Generic Name

Wakix

Mechanism

Wakix (solriamfetol) is a selective dopamine reuptake inhibitor that also targets the norepinephrine transporter (NET).
• Inhibits the dopamine transporter (DAT) → ↑ extracellular dopamine in the CNS, enhancing wakefulness and alertness.
• Partial blockade of NET contributes to norepinephrine‑mediated arousal pathways.
• No affinity for serotonin or adenosine receptors, limiting serotonergic side‑effects common to other stimulants.

Pharmacokinetics

• Absorption: Oral bioavailability ~47 % when taken with food; peak plasma concentrations (T_max) 2.6 h post‑dose.
• Distribution: Volume of distribution ≈0.4 L/kg. Minimal plasma protein binding.
• Metabolism: Primarily glucuronidated by UDP‑glucuronosyltransferase (UGT) enzymes; negligible CYP involvement → minimal drug‑drug interaction.
• Elimination: Renally excreted (≈80 % unchanged); terminal half‑life 9–10 h.
• Special Populations:
• Renal impairment: Dose reduction in moderate CKD (eGFR < 60 mL/min/1.73 m²).
• Hepatic impairment: Use with caution; no data in severe hepatic disease.

Indications

• Narcolepsy: Chronic treatment for excessive daytime sleepiness (EDS).
• Obstructive Sleep Apnea (OSA): Adjunct to CPAP to improve wakefulness when residual EDS persists.
• Off‑label: Emerging evidence for shift‑work sleep disorder, but not FDA‑approved.

Contraindications

• Contraindicated in: Patients with a history of uncontrolled hypertension, severe cardiovascular disease, or psychosis.
• Warnings:
• ↑blood pressure and heart rate → monitor cardiovascular status.
• Potential for anxiety, insomnia, and mood lability.
• Sympathomimetic effect may precipitate seizures in susceptible individuals.
• Caution with MAO inhibitors (though interaction risk is low, clinical overlap exists).

Dosing

• Take with or without food; avoid taking late in the day to prevent insomnia.
• If BID dosing is used, keep the interval ≥12 h.

Adverse Effects

Common (≥5 %)
• Headache
• Nausea / GI upset
• Insomnia/poor sleep quality
• Increased blood pressure (systolic/diastolic)
• Anxiety / nervousness

Serious (≤1 %)
• Severe hypertension or tachycardia
• Psychotic episodes or mood disorders (especially in predisposed patients)
• Seizure precipitation
• Severe GI bleeding (rare)

Monitoring

• Blood pressure & heart rate: baseline, 2 weeks, 4 weeks, then quarterly.
• Weight & appetite: baseline + every 4 weeks (appetite suppression noted).
• Psychiatric assessment: baseline, 2 weeks, 6 weeks; watch for mood changes.
• Renal function: baseline eGFR; repeat if CKD suspected.

Clinical Pearls

1. Start Low, Go Slow: Begin at 37.5 mg once daily; titrate only when EDS persists and when vital signs remain stable.
2. Avoid Late‑Day Dosing: Initiate first dose in the early morning; late or evening use strongly associated with insomnia.
3. Cardiovascular Vigilance: Because of modest BP effects, patients on antihypertensives may need dose adjustments or closer monitoring.
4. No Significant CYP Interaction: Solriamfetol’s metabolite profile avoids the “drug‑drugs interaction peril” common with many stimulants.
5. Adjunct in CPAP‑Noncompliant OSA: Early data shows improved wakefulness when combined with CPAP in patients who continue to experience residual EDS.
6. Psychiatric Screening: Patients with a history of bipolar disorder or schizophrenia should be consulted with psychiatry prior to initiation.
7. Transition Care: When switching from modafinil or methylphenidate, stop the old drug at least 48 hours before the first solriamfetol dose to mitigate additive psychostimulant effects.

> Key Takeaway: Wakix is a targeted wakefulness agent that offers a favorable interaction profile while improving daytime alertness in narcolepsy and OSA. Early titration and vigilant cardiovascular monitoring are the cornerstones of safe, effective use.