Thioridazine (Mellaril) - Uses, Dose, MOA, Brands, Side effects

Thioridazine (Mellaril) is a typical antipsychotic drug that is nowadays rarely used to treat psychosis and schizophrenia.

Thioridazine (Mellaril) Uses:

Schizophrenia:
- Thioridazine (Mellaril) is an anti-psychotic drug that is not commonly used as a first-line of treatment in patients with psychosis or schizophrenia.
- It is indicated only if the person has failed a trial of at least two antipsychotic drugs due to either intolerable side effects or because of a lack of efficacy.

Thioridazine (Mellaril) Dose in Adults

Thioridazine (Mellaril) Dose in the treatment of Schizophrenia:

It is administered orally in a dose of 50 to 100 mg three times a day initially. The dose is then gradually increased in increments at weekly intervals up to a maximum dose of 800 mg per day.
The usual dose is 300 mg per day given in two to four divided doses.
Discontinuation of therapy:
- The drug should be tapered off before discontinuing it completely. Slow tapering is advised to avoid withdrawal symptoms such as gastrointestinal symptoms, headache, and lack of sleep.
- In certain situations, abrupt withdrawal may be advised when the drug has to be discontinued primarily because of adverse drug reactions or intolerable side effects.
- It is important to monitor the patient while discontinuing the drug so as to avoid the recurrence of the disease.
Switching antipsychotics:
- Antipsychotics, like other neuropsychiatric symptoms, maybe either switched to another antipsychotic drug by slowly reducing the dose of one and building the dose of the new antipsychotic drug. It can also be abruptly discontinued and the new antipsychotic drug may be started at full dose.
- Occasionally, when the risks of recurrence are very high, it is best to maintain the patient on one antipsychotic while slowly increasing the dose of the other. Once the new antipsychotic drug is in the therapeutic dose range, the first antipsychotic may be slowly tapered off.
- Most psychiatrists prefer the overlapping method rather than abruptly discontinuing the medicines.

Thioridazine (Mellaril) Dose in Children

Note: It is best to use second-generation antipsychotic medicines when treating children with behavioral problems and schizophrenia.

Thioridazine (Mellaril) Dose in the treatment of Schizophrenia, refractory:

Note: It is important to keep the following points in mind when using thioridazine in children with schizophrenia:

Use the lowest effective dose
Use second-generation antipsychotics preferably
Use it only if the child has been given a trial of at least two antipsychotic medicines.
Children 6 years of age or older:
- It is given in a dose of 0.5 mg/kg/day orally in 2 to 3 divided doses. The maximum initial dose is 50 mg/dose. The dose is then gradually titrated until either a clinical response is achieved or up to a maximum daily dose of 3 mg/kg/day.

Thioridazine (Malleril) Pregnancy Risk Category: N

Even though case reports involving maternal thioridazine use in pregnancy have published some outcome information, the majority of information is available for phenothiazines.
After maternal use of phenothiazines, newborn infants have experienced jaundice and hypo- or hyperreflexia.
The use of antipsychotics during pregnancy's third trimester can lead to abnormal muscle movements and withdrawal symptoms in newborns after delivery.
The newborn can experience agitation, feeding disorders, hypotonia, and hypertonia as well as respiratory distress, somnolence, and tremor.
These symptoms may be self-limiting or may require hospitalization. To reduce the risk of EPS, use the lowest effective maternal dose when it is necessary.
Thioridazine has been linked to increased prolactin levels, which can lead to amenorrhea among women and impotence among men. Thioridazine may cause false pregnancy tests.

Use of Thioridazine while breastfeeding

It is unknown if breast milk contains thioridazine.
Infants who have been exposed to antipsychotic drugs should be closely monitored for any signs of adverse reactions.
Routine monitoring of serum concentrations in infants is not recommended.

Dose in Kidney Disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution (hepatic metabolism).

