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FDA approves lofexidine for opioid withdrawal symptoms.
The FDA approved lofexidine (Lucemyra, Catalent Pharma Solutions) in May for treatment of opioid withdrawal symptoms in adults. Lofexidine is a selective alpha-2 adrenergic agonist that reduces the release of norepinephrine, which decreases sympathetic tone.1 Reduction in norepinephrine is believed to be key in mitigating symptoms of opioid withdrawal.
The efficacy of lofexidine was evaluated in two phase 3 randomized double-blind placebo-controlled trials of patients meeting DSM-IV criteria for opioid dependence.2,3 In the first phase 3 trial, 602 patients received either lofexidine 2.88 mg total daily dose, 2.16 mg total daily dose, or matching placebo. The coprimary efficacy endpoints were the mean Short Opiate Withdrawal Scale of Gossop (SOWS-Gossop) on days 1 through 7 on treatment and the proportion of patients who completed seven days of therapy. Mean difference in scores between both lofexidine groups and placebo was found to be statistically in favor of lofexidine, indicating lessened withdrawal symptoms. Patients on lofexidine were also more likely to complete seven days of therapy than those on placebo. Those discontinuing treatment cited lack of efficacy.
In the second trial, 264 patients received either lofexidine 2.88 mg total daily dose or matching placebo. The coprimary efficacy endpoints were the mean SOWS-Gossop score on days 1 through 5 on treatment and the proportion of patients who completed five days of therapy. As with the first study, patients on lofexidine were found to have statistical reductions in SOWS-Gossop on days 1 through 5 and a statistically higher proportion of patients retained on therapy at day 5.
A study comparing lofexidine/methadone versus buprenorphine/naloxone in detoxification demonstrated noninferiority of buprenorphine compared to lofexidine.4
The safety of lofexidine was assessed across three randomized double-blind placebo-controlled trials. The trials enrolled 935 patients on short-acting opioids experiencing withdrawal. The combined dataset presented a similar safety profile and the drug was well tolerated. Adverse reactions that were reported in more than 10% of patients on lofexidine included orthostatic hypotension, bradycardia, dizziness, somnolence, sedation, and dry mouth.1
Geriatric use of lofexidine has not been determined; caution is advised. Safety in pregnant and/or lactating women has not been established.
Lofexidine is dosed 0.54 mg orally four times daily with 6 hours between each dose. Subsequent dosing should be guided by symptom presentation and tolerability of side effects. The maximum total daily dosage is 2.88 mg. Lofexidine is administered for the first 5 to 7 days after last use of opioids, and can be continued for up to 14 days.
Dose adjustments are recommended in renal insufficiency. Patients with an eGFR between 30 ml/min/1.73m2 to 89.9 ml/min/1.73m2 should receive 0.54 mg four times daily, a maximum total daily dose of 2.16 mg. Patients with an eGFR <30 ml/min/1.73m2, ESRD, or on dialysis should receive 0.18 mg four times daily, a maximum total daily dose of 0.72 mg.
Dose adjustments are recommended in hepatic insufficiency and are dependent on the Child-Pugh score: Mild (score 5 to 6), give a maximum total daily dose of 2.16 mg; Moderate (score 7 to 9), give a maximum total daily dose of 1.44 mg; Severe (score >9), give a maximum total daily dose of 0.72 mg.