clonidine/chlorthalidone (Rx)

Hypertension

Not indicated for initial therapy

If the fixed dose combination represents the dose appropriate to the individual patient's needs, it may be more convenient than the separate components

Usual dose: 0.1-0.3 mg/15 mg PO qDay or q12hr

Maximum: 0.6 mg/30 mg PO qDay

Renal Impairment

Use caution in dosing/titrating patients with renal dysfunction

Cumulative effects of thiazides may develop with impaired renal function; dose adjustment may be necessary; azotemia may be precipitated

Hepatic Impairment

Use caution; not studied

Administration

Combination may be substituted for the titrated individual components

Withdraw gradually over a period of 2-4 days

Safety/efficacy not established

May benefit from lower initial dose

Contraindicated (0)

Serious - Use Alternative (76)

• adagrasib

  adagrasib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a P-gp inhibitor, with sensitive P-gp substrates unless otherwise recommended in the prescribing information for these substrates.

• alfentanil

  clonidine, alfentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• aminolevulinic acid oral

  aminolevulinic acid oral, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  chlorthalidone increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

• amitriptyline

  amitriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• amoxapine

  amoxapine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• atenolol

  clonidine, atenolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• azelastine

  clonidine, azelastine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

• betaxolol

  clonidine, betaxolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• bisoprolol

  clonidine, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• bremelanotide

  bremelanotide will decrease the level or effect of clonidine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brigatinib

  brigatinib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

• buprenorphine

  clonidine, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• buprenorphine buccal

  clonidine, buprenorphine buccal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• buprenorphine subdermal implant

  clonidine, buprenorphine subdermal implant. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• buprenorphine transdermal

  clonidine, buprenorphine transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• buprenorphine, long-acting injection

  clonidine, buprenorphine, long-acting injection. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• butorphanol

  clonidine, butorphanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• calcium/magnesium/potassium/sodium oxybates

  clonidine, calcium/magnesium/potassium/sodium oxybates. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• clomipramine

  clomipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• codeine

  clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• desipramine

  desipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• diltiazem

  clonidine, diltiazem. unknown mechanism. Avoid or Use Alternate Drug. Reports of sinus bradycardia resulting in hospitalization and pacemaker insertion reported with concomitant use. Possible life-threatening effect, monitor closely.

• doxepin

  doxepin decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• esmolol

  clonidine, esmolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• ethanol

  clonidine, ethanol. Either increases toxicity of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• hydrocodone

  clonidine, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• hydromorphone

  clonidine, hydromorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• imipramine

  imipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• iobenguane I 131

  clonidine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• isocarboxazid

  isocarboxazid, chlorthalidone. Other (see comment). Contraindicated. Comment: Additive hypotensive effects may be seen when MAOI's are combined with antihypertensives.

• levobunolol

  clonidine, levobunolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• lofepramine

  lofepramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• lofexidine

  lofexidine, chlorthalidone. 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.
  
  lofexidine, clonidine. 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.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.

• methyl aminolevulinate

  chlorthalidone, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• macimorelin

  clonidine, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that may transiently elevate growth hormone (GH) concentrations may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin.

• maprotiline

  maprotiline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• meperidine

  clonidine, meperidine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• methadone

  clonidine, methadone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• metoclopramide intranasal

  clonidine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metoprolol

  clonidine, metoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• mirtazapine

  mirtazapine decreases effects of clonidine by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Risk of hypertensive urgency.

• mobocertinib

  mobocertinib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.

• morphine

  clonidine, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• nadolol

  clonidine, nadolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• nalbuphine

  clonidine, nalbuphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• nebivolol

  clonidine, nebivolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• nortriptyline

  nortriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• olopatadine intranasal

  clonidine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  olutasidenib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.

• opium tincture

  clonidine, opium tincture. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• orphenadrine

  clonidine, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

• oxycodone

  clonidine, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• oxymorphone

  clonidine, oxymorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• pacritinib

  pacritinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• pentazocine

  clonidine, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• perampanel

  clonidine, perampanel. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• ponesimod

  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.

• propranolol

  clonidine, propranolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• protriptyline

  protriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• remifentanil

  clonidine, remifentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• sodium oxybate

  clonidine, sodium oxybate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• sotalol

  clonidine, sotalol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• sotorasib

  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 modifications

• squill

  chlorthalidone increases toxicity of squill by Other (see comment). Avoid or Use Alternate Drug. Comment: Potassium depletion may enhance toxicity of squill.

• sufentanil

  clonidine, sufentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• sufentanil SL

  clonidine, sufentanil SL. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• tapentadol

  clonidine, tapentadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• thalidomide

  clonidine, thalidomide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

• timolol

  clonidine, timolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• tramadol

  clonidine, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• trazodone

  trazodone decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• tretinoin

  chlorthalidone, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  chlorthalidone, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• trimipramine

  trimipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

Monitor Closely (286)

• abrocitinib

  abrocitinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor and titrate dose of P-gp substrate appropriately.

• acebutolol

  acebutolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.
  
  acebutolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• aceclofenac

  aceclofenac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• acrivastine

  acrivastine and clonidine both increase sedation. Use Caution/Monitor.

• acemetacin

  acemetacin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• albiglutide

  chlorthalidone decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• albuterol

  albuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• aldesleukin

  aldesleukin increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
  
  aldesleukin increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• alprazolam

  clonidine, alprazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• amifostine

  amifostine, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

• amifostine

  amifostine, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

• amiloride

  amiloride increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• amiodarone

  clonidine, amiodarone. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration increases risk of bradycardia, sinus arrest, and AV block; monitor heart rate in patients on concomitant drugs that slow heart rate.

• amisulpride

  amisulpride and clonidine both increase sedation. Use Caution/Monitor.

• arformoterol

  arformoterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• aripiprazole

  clonidine, aripiprazole. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• asenapine

  asenapine and clonidine both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  asenapine transdermal and clonidine both increase sedation. Use Caution/Monitor.

• aspirin

  aspirin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• aspirin rectal

  aspirin rectal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• aspirin/citric acid/sodium bicarbonate

  aspirin/citric acid/sodium bicarbonate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• atenolol

  atenolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  atenolol, 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, atenolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

• avanafil

  avanafil increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
  
  avanafil increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• avapritinib

  avapritinib and clonidine both increase sedation. Use Caution/Monitor.

• beclomethasone, inhaled

  beclomethasone, inhaled increases toxicity of chlorthalidone by increasing elimination. Use Caution/Monitor. May increase the hypokalemic effects of thiazide diuretics.

• benazepril

  benazepril, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

• bendroflumethiazide

  bendroflumethiazide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• benperidol

  clonidine, benperidol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen and clonidine both increase sedation. Use Caution/Monitor.

• betaxolol

  betaxolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clonidine, betaxolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.
  
  betaxolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

• bisoprolol

  bisoprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  bisoprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

• blinatumomab

  blinatumomab increases levels of clonidine by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

• bretylium

  chlorthalidone, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

• bretylium

  clonidine, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

• brexanolone

  brexanolone, clonidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  brexpiprazole and clonidine both increase sedation. Use Caution/Monitor.

• brimonidine

  brimonidine and clonidine both increase sedation. Use Caution/Monitor.

• brivaracetam

  brivaracetam and clonidine both increase sedation. Use Caution/Monitor.

• brodalumab

  brodalumab, 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, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• bumetanide

  bumetanide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and clonidine both increase sedation. Use Caution/Monitor.

• buprenorphine transdermal

  buprenorphine transdermal and clonidine both increase sedation. Use Caution/Monitor.

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and clonidine both increase sedation. Use Caution/Monitor.
  
  buprenorphine, long-acting injection decreases effects of chlorthalidone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.

• calcifediol

  chlorthalidone increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

• carbidopa

  carbidopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

• candesartan

  candesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• captopril

  captopril, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

• carbenoxolone

  chlorthalidone and carbenoxolone both decrease serum potassium. Use Caution/Monitor.

• carbidopa

  carbidopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

• carvedilol

  carvedilol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• celecoxib

  celecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• celiprolol

  celiprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.
  
  celiprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorthalidone decreases levels of celiprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• cenobamate

  cenobamate, clonidine. Either increases effects of the other by sedation. Use Caution/Monitor.

• chlorothiazide

  chlorothiazide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• chlordiazepoxide

  clonidine, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• chlorpromazine

  clonidine, chlorpromazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• cholestyramine

  cholestyramine decreases levels of chlorthalidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• choline magnesium trisalicylate

  choline magnesium trisalicylate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• citalopram

  clonidine, citalopram. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• clobazam

  clonidine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clonazepam

  clonidine, clonazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced CNS depressant effects.

• clorazepate

  clonidine, clorazepate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• clozapine

  clonidine, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• cornsilk

  cornsilk increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

• cyclopenthiazide

  chlorthalidone and cyclopenthiazide both decrease serum potassium. Use Caution/Monitor.

• daridorexant

  clonidine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• deflazacort

  chlorthalidone and deflazacort both decrease serum potassium. Use Caution/Monitor.

