Alsuma

Read the Patient Information Leaflet available from your pharmacist before you start using sumatriptan and each time you get a refill. Ask your doctor or pharmacist if you have any questions.This medication can be injected by using a syringe/needle, an auto-injector, or a needle-free device (depending on the brand prescribed). Learn all preparation and usage instructions in the product package. If any of the information is unclear, consult your doctor or pharmacist. Make sure you understand the correct technique for injection and how to properly dispose of needles, syringes, auto-injectors, needle-free devices, and unused medication.Inject the medication just below the skin as soon as the symptoms of your migraine/headache appear. Before injecting each dose with a syringe and needle or an auto-injector, clean the injection site with rubbing alcohol. If using a needle-free device, your skin should be clean and dry before injecting. This medication should never be injected directly into a vein (IV) or into a muscle (IM). Also, never inject this medication through clothing.If there is no improvement in your symptoms, do not take any more doses of this medication before talking to your doctor. If your symptoms are only partly relieved, or if your headache comes back, you may use a second injection after one hour or as directed by your doctor. Do not use more than 2 injections (12 milligrams) in a 24-hour period. Do not reuse the syringe or the needle-free device. If you are using an auto-injector device, it may be re-used.If your symptoms are only partly relieved or your headache returns, 2 hours after the injection you may switch to sumatriptan taken by mouth instead of using a second injection. After the initial injection you may take sumatriptan by mouth every 2 hours if needed to a maximum of 100 milligrams of tablets in a 24-hour period.If you have never taken this medication before and you have risk factors for heart disease (see Precautions), you may need to be monitored for rare but serious side effects (e.g., chest pain) when you take the first dose. Your doctor may ask you to take the first dose in the office.Your dosage is based on your medical condition and response to therapy. Tell your doctor if your condition does not improve or worsens.Overuse of drugs to treat sudden migraine attacks can lead to worsening of headache (medication overuse headache) or rebound headache. Therefore, do not use this medication more often or for longer than prescribed. Tell your doctor if you need to use this medication more often, if the medication is not working as well, or if you have more frequent or worse headaches. Your doctor may need to change your medication and/or add a separate medication to help prevent the headaches.

See also How to Use section.Before using sumatriptan, tell your doctor or pharmacist if you are allergic to it; or to other triptan drugs (e.g., zolmitriptan, rizatriptan); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.This medication should not be taken if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: heart disease (e.g., chest pain, heart attack), decreased blood flow in the brain (e.g., stroke, transient ischemic attack), blood circulation disease (e.g., ischemic bowel disease), uncontrolled high blood pressure (hypertension), certain types of headaches (hemiplegic or basilar migraine), liver disease.Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain blood circulation disorders (e.g., Raynaud's disease), seizures.Tell your doctor if you have the following risk factors for heart disease: diabetes, family history of heart disease, high blood pressure (controlled), high cholesterol, overweight, smoker, female after menopause, male over age 40.If you are at high risk for heart disease, your doctor may want to check your heart before prescribing sumatriptan.This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely.The risk of heart disease, liver disease, and high blood pressure increases with age. The manufacturer does not recommend the use of sumatriptan in the elderly since they may be more sensitive to the side effects, including an increase in blood pressure.This medication should be taken only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.This drug passes into breast milk and may have undesirable effects on a nursing infant. Avoid breastfeeding for at least 12 hours after using sumatriptan. Consult your doctor before breast-feeding.

Included as part of the PRECAUTIONS section.

Tell your healthcare provider about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Alsuma and other medicines may affect each other, causing side effects.

