Hydergine

1. Hydergine

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (capsules, tablets, sublingual tablets, or oral solution):
  • Adults: 1 to 2 milligrams (mg) three times a day.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• any changes in memory, alertness, mood, appetite, energy level, or ability to care for yourself.

Common side effects may include:

• nausea or other stomach discomfort.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In the U.S.

• Hydergine

Available Dosage Forms:

• Tablet
• Capsule, Liquid Filled
• Solution

Therapeutic Class: Antimigraine

Chemical Class: Ergot Alkaloid

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Almotriptan
• Amprenavir
• Atazanavir
• Azithromycin
• Clarithromycin
• Dirithromycin
• Erythromycin
• Fosamprenavir
• Frovatriptan
• Indinavir
• Josamycin
• Ketoconazole
• Mepartricin
• Miokamycin
• Naratriptan
• Nefazodone
• Nelfinavir
• Ritonavir
• Rizatriptan
• Rokitamycin
• Roxithromycin
• Saquinavir
• Spiramycin
• Sumatriptan
• Troleandomycin
• Voriconazole
• Zolmitriptan

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Fluconazole
• Fluvoxamine
• Telithromycin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Delavirdine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Liver disease—Higher blood levels of ergoloid mesylates may occur, increasing the chance of side effects

• Low blood pressure or
• Other mental problems or
• Slow heartbeat—Ergoloid mesylates may make the condition worse

T1999-75

Hydergine®

(ergoloid mesylates) Tablets, USP (ORAL)

(ergoloid mesylates) Liquid, USP

Hydergine® LC

(ergoloid mesylates, USP) Liquid Capsules

Rx only

Hydergine® Tablet 1 mg and
Hydergine® LC Liquid Capsule 1 mg

Each contains ergoloid mesylates, USP as follows: dihydroergocornine mesylate 0.333 mg, dihydroergocristine mesylate 0.333 mg, and dihydroergocryptine (dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine in the proportion of 2:1) mesylate 0.333 mg, representing a total of 1 mg.

Inactive Ingredients

Oral Tablets: lactose, povidone, starch, stearic acid, and talc.

Liquid Capsules: ascorbic acid, gelatin, glycerin, methylparaben, polyethylene glycol, propylparaben, propylene glycol, sorbitol, and titanium dioxide.

Hydergine® Liquid 1 mg/mL

Each mL contains ergoloid mesylates, USP as follows: dihydroergocornine mesylate 0.333 mg, dihydroergocristine mesylate 0.333 mg, and dihydroergocryptine (dihydro-alpha-ergocryptine and dihydro-beta-ergocryptine in the proportion of 2:1) mesylate 0.333 mg, representing a total of 1mg; alcohol, 28.5% by volume.

Inactive Ingredients: alcohol, glycerin, propylene glycol, and purified water.

Pharmacokinetic Properties

Pharmacokinetic studies have been performed in normal volunteers with the help of radiolabelled drug as well as employing a specific radioimmunoassay technique. From the urinary excretion quotient of orally and intravenously administered tritium-labelled Hydergine® (ergoloid mesylates) the absorption of ergoloid was calculated to be 25%. Following oral administration, peak levels of 0.5 ngEq/mL/mg were achieved within 1.5-3 hr. Bioavailability studies with the specific radioimmunoassay confirm that ergoloid is rapidly absorbed from the gastrointestinal tract, with mean peak levels of 0.05-0.13 ng/mL/mg (with extremes of 0.03 and 0.18 ng/mL/mg) achieved within 0.6-1.3 hr (with extremes of 0.4 and 2.8 hr). The finding of lower peak levels of ergoloid compared to the total drug-metabolite composite is consistent with a considerable first pass liver metabolism, with less than 50% of the therapeutic moiety reaching the systemic circulation. The elimination of radioactivity, representing ergoloid plus metabolites bearing the radiolabel, was biphasic with half-lives of 4 and 13 hr. The mean half-life of unchanged ergoloid in plasma is about 2.6-5.1 hr; after 3 half-lives ergoloid plasma levels are less than 10% of radioactivity levels, and by 24 hr no ergoloid is detectable.

Bioequivalence studies were performed comparing Hydergine® (ergoloid mesylates) oral tablets (administered orally) with Hydergine® (ergoloid mesylates) sublingual tablets (administered sublingually), Hydergine® (ergoloid mesylates) oral tablets with Hydergine® (ergoloid mesylates) liquid, and Hydergine® (ergoloid mesylates) oral tablets with Hydergine® LC (ergoloid mesylates, USP) liquid capsules. The oral tablet, sublingual tablet, and liquid capsule oral forms were shown to be bioequivalent. Within the bioequivalence limits, the liquid capsule showed a statistically significant (12%) greater bioavailability than the oral tablet. In the study comparing the oral tablet and liquid forms, both forms tested showed an equivalent rate of absorption and an equivalent peak plasma concentration (Cmax).

Hydergine® (ergoloid mesylates) preparations have not been found to produce serious side effects. Transient nausea and gastric disturbances have been reported. Hydergine® (ergoloid mesylates) preparations do not possess the vasoconstrictor properties of the natural ergot alkaloids.

Applies to ergoloid mesylates: capsule liquid filled, solution, tablet

Along with its needed effects, ergoloid mesylates (the active ingredient contained in Hydergine) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur while taking ergoloid mesylates:

• Dizziness or lightheadedness when getting up from a lying or sitting position
• drowsiness
• skin rash
• slow pulse

• Blurred vision
• dizziness
• fainting
• flushing
• headache
• loss of appetite
• nausea or vomiting
• stomach cramps
• stuffy nose

Some side effects of ergoloid mesylates may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Soreness under tongue (with sublingual use)

Applies to ergoloid mesylates: compounding powder, oral capsule, oral solution, oral tablet, sublingual tablet

General

The most commonly reported adverse events have included transient nausea and gastric disturbances.[Ref]

Gastrointestinal

Frequency not reported: Nausea, gastric disturbances[Ref]

Some side effects of Hydergine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.