Ubrelvy
Ubrelvy
Generic Name
Ubrelvy
Mechanism
- Selective 5‑HT1F receptor agonist
- Stimulates presynaptic 5‑HT1F receptors on trigeminovascular neurons.
- Inhibits the release of pro‑inflammatory neuropeptides (substance P, CGRP, glutamate) from trigeminal endings.
- Reduces central neuronal excitability in the migraine pain pathway without activating vascular 5‑HT1B/D receptors → no vasoconstriction.
- Clinical outcome: Rapid onset of migraine pain relief (typically within 30–60 min).
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Pharmacokinetics
| Parameter | Detail |
| Absorption | Oral tablets; peak plasma concentration (T_max) ~0.9–1 h post‑dose. |
| Bioavailability | ~21 % (oral). |
| Distribution | Highly lipophilic; crosses blood‑brain barrier. Protein binding ~90 % (primarily albumin). |
| Metabolism | Predominantly CYP3A4‑mediated; minor CYP2D6 route. |
| Elimination | 70 % renal, 30 % fecal. Terminal half‑life ~1‑2 h (dose‑dependent). |
| Special Populations |
• Renal impairment: modest increase in exposure; no dose adjustment needed. • Hepatic impairment: exposure ↑, but not clinically significant; use cautiously. • Elderly: similar PK; monitor for CNS effects. |
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Indications
- Acute treatment of migraine with or without aura in adults.
- Can be used in patients with cardiovascular disease (hypertension, coronary artery disease) as it avoids vasoconstriction.
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Contraindications
| Category | Key Points |
| Contraindications |
• Hypersensitivity to lasmiditan or excipients. • Uncontrolled severe hypertension. • Susceptibility to seizures (e.g., epilepsy, CNS damage). |
| Warnings |
• CNS depression: dizziness, fatigue, impaired cognition—avoid driving or operating machinery until symptoms resolve. • Cardiovascular: Although vasoconstriction is absent, monitor ECG and QT interval in patients with known conduction abnormalities (QTc > 500 ms). • Drug interactions: CYP3A4 inhibitors/inducers can increase/decrease lasmiditan levels. Avoid concomitant use of potent CYP3A4 inhibitors (e.g., ketoconazole). |
| Precautions |
• Pregnancy/Lactation: Category B; limited data—use only if benefit outweighs risk. • Alcohol: may potentiate CNS side effects. • Opioid analgesics: risk of additive CNS depression. |
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Dosing
| Dose | Recommended Use |
| 23 mg | Initial dose for mild‑to‑moderate pain or when rapid onset desired. • Can be repeated after 2 h if pain persists. • Max 2 doses per migraine (46 mg total). |
| 15 mg | For patients at higher risk of CNS side effects (e.g., elderly, concomitant CNS depressants). • Can repeat once 2 h later. |
| 47 mg | Double‑dose: 23 mg + 24 mg (23 mg dose + 24 mg staggered after ≥2h) for severe attacks; not a single 47 mg tablet. |
| Administration | Oral tablets taken on an empty stomach or with light food. Take promptly after migraine onset. |
> Note: Adjust dose for body weight and age only if clinically indicated; no formal dose adjustment protocol for renal/hepatic impairment.
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Adverse Effects
- Common (≥10 %): dizziness, fatigue, paresthesia, nausea, vertigo, blurred vision, sedation, myalgia, cough.
- Serious (≤1 %):
- CNS: severe depression, psychosis, seizures, altered mentation.
- Cardiovascular: palpitations, arrhythmia, hypertension spikes (rare).
- Gastrointestinal: severe nausea/vomiting.
> *Adverse effect profile aligns with CNS depressant class; careful monitoring in at‑risk patients.*
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Monitoring
- Baseline: BP, heart rate, ECG (QTc) for patients with conduction abnormalities.
- During Treatment:
- Observe for sedation and CNS depression in the first 2–3 h.
- Reassess BP if history of hypertension or taking antihypertensives.
- Follow‑up: Evaluate migraine frequency response after 2–3 weeks; adjust dosing or consider alternative therapies if inadequate relief.
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Clinical Pearls
1. Vascular‑Safety Advantage – Because lasmiditan is a selective 5‑HT1F agonist, it is a *first‑line* acute migraine therapy in patients with cardiovascular disease or *contraindicated* for triptans.
2. Rapid Onset but Short Half‑Life – Expect pain relief within 30–60 min; keep in mind the short terminal half‑life when considering repeat dosing (>2 h interval).
3. CNS Side‑Effects Guide Patient Counseling – Inform patients that ‘lightness’ and drowsiness may impair driving or operating machinery for *up to 4 h* after dosing; advise safe transport options.
4. CYP3A4 Interaction – Recognize that ketoconazole, itraconazole, ritonavir can raise plasma lasmiditan levels; for such patients, consider the 15 mg starting dose and careful titration.
5. Double‑Dose Strategy – For severe attacks, a *23 mg + 23 mg* staggered dose (total 46 mg) may be superior to a single 23 mg, but data are limited; always reassure the patient about potential CNS effects.
6. No Dose Adjustment in Mild–Moderate Renal Impairment – Unlike many triptans, lasmiditan can be used unchanged in patients with CrCl ≥ 30 mL/min.
7. Patient Selection – Prior migraine history can predict response; patients who have failed at least two other acute agents may benefit from a trial of Ubrelvy.
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