• dexmethylphenidate

  dexmethylphenidate increases toxicity of clonidine by unknown mechanism. Use Caution/Monitor.

• diazepam

  clonidine, diazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• dichlorphenamide

  dichlorphenamide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• diclofenac

  diclofenac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  difelikefalin and clonidine both increase sedation. Use Caution/Monitor.

• diflunisal

  diflunisal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• digoxin

  digoxin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorthalidone increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Hypokalemia increases digoxin effects.

• dobutamine

  dobutamine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• dopexamine

  dopexamine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• doxazosin

  clonidine, doxazosin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

• doxylamine

  clonidine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• dronabinol

  clonidine, dronabinol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• droperidol

  clonidine, droperidol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• drospirenone

  drospirenone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• dulaglutide

  dulaglutide, clonidine. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

• dupilumab

  dupilumab, 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, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• elacestrant

  elacestrant will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduce dose of P-gp substrates per their Prescribing Information when minimal concentration changes may lead to serious or life-threatening adverse reactions.

• elranatamab

  elranatamab will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• eluxadoline

  eluxadoline increases levels of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

• empagliflozin

  empagliflozin, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of empagliflozin with diuretics results in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

• epcoritamab

  epcoritamab, clonidine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab 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. .

• ephedrine

  ephedrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• epinephrine

  epinephrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• epinephrine inhaled

  clonidine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  epinephrine racemic and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• eprosartan

  eprosartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• escitalopram

  clonidine, escitalopram. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• esketamine intranasal

  esketamine intranasal, clonidine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
  
  esketamine intranasal, clonidine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .

• esmolol

  esmolol, 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, esmolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.
  
  esmolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• estazolam

  clonidine, estazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• ethacrynic acid

  ethacrynic acid and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• etodolac

  etodolac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• exenatide injectable solution

  chlorthalidone decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• exenatide injectable suspension

  chlorthalidone decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• fenoprofen

  fenoprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fentanyl

  fentanyl decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• fentanyl intranasal

  fentanyl intranasal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• fentanyl transdermal

  fentanyl transdermal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• fentanyl transmucosal

  fentanyl transmucosal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• ferric maltol

  ferric maltol, clonidine. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• flibanserin

  flibanserin increases levels of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Increase monitoring of concentrations of drugs transported by P-gp that have a narrow therapeutic index if coadministered with flibanserin.

• fluoxetine

  clonidine, fluoxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• fluphenazine

  clonidine, fluphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• flurazepam

  clonidine, flurazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• flurbiprofen

  flurbiprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fluvoxamine

  fluvoxamine, clonidine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. CNS derpressant effects enhanced.

• formoterol

  formoterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• furosemide

  furosemide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• ganaxolone

  clonidine and ganaxolone both increase sedation. Use Caution/Monitor.

• gentamicin

  chlorthalidone and gentamicin both decrease serum potassium. Use Caution/Monitor.

• glofitamab

  glofitamab, 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 phenylbutyrate

  glycerol 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.

• guanfacine

  clonidine, guanfacine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

• haloperidol

  clonidine, 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.

• hydrochlorothiazide

  chlorthalidone and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.

• hydroxyzine

  clonidine, hydroxyzine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• ibuprofen

  ibuprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ibuprofen IV

  ibuprofen IV increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.
  
  chlorthalidone will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• iloperidone

  clonidine, iloperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• indacaterol, inhaled

  chlorthalidone, indacaterol, inhaled. serum potassium. Use Caution/Monitor. Combination may increase risk of hypokalemia.
  
  indacaterol, inhaled, chlorthalidone. Other (see comment). Use Caution/Monitor. Comment: Caution is advised in the coadministration of indacaterol neohaler with non-potassium-sparing diuretics.

• indapamide

  chlorthalidone and indapamide both decrease serum potassium. Use Caution/Monitor.

• indomethacin

  indomethacin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• insulin degludec

  chlorthalidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.
  
  clonidine, 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 aspart

  chlorthalidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.
  
  clonidine, 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 inhaled

  chlorthalidone decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.
  
  clonidine, 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.

• irbesartan

  irbesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• isavuconazonium sulfate

  isavuconazonium 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.

• isoproterenol

  isoproterenol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• ivabradine

  ivabradine, 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.

• ixekizumab

  ixekizumab, 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.

• juniper

  juniper, chlorthalidone. Other (see comment). Use Caution/Monitor. Comment: Juniper may potentiate or interfere with diuretic therapy. Juniper has diuretic effects, but may cause kidney damage at large doses.

• ketoprofen

  ketoprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ketorolac

  ketorolac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ketorolac intranasal

  ketorolac intranasal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• labetalol

  labetalol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lasmiditan

  lasmiditan, 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.

• lemborexant

  lemborexant, 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.

• levalbuterol

  levalbuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• levodopa

  levodopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
  
  levodopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

• levomilnacipran

  levomilnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor. Because levomilnacipran decreases reuptake of NE, it may antagonize clonidine antihypertensive effect.

• lily of the valley

  chlorthalidone increases toxicity of lily of the valley by Other (see comment). Use Caution/Monitor. Comment: Increased risk of cardiac toxicity due to K+ depletion.

• liraglutide

  chlorthalidone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• lithium

  chlorthalidone increases toxicity of lithium by decreasing elimination. Use Caution/Monitor.

• lonapegsomatropin

  lonapegsomatropin 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 substrates

• lorazepam

  clonidine, lorazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• lornoxicam

  lornoxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• losartan

  losartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine

  clonidine, loxapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• loxapine inhaled

  clonidine, loxapine inhaled. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• lurasidone

  lurasidone increases effects of chlorthalidone 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.
  
  lurasidone 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.

• maitake

  maitake increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).

• methyldopa

  clonidine, methyldopa. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

• maraviroc

  maraviroc, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

• meclofenamate

  meclofenamate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mefenamic acid

  mefenamic acid increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meloxicam

  meloxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaproterenol

  metaproterenol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• methoxsalen

  methoxsalen, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methyclothiazide

  chlorthalidone and methyclothiazide both decrease serum potassium. Use Caution/Monitor.

• methylphenidate transdermal

  methylphenidate transdermal decreases effects of chlorthalidone by anti-hypertensive channel blocking. Use Caution/Monitor.

• metolazone

  chlorthalidone and metolazone both decrease serum potassium. Use Caution/Monitor.

• metoprolol

  metoprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.
  
  metoprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.

• metyrosine

  clonidine, metyrosine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• mometasone inhaled

  mometasone inhaled increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may increase hypokalemic effect of loop diuretics.

• midazolam intranasal

  midazolam 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.

• milnacipran

  milnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor.

• mycophenolate

  chlorthalidone will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabilone

  clonidine, nabilone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• nabumetone

  nabumetone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nadolol

  nadolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nadolol, 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.

• naproxen

  naproxen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nebivolol

  nebivolol, 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.

• nebivolol

  nebivolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• neratinib

  neratinib 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.

• nitazoxanide

  nitazoxanide, chlorthalidone. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.

• nitroglycerin rectal

  nitroglycerin rectal, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .
  
  nitroglycerin rectal, clonidine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

• nitroprusside sodium

  nitroprusside sodium, clonidine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

• norepinephrine

  norepinephrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• olanzapine

  clonidine, olanzapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• oliceridine

  oliceridine decreases effects of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor for signs of diminished diuresis and/or effects on blood pressure and increase dosage of the diuretic as needed. .

• olmesartan

  olmesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• olodaterol inhaled

  chlorthalidone and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

• omaveloxolone

  omaveloxolone 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.

• oritavancin

  oritavancin 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 index

• ospemifene

  chlorthalidone, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• oxaprozin

  oxaprozin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxazepam

  clonidine, oxazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• palbociclib

  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 palbociclib

• paliperidone

  clonidine, paliperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• parecoxib

  parecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• paroxetine

  clonidine, paroxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• penbutolol

  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.
  
  penbutolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• perphenazine

  clonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• pindolol

  pindolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pimozide

  clonidine, pimozide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• pindolol

  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.

• pirbuterol

  pirbuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• piroxicam

  piroxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pirtobrutinib

  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.

• pitolisant

  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.

• pivmecillinam

  pivmecillinam, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• porfimer

  chlorthalidone, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• potassium acid phosphate

  potassium acid phosphate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• potassium chloride

  potassium chloride increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• potassium citrate

  potassium citrate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pramipexole

  clonidine, pramipexole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• prazosin

  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.

• probenecid

  chlorthalidone will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• prochlorperazine

  clonidine, prochlorperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• promethazine

  clonidine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• propranolol

  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.
  
  propranolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quazepam

  clonidine, quazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• sacubitril/valsartan

  sacubitril/valsartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

  clonidine, quetiapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• ribociclib

  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.

• risperidone

  clonidine, risperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• ritlecitinib

  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.

• rolapitant

  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 2b

  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.

• ropinirole

  clonidine, ropinirole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• rotigotine

  clonidine, rotigotine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• rufinamide

  clonidine, rufinamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• salicylates (non-asa)

  salicylates (non-asa) increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• salmeterol

  salmeterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• salsalate

  salsalate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sarilumab

  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.

