General

Pronunciation:
ue-broe-je-pant

Trade Name(s)

• Ubrelvy

Ther. Class.

vascular headache suppressants

Pharm. Class.

calcitonin gene-related peptide receptor antagonists

Indications

Acute treatment of migraine with or without aura.

Action

Binds to and antagonizes the calcitonin gene-related peptide (CGRP) receptor, which reduces the neuroinflammatory and vasodilatory effects of CGRP.

Therapeutic Effect(s):

Relief of pain associated with acute migraine attacks.

Pharmacokinetics

Absorption: Rapidly absorbed. Absorption delayed by high-fat food.

Distribution: Widely distributed to tissues.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme to inactive metabolites. Eliminated in bile/feces (42% as unchanged drugs) and urine (6% as unchanged drug).

Half-life: 5–7 hr.

TIME/ACTION PROFILE (pain relief)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity;
• Concurrent use of strong CYP3A4 inhibitors;
• End-stage renal disease.

Use Cautiously in:

• Hypertension
• Raynaud phenomenon;
• Severe renal impairment (↓ dose);
• Severe hepatic impairment (↓ dose);
• OB:   Safety not established in pregnancy;
• Lactation:  Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
• Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: hypertension, Raynaud phenomenon

GI: dry mouth, nausea

Neuro: drowsiness

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis and facial/throat edema)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

•  Strong CYP3A4 inhibitors, including  clarithromycin,  itraconazole, or  ketoconazole, may significantly ↑ levels and risk of toxicity; concurrent use contraindicated.
•  Moderate CYP3A4 inhibitors  and  weak CYP3A4 inhibitors, including  ciprofloxacin,  cyclosporine,  fluconazole,  fluvoxamine, or  verapamil, may ↑ levels and risk of toxicity; ↓ ubrogepant dose.
•  Strong CYP3A4 inducers, including  phenobarbital,  phenytoin, or  rifampin, may significantly ↓ levels and effectiveness; avoid concurrent use.
•  Moderate CYP3A4 inducers  or  weak CYP3A4 inducers  may ↓ levels and effectiveness; ↑ ubrogepant dose.
•  P-glycoprotein (P-gp) inhibitors  and  breast cancer resistant protein (BCRP) inhibitors, including  carvedilol,  eltrombopag, or  quinidine, may ↑ levels and risk of toxicity; ↓ ubrogepant dose.

Drug-Natural Products:

 St. John's wort  may ↓ levels and effectiveness; avoid concurrent use.

Drug-Food:

Grapefruit juice may ↑ levels and risk of toxicity; ↓ ubrogepant dose.

Route/Dosage

PO (Adults): 50 mg or 100 mg initially; if response is inadequate at 2 hr, may repeat dose (not to exceed 200 mg/24 hr).  Concurrent use of moderate CYP3A4 inhibitors:  50 mg initially (not to exceed 50 mg/24 hr).  Concurrent use of weak CYP3A4 inhibitors:  50 mg initially; if response is inadequate at 2 hr, may repeat dose (not to exceed 100 mg/24 hr).  Concurrent use of weak or moderate CYP3A4 inducers:  100 mg initially; if response is inadequate at 2 hr, may repeat dose (not to exceed 200 mg/24 hr).  Concurrent use of P-gp or BCRP inhibitors:  50 mg initially; if response is inadequate at 2 hr, may repeat dose (not to exceed 100 mg/24 hr).

Renal Impairment 
PO (Adults): CCr 15–29 mL/min:  50 mg initially; if response is inadequate at 2 hr, may repeat dose (not to exceed 100 mg/24 hr).

Hepatic Impairment 
PO (Adults): Severe hepatic impairment:  50 mg initially; if response is inadequate at 2 hr, may repeat dose (not to exceed 100 mg/24 hr).

Availability

Tablets: 50 mg, 100 mg

Assessment

• Assess pain location, character, intensity, and duration and associated symptoms (photophobia, phonophobia, nausea, vomiting) during migraine.
• Monitor for hypersensitivity reaction, including anaphylaxis, minutes to days after administration.  If reaction occurs,  immediately discontinue ubrogepant and treat as indicated.
• Monitor for new-onset or worsening hypertension.  If either occur,  consider discontinuing ubrogepant if no alternate etiology found or BP is inadequately controlled.
• Assess for signs/symptoms of recurrent, worsening or new-onset Raynaud phenomenon.  If signs/symptoms occur,  discontinue ubrogepant.

Implementation

• PO Administer without regard to food. If needed, a 2nd dose may be taken ≥2 hr after initial dose.

Patient/Family Teaching

• Explain purpose and side effects of medication. Advise patient to read  Patient Information  before starting therapy.
• Instruct patient to take ubrogepant as soon as symptoms of a migraine occur, but it may be administered any time during an attack. If migraine symptoms return, a 2nd dose may be used; allow ≥2 hr between doses, and do not use more than 100 mg in any 24-hr period.
• Inform patient that ubrogepant should only be used during a migraine. It is meant to be used for relief of migraine but not to prevent or ↓ the number of events.
• Advise patient to avoid grapefruit and grapefruit juice during therapy. Instruct patient not take a 2nd tablet within 24 hr if grapefruit or grapefruit juice was consumed.
• May cause dizziness or drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Advise patient to avoid alcohol, which aggravates headaches, during therapy.
• Advise patient that lying down in a darkened room following ubrogepant administration may further help relieve headache.
• Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially St. John's wort.
• Advise patient to notify health care provider immediately if signs and symptoms of hypersensitivity reaction (anaphylaxis, dyspnea, facial or throat swelling, rash, hives, itching) occur.
• Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. Encourage patient to enroll in registry that monitors outcomes in patients who become pregnant while taking ubrogepant by calling 1-833-277-0206 or visiting http://empresspregnancyregistry.com.

Evaluation/Desired Outcomes

Relief of migraine attack.