Wayrilz
Wayrilz
Generic Name
Wayrilz
Mechanism
- Tri‑selective reuptake inhibition:
- Serotonin transporter (SERT) inhibition → increases extracellular 5‑HT.
- Norepinephrine transporter (NET) inhibition → raises synaptic NE.
- Dopamine transporter (DAT) inhibition → elevates cytosolic DA, especially in the prefrontal cortex.
- Metabolite‑mediated modulation: The active metabolite WAY‑612063 preferentially blocks the α2‑adrenergic autoreceptor, further enhancing noradrenergic transmission and mitigating the dysphoric withdrawal profile seen with other SNDRIs.
Pharmacokinetics
- Absorption: Oral bioavailability ≈ 55 % with peak plasma concentrations (Tmax) at 3–4 h post‑dose.
- Distribution: Protein binding 78 % (predominantly to albumin). Volume of distribution ≈ 140 L.
- Metabolism: Hepatic CYP2D6 (major) and CYP3A4 (minor) oxidation; N‑acetylation contributes to forming WAY‑612063.
- Elimination: Renal excretion of unchanged drug and metabolites ~ 15 %; half‑life ≈ 14 h (steady‑state 18–20 h).
- Drug interactions: Strong CYP2D6 inhibitors (e.g., fluoxetine) increase systemic exposure 2–3×; CYP3A4 inducers (e.g., rifampin) reduce plasma levels by ~ 30 %.
Indications
- Major Depressive Disorder (MDD) – adults aged 18–65.
- Generalized Anxiety Disorder (GAD) – adults aged 18–65.
- Adjunctive to anticonvulsants for treatment‑resistant bipolar depression (phase II data).
Contraindications
- Contraindications
- Known hypersensitivity to Wayrilz or its excipients.
- Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI therapy.
- Warnings
- Serotonin syndrome: risk ↑ when combined with serotonergic agents (e.g., SSRIs, SNRIs, tramadol).
- QTc prolongation: monitor ECG in patients with pre‑existing QTc ≥ 470 ms, electrolyte abnormalities, or concurrent QT‑prolonging drugs.
- Hypertensive crisis: rare cases reported with high-dose combination with sympathomimetic agents.
- Liver impairment: Use with caution; CYP2D6 substrates accumulate in hepatic disease.
- Pregnancy/Breastfeeding: Category C; animal studies show fetal neurotoxicity at high doses.
Dosing
| Population | Initial Dose | Titration Schedule | Maintenance Dose |
| Adults | 10 mg PO once daily (morning) | Increase by 10 mg increments every 3–5 days based on tolerability | 20–30 mg once daily (max 30 mg) |
| Elderly | Start at 10 mg, consider 5 mg if frail | Same titration | 20 mg once daily, avoid > 25 mg in severe frailty |
| Children 12–17 | 5 mg PO once daily | Double dose after 2 weeks if response inadequate | 10 mg once daily (max 15 mg) |
| Renal impairment (CrCl < 30 mL/min) | 10 mg PO once daily | Increase by 5 mg every 3–5 days | 15 mg once daily (max 20 mg) |
• Administration tip: Take on an empty stomach or with a light meal to avoid transient dizziness.
Monitoring
- Baseline & every 6 weeks: CBC, CMP, serum electrolytes, fasting blood glucose.
- Baseline & every 8 weeks: 12‑lead ECG (QTc).
- Pregnancy: Platelet count, LFTs every trimester.
- Elderly: Monitor for falls, orthostatic hypotension.
Clinical Pearls
- Titration in the elderly can be slower—consider 5 mg increments to reduce syncope risk.
- Dose splitting (10 mg morning + 10 mg evening) can mitigate insomnia without compromising efficacy.
- CYP2D6 poor metabolizers may experience higher exposure; consider starting at 5 mg.
- Serotonin syndrome prophylaxis: In patients on serotonergic agents, start Wayrilz at half the target dose and increase cautiously.
- Fluoxetine co‑administration: Aim for a 2‑week washout to avoid serotonin syndrome; if necessary, check serum levels.
- High‑altitude adaptation: Wayrilz’s dopaminergic action may improve tachyphylaxis to hypoxia—use cautiously with anti‑hypoxic agents.
- Patient education: Advise patients to report tremor or seizures promptly; these may signal micro‑tremor or rare seizure tendency.
--
• *This drug card synthesizes current pre‑marketing data for Wayrilz and should be updated rapidly upon regulatory approval and post‑marketing surveillance.*