Side effects of Thioridazine (Mellaril):

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

Contraindications to Thioridazine (Mellaril):

Severe CNS depression;
Severe hyper/hypotensive cardiac disease;
Coma.
In combination with other drugs known to prolong QTc intervals, CYP2D6 inhibits (fluoxetine, paroxetine, and/or fluvoxamine, propranolol, or pindolol);
In patients with congenital long QT syndrome or a history of cardiac arrhythmias.
Patients with a genetic defect leading to decreased activity of CYP2D6

Warnings and Precautions

Arrhythmias: [US Boxed Warning]:
- It has been demonstrated that it prolongs the QTc interval in dose-related ways; this could potentially lead to Torsades De Pointes or sudden death.
- Patients with schizophrenia should not be given thioridazine if they have not responded to other antipsychotic drugs.
- Patients with bradycardia and hypokalemia may be at greater risk of sudden death or torsades-de-pointes.
- Patients who have symptoms such as dizziness, palpitations or syncope should be referred to a Holter monitor and a cardiac exam.
- Patients with QTc greater than 500 msec should be stopped from receiving therapy.
Anticholinergic effects
- It may cause constipation, xerostomia, and blurred vision.
- Thioridazine is a neuroleptic with a higher potency than other neuroleptics.
Blood dyscrasias:
- Clinical trials have reported leukopenia, neutropenia, and/or agranulocytosis (sometimes deadly) in postmarketing reports.
- The presence of risk factors, such as low WBC, or a history of drug-induced neurotoxicity, should prompt periodic blood counts assessment.
- Stop treatment immediately if blood dyscrasias develop or absolute neutrophil count is below 1,000/mm³.
CNS depression:
- CNS depression can lead to mental or physical impairments.
- Patients should be cautious about driving, operating machinery, and other tasks that require mental alertness.
Esophageal dysmotility/Aspiration:
- Antipsychotic use has been linked to esophageal dysmotility, aspiration, and increased risk with age.
- Patients at high risk of aspiration pneumonia (i.e. Alzheimer's disease) should be treated with caution, especially patients over 75 years old.
Extrapyramidal symptoms:
- Extrapyramidal symptoms (EPS) may include pseudoparkinsonism and acute dystonic reactions.
- Higher doses of antipsychotics and use by males (and younger patients) can increase the risk of dystonia (and other EPS).
- The following factors are associated with higher vulnerability to tardive dyskinesia: older age, female gender, postmenopausal status, and Parkinson's disease symptoms.
- You may consider discontinuing therapy if you experience tardive dyskinesia symptoms.
Hyperprolactinemia:
- Hyperprolactinemia is a condition that results in an increase in prolactin levels.
- The clinical significance of hyperprolactinemia for patients with breast cancer or other prolactin-dependent tumors is not known.
Neuroleptic malignant syndrome (NMS):
- This may be due to NMS. Monitor for changes in mental status, fever, the rigidity of the muscles, and/or other signs that could indicate NMS.
- After recovery from NMS, it is important to carefully consider reintroduction. If an antipsychotic agent was resumed, be sure to monitor for NMS.
Ocular effects
- Patients who take more than the recommended doses of this medication may develop pigmentary retinopathy. This is characterized by a decrease in visual acuity and brownish-colored vision.
- Patients who consume 600 mg or more of this medication should have their eyes examined at least once a month.
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
- It is possible to have impaired core body temperature regulation.
- Be careful with heat exposure, strenuous exercise, heat, dehydration and any concomitant anticholinergic medication (Kwok 2005; Martinez2002).
Cardiovascular disease
- Patients with severe cardiovascular disease should be cautious. Patients with QTc intervals >450 msec should not be initiated.
Dementia: [US Boxed Warning]
- Antipsychotics have a higher death rate than placebo for dementia-related psychosis in the elderly.
- The majority of deaths were either from cardiovascular disease (eg heart failure, sudden death, etc.) or infectious diseases (eg pneumonia).
- Patients with Parkinson's disease dementia or Lewy body dementia should be cautious due to the increased risk of adverse effects and increased sensitivity for extrapyramidal effects. Also, there is the possibility of irreversible cognitive decline or death.
- The APA recommends that second-generation antipsychotics be preferred to first-generation antipsychotics for elderly patients with dementia-related schizophrenia.
- This is because there is a greater risk of harm than second-generation antipsychotics.
- Thioridazine has not been approved for the treatment of dementia-related psychosis.
Hepatic impairment
- Patients with hepatic impairment should be cautious.
Seizure disorder:
- Patients at high risk of seizures should be cautious; first-generation antipsychotics might lower the seizure threshold.

