Professional Drug Information > Imitrex

Sumatriptan (Systemic)

VA CLASSIFICATION
Primary: CN105

Commonly used brand name(s): Imitrex.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antimigraine agent—

Indications

General considerations
Sumatriptan should not be prescribed for a patient who has not previously been diagnosed as a migraineur, or administered to a migraineur with atypical symptoms, until it has been determined that the patient's headache is not occurring secondary to an evolving potentially serious neurological condition (e.g., cerebrovascular accident or subarachnoid hemorrhage). ^{{42} {43}}

Accepted

Headache, migraine (treatment)—Sumatriptan is indicated to relieve (abort) acute migraine headaches (with or without aura) ^{{01} {02} {03} {04} {05} {06} {07} {08}} in patients who do not obtain sufficient relief with analgesics, such as acetaminophen, aspirin, or nonsteroidal anti-inflammatory drugs (NSAIDs). ^{{09} {10} {11}} Sumatriptan also relieves the nausea, vomiting, photophobia, and phonophobia that frequently occur in association with migraine headaches ^{{01} {03} {04} {07} {08}}.
—When incapacitating migraines occur more frequently than twice a month ^{{09} {12} {13}}, prophylactic treatment is recommended to reduce the severity and duration, as well as the number, of headaches. Sumatriptan is not used for this purpose. Beta-adrenergic blocking agents ^{{09} {11} {12} {13} {14}}, calcium channel blocking agents ^{{09} {11} {12} {13} {14}}, tricyclic antidepressants ^{{09} {11} {12} {13} {14}}, monoamine oxidase inhibitors ^{{09} {11} {12} {13} {14}}, methysergide ^{{09} {11} {12} {13} {14}}, pizotyline (pizotifen [not commercially available in the U.S.]) ^{{09} {11}}, and sometimes cyproheptadine ^{{09} {11} {12} {13}} (especially in children) ^{13} are used for prophylaxis. Other measures that may reduce the need for medication in migraineurs include identification and avoidance of headache precipitants ^{{12} {13} {14} {15}} and relaxation and/or biofeedback techniques ^{12}.

Headache, cluster (treatment)—Sumatriptan injection is indicated for the relief of acute cluster headache episodes ^{{49} {52}}. Cluster headaches may occur daily, often more than once a day, for several months (a cluster period), followed by a headache-free interval ^{{09} {13} {14} {15}}.

Unaccepted
Sumatriptan is not recommended for long-term migraine prophylaxis ^{02}.

Sumatriptan is not recommended for treatment of basilar artery migraine or hemiplegic migraine. Efficacy and safety in these conditions have not been established. ^{{01} {02} {38}}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Synthetic. Sumatriptan is structurally related to serotonin (5-hydroxytryptamine, 5-HT) ^{{17} {19}}
Molecular weight—
    Sumatriptan succinate: 413.5 ^{20}

pKa—


Sumatriptan succinate ^{02}:
    pKa ₁ (succinic acid)—4.21 and 5.67
    pKa ₂ (tertiary amine group)—9.63
    pKa ₃ (sulfonamide group)— > 12

    Sumatriptan succinate: Readily soluble in water and in 0.9% sodium chloride solution. ^{{01} {02}}

Mechanism of action/Effect:

Although sumatriptan's mechanism of action has not been established, ^{{17} {19}} suppression of migraine headaches may result from sumatriptan-induced decreases in the firing of serotonergic (5-hydroxytryptaminergic, 5-HT) neurons. ^{22} Specifically, it is thought that agonist activity at the 5-HT _1D receptor subtype provides relief of acute headache. ^{{23} {24}} Sumatriptan is a highly selective agonist at this receptor subtype; ^{{01} {17} {18} {21} {23}} it has no significant activity at other 5-HT receptor subtypes ^{{01} {02} {17} {19}} or at adrenergic, dopaminergic, muscarinic, or benzodiazepine receptors. ^{{01} {17} {19} {21}}

It has been proposed that constriction of cerebral blood vessels resulting from 5-HT _1D receptor stimulation reduces the pulsation that may be responsible for the pain of vascular headaches. ^{{02} {17} {18} {19}} Studies in humans have shown that blood flow velocity in the middle cerebral arteries is significantly reduced during a migraine on the side of the headache, that relief of the headache by sumatriptan is accompanied by return of the blood flow velocity in these vessels to normal, and that sumatriptan treatment does not induce other changes in cerebral hemispheric blood flow. ^{{17} {25} {26}} However, other studies have not consistently shown a significant correlation between dilatation of cerebral blood vessels and pain or other symptoms of migraine headaches, or between medication-induced vasoconstriction and relief of these headaches. ^{22}

