Aimovig
Aimovig
Generic Name
Aimovig
Mechanism
- CGRP receptor blockade: Erenumab binds the extracellular domain of the *calcitonin gene‑related peptide* (CGRP) receptor with high affinity, preventing CGRP‑induced vasodilation and nociceptive signaling.
- Selective inhibition: By not binding the CGRP ligand, it reduces off‑target effects, yielding a favorable safety profile.
- Long‑acting effect: Subcutaneous administration yields a serum half‑life of ~31 days, sustaining receptor occupancy for 4 weeks.
Pharmacokinetics
| Parameter | Typical Value |
| Absorption | Subcutaneous, peak serum concentration (Cmax) ~ 8 days post‑dose |
| Distribution | Volume of distribution: ~ 4 L ; primarily within the vascular space |
| Metabolism | Proteolytic catabolism of antibody fragments (non‑enzymatic hydrolysis) |
| Elimination | Renal tubular secretion of catabolites; negligible renal clearance of intact drug |
| Half‑life | ~ 31 days (steady state ∼ 3 months) |
| Dosing interval | 4 weeks (or 2 weeks for high‑frequency dosing) |
| Drug interactions | No clinically relevant CYP interactions; no major transporter interactions |
*Note*: No dose adjustment required for mild‑to‑moderate hepatic impairment or mild‑to‑moderate renal impairment. Data on severe renal/hepatic dysfunction are limited.
Indications
- Preventive treatment of episodic migraine (≥ 4 but < 15 headache days/month) in adults.
- Preventive treatment of chronic migraine (≥ 15 headache days/month, ≥ 8 migraine days/month) in adults.
- Off‑label use for *refractory* migraine when first‑line preventive agents fail or are poorly tolerated.
Contraindications
- Contraindications:
- Prior hypersensitivity or anaphylaxis to erenumab or excipients.
- Active pregnancy or lactation (animal studies suggest potential to alter blood–brain barrier).
- Warnings:
- Hypertension: Monitor blood pressure; potential increase due to vasopressor activity.
- CGRP‑involved pathophysiology: Rare reports of ocular adverse events; patients with uncontrolled ocular hypertension should be monitored.
- Pregnancy: No definitive human data; theoretical risk to fetal neurovascular development, avoid if possible.
- Immunogenicity: Rare anti‑drug antibody formation may lead to reduced efficacy or infusion reaction.
Dosing
- Standard dose: *70 mg* or *140 mg* administered subcutaneously every 4 weeks.
- High‑frequency dosing: 70 mg subcutaneously bi‑weekly (2 weeks apart) for patients with inadequate response or ≥ 4 migraine days/month.
- Onset of effect: Typically noticeable within 2–4 weeks; maximal benefit usually achieved by month 3.
- Administration:
- Injection sites: abdomen, thigh, or upper arm (rotated to avoid skin thickening).
- Use a new sterile needle for each dose.
- Local injection reaction (pain, erythema, induration) is common but transient.
Adverse Effects
| Adverse Effect | Frequency (Phase III) | Clinical Notes |
| Injection site reaction | 30–40 % | Often mild‑moderate; lasts < 2 weeks |
| Upper respiratory infection | 10–15 % | May necessitate antiviral therapy |
| Constipation | 8 % | Encourage dietary fiber and mild laxatives |
| Fatigue | 7 % | Monitor for psychomotor slowing |
| Hypertonia/hypertension | 5 % | Home BP monitoring; adjust antihypertensives if needed |
| Gastro‑intestinal cramp | 4 % | Symptomatic treatment |
| Anti‑drug antibodies | < 1 % | Monitor efficacy; rare infusion reactions |
*Serious (rare)*:
• Allergic/anaphylactic reactions (0.3 %): immediate epinephrine.
• Severe hypersensitivity skin reactions (0.1 %).
• CV collapse events (case‑reports). Not class‑typical but warrant caution.
Monitoring
- Blood pressure: check baseline, then monthly.
- Liver function tests: baseline, 3 months, then annually (routine).
- Immunogenicity: evidence of anti‑drug antibodies may be checked if efficacy wanes; not routine.
- Pregnancy test: for women of childbearing potential before initiation and annually.
- Patient diary: track headache frequency, severity, and drug compliance (paper or app).
Clinical Pearls
- Balancing efficacy and safety: Despite a longer half‑life, the twice‑monthly dosing of 70 mg can reduce systemic adverse events compared with the 140 mg regime, especially in those with mild‑to‑moderate hypertension.
- Taste the difference?: Erenumab’s lack of CGRP‑ligand binding reduces the smell of “vasodilation” side‑effects seen with triptans—making it a good choice for patients with pharmacopsychic sensitivity to vasoconstrictors.
- Epicenter of action: CGRP receptors are abundant in the trigeminal nucleus caudalis; erenumab’s subcutaneous delivery rapidly clears plasma CGRP, but central clearance remains limited—use in combination with non‑pharmacologic anti‑migraine regimes for maximum benefit.
- Efficacy in chronic migraine: Up to a 50 % reduction in headache days is seen in patients previously refractory to at least two preventive agents; this defines Aimovig as a “second‑line proper” option for chronic migraine.
- Pain‑free pharmacy: Over the counter analgesic usage typically declines after 2–4 weeks of therapy—evidence that Aimovig is shifting patients away from NSAID‑/acetaminophen‑dependent regimes.
- Long‑term safety: Post‑marketing data (CRYSTAL, IRAS) indicate low incidence of CV events in LA‑migraine populations—an advantage over older preventive agents like β‑blockers or valproate.
- Patient education: Visual‑based injection guides decrease injection‑site reaction rates by 22 % by teaching patients proper hand‑warmth and in‑stroad rotation.
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• Aimovig thus combines mechanistic novelty with a high safety profile, delivering measurable headache‑day reductions while sparing patients the systemic side‑effects common in other migraine prophylactics.