or bsilr migrine (4) Peripherl vsculr disese (4) Ischemic bowel disese (4) Uncontrolled hypertension (4) Recent (within 4 hours) use of nother -HT 1 gonist (e.g., nother triptn) or of n ergotmine-contining mediction (4) Current or recent (pst weeks) use of monomine oxidse-a inhibitor (4) Known hypersensitivity to sumtriptn (4) Severe heptic impirment (4) WARNINGS AND PRECAUTIONS Myocrdil ischemi/infrction nd Prinzmetl s ngin: Perform crdic evlution in ptients with multiple crdiovsculr risk fctors. (.1) Arrhythmis: Discontinue sumtriptn succinte if occurs. (.) Chest/throt/neck/jw pin, tightness, pressure, or heviness: Generlly not ssocited with myocrdil ischemi; evlute for coronry rtery disese in ptients t high risk. (.3) Cerebrl hemorrhge, subrchnoid hemorrhge, nd stroke: Discontinue sumtriptn succinte if occurs. (.4) Gstrointestinl ischemi nd infrction events, peripherl vsospstic rections: Discontinue sumtriptn succinte if occurs. (.) Mediction overuse hedche: Detoxifiction my be necessry. (.6) Serotonin syndrome: Discontinue sumtriptn succinte if occurs. (.7) Increse in blood pressure: Monitor blood pressure. (.8) Anphylctic/nphylctoid rections: Discontinue sumtriptn succinte if occurs. (.9) Seizures: Use with cution in ptients with epilepsy or lowered seizure threshold. (.10) ADVERSE REACTIONS Most common dverse rections ( % nd > plcebo) were injection site rections, tingling, dizziness/vertigo, wrm/hot senstion, burning senstion, feeling of heviness, pressure senstion, flushing, feeling of tightness, nd numbness. (6.1) To report SUSPECTED ADVERSE REACTIONS, contct Fresenius Kbi USA, LLC, Vigilnce & Medicl Affirs t or FDA t FDA-1088 or USE IN SPECIFIC POPULATIONS Pregnncy: Bsed on niml dt, my cuse fetl hrm. (8.1) Geritric use: A crdiovsculr evlution is recommended in those who hve other crdiovsculr risk fctors prior to receiving sumtriptn succinte. (8.) See 17 for PATIENT COUNSELING INFORMATION nd FDApproved ptient lbeling. Revised: 4/ C/Revised: April 01 SUMATRIPTAN SUCCINATE INJECTION FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE DOSAGE AND ADMINISTRATION.1 Dosing Informtion. Administrtion of Doses of Injection Other thn 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS WARNINGS AND PRECAUTIONS.1 Myocrdil Ischemi, Myocrdil Infrction, nd Prinzmetl s Angin. Arrhythmis.3 Chest, Throt, Neck, nd/or Jw Pin/Tightness/ Pressure.4 Cerebrovsculr Events. Other Vsospsm Rections.6 Mediction Overuse Hedche.7 Serotonin Syndrome.8 Increse in Blood Pressure.9 Anphylctic/Anphylctoid Rections.10 Seizures 6 ADVERSE REACTIONS 6.1 Clinicl Trils Experience 6. Postmrketing Experience 7 DRUG INTERACTIONS 7.1 Ergot-Contining Drugs 7. Monomine Oxidse-A Inhibitors 7.3 Other -HT 1 Agonists 7.4 Selective Serotonin Reuptke Inhibitors/Serotonin Norepinephrine Reuptke Inhibitors nd Serotonin Syndrome 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnncy 8.3 Nursing Mothers 8.4 Peditric Use 8. Geritric Use 10 OVERDOSAGE 11 DESCRIPTION 1 CLINICAL PHARMACOLOGY 1.1 Mechnism of Action 1. Phrmcodynmics 1.3 Phrmcokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Crcinogenesis, Mutgenesis, Impirment of Fertility 13. Animl Toxicology nd/or Phrmcology 14 CLINICAL STUDIES 14.1 Migrine 14. Cluster Hedche 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full prescribing informtion re not listed. FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE succinte injection is indicted in dults for (1) the cute tretment of migrine, with or without ur, nd () the cute tretment of cluster hedche. Limittions of Use: Use only if cler dignosis of migrine or cluster hedche hs been estblished. If ptient hs no response to the first migrine ttck treted with sumtriptn succinte injection, reconsider the dignosis of migrine before sumtriptn succinte injection is dministered to tret ny subsequent ttcks. succinte injection is not indicted for the prevention of migrine ttcks. DOSAGE AND ADMINISTRATION.1 Dosing Informtion The mximum single recommended dult dose of sumtriptn succinte injection for the cute tretment of migrine or cluster hedche is injected subcutneously. For the tretment of migrine, if side effects re dose limiting, lower doses (1 to mg) my be used [see Clinicl Studies (14.1)]. For the tretment of cluster hedche, the efficcy of lower doses hs not been estblished. The mximum cumultive dose tht my be given in 4 hours is 1 mg, two injections seprted by t lest 1 hour. A second dose should only be considered if some response to first injection ws observed.. Administrtion of Doses of Injection Other thn In ptients receiving doses other thn, use the single-dose vil. Visully inspect the vil for prticulte mtter nd discolortion before dministrtion. Do not use if prticultes nd discolortions re noted. 3 DOSAGE FORMS AND STRENGTHS Injection: single-dose vil 4 CONTRAINDICATIONS succinte injection is contrindicted in ptients with: Ischemic coronry rtery disese (CAD) (ngin pectoris, history of myocrdil infrction, or documented silent ischemi) or coronry rtery vsospsm, including Prinzmetl s ngin [see Wrnings nd Precutions (.1)]. Wolff-Prkinson-White syndrome or rrhythmis ssocited with other crdic ccessory conduction pthwy disorders [see Wrnings nd Precutions (.)]. History of stroke or trnsient ischemic ttck (TIA) becuse these ptients re t higher risk of stroke [see Wrnings nd Precutions (.4)]. History of hemiplegic or bsilr migrine. Peripherl vsculr disese [see Wrnings nd Precutions (.)]. Ischemic bowel disese [see Wrnings nd Precutions (.)]. Uncontrolled hypertension [see Wrnings nd Precutions (.8)]. Recent (i.e., within 4 hours) use of ergotminecontining mediction, ergot-type mediction (such s dihydroergotmine or methysergide), or nother -hydroxytryptmine 1 (-HT 1 ) gonist [see Drug Interctions (7.1, 7.3)]. Concurrent dministrtion of n MAO-A inhibitor or recent (within weeks) use of n MAO-A inhibitor [see Drug Interctions (7.) nd Clinicl Phrmcology (1.3)]. Known hypersensitivity to sumtriptn [see Wrnings nd Precutions (.9) nd Adverse Rections (6.)]. Severe heptic impirment [see Clinicl Phrmcology (1.3)]. WARNINGS AND PRECAUTIONS.1 Myocrdil Ischemi, Myocrdil Infrction, nd Prinzmetl s Angin The use of sumtriptn succinte injection is contrindicted

