Lofexidine

Indications

Lofexidine is used for: Opioid Withdrawal

Adult Dose

Opioid Withdrawal Indicated for mitigation of withdrawal symptoms to facilitate abrupt opioid discontinuation in adults; for short-term use (see Dosing Considerations) Starting dose: Three 0.18-mg tablets (0.54 mg) PO QID (5-6 hr between doses) during the period of peak withdrawal symptoms (generally the first 5-7 days after last opioid use) Not to exceed a total daily dose of 2.88 mg (16 tablets) No single dose should exceed 0.72 mg (4 tablets) Treatment may be continued for up to 14 days with dosing guided by symptoms Dose should be reduced, held, or discontinued for individuals who demonstrate a greater sensitivity Lower doses may be appropriate as opioid withdrawal symptoms wane Discontinue by gradually reducing dose over a 2- to 4-day period to mitigate lofexidine withdrawal symptoms (eg, reducing by 1 tablet per dose every 1-2 days) Hepatic impairment Mild (Child-Pugh score 5-6): 3 tablets QID (2.16 mg/day) Moderate (Child-Pugh score 7-9): 2 tablets QID (1.44 mg/day) Severe (Child-Pugh score >9): 1 tablet QID (0.72 mg/day)

Child Dose

Renal Dose

Renal impairment Mild or moderate (eGFR 30-89.9 mL/min/1.73 m²): 2 tablets QID (1.44 mg/day) Severe (eGFR <30 mL/min/1.73 m²), ESRD, or dialysis: 1 tablet QID (0.72 mg/day) May be administered without regard to timing of dialysis

Administration

May take with or without food

Contra Indications

Precautions

May cause hypotension, bradycardia, and syncope; monitor vital signs before dosing and symptoms related to bradycardia and orthostasis; avoid use in patients with severe coronary insufficiency, recent myocardial infarction, cerebrovascular disease, chronic renal failure, and in patients with marked bradycardia Increased risk of QT prolongation; monitor ECG in congestive heart failure, bradyarrhythmias, hepatic impairment, renal impairment, or patients taking medications that lead to QT prolongation (eg, methadone); correct any electrolyte abnormalities (eg, hypokalemia, hypomagnesemia) prior to initiating treatment Patients administering therapy in outpatient setting should be capable of and instructed on self-monitoring for hypotension, orthostasis, bradycardia, and associated symptoms; instruct outpatients to withhold doses when experiencing symptoms of hypotension or bradycardia and to contact health care provider for guidance on how to adjust dosing; if clinically significant or symptomatic hypotension and/or bradycardia occur, next dose should be reduced in amount, delayed, or skipped

Pregnancy-Lactation

Pregnancy There are no available data regarding use in pregnant women Animal data In animal studies, lofexidine decreased breeding rate and increased resorptions at exposures below human exposure Impact of lofexidine on male fertility has not be adequately characterized in animal studies Lactation No information is available regarding the presence of lofexidine or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production Caution if administered to breastfeeding women The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for the drug and any potential adverse effects on the breastfed child or from the underlying maternal condition

Interactions

Avoid use in combination with medications that decrease pulse or blood pressure to avoid the risk of excessive bradycardia and hypotension Methadone and lofexidine both prolong the QT interval; monitor ECG when used concomitantly Coadministration with naltrexone may reduce efficacy of oral naltrexone Coadministration with CYP2D6 inhibitors Concomitant use of paroxetine resulted in increased plasma levels of lofexidine; monitor for symptoms of orthostasis and bradycardia with concomitant use of a CYP2D6 inhibitor Coadministration with CNS depressants Lofexidine potentiates CNS depressive effects of benzodiazepines and is expected to potentiate CNS depressive effects of alcohol, barbiturates, and other sedating drugs Advise patients to inform healthcare provider of other medications they are taking, including alcohol In an outpatient setting, advise patients to be careful or to avoid doing activities such as driving or operating heavy machinery

Adverse Effects

Side effects of Lofexidine : >10% Insomnia (51-55%) Orthostatic hypotension (29-42%) Bradycardia (24-32%) Hypotension (30%) Dizziness (19-23%) Somnolence (11-13%) Sedation (12-13%) Dry mouth (10-11%) 1-10% Syncope: (0.9-1.4%) Tinnitus: (0.9-3.2%)

Mechanism of Action

Centrally acting alpha2-agonist that binds to receptors on adrenergic neurons; this reduces the release of norepinephrine and decreases sympathetic tone