It has also been proposed that neurogenic inflammation in areas innervated by the trigeminal nerve may contribute to the development of migraine headaches. ^{{17} {19} {21} {23} {27}} Although the cause of the inflammation has not been established, there is some evidence that serotonergic mechanisms may be involved. ^{{17} {18}} Sumatriptan may also relieve migraines by decreasing release of neuropeptides and other mediators of inflammation ^{{17} {19} {21}} and by reducing extravasation of plasma proteins. ^{{17} {18} {19} {28}} A study in humans has demonstrated that concentrations of calcitonin gene-related peptide, a substance that increases vascular permeability and promotes plasma protein extravasation, ^{17} are elevated during a migraine and return to normal as the headache is relieved by sumatriptan. ^{29}

Absorption:

Nasal—Rapid; bioavailability is low (approximately 17%), primarily because of presystemic hepatic metabolism and incomplete absorption. ^{56}

Oral—Rapid; ^{{02} {30}} bioavailability is low (approximately 15% of a dose), ^{{01} {17} {30} {49}} primarily because of presystemic hepatic metabolism ^{{02} {17} {19} {30}} and, to a lesser extent, because of incomplete absorption. ^{{02} {19} {30}} The rate and extent of absorption are not affected to a clinically significant extent by administration with food ^{{02} {17} {19}} or by the gastric stasis that may accompany migraine headaches. ^{{17} {18} {30} {31}}

Subcutaneous—Rapid; bioavailability is approximately 97% ^{{01} {02} {19} {30} {49}} of that achieved with an intravenous injection. ^{01}

Distribution:

Sumatriptan is rapidly and extensively distributed to tissues ^{{17} {30}} but passage across the blood-brain barrier is limited. ^{{17} {19} {28} {29}}

Protein binding:

In plasma—Low (14 to 21%) ^{{01} {02} {17} {19} {30}}

Biotransformation:

Hepatic ^{02} and extensive; ^{02} approximately 80% of a dose is metabolized. ^{{17} {18} {19} {30}} The major metabolite is an inactive indole acetic acid derivative. ^{{02} {17} {18} {19} {30}}

In vitrostudies with human hepatic microsomes indicate that sumatriptan is metabolized by monoamine oxidase (MAO), primarily the A isoenzyme (MAO-A). ^{42}

Half-life:


Distribution:

Subcutaneous administration: Approximately 15 minutes ^{01}



Elimination:

Subcutaneous ^{{02} {17} {18}} or oral ^{{01} {02} {17} {18}} administration: Approximately 2.5 hours. One study reported a terminal half-life of approximately 7 hours that became apparent about 12 hours after administration of multiple oral doses ^{{18} {19} {30}}, but did not contribute substantially to the overall disposition of the medication. ^{{18} {30}}

Nasal administration: Approximately 2 hours. ^{56}


Onset of action:


Nasal:

Within 15 minutes ^{56}



Oral:

Within ^{07} 30 minutes ^{{02} {07}}



Subcutaneous:

Relief of headache pain: Within 10 minutes ^{{01} {03}}

Relief of migraine-associated nausea, vomiting, photophobia, phonophobia: Within 20 minutes ^{03}


Time to peak serum concentration

Nasal (single 5-mg, 10-mg, or 20-mg dose): Between 1 and 1.5 hours ^{57}

Oral (single 100-mg dose): Approximately 2 hours ^{{17} {19} {30} {49}} (range, 0.5 to 5 hours). ^{02} The wide interindividual variability found in pharmacokinetic studies may be related to the appearance of multiple peaks in the concentration over time. ^{{17} {18} {19} {30}} Approximately 80% of the maximum value is achieved within 45 minutes. ^{{17} {30}}

Subcutaneous (single 6-mg dose): Approximately 12 minutes ^{01} (range, 5 to 20 minutes). ^{{17} {30}}

Peak serum concentration:

Nasal (5-mg and 20-mg dose): Approximately 5 nanograms per mL (0.012 micromoles/L) and 16 nanograms/mL (0.039 micromoles/L), respectively. ^{57}

Oral (single 100-mg dose): Approximately 54 nanograms per mL ^{{17} {19} {30}} (0.13 micromoles/L) (range, 26.7 to 137 nanograms per mL ^{30} [0.06 to 0.33 micromoles/L]).

Subcutaneous (single 6-mg dose): Approximately 72 to 74 nanograms per mL; ^{{01} {17} {19} {30}} (0.17 to 0.18 micromoles/L) (range, 54.9 to 108.4 nanograms per mL ^{30} [0.13 to 0.26 micromoles/L]).


Time to peak effect


Relief of headache (i.e., moderate or severe pain being reduced to mild or no pain):

Oral (single 100-mg dose): Within 2 hours in 50 to 75%, ^{{02} {06} {07}} and within 4 hours in an additional 15 to 25%, ^{02} of patients.