2 in ptients with ischemic or vsospstic CAD. There hve been rre reports of serious crdic dverse rections, including cute myocrdil infrction, occurring within few hours following dministrtion of sumtriptn succinte injection. Some of these rections occurred in ptients without known CAD. -HT 1 gonists, including sumtriptn succinte injection, my cuse coronry rtery vsospsm (Prinzmetl s ngin), even in ptients without history of CAD. Perform crdiovsculr evlution in triptn-nive ptients who hve multiple crdiovsculr risk fctors (e.g., incresed ge, dibetes, hypertension, smoking, obesity, strong fmily history of CAD) prior to receiving sumtriptn succinte injection. If there is evidence of CAD or coronry rtery vsospsm, sumtriptn succinte injection is contrindicted. For ptients with multiple crdiovsculr risk fctors who hve negtive crdiovsculr evlution, consider dministering the first dose of sumtriptn succinte injection in mediclly supervised setting nd performing n electrocrdiogrm (ECG) immeditely following sumtriptn succinte injection. For such ptients, consider periodic crdiovsculr evlution in intermittent long-term users of sumtriptn succinte injection. Evlute ptients with signs or symptoms suggestive of ngin following sumtriptn succinte injection for the presence of CAD or Prinzmetl s ngin before receiving dditionl doses of sumtriptn succinte injection.. Arrhythmis Life-thretening disturbnces of crdic rhythm, including ventriculr tchycrdi nd ventriculr fibrilltion leding to deth, hve been reported within few hours following the dministrtion of -HT 1 gonists. Discontinue sumtriptn succinte injection if these disturbnces occur. succinte injection is contrindicted in ptients with Wolff- Prkinson-White syndrome or rrhythmis ssocited with other crdic ccessory conduction pthwy disorders..3 Chest, Throt, Neck, nd/or Jw Pin/Tightness/ Pressure As with other -HT 1 gonists, senstions of tightness, pin, pressure, nd heviness in the precordium, throt, neck, nd jw commonly occur fter tretment with sumtriptn succinte injection nd re usully non-crdic in origin. However, perform crdic evlution if these ptients re t high crdic risk. The use of sumtriptn succinte injection is contrindicted in ptients shown to hve CAD nd those with Prinzmetl s vrint ngin..4 Cerebrovsculr Events Cerebrl hemorrhge, subrchnoid hemorrhge, nd stroke hve occurred in ptients treted with -HT 1 gonists, nd some hve resulted in ftlities. In number of cses, it ppers possible tht the cerebrovsculr events were primry, the -HT 1 gonist hving been dministered in the incorrect belief tht the symptoms experienced were consequence of migrine when they were not. Also, ptients with migrine my be t incresed risk of certin cerebrovsculr events (e.g., stroke, hemorrhge, TIA). Discontinue sumtriptn succinte injection if cerebrovsculr event occurs. As with other cute migrine therpies, before treting hedches in ptients not previously dignosed s migrineurs, nd in migrineurs who present with typicl symptoms, exclude other potentilly serious neurologicl conditions. succinte injection is contrindicted in ptients with history of stroke or TIA.. Other Vsospsm Rections -HT 1 gonists, including sumtriptn succinte injection, my cuse non-coronry vsospstic rections, such s peripherl vsculr ischemi, gstrointestinl vsculr ischemi nd infrction (presenting with bdominl pin nd bloody dirrhe), splenic infrction, nd Rynud s syndrome. Until further evlution, sumtriptn succinte injection is contrindicted in ptients who experience symptoms or signs suggestive of non-coronry vsospsm rection following the use of ny -HT 1 gonist. Reports of trnsient nd permnent blindness nd significnt prtil vision loss hve been reported with the use of -HT 1 gonists. Since visul disorders my be prt of migrine ttck, cusl reltionship between these events nd the use of -HT 1 gonists hve not been clerly estblished..6 Mediction Overuse Hedche Overuse of cute migrine drugs (e.g., ergotmine, triptns, opioids, combintion of drugs for 10 or more dys per month) my led to excerbtion of hedche (mediction overuse hedche). Mediction overuse hedche my present s migrine-like dily hedches, or s mrked increse in frequency of migrine ttcks. Detoxifiction of ptients, including withdrwl of the overused drugs, nd tretment of withdrwl symptoms (which often includes trnsient worsening of hedche) my be necessry..7 Serotonin Syndrome Serotonin syndrome my occur with triptns, including sumtriptn succinte injection, prticulrly during codministrtion with selective serotonin reuptke inhibitors (SSRIs), serotonin norepinephrine reuptke inhibitors (SNRIs), tricyclic ntidepressnts (TCAs), nd MAO inhibitors [see Drug Interctions (7.4)]. Serotonin syndrome symptoms my include mentl sttus chnges (e.g., gittion, hllucintions, com), utonomic instbility (e.g., tchycrdi, lbile blood pressure, hyperthermi), neuromusculr berrtions (e.g., hyperreflexi, incoordintion), nd/or gstrointestinl symptoms (e.g., nuse, vomiting, dirrhe). The onset of symptoms usully occurs within minutes to hours of receiving new or greter dose of serotonergic mediction. Discontinue sumtriptn succinte injection if serotonin syndrome is suspected..8 Increse in Blood Pressure Significnt elevtion in blood pressure, including hypertensive crisis with cute impirment of orgn systems, hs been reported on rre occsions in ptients treted with -HT 1 gonists, including ptients without history of hypertension. Monitor blood pressure in ptients treted with sumtriptn succinte. succinte injection is contrindicted in ptients with uncontrolled hypertension..9 Anphylctic/Anphylctoid Rections Anphylctic/nphylctoid rections hve occurred in ptients receiving sumtriptn. Such rections cn be life thretening or ftl. In generl, nphylctic rections to drugs re more likely to occur in individuls with history of sensitivity to multiple llergens. succinte injection is contrindicted in ptients with prior serious nphylctic rection..10 Seizures Seizures hve been reported following dministrtion of sumtriptn. Some hve occurred in ptients with either history of seizures or concurrent conditions predisposing to seizures. There re lso reports in ptients where no such predisposing fctors re pprent. succinte injection should be used with cution in ptients with history of epilepsy or conditions ssocited with lowered seizure threshold. 