5 ms·

I expect we will see a slew of out-of-patent drugs re-created with deuterium atoms for marginal clinical benefit and then sold under patent again.

adenadel 10y ago
That might happen, but nothing would stop people from using the much cheaper generic of the original drug.
- colinbartlett 10y ago
  Nothing except their doctor recommending the more expensive name brand drug, which happens all the time. I'm sure there are many reasons why this happens including drug companies having cosy relationships with doctors and also consumer advertising causing patients to request specific drugs. Take Nexium.[1] I'm no expert, but I understand Nexium to be esomeprazole, the s-isomer of omeprazole which is to say it's a mirror image chemically. Yet it's the second most prescribed drug in America. 1. http://scienceblogs.com/denialism/2012/01/09/why-no-one-should-take-nexium/ http://scienceblogs.com/denialism/2012/01/09/why-no-one-shou...
  - LoSboccacc 10y ago
    and hospitals.
  - mikeash 10y ago
    If it's a prescription drug, then the doctor might write a prescription for the name brand drug. It's possible for a prescription not to allow a generic substitute, and it seems particularly easy to do in a case like this where the name-brand drug is not identical to the generic.
  - maxerickson 10y ago
    It's not the mirror image of omeprozle (Prilosec, which is both isomers), it's just manufactured so that only one isomer is present in the pills. The same gag with https://en.wikipedia.org/wiki/Levocetirizine https://en.wikipedia.org/wiki/Levocetirizine and cetirizine. Levocetirizine just became available OTC in the US and costs 3x more than generic cetirizine (for dubious benefit).
  - thescriptkiddie 10y ago
    I know that this isn't an option everywhere, but I get my healthcare through an HMO and they will have quite the opposite philosophy. Instead of trying to sell the patient on more expensive drugs, they will actually refuse to prescribe or cover drugs that have a cheaper alternative.
    - maxerickson 10y ago
      Most US insurance plans have a formulary and will not cover all drugs. I've fortunately not had much need for prescription drugs but have almost always been prescribed cheap generics. I think this is a fairly common experience.
  - ksenzee 10y ago
    There can be a real benefit to isomer drugs. They get prescribed way more than they need to, no question, but that doesn't make them entirely useless. For example, desvenlafaxine (Pristiq) is the R-isomer of venlafaxine (Effexor). You'd think it would be a useless me-too drug, but in fact it's metabolized differently, which affects people with CYP450 mutations. Ultrarapid metabolizers will end up with way too little Effexor in their system, whereas Pristiq will work fine for them. Other way around with poor metabolizers: they don't metabolize Effexor well enough, so they'll get worse side effects. (See http://psychopharmacologyinstitute.com/antidepressants/snris/venlafaxine-desvenlafaxine-differences-similarities/ http://psychopharmacologyinstitute.com/antidepressants/snris... and specifically http://psychopharmacologyinstitute.com/wp-content/uploads/12-Metabolizer-types.png. http://psychopharmacologyinstitute.com/wp-content/uploads/12...) Ideally we'd all know our CYP450 profile, or our doctors would, so they could prescribe older and cheaper drugs when they work well enough, and save the new expensive stuff for patients who need it. Maybe someday medicine will come around to using the tools it already has at hand. Sigh.
    - maxerickson 10y ago
      That it is sometimes important makes the (apparent) sham use of the distinction all the much worse.
  - DanBC 10y ago
    > I'm sure there are many reasons why this happens A simpler reason is that the drop-down on computerised notes systems sometimes puts the more expensive version first. https://twitter.com/drmarkporter/status/765569736423927813 https://twitter.com/drmarkporter/status/765569736423927813 > Q for SystmOne GPs: is there a simple way to ensure default drugs offered when prescribing are cheapest versions most commonly prescribed? https://twitter.com/drmarkporter/status/765570038048911360 https://twitter.com/drmarkporter/status/765570038048911360 > For context: our default omeprazole version (20mg) is currently 5 times price of one 4 down. Easily repeated costly error when busy.
- cmdrfred 10y ago
  In order to get a generic approved you need to do testing that shows your drug works in the same way as the original. In order to have a control you need to have the original drug, thus a pharma company can stop production on a drug while still under patent and replace it with this "new" drug (often the same drug with an antacid added) thus making generic approval much more difficult and costly.
cstross 10y ago
Not in this case; the main effect of deuteration is to slow the rate at which the active drug is metabolized and excreted. Now, that might not sound significant — but patient compliance with medication regimes is a significant sticking point in clinical practice; people are generally just terrible about taking their meds on schedule. If you can replace a twice-a-day tablet with a once-a-day treatment, that's a big win for the subset of patients who are forgetful/unreliable at taking their meds twice a day — and in a disease where the symptoms progress to dementia, that's important. More on medication compliance here (some of it quite hair-raising): https://en.wikipedia.org/wiki/Adherence_(medicine) https://en.wikipedia.org/wiki/Adherence_(medicine)
- zkms 10y ago
  > Not in this case; the main effect of deuteration is to slow the rate at which the active drug is metabolized and excreted. this reminds me of deuterating DMT (dimethyltryptamine) in order to fortify bonds that are targeted by MAO -- to avoid the need for pretreatment with a MAO inhibitor (a MAOI -- which tend to be nasty because of all their interactions)
a3n 10y ago
I take two Janumet (metformin and sitagliptin) per day, made by Merk and still in-patent. They make an XR (extended release) version, where you only take one per day. I can see a deuterium version extending the patent rails for another N years.