Subcutaneous (single 6-mg dose): Within 1 hour in 70%, and within 2 hours in an additional 12%, of patients. ^{{01} {03} {04} {05}}



Relief of associated symptoms (nausea, vomiting, photophobia, phonophobia) :

Oral (single 100-mg dose): Within 2 hours. ^{07}

Subcutaneous (single 6-mg dose): Within 1 hour in 68%, and within 2 hours in an additional 13%, of patients. ^{04}


Duration of action:

Return of migraine headache occurs within 24 to 48 hours in approximately 40% of patients who initially obtain a beneficial response to sumatriptan, i.e., after moderate or severe headache pain has been reduced to mild or no pain. ^{{04} {05} {06} {07} {08}} Whether this represents development of a new migraine or breakthrough of a prolonged migraine after the effects of sumatriptan have worn off has not been established. ^{{03} {19}}

Elimination:
    Renal, via active renal tubular secretion, ^{{17} {18} {19}} following hepatic metabolism. ^{{02} {17} {19}} Approximately 80% of a dose is eliminated as metabolites. ^{{01} {17} {18} {19}} After nasal administration, approximately 3% of the dose is eliminated as unchanged sumatriptan and 35% as the indole acetic acid metabolite. ^{56} After oral administration, approximately 57% of a dose is eliminated in the urine (3% of the dose as unchanged sumatriptan, 35% as the indole acetic acid metabolite, and 8% as the glucuronide conjugate of the indole acetic acid metabolite) and another 38% of the dose is eliminated in the feces (9% as unchanged sumatriptan and 11% as the indole acetic acid metabolite). ^{{17} {30}} After subcutaneous administration, approximately 22% of a dose is eliminated in the urine as unchanged sumatriptan and another 38% as the indole acetic acid metabolite. ^{01} Only 0.6% and 3.3% of a dose are eliminated in the feces as unchanged sumatriptan and the indole acetic acid metabolite, respectively. ^{{17} {30}}
    The effects of renal function impairment on clearance of sumatriptan have not been studied. ^{{01} {18}} Approximately 80% of the total clearance is via hepatic biotransformation; therefore, hepatic function impairment may produce clinically significant elevations in the bioavailability of orally administered sumatriptan. ^{{17} {18} {49}} However, the elevation in the bioavailability of intranasal sumatriptan is not clinically significant. ^{56}


Precautions to Consider

Tumorigenicity

No evidence of tumorigenicity was found in a 104-week study in rats given sumatriptan by oral gavage in quantities sufficient to achieve peak concentrations up to > 100 times higher than are achieved in humans with a 6-mg subcutaneous dose. Also, although no evidence of tumorigenicity was found in a 78-week study in mice given sumatriptan continuously in drinking water, this study did not use the maximum tolerated dose and is therefore considered inadequate for evaluating potential tumorigenicity in the mouse. ^{01}

Mutagenicity

No evidence of mutagenicity was found in a variety of in vitro and in vivo studies ^{02}.

Pregnancy/Reproduction
Fertility—
No adverse effects on fertility were found in reproduction studies ^{{01} {02}} in rats given up to 60 mg per kg of body weight (mg/kg) per day subcutaneously or up to 500 mg/kg per day orally. ^{02}

Pregnancy—
Adequate and well-controlled studies have not been done in pregnant women ^{{01} {02}}.

Studies in rats receiving daily subcutaneous injections of sumatriptan prior to and during pregnancy showed no evidence of teratogenicity or embryolethality ^{01}. Also, embryolethality did not occur in studies in rats receiving sumatriptan intravenously throughout organogenesis in doses producing plasma concentrations > 50 times higher than those produced by the recommended human subcutaneous dose ^{01}. However, maternal toxicity and embryotoxicity occurred in rats given oral doses of 1000 mg/kg per day, but not those given 500 mg/kg per day, during organogenesis ^{02}. Also, term fetuses from Dutch Stride rabbits treated during organogenesis with oral sumatriptan exhibited an increased incidence of cervicothoracic vascular defects and minor skeletal abnormalities ^{01}. The functional significance of these abnormalities is not known ^{01}. In other studies, daily administration of sumatriptan to pregnant rabbits throughout the period of organogenesis using oral doses of 100 mg/kg per day ^{02} or intravenous doses sufficient to produce peak concentrations > 3 times those produced in humans after a 6-mg subcutaneous dose ^{01} resulted in maternal toxicity and/or embryolethality.

FDA Pregnancy Category C ^{01}.

Breast-feeding

Sumatriptan is distributed into human breast milk ^{49}. However, problems in humans have not been documented ^{{01} {02}}.