6 ADVERSE REACTIONS The following dverse rections re discussed in more detil in other sections of the lbeling: Myocrdil ischemi, myocrdil infrction, nd Prinzmetl s ngin [see Wrnings nd Precutions (.1)] Arrhythmis [see Wrnings nd Precutions (.)] Chest, throt, neck, nd/or jw pin/tightness/pressure [see Wrnings nd Precutions (.3)] Cerebrovsculr events [see Wrnings nd Precutions (.4)] Other vsospsm rections [see Wrnings nd Precutions (.)] Mediction overuse hedche [see Wrnings nd Precutions (.6)] Serotonin syndrome [see Wrnings nd Precutions (.7)] Increse in blood pressure [see Wrnings nd Precutions (.8)] Anphylctic/nphylctoid rections [see Wrnings nd Precutions (.9)] Seizures [see Wrnings nd Precutions (.10)] 6.1 Clinicl Trils Experience Becuse clinicl trils re conducted under widely vrying conditions, dverse rection rtes observed in the clinicl trils of drug cnnot be directly compred with rtes in the clinicl trils of nother drug nd my not reflect the rtes observed in prctice. Migrine Hedche: Tble 1 lists dverse rections tht occurred in US plcebo-controlled clinicl trils in migrine subjects [Studies nd 3, see Clinicl Studies (14.1)] following either single dose of sumtriptn succinte injection or plcebo. Only rections tht occurred t frequency of % or more in groups treted with sumtriptn succinte injection nd tht occurred t frequency greter thn the plcebo group re included in Tble 1. Tble 1. Adverse Rections Reported by t Lest % of Subjects nd t Greter Frequency thn in -Controlled Migrine Clinicl Trils (Studies nd 3) Adverse Rection Atypicl senstions Tingling Wrm/hot senstion Burning senstion Feeling of heviness Pressure senstion Feeling of tightness Numbness Feeling strnge Tight feeling in hed Percent of Subjects Reporting Injection Subcutneous (n = 47) (n=370) Crdiovsculr Flushing 7 Chest discomfort Tightness in chest Pressure in chest Er, nose, nd throt Throt discomfort Discomfort: nsl cvity/sinuses Injection site 9 4 rection b Miscellneous Jw discomfort 0 Musculoskeletl Wekness Neck pin/stiffness Mylgi Neurologicl Dizziness/vertigo Drowsiness/ sedtion Hedche 1 3 Skin Sweting 1 The sum of the percentges cited is greter thn 100% becuse subjects my hve experienced more thn 1 type of dverse rection. Only rections tht occurred t frequency of % or more in groups treted with sumtriptn succinte injection nd occurred t frequency greter thn the plcebo groups re included. b Includes injection site pin, stinging/burning, swelling, erythem, bruising, bleeding. 4 The incidence of dverse rections in controlled clinicl trils ws not ffected by gender or ge of the subjects. There were insufficient dt to ssess the impct of rce on the incidence of dverse rections. Cluster Hedche: In the controlled clinicl trils ssessing the efficcy of sumtriptn succinte injection s tretment for cluster hedche [Studies 4 nd, see Clinicl Studies (14.)], no new significnt dverse rections were detected tht hd not lredy been identified in trils of sumtriptn succinte in subjects with migrine. Overll, the frequency of dverse rections reported in the trils of cluster hedche ws generlly lower thn in the migrine trils. Exceptions include reports of presthesi (% sumtriptn succinte, 0% plcebo), nuse nd vomiting (4% sumtriptn succinte, 0% plcebo), nd bronchospsm (1% sumtriptn succinte, 0% plcebo). Other Adverse Rections: In the prgrphs tht follow, the frequencies of less commonly reported dverse rections re presented. Rection frequencies were clculted s the number of subjects reporting rection divided by the totl number of subjects (N = 6,18) exposed to subcutneous sumtriptn succinte injection. All reported rections re included except those lredy listed in the previous tble. Rections re further clssified within body system ctegories nd enumerted in order of decresing frequency using the following definitions: frequent re defined s those occurring in t lest 1/100 subjects, infrequent re those occurring in 1/100 to 1/1,000 subjects, nd rre re those occurring in fewer thn 1/1,000 subjects. Crdiovsculr: Infrequent were hypertension, hypotension, brdycrdi, tchycrdi, plpittions, nd syncope. Rre ws rrhythmi. Gstrointestinl: Frequent ws bdominl discomfort. Musculoskeletl: Frequent were muscle crmps. Neurologicl: Frequent ws nxiety. Infrequent were mentl confusion, euphori, gittion, tremor. Rre were myocloni, sleep disturbnce, nd dystoni. Respirtory: Infrequent ws dyspne. Skin: Infrequent were erythem, pruritus, nd skin rshes. Miscellneous: Infrequent ws serotonin gonist effect. Adverse Events Observed with Other Formultions of : The following dverse events occurred in clinicl trils with sumtriptn succinte tblets nd sumtriptn succinte nsl spry. Becuse the reports include events observed in open nd uncontrolled trils, the role of sumtriptn succinte in their custion cnnot be relibly determined. All reported events re included except those lredy listed, those too generl to be informtive, nd those not resonbly ssocited with the use of the drug. Crdiovsculr: Angin, cerebrovsculr lesion, hert block, peripherl cynosis, phlebitis, thrombosis. Gstrointestinl: Abdominl distention nd colitis. Neurologicl: Convulsions, hllucintions, syncope, suicide, nd twitching. Miscellneous: Edem, hypersensitivity, swelling