Flupentixol (Fluanxol) - Uses, Dose, Side effects, MOA, Brands

Flupentixol (Fluanxol) is a typical antipsychotic drug that is used in patients with schizophrenia and other psychotic behavioral problems.

Flupentixol Uses:

  • Schizophrenia:

    • Used in the maintenance therapy of chronic schizophrenic patients whose main manifestations do not include excitement, hyperactivity, or agitation.

Flupentixol (Fluanxol) Dose in Children

Flupentixol (Fluanxol) Dose in the treatment of Schizophrenia:

Note: Initiate with oral therapy; upon stabilization, patients may then be transitioned to the depot injection.

IM (depot):

  • Initial:
    • Patients who are naive to treatment with long-acting depot antipsychotics:
      • Administer a test dose of 5 to 20 mg (5 mg dose is recommended in elderly, frail, cachectic patients or patients with a predisposition to extrapyramidal reactions).
      • Closely monitor therapeutic response and for the appearance of extrapyramidal symptoms over the following 5 to 10 days.
      • Oral antipsychotic drugs may be continued, but the dosage should be reduced during this overlapping period and eventually discontinued.
    • Patients with prior exposure and good tolerance of long-acting depot antipsychotics:
      • 20 to 40 mg
    • Maintenance:
      • 20 to 40 mg may be given 4 to 10 days after initial injection (if well tolerated), followed by a usual maintenance dose of 20 to 40 mg every 2 to 3 weeks.
      • The dose is individualized and titrated in maximum increments of 20 mg or less than 20 mg (doses more than 80 mg are not usually necessary but have been used in some patients).
      • The dose should be maintained at the lowest effective dose.

Oral:

  • Initial: 1 mg 3 times per day; dose may be increased by 1 mg every 2 to 3 days based on tolerance and control of symptoms.
  • Usual maintenance dosage: 3 to 6 mg per day in divided doses (doses of 12 mg or more than 12 mg per day have been used in some patients).

Conversion from oral tablets to maintenance dosing with IM injection (decanoate):

Note: When transitioning to the depot injection, continue oral therapy at decreasing dosages for the first week following the initial injection.

    • If IM administration every 2 weeks: Use decanoate dose equal to 4 times the total everyday oral dose
    • If IM administration every 4 weeks: Use decanoate dose equal to 8 times the total ever oral dose

Conversion from other antipsychotic depot formulations to IM flupentixol decanoate: Conversion ratios to calculate the equivalent dose:

    • Flupentixol decanoate 40 mg = fluphenazine decanoate 25 mg
    • Flupentixol decanoate 40 mg = zuclopenthixol decanoate 200 mg
    • Flupentixol decanoate 40 mg = haloperidol decanoate 50 mg

Use in Children:

Not indicated.

Flupentixol Pregnancy Category: C

  • Pregnant women are not subject to adequate, well-controlled studies.
  • Use of antipsychotics during pregnancy's third trimester can lead to abnormal muscle movements and withdrawal symptoms in the newborns after delivery.
  • The newborn can experience agitation, hypotonia or hypertonia as well as feeding disorder, respiratory distress and somnolence. These symptoms may be self-limiting, or may require hospitalization.
  • Erectile dysfunction, amenorrhea and decreased libido have all been reported. Dose reduction or discontinuation of therapy may be necessary for more severe side effects.

Use Flupentixol while breastfeeding

  • Flupentixol can be found in low levels in breast milk when taken as a therapeutic dose.
  • Nursing infants are unlikely to experience adverse effects if the therapeutic dose range is followed.

Dose in Kidney Disease:

  • The manufacturer’s product labeling recommendations are unclear.
  • Use in renal insufficiency is contraindicated however the labeling also suggests that dosage adjustments are not necessary for renal impairment; flupentixol systemic exposure is not likely to be influenced by renal impairment as the drug undergoes extensive hepatic metabolism and is primarily excreted in the feces.

Dose in Liver disease:

The manufacturer's labeling doesn't provide any dosage adjustments; flupentixol undergoes extensive hepatic metabolism. Use caution.

