The US FDA has approved the alpha-adrenergic agonist lofexidine HCl (Lucemyra®) for the treatment of opioid withdrawal symptoms.
- First non-opioid approved for treating opioid withdrawal symptoms
- Approved for up to 14 days after discontinuation of opioids
- Alpha-2 adrenergic agonist, suppresses sympathetic outflow
- Originally developed in 1980s for management of hypertension
- Most common side effects: hypotension, bradycardia, sedation and dizziness
- Alternative treatments for opioid withdrawal: gradual opioid dose taper, switch to less addictive opioids (e.g., methadone, buprenorphine), use opioid receptor antagonists (naltrexone)
- 2 Phase III clinical trials, 866 patients
- Both randomized placebo-controlled
- Patients selected via DSM-IV opioid withdrawal, SOWS-Gossop scale
- Approved for opioid withdrawal since 1992 in UK
What is an alpha-2 agonist?
Lofexidine and other alpha-2 adrenergic agonists (e.g., clonidine, guanfacine) are drugs that stimulate alpha-2 adrenergic receptors in the central nervous system. These receptors normally sense epinephrine and norepinephrine levels and respond to stimulation by shutting down norepinephrine secretion. Activation of these receptors by drugs decreases the amount of norepinephrine (and its metabolite epinephrine) in the blood.
Other alpha-2 agonists are used as 2nd line agents in the management of hypertension and in the treatment of ADHD.