synergism. Use Caution/Monitor. CNS derpressant effects enhanced.ganaxoloneclonidine and ganaxolone both increase sedation. Use Caution/Monitor.glofitamabglofitamab, clonidine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .glycerol phenylbutyrateglycerol phenylbutyrate will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glycerol phenylbutyrate is a weak inducer of CYP3A4. Monitor for decreased efficacy of CYP3A4 substrates that have a narrow therapeutic index.guanfacineclonidine, guanfacine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.haloperidolclonidine, haloperidol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.clonidine increases toxicity of haloperidol by Other (see comment). Use Caution/Monitor. Comment: High doses of clonidine IV may increase arrhythmogenic potential (QT-prolongation, ventricular fibrillation) of high dose haloperidol IV in patients experiencing alcoholic delirium.hydroxyzineclonidine, hydroxyzine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.iloperidoneclonidine, iloperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.insulin degludecclonidine, insulin degludec. Other (see comment). Modify Therapy/Monitor Closely. Comment: Clonidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; clonidine may also mask hypoglycemic symptoms.insulin degludec/insulin aspartclonidine, insulin degludec/insulin aspart. Other (see comment). Modify Therapy/Monitor Closely. Comment: Clonidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; clonidine may also mask hypoglycemic symptoms.insulin inhaledclonidine, insulin inhaled. Other (see comment). Modify Therapy/Monitor Closely. Comment: Clonidine may either increase or decrease the blood glucose lowering effect of antidiabetic agents; clonidine may also mask hypoglycemic symptoms.isavuconazonium sulfateisavuconazonium sulfate will increase the level or effect of clonidine by Other (see comment). Use Caution/Monitor. Isavuconazonium sulfate, an inhibitor of P-gp and CYP3A4, may increase the effects or levels of sensitive P-gp or CYP3A4 substrates, which may require dose adjustment.ivabradineivabradine, clonidine. Either decreases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Most patients receiving ivabradine will also be treated with a beta-blocker. The risk of bradycardia increases with coadministration of drugs that slow heart rate (eg, digoxin, amiodarone, beta-blockers). Monitor heart rate in patients taking ivabradine with other negative chronotropes.ixekizumabixekizumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, ixekizumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of ixekizumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.lasmiditanlasmiditan, clonidine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.lemborexantlemborexant, clonidine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.levodopalevodopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.levomilnacipranlevomilnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor. Because levomilnacipran decreases reuptake of NE, it may antagonize clonidine antihypertensive effect.lonapegsomatropinlonapegsomatropin will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substrateslorazepamclonidine, lorazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.loxapineclonidine, loxapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.loxapine inhaledclonidine, loxapine inhaled. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.lurasidonelurasidone increases effects of clonidine by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.methyldopaclonidine, methyldopa. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.metoprololmetoprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.clonidine, metoprolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.metyrosineclonidine, metyrosine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.midazolam intranasalmidazolam intranasal, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.milnacipranmilnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor.nabiloneclonidine, nabilone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.nadololnadolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.nebivololnebivolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.clonidine, nebivolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.neratinibneratinib increases levels of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Neratinib inhibits P-gp transport. Caution if coadministered with a P-gp substrate with a narrow therapeutic index.nitroglycerin rectalnitroglycerin rectal, clonidine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .nitroprusside sodiumnitroprusside sodium, clonidine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.olanzapineclonidine, olanzapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.omaveloxoloneomaveloxolone will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP3A4 substrates. Check prescribing information of substrate if dosage modification is needed. oritavancinoritavancin will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Oritavancin is a weak CYP3A4 inducer; caution if coadministered with CYP3A4 substrates that have a narrow therapeutic indexoxazepamclonidine, oxazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.palbociclibpalbociclib will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. The dose of sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced if coadministered with palbociclibpaliperidoneclonidine, paliperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.paroxetineclonidine, paroxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.penbutololpenbutolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.perphenazineclonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.pimozideclonidine, pimozide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.pindololpindolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.pirtobrutinibpirtobrutinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Pirtobrutinib (a P-gp inhibitor) may increase plasma concentrations of sensitive P-gp substrates, which may increase the risk of adverse reactions related to these substrates. pitolisantpitolisant will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Pitolisant is a borderline/weak inducer of CYP3A4. Monitor sensitive CYP3A4 substrates for reduced effectiveness if coadministered.pramipexoleclonidine, pramipexole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.prazosinclonidine, prazosin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.prochlorperazineclonidine, prochlorperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.promethazineclonidine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.propranololpropranolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.quazepamclonidine, quazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.quetiapineclonidine, quetiapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.ribociclibribociclib will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.risperidoneclonidine, risperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.ritlecitinibritlecitinib will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Ritlecitinib inhibits CYP3A4 substrates; coadministration increases AUC and peak plasma concentration sensitive substrates, which may increase risk of adverse reactions. Additional monitoring and dosage adjustment may be needed in accordance with product labeling of CYP3A substrates. rolapitantrolapitant will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Oral rolapitant (P-gp inhibitor) may increase plasma concentrations of P-gp substrates and may result in potential adverse reactions. Monitor possible adverse reactions if concomitant use of P-gp substrates and rolapitant can not be avoided.ropeginterferon alfa 2bropeginterferon alfa 2b will increase the level or effect of clonidine by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.ropiniroleclonidine, ropinirole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.rotigotineclonidine, rotigotine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.rufinamideclonidine, rufinamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.sarilumabsarilumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of cytokines such as IL-6. Elevated IL-6 concentration may down-regulate CYP activity, such as in patients with RA, and, hence, increase drug levels compared with subjects without RA. Blockade of IL-6 signaling by IL-6 antagonists (eg, sarilumab) might reverse the inhibitory effect of IL-6 and restore CYP activity, leading to decreased drug concentrations. Caution when initiating or discontinuing sarilumab if coadministered with CYP450 substrates, especially those with a narrow therapeutic index.schisandraschisandra will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.secukinumabsecukinumab, clonidine. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, secukinumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.serdexmethylphenidate/dexmethylphenidateserdexmethylphenidate/dexmethylphenidate increases toxicity of clonidine by unknown mechanism. Use Caution/Monitor.sertralineclonidine, sertraline. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.sofosbuvir/velpatasvirsofosbuvir/velpatasvir increases levels of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Velpatasvir inhibits CYP3A4. Caution if coadministered with drugs with narrow therapeutics indexes.somapacitansomapacitan will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessomatrogonsomatrogon will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessomatropinsomatropin will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Limited published data indicate that growth hormone treatment increases cytochrome P450 (CYP450)-mediated antipyrine clearance. Caution with sensitive CYP substratessotalolsotalol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.stiripentolstiripentol, clonidine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.tadalafiltadalafil increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.teclistamabteclistamab will increase the level or effect of clonidine by altering metabolism. Use Caution/Monitor. Teclistamab causes release of cytokines that may suppress activity of CYP450 enzymes, resulting in increased