Version July 2025
Thioridazine has been shown to prolong the QTc interval in a dose-related manner. Drugs with this potential, including thioridazine, have been associated with torsades de pointes–type arrhythmias and sudden death. Because of its potential for significant, possibly life-threatening, proarrhythmic effects, reserve thioridazine use for the treatment of patients with schizophrenia who do not experience an acceptable response to adequate courses of treatment with other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose because of intolerable adverse effects from those drugs.
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 and 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was approximately 4.5% compared with a rate of approximately 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Thioridazine is not approved for the treatment of patients with dementia-related psychosis.
Note: In the management of pediatric patients with schizophrenia or severe behavioral problems, use has generally been replaced by second-generation antipsychotics (Ref)
Schizophrenia, refractory: Note: Before initiating treatment with thioridazine, it is strongly recommended that a patient be given at least 2 trials, each with a different antipsychotic drug product, at an adequate dose and for an adequate duration. Dosage should be individualized; use lowest effective dose and shortest effective duration; periodically reassess the need for continued treatment.
Children ≥6 years and Adolescents: Oral: Initial: 0.5 mg/kg/day in 2 to 3 divided doses; maximum initial dose: 50 mg/dose based on adult experience; gradually titrate to clinical response up to a maximum daily dose: 3 mg/kg/day
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution due to hepatic metabolism; accumulation may occur.
(For additional information see "Thioridazine: Drug information")
Dosage guidance:
Safety: Dose-dependent QTc interval prolongation: Avoid use in patients with baseline QTc >450 msec or with risk factors for QTc prolongation. In patients with QTc >500 msec or QTc increase >60 msec on treatment, consider switching antipsychotics or lowering thioridazine dose (Ref). Antipsychotics are not indicated for use in catatonia and may worsen psychosis and increase the risk for neuroleptic malignant syndrome in patients with catatonia (Ref).
Clinical considerations: Consult a psychiatry specialist for all management decisions; select antipsychotic carefully based on patient preference, clinical characteristics, history, comorbidities, and medication adverse effects profile (Ref).
Schizophrenia (alternative agent):
Note: Not a first- or second-line agent.
Oral: Initial: 50 to 100 mg 3 times daily; may increase total daily dose based on response and tolerability in increments of 100 to 150 mg every 3 to 4 days; monitor for anticholinergic effects, orthostatic hypotension, and sedation during titration. Usual dosage: 200 to 600 mg/day in 1 to 3 divided doses; use lowest effective maintenance dose. Some patients have required titration to 800 mg/day to achieve an adequate response; however, the risk of adverse effects (eg, ocular) is increased. Maximum: 800 mg/day (Ref).
Discontinuation of therapy: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (Ref).
Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution (hepatic metabolism).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: ECG changes, hypotension, orthostatic hypotension, peripheral edema, prolonged QT Interval on ECG, torsades de pointes
Central nervous system: Confusion (sundowning), disruption of temperature regulation (Martinez 2002), drowsiness, drug-induced Parkinson disease, extrapyramidal reaction, headache, hyperactive behavior, lethargy, psychotic reaction, restlessness, seizure, tardive dyskinesia (Lehman 2004)
Dermatologic: Dermatitis, hyperpigmentation (Lehman 2004), pallor, skin photosensitivity, skin rash, urticaria
Endocrine & metabolic: Amenorrhea, galactorrhea not associated with childbirth, weight gain (Lehman 2004)
Gastrointestinal: Constipation, diarrhea, nausea, parotid gland enlargement, vomiting, xerostomia
Genitourinary: Breast engorgement, inhibited ejaculation, priapism, sexual difficulty (La Torre 2013), sexual disorder (La Torre 2013)
Hematologic & oncologic: Agranulocytosis, leukopenia
Ophthalmic: Blurred vision, corneal opacity (Lehman 2004), retinitis pigmentosa
Respiratory: Nasal congestion
Severe CNS depression; severe hyper-/hypotensive heart disease; coma; in combination with other drugs that are known to prolong the QTc interval, CYP2D6 inhibitors (fluoxetine, paroxetine), and/or fluvoxamine, propranolol, or pindolol; in patients with congenital long QT syndrome or a history of cardiac arrhythmias; patients known to have genetic defect leading to reduced levels of activity of CYP2D6
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Arrhythmias: [US Boxed Warning]: Has been shown to prolong the QTc interval in a dose-related manner; this may potentially cause torsades de pointes and sudden death. Therefore, thioridazine should be reserved for patients with schizophrenia who have an insufficient response to adequate levels of other antipsychotic drugs. Risk of torsades de pointes and/or sudden death may be higher with in patients with bradycardia, hypokalemia, the presence of congenital prolongation of the QTc interval, reduced activity of cytochrome P450 (CYP-450) 2D6, or concomitant use of other drugs that prolong the QTc interval, inhibit CYP2D6, or interfere with the clearance of thioridazine. Consider a cardiac evaluation (including Holter monitoring) in patients who experience symptoms that may be associated with Torsades de Pointes (dizziness, palpitations, syncope).
