Ikaran

Ikaran - General Information

A 9,10alpha-dihydro derivative of ergotamine. It is used as a vasoconstrictor, specifically for the therapy of migraine disorders. [PubChem]

 

Pharmacology of Ikaran

Ikaran is indicated for the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes. Ikaran binds with high affinity to 5-HT_1Da and 5-HT_1Db receptors. It also binds with high affinity to serotonin 5-HT_1A, 5-HT_2A, and 5-HT_2C receptors, noradrenaline a2A, a2B and a receptors, and dopamine D2L and D3 receptors. The therapeutic activity of Ikaran in migraine is generally attributed to the agonist effect at 5-HT_1D receptors.

 

Ikaran for patients

To assure safe and effective use of D.H.E. 45® (dihydroergotamine mesylate) Injection, USP, the information and instructions provided in the patient Information sheet should be discussed with patients.

Patients should be advised to report to the physician immediately any of the following: numbness or tingling in the fingers and toes, muscle pain in the arms and legs, weakness in the legs, pain in the chest, temporary speeding or slowing of the heart rate, swelling, or itching. Prior to the initial use of the product by a patient the prescriber should take steps to ensure that the patient understands how to use the product as provided.

INSTRUCTION FOR PATIENTS ON SUBCUTANEOUS SELF-INJECTION

Before self-injecting D.H.E. 45® (dihydroergotamine mesylate) Injection USP by subcutaneous administration, you will need to obtain professional instruction on how to properly administer your medication. Below are some of the steps you should follow carefully. Read this leaflet completely before using this medication.

This leaflet does not contain all of the information on D.H.E. 45® (dihydroergotamine mesylate) Injection, USP. Your pharmacist and/or health care provider can provide more detailed information.

Purpose of your Medication

D.H.E. 45® (dihydroergotamine mesylate) Injection, USP 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.

Do not use D.H.E. 45® (dihydroergotamine mesylate) Injection, USP If you:

• are pregnant or nursing.
• have any disease affecting your heart, arteries, or circulation.

Important questions to consider before using D.H.E. 45® (dihydroergotamine mesylate) Injection, USP

Please answer the following questions before you use your D.H.E. 45® (dihydroergotamine mesylate) Injection, USP. If you answer YES to any of these questions or are unsure of the answer, you should talk to your doctor before using D.H.E. 45® (dihydroergotamine mesylate) Injection USP.

• 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, diabates, smoking, strong family history of heart disease, or you are 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?

REMEMBER TO TELL YOUR DOCTOR IF YOU HAVE ANSWERED YES TO ANY OF THESE QUESTIONS BEFORE YOU USE D.H.E. 45® (dihydroergotamine mesylate) Injection, USP

Side Effects To Watch Out For

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.

Dosage

Your doctor will have told you what dose to use for each migraine attack. Should you get another migraine attack in the same day as the attack you treated, you must not treat it with D.H.E. 45® (dihydroergotamine mesylate) Injection, USP unless at least 6 hours have elapsed since your last injection. No more than 6 ml of D.H.E. 45® (dihydroergotamine mesylate) Injection, USP should be injected during a one-week period.

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.

How to use the D.H.E. 45® (dihydroergotamine mesylate) Injection, USP

1. Use available training materials.

• Read and follow the instructions in the patient instruction booklet which is provided with the D.H.E. 45® (dihydroergotamine mesylate) Injection, USP package before attempting to use the product.
• If there are any questions concerning the use of your D.H.E. 45® (dihydroergotamine mesylate) Injection, USP, ask your Doctor or pharmacist.

2. Preparing for the Injection.

• Carefully examine the ampul (glass vial) of D.H.E. 45® (dihydroergotamine mesylate) Injection, USP for any cracks or breaks, and the liquid for discoloration, cloudiness, or particles. If any of these defects are present use a new ampul, make certain it is intact, and return the defective ampul to your doctor or pharmacy. Once you open an ampul, If it is not used within an hour, it should be thrown away.

3. Locating an Injection Site

Administer your subcutaneous injection in the middle of your thigh, well above the knee.