Thioridazine: Drug Interaction

Risk Factor C (Monitor therapy)
Acetylcholinesterase Inhibitors	May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors.
Acetylcholinesterase Inhibitors (Central)	May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients.
Alcohol (Ethyl)	CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).
Alfuzosin	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Alizapride	May enhance the CNS depressant effect of CNS Depressants.
Amifampridine	Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine.
Aminolevulinic Acid (Topical)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical).
Amphetamines	Antipsychotic Agents may diminish the stimulatory effect of Amphetamines.
Amphetamines	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Amphetamines.
Antacids	May decrease the absorption of Antipsychotic Agents (Phenothiazines).
Anticholinergic Agents	May enhance the adverse/toxic effect of other Anticholinergic Agents.
Antimalarial Agents	May increase the serum concentration of Antipsychotic Agents (Phenothiazines).
Antipsychotic Agents (Second Generation [Atypical	Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]).
ARIPiprazole	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations.
Barbiturates	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Benperidol	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Beta-Blockers	Antipsychotic Agents (Phenothiazines) may enhance the hypotensive effect of Beta-Blockers. Beta-Blockers may decrease the metabolism of Antipsychotic Agents (Phenothiazines). Antipsychotic Agents (Phenothiazines) may decrease the metabolism of BetaBlockers. Exceptions: Atenolol; Levobunolol; Metipranolol; Nadolol.
Blood Pressure Lowering Agents	May enhance the hypotensive effect of HypotensionAssociated Agents.
Botulinum Toxin-Containing Products	May enhance the anticholinergic effect of Anticholinergic Agents.
Brexanolone	CNS Depressants may enhance the CNS depressant effect of Brexanolone.
Brexpiprazole	CYP2D6 Inhibitors (Moderate) may increase the 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.
Brimonidine (Topical)	May enhance the CNS depressant effect of CNS Depressants.
Brimonidine (Topical)	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Cannabis	May enhance the CNS depressant effect of CNS Depressants.
Chloral Betaine	May enhance the adverse/toxic effect of Anticholinergic Agents.
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of Antipsychotic Agents (Phenothiazines).
Chlorphenesin Carbamate	May enhance the adverse/toxic effect of CNS Depressants.
Clarithromycin	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Clarithromycin. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CloBAZam	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
CloZAPine	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of CloZAPine.
CloZAPine	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
CNS Depressants	May enhance the adverse/toxic effect of other CNS Depressants.
Cobicistat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
CYP2D6 Substrates (High risk with Inhibitors)	CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). Exceptions: Tamoxifen.
Deutetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased.
Diazoxide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Dimethindene (Topical	May enhance the CNS depressant effect of CNS Depressants.
Doxylamine	May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended.
Dronabinol	May enhance the CNS depressant effect of CNS Depressants.
Droperidol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Esketamine	May enhance the CNS depressant effect of CNS Depressants.
Fesoterodine	CYP2D6 Inhibitors may increase serum concentrations of the active metabolite(s) of Fesoterodine.
Flupentixol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Flupentixol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased.
Guanethidine	Antipsychotic Agents may diminish the therapeutic effect of Guanethidine.
Haloperidol	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Herbs (Hypotensive Properties	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
HydrOXYzine	May enhance the CNS depressant effect of CNS Depressants.
Hypotension-Associated Agents	Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.
Imatinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Indoramin	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Indoramin.
Itopride	Anticholinergic Agents may diminish the therapeutic effect of Itopride.
Kava Kava	May enhance the adverse/toxic effect of CNS Depressants.
Lithium	May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine.
Lormetazepam	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Lumefantrine	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Magnesium Sulfate	May enhance the CNS depressant effect of CNS Depressants.
Melatonin	May enhance the adverse/toxic effect of Thioridazine.
Methylphenidate	Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents.
Metoprolol	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Metoprolol.
MetyroSINE	CNS Depressants may enhance the sedative effect of MetyroSINE.
MetyroSINE	May enhance the adverse/toxic effect of Antipsychotic Agents.
Mianserin	May enhance the anticholinergic effect of Anticholinergic Agents.
Minocycline	May enhance the CNS depressant effect of CNS Depressants.
