brands

Class

• Neuroscience-based Nomenclature: dopamine reuptake inhibitor (D-RI)
• Wake-promoting

Provake commonly prescribed for

(Bold for FDA approved)

How Provake works

• Unknown, but clearly different from classical stimulants such as methylphenidate and amphetamine

• Binds to and requires the presence of the dopamine transporter; also requires the presence of alpha adrenergic receptors

• Hypothetically acts as an inhibitor of the dopamine transporter

• Increases neuronal activity selectively in the hypothalamus

• Presumably enhances activity in hypothalamic wakefulness center (TMN, tuberomammillary nucleus) within the hypothalamic sleep-wake switch by an unknown mechanism

• Activates TMN that release histamine

• Activates other hypothalamic neurons that release orexin/hypocretin

How long until Provake works

• Can immediately reduce daytime sleepiness and improve cognitive task performance within 2 hours of first dosing

• Can take several days to optimize dosing and clinical improvement

Notable Side Effects

• Headache (dose-dependent)

• Anxiety, nervousness, insomnia

• Dry mouth, diarrhea, nausea, anorexia

• Pharyngitis, rhinitis, infection

• Hypertension

• Palpitations

Life Threatening Side Effects

• Transient ECG ischemic changes in patients with mitral valve prolapse or left ventricular hypertrophy have been reported (rare)

• Rare activation of (hypo)mania, anxiety, hallucinations, or suicidal ideation

• Rare severe dermatologic reactions (Stevens–Johnson syndrome and others)

• Angioedema, anaphylactoid reactions, and multi-organ hypersensitivity reactions have been reported

weight gain

unusual

sedation

unusual

What to do about Provake side effects

• Wait

• Lower the dose

• Give only once daily

• Give smaller split doses 2 or more times daily

• For activation or insomnia, do not give in the evening

• If unacceptable side effects persist, discontinue use

• For life-threatening or dangerous side effects, discontinue immediately (e.g., at first sign of a drug-related rash)

usual dosage range

• 200 mg/day in the morning

Dosage Forms

• Tablet 100 mg, 200 mg (scored)

long term use

• Efficacy in reducing excessive sleepiness in sleep disorders has been demonstrated in 9- to 12-week trials

• Unpublished data show safety for up to 136 weeks

• The need for continued treatment should be reevaluated periodically

habit forming

• Schedule IV; may have some potential for abuse but unusual in clinical practice

Renal Impairment

• Use with caution; dose reduction is recommended

Hepatic Impairment

• Reduce dose by half in severely impaired patients

Cardiac Impairment

• Use with caution

• Not recommended for use in patients with a history of left ventricular hypertrophy, ischemic ECG changes, chest pain, arrhythmias, or recent myocardial infarction

Elderly

• Limited experience in patients over 65

• Clearance of modafinil may be reduced in elderly patients

Children and Adolescents

• Safety and efficacy not established under age 16

• Can be used cautiously by experts for children and adolescents

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• Intrauterine growth restriction and spontaneous abortion have been reported with armodafinil and modafinil

• In animal studies, developmental toxicity was observed at clinically relevant plasma exposures of armodafinil and modafinil

• Use in women of childbearing potential requires weighing potential benefits to the mother against potential risks to the fetus

• Generally, modafinil should be discontinued prior to anticipated pregnancies

Breast Feeding

• Unknown if modafinil is secreted in human breast milk, but all psychotropics are assumed to be secreted in breast milk

• Recommended either to discontinue drug or bottle feed