Especially tell your healthcare provider if you take:

• selective serotonin reuptake inhibitors (SSRIs) such as escitalopram (Lexapro), sertraline (Zoloft), citalopram (Celexa), paroxetine (Paxil), fluoxetine (Prozac, Sarafem, Symbyax), and fluvoxamine (Luvox)
• serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine (Cymbalta) venlafaxine (Effexor)
• monoamine oxidase inhibitors (MAOIs) such as tranylcypromine (Parnate), phenelzine (Nardil), selegiline (Eldepryl, Zelapar), isocarboxazid (Marplan), and rasagiline (Azilect)
• other ergot-containing medications such as dihydroergotamine (D.H.E. 45, MIGRANAL) or methysergide
• other triptans such as sumatriptan (Imitrex, Treximet), eletriptan (Relpax), almotriptan (Axert), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), and zolmitriptan (Zomig)

Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.

Know the medicines you take. Keep a list of them to show your healthcare provider or pharmacist when you get a new medicine.

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. Alsuma may pass into your breast milk and may harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take Alsuma.

Infant exposure to Alsuma can be minimized by avoiding breastfeeding for 12 hours after treatment with Alsuma.

In the U.S.

• Alsuma
• Imitrex
• Imitrex Stat Dose Refill
• Sumavel DosePro
• Zembrace Symtouch

Available Dosage Forms:

• Kit
• Solution

Therapeutic Class: Antimigraine

Pharmacologic Class: Serotonin Receptor Agonist, 5-HT1

Dosing Information

The maximum single recommended dose of Alsuma is 6 mg injected subcutaneously.

The maximum recommended dose that may be given in 24 hours is two doses of Alsuma separated by at least 1 hour. Controlled clinical trials have failed to show a clear benefit with the administration of a second 6 mg dose in patients who have failed to respond to a first dose. A second 6 mg dose should only be considered if some response to a first injection was observed.

Administration Using Alsuma

Alsuma is only for subcutaneous use. Intramuscular or intravascular delivery must be avoided. Patients should be directed to use injection sites with an adequate skin and subcutaneous thickness to accommodate the length of the needle.

Alsuma is for single use only. Visually inspect the medication for particulate matter and discoloration before administration. Do not use if particulates and discolorations are noted. Discard unused portions. [see Patient Counseling Information (17.8)]

Mechanism of Action

Sumatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro-inflammatory neuropeptide release.

Pharmacodynamics

Blood Pressure:

Significant elevation in blood pressure, including hypertensive crisis, has been reported in patients with and without a history of hypertension [see Warnings and Precautions (5.8)].

Peripheral (Small) Arteries:

In healthy volunteers (N = 18), a trial evaluating the effects of sumatriptan on peripheral (small vessel) arterial reactivity failed to detect a clinically significant increase in peripheral resistance.

Heart Rate:

Transient increases in blood pressure observed in some subjects in clinical trials carried out during sumatriptan's development as a treatment for migraine were not accompanied by any clinically significant changes in heart rate.

Pharmacokinetics

Absorption and Bioavailability:

The bioavailability of sumatriptan via subcutaneous site injection to 18 healthy male subjects was 97% ± 16% of that obtained following intravenous injection.

After a single 6-mg subcutaneous manual injection into the deltoid area of the arm in 18 healthy males (age: 24 ± 6 years, weight: 70 kg), the maximum serum concentration (Cmax) of sumatriptan was (mean ± standard deviation) 74 ± 15 ng/mL and the time to peak concentration (Tmax) was 12 minutes after injection (range: 5 to 20 minutes). In this trial, the same dose injected subcutaneously in the thigh gave a Cmax of 61 ± 15 ng/mL by manual injection versus 52 ± 15 ng/mL by autoinjector techniques. The Tmax or amount absorbed was not significantly altered by either the site or technique of injection.

Distribution:

Protein binding, determined by equilibrium dialysis over the concentration range of 10 to 1,000 ng/mL, is low, approximately 14% to 21%. The effect of sumatriptan on the protein binding of other drugs has not been evaluated.

Following a 6-mg subcutaneous injection into the deltoid area of the arm in 9 males ( mean age: 33 years, mean weight: 77 kg) the volume of distribution central compartment of sumatriptan was 50 ± 8 liters and the distribution half-life was 15 ± 2 minutes.