Mirtazapine	CNS Depressants may enhance the CNS depressant effect of Mirtazapine.
Molsidomine	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nabilone	May enhance the CNS depressant effect of CNS Depressants.
Naftopidil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nebivolol	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol.
Nicergoline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nicorandil	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Nitroglycerin	Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption.
Nitroprusside	Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside.
OLANZapine	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Ondansetron	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Panobinostat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Peginterferon Alfa-2b	May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Pentamidine (Systemic)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Pentoxifylline	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Pholcodine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine.
Phosphodiesterase 5 Inhibitors	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Pitolisant	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Pitolisant.
Porfimer	Photosensitizing Agents may enhance the photosensitizing effect of Porfimer.
Prostacyclin Analogues	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
QT-prolonging Antidepressants (Moderate Risk)	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Class IC Antiarrhythmics (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Kinase Inhibitors (Moderate Risk)	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Miscellaneous Agents (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone.
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QT-prolonging Quinolone Antibiotics (Moderate Risk)	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
QUEtiapine	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QUEtiapine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Quinagolide	Antipsychotic Agents may diminish the therapeutic effect of Quinagolide.
Quinagolide	May enhance the hypotensive effect of Blood Pressure Lowering Agents.
Ramosetron	Anticholinergic Agents may enhance the constipating effect of Ramosetron.
RisperiDONE	QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of RisperiDONE. QT-prolonging Antipsychotics (Moderate Risk) may increase the serum concentration of RisperiDONE. Specifically, thioridazine may increase concentrations of risperidone. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Rufinamide	May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.
Selective Serotonin Reuptake Inhibitors	CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced.
Serotonin Modulators	May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline.
Serotonin Reuptake Inhibitor/Antagonists	Antipsychotic Agents (Phenothiazines) may enhance the adverse/toxic effect of Serotonin Reuptake Inhibitor/Antagonists. Specifically, this may be manifest as symptoms consistent with serotonin syndrome or neuroleptic malignant syndrome. Serotonin Reuptake Inhibitor/Antagonists may enhance the hypotensive effect of Antipsychotic Agents (Phenothiazines).
Tamsulosin	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Tamsulosin.
Tetrabenazine	May enhance the adverse/toxic effect of Antipsychotic Agents.
Tetrahydrocannabinol	May enhance the CNS depressant effect of CNS Depressants.
Tetrahydrocannabinol and Cannabidiol	May enhance the CNS depressant effect of CNS Depressants.
Thiazide and Thiazide-Like Diuretics	Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics.
Thiopental	Antipsychotic Agents (Phenothiazines) may enhance the adverse/toxic effect of Thiopental.
Topiramate	Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.
Trimeprazine	May enhance the CNS depressant effect of CNS Depressants.
Verteporfin	Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin.
Voriconazole	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk.
Risk Factor D (Consider therapy modification)
Amifostine	Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered.
Anti-Parkinson Agents (Dopamine Agonist)	Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Anti-Parkinson Agents (Dopamine Agonist) may diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Management: Avoid concomitant therapy if possible and monitor for decreased effects of both agents when these combinations cannot be avoided. Atypical antipsychotics such as clozapine and quetiapine may be less likely to reduce the effects of antiParkinson agents.
Blonanserin	CNS Depressants may enhance the CNS depressant effect of Blonanserin.
Buprenorphine	CNS Depressants may enhance the CNS depressant effect 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.
Chlormethiazole	May enhance the CNS depressant effect 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.
Chlorpheniramine	May enhance the arrhythmogenic effect of Thioridazine. Thioridazine may increase the serum concentration of Chlorpheniramine. Management: Avoid this combination when possible. If used, monitor closely for arrhythmia as well as general toxicity of chlorpheniramine.
Domperidone	QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk.
DOXOrubicin (Conventional	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to moderate CYP2D6 inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided.