Side effects of Flupentixol (Fluanxol):

  • Cardiovascular:

    • Palpitations
    • Syncope

  • Central Nervous System:

    • Extrapyramidal Reaction Including
      • Akathisia
      • Tardive Dyskinesia
      • Drug-Induced Parkinson’s Disease
      • Dystonia
    • Depression
    • Dizziness
    • Insomnia
    • Opisthotonos
    • Psychomotor Agitation
    • Restlessness
    • Drowsiness
    • Fatigue
    • Headache
    • Hyperreflexia
    • Hypertonia
    • Hypomania
    • Seizure

  • Dermatologic:

    • Eczema
    • Erythema
    • Exfoliative Dermatitis
    • Pruritus
    • Seborrhea
    • Contact Dermatitis
    • Diaphoresis
    • Skin Rash
    • Urticaria

  • Endocrine & Metabolic:

    • Amenorrhea
    • Decreased Libido
    • Increased Libido
    • Weight Changes
    • Galactorrhea
    • Gynecomastia
    • Hyperprolactinemia

  • Gastrointestinal:

    • Constipation
    • Nausea
    • Paralytic Ileus
    • Sialorrhea
    • Xerostomia

  • Genitourinary:

    • Impotence
    • Urination Disorder

  • Hematologic & Oncologic:

    • Eosinophilia

  • Hepatic:

    • Increased Serum ALT
    • Increased Serum AST
    • Increased Serum Alkaline Phosphatase
    • Jaundice

  • Neuromuscular & Skeletal:

    • Tremor

  • Ophthalmic:

    • Cataract
    • Oculogyric Crisis
    • Blurred Vision

Contraindications to Flupentixol (Fluanxol):

  • Hypersensitivity to flupentixol, thioxanthenes or any other component of the formulation
  • Acute intoxication (a barbiturate or ethanol, or opioid)
  • Any cause of CNS depression;
  • coma
  • Psychoneurotic patients
  • Patients with severe agitation and psychotic symptoms, or patients suffering from confusion and/or agitation in the elderly;
  • Subcortical brain injury suspected or confirmed
  • severe cardiovascular disease/circulatory failure
  • Cerebrovascular and renal insufficiency
  • Liver damage
  • Concomitant use of large amounts of hypnotics
  • Because of similarities in chemical structure, and/or pharmacologic effects, cross-sensitivity between thioxanthenes derivatives and phenothiazine derivatives is possible.

Warnings and precautions

  • Modified cardiac conduction

    • Antipsychotics may alter cardiac conduction. Life-threatening arrhythmias have been reported with therapeutic doses.
    • Be cautious with vulnerable patients (e.g., decompensated heart failure, arrhythmias significant bradycardia and recent MI).
    • Before using, correct electrolyte abnormalities such as hypomagnesemia or hypokalemia.
    • Decanoate can have long-lasting adverse effects.
    • Patients with QT prolongation should be avoided.

  • Anticholinergic effects

    • It may cause blurred vision, urinary retention and constipation.
    • Neuroleptics are less potent than other flupentixols. They have a lower cholinergic blockade.

  • Blood dyscrasias

    • Antipsychotic use has been linked to leukopenia and agranulocytosis as well as neutropenia and granulocytopenia. Regular monitoring of CBC is highly recommended.

  • CNS effects

    • Flupentixol may be sedating for some patients. Patients with CNS depression must be cautious about using flupentixol.

  • Diabetic ketoacidosis, (DKA)

    • DKA was observed in patients without a history of hyperglycemia. It is recommended that you monitor your blood glucose and body fat.

  • Esophageal dysmotility/aspiration

    • Antipsychotic use has been linked to esophageal dysmotility, aspiration, and increased risk with age.
    • Patients at high risk of aspiration pneumonia (ie Alzheimer's disease) should be treated with caution, especially if they are older than 75 years.

  • Extrapyramidal symptoms (EPS).

    • Extrapyramidal symptoms, severe dystonic reactions, akathisia and pseudo parkinsonism may occur.
    • Higher doses, higher dosages, males, conventional antipsychotics and younger patients may increase the risk of dystonia (and other EPS).
    • There are several factors that increase the vulnerability to tardive dyskinesia, including older age, female gender, postmenopausal status and pseudo parkinsonism symptoms. Also, there are concurrent medical conditions such as diabetes, prior brain damage, alcoholism and poor treatment response.
    • You should consider discontinuing therapy if you experience tardive dyskinesia symptoms.

  • Neuroleptic malignant Syndrome (NMS). [Canadian Boxed Warn]

    • The use of antipsychotic drugs, such as flupentixol, has been linked to NMS. Monitor for changes in mental status and/or autonomic instability. Myoglobinuria and/or acute kidney failure. (Risk may be greater for patients with Parkinson disease and Lewy body dementia).
    • Stop all antipsychotic treatment immediately if you notice the onset or recurrence of NMS.

