Migranal

What is Migranal?

Migranal (dihydroergotamine mesylate) Nasal Spray is intended to treat an active migraine headache. Do not try to use it to prevent a headache if you have no symptoms. Do not use it to treat common tension headache or a headache that is not at all typical of your usual migraine headache.

Administration of Migranal Nasal Spray, should not exceed the dosing guidelines and should not be used for chronic daily administration.

There have been reports of fibrosis (stiffening) in the lung or kidney areas in patients following prolonged daily use of injectable dihydroergotamine mesylate. Rarely, prolonged daily use of other ergot alkaloid drugs (the class of drugs to which Migranal Nasal Spray belongs) has been associated with heart valvular fibrosis. Rare cases have also been reported in association with the use of injectable dihydroergotamine mesylate; however, in those cases, patients also received drugs known to be associated with heart valvular fibrosis.

Description

MIGRANAL is ergotamine hydrogenated in the 9,10 position as the mesylate salt. MIGRANAL is known chemically as ergotaman-3’, 6’, 18-trione, 9,10-dihydro-12’-hydroxy-2’-methyl-5’- (phenylmethyl)-, (5’α)-, monomethane-sulfonate. Its molecular weight is 679.78 and its empirical formula is C33H37N5O5•CH4O3S.

The chemical structure is:

MIGRANAL (dihydroergotamine mesylate) Nasal Spray is provided for intranasal administration as a clear, colorless to light yellow aqueous solution in an amber glass vial containing:

• dihydroergotamine mesylate ………4 mg
•  
• caffeine, anhydrous ……..10 mg
•  
• dextrose, anhydrous ……..50 mg
•  
• carbon dioxide ………….qs 

purified water.. ……..qs 1 mL

Each milliliter contains

• Dihydroergotamine mesylate …………4 mg

(equivalent to 3.43 mg dihydroergotamine)

Mechanism of Action

Dihydroergotamine binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors. It also binds with high affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline α2A, α2B and α1 receptors, and dopamine D2L and D3 receptors.

The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT1D receptors. Two current theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine. One theory suggests that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release. In addition, dihydroergotamine possesses oxytocic properties.

What is the most important information I should know about Migranal?

The solution used in Migranal Nasal Spray (4 mg/mL) is intended for intranasal use and must not be injected.

Who should not use Migranal?

Do not use Migranal Nasal Spray if you:

• Are pregnant or nursing.
• have any disease affecting your heart, arteries, or circulation.
• are taking certain anti-HIV medications (protease inhibitors).
• are taking a macrolide antibiotic such as troleandomycin, clarithromycin or erythromycin.

What should I tell my healthcare provider before using Migranal?

Please answer the following questions before you use your Migranal Nasal Spray. If you answer YES to any of these questions or are unsure of the answer, you should talk to your doctor before using Migranal Nasal Spray.

• Do you have high blood pressure?
• Do you have chest pain, shortness of breath, heart disease, or have you had any surgery on your heart arteries?
• Do you have risk factors for heart disease (such as high blood pressure, high cholesterol, obesity, diabetes, smoking, strong family history of heart disease, or are you postmenopausal or a male over 40)?
• Do you have any problems with blood circulation in your arms or legs, fingers, or toes?
• Are you pregnant? Do you think you might be pregnant? Are you trying to become pregnant? Are you sexually active and not using birth control? Are you breast feeding?
• Have you ever had to stop taking this or any other medication because of an allergy or bad reaction?
• Are you taking any other migraine medications, erythromycin or other antibiotics, or medications for blood pressure prescribed by your doctor, or other medicines obtained from your drugstore without a doctor’s prescription?
• Do you smoke?
• Have you had, or do you have, any disease of the liver or kidney?
• Is this headache different from your usual migraine attacks?
• Are you using Migranal Nasal Spray or other dihydroergotamine mesylate containing drugs on a daily basis?
• Are you taking a protease inhibitor for HIV therapy?
• Are you taking a macrolide class of antibiotic?

Serious or potentially life-threatening reductions in blood flow to the brain or extremities have been reported rarely due to interactions between Migranal Nasal Spray and protease inhibitors or macrolide antibiotics.

Remember to tell your doctor if you have answered yes to any of these questions before you use Migranal Nasal Spray.

How should I use Migranal?

1. Use available training materials.

• Read and follow the instructions in the administration instructions which are provided with the Migranal Nasal Spray package before attempting to use the product.
• If there are any questions concerning the use of your Migranal (dihydroergotamine mesylate) Nasal Spray, ask your doctor or pharmacist, or contact Bausch Health US, LLC at 1-800-321-4576.

2. Check the contents of the package:

• 8 Nasal Spray Vials
• 8 Nasal Sprayers
• Administration Instructions
• Package Insert

3. Assemble the sprayer:
Assemble your nasal sprayer only when you are ready to use it.

• Lift tab to bend back blue cover. In one piece, completely remove the blue cover and metal seal in a circular motion. Keeping the vial upright, remove rubber stopper. Set vial aside.
• Remove plastic cover from the bottom of pump unit. Insert spray pump into vial and turn clockwise until securely fastened.