• schisandra

  schisandra will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• secukinumab

  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/dexmethylphenidate

  serdexmethylphenidate/dexmethylphenidate increases toxicity of clonidine by unknown mechanism. Use Caution/Monitor.

• sertraline

  clonidine, sertraline. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• shark cartilage

  chlorthalidone, shark cartilage. Other (see comment). Use Caution/Monitor. Comment: May lead to hypercalcemia (theoretical).

• sodium sulfate/?magnesium sulfate/potassium chloride

  sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol

  chlorthalidone and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

• sodium sulfate/potassium sulfate/magnesium sulfate

  sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sofosbuvir/velpatasvir

  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.

• somapacitan

  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 substrates

• somatrogon

  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 substrates

• somatropin

  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 substrates

• sotalol

  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.
  
  sotalol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• spironolactone

  spironolactone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• stiripentol

  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.

• succinylcholine

  succinylcholine increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sulfasalazine

  sulfasalazine increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sulindac

  sulindac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tadalafil

  tadalafil increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
  
  tadalafil increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• talquetamab

  talquetamab will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• telmisartan

  telmisartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• teclistamab

  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.

• teduglutide

  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 ethyl

  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.

• temazepam

  clonidine, temazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• temocillin

  temocillin, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• terbutaline

  terbutaline and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• thioridazine

  clonidine, thioridazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• thiothixene

  clonidine, thiothixene. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• ticarcillin

  ticarcillin, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• timolol

  timolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.

• tolfenamic acid

  tolfenamic acid increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• triazolam

  clonidine, triazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• tolmetin

  tolmetin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tolvaptan

  tolvaptan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• toremifene

  chlorthalidone, toremifene. Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics decrease renal calcium excretion and may increase risk of hypercalcemia in patients taking toremifene.

• torsemide

  torsemide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• triamterene

  triamterene increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• trientine

  chlorthalidone decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

• trifluoperazine

  clonidine, trifluoperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• trofinetide

  trofinetide will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).

• umeclidinium bromide/vilanterol inhaled

  umeclidinium bromide/vilanterol inhaled and chlorthalidone both decrease serum potassium. Modify Therapy/Monitor Closely. Electrocardiographic changes and/or hypokalemia associated with non?potassium-sparing diuretics may worsen with concomitant beta-agonists, particularly if recommended dose is exceeded

• ustekinumab

  ustekinumab, 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, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• valsartan

  valsartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• verapamil

  clonidine, verapamil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.
  
  verapamil, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.

• vilanterol/fluticasone furoate inhaled

  vilanterol/fluticasone furoate inhaled and chlorthalidone both decrease serum potassium. Modify Therapy/Monitor Closely. Beta-agonists may acutely worsen ECG changes and/or hypokalemia resulting from non-potassium-sparing diuretics

• vilazodone

  clonidine, vilazodone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• vitamin D

  chlorthalidone increases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Combination may increase hypercalcemic effect of vitamin D analogs. Use with caution.

• voclosporin

  voclosporin will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Coadministration of voclosporin (a P-gp inhibitor) increases exposure and risk of adverse reactions of P-gp substrates. For certain P-gp substrates with a narrow therapeutic window, refer to prescribing information of these substrates for dosage modifications, if needed.

• vortioxetine

  clonidine, vortioxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• xipamide

  xipamide increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor.
  
  xipamide increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor.

• ziprasidone

  clonidine, ziprasidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• zotepine

  clonidine, zotepine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

Minor (152)

• acarbose

  chlorthalidone decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, acarbose. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• aceclofenac

  chlorthalidone will increase the level or effect of aceclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• agrimony

  agrimony increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• acemetacin

  chlorthalidone will increase the level or effect of acemetacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acyclovir

  chlorthalidone will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• agrimony

  agrimony increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• albuterol

  albuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• aminohippurate sodium

  chlorthalidone will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• arformoterol

  arformoterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• aspirin

  chlorthalidone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin rectal

  chlorthalidone will increase the level or effect of aspirin rectal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin/citric acid/sodium bicarbonate

  chlorthalidone will increase the level or effect of aspirin/citric acid/sodium bicarbonate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• balsalazide

  chlorthalidone will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• bendroflumethiazide

  bendroflumethiazide will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• birch

  birch increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• bitter melon

  bitter melon, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• brimonidine

  brimonidine increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  brimonidine increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• budesonide

  budesonide, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• chlorpropamide

  clonidine decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, chlorpropamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• calcitriol topical

  calcitriol topical, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential additive hypercalcemia.

• calcium acetate

  chlorthalidone increases levels of calcium acetate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium carbonate

  chlorthalidone increases levels of calcium carbonate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium chloride

  chlorthalidone increases levels of calcium chloride by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium citrate

  chlorthalidone increases levels of calcium citrate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium gluconate

  chlorthalidone increases levels of calcium gluconate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• carbenoxolone

  chlorthalidone, carbenoxolone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

• cefadroxil

  cefadroxil will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefamandole

  cefamandole will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  cefpirome will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celecoxib

  chlorthalidone will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cephalexin

  cephalexin will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorothiazide

  chlorothiazide will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpropamide

  chlorthalidone will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.
  
  chlorthalidone decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• choline magnesium trisalicylate

  chlorthalidone will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• colestipol

  colestipol decreases levels of chlorthalidone by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cornsilk

  cornsilk increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• corticotropin

  corticotropin, chlorthalidone. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

• cortisone

  cortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• cosyntropin

  cosyntropin, chlorthalidone. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

• cyclopenthiazide

  chlorthalidone will increase the level or effect of cyclopenthiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclosporine

  clonidine increases levels of cyclosporine by unknown mechanism. Minor/Significance Unknown.

• deflazacort

  deflazacort, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• dexamethasone

  dexamethasone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• diazoxide

  diazoxide, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperglycemia.

• diclofenac

  chlorthalidone will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• diflunisal

  chlorthalidone will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• dobutamine

  dobutamine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• dopexamine

  dopexamine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• ephedrine

  ephedrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epinephrine

  epinephrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epinephrine racemic

  epinephrine racemic, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epoprostenol

  epoprostenol increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

• etodolac

  chlorthalidone will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fenbufen

  chlorthalidone will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fenoprofen

  chlorthalidone will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fludrocortisone

  fludrocortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• flurbiprofen

  chlorthalidone will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fo-ti

  fo-ti increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia (theoretical).

• folic acid

  chlorthalidone decreases levels of folic acid by increasing renal clearance. Minor/Significance Unknown.

• formoterol

  formoterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• forskolin

  forskolin increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  forskolin increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• ganciclovir

  chlorthalidone will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• glimepiride

  clonidine decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, glimepiride. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• glimepiride

  chlorthalidone decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• glipizide

  chlorthalidone decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine, glipizide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  clonidine decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• glyburide

  clonidine, glyburide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• goldenrod

  goldenrod increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin aspart

  clonidine decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, insulin aspart. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• hydrochlorothiazide

  chlorthalidone will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• hydrocortisone

  hydrocortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• ibuprofen

  chlorthalidone will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indapamide

  chlorthalidone will increase the level or effect of indapamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indomethacin

  chlorthalidone will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• insulin aspart

  chlorthalidone decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin detemir

  clonidine decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  chlorthalidone decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine, insulin detemir. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• insulin glargine

  chlorthalidone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine, insulin glargine. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  clonidine decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• insulin glulisine

  clonidine, insulin glulisine. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• insulin lispro

  chlorthalidone decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, insulin lispro. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• insulin NPH

  clonidine, insulin NPH. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  clonidine decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  chlorthalidone decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin regular human

  clonidine decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, insulin regular human. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• isoproterenol

  isoproterenol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• maitake

  maitake increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• ketoprofen

  chlorthalidone will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  chlorthalidone will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  chlorthalidone will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• L-methylfolate

  chlorthalidone decreases levels of L-methylfolate by increasing renal clearance. Minor/Significance Unknown.

• levalbuterol

  levalbuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• lornoxicam

  chlorthalidone will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• magnesium chloride

  chlorthalidone decreases levels of magnesium chloride by increasing renal clearance. Minor/Significance Unknown.

• magnesium citrate

  chlorthalidone decreases levels of magnesium citrate by increasing renal clearance. Minor/Significance Unknown.

• magnesium hydroxide

  chlorthalidone decreases levels of magnesium hydroxide by increasing renal clearance. Minor/Significance Unknown.

• magnesium oxide

  chlorthalidone decreases levels of magnesium oxide by increasing renal clearance. Minor/Significance Unknown.

• magnesium sulfate

  chlorthalidone decreases levels of magnesium sulfate by increasing renal clearance. Minor/Significance Unknown.