4. Drawing the Medication into the Syringe

• Wash your hands thoroughly with soap and water.
• Check the dose of your medication
• Look to see if there is any liquid at the top of the ampul. If there is, gently flick the ampul with your finger to get all the liquid into the bottom portion of the ampul.
• Hold the bottom of the ampul in one hand. Clean the ampul neck with an alcohol wipe using your other hand. Then place the alcohol wipe around the neck of the ampul and break it open by pressing your thumb against the neck of the ampul.
• Tilt the ampul down at a 45° angle. Insert the needle into the solution in the ampul.
• Draw up the medication by pulling back the plunger slowly and steadily until you reach your dose.
• Check the syringe for air bubbles. Hold it with the needle pointing upward. If there are air bubbles, tap your finger against the barrel of the syringe to get the bubbles to the top. Slowly and carefully push the plunger up so that the bubbles are pushed out through the needle and you see a drop of medication.
• When there are no air bubbles check the dose of the medication. If the dose is incorrect, repeat steps 6 through 8 until you draw up the right dose.

5. Preparing the Injection Site.

• With a new alcohol wipe, clean the selected injection site thoroughly with a firm, circular motion from inside to outside. Wait for the injection site to dry before injecting.

6. Administering the Injection

• Hold the syringe/needle in your right hand.
• With your left hand, firmly grasp about a 1-inch fold of skin at the injection site.
• Push the needle shaft, bevel side up, all the way into the fold of skin at a 45° to 90° angle, then release the fold of skin.
• While holding the syringe with your left hand, use your right hand to draw back slightly on the plunger.
• If you do not see any blood coming back into the syringe, inject the medication by pushing down on the plunger. If you do see blood in the syringe, that means the needle has penetrated a vein. If this happens pull the needle/syringe out of the skin slightly and draw back on the plunger again. If no blood is seen this time, inject the medication.
• Use your right hand to pull the needle out of your skin quickly at the same angle you injected it. Immediately press the alcohol wipe on the injection site and rub.

Check the expiration date printed an the ampul containing medication. If the expiration date has passed, do not use it.

Answers to patients' questions about D. H. E. 45® (dihydroergotamine mesylate) Injection, USP

What if I need help in using my D.H.E. 45® (dihydroergotamine mesylate) Injection, USP?

If you have any questions or if you need help in opening, putting together, or using D.H.E. 45® (dihydroergotamine mesylate) Injection, USP, speak to your doctor or pharmacist.

How much medication should I use and how often?

Your doctor will have told you what dose to use for each migraine attack. Should you get another migraine attack in the same day as the attack you treated, you must not treat it with D.H.E. 45® (dihydroergotamine mesylate) Injection, USP unless at least 6 hours have elapsed since your last injection. No more than 6 mL of D.H.E. 45® (dihydroergotamine mesylate) Injection, USP should be injected during a one-week period. Do not use more than this amount unless instructed to do so by your doctor.

If you have any other unanswered question about D.H.E. 45® (dihydroergotamine mesylate) Injection, USP, consult your doctor or pharmacist.

 

Ikaran Interactions

Vasoconstrictors: D.H.E. 45® (dihydroergotamine mesylate) Injection, USP should not be used with peripheral vasoconstrictors because the combination may cause synergistic elevation of blood pressure.

Sumatriptan: Sumatriptan has been reported to cause coronary artery vasospasm, and its effect could be additive with D.H.E. 45® (dihydroergotamine mesylate) Injection, USP. Sumatriptan and D.H.E. 45® (dihydroergotamine mesylate) Injection, USP should not be taken within 24 hours of each other..

Beta Blockers: Although the results of a clinical study did not indicate a safe problem associated with the administration of D.H.E. 45® (dihydroergotamine mesylate) Injection, USP to subjects already receiving propranolol, there have been reports that propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.

Nicotine: Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy.

Macrolide Antibiotics (e. g. erythromycin and troleandomycin): Agents of the ergot alkaloid class, of which D.H.E. 45® (dihydroergotamine mesylate) Injection, USP is a member, have been shown to interact with antibiotics of the macrolide class, resulting in increased plasma levels of unchanged alkaloids and peripheral vasoconstriction. Vasospastic reactions have been reported with therapeutic doses of ergotamine-containing drugs when co-administered with these antibiotics.

SSRI's: Weakness hyperreflexia, and incoordination have been reported rarely when 5-HT₁ agonists have been co-administered with SSRI's (e. g. fluoxetine, fluvoxamine, paroxetine, sertraline). There have been no reported cases from spontaneous reports of drug interaction between SSRI's and D.H.E. 45® (dihydroergotamine mesylate) Injection, USP.

Oral Contraceptives: The effect of oral contraceptives on the pharmacokinetics of D.H.E. 45® (dihydroergotamine mesylate) Injection, USP has not been studied.

 

Ikaran Contraindications

D.H.E. 45® (dihydroergotamine mesylate) Injection, USP should not be given to patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal's variant angina.

Because D.H.E. 45® (dihydroergotamine mesylate) Injection, USP may increase blood pressure, it should not be given to patients with uncontrolled hypertension.

D.H.E. 45® (dihydroergotamine mesylate) Injection, USP, 5-HT₁ agonists (e.g., sumatriptan) ergotamine-containing or ergot-type medications or methysergide should not be used within 24 hours of each other.

D.H.E. 45® (dihydroergotamine mesylate) Injection, USP should not be administered to patients with hemiplegic or basilar migraine.

In addition to those conditions mentioned above, D.H.E. 45® (dihydroergotamine mesylate) Injection, USP is also contraindicated in patients with known peripheral arterial disease, sepsis, following vascular surgery and severely impaired hepatic or renal function.

D.H.E. 45® (dihydroergotamine mesylate) Injection USP may cause fetal harm when administered to a pregnant woman. Dihydroergotamine possesses oxytocic properties and therefore, should not be administered during pregnancy. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

There are no adequate studies of dihydroergotamine in human pregnancy, but developmental toxicity has been demonstrated in experimental animals. In embryo-fetal development studies of dihydroergotamine mesylate nasal spray, intranasal administration to pregnant rats throughout the period of organogenesis resulted in decreased fetal body weights and/or skeletal ossification at doses of 0.16 mg/day (associated with maternal plasma dihydroergotamine exposures [AUC] approximately 0.4-1.2 times the exposures in humans receiving the MADE of 4 mg) or greater. A no effect level for embryo-fetal toxicity was not established in rats. Delayed skeletal ossification was also noted in rabbit fetuses following intranasal administration of 3.6 mg/day (maternal exposures approximately 7 times human exposures at the MRDD) during organogenesis. A no effect level was seen at 1.2 mg/day (maternal exposures approximately 2.5 times human exposures at the MRDD). When dihydroergotamine mesylate nasal spray was administered intranasally to female rats during pregnancy and lactation, decreased body weights and impaired reproductive function (decreased mating indices) were observed in the offspring at doses of 0.16 mg/day or greater. A no effect level was not established. Effects on development occurred at doses below those that produced evidence of significant maternal toxicity in these studies. Dihydroergotamine-induced intrauterine growth retardation has been attributed to reduced uteroplacental blood flow resulting from prolonged vasoconstriction of the uterine vessels and/or increased myometrial tone.

D.H.E. 45® (dihydroergotamine mesylate) Injection, USP is contraindicated in patients who have previously shown hypersensitivity to ergot alkaloids.

Dihydroergotamine mesylate should not be used by nursing mothers.

Dihydroergotamine mesylate should not be used with peripheral and central vasoconstrictors because the combination may result in additive or synergistic elevation of blood pressure.

 