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, paralytic ileus, urinary retention, BPH, xerostomia, or visual problems. Relative to other neuroleptics, thioridazine has a high potency of cholinergic blockade (Richelson 1999).
• Blood dyscrasias: Leukopenia, neutropenia, and/or agranulocytosis (sometimes fatal) have been reported in clinical trials and postmarketing reports with antipsychotic use; presence of risk factors (eg, preexisting low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
• Esophageal dysmotility/Aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (ie, Alzheimer disease), particularly in patients >75 years (Herzig 2017; Maddalena 2004).
• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia. Risk of dystonia (and possibly other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Keepers 2020]; Soares-Weiser 2007).
• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability (Landi 2005; Seppala 2018).
• Hyperprolactinemia: Use associated with increased prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.
• Neuroleptic malignant syndrome (NMS): May be associated with NMS; monitor for mental status changes, fever, muscle rigidity, and/or autonomic instability. Following recovery from NMS, reintroduction of drug therapy should be carefully considered; if an antipsychotic agent is resumed, monitor closely for NMS.
• Ocular effects: May cause pigmentary retinopathy, characterized by diminution of visual acuity, brownish coloring of vision, and impairment of night vision, in patients exceeding recommended doses. Periodic eye examinations are recommended in patients receiving 600 mg/day or more (Oshika 1995).
• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia).
• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects (Kwok 2005; Martinez 2002).
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with severe cardiovascular disease. Do not initiate therapy in patients with a QTc interval >450 msec.
• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death. The APA recommends giving preference to second generation antipsychotics over first generation antipsychotics in elderly patients with dementia-related psychosis due to a potentially greater risk of harm relative to second generation antipsychotics (APA [Reus 2016]). Thioridazine is not approved for the treatment of dementia-related psychosis.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Seizure disorder: Use with caution in patients at risk of seizures; first-generation antipsychotics may lower the seizure threshold (APA [Keepers 2020]).
Other warnings/precautions:
• Discontinuation of therapy: When discontinuing antipsychotic therapy, gradually taper antipsychotics to avoid physical withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternating feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).
Risk of dystonia is increased with the use of high potency and higher doses of conventional antipsychotics and in males and younger patients. Use with caution in children and adolescents; adverse effects due to elevated prolactin levels have been observed; long-term effects on growth or sexual maturation have not been evaluated. Similar to adult experience, the American Academy of Child and Adolescent Psychiatry (AACAP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (AACAP [McClellan 2007]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 10 mg, 25 mg, 50 mg, 100 mg
Yes
Tablets (Thioridazine HCl Oral)
10 mg (per each): $0.54 - $0.60
25 mg (per each): $0.76 - $0.84
50 mg (per each): $0.95 - $1.05
100 mg (per each): $1.09 - $1.19
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer with water, food, or milk to decrease GI upset
Store at 20°C to 25°C (68°F to 77°F). Protect from light.
Management of schizophrenic patients who fail to respond adequately to treatment with other antipsychotic drugs, either because of insufficient effectiveness or the inability to achieve an effective dose because of intolerable adverse effects from those medications (FDA approved in pediatric patients [age not specified] and adults). Note: In the management of pediatric patients with schizophrenia or severe behavioral problems, use has generally been replaced by second-generation antipsychotics (AACAP [McClellan 2013]). Before initiating treatment with thioridazine, it is strongly recommended that a patient be given at least 2 trials, each with a different antipsychotic drug product, at an adequate dose and for an adequate duration.
