of clonidine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.palbociclibMonitor Closely (1)palbociclib 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 palbociclibpaliperidoneMonitor Closely (1)clonidine, paliperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.paroxetineMonitor Closely (1)clonidine, paroxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.penbutololMonitor Closely (1)penbutolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.pentazocineSerious - Use Alternative (1)clonidine, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.perampanelSerious - Use Alternative (1)clonidine, perampanel. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.perphenazineMonitor Closely (1)clonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.pimozideMonitor Closely (1)clonidine, pimozide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.pindololMonitor Closely (1)pindolol, 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.pioglitazoneMinor (2)clonidine decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. clonidine, pioglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.pirtobrutinibMonitor Closely (1)pirtobrutinib 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. pitolisantMonitor Closely (1)pitolisant 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.ponesimodSerious - Use Alternative (1)ponesimod, clonidine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Consult cardiologist if considering treatment. Coadministration of ponesimod with drugs that decrease HR may have additive effects on decreasing HR and should generally not be initiated in these patients.pramipexoleMonitor Closely (1)clonidine, pramipexole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.prazosinMonitor Closely (1)clonidine, prazosin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.prochlorperazineMonitor Closely (1)clonidine, prochlorperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.promethazineMonitor Closely (1)clonidine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.propranololMonitor Closely (1)propranolol, 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.Serious - Use Alternative (1)clonidine, propranolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.protriptylineSerious - Use Alternative (1)protriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.quazepamMonitor Closely (1)clonidine, quazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.quetiapineMonitor Closely (1)clonidine, quetiapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.reishiMinor (1)reishi increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.remifentanilSerious - Use Alternative (1)clonidine, remifentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.repaglinideMinor (2)clonidine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. clonidine, repaglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.ribociclibMonitor Closely (1)ribociclib 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.risperidoneMonitor Closely (1)clonidine, risperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.ritlecitinibMonitor Closely (1)ritlecitinib 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. rolapitantMonitor Closely (1)rolapitant 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 2bMonitor Closely (1)ropeginterferon 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.ropiniroleMonitor Closely (1)clonidine, ropinirole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.rosiglitazoneMinor (2)clonidine decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. clonidine, rosiglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.rotigotineMonitor Closely (1)clonidine, rotigotine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.rufinamideMonitor Closely (1)clonidine, rufinamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.sarilumabMonitor Closely (1)sarilumab, 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.saxagliptinMinor (2)clonidine decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. clonidine, saxagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.schisandraMonitor Closely (1)schisandra will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.secukinumabMonitor Closely (1)secukinumab, 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/dexmethylphenidateMonitor Closely (1)serdexmethylphenidate/dexmethylphenidate increases toxicity of clonidine by unknown mechanism. Use Caution/Monitor.sertralineMonitor Closely (1)clonidine, sertraline. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.shepherd's purseMinor (1)shepherd's purse, clonidine. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.sitagliptinMinor (2)clonidine decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. clonidine, sitagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.sodium oxybateSerious - Use Alternative (1)clonidine, sodium oxybate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.sofosbuvir/velpatasvirMonitor Closely (1)sofosbuvir/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.somapacitanMonitor Closely (1)somapacitan 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 substratessomatrogonMonitor Closely (1)somatrogon 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 substratessomatropinMonitor Closely (1)somatropin 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 substratessotalolMonitor Closely (1)sotalol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.Serious - Use Alternative (1)clonidine, sotalol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.sotorasibSerious - Use Alternative (1)sotorasib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modificationsstiripentolMonitor Closely (1)stiripentol, 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.sufentanilSerious - Use Alternative (1)clonidine, sufentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.sufentanil SLSerious - Use Alternative (1)clonidine, sufentanil SL. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.tacrolimusMinor (1)clonidine increases levels of tacrolimus by unknown mechanism. Minor/Significance Unknown.tadalafilMonitor Closely (1)tadalafil increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.tapentadolSerious - Use Alternative (1)clonidine, tapentadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.teclistamabMonitor Closely (1)teclistamab 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 exposure of CYP substrates. Monitor for increased concentrations or toxicities of sensitive CYP substrates. Adjust dose of CYP substrate drug as needed. teduglutideMonitor Closely (1)teduglutide increases levels of clonidine by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.telotristat ethylMonitor Closely (1)telotristat ethyl will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Telotristat ethyl induces CYP3A4 and may reduce systemic exposure of sensitive CYP3A4 substrates. Monitor for suboptimal efficacy and consider increasing the dose of the CYP3A4 substrate.temazepamMonitor Closely (1)clonidine, temazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.thalidomideSerious - Use Alternative (1)clonidine, thalidomide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.thioridazineMonitor Closely (1)clonidine, thioridazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.thiothixeneMonitor Closely (1)clonidine, thiothixene. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.timololMonitor Closely (1)timolol, 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.Serious - Use Alternative (1)clonidine, timolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.tizanidineMinor (1)tizanidine increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.tolazamideMinor (2)clonidine decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. clonidine, tolazamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.tolbutamideMinor (2)clonidine decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. clonidine, tolbutamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.tramadolSerious - Use Alternative (1)clonidine, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.trazodoneSerious - Use Alternative (1)trazodone decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.treprostinilMinor (1)treprostinil increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.triazolamMonitor Closely (1)clonidine, triazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.trifluoperazineMonitor Closely (1)clonidine, trifluoperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.trimipramineSerious - Use Alternative (1)trimipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.trofinetideMonitor Closely (1)trofinetide will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.