Eliglustat	CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Eliglustat. Management: Reduce the eliglustat dose to 84 mg daily. Avoid use of eliglustat in combination with a moderate CYP2D6 inhibitor and a strong or moderate CYP3A4 inhibitor.
Flunitrazepam	CNS Depressants may enhance the CNS depressant effect of Flunitrazepam.
HYDROcodone	CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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.
Iohexol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 anticonvulsants.
Iomeprol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 anticonvulsants.
Iopamidol	Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 anticonvulsants.
Mequitazine	Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged.
Methotrimeprazine	CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established.
Obinutuzumab	May enhance the hypotensive effect 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.
Opioid Agonists	CNS Depressants may enhance the CNS depressant effect 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.
OxyCODONE	CNS Depressants may enhance the CNS depressant effect 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.
Perampanel	May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination.
Pramlintide	May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract.
Secretin	Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin.
Sodium Oxybate	May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated.
Suvorexant	CNS Depressants may enhance the CNS depressant effect 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.
Tamoxifen	CYP2D6 Inhibitors (Moderate) may decrease serum concentrations of the active metabolite(s) of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the metabolic formation of highly potent active metabolites. Management: Consider alternatives with less of an inhibitory effect on CYP2D6 activity when possible.
Tapentadol	May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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.
Zolpidem	CNS Depressants may enhance the CNS depressant effect 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 Factor X (Avoid combination)
Aclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.
Aminolevulinic Acid (Systemic)	Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic).
Amisulpride	Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs.
Amisulpride	May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk).
Asunaprevir	May increase the serum concentration of Thioridazine.
Azelastine (Nasal)	CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).
Bromopride	May enhance the adverse/toxic effect of Antipsychotic Agents.
Bromperidol	Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Bromperidol may diminish the hypotensive effect of Blood Pressure Lowering Agents.
Bromperidol	May enhance the CNS depressant effect of CNS Depressants.
Cimetropium	Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium.
CYP2D6 Inhibitors	May increase the serum concentration of Thioridazine.
Dapoxetine	May enhance the arrhythmogenic effect of Thioridazine. Dapoxetine may increase the serum concentration of Thioridazine.
Dronedarone	Thioridazine may enhance the QTc-prolonging effect of Dronedarone.
Eluxadoline	Anticholinergic Agents may enhance the constipating effect of Eluxadoline.
FLUoxetine	May enhance the QTc-prolonging effect of Thioridazine. FLUoxetine may increase the serum concentration of Thioridazine.
FluvoxaMINE	May increase the serum concentration of Thioridazine.
Glycopyrrolate (Oral Inhalation)	Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation).
Glycopyrronium (Topical)	May enhance the anticholinergic effect of Anticholinergic Agents.
Ipratropium (Oral Inhalation)	May enhance the anticholinergic effect of Anticholinergic Agents.
Levosulpiride	Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride.
Metoclopramide	May enhance the adverse/toxic effect of Antipsychotic Agents.
Moclobemide	May increase the serum concentration of Thioridazine.
Orphenadrine	CNS Depressants may enhance the CNS depressant effect of Orphenadrine.
Oxatomide	May enhance the anticholinergic effect of Anticholinergic Agents.
Oxomemazine	May enhance the CNS depressant effect of CNS Depressants.
Paraldehyde	CNS Depressants may enhance the CNS depressant effect of Paraldehyde.
Pimozide	May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk).
Piribedil	Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended.
Potassium Chloride	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride.
Potassium Citrate	Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate.
QT-prolonging Agents (Highest Risk)	May enhance the QTc-prolonging effect of Thioridazine. Exceptions: Dronedarone; QuiNIDine.
QuiNIDine	Thioridazine may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Thioridazine.
Revefenacin	Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin.
Rolapitant	May increase the serum concentration of Thioridazine.
Saquinavir	May enhance the QTc-prolonging effect of Thioridazine.
Sulpiride	Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride.
Thalidomide	CNS Depressants may enhance the CNS depressant effect of Thalidomide.
Tiotropium	Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium.
Umeclidinium	May enhance the anticholinergic effect of Anticholinergic Agents.