Thioridazine may be confused with thiothixene, Thorazine
Mellaril may be confused with Elavil, Mebaral
Beers Criteria: Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of stroke and a greater rate of cognitive decline and mortality in patients with dementia. Evidence also suggests there may be an increased risk of mortality with use independent of dementia. Avoid antipsychotics for behavioral problems associated with dementia or delirium unless alternative nonpharmacologic therapies have failed and patient may harm self or others. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults. Use of antipsychotics may be appropriate for FDA approved indications including schizophrenia, bipolar disorder, Parkinson disease psychosis, adjunctive therapy in major depressive disorder, or for short-term use as an antiemetic (Beers Criteria [AGS 2023]).
Substrate of CYP2C19 (Minor), CYP2D6 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2D6 (Moderate); Induces CYP3A4 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acetylcholinesterase Inhibitors: May decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Acetylcholinesterase Inhibitors. Risk C: Monitor
Aclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Acrivastine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Adagrasib: May increase QTc-prolonging effects of Thioridazine. Adagrasib may increase serum concentration of Thioridazine. Risk X: Avoid
Agents With Seizure Threshold Lowering Potential: May increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Aldesleukin: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Aminolevulinic Acid (Systemic): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Systemic). Risk X: Avoid
Aminolevulinic Acid (Topical): Photosensitizing Agents may increase photosensitizing effects of Aminolevulinic Acid (Topical). Risk C: Monitor
Amitriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Amitriptyline. CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Amitriptyline. Risk C: Monitor
Amoxapine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Amoxapine. Risk C: Monitor
Antacids: May decrease absorption of Antipsychotic Agents (Phenothiazines). Risk C: Monitor
Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (First Generation [Typical]) may decrease therapeutic effects of Anti-Parkinson Agents (Dopamine Agonist). Management: Avoid concomitant therapy if possible. If antipsychotic use is necessary, consider using atypical antipsychotics such as clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider Therapy Modification
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole Lauroxil: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of ARIPiprazole Lauroxil. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: CYP2D6 Inhibitors (Moderate) may increase serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy, indication, or dosage form. Consult full interaction monograph for specific recommendations. Risk C: Monitor
Artemether and Lumefantrine: May increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Atogepant: CYP3A4 Inducers (Weak) may decrease serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with CYP3A4 inducers. When used for treatment of chronic migraine, use of atogepant with CYP3A4 inducers should be avoided. Risk D: Consider Therapy Modification
Atomoxetine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Atomoxetine. Risk C: Monitor
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Benperidol. Risk C: Monitor
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benzgalantamine-Galantamine: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Benztropine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Benztropine. Risk C: Monitor
Beta-Blockers: Antipsychotic Agents (Phenothiazines) may increase hypotensive effects of Beta-Blockers. Beta-Blockers may decrease metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease metabolism of Beta-Blockers. Risk C: Monitor
Biperiden: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Biperiden. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Bornaprine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, tardive dyskinesia symptoms may be potentiated. Risk C: Monitor
Botulinum Toxin-Containing Products: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Brexpiprazole: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Brexpiprazole. Management: If brexpiprazole is to be used together with both a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor, the brexpiprazole dose should be reduced to 25% of the usual dose when treating indications other than major depressive disorder. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Bromopride: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Buclizine. Risk C: Monitor
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cabergoline: May decrease therapeutic effects of Antipsychotic Agents. Risk X: Avoid
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of Cannabinoid-Containing Products. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
CarBAMazepine: CYP3A4 Inducers (Weak) may decrease serum concentration of CarBAMazepine. Risk C: Monitor
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Carvedilol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Carvedilol. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chloroquine: Thioridazine may increase QTc-prolonging effects of Chloroquine. Chloroquine may increase serum concentration of Thioridazine. Risk X: Avoid
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Chlorprothixene: May increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Cimetropium. Risk X: Avoid
ClomiPRAMINE: May increase QTc-prolonging effects of Thioridazine. Thioridazine may increase serum concentration of ClomiPRAMINE. Thioridazine may increase active metabolite exposure of ClomiPRAMINE. Risk X: Avoid
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Cyclizine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
