Dosing Tips

• Clinical duration of action often differs from pharmacokinetic half-life

✽ Immediate-release d,l-amphetamine has 3–6 hour duration of clinical action

✽ Extended-release d,l-amphetamine has up to 8-hour duration of clinical action

• Adderall XR is controlled-release and should therefore not be chewed but rather should only be swallowed whole

✽ Controlled-release delivery of d,l-amphetamine is sufficiently long in duration to allow elimination of lunchtime dosing

✽ This innovation can be an important practical element in stimulant utilization, eliminating the hassle and pragmatic difficulties of lunchtime dosing at school, including storage problems, potential diversion, and the need for a medical professional to supervise dosing away from home

• Avoid dosing late in the day because of the risk of insomnia

• May be possible to dose only during the school week for some ADHD patients

• Off-label uses are dosed the same as for ADHD

✽ May be able to give drug holidays over the summer in order to reassess therapeutic utility and effects on growth and to allow catch-up from any growth suppression as well as to assess any other side effects and the need to reinstitute stimulant treatment for the next school term

• Side effects are generally dose-related

• Taking with food may delay peak actions for 2–3 hours

Overdose

• Rarely fatal; panic, hyperreflexia, rhabdomyolysis, rapid respiration, confusion, coma, hallucinations, convulsions, arrhythmia, change in blood pressure, circulatory collapse

Long-Term Use

• Often used long-term for ADHD when ongoing monitoring documents continued efficacy

• Dependence and/or abuse may develop

• Tolerance to therapeutic effects may develop in some patients

• Long-term stimulant use may be associated with growth suppression in children (controversial)

• Periodic monitoring of weight, blood pressure, CBC, platelet counts, and liver function may be prudent

Habit Forming

• High abuse potential, Schedule II drug

• Patients may develop tolerance, psychological dependence

How to Stop

• Taper to avoid withdrawal effects

• Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder and may require follow-up and reinstitution of treatment

• Careful supervision is required during withdrawal from abusive use since severe depression may occur

Pharmacokinetics

• Adderall and Adderall XR are a mixture of d-amphetamine and l-amphetamine salts in the ratio of 3:1

• A single dose of Adderall XR 20 mg gives drug levels of both d-amphetamine and l-amphetamine comparable to Adderall immediate-release 20 mg administered in 2 divided doses 4 hours apart

• In adults, half-life for d-amphetamine is 10 hours and for l-amphetamine is 13 hours

• For children ages 6–12, half-life for d-amphetamine is 9 hours and for l-amphetamine is 11 hours

Drug Interactions

• May affect blood pressure and should be used cautiously with agents used to control blood pressure

• Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid, ascorbic acid, fruit juices, etc.) and urinary acidifying agents (ammonium chloride, sodium phosphate, etc.) lower amphetamine plasma levels, so such agents can be useful to administer after an overdose but may also lower therapeutic efficacy of amphetamines

• Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) and urinary alkalinizing agents (acetazolamide, some thiazides) increase amphetamine plasma levels and potentiate amphetamine’s actions

• Desipramine and protryptiline can cause striking and sustained increases in brain concentrations of amphetamine and may also add to amphetamine’s cardiovascular effects

• Theoretically, other agents with norepinephrine reuptake blocking properties, such as venlafaxine, duloxetine, atomoxetine, milnacipran, and reboxetine, could also add to amphetamine’s CNS and cardiovascular effects

• Amphetamines may counteract the sedative effects of antihistamines

• Haloperidol, chlorpromazine, and lithium may inhibit stimulatory effects of amphetamines

• Theoretically, atypical antipsychotics should also inhibit stimulatory effects of amphetamines

• Theoretically, amphetamines could inhibit the antipsychotic actions of antipsychotics

• Theoretically, amphetamines could inhibit the mood-stabilizing actions of atypical antipsychotics in some patients

• Combinations of amphetamines with mood stabilizers (lithium, anticonvulsants, atypical antipsychotics) is generally something for experts only, when monitoring patients closely and when other options fail

• Absorption of phenobarbital, phenytoin, and ethosuximide is delayed by amphetamines

• Amphetamines inhibit adrenergic blockers and enhance adrenergic effects of norepinephrine

• Amphetamines may antagonize hypotensive effects of veratrum alkaloids and other antihypertensives

• Amphetamines increase the analgesic effects of meperidine

• Amphetamines contribute to excessive CNS stimulation if used with large doses of propoxyphene

• Amphetamines can raise plasma corticosteroid levels

• MAOIs slow absorption of amphetamines and thus potentiate their actions, which can cause headache, hypertension, and rarely hypertensive crisis and malignant hyperthermia, sometimes with fatal results

• Use with MAOIs, including within 14 days of MAOI use, is not advised, but this can sometimes be considered by experts who monitor depressed patients closely when other treatment options for depression fail