Kapvay
Kapvay™
Generic Name
Kapvay™
Mechanism
- Pro‑drug Activation – Lisdexamfetamine is inactive until enzymatically cleaved by red‑blood‑cell‑derived red‑blood‑cell amidotransferase to dextroamphetamine and lysine.
- Neurotransmitter Release – Dextroamphetamine blocks the dopamine and norepinephrine transporters (DAT and NET) and induces reverse transport, increasing synaptic concentrations of dopamine and norepinephrine in pre‑frontal and striatal circuits.
- Modulation of Attention Networks – Elevated catecholamine tone enhances executive control, working memory, and inhibitory control—core deficits in ADHD.
- Reduced Abuse Liability – The enzymatic activation requires intracellular processing, delaying peak effect and reducing the “rush” that underlies stimulant misuse.
Pharmacokinetics
| Parameter | Typical Value (children 6‑12) | Comments |
| Absorption | Peak plasma concentration (Cmax) at 2–5 hrs (after breakfast). | Oral bioavailability ~95 %. |
| Metabolism | Cleavage by cytosolic amidation → dextroamphetamine; minor hepatic oxidation. | No clinically relevant drug–drug interactions via CYP450. |
| Elimination | Renal excretion (~80 %) of unchanged dextroamphetamine and metabolite. | T½ 5–11 hrs; dose proportional. |
| Food effect | Minimal; co‑administration with food delays but does not reduce Cmax. |
Indications
- ADHD in patients aged 6–12 years (FDA; 2012).
- In many countries (Australia, Canada, EU) also indicated for adult ADHD (≥ 12 yrs).
Contraindications
| Category | Key Points |
| Contraindications |
• Hypersensitivity to lisdexamfetamine or any component. • Concomitant use of monoamine‑oxidase inhibitor (MAOI) within 14 days. |
| Warnings |
• Cardiovascular: Hypertension, tachycardia, arrhythmias; avoid in severe congenital heart disease or uncontrolled hypertension. • Psychiatric: Pre‑existing mania or severe depression; risk of increased aggression, irritability, suicidal ideation. |
| Precautions |
• Use caution in patients with growth concerns; monitor height/weight. • In patients with seizure disorders, use only if seizure control is satisfactory. |
Dosing
| Developmental Stage | Starting Dose | Titration | Max Dose | Frequency |
| Children (6‑12 yrs) | 18 mg (tablet) | Increase by 1 mg every 7 days if needed | 36 mg | Once daily (breakfast) |
| Adults (≥ 12 yrs, non‑pediatric) | 36 mg (tablet) or 18 mg (capsule) | Increase by 18 mg every 7 days | 72 mg | Once daily (breakfast) |
• Administration: Swallow whole; do not crush or chew.
• Special populations:
• Renal impairment: No dose adjustment needed.
• Hepatic impairment: Mild–moderate: start at lower dose and titrate cautiously.
• Pediatric patients: Begin at 18 mg and titrate; avoid exceeding 36 mg.
Adverse Effects
- Common
- Insomnia, decreased appetite, weight loss, dry mouth, headache.
- GI upset (nausea, abdominal pain).
- Increased heart rate and blood pressure.
- Serious
- Cardiovascular arrhythmias, hypertensive crises.
- Severe psychiatric events: mania, psychosis, suicidal ideation.
- Growth suppression in children (weight and height).
Monitoring
| Parameter | Frequency | Clinical Rationale |
| Weight & BMI | Monthly for the first 6 months, then every 3–6 months | Detect weight loss/growth delay. |
| Blood Pressure & Pulse | At baseline, then bi‑weekly for first 2 months, then quarterly | Detect hypertension/tachycardia. |
| Growth (height) | Every 6–12 months in children | Monitor growth suppression. |
| Psychiatric status | Baseline, then bi‑weekly for first month, then monthly | Identify emergent mood or behavior changes. |
| Drug‑level testing | Not routinely needed | Only if abuse suspected. |
Clinical Pearls
1. Abuse‑prevention advantage – Because lisdexamfetamine requires intracellular enzymatic conversion, the onset is delayed (~2 hrs), reducing the “high” and lowering the risk of diversion.
2. Holiday taper strategy – Many patients benefit from a 3‑day taper before school holidays or during exam periods to reduce jitteriness or insomnia.
3. Co‑administration with other stimulants – Avoid concomitant use of other stimulants to reduce cardiovascular risk; if necessary, use a 4‑hour interval.
4. Growth concerns – Document baseline height and weight; counsel caregivers that transient weight loss may precede a plateau but typically normal growth resumes once dosage stabilizes.
5. Seizure threshold – While not an absolute contraindication, use caution in patients with a history of seizures; monitor for increased seizure activity.
6. Patient education on food – Although food does not significantly alter efficacy, advise taking with breakfast to improve absorption and mitigate post‑prandial GI upset.
Kapvay represents an evidence‑based, lower‑abuse‑potential therapeutic option for pediatric ADHD, offering sustained catecholamine elevation and improved executive function while maintaining a favorable safety profile when appropriately monitored.