CYP2D6 Inhibitors (Moderate): May increase serum concentration of Thioridazine. Risk X: Avoid
CYP2D6 Inhibitors (Strong): May increase serum concentration of Thioridazine. Risk X: Avoid
CYP2D6 Inhibitors (Weak): May increase serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider Therapy Modification
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dapoxetine: May increase serum concentration of Thioridazine. Risk X: Avoid
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Desipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Desipramine. Risk C: Monitor
Deutetrabenazine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Deutetrabenazine. Risk C: Monitor
Deutetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may increase adverse/toxic effects of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor
Dextromethorphan: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Dextromethorphan. Risk C: Monitor
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Dicyclomine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dicyclomine. Risk C: Monitor
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Dimethindene (Systemic). Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dinutuximab Beta: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Domperidone: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid
Donepezil: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
DOXOrubicin (Conventional): CYP2D6 Inhibitors (Moderate) may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroNABinol: Agents with Clinically Relevant Anticholinergic Effects may increase tachycardic effects of DroNABinol. Risk X: Avoid
Dronedarone: Thioridazine may increase QTc-prolonging effects of Dronedarone. Risk X: Avoid
Eliglustat: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Eliglustat. Management: Eliglustat dose is 84 mg daily with CYP2D6 inhibitors. Use is contraindicated (COI) when also combined with strong CYP3A4 inhibitors. When also combined with a moderate CYP3A4 inhibitor, use is COI in CYP2D6 EMs or IMs and should be avoided in CYP2D6 PMs. Risk D: Consider Therapy Modification
Elranatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Eluxadoline. Risk X: Avoid
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Epcoritamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Fesoterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Fesoterodine. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
FLUoxetine: May increase serum concentration of Thioridazine. Risk X: Avoid
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
FluvoxaMINE: May increase serum concentration of Thioridazine. Risk X: Avoid
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Gastrointestinal Agents (Prokinetic). Risk C: Monitor
Gepotidacin: May decrease anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Glofitamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Oral Inhalation). Risk X: Avoid
Glycopyrrolate (Systemic): Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Glycopyrrolate (Systemic). Risk C: Monitor
Glycopyrronium (Topical): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Guanethidine: Antipsychotic Agents may decrease therapeutic effects of Guanethidine. Risk C: Monitor
Haloperidol: May increase QTc-prolonging effects of Thioridazine. Thioridazine may increase serum concentration of Haloperidol. Risk X: Avoid
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider Therapy Modification
Huperzine A: May increase neurotoxic (central) effects of Antipsychotic Agents. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Iloperidone: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Iloperidone. CYP2D6 Inhibitors (Moderate) may decrease active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P95 may be decreased. CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Iloperidone. Specifically, concentrations of the metabolite P88 may be increased. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Imatinib: May increase serum concentration of CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive). Risk C: Monitor
Imipramine: May increase QTc-prolonging effects of Thioridazine. Thioridazine may increase active metabolite exposure of Imipramine. Thioridazine may increase serum concentration of Imipramine. Risk X: Avoid
Indoramin: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Indoramin. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Ipratropium (Nasal): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Ipratropium (Oral Inhalation): May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Itopride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Itopride. Risk C: Monitor
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Letermovir: Thioridazine may decrease therapeutic effects of Letermovir. Risk X: Avoid
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Levoketoconazole. Risk X: Avoid
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Levosulpiride. Risk X: Avoid
Lithium: May increase neurotoxic effects of Antipsychotic Agents. Lithium may decrease serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor
Lofepramine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Lofepramine. The active metabolite of lofepramine is desipramine. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Maprotiline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Maprotiline. Risk C: Monitor
Melatonin: May increase adverse/toxic effects of Thioridazine. Risk C: Monitor
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Melperone: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Mequitazine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Mequitazine. Risk X: Avoid
Metergoline: Antipsychotic Agents may decrease therapeutic effects of Metergoline. Metergoline may decrease therapeutic effects of Antipsychotic Agents. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxsalen (Systemic): Photosensitizing Agents may increase photosensitizing effects of Methoxsalen (Systemic). Risk C: Monitor