4. Using the sprayer:

• Remove cap from spray unit. Holding the vial upright, point nasal sprayer away from face and pump 4 times before using. DO NOT PUMP MORE THAN 4 TIMES. (Although some medication will spray out, there is enough medication in each vial to allow you to prepare your nasal spray pump properly and still receive a full treatment of Migranal.)
• Spray once into each nostril. Do not tilt head back or sniff through your nose while spraying or immediately after. Wait 15 minutes. Spray once again into each nostril.

5. After completing these instructions:

• Carefully dispose of the nasal spray pump with the vial.

Dosing Information

• Each vial contains one complete dose of Migranal Nasal Spray, which is 1 spray in each nostril followed in 15 minutes by an additional spray in each nostril, for a total of 4 sprays.
• Studies have shown no benefit from acute doses greater than 2 mg (4 sprays) for a single administration. The safety of doses greater than 3 mg in a 24 hour period has not been established.
• The safety of doses greater than 4 mg in a 7-day period has not been established.
• Migranal Nasal Spray, should not be used for chronic daily administration.

Learn what to do in case of an Overdose

If you have used more medication than you have been instructed, contact your doctor, hospital emergency department, or nearest poison control center immediately.

What if I need help in using my Migranal Nasal Spray?

If you have any questions or if you need help in opening, putting together, or using Migranal Nasal Spray, speak to your doctor or pharmacist, or contact Bausch Health US, LLC at 1-800-321-4576 or visit www.migranal.com.

How much medication should I use and how often?

Each vial contains one complete dose of Migranal Nasal Spray, which is 1 spray in each nostril, followed by an additional spray in each nostril 15 minutes later for a total of 4 sprays. Do not use more than this amount unless instructed to do so by your doctor. Migranal Nasal Spray is not intended for chronic daily use.

Why do I have to prime or pump the Nasal Sprayer 4 times before using? Am I wasting the medication?

You have to prime the Nasal Sprayer 4 times to make sure that you get the proper amount of medication when you use it. Although you will see some medication spray out, there is still enough medication in each vial to allow you to prepare your sprayer properly and still receive a full dose of Migranal Nasal Spray.

Can I assemble the medication vial and the Nasal Sprayer so it is ready before I need to use it?

No. The brown (amber) glass vial containing your medication must remain unopened until you are ready to use it. It may not be fully effective if opened and not used within 8 hours.

Can I reuse my Migranal Nasal Sprayer?

No. After completing the full dose, you must carefully dispose of your Migranal Nasal Sprayer and the opened vial. You should use a new unit for your next migraine attack. Each Unit contains a new Nasal Sprayer, and a vial of Migranal Nasal Spray medication.

Can I use Migranal Nasal Spray if I have a stuffy nose, cold, or allergies?

Yes. Migranal Nasal Spray can be used if you have a stuffy nose, cold, or allergies. However, if you are taking any medications for your cold, or allergies, even those you can buy without a doctor’s prescription, speak with your doctor before using Migranal Nasal Spray.

Do I need to sniff the medication when I spray it in my nostril?

No, you should not sniff because Migranal Nasal Spray should remain in the nose so that it can be absorbed into the bloodstream through the lining of the nose. If you have any other unanswered questions about Migranal Nasal Spray, consult your doctor or pharmacist.

What are the possible side effects of Migranal?

In clinical trials, most migraine patients have used Migranal Nasal Spray without serious side effects. You may experience some nasal congestion or irritation, altered sense of taste, sore throat, nausea, vomiting, dizziness, and fatigue after using Migranal Nasal Spray. These side effects are temporary and usually do not require you to stop using Migranal Nasal Spray. Although the following reactions rarely occur, they can be serious and should be reported to your physician immediately:

• Numbness or tingling in your fingers and toes
• Pain, tightness, or discomfort in your chest
• Muscle pain or cramps in your arms and legs
• Weakness in your legs
• Temporary speeding or slowing of your heart rate
• Swelling or itching

How should I store Migranal?

• Keep medication in a safe place away from children
• Keep Migranal Nasal Spray away from heat and light.
• Do not expose Migranal Nasal Spray to temperatures over 77°F.
• Never refrigerate or freeze Migranal Nasal Spray.
• Do not keep an opened Migranal Nasal Spray vial for more than 8 hours.
  Check the expiration date printed on the vial containing medication. If the expiration date has passed, do not use it.

Important Notes:

• Once a Migranal Nasal Spray vial has been opened, it must be thrown away after 8 hours.

What are the ingredients in Migranal?

Active ingredient: dihydroergotamine mesylate

Inactive ingredients: caffeine, anhydrous dextrose, carbon dioxide, water

Label

PRINCIPAL DISPLAY PANEL – 4 MG/ML KIT CARTON

• NDC 0187-0245-03
• Rx only
• MIGRANAL®
• (dihydroergotamine mesylate)
  NASAL SPRAY
• This Kit Contains:
• 8 MIGRANAL Vials
• 8 MIGRANAL Nasal Sprayers

Administration Instructions

Package Insert

FOR NASAL USE ONLY
NOT FOR INJECTION

• 4 mg/mL (1 mL/Vial)