Monday, July 7, 2008

Maybe you shouldn't try this at home

Lisdexamfetamine (Vyvanse) is a relatively new drug. Literature on this medication began to appear in Pub Med about a year ago. It is classified as a "prodrug," which means that it is taken in an inactive form, which then becomes active in the body.

According to the first reviews written about lisdexamfetamine, it supposedly has less abuse potential than dextroamphetamine (Dexedrine, and in combination with other compounds, Adderall), two other medications popular for treating attention deficit-hyperactivity disorder.

However, that doesn't mean toxicity is not an issue. In the words of the researchers themselves, this is what happened when lisdexamfetamine was given to a group of rats:

In an acute study, LDX doses of 60 mg/kg and higher caused increased motor activity. At 1000 mg/kg, one rat died and another was euthanized. In a 7-day repeat-dose study, all rats dosed with LDX (14 per dose group for each sex) showed increased activity; 10 male rats and 11 female rats at 300 mg/kg/day and 3 female rats at 100 mg/kg/day were euthanized because of self-mutilation and 1 male rat at 300 mg/kg/day was found dead. In a 28-day study, only rats at 80 mg/kg showed signs of self-mutilation and thin body condition. In both the 7- and 28-day studies, LDX caused significant changes in some blood chemistry parameters (e.g. blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase) and organ weights (e.g. particularly heart, liver, brain, and spleen).

Self-mutilation is absolutely not a benign or neutral side effect.

"...the apparent lethal dose of LDX in rats is more than five times higher than the LD(50) of orally administered d-amphetamine, supporting a putative protective effect of conjugating amphetamine with lysine."

OK, whew! Apparently since rats were less self-destructive on this medication than they were on dextroamphetamine, they were good to go with the marketing!

Now, an article is showing up in Pub Med with the following title:

Poison Centers Detect an Unexpectedly Frequent Number of Adverse Drug Reactions to Lisdexamfetamine.

And the first sentence of MedLine Plus fact sheet on this medication is, "Lisdexamfetamine can be habit-forming." This about a medication that is supposedly designed to reduce abuse potential!

I cannot access the article online, but as soon as I can get the text, I'll be sure to share it.

Because of the toxicity issue, I want to post known side effects, as listed on MedLine Plus' fact sheet. If you experience any of these, consult your prescribing physician immediately:

restlessness
mood swings
irritability
difficulty falling asleep or staying asleep
uncontrollable shaking of a part of the body
dizziness
headache
dry mouth
stomach pain
nausea
vomiting
loss of appetite
weight loss
fever
fast or pounding heartbeat
chest pain
shortness of breath
fainting
seizures
hallucinating (seeing things or hearing voices that do not exist)
aggression
frenzied, abnormally excited mood
seizures
tics
blisters
rash

I am having a hard time with a medication that was supposed to be a kindler, gentler form of a very potent--and popular--medication having some seemingly serious problems that for some reason...are just buried in the literature.

Faraone SV, Upadhyaya HP. The effect of stimulant treatment for ADHD on later substance abuse and the potential for medication misuse, abuse, and diversion. J Clin Psychiatry. 2007 Nov;68(11):e28.

Blick SK, Keating GM. Lisdexamfetamine. Paediatr Drugs. 2007;9(2):129-35; discussion 136-8.

Biederman J, Krishnan S, Zhang Y, McGough JJ, Findling RL. Efficacy and tolerability of lisdexamfetamine dimesylate (NRP-104) in children with attention-deficit/hyperactivity disorder: a phase III, multicenter, randomized, double-blind, forced-dose, parallel-group study. Clin Ther. 2007 Mar;29(3):450-63.

Krishnan S, Montcrief S. Toxicity profile of lisdexamfetamine dimesylate in three independent rat toxicology studies. Basic Clin Pharmacol Toxicol. 2007 Oct;101(4):231-40.

Spiller HA, Griffith JRK, Anderson DL, Weber JA, Aleguas A. Poison Centers Detect an Unexpectedly Frequent Number of Adverse Drug Reactions to Lisdexamfetamine. Ann Pharmacother. 2008 Jul 1.

http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a607047.html

1 comment:

mijiji said...

Do you realize that the absurdly high dosage they gave to rats doesn't say anything about the effects of a normal dose of vyvanse? Even the lowest dose mentioned, 60mg/kg, would come to a 4,200mg dose for a 150lb (70kg) individual. Clinical dosages range from 20mg - 70mg. That comes out to roughly .5% - 1.75% of the dose they gave to rats. This would be like saying a red bull is harmful to humans because dose of equivalent to 10,000mg of caffeine will kill a rat.