dihydroergotamine

Absorption: Rapidly absorbed following IM and SUBQ administration and 32% absorbed from nasal mucosa. IV administration results in complete bioavailability.

Distribution: Unknown.

Protein Binding: 90%.

Metabolism/Excretion: Highly metabolized (90%) by the liver. Some metabolites are active.

Half-Life: 10 hours.

Time/Action Profile ⬆ ⬇

(relief of headache)

ROUTE	ONSET	PEAK	DURATION
Nasal	within 30 min	unknown	unknown
IM, SUBQ	15–30 min	15 min–2 hr	8 hr
IV	<5 min	15 min–2 hr	8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Peripheral arterial disease;
Ischemic heart disease or Prinzmetal's angina;
Uncontrolled hypertension;
Sepsis;
Following vascular surgery;
Severe hepatic impairment;
Severe renal impairment;
Malnutrition;
Known alcohol intolerance (injection only);
Concurrent use of strong CYP3A4 enzyme inhibitors;
Use of other ergot-type medications or triptans with the previous 24 hr;
Concurrent use of other vasoconstrictor medications;
OB: Pregnancy (may cause preterm labor);
Lactation: Lactation.

Use Cautiously in:

Risk factors for ischemic heart disease (hypertension, hypercholesterolemia, smoker, obesity, diabetes, family history, postmenopausal females, or males >40 yr);
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypertension, angina pectoris, coronary artery vasospasm, intermittent claudication, MI, VENTRICULAR ARRHYTHMIA

EENT: nasopharyngitis, rhinitis, altered smell, ear discomfort, epistaxis, nasal discomfort, pharyngitis, rhinorrhea, sinusitis

GI: abdominal pain, nausea, diarrhea, vomiting, colonic ischemia, polydipsia

MS: extremity stiffness, muscle pain, stiff neck, stiff shoulders

Neuro: dizziness, dysgeusia, fatigue, headache, INTRACRANIAL HEMORRHAGE, leg weakness, numbness or tingling in fingers or toes, sedation, STROKE

Resp: pleural fibrosis

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors, including clarithromycin, erythromycin, itraconazole, ketoconazole, and protease inhibitors may produce serious, life-threatening peripheral ischemia; concurrent use contraindicated.
Concurrent use with vasoconstrictors may significantly ↑ BP; concurrent use contraindicated.
Concurrent use with triptans or other ergot-type medicationsmay result in prolonged vasoconstriction; allow 24 hr between use; concurrent use contraindicated.
Concurrent use with beta blockers, oral contraceptives, or nicotine (heavy smoking) may ↑ risk of peripheral vasoconstriction.
Antagonizes the antianginal effects of nitrates.

Route/Dosage ⬆ ⬇

IM SC (Adults ): 1 mg; may repeat in 1 hr to a total of 3 mg (not to exceed 3 mg/day or 6 mg/wk).
IV (Adults ): 0.5 mg; may repeat in 1 hr (not to exceed 2 mg/day or 6 mg/wk). For chronic intractable headache, 0.5–1 mg every 8 hr may be given until relief (not to exceed 6 mg/wk).
(Adults ): Migranal: 1 spray (0.5 mg) in each nostril, repeat after 15 min (2 mg total dose or 4 sprays); not to exceed 3 mg (3 doses or 6 sprays)/24 hr or 4 mg (4 doses or 8 sprays)/wk. Trudhesa: 1 spray (0.725 mg) in each nostril; may repeat, if needed, after a minimum of 1 hr; not to exceed 2.9 mg (2 doses or 4 sprays)/24 hr or 4.35 mg (3 doses or 6 sprays)/wk.

Availability ⬆ ⬇

(Generic available)

Nasal spray: 0.5 mg/spray (Migranal); 0.725 mg/spray (Trudhesa)
Solution for injection: 1 mg/mL (contains alcohol)

Assessment ⬆ ⬇

Assess frequency, location, duration, and characteristics (pain, nausea, vomiting, visual disturbances) of chronic headaches. During acute attack, assess type, location, and intensity of pain before and 60 min after administration.
Monitor BP and peripheral pulses periodically during therapy. Report any increases in BP.
Assess for signs of ergotism (cold, numb fingers and toes; nausea; vomiting; headache; muscle pain; weakness).
Assess for nausea and vomiting. Ergotamine stimulates the chemoreceptor trigger zone. For adults, metoclopramide 10 mg IV may be administered 3–5 min before administration of dihydroergotamine IV. In children, metoclopramide or a phenothiazine antiemetic may be given orally as prophylaxis 1 hr before administration of dihydroergotamine IV. Oral administration may decrease risk of extrapyramidal and other side effects encountered with IV administration.

Toxicity and Overdose:

Toxicity is manifested by severe ergotism (chest pain, abdominal pain, persistent paresthesia in the extremities) and gangrene. Vasodilators, dextran, or heparin may be ordered to improve circulation.

Implementation ⬆ ⬇

Administer as soon as patient reports prodromal symptoms or headache.
Prime pump 4 times before use. Once the nasal spray applicator has been prepared, it should be discarded with any remaining drug in opened vial after 8 hrs.

IV Administration:

Dihydroergotamine may be administered undiluted.
Rate: Administer each dose over 1 min.

Patient/Family Teaching ⬆ ⬇

Instruct patient to use dihydroergotamine at the first sign of an impending headache and not to exceed the maximum dose prescribed.Caution patient not to take dihydroergotamine within 24 hr of other vascular headache suppressants.
- Encourage patient to rest in a quiet, dark room after taking ergotamine.
- Review symptoms of toxicity. Instruct patient to report these promptly.
- Caution patient not to smoke and to avoid exposure to cold; these vasoconstrictors may further impair peripheral circulation.
- May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to the drug is known.
- Advise patient to avoid alcohol, which may precipitate vascular headaches.
- May cause fetal harm. Advise females of reproductive potential avoid dihydroergotamine use during pregnancy and breastfeeding during and for 3 days after last dose. Instruct patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. May cause preterm labor.
IM: SC: Inject at the first sign of a headache and repeat at 1-hr intervals up to 3 doses. Once minimal effective dose is determined, adjust dose for subsequent attacks.
Instruct patient in proper use of nasal spray. Prime nasal sprayer 4 times before dose. Administer 1 spray to each nostril followed in 15 min by an additional spray in each nostril for a total of 4 sprays. Do not tilt head or sniff following spray. Do not use more than amount instructed, may lead to overuse headache. Discard ampule within 8 hr of opening. Do not refrigerate. Assembly may be used for 4 treatments; then discard.
- Advise patient not to use Migranal to prevent a headache if there are no symptoms or if headache is different from typical migraine.
- Instruct patient to notify health care professional if numbness or tingling in fingers or toes; pain, tightness, or discomfort in chest; muscle pain or cramps in arms or legs; weakness in legs; temporary speeding or slowing of heart rate; or swelling or itching occurs.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