Dexmethylphenidate Hydrochloride

Pronunciation: (dex-METH-il-FEN-i-date HYE-droe-KLOR-ide)
Class: CNS stimulant

Trade Names

Dexmethylphenidate hydrochloride
- Tablets 2.5 mg
- Tablets 5 mg
- Tablets 10 mg

Focalin
- Tablets 2.5 mg
- Tablets 5 mg
- Tablets 10 mg

Focalin XR
- Capsules, ER 5 mg
- Capsules, ER 10 mg
- Capsules, ER 15 mg
- Capsules, ER 20 mg
- Capsules, ER 30 mg
- Capsules, ER 40 mg

Pharmacology

Exact mechanism of action is unknown; however, the drug may block the reuptake of norepinephrine and dopamine into presynaptic neurons and increase the release of these monoamines into extranational spaces.

Pharmacokinetics

Absorption

Readily absorbed. T _max is 1 to 1.5 h for immediate-release. For the ER, time to the first peak is 1.5 h and time to the second peak is 6.5 h. Absolute bioavailability is 22% to 25%. High-fat food increased tablet T _max to 2.9 h.

Distribution

Vd is approximately 2.65 L/kg. Racemic methylphenidate is bound to plasma proteins by 12% to 15%, independent of concentration.

Metabolism

Metabolized by de-esterification to d-ritalinic acid (inactive).

Elimination

Approximately 90% recovered in urine (approximately 80% as ritalinic acid). The half-life is approximately 2 to 4.5 h.

Special Populations

Renal Function Impairment

Renal impairment is expected to have little effect on the pharmacokinetics of dexmethylphenidate.

Hepatic Function Impairment

Differences in pharmacokinetics have not been defined.

Gender

In adults, the AUC was 25% to 35% higher in women compared with men. Parameters were similar for boys and girls.

Race

Differences in pharmacokinetics have not been defined.

Indications and Usage

Treatment of attention deficit hyperactivity disorder (ADHD).

Contraindications

Family history or diagnosis of Tourette syndrome; glaucoma; hypersensitivity to methylphenidate or other components of product; MAOI treatment and within 14 days following discontinuation of an MAOI; marked anxiety, tension, or agitation; motor tics.

Dosage and Administration

Patients new to methylphenidate or taking stimulants other than methylphenidate
Immediate-release tablets Adults and Children 6 y of age and older

PO 2.5 mg twice daily; adjust dose in 2.5 to 5 mg increments at weekly intervals (max, 10 mg twice daily).

Focalin XR Adults

PO 10 mg once daily; adjust dose in 10 mg increments at weekly intervals (max, 40 mg once daily).

Children 6 y of age and older

PO 5 mg once daily; adjust dose in 5 mg increments at weekly intervals (max, 30 mg once daily).

Patients currently receiving methylphenidate switching to Focalin XR
Adults and Children 6 y of age and older

PO Starting dose is 50% of the dose of racemic methylphenidate (max, 20 mg/day immediate-release or 40 mg/day ER for adults; 20 mg/day immediate-release or 30 mg/day ER for children).

Conversion from dexmethylphenidate immediate-release tablets to Focalin XR
Adults and Children 6 y of age and older

PO Use same daily dose of dexmethylphenidate immediate-release tablets when switching to Focalin XR (max, 40 mg/day for adults; 30 mg/day for children).

General Advice

Administer without regard to meals. Administer with food if GI upset occurs.
Administer tablets at least 4 h apart.
Administer Focalin XR once daily in the morning.
Do not crush, chew, or divide contents of Focalin XR .
For patients who have difficulty swallowing Focalin XR , the capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. Patients should consume the mixture immediately without chewing. Do not prepare the drug and applesauce mixture ahead of time and store for future use.

Storage/Stability

Store between 59° and 86°F. Protect tablets from light and moisture.

Drug Interactions

Acid suppressants, antacids

Coadministration could alter the release of dexmethylphenidate ER capsules.

Anticonvulsants (eg, phenytoin), coumarin anticoagulants (eg, warfarin), SSRIs (eg, fluoxetine), tricyclic antidepressants (eg, amitriptyline)

Effects may be increased by dexmethylphenidate, necessitating a decrease in dosage.

Antihypertensive agents (eg, clonidine)

Effects may be decreased by dexmethylphenidate. Although an interaction has not been established, serious adverse reactions have been associated with coadministration of clonidine.

Halogenated anesthetics

Coadministration may cause a sudden increase in BP during surgery.