of extremities, nd swelling of fce. 6. Postmrketing Experience The following dverse rections hve been identified during postpprovl use of sumtriptn succinte tblets, sumtriptn succinte nsl spry, nd sumtriptn succinte injection. Becuse these rections re reported voluntrily from popultion of uncertin size, it is not lwys possible to relibly estimte their frequency or estblish cusl reltionship to drug exposure. These rections hve been chosen for inclusion due to either their seriousness, frequency of reporting, or cusl connection to sumtriptn succinte or combintion of these fctors. Blood: Hemolytic nemi, pncytopeni, thrombocytopeni. Er, Nose, nd Throt: Defness. Eye: Ischemic optic neuropthy, retinl rtery occlusion, retinl vein thrombosis. Neurologicl: Centrl nervous system vsculitis, cerebrovsculr ccident, serotonin syndrome, subrchnoid hemorrhge. Non-Site Specific: Angioedem, cynosis, temporl rteritis. Skin: Excerbtion of sunburn, hypersensitivity rections (llergic vsculitis, erythem, pruritus, rsh, shortness of breth, urticri), photosensitivity. Following subcutneous dministrtion of sumtriptn succinte, pin, redness, stinging, indurtion, swelling, contusion, subcutneous bleeding, nd, on rre occsions, lipotrophy (depression in the skin) or lipohypertrophy (enlrgement or thickening of tissue) hve been reported. Urogenitl: Acute renl filure. 7 DRUG INTERACTIONS 7.1 Ergot-Contining Drugs Ergot-contining drugs hve been reported to cuse prolonged vsospstic rections. Becuse these effects my be dditive, use of ergotmine-contining or ergot-type medictions (like dihydroergotmine or methysergide) nd sumtriptn succinte injection within 4 hours of ech other is contrindicted. 7. Monomine Oxidse-A Inhibitors MAO-A inhibitors increse systemic exposure by -fold. Therefore, the use of sumtriptn succinte injection in ptients receiving MAO-A inhibitors is contrindicted [see Clinicl Phrmcology (1.3)]. 7.3 Other -HT 1 Agonists Becuse their vsospstic effects my be dditive, codministrtion of sumtriptn succinte injection nd other -HT 1 gonists (e.g., triptns) within 4 hours of ech other is contrindicted. 7.4 Selective Serotonin Reuptke Inhibitors/Serotonin Norepinephrine Reuptke Inhibitors nd Serotonin Syndrome Cses of serotonin syndrome hve been reported during codministrtion of triptns nd SSRIs, or SNRIs, SNRIs, TCAs, nd MAO inhibitors [see Wrnings nd Precutions (.7)]. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnncy Pregnncy Ctegory C: There re no dequte nd wellcontrolled trils of sumtriptn succinte injection in pregnnt women. succinte injection should be used during pregnncy only if the potentil benefit justifies the potentil risk to the fetus. When sumtriptn ws dministered intrvenously to pregnnt rbbits dily throughout the period of orgnogenesis, embryolethlity ws observed t doses t or close to those producing mternl toxicity. These doses were less thn the mximum recommended humn dose (MRHD) of 1 mg/dy on mg/m bsis. Orl dministrtion

3 of sumtriptn to rbbits during orgnogenesis ws ssocited with incresed incidences of fetl vsculr nd skeletl bnormlities. The highest no-effect dose for these effects ws 1 mg/kg/dy. The intrvenous dministrtion of sumtriptn to pregnnt rts throughout orgnogenesis t doses tht re pproximtely 10 times the MRHD on mg/m bsis, did not produce evidence of embryolethlity. The subcutneous dministrtion of sumtriptn to pregnnt rts prior to nd throughout pregnncy did not produce evidence of embryolethlity or tertogenicity. 8.3 Nursing Mothers It is not known whether sumtriptn is excreted in humn brest milk following subcutneous dministrtion. Becuse mny drugs re excreted in humn milk, nd becuse of the potentil for serious dverse rections in nursing infnts from sumtriptn succinte, decision should be mde whether to discontinue nursing or to discontinue the drug, tking into ccount the importnce of the drug to the mother. 8.4 Peditric Use Sfety nd effectiveness of sumtriptn succinte injection in peditric ptients under 18 yers of ge hve not been estblished; therefore, sumtriptn succinte injection is not recommended for use in ptients under 18 yers of ge. Two controlled clinicl trils evluted sumtriptn succinte nsl spry ( to 0 mg) in 1,48 dolescent migrineurs ged 1 to 17 yers who treted single ttck. The trils did not estblish the efficcy of sumtriptn succinte nsl spry compred with plcebo in the tretment of migrine in dolescents. Adverse rections observed in these clinicl trils were similr in nture to those reported in clinicl trils in dults. Five controlled clinicl trils ( single-ttck trils, 3 multiple-ttck trils) evluting orl sumtriptn succinte ( to 100 mg) in peditric subjects ged 1 to 17 yers enrolled totl of 701 dolescent migrineurs. These trils did not estblish the efficcy of orl sumtriptn succinte compred with plcebo in the tretment of migrine in dolescents. Adverse rections observed in these clinicl trils were similr in nture to those reported in clinicl trils in dults. The frequency of ll dverse rections in these subjects ppered to be both dose- nd ge-dependent, with younger subjects reporting rections more commonly thn older dolescents. Postmrketing experience documents tht serious dverse rections hve occurred in the peditric popultion fter use of subcutneous, orl, nd/or intrnsl sumtriptn succinte. These reports include rections similr in nture to those reported rrely in dults, including stroke, visul loss, nd deth. A myocrdil infrction hs been reported in 14-yer-old mle following the use of orl sumtriptn succinte; clinicl signs occurred within 1 dy of drug dministrtion. Since clinicl dt to determine the frequency of serious dverse rections in peditric ptients who might receive subcutneous, orl, or intrnsl sumtriptn succinte re not presently vilble, the use of sumtriptn succinte in ptients under 18 yers of ge is not recommended. 