💊 Dual Orexin Antagonist Dose Titration Simulator

Standard Adult DORA Dosing

Healthy adults start at the standard labeled dose.

• 20 mg: Standard adult dose (nightly starting dose)
• 5–13 h: Half-life range (varies by agent)
• CYP3A4: Primary clearance (hepatic metabolism)
• 30–60 min: Time to peak (oral absorption)

Mechanism of Action

Blocks orexin receptors to quiet wake-promoting signals.

Standard Titration Rule

Full dose applies only when organ function is normal.

Baseline Safety Margin

Plasma exposure stays within predictable, well-tolerated limits.

Elderly Dose Adjustment

Aging slows clearance, so the starting dose drops.

• ~25%: Elderly dose reduction (lower starting dose)
• ↓ 30–40%: Hepatic blood flow (by age 65+)
• 2–3×: Falls risk increase (with excess sedation)
• 15 mg: Recommended max age dose (typical elderly ceiling)

Pharmacokinetic Aging

Slower hepatic flow prolongs drug exposure in elders.

Fall and Fracture Risk

Next-day sedation raises fall risk in older adults.

Conservative Starting Point

Lower dose first, then titrate carefully upward.

Hepatic Impairment Dose Reduction

A struggling liver clears the drug much slower.

• 0.55×: Moderate impairment factor (clearance capacity)
• Avoid use: Severe impairment guidance (not recommended)
• ~80%: AUC increase (moderate) (vs normal liver)
• Child-Pugh: Monitoring parameter (score at baseline)

Reduced Metabolic Capacity

CYP3A4 activity falls as liver injury worsens.

Drug Accumulation Risk

Slower clearance lets plasma levels build up.

Severe Impairment Caution

Severe impairment usually means avoiding the drug.

Concurrent CNS Depressant Use

Combined sedatives stack respiratory and sedation risk.

• ~1.8×: Sedation risk multiplier (with co-administration)
• Opioids, BZDs: Common interacting classes (alcohol also included)
• ~30%: Recommended dose cut (when combined)
• Elevated: Respiratory depression flag (monitor closely)

Additive CNS Depression

Two sedating drugs compound drowsiness together.

Respiratory Safety Concern

Combined depressants can blunt breathing drive.

Dose Reduction Strategy

Lower the DORA dose whenever depressants are present.

Optimized Individualized Starting Dose

Age, liver function, and drugs combine into one dose.

• Dynamic: Final personalized dose (from all three factors)
• 3: Factors integrated (age, hepatic, CNS drugs)
• Start low: Titration approach (reassess and adjust)
• Lowest effective dose: Goal (minimize sedation harm)

Multiplicative Risk Model

Each risk factor multiplies down the safe dose.

Personalized Titration

Every patient gets a uniquely calculated starting dose.

Ongoing Reassessment

Reassess dose as liver function or drugs change.