adenadel 10y ago

That might happen, but nothing would stop people from using the much cheaper generic of the original drug.

colinbartlett 10y ago
Nothing except their doctor recommending the more expensive name brand drug, which happens all the time. I'm sure there are many reasons why this happens including drug companies having cosy relationships with doctors and also consumer advertising causing patients to request specific drugs. Take Nexium.[1] I'm no expert, but I understand Nexium to be esomeprazole, the s-isomer of omeprazole which is to say it's a mirror image chemically. Yet it's the second most prescribed drug in America. 1. http://scienceblogs.com/denialism/2012/01/09/why-no-one-should-take-nexium/ http://scienceblogs.com/denialism/2012/01/09/why-no-one-shou...
- LoSboccacc 10y ago
  and hospitals.
- mikeash 10y ago
  If it's a prescription drug, then the doctor might write a prescription for the name brand drug. It's possible for a prescription not to allow a generic substitute, and it seems particularly easy to do in a case like this where the name-brand drug is not identical to the generic.
- maxerickson 10y ago
  It's not the mirror image of omeprozle (Prilosec, which is both isomers), it's just manufactured so that only one isomer is present in the pills. The same gag with https://en.wikipedia.org/wiki/Levocetirizine https://en.wikipedia.org/wiki/Levocetirizine and cetirizine. Levocetirizine just became available OTC in the US and costs 3x more than generic cetirizine (for dubious benefit).
- thescriptkiddie 10y ago
  I know that this isn't an option everywhere, but I get my healthcare through an HMO and they will have quite the opposite philosophy. Instead of trying to sell the patient on more expensive drugs, they will actually refuse to prescribe or cover drugs that have a cheaper alternative.
  - maxerickson 10y ago
    Most US insurance plans have a formulary and will not cover all drugs. I've fortunately not had much need for prescription drugs but have almost always been prescribed cheap generics. I think this is a fairly common experience.
- ksenzee 10y ago
  There can be a real benefit to isomer drugs. They get prescribed way more than they need to, no question, but that doesn't make them entirely useless. For example, desvenlafaxine (Pristiq) is the R-isomer of venlafaxine (Effexor). You'd think it would be a useless me-too drug, but in fact it's metabolized differently, which affects people with CYP450 mutations. Ultrarapid metabolizers will end up with way too little Effexor in their system, whereas Pristiq will work fine for them. Other way around with poor metabolizers: they don't metabolize Effexor well enough, so they'll get worse side effects. (See http://psychopharmacologyinstitute.com/antidepressants/snris/venlafaxine-desvenlafaxine-differences-similarities/ http://psychopharmacologyinstitute.com/antidepressants/snris... and specifically http://psychopharmacologyinstitute.com/wp-content/uploads/12-Metabolizer-types.png. http://psychopharmacologyinstitute.com/wp-content/uploads/12...) Ideally we'd all know our CYP450 profile, or our doctors would, so they could prescribe older and cheaper drugs when they work well enough, and save the new expensive stuff for patients who need it. Maybe someday medicine will come around to using the tools it already has at hand. Sigh.
  - maxerickson 10y ago
    That it is sometimes important makes the (apparent) sham use of the distinction all the much worse.
- DanBC 10y ago
  > I'm sure there are many reasons why this happens A simpler reason is that the drop-down on computerised notes systems sometimes puts the more expensive version first. https://twitter.com/drmarkporter/status/765569736423927813 https://twitter.com/drmarkporter/status/765569736423927813 > Q for SystmOne GPs: is there a simple way to ensure default drugs offered when prescribing are cheapest versions most commonly prescribed? https://twitter.com/drmarkporter/status/765570038048911360 https://twitter.com/drmarkporter/status/765570038048911360 > For context: our default omeprazole version (20mg) is currently 5 times price of one 4 down. Easily repeated costly error when busy.
cmdrfred 10y ago
In order to get a generic approved you need to do testing that shows your drug works in the same way as the original. In order to have a control you need to have the original drug, thus a pharma company can stop production on a drug while still under patent and replace it with this "new" drug (often the same drug with an antacid added) thus making generic approval much more difficult and costly.

cstross 10y ago

Not in this case; the main effect of deuteration is to slow the rate at which the active drug is metabolized and excreted. Now, that might not sound significant — but patient compliance with medication regimes is a significant sticking point in clinical practice; people are generally just terrible about taking their meds on schedule. If you can replace a twice-a-day tablet with a once-a-day treatment, that's a big win for the subset of patients who are forgetful/unreliable at taking their meds twice a day — and in a disease where the symptoms progress to dementia, that's important. More on medication compliance here (some of it quite hair-raising): https://en.wikipedia.org/wiki/Adherence_(medicine) https://en.wikipedia.org/wiki/Adherence_(medicine)

zkms 10y ago
> Not in this case; the main effect of deuteration is to slow the rate at which the active drug is metabolized and excreted. this reminds me of deuterating DMT (dimethyltryptamine) in order to fortify bonds that are targeted by MAO -- to avoid the need for pretreatment with a MAO inhibitor (a MAOI -- which tend to be nasty because of all their interactions)

a3n 10y ago

I take two Janumet (metformin and sitagliptin) per day, made by Merk and still in-patent. They make an XR (extended release) version, where you only take one per day. I can see a deuterium version extending the patent rails for another N years.