• meclofenamate

  chlorthalidone will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  chlorthalidone will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meloxicam

  chlorthalidone will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mesalamine

  chlorthalidone will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metaproterenol

  metaproterenol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• metformin

  chlorthalidone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• methyclothiazide

  chlorthalidone will increase the level or effect of methyclothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• miglitol

  clonidine decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, miglitol. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• methylprednisolone

  methylprednisolone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• metolazone

  chlorthalidone will increase the level or effect of metolazone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• miglitol

  chlorthalidone decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• minoxidil

  chlorthalidone increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

• nabumetone

  chlorthalidone will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• naproxen

  chlorthalidone will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nateglinide

  clonidine decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, nateglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• noni juice

  noni juice increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• octacosanol

  octacosanol increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• norepinephrine

  norepinephrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• octacosanol

  octacosanol increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• oxaprozin

  chlorthalidone will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• parecoxib

  chlorthalidone will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• pioglitazone

  clonidine, pioglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• pirbuterol

  pirbuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• reishi

  reishi increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• piroxicam

  chlorthalidone will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• prednisolone

  prednisolone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• prednisone

  prednisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• reishi

  reishi increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• repaglinide

  chlorthalidone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  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.

• rose hips

  rose hips will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• rosiglitazone

  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.

• rosiglitazone

  chlorthalidone decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• salicylates (non-asa)

  chlorthalidone will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• salmeterol

  salmeterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• salsalate

  chlorthalidone will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• saxagliptin

  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.
  
  chlorthalidone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• shepherd's purse

  shepherd's purse, chlorthalidone. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.
  
  shepherd's purse, clonidine. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

• sitagliptin

  clonidine, sitagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• sulfadiazine

  chlorthalidone increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

• tacrolimus

  clonidine increases levels of tacrolimus by unknown mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  chlorthalidone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  chlorthalidone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• sulfasalazine

  chlorthalidone will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfisoxazole

  chlorthalidone increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

  chlorthalidone will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• terbutaline

  terbutaline, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.
  
  chlorthalidone, terbutaline. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

• tizanidine

  tizanidine increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.
  
  tizanidine increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tolazamide

  chlorthalidone decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  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.

• tolbutamide

  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.
  
  chlorthalidone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• tolfenamic acid

  chlorthalidone will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• treprostinil

  treprostinil increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• tolmetin

  chlorthalidone will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• treprostinil

  treprostinil increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• triamcinolone acetonide injectable suspension

  triamcinolone acetonide injectable suspension, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• trilostane

  trilostane, chlorthalidone. Other (see comment). Minor/Significance Unknown. Comment: Trilostane reduces K+ loss while maintaining the natriuretic effect. Mechanism: inhibition of mineralocorticoid steroid synthesis.

• trimethoprim

  chlorthalidone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• valganciclovir

  chlorthalidone will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• verteporfin

  chlorthalidone, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

• vildagliptin

  clonidine, vildagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• willow bark

  chlorthalidone will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• abrocitinib

  Monitor Closely (1)abrocitinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor and titrate dose of P-gp substrate appropriately.

• acarbose

  Minor (3)clonidine decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, acarbose. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of acarbose by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• acebutolol

  Monitor Closely (2)acebutolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.
  
  acebutolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• aceclofenac

  Monitor Closely (1)aceclofenac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of aceclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acemetacin

  Monitor Closely (1)acemetacin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of acemetacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• acrivastine

  Monitor Closely (1)acrivastine and clonidine both increase sedation. Use Caution/Monitor.

• acyclovir

  Minor (1)chlorthalidone will increase the level or effect of acyclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• adagrasib

  Serious - Use Alternative (1)adagrasib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid coadministration of adagrasib, a P-gp inhibitor, with sensitive P-gp substrates unless otherwise recommended in the prescribing information for these substrates.

• agrimony

  Minor (2)agrimony increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  agrimony increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• albiglutide

  Monitor Closely (1)chlorthalidone decreases effects of albiglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• albuterol

  Monitor Closely (1)albuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)albuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• aldesleukin

  Monitor Closely (2)aldesleukin increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
  
  aldesleukin increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• alfentanil

  Serious - Use Alternative (1)clonidine, alfentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• alprazolam

  Monitor Closely (1)clonidine, alprazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• amifostine

  Monitor Closely (2)amifostine, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.
  
  amifostine, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

• amiloride

  Monitor Closely (1)amiloride increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• aminohippurate sodium

  Minor (1)chlorthalidone will increase the level or effect of aminohippurate sodium by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aminolevulinic acid oral

  Serious - Use Alternative (1)aminolevulinic acid oral, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  Serious - Use Alternative (1)chlorthalidone increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

• amiodarone

  Monitor Closely (1)clonidine, amiodarone. Either decreases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration increases risk of bradycardia, sinus arrest, and AV block; monitor heart rate in patients on concomitant drugs that slow heart rate.

• amisulpride

  Monitor Closely (1)amisulpride and clonidine both increase sedation. Use Caution/Monitor.

• amitriptyline

  Serious - Use Alternative (1)amitriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• amoxapine

  Serious - Use Alternative (1)amoxapine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• arformoterol

  Monitor Closely (1)arformoterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)arformoterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• aripiprazole

  Monitor Closely (1)clonidine, aripiprazole. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• asenapine

  Monitor Closely (1)asenapine and clonidine both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  Monitor Closely (1)asenapine transdermal and clonidine both increase sedation. Use Caution/Monitor.

• aspirin

  Monitor Closely (1)aspirin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of aspirin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin rectal

  Monitor Closely (1)aspirin rectal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Minor (1)chlorthalidone will increase the level or effect of aspirin rectal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• aspirin/citric acid/sodium bicarbonate

  Monitor Closely (1)aspirin/citric acid/sodium bicarbonate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of aspirin/citric acid/sodium bicarbonate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• atenolol

  Monitor Closely (3)atenolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  atenolol, 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, atenolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.Serious - Use Alternative (1)clonidine, atenolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• avanafil

  Monitor Closely (2)avanafil increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
  
  avanafil increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• avapritinib

  Monitor Closely (1)avapritinib and clonidine both increase sedation. Use Caution/Monitor.

• azelastine

  Serious - Use Alternative (1)clonidine, azelastine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

• balsalazide

  Minor (1)chlorthalidone will increase the level or effect of balsalazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• beclomethasone, inhaled

  Monitor Closely (1)beclomethasone, inhaled increases toxicity of chlorthalidone by increasing elimination. Use Caution/Monitor. May increase the hypokalemic effects of thiazide diuretics.

• benazepril

  Monitor Closely (1)benazepril, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced hypotensive effects. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

• bendroflumethiazide

  Monitor Closely (1)bendroflumethiazide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)bendroflumethiazide will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• benperidol

  Monitor Closely (1)clonidine, benperidol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)benzhydrocodone/acetaminophen and clonidine both increase sedation. Use Caution/Monitor.

• betaxolol

  Monitor Closely (3)betaxolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clonidine, betaxolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.
  
  betaxolol, 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, betaxolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• birch

  Minor (1)birch increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• bisoprolol

  Monitor Closely (2)bisoprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  bisoprolol, 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, bisoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• bitter melon

  Minor (1)bitter melon, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• blinatumomab

  Monitor Closely (1)blinatumomab increases levels of clonidine by decreasing metabolism. Modify Therapy/Monitor Closely. Treatment initiation causes transient release of cytokines that may suppress CYP450 enzymes; highest drug-drug interaction risk is during the first 9 days of the first cycle and the first 2 days of the 2nd cycle in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index.

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of clonidine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• bretylium

  Monitor Closely (2)clonidine, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.
  
  chlorthalidone, bretylium. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Each drug may cause hypotension.

• brexanolone

  Monitor Closely (1)brexanolone, clonidine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (1)brexpiprazole and clonidine both increase sedation. Use Caution/Monitor.

• brigatinib

  Serious - Use Alternative (1)brigatinib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

• brimonidine

  Monitor Closely (1)brimonidine and clonidine both increase sedation. Use Caution/Monitor.Minor (2)brimonidine increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  brimonidine increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• brivaracetam

  Monitor Closely (1)brivaracetam and clonidine both increase sedation. Use Caution/Monitor.

• brodalumab

  Monitor Closely (1)brodalumab, 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, brodalumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of brodalumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• budesonide

  Minor (1)budesonide, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• bumetanide

  Monitor Closely (1)bumetanide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• buprenorphine

  Serious - Use Alternative (1)clonidine, buprenorphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• buprenorphine buccal

  Serious - Use Alternative (1)clonidine, buprenorphine buccal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• buprenorphine subdermal implant

  Monitor Closely (1)buprenorphine subdermal implant and clonidine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clonidine, buprenorphine subdermal implant. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• buprenorphine transdermal

  Monitor Closely (1)buprenorphine transdermal and clonidine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)clonidine, buprenorphine transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• buprenorphine, long-acting injection

  Monitor Closely (2)buprenorphine, long-acting injection and clonidine both increase sedation. Use Caution/Monitor.
  
  buprenorphine, long-acting injection decreases effects of chlorthalidone by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Opioids can reduce diuretic efficacy by inducing antidiuretic hormone release.Serious - Use Alternative (1)clonidine, buprenorphine, long-acting injection. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• butorphanol

  Serious - Use Alternative (1)clonidine, butorphanol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• calcifediol

  Monitor Closely (1)chlorthalidone increases toxicity of calcifediol by Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics may increase serum calcium by decreasing urinary calcium excretion.