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methscopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Methscopolamine. Risk C: Monitor
Metoclopramide: May increase adverse/toxic effects of Antipsychotic Agents. Risk X: Avoid
Metoprolol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Metoprolol. Risk C: Monitor
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
MetyroSINE: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for extrapyramidal symptoms and excessive sedation may be increased. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Mosunetuzumab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Nebivolol. Risk C: Monitor
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
NiMODipine: CYP3A4 Inducers (Weak) may decrease serum concentration of NiMODipine. Risk C: Monitor
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Nortriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Nortriptyline. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
Olmutinib: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Olmutinib. Risk C: Monitor
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Ondansetron: May increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxatomide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyBUTYnin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of OxyBUTYnin. Risk C: Monitor
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Peginterferon Alfa-2b: May decrease serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Risk C: Monitor
Pentamidine (Systemic): May increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Perphenazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Perphenazine. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Perphenazine. Risk C: Monitor
Pholcodine: Blood Pressure Lowering Agents may increase hypotensive effects of Pholcodine. Risk C: Monitor
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pimavanserin: May increase QTc-prolonging effects of Thioridazine. Thioridazine may decrease serum concentration of Pimavanserin. Risk X: Avoid
Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Pindolol: Thioridazine may increase serum concentration of Pindolol. Pindolol may increase serum concentration of Thioridazine. Risk X: Avoid
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Piperaquine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Piribedil: Antipsychotic Agents may decrease therapeutic effects of Piribedil. Piribedil may decrease therapeutic effects of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid
Pitolisant: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Pitolisant. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Porfimer: Photosensitizing Agents may increase photosensitizing effects of Porfimer. Risk X: Avoid
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may increase ulcerogenic effects of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid
Pramlintide: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promethazine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Promethazine. Risk C: Monitor
Propantheline: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Propantheline. Risk C: Monitor
Propiverine: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor
Propranolol: May increase serum concentration of Thioridazine. Thioridazine may increase serum concentration of Propranolol. Risk X: Avoid
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Protriptyline: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Protriptyline. Risk C: Monitor
QT-prolonging Agents (Highest Risk): May increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
QT-prolonging Agents (Moderate Risk): May increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Quinagolide: Antipsychotic Agents may decrease therapeutic effects of Quinagolide. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
QuiNIDine: Thioridazine may increase QTc-prolonging effects of QuiNIDine. QuiNIDine may increase serum concentration of Thioridazine. Risk X: Avoid
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may increase constipating effects of Ramosetron. Risk C: Monitor
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Revefenacin. Risk X: Avoid
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
RisperiDONE: May increase QTc-prolonging effects of Thioridazine. Thioridazine may increase serum concentration of RisperiDONE. Risk X: Avoid
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Rivastigmine. Rivastigmine may decrease therapeutic effects of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider Therapy Modification
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
Saquinavir: Antipsychotic Agents (Phenothiazines) may increase arrhythmogenic effects of Saquinavir. Risk X: Avoid
Scopolamine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Scopolamine. Risk C: Monitor
Secretin: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider Therapy Modification
Serotonergic Agents (High Risk): May increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor
Sertindole: Thioridazine may increase QTc-prolonging effects of Sertindole. Thioridazine may increase serum concentration of Sertindole. Risk X: Avoid
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sirolimus (Conventional): CYP3A4 Inducers (Weak) may decrease serum concentration of Sirolimus (Conventional). Risk C: Monitor
Sirolimus (Protein Bound): CYP3A4 Inducers (Weak) may decrease serum concentration of Sirolimus (Protein Bound). Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Sofpironium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Sofpironium. Risk X: Avoid
Sulpiride: Antipsychotic Agents may increase adverse/toxic effects of Sulpiride. Risk X: Avoid