Pediatrics and adolescents
Appropriate studies on the relationship of age to the effects of sumatriptan have not been done in patients up to 18 years of age. Safety and efficacy have not been established. ^{{01} {02}}


Geriatrics


Information on the relationship of age to the effects of sumatriptan in geriatric patients is extremely limited ^{02}. No unusual adverse, age-related phenomena occurred in patients older than 60 years of age who participated in clinical trials ^{01}. However, most published studies report excluding patients older than 65 years of age ^{{04} {05} {07} {08} {16}}. Studies in a limited number of healthy subjects 65 to 86 years of age found no differences in pharmacokinetic parameters between these older individuals and younger subjects ^{{01} {02} {17} {18} {30}}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Antidepressants, selective 5-hydroxytryptamine uptake inhibitor or
Lithium or
» Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline    (concurrent use of any of these agents with sumatriptan may lead to a potentially dangerous hyperserotonergic state or other adverse effects; sumatriptan should be used with caution in patients receiving these medications ^{{02} {18} {39} {51}})

    (sumatriptan is metabolized by the MAO-A isoenzyme; pretreatment of human subjects with an MAO-A inhibitor has been shown to decrease sumatriptan clearance, resulting in substantial increases in the area under the sumatriptan plasma concentration-time curve and the sumatriptan half-life. MAOIs that inhibit the MAO-A isoenzyme include furazolidone, isocarboxazid, moclobemide, phenelzine, toloxatone, and tranylcypromine. MAOIs that inhibit only the MAO-B isoenzyme, such as selegiline, did not produce these effects ^{44})


    (oral and intranasal sumatriptan should not be used during or within 14 days following administration of an MAO inhibitor; concurrent use of sumatriptan injection with MAO inhibitors is not generally recommended; however, concurrent use would require a dosage adjustment of sumatriptan injection ^{50})


Dihydroergotamine or
Ergotamine or
Methysergide    (a delay of 24 hours between administration of dihydroergotamine, ergotamine, or methysergide and sumatriptan is recommended because of the possibility of additive and/or prolonged vasoconstriction ^{{01} {02} {38}})


Selective serotonin reuptake inhibitors, such as:
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline    (concurrent use may result in weakness, hyperreflexia, and incoordination; careful monitoring is recommended)

^{56}

Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Blood pressure and
Peripheral vascular resistance    (may be increased, although increases are generally mild and transient; in clinical studies, clinically significant blood pressure elevations [increase in systolic pressure by 20 mm Hg or to 180 mm Hg; increase in diastolic pressure by 15 mm Hg or to 105 mm Hg] occurred in fewer than 1% of the patients; ^{01} blood pressure changes after oral administration are smaller and occur more slowly than after subcutaneous administration ^{02})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Coronary artery disease, especially:
Angina pectoris
Myocardial infarction, history of
Myocardial ischemia, silent documented
Prinzmetal's angina or
» Other conditions in which coronary vasoconstriction would be detrimental    (although sumatriptan has only a slight vasoconstrictive effect on coronary arteries, ^{17} sumatriptan-induced myocardial ischemia has been documented, ^{{01} {32} {33} {49}} primarily in patients with a history of coronary artery disease or susceptibility to coronary artery vasospasm ^{01})


» Hypertension, uncontrolled    (may be exacerbated ^{{01} {02}})


Risk-benefit should be considered when the following medical problems exist
Cardiac arrhythmias, especially:^{02}
» Tachycardia or^{02}
» Cerebrovascular accident, history of^{02}    (sumatriptan may cause cerebral hemorrhage, subarachnoid hemorrhage, or stroke; caution should be used when administering in patients at risk for cerebrovascular events ^{49})


» Coronary artery disease, predisposition to    (sumatriptan has rarely caused serious coronary adverse effects; patients in whom coronary artery disease is a possibility on the basis of age or the presence of other risk factors, such as diabetes, hypercholesterolemia, obesity, a strong family history of coronary artery disease, or tobacco smoking should be evaluated for the presence of cardiovascular disease before sumatriptan is prescribed; even after a satisfactory evaluation, the advisability of administering the patient's first dose under medical supervision should be considered ^{{44} {45}})


» Hepatic function impairment or
Renal function impairment    (caution is recommended because clearance of sumatriptan may be impaired; ^{01} because about 80% of the total clearance is via hepatic biotransformation, hepatic function impairment should be more likely than renal function impairment to produce clinically significant increases in sumatriptan concentration; dosage adjustment is recommended in patients with hepatic impairment ^{{17} {18} {49}})


Hypertension, controlled    (elevations of systolic and diastolic blood pressure may occur, especially after subcutaneous administration, although these effects are generally mild and transient in hypertensive patients whose blood pressure is adequately controlled by medication; in clinical studies, patients with controlled hypertension experienced mean peak increases of 6 mm Hg, which usually started within 30 minutes after subcutaneous administration and persisted for less than an hour ^{01})