• calcitriol topical

  Minor (1)calcitriol topical, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential additive hypercalcemia.

• calcium acetate

  Minor (1)chlorthalidone increases levels of calcium acetate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium carbonate

  Minor (1)chlorthalidone increases levels of calcium carbonate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium chloride

  Minor (1)chlorthalidone increases levels of calcium chloride by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium citrate

  Minor (1)chlorthalidone increases levels of calcium citrate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium gluconate

  Minor (1)chlorthalidone increases levels of calcium gluconate by decreasing renal clearance. Minor/Significance Unknown. Risk of alkalosis, hypercalcemia.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)clonidine, calcium/magnesium/potassium/sodium oxybates. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• candesartan

  Monitor Closely (1)candesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• captopril

  Monitor Closely (1)captopril, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Increased risk of nephrotoxicity. Monitor blood pressure and renal function.

• carbenoxolone

  Monitor Closely (1)chlorthalidone and carbenoxolone both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorthalidone, carbenoxolone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

• carbidopa

  Monitor Closely (2)carbidopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.
  
  carbidopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

• carvedilol

  Monitor Closely (1)carvedilol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cefadroxil

  Minor (1)cefadroxil will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefamandole

  Minor (1)cefamandole will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cefpirome

  Minor (1)cefpirome will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celecoxib

  Monitor Closely (1)celecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of celecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• celiprolol

  Monitor Closely (3)celiprolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.
  
  celiprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorthalidone decreases levels of celiprolol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• cenobamate

  Monitor Closely (1)cenobamate, clonidine. Either increases effects of the other by sedation. Use Caution/Monitor.

• cephalexin

  Minor (1)cephalexin will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlordiazepoxide

  Monitor Closely (1)clonidine, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• chlorothiazide

  Monitor Closely (1)chlorothiazide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorothiazide will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• chlorpromazine

  Monitor Closely (1)clonidine, chlorpromazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• chlorpropamide

  Minor (4)clonidine decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, chlorpropamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of chlorpropamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  chlorthalidone will increase the level or effect of chlorpropamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cholestyramine

  Monitor Closely (1)cholestyramine decreases levels of chlorthalidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• choline magnesium trisalicylate

  Monitor Closely (1)choline magnesium trisalicylate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Minor (1)chlorthalidone will increase the level or effect of choline magnesium trisalicylate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• citalopram

  Monitor Closely (1)clonidine, citalopram. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• clobazam

  Monitor Closely (1)clonidine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clomipramine

  Serious - Use Alternative (1)clomipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• clonazepam

  Monitor Closely (1)clonidine, clonazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Enhanced CNS depressant effects.

• clorazepate

  Monitor Closely (1)clonidine, clorazepate. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• clozapine

  Monitor Closely (1)clonidine, clozapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• codeine

  Serious - Use Alternative (1)clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• colestipol

  Minor (1)colestipol decreases levels of chlorthalidone by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.

• cornsilk

  Monitor Closely (1)cornsilk increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).Minor (1)cornsilk increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• corticotropin

  Minor (1)corticotropin, chlorthalidone. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

• cortisone

  Minor (1)cortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• cosyntropin

  Minor (1)cosyntropin, chlorthalidone. pharmacodynamic synergism. Minor/Significance Unknown. Possible enhanced electrolyte loss.

• cyclopenthiazide

  Monitor Closely (1)chlorthalidone and cyclopenthiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of cyclopenthiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• cyclosporine

  Minor (1)clonidine increases levels of cyclosporine by unknown mechanism. Minor/Significance Unknown.

• daridorexant

  Monitor Closely (1)clonidine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• deflazacort

  Monitor Closely (1)chlorthalidone and deflazacort both decrease serum potassium. Use Caution/Monitor.Minor (1)deflazacort, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• desipramine

  Serious - Use Alternative (1)desipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• dexamethasone

  Minor (1)dexamethasone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• dexmethylphenidate

  Monitor Closely (1)dexmethylphenidate increases toxicity of clonidine by unknown mechanism. Use Caution/Monitor.

• diazepam

  Monitor Closely (1)clonidine, diazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• diazoxide

  Minor (1)diazoxide, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hyperglycemia.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• diclofenac

  Monitor Closely (1)diclofenac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of diclofenac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• difelikefalin

  Monitor Closely (1)difelikefalin and clonidine both increase sedation. Use Caution/Monitor.

• diflunisal

  Monitor Closely (1)diflunisal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of diflunisal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• digoxin

  Monitor Closely (2)chlorthalidone increases effects of digoxin by pharmacodynamic synergism. Use Caution/Monitor. Hypokalemia increases digoxin effects.
  
  digoxin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diltiazem

  Serious - Use Alternative (1)clonidine, diltiazem. unknown mechanism. Avoid or Use Alternate Drug. Reports of sinus bradycardia resulting in hospitalization and pacemaker insertion reported with concomitant use. Possible life-threatening effect, monitor closely.

• dobutamine

  Monitor Closely (1)dobutamine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)dobutamine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• dopexamine

  Monitor Closely (1)dopexamine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)dopexamine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• doxazosin

  Monitor Closely (1)clonidine, doxazosin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

• doxepin

  Serious - Use Alternative (1)doxepin decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• doxylamine

  Monitor Closely (1)clonidine, doxylamine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• dronabinol

  Monitor Closely (1)clonidine, dronabinol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• droperidol

  Monitor Closely (1)clonidine, droperidol. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• drospirenone

  Monitor Closely (1)drospirenone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• dulaglutide

  Monitor Closely (1)dulaglutide, clonidine. Other (see comment). Use Caution/Monitor. Comment: Dulaglutide slows gastric emptying and may impact absorption of concomitantly administered oral medications; be particularly cautious when coadministered with drugs that have a narrow therapeutic index.

• dupilumab

  Monitor Closely (1)dupilumab, 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, dupilumab could normalize the formation of CYP450 enzymes. Upon initiation or discontinuation of dupilumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• elacestrant

  Monitor Closely (1)elacestrant will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduce dose of P-gp substrates per their Prescribing Information when minimal concentration changes may lead to serious or life-threatening adverse reactions.

• elranatamab

  Monitor Closely (1)elranatamab will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• eluxadoline

  Monitor Closely (1)eluxadoline increases levels of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

• empagliflozin

  Monitor Closely (1)empagliflozin, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of empagliflozin with diuretics results in increased urine volume and frequency of voids, which might enhance the potential for volume depletion.

• epcoritamab

  Monitor Closely (1)epcoritamab, clonidine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab 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. .

• ephedrine

  Monitor Closely (1)ephedrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)ephedrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epinephrine

  Monitor Closely (1)epinephrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)epinephrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epinephrine inhaled

  Monitor Closely (1)clonidine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (1)epinephrine racemic and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)epinephrine racemic, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• epoprostenol

  Minor (1)epoprostenol increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

• eprosartan

  Monitor Closely (1)eprosartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• escitalopram

  Monitor Closely (1)clonidine, escitalopram. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• esketamine intranasal

  Monitor Closely (2)esketamine intranasal, clonidine. Either increases toxicity of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Closely monitor blood pressure with concomitant use of esketamine nasal with stimulants. .
  
  esketamine intranasal, clonidine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• esmolol

  Monitor Closely (3)clonidine, esmolol. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.
  
  esmolol, clonidine. Mechanism: pharmacodynamic synergism. Modify Therapy/Monitor Closely. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.
  
  esmolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)clonidine, esmolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• estazolam

  Monitor Closely (1)clonidine, estazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• ethacrynic acid

  Monitor Closely (1)ethacrynic acid and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• ethanol

  Serious - Use Alternative (1)clonidine, ethanol. Either increases toxicity of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• etodolac

  Monitor Closely (1)etodolac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of etodolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• exenatide injectable solution

  Monitor Closely (1)chlorthalidone decreases effects of exenatide injectable solution by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• exenatide injectable suspension

  Monitor Closely (1)chlorthalidone decreases effects of exenatide injectable suspension by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• fenbufen

  Minor (1)chlorthalidone will increase the level or effect of fenbufen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fenoprofen

  Monitor Closely (1)fenoprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of fenoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fentanyl

  Monitor Closely (1)fentanyl decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• fentanyl intranasal

  Monitor Closely (1)fentanyl intranasal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• fentanyl transdermal

  Monitor Closely (1)fentanyl transdermal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• fentanyl transmucosal

  Monitor Closely (1)fentanyl transmucosal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• ferric maltol

  Monitor Closely (1)ferric maltol, clonidine. Either increases levels of the other by unspecified interaction mechanism. Modify Therapy/Monitor Closely. Coadministration of ferric maltol with certain oral medications may decrease the bioavailability of either ferric maltol and some oral drugs. For oral drugs where reductions in bioavailability may cause clinically significant effects on its safety or efficacy, separate administration of ferric maltol from these drugs. Duration of separation may depend on the absorption of the medication concomitantly administered (eg, time to peak concentration, whether the drug is an immediate or extended release product).

