Colistimethate Sodium and Lofexidine Hydrochloride

• Generic Name: colistimethate
• Dosage Forms: n.a.
• Other Brand Names: Coly Mycin M

Treatment of acute or chronic infections caused by certain susceptible gram-negative bacteria (e.g., Enterobacter aerogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa).

Used only when the causative agent is susceptible and other more effective and less toxic anti-infectives are contraindicated or ineffective.

May be useful alone or in conjunction with other anti-infectives for treatment of infections caused by multiple-drug resistant gram-negative bacteria, such as respiratory tract infections in cystic fibrosis patients caused by multiple-drug resistant Ps. aeruginosa.

Not indicated for infections caused by Proteus or Neisseria.

Administered by oral inhalation via nebulization in adult and pediatric cystic fibrosis patients for early treatment of Ps. aeruginosa respiratory tract infections and for suppressive therapy in those colonized with Ps. aeruginosa.

Safety and efficacy not established and the drug is not labeled by FDA for administration via nebulization. Adverse respiratory effects (e.g., bronchoconstriction) have occurred with this route and there has been at least one fatality in a patient who self-administered a nebulizer treatment using a premixed solution of the drug. (See Respiratory Effects under Cautions.)

• 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.