Treatment of Opioid Withdrawal Symptoms

The next issue of The Medical Letter (Issue 1551, July 16, 2018) includes an article on lofexidine (Lucemyra), a new drug for management of opioid withdrawal symptoms. Lofexidine is new in the sense that it was only recently approved by the FDA, but the drug has been approved in Europe for many years for the same indication.

Lofexidine is a centrally-acting alpha2-adrenergic agonist similar to clonidine (Catapres, and generics), which is FDA-approved only for treatment of hypertension, but is also used off-label for treatment of opioid withdrawal symptoms. Buprenorphine and methadone are the drugs of choice for management of opioid withdrawal symptoms, but alpha2-adrenergic agonists offer a nonopioid (albeit less effective) alternative. Their mechanism of action in reducing opioid withdrawal symptoms appears to be moderation of sympathetic overactivity. Their main drawback is that they cause hypotension.

The cost of one week’s treatment with Lucemyra, just for the drug, at the lowest usual initial dosage is $1738. The cost of a one-week supply of generic clonidine is $1. If you used Catapres, the brand-name product, the cost would be $52.80. Could one alpha2-adrenergic agonist really be that much better than another? There are three controlled trials comparing the two, all published in Drug and Alcohol Dependence in 1997 and 1998. They all come to the conclusion that the two drugs are almost identical in their efficacy in reducing symptoms, but clonidine is more troublesome in causing hypotension.1-3

Neither drug, it bears repeating, is the best choice for this indication. A recent article in The New England Journal of Medicine makes a strong case for overturning the bureaucratic roadblocks that limit the prescribing of buprenorphine.4

  1. A Kahn et al. Double-blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. Drug Alcohol Depend 1997; 44:57.
  2. SK Lin et al. Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal. Drug Alcohol Depend 1997; 48:127.
  3. T Carnwath and J Hardman. Randomised double-blind comparison of lofexidine and clonidine in the out-patient treatment of opiate withdrawal. Drug Alcohol Depend 1998; 50:251.
  4. SE Wakeman and ML Barnett. Primary care and the opioid-overdose crisis – buprenorphine myths and realities. N Engl J Med 2018; 379:1.

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  1. A.T. Scherer MD says:

    Some day perhaps there will be criminal prosecution as deserved of the FDA for approving and pharmaceutical companies for such shenanigans. Just as there should have been for the colchicine approval several years ago. Amazing what some companies will sink to in the attempt to make money.

  2. Richard Swint,MD says:

    Dr. Scherer is right. He should have added make money by fraud utilizing government employees. Richard Swint,MD

  3. Loretta Collins, LGPC says:

    I couldn’t agree more. The government talks about the opioid crisis, but it is just lip service. This will sound horrible, but until more Congressional relatives and children die from opioid use disorder (OUD), nothing meaningful will be done. The Fat Cats of Pharma will keep lining their pockets, and the government and FDA will let them.

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