Sunosi
Sunosi
Generic Name
Sunosi
Mechanism
Sunosi (solriamfetol) is a selective dopamine‑ and norepinephrine‑reuptake inhibitor (DNRI).
• Increases synaptic concentrations of dopamine and norepinephrine by blocking their transporters.
• Enhances cortical arousal and vigilance circuits without stimulating histamine or cholinergic pathways.
• Acts primarily on the central nervous system, providing wake‑promoting effects without impairing REM sleep architecture.
Pharmacokinetics
| Parameter | Key Points | Clinical Relevance |
| Route | Oral | Convenient for outpatient use |
| Absorption | Peak plasma concentration 1–2 h post‑dose | Dose within 30 min of waking is optimal |
| Bioavailability | ~100 % | Dose adjustments rarely required for absorption |
| Half‑life | 8–9 h (steady‑state) | Allows once‑daily dosing with minimal accumulation |
| Metabolism | Primarily hydroxylated by CYP1A2 & CYP2D6; minor CYP3A4 involvement | Concomitant strong CYP1A2 inhibitors (e.g., fluvoxamine) may increase exposure |
| Elimination | Renal excretion of unchanged drug & metabolites | Dose adjustment in severe renal impairment (CrCl <15 mL/min) |
Indications
- Narcolepsy with excessive daytime sleepiness (EDS).
- Obstructive sleep apnea (OSA)‑related excessive daytime sleepiness (EDS).
- Approved as a standalone therapy or as adjunctive therapy *next to* conventional stimulants (e.g., modafinil) when those agents are insufficient or contraindicated.
Contraindications
- Severe hepatic impairment (Child‑Pugh C) – not evaluated.
- Uncontrolled hypertension or cardiovascular disease (e.g., recent MI, unstable angina) – may increase cardiovascular risk.
- Concurrent use with MAO inhibitors or sympathomimetic agents – risk of hypertensive crisis.
- History of hyperthyroidism or pheochromocytoma – contraindicated.
- Pregnancy Category N – use only if benefits outweigh risks.
- Bipolar disorder – risk of mania.
Warnings
• Monitor blood pressure and heart rate on initiation and at 1‑month intervals.
• Potential for drug‑drug interactions with CYP1A2 & CYP2D6 inhibitors or inducers.
• Report any sudden changes in sleep patterns or orthostatic symptoms immediately.
Dosing
1. Starting dose:
• *Narcolepsy and OSA‑EDS:* 150 mg once daily in the morning (≥30 min after waking).
2. Maintenance dose:
• Increase to 300 mg once daily if inadequate response; maximum 450 mg once daily (data sparse).
3. Formulation: Immediate‑release tablets; can be taken with or without food.
4. Adjustments:
• Renal impairment: CrCl 30–49 mL/min – consider 75 mg BID or 150 mg QD.
• Hepatic impairment: Reduce dose or avoid in severe cases.
Titration should be stepwise to reduce adverse events; avoid abrupt discontinuation.
Adverse Effects
| Adverse Effect | Frequency | Notes |
| Headache | Up to 20% | Common; often dose‑related |
| Nausea & vomiting | ~10% | Can be mitigated with food |
| Insomnia or sleep disturbance | 5–10% | Rare but significant; review timing |
| Dry mouth | 8% | #### |
| Increased blood pressure | <5% | Monitor, taper if persistent |
| Palpitations / tachycardia | <4% | Evaluate cardiovascular status |
| Anxiety / agitation | <4% | Observe in patients with psychiatric history |
| Serious – Hypertensive crisis, QT prolongation | Rare | Monitor ECG in high‑risk patients |
| Allergic reactions | <1% | Rash, pruritus |
Monitoring
- Blood Pressure & Heart Rate – baseline, 2–4 weeks, then every 3 months.
- Renal Function (CrCl) – baseline, then annually or sooner if clinically indicated.
- Sleep Diary & Epworth Sleepiness Scale (ESS) – track efficacy and tolerability.
- Adverse Event Log – particularly cardiovascular symptoms.
- Drug‑Drug Interaction Screening – check for potent inducers/inhibitors of CYP1A2 & CYP2D6.
Clinical Pearls
- Early Morning Dose: Initiate in the morning to align with wake‑promoting pharmacodynamics; evening dosing risks insomnia.
- Avoid Co‑administration with MAO‑I’s – can precipitate severe hypertension; requires 14‑day washout.
- Use in OSA Patients with CPAP Adherence Issues: Sunosi can bridge daytime wakefulness deficits when CPAP compliance is intermittent.
- Dose Titration Strategy: Start at 150 mg QD; if %ESS improvement <10% after 4 weeks, increase to 300 mg.
- Special Population – Renal Impairment: Lower the daily dose; consider alternate therapy if CrCl <30 mL/min.
- Patient Education: Stress irritable mood or agitation; advise on potential cardiac symptoms and when to seek care.
- Drug Interactions: Caution with fluoxetine (strong CYP1A2 inhibitor) – monitor for increased plasma levels.
- Clinically Indicated Use Over Stimulants: Sunosi offers benefit in patients who cannot tolerate stimulants such as methylphenidate or amphetamines due to euphoric or abuse potential.
Key Takeaway: Sunosi uniquely restores wakefulness by targeting dopaminergic and noradrenergic pathways, providing a safer profile in patients with narcolepsy or OSA‑related EDS, especially when stimulant intolerance or contraindications exist.