  • Ocular:

    • Rarely, lenses become opaque after use.
    • Similar drugs have been linked to photosensitivity, pigmentary retinopathy, corneal and pigmentary retinopathy, and lenticular deposits.

  • Orthostatic hypotension

    • Orthostatic hypotension may occur; caution is advised in patients who are at high risk or those who cannot tolerate temporary hypotensive episodes (cerebrovascular diseases, hypovolemia, heart disease, concurrent medication use, and/or hypotension/bradycardia).

  • Temperature regulation

    • It is possible to have impaired core body temperature regulation. Be careful with heat exposure, strenuous exercise, dehydration and any concomitant anticholinergic medication.

  • Venous thromboembolism, (VTE)

    • VTE has been reported when antipsychotics are used. It is important to assess VTE risk before and during therapy.

  • Cardiovascular disease

    • Patients at high risk of cerebrovascular accidents or with a history should be cautious.
    • Patients with severe cardiovascular disease should not use this medication.

  • Dementia

    • Antipsychotics can increase the risk of death in elderly patients suffering from dementia-related psychosis.
    • In elderly patients with dementia-related psychosis, there has been an increase in the incidence of cerebrovascular adverse event (including fatalities).
    • The majority of deaths were either from cardiovascular disease (eg heart failure, sudden death, etc.) or from infectious diseases (eg pneumonia).
    • Flupentixol has not been approved for elderly patients suffering from dementia or dementia-related psychosis.

  • Hepatic impairment

    • Patients with liver damage should not use this medication.

  • Prolactin-dependent tumors

    • It is associated with higher prolactin levels. However, the clinical significance and clinical significance of hyperprolactinemia in patients suffering from breast cancer or other prolactin dependent tumors is not known.

  • Renal impairment

    • Patients with severe renal impairment should not use this medication.

  • Seizure disorder

    • Patients at high risk of seizures should be cautious, especially those who have had seizures in the past, brain damage, alcoholism, head trauma or are receiving concurrent treatment with medication that could lower their seizure threshold.

Flupentixol: 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).

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.

Amphetamines

Antipsychotic Agents may diminish the stimulatory effect of Amphetamines.

Anticholinergic Agents

May enhance the adverse/toxic effect of other Anticholinergic Agents.

Botulinum Toxin-Containing Products

May enhance the anticholinergic effect of Anticholinergic Agents.

Brexanolone

CNS Depressants may enhance the CNS depressant effect of Brexanolone.

Brimonidine (Topical)

May enhance the CNS depressant effect of CNS Depressants.

BuPROPion

May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential.

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 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.

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.

Deutetrabenazine

May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased.

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.

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.

HydrOXYzine

May enhance the CNS depressant effect of CNS Depressants.

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.

Magnesium Sulfate

May enhance the CNS depressant effect of CNS Depressants.

Methylphenidate

Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents.

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.

Mirabegron

Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron.

Mirtazapine

CNS Depressants may enhance the CNS depressant effect of Mirtazapine.

Nabilone

May enhance the CNS depressant effect of CNS Depressants.

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.

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.

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.

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 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. Exceptions: Amisulpride; CloZAPine; Droperidol; Flupentixol; Pimozide.

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.

Quinagolide

Antipsychotic Agents may diminish the therapeutic effect of Quinagolide.

Ramosetron

Anticholinergic Agents may enhance the constipating effect of Ramosetron.

Rufinamide

May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced.

Saquinavir

QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Saquinavir. 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.

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.

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.

Topiramate

Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.

Trimeprazine

May enhance the CNS depressant effect of CNS Depressants.

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)

Anti-Parkinson Agents (Dopamine Agonist)

May diminish the therapeutic effect of Antipsychotic Agents (First Generation [Typical]). Antipsychotic Agents (First Generation [Typical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). 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 anti-Parkinson 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other 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.

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.

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.

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.

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.

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).

Azelastine (Nasal)

CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal).

Bromopride

May enhance the adverse/toxic effect of Antipsychotic Agents.

Bromperidol

May enhance the CNS depressant effect of CNS Depressants.

Cimetropium

Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium.

Eluxadoline

Anticholinergic Agents may enhance the constipating effect of Eluxadoline.

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.

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 Flupentixol.

Revefenacin

Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin.

