Lofexidine Hydrochloride and Telotristat Etiprate

• Generic Name: lofexidine
• Dosage Forms: n.a.
• Other Brand Names: Lucemyra

Used for mitigation of opiate withdrawal symptoms to facilitate abrupt opiate discontinuance.

Not a treatment for opiate use disorder (OUD); use in patients with OUD only in conjunction with a comprehensive treatment program.

In patients with OUD, opiate withdrawal management (i.e., detoxification) generally involves short-term use of tapering dosages of buprenorphine (opiate partial agonist) or methadone (full opiate agonist) to reduce withdrawal symptoms. However, α2-adrenergic agonists (e.g., lofexidine, clonidine) also used for symptomatic relief of noradrenergic-mediated opiate withdrawal symptoms (e.g., lacrimation, sweating, shivering, rhinorrhea) in inpatient and outpatient settings and may allow for withdrawal over a shorter period of time.

α2-Adrenergic agonists appear to be less effective than buprenorphine or methadone for management of opiate withdrawal; some experts suggest α2-adrenergic agonists may be most useful in withdrawal management as adjuncts to opiate agonists or partial agonists, to facilitate transition to opiate antagonist (naltrexone) treatment for relapse prevention, or when opiate agonist or partial agonist therapy is contraindicated, unacceptable, or unavailable.

Concomitant supportive therapy for other withdrawal symptoms (e.g., abdominal cramping, diarrhea, nausea and vomiting, muscle spasms, anxiety or restlessness, insomnia) often used.

Several small comparative studies suggest lofexidine and clonidine have similar efficacy in managing opiate withdrawal symptoms but lofexidine may cause less hypotension. Must also consider greater cost of lofexidine compared with off-label clonidine use.

Because of potential for hypotension and bradycardia, some experts state that α2-adrenergic agonists are not drugs of choice for opiate withdrawal management in geriatric patients or patients with coronary insufficiency, ischemic heart disease, bradycardia, or cerebrovascular disease.

In patients receiving long-term opiate analgesia, withdrawal symptoms generally managed by slow tapering of the opiate analgesic dosage.

• Generic Name: telotristat
• Dosage Forms: n.a.
• Other Brand Names: Xermelo

Used (in combination with somatostatin analog therapy) for treatment of carcinoid syndrome diarrhea inadequately controlled by somatostatin analog therapy alone (designated an orphan drug by FDA for the treatment of carcinoid syndrome in patients with neuroendocrine tumors).

Carcinoid syndrome, a condition associated with serotonin overproduction, is characterized by flushing, diarrhea, wheezing, occasionally congestive heart failure, and various other manifestations. Although somatostatin analogs (e.g., octreotide, lanreotide) are standard treatment for carcinoid syndrome and are effective initially in most patients, some patients may not respond adequately or may develop recurrent symptoms, including diarrhea, despite therapy.

In clinical studies, telotristat ethyl reduced the frequency of daily bowel movements in patients with carcinoid syndrome diarrhea. Reductions in other symptoms of carcinoid syndrome (e.g., abdominal pain, flushing) not observed.