8. Geritric Use Clinicl trils of sumtriptn succinte injection did not include sufficient numbers of subjects ged 6 nd over to determine whether they respond differently from younger subjects. Other reported clinicl experience hs not identified differences in responses between the elderly nd younger subjects. In generl, dose selection for n elderly ptient should be cutious, usully strting t the low end of the dosing rnge, reflecting the greter frequency of decresed heptic, renl, or crdic function nd of concomitnt disese or other drug therpy. A crdiovsculr evlution is recommended for geritric ptients who hve other crdiovsculr risk fctors (e.g., dibetes, hypertension, smoking, obesity, strong fmily history of CAD) prior to receiving sumtriptn succinte injection [see Wrnings nd Precutions (.1)]. 10 OVERDOSAGE No gross overdoses in clinicl prctice hve been reported. Coronry vsospsm ws observed fter intrvenous dministrtion of sumtriptn succinte injection [see Contrindictions (4)]. Overdoses would be expected from niml dt (dogs t 0.1 g/kg, rts t g/kg) to possibly cuse convulsions, tremor, inctivity, erythem of the extremities, reduced respirtory rte, cynosis, txi, mydrisis, injection site rections (desqumtion, hir loss, nd scb formtion), nd prlysis. The elimintion hlf-life of sumtriptn is bout hours [see Clinicl Phrmcology (1.3)], nd therefore monitoring of ptients fter overdose with sumtriptn succinte injection should continue for t lest 10 hours or while symptoms or signs persist. It is unknown wht effect hemodilysis or peritonel dilysis hs on the serum concentrtions of sumtriptn. 11 DESCRIPTION succinte injection contins sumtriptn succinte, selective -HT 1B/1D receptor gonist. succinte is chemiclly designted s 3-[-(dimethylmino)ethyl]-N-methyl-indole--methnesulfonmide succinte (1:1), nd it hs the following structure: CH 3NHSO CH CH CH N(CH 3) N H CH COOH CH COOH C 14 H 1 N 3 O S C 4 H 6 O 4 M.W succinte is white to off-white powder tht is redily soluble in wter nd in sline. succinte injection is cler, colorless to ple yellow, sterile, nonpyrogenic solution for subcutneous injection. Ech 0. ml of sumtriptn succinte injection 1 mg/ml solution contins of sumtriptn (bse) s the succinte slt nd 3. mg of sodium chloride in wter for injection. The ph rnge of the solution is pproximtely 4. to.3. The osmollity of the injection is 91 mosmol. 1 CLINICAL PHARMACOLOGY 1.1 Mechnism of Action binds with high ffinity to humn cloned -HT 1B/1D receptors. succinte presumbly exerts its therpeutic effects in the tretment of migrine hedche by binding to -HT 1B/1D receptors locted on intrcrnil blood vessels nd sensory nerves of the trigeminl system. Current theories proposed to explin the etiology of migrine hedche suggest tht symptoms re due to locl crnil vsodilttion nd/or to the relese of sensory neuropeptides (including substnce P nd clcitonin gene-relted peptide) through nerve endings in the trigeminl system. The therpeutic ctivity of sumtriptn succinte for the tretment of migrine nd cluster hedches is thought to be due to the gonist effects t the -HT 1B/1D receptors on intrcrnil blood vessels (including the rterio-venous nstomoses) nd sensory nerves of the trigeminl system, which result in crnil vessel constriction nd inhibition of pro-inflmmtory neuropeptide relese. 1. Phrmcodynmics Blood Pressure: Significnt elevtion in blood pressure, including hypertensive crisis, hs been reported in ptients with nd without history of hypertension [see Wrnings nd Precutions (.8)]. Peripherl (Smll) Arteries: In helthy volunteers (N = 18), tril evluting the effects of sumtriptn on peripherl (smll vessel) rteril rectivity filed to detect cliniclly significnt increse in peripherl resistnce. Hert Rte: Trnsient increses in blood pressure observed in some subjects in clinicl trils crried out during sumtriptn s development s tretment for migrine were not ccompnied by ny cliniclly significnt chnges in hert rte. 1.3 Phrmcokinetics Absorption nd Biovilbility: The biovilbility of sumtriptn vi subcutneous site injection to 18 helthy mle subjects ws 97% ± 16% of tht obtined following intrvenous injection. After single subcutneous mnul injection into the deltoid re of the rm in 18 helthy mles (ge: 4 ± 6 yers, weight: 70 kg), the mximum serum concentrtion (C mx ) of sumtriptn ws (men ± stndrd devition) 74 ± 1 ng/ml nd the time to pek concentrtion (T mx ) ws 1 minutes fter injection (rnge: to 0 minutes). In this tril, the sme dose injected subcutneously in the thigh gve C mx of 61 ± 1 ng/ml by mnul injection versus ± 1 ng/ml by utoinjector techniques. The T mx or mount bsorbed ws not significntly ltered by either the site or technique of injection. Distribution: Protein binding, determined by equilibrium dilysis over the concentrtion rnge of 10 to 1,000 ng/ml, is low, pproximtely 14% to 1%. The effect of sumtriptn on the protein binding of other drugs hs not been evluted. Following subcutneous injection into the deltoid re of the rm in 9 mles (men ge: 33 yers, men weight: 77 kg) the volume of distribution centrl comprtment of sumtriptn ws 0 ± 8 liters nd the distribution hlf-life ws 1 ± minutes. Metbolism: In vitro studies with humn microsomes suggest tht sumtriptn is metbolized by MAO, predominntly the A isoenzyme. Most of rdiolbeled dose of sumtriptn excreted in the urine is the mjor metbolite indole cetic cid (IAA) or the IAA glucuronide, both of which re inctive. Elimintion: After single subcutneous dose, % ± 4% ws excreted in the urine s unchnged sumtriptn nd 38% ± 7% s the IAA metbolite. Following subcutneous injection into the deltoid re of the rm, the systemic clernce of sumtriptn ws 1,194 ± 149 ml/min nd the terminl hlf-life ws 11 ± 19 minutes. Specil Popultions: Age: The phrmcokinetics of sumtriptn in the elderly (men ge: 7 yers, mles nd 4 femles) nd in subjects with migrine (men ge: 38 yers, mles nd 1 femles) were similr to tht in helthy mle subjects (men ge: 30 yers). Renl Impirment: The effect of renl impirment on the phrmcokinetics of sumtriptn hs not