Additional information about Ikaran

Ikaran Indication: For the acute treatment of migraine headaches with or without aura and the acute treatment of cluster headache episodes.
Mechanism Of Action: Two theories have been proposed to explain the efficacy of 5-HT_1D receptor agonists in migraine: 1) activation of 5-HT_1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache and 2) activation of 5-HT_1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
Drug Interactions: Acebutolol Ischemia with risk of gangrene
Almotriptan Possible severe and prolonged vasoconstriction
Amprenavir Amprenavir increases the effect and toxicity of ergot derivative
Atazanavir Atazanavir increases the effect and toxicity of ergot derivative
Atenolol Ischemia with risk of gangrene
Betaxolol Ischemia with risk of gangrene
Bevantolol Ischemia with risk of gangrene
Bisoprolol Ischemia with risk of gangrene
Carteolol Ischemia with risk of gangrene
Carvedilol Ischemia with risk of gangrene
Clarithromycin Risk of ergotism and severe ischemia with this association
Delavirdine The antiretroviral agent may increase the ergot derivative
Efavirenz The antiretroviral agent may increase the ergot derivative
Eletriptan Possible severe and prolonged vasoconstriction
Erythromycin Possible ergotism and severe ischemia with this combination
Esmolol Ischemia with risk of gangrene
Fluconazole Possible ergotism and severe ischemia with this combination
Fluoxetine Possible ergotism and severe ischemia with this combination
Fluvoxamine Possible ergotism and severe ischemia with this combination
Fosamprenavir Amprenavir increases the effect and toxicity of ergot derivative
Frovatriptan Possible severe and prolonged vasoconstriction
Indinavir Indinavir increases the effect and toxicity of ergot derivative
Isosorbide Dinitrate Possible antagonism of action
Isosorbide Mononitrate Possible antagonism of action
Itraconazole Possible ergotism and severe ischemia with this combination
Josamycin Possible ergotism and severe ischemia with this combination
Ketoconazole Possible ergotism and severe ischemia with this combination
Labetalol Ischemia with risk of gangrene
Metoprolol Ischemia with risk of gangrene
Nadolol Ischmeia with risk of gangrene
Naratriptan Possible severe and prolonged vasoconstriction
Nefazodone Possible ergotism and severe ischemia with this combination
Nelfinavir Nelfinavir increases the effect and toxicity of ergot derivative
Nitroglycerin Possible antagonism of action
Penbutolol Ischemia with risk of gangrene
Pindolol Ischemia with risk of gangrene
Posaconazole Contraindicated co-administration
Practolol Ischemia with risk of gangrene
Propranolol Ischemia with risk of gangrene
Ritonavir The protease inhibitor increases the effect and toxicity of ergot derivative
Rizatriptan Possible severe and prolonged vasoconstriction
Saquinavir The protease inhibitor increases the effect and toxicity of ergot derivative
Sibutramine Possible serotoninergic syndrome with this combination
Sotalol Ischemia with risk of gangrene
Sumatriptan Possible severe and prolonged vasoconstriction
Telithromycin Risk of ergotism and severe ischemia with this association
Timolol Ischemia with risk of gangrene
Troleandomycin Possible ergotism and severe ischemia with this combination
Voriconazole Voriconazole increases the effect and toxicity of ergot derivative
Zileuton Possible ergotism and severe ischemia with this combination
Zolmitriptan Possible severe and prolonged vasoconstriction
Amyl Nitrite Possible antagonism of action
Erythrityl Tetranitrate Possible antagonism of action
Oxprenolol Ischemia with risk of gangrene
Food Interactions: Not Available
Generic Name: Dihydroergotamine
Synonyms: 9,10-dihydro-ergotamine; Dihidroergotamina [INN-Spanish]; Dihydroergotamine mesylate; Dihydroergotamine methanesulfonate; Dihydroergotamine monomethanesulfonate; Dihydroergotaminum [INN-Latin]
Drug Category: Analgesics; Vasoconstrictor Agents; Sympatholytics; Anti-migraine Agents
Drug Type: Small Molecule; Approved

Other Brand Names containing Dihydroergotamine: Agit; Angionorm; D.H.E.; D.H.E. 45; DET MS; DHE-45; Dergotamine; Diergo; Dihydergot; Dirgotarl; Endophleban; Ergomimet; Ergont; Ergotonin; Ikaran; Migranal; Morena; Orstanorm; Tonopres; Verladyn;
Absorption: Interpatient variable and may be dependent on the administration technique
Toxicity (Overdose): Side effects include abdominal pain, abnormal speech, coma, confusion, convulsions, hallucinations, increase and/or decrease in blood pressure, nausea, numbness, tingling, pain, and a bluish color of your fingersand toes, slowed breathing, vomiting
Protein Binding: 93% (to plasma proteins)
Biotransformation: Hepatic
Half Life: 9 hours
Dosage Forms of Ikaran: Liquid Intravenous
Liquid Nasal
Chemical IUPAC Name: Not Available
Chemical Formula: C33H37N5O5
Dihydroergotamine on Wikipedia: https://en.wikipedia.org/wiki/Dihydroergotamine
Organisms Affected: Humans and other mammals