• flibanserin

  Monitor Closely (1)flibanserin increases levels of clonidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Increase monitoring of concentrations of drugs transported by P-gp that have a narrow therapeutic index if coadministered with flibanserin.

• fludrocortisone

  Minor (1)fludrocortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• fluoxetine

  Monitor Closely (1)clonidine, fluoxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• fluphenazine

  Monitor Closely (1)clonidine, fluphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• flurazepam

  Monitor Closely (1)clonidine, flurazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• flurbiprofen

  Monitor Closely (1)flurbiprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of flurbiprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• fluvoxamine

  Monitor Closely (1)fluvoxamine, clonidine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. CNS derpressant effects enhanced.

• fo-ti

  Minor (1)fo-ti increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia (theoretical).

• folic acid

  Minor (1)chlorthalidone decreases levels of folic acid by increasing renal clearance. Minor/Significance Unknown.

• formoterol

  Monitor Closely (1)formoterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)formoterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• forskolin

  Minor (2)forskolin increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.
  
  forskolin increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• furosemide

  Monitor Closely (1)furosemide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• ganaxolone

  Monitor Closely (1)clonidine and ganaxolone both increase sedation. Use Caution/Monitor.

• ganciclovir

  Minor (1)chlorthalidone will increase the level or effect of ganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• gentamicin

  Monitor Closely (1)chlorthalidone and gentamicin both decrease serum potassium. Use Caution/Monitor.

• glimepiride

  Minor (3)clonidine decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, glimepiride. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of glimepiride by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• glipizide

  Minor (3)clonidine, glipizide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of glipizide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• glofitamab

  Monitor Closely (1)glofitamab, 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. .

• glyburide

  Minor (3)clonidine, glyburide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of glyburide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• glycerol phenylbutyrate

  Monitor Closely (1)glycerol 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.

• goldenrod

  Minor (1)goldenrod increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• guanfacine

  Monitor Closely (1)clonidine, guanfacine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

• haloperidol

  Monitor Closely (2)clonidine, 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.

• hydrochlorothiazide

  Monitor Closely (1)chlorthalidone and hydrochlorothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of hydrochlorothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• hydrocodone

  Serious - Use Alternative (1)clonidine, hydrocodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• hydrocortisone

  Minor (1)hydrocortisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• hydromorphone

  Serious - Use Alternative (1)clonidine, hydromorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• hydroxyzine

  Monitor Closely (1)clonidine, hydroxyzine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• ibuprofen

  Monitor Closely (1)ibuprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of ibuprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ibuprofen IV

  Monitor Closely (2)chlorthalidone will increase the level or effect of ibuprofen IV by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.
  
  ibuprofen IV increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. NSAIDs may decrease the therapeutic effects of thiazide-like diuretics; may also enhance nephrotoxic effects.

• iloperidone

  Monitor Closely (1)clonidine, iloperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• imipramine

  Serious - Use Alternative (1)imipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• indacaterol, inhaled

  Monitor Closely (2)chlorthalidone, indacaterol, inhaled. serum potassium. Use Caution/Monitor. Combination may increase risk of hypokalemia.
  
  indacaterol, inhaled, chlorthalidone. Other (see comment). Use Caution/Monitor. Comment: Caution is advised in the coadministration of indacaterol neohaler with non-potassium-sparing diuretics.

• indapamide

  Monitor Closely (1)chlorthalidone and indapamide both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of indapamide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• indomethacin

  Monitor Closely (1)indomethacin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of indomethacin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• insulin aspart

  Minor (3)chlorthalidone decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of insulin aspart by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, insulin aspart. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• insulin degludec

  Monitor Closely (2)chlorthalidone decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.
  
  clonidine, 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 aspart

  Monitor Closely (2)chlorthalidone decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.
  
  clonidine, 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 detemir

  Minor (3)clonidine decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  chlorthalidone decreases effects of insulin detemir by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine, insulin detemir. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• insulin glargine

  Minor (3)chlorthalidone decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine, insulin glargine. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  clonidine decreases effects of insulin glargine by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• insulin glulisine

  Minor (3)clonidine, insulin glulisine. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of insulin glulisine by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• insulin inhaled

  Monitor Closely (2)chlorthalidone decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Diuretics may cause hyperglycemia and glycosuria in patients with diabetes mellitus, possibly by diuretic-induced hpokalemia.
  
  clonidine, 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.

• insulin lispro

  Minor (3)chlorthalidone decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of insulin lispro by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, insulin lispro. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• insulin NPH

  Minor (3)clonidine, insulin NPH. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  clonidine decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  chlorthalidone decreases effects of insulin NPH by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• insulin regular human

  Minor (3)clonidine decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, insulin regular human. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of insulin regular human by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• iobenguane I 131

  Serious - Use Alternative (1)clonidine will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• irbesartan

  Monitor Closely (1)irbesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• isavuconazonium sulfate

  Monitor Closely (1)isavuconazonium 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.

• isocarboxazid

  Serious - Use Alternative (1)isocarboxazid, chlorthalidone. Other (see comment). Contraindicated. Comment: Additive hypotensive effects may be seen when MAOI's are combined with antihypertensives.

• isoproterenol

  Monitor Closely (1)isoproterenol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)isoproterenol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• ivabradine

  Monitor Closely (1)ivabradine, 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.

• ixekizumab

  Monitor Closely (1)ixekizumab, 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.

• juniper

  Monitor Closely (1)juniper, chlorthalidone. Other (see comment). Use Caution/Monitor. Comment: Juniper may potentiate or interfere with diuretic therapy. Juniper has diuretic effects, but may cause kidney damage at large doses.

• ketoprofen

  Monitor Closely (1)ketoprofen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of ketoprofen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac

  Monitor Closely (1)ketorolac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of ketorolac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• ketorolac intranasal

  Monitor Closely (1)ketorolac intranasal increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Minor (1)chlorthalidone will increase the level or effect of ketorolac intranasal by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• L-methylfolate

  Minor (1)chlorthalidone decreases levels of L-methylfolate by increasing renal clearance. Minor/Significance Unknown.

• labetalol

  Monitor Closely (1)labetalol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lasmiditan

  Monitor Closely (1)lasmiditan, 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.

• lemborexant

  Monitor Closely (1)lemborexant, 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.

• levalbuterol

  Monitor Closely (1)levalbuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)levalbuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• levobunolol

  Serious - Use Alternative (1)clonidine, levobunolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• levodopa

  Monitor Closely (2)levodopa increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.
  
  levodopa increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

• levomilnacipran

  Monitor Closely (1)levomilnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor. Because levomilnacipran decreases reuptake of NE, it may antagonize clonidine antihypertensive effect.

• lily of the valley

  Monitor Closely (1)chlorthalidone increases toxicity of lily of the valley by Other (see comment). Use Caution/Monitor. Comment: Increased risk of cardiac toxicity due to K+ depletion.

• liraglutide

  Monitor Closely (1)chlorthalidone decreases effects of liraglutide by pharmacodynamic antagonism. Use Caution/Monitor. Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Monitor glycemic control especially when initiating, discontinuing, or increasing thiazide diuretic dose.

• lithium

  Monitor Closely (1)chlorthalidone increases toxicity of lithium by decreasing elimination. Use Caution/Monitor.

• lofepramine

  Serious - Use Alternative (1)lofepramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• lofexidine

  Serious - Use Alternative (2)lofexidine, chlorthalidone. 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.
  
  lofexidine, clonidine. 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.

• lonapegsomatropin

  Monitor Closely (1)lonapegsomatropin 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 substrates

• lorazepam

  Monitor Closely (1)clonidine, lorazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• lornoxicam

  Monitor Closely (1)lornoxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of lornoxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• losartan

  Monitor Closely (1)losartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine

  Monitor Closely (1)clonidine, loxapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• loxapine inhaled

  Monitor Closely (1)clonidine, loxapine inhaled. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• lumacaftor/ivacaftor

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.

• lurasidone

  Monitor Closely (2)lurasidone increases effects of chlorthalidone 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.
  
  lurasidone 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.

• macimorelin

  Serious - Use Alternative (1)clonidine, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that may transiently elevate growth hormone (GH) concentrations may impact the accuracy of the macimorelin diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin.

• magnesium chloride

  Minor (1)chlorthalidone decreases levels of magnesium chloride by increasing renal clearance. Minor/Significance Unknown.

• magnesium citrate

  Minor (1)chlorthalidone decreases levels of magnesium citrate by increasing renal clearance. Minor/Significance Unknown.

• magnesium hydroxide

  Minor (1)chlorthalidone decreases levels of magnesium hydroxide by increasing renal clearance. Minor/Significance Unknown.

• magnesium oxide

  Minor (1)chlorthalidone decreases levels of magnesium oxide by increasing renal clearance. Minor/Significance Unknown.

• magnesium sulfate

  Minor (1)chlorthalidone decreases levels of magnesium sulfate by increasing renal clearance. Minor/Significance Unknown.