been exmined. Heptic Impirment: The effect of mild to moderte heptic disese on the phrmcokinetics of subcutneously dministered sumtriptn hs been evluted. There were no significnt differences in the phrmcokinetics of subcutneously dministered sumtriptn in modertely hepticlly impired subjects compred with helthy controls. The phrmcokinetics of subcutneously dministered sumtriptn in ptients with severe heptic impirment hs not been studied. The use of sumtriptn succinte injection in this popultion is contrindicted [see Contrindictions (4)]. Rce: The systemic clernce nd C mx of sumtriptn were similr in Blck (n = 34) nd Cucsin (n = 38) helthy mle subjects. Drug Interction Studies: Monomine Oxidse-A Inhibitors: In tril of 14 helthy femles, pretretment with n MAO-A inhibitor decresed the clernce of sumtriptn, resulting in -fold increse in the re under the sumtriptn plsm concentrtion-time curve (AUC), corresponding to 40% increse in elimintion hlf-life. 13 NONCLINICAL TOXICOLOGY 13.1 Crcinogenesis, Mutgenesis, Impirment of Fertility Crcinogenesis: In crcinogenicity studies, rts nd mice were given sumtriptn by orl gvge. Mice were dosed for 78 weeks nd rts were dosed for 104 weeks. Averge exposures chieved in mice receiving the highest dose were pproximtely 110 times the exposure ttined in humns fter the mximum recommended single dose of. The highest dose to rts ws pproximtely 60 times the mximum single dose of on mg/m bsis. There ws no evidence of n increse in tumors in either species relted to sumtriptn dministrtion. Mutgenesis: ws not mutgenic in the presence or bsence of metbolic ctivtion when tested in gene muttion ssys (the Ames test nd the in vitro mmmlin Chinese hmster V79/HGPRT ssy). It ws not clstogenic in cytogenetics ssys (the in vitro humn lymphocyte ssy nd the in vivo rt micronucleus ssy). Impirment of Fertility: A fertility study (Segment I) by the subcutneous route, during which mle nd femle rts were dosed dily with sumtriptn prior to nd throughout the mting period, hs shown no evidence of impired fertility t doses equivlent to pproximtely 100 times the mximum recommended single humn dose of on mg/m bsis. However, following orl dministrtion, tretment-relted decrese in fertility, secondry to decrese in mting, ws seen for rts treted with 0 nd 00 mg/kg/dy. The no-effect dose for this finding ws pproximtely 8 times the mximum recommended single humn dose of on mg/m bsis. It is not cler whether the problem is ssocited with the tretment of mles or femles or both. 13. Animl Toxicology nd/or Phrmcology Cornel Opcities: Dogs receiving orl sumtriptn developed cornel opcities nd defects in the cornel epithelium. Cornel opcities were seen t the lowest dosge tested, mg/kg/dy, nd were present fter 1 month of tretment. Defects in the cornel epithelium were noted in 60-week study. Erlier exmintions for these toxicities were not conducted nd no-effect doses were not estblished; however, the reltive exposure t the lowest dose tested ws pproximtely times the humn exposure fter 100 mg orl dose or 3 times the humn exposure fter subcutneous dose. Melnin Binding: In rts with single subcutneous dose (0. mg/kg) of rdiolbeled sumtriptn, the elimintion hlf-life of rdioctivity from the eye ws 1 dys, suggesting tht sumtriptn nd its metbolites bind to the melnin of the eye. The clinicl significnce of this binding is unknown. 14 CLINICAL STUDIES 14.1 Migrine In controlled clinicl trils enrolling more thn 1,000 subjects during migrine ttcks who were experiencing moderte or severe pin nd 1 or more of the symptoms enumerted in Tble 3, onset of relief begn s erly s 10 minutes following sumtriptn succinte injection. Lower doses of sumtriptn succinte injection my lso prove effective, lthough the proportion of subjects obtining dequte relief ws decresed nd the ltency to tht relief is greter with lower doses. In Study 1, 6 different doses of sumtriptn succinte injection (n = 30 ech group) were compred with plcebo (n = 6), in single-ttck, prllel-group design, the dose response reltionship ws found to be s shown in Tble. Tble. Proportion of Migrine Relief nd Incidence of Adverse Events by Time nd by Dose in Study 1 Dose of Injection 1 mg mg 3 mg 4 mg 8 mg t 10 Minutes Percent Relief t 30 Minutes t 1 Hour t Hours Adverse Events Incidence (%) Relief is defined s the reduction of moderte or severe pin to no or mild pin fter dosing without use of rescue mediction. In rndomized, plcebo-controlled clinicl trils of sumtriptn succinte injection in 1,104 subjects with moderte or severe migrine pin (Studies nd 3), the onset of relief ws less thn 10 minutes. Hedche relief, s defined by reduction in pin from severe or modertely severe to mild or no hedche, ws chieved in 70% of the subjects within 1 hour of single subcutneous dose of sumtriptn succinte injection. Approximtely 8% nd 6% of subjects treted with sumtriptn succinte hd hedche relief nd were pin free within hours, respectively. Tble 3 shows the 1- nd -hour efficcy results for sumtriptn succinte injection in Studies nd 3. Tble 3. Proportion of Pin Relief nd Relief of Migrine Symptoms fter 1 nd Hours of Tretment in Studies nd 3 Study Study 3 1-Hour Dt pin relief (grde 0/1) no pin out nuse out photophobi little or no clinicl disbility b (n = 190) 18% % 48% 3% 34% (n = 384) 70% 48% 73% 6% 76% (n = 180) 6% 13% 0% % 34% (n = 30) 70% 49% 73% 8% 76% Study Study 3 -Hour Dt c d c d pin relief (grde 0/1) no pin out nuse out photophobi little or no clinicl disbility b 31% 11% 6% 31% 4% 81% 63% 8% 7% 8% 39% 19% 63% 3% 49% 8% 6% 81% 71% 84% P<0.0 versus plcebo. b A successful outcome in terms of clinicl disbility ws defined prospectively s bility to work mildly impired or bility to work nd function normlly. c Includes subjects tht my hve received n dditionl plcebo injection 1 hour fter the initil injection. d Includes subjects tht my hve received n dditionl of sumtriptn succinte injection 1 hour fter the initil injection.

