pharmacodynamic synergism. Use Caution/Monitor. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.protriptylineSerious - Use Alternative (1)protriptyline decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.quetiapineMonitor Closely (1)guanfacine, quetiapine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.quinupristin/dalfopristinMonitor Closely (1)quinupristin/dalfopristin will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.reishiMinor (1)reishi increases effects of guanfacine by pharmacodynamic synergism. Minor/Significance Unknown.repaglinideMinor (2)guanfacine decreases effects of repaglinide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. guanfacine, repaglinide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.ribociclibMonitor Closely (1)ribociclib will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.rifabutinMonitor Closely (1)rifabutin will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.rifampinMonitor Closely (1)rifampin will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.rifapentineMonitor Closely (1)rifapentine will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.risperidoneMonitor Closely (1)guanfacine, risperidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.ritonavirMonitor Closely (1)ritonavir will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. ropeginterferon alfa 2bSerious - Use Alternative (1)ropeginterferon alfa 2b and guanfacine both increase Other (see comment). Avoid or Use Alternate Drug. Narcotics, hypnotics or sedatives can produce additive neuropsychiatric side effects. Avoid use and monitor patients receiving the combination for effects of excessive CNS toxicity.rosiglitazoneMinor (2)guanfacine decreases effects of rosiglitazone by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. guanfacine, rosiglitazone. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.saquinavirMonitor Closely (1)saquinavir will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.saxagliptinMinor (2)guanfacine decreases effects of saxagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. guanfacine, saxagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.schisandraMonitor Closely (1)schisandra will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.secobarbitalMonitor Closely (1)secobarbital will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.sertralineMonitor Closely (1)sertraline will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.shepherd's purseMinor (1)shepherd's purse, guanfacine. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.sitagliptinMinor (2)guanfacine decreases effects of sitagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. guanfacine, sitagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.sofosbuvir/velpatasvirMonitor Closely (1)sofosbuvir/velpatasvir will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.sotalolMinor (1)sotalol, guanfacine. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.St John's WortMonitor Closely (1)St John's Wort will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inducers significantly reduce guanfacine plasma concentrations and elimination half-life. If coadministered, more frequent dosing of the IR product may be required to achieve or maintain the desired hypotensive response. For patients with ADHD, FDA-approved labeling for ER guanfacine recommends that, if coadministered, doubling the recommended dose of guanfacine should be considered.stiripentolMonitor Closely (2)stiripentol, guanfacine. 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. stiripentol, guanfacine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.tadalafilMonitor Closely (1)tadalafil increases effects of guanfacine by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.thioridazineMonitor Closely (1)guanfacine, thioridazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.thiothixeneMonitor Closely (1)guanfacine, thiothixene. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.timololMonitor Closely (1)timolol, guanfacine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Non selective beta blocker administration during withdrawal from centrally acting alpha agonists may result in rebound hypertension.tipranavirMonitor Closely (1)tipranavir will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available.tizanidineMinor (1)tizanidine increases effects of guanfacine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.tolazamideMinor (2)guanfacine decreases effects of tolazamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. guanfacine, tolazamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.tolbutamideMinor (2)guanfacine decreases effects of tolbutamide by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. guanfacine, tolbutamide. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.trazodoneSerious - Use Alternative (1)trazodone decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.treprostinilMinor (1)treprostinil increases effects of guanfacine by pharmacodynamic synergism. Minor/Significance Unknown.trifluoperazineMonitor Closely (1)guanfacine, trifluoperazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.trimipramineSerious - Use Alternative (1)trimipramine decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valproic acidMonitor Closely (1)guanfacine increases levels of valproic acid by unknown mechanism. Use Caution/Monitor. Both 3-hydroxy guanfacine (metabolite) and valproic acid are metabolized by glucuronidation, possibly resulting in competitive inhibition.verapamilMonitor Closely (1)verapamil will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. vildagliptinMinor (2)guanfacine decreases effects of vildagliptin by pharmacodynamic antagonism. Minor/Significance Unknown. Diminished symptoms of hypoglycemia. guanfacine, vildagliptin. Other (see comment). Minor/Significance Unknown. Comment: Decreased symptoms of hypoglycemia. Mechanism: decreased hypoglycemia induced catecholamine production.voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Strong or moderate CYP3A4 inhibitors significantly increase guanfacine plasma concentrations. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if coadministered, the guanfacine dosage should be decreased to half of the recommended dose. Specific recommendations for immediate-release (IR) guanfacine are not available. voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of guanfacine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.xipamideMonitor Closely (1)xipamide increases effects of guanfacine by pharmacodynamic synergism. Use Caution/Monitor.ziprasidoneMonitor Closely (1)guanfacine, ziprasidone. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.zotepineMonitor Closely (1)guanfacine, zotepine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium. >10% Xerostomia (10-60%) Somnolence (5-39%) Headache (0.2-26%) Dizziness (2-15%) Constipation (2-16%) Fatigue (2-15%) Abdominal pain (11%) Extended-release tablets Somnolence (6-38%) Headache (23%) Dizziness (6-16%) Decreased appetite (6-15%) Fatigue (2-14%) Abdominal pain (11%) 1-10% Hypotension (7%) Asthenia (2-7%) Impotence (0-7%) Lethargy (6%) Dizziness (6%) Irritability (6%) Nausea (3-6%) Decreased appetite (5%) Weakness (1-5%) Insomnia (3-4%) Bradycardia (3%) Palpitations (3%) Confusion (3%) Depression (3%) Dyspnea (3%) Alopecia (3%) Dermatitis (3%) Diaphoresis (3%) Pruritus (3%) Dyspepsia (3%) Dysphagia (3%) Hypokinesia (3%) Leg cramps (3%) Extended-release tablets Hypotension (7%) Insomnia (7%) Irritability (6%) Lethargy (6%) Nausea (6%) Postural dizziness (5%) Bradycardia (5%) Diarrhea (5%) Anxiety (5%) Dry mouth (3-4%) Constipation (3%) Increased weight (3%) Rash (3%) Nightmare (2%) Enuresis (2%) Frequency Not Defined Orthostatic hypotension Exfoliation Rash Arthralgia Myalgia Extended-release tablets Atrioventricular block Asthenia Chest pain Hypersensitivity Increased alanine aminotransferase Convulsion Increased urinary frequency Hypertension Pallor Postmarketing Reports Cardiovascular: Bradycardia, palpitations, syncope, tachycardia, rebound hypertension, hypertensive encephalopathy CNS: Paresthesias, vertigo GI: Abdominal pain, constipation, diarrhea, dyspepsia Liver/biliary: Abnormal LFTs Musculoskeletal: Arthralgia, leg cramps, leg pain, myalgia Psychiatric: Agitation, anxiety, confusion, depression, hallucinations, insomnia, nervousness Reproductive: Impotence Respiratory: Dyspnea Skin: Alopecia, dermatitis, exfoliative dermatitis, pruritus, rash Sensory: Blurred vision, alterations in taste Urinary: Nocturia, urinary frequency Other: Asthenia, chest pain, edema, malaise, tremor Extended-release tablets General: Edema, malaise, tremor Cardiovascular: Palpitations, tachycardia, rebound hypertension, hypertensive encephalopathy Central nervous system: Paresthesias, vertigo Eye disorders: blurred vision Musculoskeletal System: Arthralgia, leg cramps, leg pain, myalgia Psychiatric: Confusion, hallucinations Reproductive system, male: Erectile dysfunction Respiratory System: Dyspnea Skin and appendages: Alopecia, dermatitis, exfoliative dermatitis, pruritus, rash Special senses: