Stimulant Dosage forms - Crouse

Learning Objectives

• Compare and contrast available stimulant dosage forms

• Recognize isomers and pro-drugs of available stimulants and their associated actions

• Counsel patients on proper administration including recommended time to administer stimulants

  • IR vs XR/SR products

  • Differences in HS vs transdermal products

• Recognize dosage form specific adverse effects

  • what’s unique to transdermal?

  • What’s unique to OROS technology?

What was the first marketed stimulant?

Benzedrine!

Points about immediate release stimulants vs Extended-release stimulants

Immediate Release

• BID dosing - usually AM +4 hours later

• Can be TID

Extended Release

• Goal is to emulate BID or TID dose and have extended duration of action 8 hours to 16 hours

What are the isomers of Amphetamine?

D-AMP

• Higher DAT activity

  • more CNS excitatory effects and suppress appetite

L-AMP

• higher NET activity

  • more cardiovascular effects

“Amphetamines have damp lamps”

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Specific products:

1. Dextroamphetamine (Dexedrine)

2. Amphetamine (racemic D and L) - Evekeo

3. Mixed amphetamine salts (3:1 ratio D:L) like Adderall

What are the isomers of Methylphenidate (Ritalin)?

• D-MPH = twice as potent as the L-isomer

  • Dexmethylphenidate (Focalin)

What are the prodrugs for Amphetamine products?

Lisdexamfetamine becomes ——> d-AMP

What are the prodrugs for Methylphenidate products?

Serdexmethylphenidate ——→ Dexmethylphenidate

• 30:70 ratio (Dexmethyl; Serdexmethyl)

• Combo product because serdexmethyl did not reach therapeutic levels until ~8 hours after admin

Amphetamine isomers —- things to know

• anything with “DEX” in it is the D-isomer

• Consists of tablets and spansules

• Dextroamphetamine and dexedrine have stronger effect than amphetamine OR drugs that mix the Adderall isomers (like Adderall)

What is Evekeo?

An amphetamine dosage form

• 1:1 ratio of DAMP to LAMP

• Amphetamine sulfate

What is Adderall XR?

AMphetamine dosage form

• Adderal is mixed salts

• Adderall XR is 3:1 ration DAMP to LAMP

• IR Adderall is BID

• The mixed salts include:

  • aspartate

  • Sulfate

  • Saccharide

What is Mydasis?

Amphetamine dosage form

• 3 types of beads in the capsule

  • IR amphetamine

  • Delayed release 1 bead (pH 5.5)

  • Delayed release 2 bead (pH 7.5)

• Duration 16 hours

Think “My Day Is very long”

Additional Amphetamine Dosage Forms

Oral suspensions:

• Dyanavel

• Adzenys ER 3:1 (Discontinued)

Orally Disintegrating Tablets

• Evekeo ODT

• Adzenys XR ODT

What is the new(ish) transdermal Dextroamphetamine dosage form?

Xelstrym!

What is the only PRESCRIPTION Methamphetamine?

Desoxyn!!!!!!!

What is Ritalin IR vs Ritalin LA?

MEthylphenidate dosage forms!

• Ritalin IR — 20 mg BID

• Ritalin LA — 40 mg QD

• Both ^^ have two peak concentration profiles !

What is Metadate CD?

Methylphenidate dosage form:

• IR 30% // XR 70%

How many peaks does Dexmethylphenidate (Focalin/XR) have?

Focalin XR has 2 peaks, as opposed to regular Focalin

• peaks 4-6 hours apart

When comparing Focalin XR to Aztarys (prodrug of methylphenidate), what do you see?

Despite Focalin XR having multiple large peaks, its concentration of d-MPH over time is actually less than the Prodrug Azstarys

What is Concerta (osmotic pump)?

A methylphenidate dosage form

• “Ghost tablet”

• Utilizes osmotic pressure to push out/release drug

Jornay PM (methylphenidate PM) PK points

• Dose it at BEDTIME

• In adults

  • <5% of the drug is available within first 10 hours after dosing

  • peak is 14 hrs

  • ~74% bioavailability of PM product vs IR given TID

What is Aptensio XR?

A methylphenidate dosage form:

• Multi layer bead

• 40% IR outer layer

• 60% controlled release inner layer (pH dependent)

• ~16 hour duration

• Bi-phasic (2 peaks)

Additional Methylphenidate dosage forms

• Quillivant XR (oral solution)

• QuilliChew ER (cheetah)

What is Daytrana?

A methylphenidate dosage form:

• TRANSDERMAL!

• 9 hour wear time // onset 2 hours after application

• Avoid heat — increases absorption !

What is DayTrana’s (methylphenidate) UNIQUE adverse effect?

Chemical Leukoderma !!!

• RASH!!!! and/or skin bleaching?

What are some important administration points for transdermal methylphenidate (Daytrana)?

• Place patch on HIP, not waist!

• Place on cool, dry skin

• If sticky side gets on fingers, wash ti quickly

• 9 hour dosing

Comparing ADHD transdermal products

Daytrana (methylphenidate)

• duration continues ~1 hour after removal — effects last up to 3 hours post removal

• >50% of methylphenidate content remains in the TD system/patch after removal

• HIP only

Xelstrym (Dextroamphetamine)

• check on patch throughout day

• 90% of D-AMP in TD patch is delivered over 9 hours

• place on hip, upper arm, chest, back, flank

BOTH:

• place on 2 hours before effect is needed

• max wear time of 9 hours

What are some other considerations/counseling points for TD stimulants (Daytrana and Xelstrym)?

• Potentially LOWER misuse risk

• If falls off, need to replace with new patch —→ CII substance

• Don’t share patches

• Write down time you put it on, and set reminder to take it off

• Dispose properly to avoid inadvertent exposure