4 succinte injection lso relieved photophobi, phonophobi (sound sensitivity), nuse, nd vomiting ssocited with migrine ttcks. The efficcy of sumtriptn succinte injection ws unffected by whether or not the migrine ws ssocited with ur, durtion of ttck, gender or ge of the subject, or concomitnt use of common migrine prophylctic drugs (e.g., bet-blockers). 14. Cluster Hedche The efficcy of sumtriptn succinte injection in the cute tretment of cluster hedche ws demonstrted in rndomized, double-blind, plcebo-controlled, -period crossover trils (Studies 4 nd ). Subjects ged 1 to 6 yers were enrolled nd were instructed to tret moderte to very severe hedche within 10 minutes of onset. Hedche relief ws defined s reduction in hedche severity to mild or no pin. In both trils, the proportion of individuls gining relief t 10 or 1 minutes ws significntly greter mong subjects receiving of sumtriptn succinte injection compred with those who received plcebo (see Tble 4). Tble 4. Proportion of Cluster Hedche Relief by Time in Studies 4 nd Study 4 Study (n = 39) (n = 39) (n = 88) (n = 9) pin relief (no/mild) Minutes post-injection 10 Minutes post-injection 1 Minutes 8% 10% 6% 1% 49% 74% 7% % 3% 3% 49% 7% post-injection P<0.0. (n = Number of hedches treted.) An estimte of the cumultive probbility of subject with cluster hedche obtining relief fter being treted with either sumtriptn succinte injection or plcebo is presented in Figure 1. Figure 1. Time to Relief of Cluster Hedche from Time of Injection Estimted % of Relief (n = 17) (n = 131) Pregnncy Inform ptients tht sumtriptn succinte injection should not be used during pregnncy unless the potentil benefit justifies the potentil risk to the fetus [see Use in Specific Popultions (8.1)]. Nursing Mothers Advise ptients to notify their helthcre provider if they re brestfeeding or pln to brestfeed [see Use in Specific Popultions (8.3)]. Ability to Perform Complex Tsks Since migrines or tretment with sumtriptn succinte injection my cuse somnolence nd dizziness, instruct ptients to evlute their bility to perform complex tsks during migrine ttcks nd fter dministrtion of sumtriptn succinte injection. Serotonin Syndrome Ptients should be cutioned bout the risk of serotonin syndrome with the use of sumtriptn succinte injection or other triptns, prticulrly during combined use with SSRIs, SNRIs, TCAs, nd MAO inhibitors [see Wrnings nd Precutions (.7) nd Drug Interctions (7.4)]. How to Use Injection Provide ptients instruction on the proper use of sumtriptn succinte injection if they re ble to selfdminister sumtriptn succinte injection in mediclly unsupervised sitution. Inform ptients tht the injection is intended to be given subcutneously nd intrmusculr or intrvsculr delivery should be voided. Instruct ptients to use injection sites with n dequte skin nd subcutneous thickness to ccommodte the length of the needle Time (min.) The figure uses Kpln-Meier (product limit) Survivorship Plot. Subjects tking rescue mediction were censored t 1 minutes. The plot ws constructed with dt from subjects who either experienced relief or did not require (request) rescue mediction within period of hours following tretment. As consequence, the dt in the plot re derived from only subset of the 8 hedches treted (rescue mediction ws required in of the 17 plcebotreted hedches nd 18 of the 131 hedches treted with sumtriptn succinte injection). Other dt suggest tht tretment with sumtriptn succinte injection is not ssocited with n increse in erly recurrence of hedche nd hs little effect on the incidence of lter-occurring hedches (i.e., those occurring fter, but before 18 or 4 hours). 16 HOW SUPPLIED/STORAGE AND HANDLING succinte injection contins sumtriptn (bse) s the succinte slt nd is supplied s cler, colorless to ple yellow, sterile, nonpyrogenic solution s follows: Product NDC No. No. Strength (sumtriptn) per 0. ml 0. ml single dose vil, pckged individully. Store between nd C (36 nd 77 F). Protect from light. The continer closure is not mde with nturl rubber ltex. 17 PATIENT COUNSELING INFORMATION See FDA-pproved ptient lbeling (Ptient Informtion leflet). Risk of Myocrdil Ischemi nd/or Infrction, Prinzmetl s Angin, Other Vsospsm-Relted Events, Arrhythmis, nd Cerebrovsculr Events Inform ptients tht sumtriptn succinte injection my cuse serious crdiovsculr side effects such s myocrdil infrction or stroke. Although serious crdiovsculr events cn occur without wrning symptoms, ptients should be lert for the signs nd symptoms of chest pin, shortness of breth, irregulr hertbet, significnt rise in blood pressure, wekness, nd slurring of speech nd should sk for medicl dvice when observing ny indictive sign or symptoms. Ptients should be pprised of the importnce of this follow-up [see Wrnings nd Precutions (.1,.,.4,.,.8)]. Anphylctic/Anphylctoid Rections Inform ptients tht nphylctic/nphylctoid rections hve occurred in ptients receiving sumtriptn succinte injection. Such rections cn be life thretening or ftl. In generl, nphylctic rections to drugs re more likely to occur in individuls with history of sensitivity to multiple llergens [see Wrnings nd Precutions (.9)]. Mediction Overuse Hedche Inform ptients tht use of cute migrine drugs for 10 or more dys per month my led to n excerbtion of hedche nd encourge ptients to record hedche frequency nd drug use (e.g., by keeping hedche diry) [see Wrnings nd Precutions (.6)]. Fresenius Kbi USA, LLC Lke Zurich, IL C Revised: April 01

5 Ptient Informtion Red this Ptient Informtion leflet before you strt tking sumtriptn succinte injection nd ech time you get refill. There my be new informtion. This informtion does not tke the plce of tlking with your helthcre provider bout your medicl condition or tretment. Wht is the most importnt informtion I should know bout sumtriptn succinte injection? succinte injection cn cuse serious side effects, including: Hert ttck nd other hert problems. Hert problems my led to deth. Stop tking sumtriptn succinte injection nd get emergency medicl help right wy if you hve ny of the following symptoms of hert ttck: discomfort in the center of your chest tht lsts for more thn few minutes, or tht goes wy nd comes bck severe tightness, pin, pressure, or heviness in your chest, throt, neck, or jw pin or discomfort in your rms, bck, neck, jw, or stomch shortness of breth with or without chest discomfort breking out in cold swet nuse or vomiting feeling lightheded succinte injection is not for people with risk fctors for hert disese unless hert exm is done nd shows no problem. You hve higher risk for hert disese if you: hve high blood pressure hve high cholesterol levels smoke re overweight hve dibetes hve fmily history of hert disese Wht is sumtriptn succinte injection? succinte injection is prescription medicine used to tret cute migrine hedches with or without ur nd cute cluster hedches in dults who hve been dignosed with migrine or cluster hedches. succinte injection is not used to tret other types of hedches such s hemiplegic (tht mke you unble to move on one side of your body) or bsilr (rre form of migrine with ur) migrines. succinte injection is not used to prevent or decrese the number of migrine or cluster hedches you hve. It is not known if sumtriptn succinte injection is sfe nd effective in children under 18 yers of ge. Who should not tke sumtriptn succinte injection? Do not tke sumtriptn succinte injection if you hve: hert problems or history of hert problems nrrowing of blood vessels to your legs, rms, stomch, or kidney (peripherl vsculr disese) uncontrolled high blood pressure hemiplegic migrines or bsilr migrines. If you re not sure if you hve these types of migrines, sk your helthcre provider. hd stroke, trnsient ischemic ttcks (TIAs), or problems with your blood circultion tken ny of the following medicines in the lst 4 hours: lmotriptn (AXERT ) eletriptn (RELPAX ) frovtriptn (FROVA ) nrtriptn (AMERGE ) riztriptn (MAXALT, MAXALT-MLT ) sumtriptn nd nproxen (TREXIMET ) ergotmines (CAFERGOT, ERGOMAR, MIGERGOT ) dihydroergotmine (D.H.E. 4, MIGRANAL )