Monitoring parameters:

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/HbA (baseline, then 1 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 the LDL level is normal; repeat every 6 months if the LDL level is >130 mg/dL);
changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (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 the 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).

How to administer Thioridazine (Mellaril)?

It can be administered orally with or without food.
To reduce the gastrointestinal side effects of the drug, it should be given with food or milk.

Mechanism of action of Thioridazine (Mellaril):

Thioridazine is a piperidine-phenothiazine that blocks postsynaptic dopaminergic and dopaminergic nerves in the brain.
It also acts at serotonin receptors, noradrenaline receptors, and histamine receptors.

Absorption is Rapid.

Protein binding: 96% to 99.3%.

Metabolism: It is metabolized in the liver primarily by sulphoxidation, demethylation (2%), and hydroxylation (limited) into its active metabolites mesoridazine and sulphoridazine.

Bioavailability is 25% to 33%

Half-life elimination is 5 to 27 hours.

Time to peak serum concentration: About 1 to 4 hours.

International Brand Names of Thioridazine:

Aldazine
Fialgin
Meleril
Mellerette
Melleril
Mellerzin
Melzin
Neubalon
Orsanil
Ridazin
Ridazine
Sequax
Simultan
Sonapax
Thinin
Thiomed
Thioridazin
Thioridazin prolongatum
Thioril
Thiosia
Thiozin
Thiozine
Winleril

Thioridazine Brand Names in Pakistan:

Thioridazine (Hcl) Suspension 10 Mg/5ml in Pakistan
Melleril	Novartis Pharma (Pak) Ltd

Thioridazine (Hcl) Tablets 10 Mg in Pakistan
Melleril	Novartis Pharma (Pak) Ltd

Thioridazine (Hcl) Tablets 25 Mg in Pakistan
Melleril	Novartis Pharma (Pak) Ltd

Thioridazine (Hcl) Tablets 100 Mg in Pakistan
Melleril	Novartis Pharma (Pak) Ltd

Thioridazine (Mellaril) - Uses, Dose, MOA, Brands, Side effects

Thioridazine (Mellaril) Uses:

Schizophrenia:

Thioridazine (Mellaril) Dose in Adults

Thioridazine (Mellaril) Dose in the treatment of Schizophrenia:

Discontinuation of therapy:

Switching antipsychotics:

Thioridazine (Mellaril) Dose in Children

Thioridazine (Mellaril) Dose in the treatment of Schizophrenia, refractory:

Children 6 years of age or older:

Thioridazine (Malleril) Pregnancy Risk Category: N

Use of Thioridazine while breastfeeding

Dose in Kidney Disease:

Dose in Liver disease:

Side effects of Thioridazine (Mellaril):

Cardiovascular:

Central Nervous System:

Dermatologic:

Endocrine & Metabolic:

Gastrointestinal:

Genitourinary:

Hematologic & Oncologic:

Ophthalmic:

Respiratory:

Contraindications to Thioridazine (Mellaril):

Warnings and Precautions

Arrhythmias: [US Boxed Warning]:

Anticholinergic effects

Blood dyscrasias:

CNS depression:

Esophageal dysmotility/Aspiration:

Extrapyramidal symptoms:

Hyperprolactinemia:

Neuroleptic malignant syndrome (NMS):

Ocular effects

Orthostatic hypotension

Temperature regulation

Cardiovascular disease

Dementia: [US Boxed Warning]

Hepatic impairment

Seizure disorder:

Monitoring parameters:

How to administer Thioridazine (Mellaril)?

Mechanism of action of Thioridazine (Mellaril):

International Brand Names of Thioridazine:

Thioridazine Brand Names in Pakistan:

Thioridazine (Hcl) Suspension 10 Mg/5ml in Pakistan

Thioridazine (Hcl) Tablets 10 Mg in Pakistan

Thioridazine (Hcl) Tablets 25 Mg in Pakistan

Thioridazine (Hcl) Tablets 100 Mg in Pakistan

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