Pressor agents (eg, dopamine)

Additive effects on BP may occur.

MAOIs (eg, phenelzine)

Discontinue MAOI therapy at least 14 days before starting dexmethylphenidate.

Adverse Reactions

Cardiovascular

Tachycardia; increase in heart rate (3 to 6 bpm); increase in BP (2 to 4 mm Hg).

CNS

Headache (39%); decreased appetite (30%); insomnia (17%); feeling jittery (12%); anxiety (11%); dizziness (6%); irritability (5%); depression, mood swings (3%); twitching (motor or vocal tics).

GI

Dry mouth (20%); abdominal pain (15%); dyspepsia, nausea, vomiting (9%); anorexia (7%).

Respiratory

Pharyngolaryngeal pain (7%); nasal congestion (5%).

Miscellaneous

Fever (5%); pruritus (3%); weight loss during prolonged therapy.

Precautions

Warnings

Drug dependence

Give dexmethylphenidate cautiously to patients with a history of drug dependence or alcohol abuse. Long-term, abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during drug withdrawal from abusive use because severe depression may occur. Withdrawal following long-term therapy may unmask symptoms of the underlying disorder that may require follow-up.

Monitor

Monitor for appearance or worsening of aggressive behavior or hostility. Periodically monitor CBC, differential, and platelet counts during prolonged therapy. Monitor growth in children.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Not for use in children younger than 6 y of age.

Bipolar illness

Use with caution to treat ADHD in patients with comorbid bipolar disorder because of possible induction of mixed/manic episode.

Dose reduction/discontinuation

Reduce dose, or discontinue therapy if necessary, if paradoxical aggravation of symptoms or other adverse reactions occur. If improvement is not observed after appropriate dosage adjustment over a 1-month period, discontinue the drug.

Growth suppression

Has been reported with long-term use of stimulants in children. Consider interrupting treatment in patient who is not growing or gaining weight as expected.

Hypertension/CV disease

Use with caution.

Maintenance/Extended treatment

Periodically evaluate long-term usefulness with periods off medication to assess patient's functioning without pharmacotherapy.

New psychotic or manic symptoms

Treatment-emergent psychotic or manic symptoms (eg, delusional thinking) can occur in children and adolescents without a history of psychotic illness or mania.

Psychosis

Symptoms of behavior disturbances and thought disorder may be exacerbated in patients with a preexisting psychotic disorder.

Seizures

Convulsive threshold may be lowered in patients with a history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, rarely, in patients without a history of seizures and no prior EEG evidence of seizures. Discontinue therapy in presence of seizures.

Sudden death

Sudden death has occurred in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities. Sudden death, stroke, and MI have occurred in adults taking stimulant drugs at usual doses for ADHD. Do not use stimulant drugs in children, adolescents, or adults with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems.

Visual disturbances

Blurring of vision and difficulties with accommodation may occur.

Overdosage

Symptoms

Agitation, cardiac arrhythmias, confusion, delirium, dryness of mucous membranes, euphoria, flushing, hallucinations, headache, hyperpyrexia, hyperreflexia, hypertension, muscle twitching, mydriasis, palpitations, seizures (may be followed by coma), sweating, tachycardia, tremors, vomiting.

Patient Information

Advise patient or caregiver to read the Medication Guide before starting therapy and with each refill.
Advise patient or caregiver that this drug is part of a total treatment program for ADHD that should also include psychological, educational, and social interventions.
Advise patient or caregiver to take without regard to meals, but to take with food if stomach upset occurs.
Caution patient or caregiver that capsules should be swallowed whole and not crushed, chewed, or divided.
If patient has difficulty swallowing capsules, advise patient or caregiver that capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The mixture should be consumed immediately without chewing. Caution patient or caregiver not to prepare the drug and applesauce mixture ahead of time and store for future use.
Advise patient or caregiver to notify school or day care personnel about medication use and administration.
Advise patient or caregiver that health care provider may periodically change the dose to obtain maximal benefit and to take as prescribed and not to stop taking or change the dose unless advised by the health care provider.
Advise patient or caregiver that health care provider may periodically discontinue medication to assess behavior and determine need to continue therapy.
Caution patient that drug may cause dizziness or drowsiness and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
Advise patient or caregiver to notify health care provider if visual changes, appetite loss, nervousness, or difficulty sleeping occur and are bothersome, or if any unusual or unexplained symptoms or feelings are noted.