» Sensitivity to sumatriptan




Side/Adverse Effects

Note: Most of the adverse effects reported with sumatriptan are mild ^{{04} {05}} and transient (lasting less than 1 hour after subcutaneous injection ^{{03} {04} {05}} and 2 hours or less after oral administration ^{02}) and resolve without treatment. ^{04} Although several deaths have been reported after administration of sumatriptan, a direct causal relationship could not be established in most cases. Most of the fatalities occurred 3 hours or more after administration and probably were spontaneous events or were caused by underlying disease. Some of the deaths were attributed to strokes, cerebral hemorrhages, or other cerebrovascular events. However, migraineurs are known to be at increased risk of cerebrovascular accidents or transient ischemic attacks; in many of these cases a cerebrovascular event, rather than a migraine, may have been causing the symptoms that led to sumatriptan administration. ^{42}
Some of the adverse events reported after administration of sumatriptan (e.g., nausea, vomiting, malaise, fatigue, dizziness, vertigo, weakness, drowsiness, sedation) often occur during and/or following a migraine headache; whether sumatriptan contributes to their occurrence has not been established. ^{{05} {17} {34}}
Although a causal relationship to sumatriptan has not been established, the following adverse events have also been reported in open, uncontrolled studies (incidences < 1%) and/or postmarketing: cardiac arrhythmias (atrial fibrillation, ventricular fibrillation, ventricular tachycardia, sinus arrhythmia), other transient changes in the electrocardiogram (ST segment elevations, other ST or T-wave changes, prolongation of PR or QTc intervals, nonsustained ventricular premature beats, isolated junctional ectopic beats, atrial ectopic beats, delayed activation of the right ventricle), hypotension, bradycardia, syncope, Prinzmetal"s angina, vasodilatation, Raynaud"s disease, acute renal failure, seizures, cerebrovascular accident, dysphagia, subarachnoid hemorrhage, polydipsia, dehydration, gastrointestinal reflux, dyspnea, erythema, pruritus, skin rashes, peptic ulceration, gallstones, swelling of extremities, transient hemiplegia, hysteria, globus hystericus, intoxication, mental depression, myoclonia, monoplegia or diplegia, dystonia, dysuria, urinary frequency, renal calculus, photosensitivity, and exacerbation of sunburn. ^{{01} {42} {44}}
Note: Sumatriptan causes corneal opacities and defects in the corneal epithelium in dogs; this raises the possibility that these changes may occur in humans. There is not systematic evaluation for these effects in clinical trials, and no specific recommendations for monitoring are being offered, but health care professionals should be aware of the possibility of changes.^{58}{59}{60}



The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent (1 to 3%) with subcutaneous administration; ^{{01} {02}} less frequent or rare (< 1%) with oral or nasal administration ^{02}
    
Chest pain, severe
    
difficulty in swallowing
    
heaviness, tightness, or pressure in chest and/or neck
Note: Although chest pain and heaviness, tightness, or pressure in the chest and neck are suggestive of angina pectoris, ^{01} monitoring of the electrocardiogram (ECG) during such symptoms in clinical studies failed to detect evidence of myocardial ischemia. ^{{18} {34}} Conversely, ECG monitoring detected new T-wave abnormalities in a small number of patients, most of whom had abnormal pretreatment ECGs, who were not experiencing relevant symptoms. ^{34} However, sumatriptan-induced coronary artery vasospasm resulting in symptomatic myocardial ischemia ^{{01} {32} {33}} and myocardial infarction ^{40} have been documented in a few patients, ^{{01} {32} {33}} primarily patients with a history of coronary artery disease or susceptibility to coronary artery vasospasm. ^{01} Several fatalities associated with such complications have been reported following administration of sumatriptan, but in most cases a causal relationship has not been established. ^{42}



Incidence rare
    
Anaphylactic or anaphylactoid reaction (changes in facial skin color; skin rash, hives, and/or itching; fast or irregular breathing; puffiness or swelling of the eyelids or around the eyes, face, or lips; shortness of breath, troubled breathing, tightness in chest, and/or wheezing)
    
dermatitis, allergic ( skin rash, hives, and/or itching)
^{42}    
seizures ^{56}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent ^{{01} {02} {34}}
    
Injection site reaction (burning, pain, or redness)
    
irritation in the nose (burning; discharge; pain; or soreness)—occurs with nasal spray only
    
nausea or vomiting
    
taste perversion (change in sense of taste)—occurs with nasal spray only

Note: Nausea and vomiting often occur in conjunction with migraine headaches; they are not necessarily caused by ^{17} (and may actually be relieved by) ^{{01} {03} {04} {07} {08}} sumatriptan. However, these effects occurred more frequently after oral than after subcutaneous administration of sumatriptan in clinical trials ^{{02} {17} {34}}, possibly because of the unpleasant taste of the dispersible tablet used in the studies ^{17}.