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Tacrolimus (Systemic): CYP3A4 Inducers (Weak) may decrease serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Talquetamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease active metabolite exposure of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives to the use of moderate CYP2D6 inhibitors with tamoxifen when possible, as the combination may be associated with reduced clinical effectiveness of tamoxifen. Risk D: Consider Therapy Modification
Tamsulosin: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Tamsulosin. Risk C: Monitor
Tarlatamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Teclistamab: May increase serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Tetrabenazine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Tetrabenazine. Specifically, concentrations of the active alpha- and beta-dihydrotetrabenazine metabolites may be increased. Risk C: Monitor
Tetrabenazine: May increase adverse/toxic effects of Antipsychotic Agents. Specifically, the risk for NMS and extrapyramidal symptoms may be increased. Risk C: Monitor
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor
Thiopental: Antipsychotic Agents (Phenothiazines) may increase adverse/toxic effects of Thiopental. Risk C: Monitor
Thiothixene: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Thiothixene. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tiapride: Agents with Clinically Relevant Anticholinergic Effects may decrease therapeutic effects of Tiapride. Risk C: Monitor
Timolol (Systemic): CYP2D6 Inhibitors (Moderate) may increase serum concentration of Timolol (Systemic). Risk C: Monitor
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tiotropium. Risk X: Avoid
Tolterodine: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Tolterodine. Risk C: Monitor
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may increase adverse/toxic effects of Topiramate. Risk C: Monitor
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Trimethobenzamide: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trimethobenzamide. Risk C: Monitor
Trimipramine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Trimipramine. Risk C: Monitor
Trospium: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Trospium. Risk C: Monitor
Ubrogepant: CYP3A4 Inducers (Weak) may decrease serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 100 mg and second dose (if needed) of 100 mg when used with a weak CYP3A4 inducer. Risk D: Consider Therapy Modification
Umeclidinium: May increase anticholinergic effects of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid
Upadacitinib: May increase serum concentration of CYP2D6 Substrates (Narrow Therapeutic Index/Sensitive). Risk C: Monitor
Valbenazine: CYP2D6 Inhibitors (Moderate) may increase active metabolite exposure of Valbenazine. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Verteporfin: Photosensitizing Agents may increase photosensitizing effects of Verteporfin. Risk C: Monitor
Vortioxetine: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Vortioxetine. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuclopenthixol: Agents with Clinically Relevant Anticholinergic Effects may increase anticholinergic effects of Zuclopenthixol. Risk C: Monitor
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Zuclopenthixol: CYP2D6 Inhibitors (Moderate) may increase serum concentration of Zuclopenthixol. Risk C: Monitor
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Because thioridazine increases prolactin concentrations, amenorrhea in women and impotence in men have been reported. False pregnancy tests may also occur with thioridazine use.
Although outcome information has been published in case reports following maternal use of thioridazine in pregnancy, most information is available for phenothiazines as a class (Erkkola 1983; Heinonen 1977; Scanlan 1972; Slone 1977; Vince 1969). Jaundice or hyper- or hyporeflexia have been reported in newborn infants following maternal use of phenothiazines. Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization.
When use in pregnancy is needed, the minimum effective maternal dose should be used to decrease the risk of EPS (ACOG 2008).
Based on experience in adult patients the following has been suggested; pediatric patients may require more frequent monitoring of some parameters as clinically indicated:
Mental status; vital signs (as clinically indicated); ECG (baseline, then periodic; do not initiate if QTc >450 msec); weight, height, BMI, waist circumference (baseline; at every visit for the first 6 months; quarterly with stable antipsychotic dose); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia); electrolytes (baseline potassium; annually and as clinically indicated); liver function (annually and as clinically indicated); fasting plasma glucose level/HbA1c (baseline, then yearly; in patients with diabetes risk factors or if gaining weight, repeat 4 months after starting antipsychotic, then yearly); lipid panel (baseline; repeat every 2 years if LDL level is normal; repeat every 6 months if LDL level is >130 mg/dL); changes in menstruation, development of galactorrhea (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 6 months; high-risk patients every 3 months); visual changes (inquire yearly); ocular examination (yearly in patients >40 years; every 2 years in younger patients) (ADA 2004; APA [Lehman 2004]; Marder 2004).
Thioridazine is a piperidine phenothiazine which blocks postsynaptic mesolimbic dopaminergic receptors in the brain; also has activity at serotonin, noradrenaline, and histamine receptors (Fenton, 2007).
Onset of action: Schizophrenia: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).
Absorption: Rapid (Vanderheeren 1977).
Distribution: Vd: 1.8 to 6.7 L/kg (Vanderheeren 1977).
Protein binding: 96% to 99.3% (Cooper 1978).
Metabolism: Hepatic metabolism by sulphoxidation (primarily), demethylation (2%), and hydroxylation (limited); active metabolites mesoridazine and sulphoridazine (Vanderheeren 1977).
Bioavailability: 25% to 33%.
Half-life elimination: 5 to 27 hours (Mårtensson 1973; Muusze 1977; Vanderheeren 1977).
Time to peak, serum: ~1 to 4 hours (Mårtensson 1973).