• maitake

  Monitor Closely (1)maitake increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of hypokalemia (theoretical interaction).Minor (1)maitake increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• maprotiline

  Serious - Use Alternative (1)maprotiline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• maraviroc

  Monitor Closely (1)maraviroc, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

• meclofenamate

  Monitor Closely (1)meclofenamate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of meclofenamate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• mefenamic acid

  Monitor Closely (1)mefenamic acid increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of mefenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meloxicam

  Monitor Closely (1)meloxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of meloxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• meperidine

  Serious - Use Alternative (1)clonidine, meperidine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• mesalamine

  Minor (1)chlorthalidone will increase the level or effect of mesalamine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metaproterenol

  Monitor Closely (1)metaproterenol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)metaproterenol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• metformin

  Minor (3)chlorthalidone decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of metformin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, metformin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.

• methadone

  Serious - Use Alternative (1)clonidine, methadone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• methoxsalen

  Monitor Closely (1)methoxsalen, chlorthalidone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methyclothiazide

  Monitor Closely (1)chlorthalidone and methyclothiazide both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of methyclothiazide by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• methyl aminolevulinate

  Serious - Use Alternative (1)chlorthalidone, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• methyldopa

  Monitor Closely (1)clonidine, methyldopa. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Sympatholytic action may worsen sinus node dysfunction and atrioventricular (AV) block.

• methylphenidate transdermal

  Monitor Closely (1)methylphenidate transdermal decreases effects of chlorthalidone by anti-hypertensive channel blocking. Use Caution/Monitor.

• methylprednisolone

  Minor (1)methylprednisolone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• metoclopramide intranasal

  Serious - Use Alternative (1)clonidine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metolazone

  Monitor Closely (1)chlorthalidone and metolazone both decrease serum potassium. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of metolazone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• metoprolol

  Monitor Closely (3)metoprolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.
  
  metoprolol, 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, metoprolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• metyrosine

  Monitor Closely (1)clonidine, metyrosine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• midazolam intranasal

  Monitor Closely (1)midazolam 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.

• miglitol

  Minor (3)clonidine decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, miglitol. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of miglitol by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• milnacipran

  Monitor Closely (1)milnacipran decreases effects of clonidine by pharmacodynamic antagonism. Use Caution/Monitor.

• minoxidil

  Minor (1)chlorthalidone increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

• mirtazapine

  Serious - Use Alternative (1)mirtazapine decreases effects of clonidine by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Risk of hypertensive urgency.

• mobocertinib

  Serious - Use Alternative (1)mobocertinib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.

• mometasone inhaled

  Monitor Closely (1)mometasone inhaled increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may increase hypokalemic effect of loop diuretics.

• morphine

  Serious - Use Alternative (1)clonidine, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• mycophenolate

  Monitor Closely (1)chlorthalidone will increase the level or effect of mycophenolate by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)clonidine, nabilone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• nabumetone

  Monitor Closely (1)nabumetone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of nabumetone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nadolol

  Monitor Closely (2)nadolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nadolol, 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, nadolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• nalbuphine

  Serious - Use Alternative (1)clonidine, nalbuphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• naproxen

  Monitor Closely (1)naproxen increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of naproxen by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• nateglinide

  Minor (3)clonidine decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.
  
  clonidine, nateglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of nateglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• nebivolol

  Monitor Closely (3)nebivolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nebivolol, 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.Serious - Use Alternative (1)clonidine, nebivolol. Either increases toxicity of the other by unspecified interaction mechanism. Avoid or Use Alternate Drug. Can increase risk of bradycardia.

• neratinib

  Monitor Closely (1)neratinib 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.

• nitazoxanide

  Monitor Closely (1)nitazoxanide, chlorthalidone. Either increases levels of the other by Mechanism: plasma protein binding competition. Use Caution/Monitor.

• nitroglycerin rectal

  Monitor Closely (2)nitroglycerin rectal, chlorthalidone. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .
  
  nitroglycerin rectal, clonidine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Observe for possible additive hypotensive effects during concomitant use. .

• nitroprusside sodium

  Monitor Closely (1)nitroprusside sodium, clonidine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects.

• noni juice

  Minor (1)noni juice increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (1)norepinephrine and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)norepinephrine, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• nortriptyline

  Serious - Use Alternative (1)nortriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• octacosanol

  Minor (2)octacosanol increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.
  
  octacosanol increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• olanzapine

  Monitor Closely (1)clonidine, olanzapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• oliceridine

  Monitor Closely (1)oliceridine decreases effects of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor for signs of diminished diuresis and/or effects on blood pressure and increase dosage of the diuretic as needed. .

• olmesartan

  Monitor Closely (1)olmesartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• olodaterol inhaled

  Monitor Closely (1)chlorthalidone and olodaterol inhaled both decrease serum potassium. Use Caution/Monitor.

• olopatadine intranasal

  Serious - Use Alternative (1)clonidine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  Serious - Use Alternative (1)olutasidenib will decrease the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.

• omaveloxolone

  Monitor Closely (1)omaveloxolone 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.

• opium tincture

  Serious - Use Alternative (1)clonidine, opium tincture. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• oritavancin

  Monitor Closely (1)oritavancin 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 index

• orphenadrine

  Serious - Use Alternative (1)clonidine, orphenadrine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

• ospemifene

  Monitor Closely (1)chlorthalidone, ospemifene. Either increases levels of the other by plasma protein binding competition. Modify Therapy/Monitor Closely.

• oxaprozin

  Monitor Closely (1)oxaprozin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of oxaprozin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• oxazepam

  Monitor Closely (1)clonidine, oxazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• oxycodone

  Serious - Use Alternative (1)clonidine, oxycodone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• oxymorphone

  Serious - Use Alternative (1)clonidine, oxymorphone. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• pacritinib

  Serious - Use Alternative (1)pacritinib will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• palbociclib

  Monitor 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 palbociclib

• paliperidone

  Monitor Closely (1)clonidine, paliperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• parecoxib

  Monitor Closely (1)parecoxib increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of parecoxib by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• paroxetine

  Monitor Closely (1)clonidine, paroxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• penbutolol

  Monitor Closely (2)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.
  
  penbutolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pentazocine

  Serious - Use Alternative (1)clonidine, pentazocine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• perampanel

  Serious - Use Alternative (1)clonidine, perampanel. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• perphenazine

  Monitor Closely (1)clonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• pimozide

  Monitor Closely (1)clonidine, pimozide. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• pindolol

  Monitor Closely (2)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.
  
  pindolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pioglitazone

  Minor (3)clonidine, pioglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of pioglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• pirbuterol

  Monitor Closely (1)pirbuterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)pirbuterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• piroxicam

  Monitor Closely (1)piroxicam increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of piroxicam by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• pirtobrutinib

  Monitor 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.

• pitolisant

  Monitor 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.

• pivmecillinam

  Monitor Closely (1)pivmecillinam, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• ponesimod

  Serious - 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.

• porfimer

  Monitor Closely (1)chlorthalidone, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• potassium acid phosphate

  Monitor Closely (1)potassium acid phosphate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• potassium chloride

  Monitor Closely (1)potassium chloride increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• potassium citrate

  Monitor Closely (1)potassium citrate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pramipexole

  Monitor Closely (1)clonidine, pramipexole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• prazosin

  Monitor 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.

• prednisolone

  Minor (1)prednisolone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• prednisone

  Minor (1)prednisone, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• probenecid

  Monitor Closely (1)chlorthalidone will increase the level or effect of probenecid by acidic (anionic) drug competition for renal tubular clearance. Use Caution/Monitor.

• prochlorperazine

  Monitor Closely (1)clonidine, prochlorperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• promethazine

  Monitor Closely (1)clonidine, promethazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• propranolol

  Monitor Closely (2)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.
  
  propranolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.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.

• protriptyline

  Serious - Use Alternative (1)protriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• quazepam

  Monitor Closely (1)clonidine, quazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• quetiapine

  Monitor Closely (1)clonidine, quetiapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• reishi

  Minor (2)reishi increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.
  
  reishi increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

• remifentanil

  Serious - Use Alternative (1)clonidine, remifentanil. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• repaglinide

  Minor (3)chlorthalidone decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  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.

• ribociclib

  Monitor 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.

• risperidone

  Monitor Closely (1)clonidine, risperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• ritlecitinib

  Monitor 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.

• rolapitant

  Monitor 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 2b

  Monitor 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.

• ropinirole

  Monitor Closely (1)clonidine, ropinirole. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• rose hips

  Minor (1)rose hips will increase the level or effect of chlorthalidone by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• rosiglitazone

  Minor (3)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.
  
  chlorthalidone decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• rotigotine

  Monitor Closely (1)clonidine, rotigotine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• rufinamide

  Monitor Closely (1)clonidine, rufinamide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• sacubitril/valsartan

  Monitor Closely (1)sacubitril/valsartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• salicylates (non-asa)

  Monitor Closely (1)salicylates (non-asa) increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of salicylates (non-asa) by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (1)salmeterol and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (1)salmeterol, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.

• salsalate

  Monitor Closely (1)salsalate increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of salsalate by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sarilumab

  Monitor 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.

• saxagliptin

  Minor (3)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.
  
  chlorthalidone decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• schisandra

  Monitor Closely (1)schisandra will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• secukinumab

  Monitor 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/dexmethylphenidate

  Monitor Closely (1)serdexmethylphenidate/dexmethylphenidate increases toxicity of clonidine by unknown mechanism. Use Caution/Monitor.

• sertraline

  Monitor Closely (1)clonidine, sertraline. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• shark cartilage

  Monitor Closely (1)chlorthalidone, shark cartilage. Other (see comment). Use Caution/Monitor. Comment: May lead to hypercalcemia (theoretical).

• shepherd's purse

  Minor (2)shepherd's purse, chlorthalidone. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.
  
  shepherd's purse, clonidine. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

• sitagliptin

  Minor (3)clonidine, sitagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• sodium oxybate

  Serious - 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.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol

  Monitor Closely (1)chlorthalidone and sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol both decrease serum potassium. Modify Therapy/Monitor Closely.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of chlorthalidone by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.

• sofosbuvir/velpatasvir

  Monitor 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.

• somapacitan

  Monitor 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 substrates

• somatrogon

  Monitor 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 substrates

• somatropin

  Monitor 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 substrates

• sotalol

  Monitor Closely (2)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.
  
  sotalol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.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.

• sotorasib

  Serious - 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 modifications

• spironolactone

  Monitor Closely (1)spironolactone increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• squill

  Serious - Use Alternative (1)chlorthalidone increases toxicity of squill by Other (see comment). Avoid or Use Alternate Drug. Comment: Potassium depletion may enhance toxicity of squill.

• stiripentol

  Monitor 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.

• succinylcholine

  Monitor Closely (1)succinylcholine increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sufentanil

  Serious - 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 SL

  Serious - 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.

• sulfadiazine

  Minor (1)chlorthalidone increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.

• sulfamethoxazole

  Minor (2)chlorthalidone increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.
  
  chlorthalidone, sulfamethoxazole. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• sulfasalazine

  Monitor Closely (1)sulfasalazine increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of sulfasalazine by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• sulfisoxazole

  Minor (1)chlorthalidone increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.

• sulindac

  Monitor Closely (1)sulindac increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of sulindac by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tacrolimus

  Minor (1)clonidine increases levels of tacrolimus by unknown mechanism. Minor/Significance Unknown.

• tadalafil

  Monitor Closely (2)tadalafil increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.
  
  tadalafil increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

• talquetamab

  Monitor Closely (1)talquetamab will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• tapentadol

  Serious - Use Alternative (1)clonidine, tapentadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• teclistamab

  Monitor 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.

• teduglutide

  Monitor 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.

• telmisartan

  Monitor Closely (1)telmisartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• telotristat ethyl

  Monitor 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.

• temazepam

  Monitor Closely (1)clonidine, temazepam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• temocillin

  Monitor Closely (1)temocillin, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• terbutaline

  Monitor Closely (1)terbutaline and chlorthalidone both decrease serum potassium. Use Caution/Monitor.Minor (2)terbutaline, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Hypokalemia.
  
  chlorthalidone, terbutaline. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypokalemic effects.

• thalidomide

  Serious - Use Alternative (1)clonidine, thalidomide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Enhanced CNS depressant effects.

• thioridazine

  Monitor Closely (1)clonidine, thioridazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• thiothixene

  Monitor Closely (1)clonidine, thiothixene. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• ticarcillin

  Monitor Closely (1)ticarcillin, chlorthalidone. Either increases levels of the other by decreasing renal clearance. Use Caution/Monitor.

• timolol

  Monitor Closely (2)timolol increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.

• tizanidine

  Minor (2)tizanidine increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.
  
  tizanidine increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

• tolazamide

  Minor (3)chlorthalidone decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  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.

• tolbutamide

  Minor (3)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.
  
  chlorthalidone decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.

• tolfenamic acid

  Monitor Closely (1)tolfenamic acid increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of tolfenamic acid by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolmetin

  Monitor Closely (1)tolmetin increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)chlorthalidone will increase the level or effect of tolmetin by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• tolvaptan

  Monitor Closely (1)tolvaptan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• toremifene

  Monitor Closely (1)chlorthalidone, toremifene. Other (see comment). Use Caution/Monitor. Comment: Thiazide diuretics decrease renal calcium excretion and may increase risk of hypercalcemia in patients taking toremifene.

• torsemide

  Monitor Closely (1)torsemide and chlorthalidone both decrease serum potassium. Use Caution/Monitor.

• tramadol

  Serious - Use Alternative (1)clonidine, tramadol. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• trazodone

  Serious - Use Alternative (1)trazodone decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• treprostinil

  Minor (2)treprostinil increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.
  
  treprostinil increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

• tretinoin

  Serious - Use Alternative (1)chlorthalidone, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  Serious - Use Alternative (1)chlorthalidone, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• triamcinolone acetonide injectable suspension

  Minor (1)triamcinolone acetonide injectable suspension, chlorthalidone. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypokalemia, especially with strong glucocorticoid activity.

• triamterene

  Monitor Closely (1)triamterene increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• triazolam

  Monitor Closely (1)clonidine, triazolam. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• trientine

  Monitor Closely (1)chlorthalidone decreases levels of trientine by increasing renal clearance. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (1)clonidine, trifluoperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• trilostane

  Minor (1)trilostane, chlorthalidone. Other (see comment). Minor/Significance Unknown. Comment: Trilostane reduces K+ loss while maintaining the natriuretic effect. Mechanism: inhibition of mineralocorticoid steroid synthesis.

• trimethoprim

  Minor (1)chlorthalidone, trimethoprim. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of hyponatremia.

• trimipramine

  Serious - Use Alternative (1)trimipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• trofinetide

  Monitor Closely (1)trofinetide will increase the level or effect of clonidine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor CYP3A4 substrates for which a small increase in plasma concentration may lead to serious toxicities if coadministered with trofinetide (a weak CYP3A4 inhibitor).

• umeclidinium bromide/vilanterol inhaled

  Monitor Closely (1)umeclidinium bromide/vilanterol inhaled and chlorthalidone both decrease serum potassium. Modify Therapy/Monitor Closely. Electrocardiographic changes and/or hypokalemia associated with non?potassium-sparing diuretics may worsen with concomitant beta-agonists, particularly if recommended dose is exceeded

• ustekinumab

  Monitor Closely (1)ustekinumab, 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, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of ustekinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• valganciclovir

  Minor (1)chlorthalidone will increase the level or effect of valganciclovir by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• valsartan

  Monitor Closely (1)valsartan increases and chlorthalidone decreases serum potassium. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• verapamil

  Monitor Closely (2)clonidine, verapamil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.
  
  verapamil, clonidine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with verapamil. Monitor heart rate in patients receiving concomitant verapamil and clonidine.

• verteporfin

  Minor (1)chlorthalidone, verteporfin. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Increased phototoxicity.

• vilanterol/fluticasone furoate inhaled

  Monitor Closely (1)vilanterol/fluticasone furoate inhaled and chlorthalidone both decrease serum potassium. Modify Therapy/Monitor Closely. Beta-agonists may acutely worsen ECG changes and/or hypokalemia resulting from non-potassium-sparing diuretics

• vilazodone

  Monitor Closely (1)clonidine, vilazodone. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• vildagliptin

  Minor (3)clonidine, vildagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.
  
  chlorthalidone decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Thiazide dosage >50 mg/day may increase blood glucose.
  
  clonidine decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia.

• vitamin D

  Monitor Closely (1)chlorthalidone increases effects of vitamin D by Other (see comment). Use Caution/Monitor. Comment: Combination may increase hypercalcemic effect of vitamin D analogs. Use with caution.

• voclosporin

  Monitor Closely (1)voclosporin will increase the level or effect of clonidine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Coadministration of voclosporin (a P-gp inhibitor) increases exposure and risk of adverse reactions of P-gp substrates. For certain P-gp substrates with a narrow therapeutic window, refer to prescribing information of these substrates for dosage modifications, if needed.

• vortioxetine

  Monitor Closely (1)clonidine, vortioxetine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

• willow bark

  Minor (1)chlorthalidone will increase the level or effect of willow bark by acidic (anionic) drug competition for renal tubular clearance. Minor/Significance Unknown.

• xipamide

  Monitor Closely (2)xipamide increases effects of chlorthalidone by pharmacodynamic synergism. Use Caution/Monitor.
  
  xipamide increases effects of clonidine by pharmacodynamic synergism. Use Caution/Monitor.

• yohimbe

  Serious - Use Alternative (1)yohimbe decreases effects of clonidine by pharmacodynamic antagonism. Contraindicated.

• ziprasidone

  Monitor Closely (1)clonidine, ziprasidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• zolpidem

  Serious - Use Alternative (1)clonidine, zolpidem. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• zotepine

  Monitor Closely (1)clonidine, zotepine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.