Thursday, September 2, 2010

Midodrine may not be there!

The latest medication which has come under FDA's radar in the last the drug that has been increasingly used by nephrologists and heaptologists--- MIDODRINE .
On Aug 17th 2010 FDA issued a proposal to withdraw midodrine from the market within 30 days. 
So I decided to look into the evidence behind using Midodrine. 
Let me start with a little background on Midodrine---- It is a alpha agonist, and acts on venous and arteriolar vasculature producing increased vascular tone. It increases sitting, standing and lying BP.So the most common side effect reported is supine hypertension.

It is surprising that there is very scarce data on the clinical effectiveness of Midodrine. So far 3 randomised trials have been done. One is 3 weeks duration, and the other two are of 1-2 days duration!!! All studies were done on patients with orthostatic hypotension .
In the 3 week trial(JAMA 1997), pts on Midodrine(10 mg tid) had significantly higher (by about 20 mmHg) 1-minute standing systolic pressure 1 hour after dosing (blood pressures were not measured at other times) for all 3 weeks.They also had a similar increase in supine and sitting BP. And 25% of the 82 pts on Midodrine  dropped out of the study(due to pilomotor reactions, supine HTN, urinary retention)
The 1 & 2 day study also showed similar improvements in standing BP.In 1 day study the supine BP was >200 systolic in 22% pts on 10mg and 45% pts on 20mg. This elevated BP lasted for 6 hours after the dose. 

The only indication midodrine is approved is for Orthostatic hypotension. This has been extrapolated, and has been commonly used in one other setting...which is for treating hypotension during dialysis. There are nearly 10 studies on this..but again..the largest of these studies had 21 participants, and with short follow up. Have a look at this review from 2004

So there seems to be no real convincing data to support Midodrine. The Shire pharmaceuticals agreed to perform post marketing trials..but failed to do any. And thats the reason for FDA's proposal. It seems unlikely that Midodrine will be available in the near future(as early as this month).So what this means is..that physicians and patients on Midodrine have to be prepared to find an alternated  drug pretty soon!