Metabolism:

In vitro studies with human microsomes suggest that sumatriptan is metabolized by MAO, predominantly the A isoenzyme. Most of a radiolabeled dose of sumatriptan excreted in the urine is the major metabolite indole acetic acid (IAA) or the IAA glucuronide, both of which are inactive.

Elimination:

After a single 6-mg subcutaneous dose, 22% ± 4% was excreted in the urine as unchanged sumatriptan and 38% ± 7% as the IAA metabolite.

Following a 6-mg subcutaneous injection into the deltoid area of the arm, the systemic clearance of sumatriptan was 1,194 ± 149 mL/min and the terminal half-life was 115 ± 19 minutes.

Special Populations:

Age: The pharmacokinetics of sumatriptan in the elderly (mean age: 72 years, 2 males and 4 females) and in subjects with migraine (mean age: 38 years, 25 males and 155 females) were similar to that in healthy male subjects (mean age: 30 years).

Renal Impairment: The effect of renal impairment on the pharmacokinetics of sumatriptan has not been examined.

Hepatic Impairment: The effect of mild to moderate hepatic disease on the pharmacokinetics of subcutaneously administered sumatriptan has been evaluated. There were no significant differences in the pharmacokinetics of subcutaneously administered sumatriptan in moderately hepatically impaired subjects compared with healthy controls. The pharmacokinetics of subcutaneously administered sumatriptan in patients with severe hepatic impairment has not been studied. The use of Alsuma in this population is contraindicated [see Contraindications (4)].

Race: The systemic clearance and Cmax of sumatriptan were similar in black (n = 34) and Caucasian (n = 38) healthy male subjects.

Drug Interaction Studies:

Monoamine Oxidase-A Inhibitors:

In a trial of 14 healthy females, pretreatment with an MAO-A inhibitor decreased the clearance of sumatriptan, resulting in a 2-fold increase in the area under the sumatriptan plasma concentration-time curve (AUC), corresponding to a 40% increase in elimination half-life.

Alsuma contains sumatriptan (base) as the succinate salt and is supplied as a clear, colorless to pale yellow, sterile, nonpyrogenic solution in a single-dose pre-filled auto-injector.

Injection Strength	Package Contents	NDC#
6 mg	Two 6 mg single dose Alsuma (sumatriptan injection) 6 mg/0.5 mL Auto-Injectors	0069-0138-02
	Alsuma Physician Insert
	Patient Instructions for Use

Store at 25°C, excursions permitted 15° to 30°C (59° to 86° F). Protect from light. Do not refrigerate.

You should not use this medication if you are allergic to sumatriptan, if you have any history of heart disease, or if you have coronary heart disease, angina, blood circulation problems, lack of blood supply to the heart, uncontrolled high blood pressure, severe liver disease, ischemic bowel disease, a history of a heart attack or stroke, or if your headache seems to be different from your usual migraine headaches.

Do not use sumatriptan within 24 hours before or after using another migraine headache medicine, including sumatriptan tablets or nasal spray, almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), rizatriptan (Maxalt), naratriptan (Amerge), zolmitriptan (Zomig), or ergot medicine such as dihydroergotamine (D.H.E. 45, Migranal), ergotamine (Ergomar, Cafergot, Migergot), dihydroergotamine (D.H.E. 45, Migranal), or methylergonovine (Methergine).

Do not use sumatriptan if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days.

Before using sumatriptan, tell your doctor if you have liver or kidney disease, seizures, high blood pressure, a heart rhythm disorder, or coronary heart disease (or risk factors such as diabetes, menopause, smoking, being overweight, having high cholesterol, having a family history of coronary artery disease, being older than 40 and a man, or being a woman who has had a hysterectomy).

Also tell your doctor if you are taking an antidepressant such as citalopram (Celexa), desvenlafaxine (Pristiq), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), or venlafaxine (Effexor).

Sumatriptan will only treat a headache that has already begun. It will not prevent headaches or reduce the number of attacks.

After using a sumatriptan injection, you must wait one (1) hour before using a second injection. Do not use more than two injections in 24 hours.