to mitigate risk of excessive bradycardia and hypotension.temazepamMonitor Closely (1)temazepam and lofexidine both increase sedation. Use Caution/Monitor.terazosinSerious - Use Alternative (1)lofexidine, terazosin. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.terbutalineMonitor Closely (1)lofexidine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.tetrabenazineMonitor Closely (1)tetrabenazine and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.thioridazineMonitor Closely (3)thioridazine and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended. thioridazine will increase the level or effect of lofexidine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Concomitant use of lofexidine with strong CYP2D6 inhibitors may increase lofexidine plasma levels. Monitor for symptoms of orthostasis and bradycardia if coadministered with a CYP2D6 inhibitor. Consider lofexidine dose reduction. thioridazine and lofexidine both increase sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)thiothixene and lofexidine both increase sedation. Use Caution/Monitor.timololSerious - Use Alternative (1)lofexidine, timolol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.tipranavirMonitor Closely (1)tipranavir will increase the level or effect of lofexidine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Concomitant use of lofexidine with strong CYP2D6 inhibitors may increase lofexidine plasma levels. Monitor for symptoms of orthostasis and bradycardia if coadministered with a CYP2D6 inhibitor. Consider lofexidine dose reduction.topiramateMonitor Closely (1)lofexidine and topiramate both increase sedation. Modify Therapy/Monitor Closely.toremifeneMonitor Closely (1)toremifene and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.torsemideSerious - Use Alternative (1)lofexidine, torsemide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.tramadolMonitor Closely (1)tramadol and lofexidine both increase sedation. Use Caution/Monitor.trandolaprilSerious - Use Alternative (1)lofexidine, trandolapril. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.trazodoneMonitor Closely (2)trazodone decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor. trazodone and lofexidine both increase sedation. Use Caution/Monitor.treprostinilSerious - Use Alternative (1)lofexidine, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.triamtereneSerious - Use Alternative (1)lofexidine, triamterene. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.triazolamMonitor Closely (1)triazolam and lofexidine both increase sedation. Use Caution/Monitor.triclabendazoleMonitor Closely (1)triclabendazole and lofexidine both increase QTc interval. Use Caution/Monitor.triclofosMonitor Closely (1)triclofos and lofexidine both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)trifluoperazine and lofexidine both increase sedation. Use Caution/Monitor.trimipramineMonitor Closely (2)trimipramine decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor. trimipramine and lofexidine both increase sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)triprolidine and lofexidine both increase sedation. Use Caution/Monitor.valbenazineMonitor Closely (1)valbenazine and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.valsartanSerious - Use Alternative (1)lofexidine, valsartan. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.vandetanibMonitor Closely (1)vandetanib and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.vemurafenibMonitor Closely (1)vemurafenib and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended.verapamilSerious - Use Alternative (1)lofexidine, verapamil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.voclosporinMonitor Closely (1)voclosporin, lofexidine. Either increases effects of the other by QTc interval. Use Caution/Monitor.vorinostatSerious - Use Alternative (1)vorinostat and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.xylometazolineMonitor Closely (1)lofexidine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)lofexidine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziconotideMonitor Closely (1)lofexidine and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (2)ziprasidone and lofexidine both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended. ziprasidone and lofexidine both increase sedation. Use Caution/Monitor. >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%) Postmarketing Reports There has been one report of QT prolongation, bradycardia, torsades de pointes, and cardiac arrest with successful resuscitation in a patient who received lofexidine and three reports of clinically significant QT prolongation in subjects concurrently receiving methadone with lofexidine Contraindications None Cautions 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 Inform patients that therapy may cause hypotension and that patients moving from a supine to an upright position may be at increased risk for hypotension and orthostatic effects Instruct patients to stay hydrated, on how to recognize symptoms of low blood pressure, and how to reduce risk of serious consequences should hypotension occur (eg, sit or lie down, carefully rise from a sitting or lying position) Advise patients in an outpatient setting that, until they learn how they respond to therapy, they should be careful or avoid doing activities such as driving or operating heavy machinery Increased risk of opioid overdose after opioid discontinuation Not a treatment for opioid use disorder Patients who complete opioid discontinuation are likely to have a reduced tolerance to opioids and are at increased risk of fatal overdose should they resume opioid use Use lofexidine in patients with opioid use disorder only in conjunction with a comprehensive management program for the treatment of opioid use disorder and inform patients and caregivers of this increased risk of overdose Sudden discontinuation of treatment Stopping abruptly can cause a marked rise in blood pressure; symptoms including diarrhea, insomnia, anxiety, chills, hyperhidrosis, and extremity pain have been observed with discontinuation Instruct patients not to discontinue therapy without consulting their healthcare provider When discontinuing therapy with tablets, gradually reduce the dose (see Dosing) Manage symptoms related to discontinuation by administering the previous dose and subsequent taper Drug interaction overview 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 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 conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Centrally acting alpha2-agonist that binds to receptors on adrenergic neurons; this reduces the release of norepinephrine and decreases sympathetic tone Absorption Absolute bioavailability: 72% Peak plasma time: 3-5 hr (single dose) Peak plasma concentration: 0.82 mg/mL (3 hr); 0.64 ng/mL (4 hr) AUC: 14.9 ng·hr/mL (3 hr); 12 ng·hr/mL (4 hr) Shows approximately dose-proportional pharmacokinetics Food does not alter pharmacokinetics Distribution Protein bound: 55% Vd: 480 L (PO); 297.9 L (IV); extensive distribution into body tissue Not preferentially taken up by blood cells Metabolism ~30% of administered dose is converted to inactive metabolites during first-pass effect associated with drug absorption from the gut Hepatic metabolized by CYP2D6 (major), CYP1A2 (minor), and CYP2C19 (minor) Elimination Half-life: ~12 hr Half-life, terminal: 11-13 hr (first dose); 17-22 hr (steady-state) Clearance: 17.6 L/hr Pharmacogenomics CYP2D6 poor metabolizers Likely that lofexidine exposure would be increased similarly to taking strong CYP2D6 inhibitors (~28%) by CYP2D6 poor metabolizers Monitor adverse events (eg, orthostatic hypotension, bradycardia) in known CYP2D6 poor metabolizers ~8% of whites and 3-8% of blacks cannot metabolize CYP2D6 substrates and are classified as poor metabolizers Oral Administration May take with or without food Storage Store in original container at controlled room temperature 25°C (77°F); excursions permitted between 15-30°C (59-86°F) Keep away from excess heat and moisture both in the pharmacy and after dispensing Do not remove desiccant packs from bottles until all tablets are used BRAND FORM. UNIT PRICE PILL IMAGE Lucemyra oral- 0.18 mg tabletCopyright © 2010 First DataBank, Inc.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs. 2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs. 3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs. 4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. 6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products. NC NOT COVERED – Drugs that are not covered by the plan. Code Definition PA Prior Authorization Drugs that require prior authorization. This restriction