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 health;
  • Vital signs (as indicated by a doctor);
  • Blood pressure (baseline); repeat 3 months after antipsychotic initiation. Then, yearly
  • Weight, height, BMI and waist circumference (baseline) Repeat this process at 4, 8 and 12 weeks after starting or changing therapy. Then, quarterly. Consider switching to another antipsychotic if you experience a weight gain of more than 5 percent.
  • CBC (as indicated by the doctor; patients who have a history of drug-induced leukopenia/neutropenia or low WBC should be monitored frequently in the first few months.
  • Electrolytes and liver function (annually, and as clinically indicated);
  • Personal and family history of diabetes, obesity, dyslipidemia, hypertension or diabetes (baseline; repeated annually);
  • Fasting plasma glucose/HbA
  • Fasting lipid panel (baseline); repeat 3 months after antipsychotics are started; if LDL levels are normal, repeat every 2 to 5 years or more if clinically necessary.
  • Changes in menstruation, libido and development of galactorrhea (at each visit during the first 12 weeks following the antipsychotic's administration or until the dose becomes stable; thereafter, annually).
  • Parkinsonian signs or abnormal involuntary movements (baseline; continue weekly until dose stabilization for at least two weeks after introduction, and for at most 2 weeks following any significant dose increases);
  • Tightening of the muscles (every 12 to 18 months; high-risk patients, every 6 months);
  • Ocular examinations (yearly for patients older than 40 years, every 2 years for younger patients).

How to administer Flupentixol (Fluanxol)?

Injection:

  • Administer by deep IM injection, preferably in the gluteus maximus; doses requiring more than 2 mL should be administered as divided doses between 2 injection sites. Do not mix with depot formulations containing sesame oil.

Do not administer Intravenously

  • Prior to the injection aspirate to ensure that inadvertent intravascular injection does not occur.

Oral:

  • Tablets may be taken with or without food. During initial therapy, may consider reducing evening dose in patients with sleep disturbance.
  • The maintenance dose may be given as a single morning dose. Missed doses should be taken at the next regularly scheduled time. Doses should not be doubled.

Mechanism of action of Flupentixol (Fluanxol):

Flupentixol, a thioxanthene derivative antipsychotic, blocks postsynaptic dopamine receptors in the CNS. This results in dopamine-mediated inhibition.

Onset:

  • IM depot: 24 to 72 hours following injection

Duration:

  • IM depot: 2 to 4 weeks

Protein binding:

  • ~99 percent

Metabolism:

  • Hepatic via sulfoxidation and dealkylation; also undergoes glucuronidation; metabolites are inactive

Bioavailability: Oral:

  • ~40 percent

Half-life elimination:

  • Oral: ~35 hours;
  • IM depot: 3 weeks

Time to peak:

  • Oral: 3-8 hours;
  • IM depot: 4 to 7 days

Excretion:

  • Mostly feces (as metabolites); urine (small amounts)

International Brand Names of Flupentixol:

  • Fluanxol Depot
  • Depixol
  • Fluanxol
  • Fluanxol Depot
  • Fluanxol Mite
  • Fluanxol
  • Jexit
  • Pentixol

Flupentixol Brand Names in Pakistan:

Flupenthixol (HCl and Decanoate) Injection 20 mg in Pakistan
Fluixol Saydon Pharmaceutical Industries (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Injection 40 mg in Pakistan
Fluixol Saydon Pharmaceutical Industries (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Injection 100 mg in Pakistan
Fluixol Saydon Pharmaceutical Industries (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Injection SR 20 mg/ml in Pakistan
Fluanxol Lundbeck Pakistan (Pvt) Ltd.
Luixol Saydon Pharmaceutical Industries (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Injection SR 40 mg/ml
Luixol Saydon Pharmaceutical Industries (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Injection SR 100 mg/ml
Fluanxol Lundbeck Pakistan (Pvt) Ltd.
Luixol Saydon Pharmaceutical Industries (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Tablets 1 mg in Pakistan
Fluanxol Lundbeck Pakistan (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Tablets 3 mg in Pakistan
Fluanxol Lundbeck Pakistan (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Tablets 0.5 mg in Pakistan
Fluanxol Lundbeck Pakistan (Pvt) Ltd.

 

Flupenthixol (HCl and Decanoate) Tablets 0.25 mg in Pakistan
Fluanxol Lundbeck Pakistan (Pvt) Ltd.
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