Incidence up to 13.5% with subcutaneous administration; less frequent (1 to 3%) or rare (< 1%) with nasal or oral administration ^{{01} {02} {34}}
    
Atypical sensations (sensation of burning, warmth, heat, numbness, tightness, or tingling; feeling cold; ``strange"" feeling)
    
discomfort in jaw, mouth, throat, tongue, nasal cavity, or sinuses
    
dizziness
    
drowsiness
    
flushing
    
lightheadedness
    
muscle aches, cramps, or stiffness
    
weakness
Note: Flushing and sensations of burning, warmth, or heat generally disappear within 10 to 30 minutes after administration of a subcutaneous dose ^{34}.



Incidence less frequent (1 to 3%) with subcutaneous administration; less frequent or rare (< 1%) with oral and nasal administration
    
Anxiety
    
general feeling of illness or tiredness
    
vision changes





Overdose
For specific information on the agents used in the management of sumatriptan overdose, see:    • Nitroglycerin in Nitrates (Systemic) .


For more information on the management of overdose or unintentional ingestion contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
Overdose has not been reported in humans. Signs and symptoms that might be anticipated, based on animal studies, include ataxia, convulsions, cyanosis, erythema of extremities, inactivity, injection site reactions (desquamation, hair loss, scab formation), mydriasis, paralysis, reduced respiratory rate, and tremor. ^{01}

Treatment of overdose
Although there is no experience with overdose of sumatriptan, treatment may involve:

To decrease absorption—Emptying the stomach by induction of emesis or performing gastric lavage (if ingested orally).

Monitoring—For continuing chest pain or other symptoms consistent with angina pectoris: Monitoring the electrocardiogram for evidence of ischemia ^{01} and administering appropriate treatment (e.g., nitroglycerin or other coronary artery vasodilators) as needed. Some patients may require further evaluation to determine whether previously undiagnosed coronary artery disease is present. See the package insert or Nitroglycerin in Nitrates (Systemic) for specific dosing guidelines for use of this product.

Monitoring of patients who have received an overdose of sumatriptan nasal spray should continue for at least 10 hours or while signs or symptoms persist ^{56}.

Supportive care—Monitoring the patient and instituting supportive treatment as needed. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Sumatriptan (Systemic).

In providing consultation, consider emphasizing» the following selected information ( = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to sumatriptan
Other medications, especially monoamine oxidase inhibitors
Other medical problems, especially cerebrovascular accident (history of); coronary artery disease, predisposition to coronary artery disease, or other conditions that may be adversely affected by coronary artery constriction; hepatic function impairment; hypertension (uncontrolled); and tachycardia

Proper use of this medication
» Not administering if atypical headache symptoms are present; checking with physician instead

Administering after onset of headache pain

Additional benefit may be obtained if the patient lies down in a quiet, dark room after administering medication

» Not using additional doses if a first dose does not provide substantial relief; additional sumatriptan is not likely to be effective in these circumstances; taking alternate medication as previously advised by physician, then checking with physician as soon as possible

» Taking additional doses, if needed, for return of migraine after initial relief was obtained, provided that prescribed limits (quantity used and frequency of administration) are not exceeded

» Compliance with prophylactic therapy, if prescribed

Proper administration of

Tablets
Swallowing whole; not breaking, crushing or chewing before taking; taking with full glass of water

Injection
Reading patient instructions provided with medication

Proper injection technique

Discarding used cartridge as directed in patient instructions, using container provided; not discarding autoinjector unit because refill cartridges are available

Nasal
Reading patient instructions provided with medication

» Proper dosing

» Proper storage

Precautions while using this medication
Checking with physician if usual dose fails to relieve three consecutive headaches, or frequency and/or severity of headaches increases

Avoiding alcohol, which aggravates headache

» Caution if drowsiness or dizziness occurs


Side/adverse effects
Contacting physician immediately if severe chest pain or signs and symptoms of anaphylactoid reaction occur

Contacting physician at once if mild pain or tightness in chest or throat occurs and persists for more than 1 hour; even if symptoms are of shorter duration, not using medication again without first consulting physician

Signs and symptoms of other potential side effects, including dysphagia, palpitation, and skin rash or eruptions


General Dosing Information
Clinical studies have not shown a correlation between the duration of a migraine prior to administration of sumatriptan and its ability to abort an acute attack ^{{04} {05} {07} {08}}. Because a recent study has shown that administration of sumatriptan during a preheadache aura may neither prevent nor significantly delay the onset of the headache ^{47}, it is recommended that sumatriptan not be administered prior to the appearance of headache pain ^{48}.

Lying down and relaxing in a quiet, darkened room after administering a dose of antimigraine medication may contribute to relief of migraines ^{{13} {35}}.

