If Adderall XR is unavailable, what else can you prescribe?

Your patient is a 34 yo man with ADHD who has been stable on Adderall XR 30mg for 15 years. He can’t get the medication due to the nationwide shortage. What else can you prescribe if Adderall XR is not available in pharmacies?

There are only two types of stimulants that are prescribed for ADHD – methylphenidate derivatives and amphetamine derivatives. These are different medications with different mechanisms of action. The 30+ stimulant pills, liquids, and patches are sophisticated delivery systems that release methylphenidate or amphetamine derivatives at different speeds and for various durations. All stimulants for ADHD are composed of varying amounts of the two enantiomers (dextro (D) or levo (L)) of either methylphenidate or amphetamine. The immediate release formulations of methylphenidate (duration of 3-4 hours) and amphetamine (duration of 4-6 hours) both need to be dosed 2-3x per day. 

For our patient: Adderall XR is a mixed amphetamine salt (75% D and 25% L amphetamine), so the closest substitute should also be an amphetamine. Adderall XR 30mg has a double-pulsed release, with 50% (Adderall 15mg) released immediately, and 50% (Adderall 15mg) released 4 hours later. Adderall XR 30mg is essentially Adderall 15mg BID, if you take the second dose 4 hours after the first dose. The XR pill is useful because people don’t need to remember to take a second dose at lunchtime. While generic Adderall remains in short supply, at times there are brand-name Adderall pills available at pharmacies. If only specific milligram doses of immediate release Adderall are available, they can be split or combined as necessary.

If neither Adderall XR nor Adderall is available, there are some newer and more expensive formulations of the same mixed amphetamine salts. Adzenys XR is a long-acting, orally dissolving tablet. Adderall XR 30mg = Adzenys XR ODT 18.8mg, due to differences in bioavailability. There is a voucher available to help with the co-pay. Mydayis is another newer and more expensive formulation of Adderall. It has a triple pulse release of Adderall, in which a third of the dose is released immediately, a third released 4 hours later, and the last third released 4 hours later. Taking Adderall XR 30mg in the morning and Adderall (immediate release) 15mg eight hours later provides comparable plasma concentrations to Mydayis 45mg daily. When switching from Adderall XR to Mydayis, we need to increase the total dosage to maintain the same clinical effects over a longer duration of time. The closest equivalent to Adderall XR 30mg (~Adderall 15mg BID) would be Mydayis 45mg (~Adderall 15mg TID, with the doses taken 4 hours apart). Round the dose to the closest available pill of Mydayis (50mg). There is also a voucher available to help with the Mydayis co-pay.

If your head is spinning a bit, that’s ok. The main point is that when your patients come to you on stimulant pills that you have never heard of before, you know that they are all derivatives of either amphetamine or methylphenidate, and that there are ways to convert between them within the class. You also know how to convert from Adderall XR to Adderall, and the names of 2 brand name versions of extended-release Adderall that may be available in the pharmacies. Take a look at the summary table below to help with these conversions, and then we’ll cover Vyvanse and two related meds.

Conversions between common amphetamine derivatives for treating ADHD

AdderallAdderall XRAdzenys XR-ODTMydayis XR Dextro-amphetamineDexedrine
Spansules (ER)
Vyvanse (lisdexam-fetamine)
Duration
per dose
4-6 h8-12 h8-12 h12-16 h4-6 h6-8 h10-14 h
Enantiomers75% D, 25% L75% D, 25% L 75% D, 25% L75% D, 25% L 100% D100% Dprodrug->
100%D
Dose equivalence (approximate)5mg BID10mg6.3mg15mg4mg BID8mg26mg
Conversion Factor from
Adderall XR
(total dose)
11Adderall x0.63 Adderall x1.5Adderall
x0.83
Adderall x0.83Adderall x2.6
Pill doses available
(in mg)
5, 7.5, 10, 12.5, 15, 20, 305, 10, 15,
20, 25, 30
3.1, 6.3, 9.4, 12.5, 15.7, 18.812.5, 25,
37.5, 50
5, 10 5, 10, 1510, 20, 30, 40, 50, 60, 70
Cost$$$$$$$$$$$$$
Scroll to right on mobile device to see full table

Vyvanse is the brand name of lisdexamfetamine, which is a prodrug. While Adderall is composed of mixed amphetamine salts (75% D, 25% L; both enantiomers are pharmacologically active), Vyvanse is converted to 100% D-amphetamine. The molecule lisdexamfetamine (using the British spelling dexamfetamine) is d-amphetamine covalently bonded to L-lysine, which prevents it from crossing the blood brain barrier.  Put another way, if one were to crush and snort a bottle of Vyvanse, there would be no euphoric effect. The same is not true for Adderall.  When taken by mouth, Vyvanse is absorbed in the gut and hydrolyzed by red blood cells at a steady state, releasing the pharmacologically active d-amphetamine molecule slowly over time. Vyvanse is often experienced as smoother – having fewer ups and downs– than Adderall XR.  Vyvanse also lasts longer, for ~12 hours. Adderall XR 30mg is ~Vyvanse 78mg, but the conversions from Adderall to Vyvanse are approximate. I would prescribe Vyvanse 70mg daily. When in doubt, start at a lower dose of a new stimulant and titrate up as needed.

D-amphetamine is also available generically as immediate release dextroamphetamine (also called Dexedrine, Dextrostat), and dexedrine spansules (an extended release capsule), which could also be used as substitutes for Adderall. Compared to Adderall, the medications with 100% D-amphetamine are less likely to cause increases in heart rate and blood pressure but are more likely to cause appetite suppression. Vyvanse at higher doses has an FDA indication for binge eating disorder.

Let’s return to our patient who can’t fill the Adderall XR 30mg prescription that has helped him for all of his adult life. What should we prescribe instead? Unfortunately, available stimulants at pharmacies are changing week to week. If one prescription gets rejected, I have the patient talk with the pharmacist to learn which stimulants in the same class (methylphenidate or amphetamine derivatives) are available, and in which strengths, before sending in another prescription. By understanding how various amphetamine medications are related and how to convert between some common options, you can choose a reasonable substitute that is accessible.


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