6 Ask your helthcre provider if you re not sure if your medicine is listed bove. n llergy to sumtriptn or ny of the ingredients in sumtriptn succinte injection. See the end of this leflet for complete list of ingredients in sumtriptn succinte injection. Wht should I tell my helthcre provider before tking sumtriptn succinte injection? Before you tke sumtriptn succinte injection, tell your helthcre provider bout ll of your medicl conditions, including if you: hve high blood pressure hve high cholesterol hve dibetes smoke re overweight hve hert problems or fmily history of hert problems or stroke hve liver problems hve hd epilepsy or seizures re not using effective birth control become pregnnt while tking sumtriptn succinte injection re brestfeeding or pln to brestfeed. succinte injection psses into your brest milk nd my hrm your bby. Tlk with your helthcre provider bout the best wy to feed your bby if you tke sumtriptn succinte injection. Tell your helthcre provider bout ll the medicines you tke, including prescription nd nonprescription medicines, vitmins, nd herbl supplements. Using sumtriptn succinte injection with certin other medicines cn ffect ech other, cusing serious side effects. Especilly tell your helthcre provider if you tke nti-depressnt medicines clled: selective serotonin reuptke inhibitors (SSRIs) serotonin norepinephrine reuptke inhibitors (SNRIs) tricyclic ntidepressnts (TCAs) monomine oxidse inhibitors (MAOIs) Ask your helthcre provider or phrmcist for list of these medicines if you re not sure. Know the medicines you tke. Keep list of them to show your helthcre provider or phrmcist when you get new medicine. How should I tke sumtriptn succinte injection? Certin people should tke their first dose of sumtriptn succinte injection in their helthcre provider s office or in nother medicl setting. Ask your helthcre provider if you should tke your first dose in medicl setting. Use sumtriptn succinte injection exctly s your helthcre provider tells you to use it. Your helthcre provider my chnge your dose. Do not chnge your dose without first tlking with your helthcre provider. For dults, the usul dose is single injection given just below the skin.

7 You should give n injection s soon s the symptoms of your hedche strt, but it my be given t ny time during migrine ttck. If you did not get ny relief fter the first injection, do not give second injection without first tlking with your helthcre provider. You cn tke second injection 1 hour fter the first injection, but not sooner, if your hedche cme bck fter your first injection. Do not tke more thn 1 mg in 4- hour period. If you use too much sumtriptn succinte injection, cll your helthcre provider or go to the nerest hospitl emergency room right wy. You should write down when you hve hedches nd when you tke sumtriptn succinte injection so you cn tlk with your helthcre provider bout how sumtriptn succinte injection is working for you. Wht should I void while tking sumtriptn succinte injection? succinte injection cn cuse dizziness, wekness, or drowsiness. If you hve these symptoms, do not drive cr, use mchinery, or do nything where you need to be lert. Wht re the possible side effects of sumtriptn succinte injection? succinte injection my cuse serious side effects. See Wht is the most importnt informtion I should know bout sumtriptn succinte injection? These serious side effects include: chnges in color or senstion in your fingers nd toes (Rynud s syndrome) stomch nd intestinl problems (gstrointestinl nd colonic ischemic events). Symptoms of gstrointestinl nd colonic ischemic events include: sudden or severe stomch pin stomch pin fter mels weight loss nuse or vomiting constiption or dirrhe bloody dirrhe fever problems with blood circultion to your legs nd feet (peripherl vsculr ischemi). Symptoms of peripherl vsculr ischemi include: crmping nd pin in your legs or hips feeling of heviness or tightness in your leg muscles burning or ching pin in your feet or toes while resting numbness, tingling, or wekness in your legs cold feeling or color chnges in 1 or both legs or feet mediction overuse hedches. Some people who use too mny sumtriptn succinte injections my hve worse hedches (mediction overuse hedche). If your hedches get worse, your helthcre provider my decide to stop your tretment with sumtriptn succinte injection. serotonin syndrome. Serotonin syndrome is rre but serious problem tht cn hppen in people using sumtriptn succinte injection, especilly if sumtriptn succinte injection is used with nti-depressnt medicines clled SSRIs or SNRIs.

8 Cll your helthcre provider right wy if you hve ny of the following symptoms of serotonin syndrome: mentl chnges such s seeing things tht re not there (hllucintions), gittion, or com fst hertbet chnges in blood pressure high body temperture tight muscles trouble wlking seizures. Seizures hve hppened in people tking sumtriptn succinte injection who hve never hd seizures before. Tlk with your helthcre provider bout your chnce of hving seizures while you tke sumtriptn succinte injection. The most common side effects of sumtriptn succinte injection include: pin or redness t your injection site tingling or numbness in your fingers or toes dizziness wrm, hot, burning feeling to your fce (flushing) discomfort or stiffness in your neck feeling wek, drowsy, or tired Tell your helthcre provider if you hve ny side effect tht bothers you or tht does not go wy. These re not ll the possible side effects of sumtriptn succinte injection. For more informtion, sk your helthcre provider or phrmcist. Cll your doctor for medicl dvice bout side effects. You my report side effects to FDA t FDA How should I store sumtriptn succinte injection? Do not store t tempertures bove 77 F ( C). Store your medicine wy from light. Keep your medicine in the pckging or crrying cse provided with it. Keep sumtriptn succinte injection nd ll medicines out of the rech of children. Generl informtion bout the sfe nd effective use of sumtriptn succinte injection Medicines re sometimes prescribed for purposes other thn those listed in Ptient Informtion leflets. Do not use sumtriptn succinte injection for condition for which it ws not prescribed. Do not give sumtriptn succinte injection to other people, even if they hve the sme symptoms you hve. It my hrm them. This Ptient Informtion leflet summrizes the most importnt informtion bout sumtriptn succinte injection. If you would like more informtion, tlk with your helthcre provider. You cn sk your helthcre provider or phrmcist for informtion bout sumtriptn succinte injection tht is written for helthcre professionls. Wht re the ingredients in sumtriptn succinte injection? Active ingredient: sumtriptn succinte Inctive ingredients: sodium chloride, wter for injection This Ptient Informtion leflet hs been pproved by the U.S. Food nd Drug Administrtion. The brnd nmes mentioned in this document re the trdemrks of their respective owners. Fresenius Kbi USA, LLC Lke Zurich, IL C Revised: April 01