Additional doses of sumatriptan should not be administered to patients who do not obtain substantial relief (reduction of initially moderate or severe headache pain to mild or no pain) within 1 or 2 hours after the initial dose ^{02}. Several clinical trials have failed to demonstrate that a second dose benefits these patients ^{{01} {03} {04} {28}}. It is recommended that an analgesic be used as ``rescue'' medication in the event of an unsatisfactory response to sumatriptan ^{02}; use of dihydroergotamine, ergotamine, or methysergide is not recommended because of the possibility of additive or prolonged vasoconstriction ^{{01} {02}}. Also, the prescriber should be contacted as soon as possible if sumatriptan is ineffective because of the possibility that the patient's symptoms are being caused by a cerebrovascular event ^{{42} {46}}. However, patients who do not respond to sumatriptan during one migraine attack may obtain a satisfactory response during subsequent attacks ^{{02} {19}}.

Return of migraine headache occurs within 24 to 48 hours in about 40% of patients who initially obtain a beneficial response to sumatriptan ^{{04} {05} {06} {07} {08}}. Whether this represents development of a new migraine or breakthrough of a prolonged migraine after the effects of sumatriptan have worn off has not been established ^{{03} {19}}. Recurrences following an initial beneficial response may be treated with additional sumatriptan ^{{01} {02} {19}}.

Tolerance to the effects of sumatriptan did not occur when the medication was used intermittently to relieve acute migraines for longer than 6 months ^{{17} {55}}.

The possibility that overuse of sumatriptan by migraineurs may lead to dependence on the medication and to the development of withdrawal (rebound) or chronic, intractable headaches (as has been documented with too-frequent use of ergotamine and/or analgesics by these patients) has not been evaluated. Some headache specialists recommend that, until more definitive information about the risk of cumulative toxicity and/or dependence is available, courses of sumatriptan treatment should not be administered more often than every five to seven days ^{39}.

For oral dosage form only
Sumatriptan tablets are to be swallowed whole ^{02} (i.e., with the film coating intact) because the unpleasant taste of the contents may cause taste disturbances and/or an increased risk of nausea and vomiting ^{{17} {34}}.

For parenteral dosage form only
Sumatriptan is not to be given intravenously ^{{01} {02}}. Clinical trials have shown that intravenous administration is associated with a higher incidence of adverse effects than subcutaneous administration ^{{17} {18} {34}}. Specifically, the risk of coronary artery vasospasm ^{{01} {02} {34}} and angina ^{02} may be increased. Long-term users with risk factors of coronary artery disease should receive periodic cardiovascular evaluations ^{49}.


Oral Dosage Forms

Note: Sumatriptan tablets contain sumatriptan succinate. However, dosage and strength are expressed in terms of sumatriptan base ^{02}.

SUMATRIPTAN TABLETS

Usual adult dose
Antimigraine agent
Oral, 25, 50 or 100 mg (base) as a single dose. If necessary, additional doses up to 100 mg may be taken at intervals of at least two hours, up to a maximum of 200 mg a day^{49}{59}. Individuals vary in response to doses of sumatriptan. The choice of dose should be made on an individual basis.^{59}
For relief of migraine headache that returns after an inital treatment with sumatriptan tablets: the dose may be repeated after two hours, up to a maximum of 200 mg once a day^{59}
For relief of migraine headache that returns after an initial treatment with sumatriptan injection, additional single oral doses of up to 100 mg a day may be given at intervals of at least two hours between tablet doses, up to a maximum of 200 mg a day.^{59}
The maximum single dose for patients with hepatic impairment should not exceed 50 mg.


Note: There is evidence that an initial doses of 50 mg and 100 mg provides substantially greater relief than a dose of 25 mg. There is also evidence that doses of 100 mg do not provide a greater effect than 50 mg.^{59}


Usual adult prescribing limits
Antimigraine agent
Oral, not more than 200-mg (base) in twenty-four hours ^{49}{59}.


Usual pediatric dose
Safety and efficacy in patients up to 18 years of age have not been established ^{49}.

Strength(s) usually available
U.S.—


25 mg (base [as the succinate salt]) (Rx) [Imitrex ( lactose)]


50 mg (base [as the succinate salt]) (Rx) [Imitrex ( lactose)]


100 mg (base [as the succinate salt]) (Rx) [Imitrex ( lactose)]^{59}

Canada—


50 mg (base [as the succinate salt]) (Rx) [Imitrex^{02} (lactose)]


100 mg (base [as the succinate salt]) (Rx) [Imitrex^{02} (lactose)]

Packaging and storage:
Store between 2 and 30 °C (36 and 86 °F), unless otherwise specified by manufacturer ^{{02} {49}}.

Auxiliary labeling:
   • Swallow tablets whole.
   • Take with a full glass of water.



Nasal Dosage Forms

SUMATRIPTAN NASAL SOLUTION

Usual adult dose
Antimigraine agent
Intranasal, 5 mg or 10 mg (1 or 2 sprays) in each nostril, respectively, or 20 mg (1 spray) into one nostril as a single dose ^{56}.
Additional doses should not be administered for the same migraine attack. However, a dose may be administered for subsequent attacks provided a minimum of two hours has elapsed since the last dose.


Usual adult prescribing limits
Antimigraine agent
Nasal, not more than 40 mg in twenty-four hours ^{56}.


Usual pediatric dose
Safety and efficacy in patients up to 18 years of age have not been established ^{56}.

Strength(s) usually available
U.S.—


5 mg (base [as the hemisulphate salt]) (Rx) [Imitrex^{56} (monobasic potassium phosphate) (anhydrous dibasic sodium phosphate) ( sulfuric acid) (sodium hydroxide) (purified water)]


20 mg (base [as the hemisulphate salt]) (Rx) [Imitrex^{56} (monobasic potassium phosphate) (anhydrous dibasic sodium phosphate) (sulfuric acid) (sodium hydroxide) (purified water )]

Canada—


5 mg (base [as the hemisulphate salt]) (Rx) [Imitrex^{56} (monobasic potassium phosphate) (anhydrous dibasic sodium phosphate) (sulfuric acid) (sodium hydroxide) (purified water )]


20 mg (base [as the hemisulphate salt]) (Rx) [Imitrex^{57} (monobasic potassium phosphate) (anhydrous dibasic sodium phosphate) (sulfuric acid) (sodium hydroxide) (purified water )]

Packaging and storage:
Store between 2 and 30 °C (36 and 86 °F), protected from light and from freezing, unless otherwise specified by manufacturer ^{01}.



Parenteral Dosage Forms

Note: Sumatriptan injection contains sumatriptan succinate. However, dosage and strength are expressed in terms of sumatriptan base ^{{01} {02}}.

SUMATRIPTAN INJECTION

Usual adult dose
Antimigraine agent
Subcutaneous, injected into the outer thigh or the outer upper arm, 6 mg (base). If a beneficial response to this dose is not obtained within one or two hours, an additional 6-mg dose may be administered, at least one hour after the first dose, if headache pain returns or increases in severity. Controlled clinical trials have not shown that there is a clear benefit associated with the administration of a second 6–mg dose in patients who failed to respond to the first injection.^{{60} {49}}


Note: Lower doses may be administered if the patient does not tolerate the usual dose. The auto-injector should not be used for this purpose; doses should be withdrawn from the single-dose vial, using a separate syringe. ^{49}
One study compared the effects of 6-mg and 8-mg subcutaneous doses of sumatriptan (base) in migraineurs. The 8-mg dose was not significantly more effective than the 6-mg dose; ^{04} therefore, doses higher than 6 mg are not recommended. ^{49}


Usual adult prescribing limits
Antimigraine agent
Single subcutaneous doses should not exceed 6 mg (base), and should be separated by at least one hour. No more than two 6-mg doses should be administered within twenty-four hours ^{{01} {02} {49}{60}}.


Note: Some clinicians recommend administering no more than two 6-mg doses within forty-eight hours ^{41}.


Usual pediatric dose
Safety and efficacy in patients up to 18 years of age have not been established ^{{01} {02} {49}}.

Strength(s) usually available
U.S.—


6 mg (base [as the succinate salt]) per 0.5 mL (Rx) [Imitrex ( sodium chloride 3.5 mg per 0.5 mL)]

Canada—


6 mg (base [as the succinate salt]) per 0.5 mL (Rx) [Imitrex]

Packaging and storage:
Store between 2 and 30 °C (36 and 86 °F), protected from light and from freezing, unless otherwise specified by manufacturer ^{01}.

Developed: 03/25/1998
Revised: 08/22/2001

References

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35. Reviewers" consensus on Vascular Headache Suppressants, Ergot Derivative–containing (Systemic) monograph, draft for USP DI 1993.
    

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38. Reviewers" consensus on draft, 2/93.
    

39. Reviewers" consensus on ballot, 4/93.
    

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41. Reviewer comments.
    

42. Imitrex package insert (Glaxo—US), Rev 8/94, Rec 10/94.
    

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48. Reviewers" response to ballot, 12/94.
    

49. Imitrex Tablets package insert (Cerenex—US), Rev 6/96, Rec 6/96.
    

50. Imitrex Injection package insert (Cerenex—US), Rev 5/96, Rec 6/96.
    

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53. MacIntyre PD, Bhargava B, Hogg KJ, et al. Effect of subcutaneous sumatriptan, a selective 5HT ₁ agonist, on the systemic, pulmonary and coronary circulation. Circulation 1993; 87: 401-5.
    

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60. Product Information: Imitrex® Injection, sumatriptan, GlaxoWellcome, Research Triangle Park, NC (PI revised 3/2001) PI Reviewed 8/2001
    

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