Permival0.5 mg+10 mg

Fluphenazine and nortriptyline combination tablets pair a low-dose antipsychotic (fluphenazine) with a tricyclic antidepressant (nortriptyline), used for the management of moderate to severe depressive states accompanied by significant anxiety, agitation, tension, or mild associated psychotic features, particularly in patients where treatment with an antidepressant alone has been inadequate. The nortriptyline component targets core depressive symptoms such as low mood and loss of interest, while the low-dose fluphenazine component addresses associated anxiety, agitation, and tension.

This combination is not first-line therapy for straightforward depression without significant anxiety or agitation, and is not indicated for schizophrenia or other primary psychotic disorders requiring full antipsychotic dosing.

Contains fluphenazine hydrochloride and nortriptyline hydrochloride as active ingredients, formulated as oral tablets, commonly containing 0.5 mg fluphenazine with 10 mg nortriptyline per tablet, marketed in some regions in a higher-strength variant as well.

Fluphenazine and nortriptyline is a combination tablet that pairs a low dose of a phenothiazine antipsychotic with a tricyclic antidepressant, used for depression accompanied by significant anxiety or agitation. The nortriptyline component works on mood by affecting noradrenaline reuptake, while the low-dose fluphenazine component provides an anti-anxiety and mildly antipsychotic effect at doses well below those used to treat schizophrenia. Because it combines two drug classes, each with cardiac and anticholinergic effects, this combination requires careful patient selection, particularly regarding cardiovascular health, and carries its own distinct set of precautions beyond those of either component alone.

Therapeutic Class: Antidepressant-Antipsychotic Combination

Fluphenazine primarily blocks dopamine D2 receptors, with a plasma half-life of approximately 14.7 hours after oral dosing. Nortriptyline, the principal active metabolite of amitriptyline, is a tricyclic antidepressant that preferentially inhibits noradrenaline reuptake over serotonin reuptake, with a considerably longer mean half-life of approximately 36 hours (range 18-60 hours). Both components are metabolized in the liver and excreted mainly via the kidney; neither is removed by dialysis.

• Taken orally, with or without food, as directed by the prescribing doctor
• Take at consistent times each day
• Full therapeutic benefit may take several weeks to become apparent; do not stop taking the medicine early due to lack of immediate effect without discussing this with your doctor
• Do not stop taking this medicine suddenly, as gradual dose reduction is generally required

The following interactions require careful assessment, given the combined cardiac, sedative, and anticholinergic properties of this combination:

• Monoamine oxidase inhibitors (MAOIs): combining tricyclic antidepressants like nortriptyline with MAOIs can cause serious, potentially fatal reactions, including serotonin syndrome and hypertensive crisis; this combination is generally avoided, with an adequate washout period required between stopping one and starting the other.
• Other QT-prolonging medicines (such as certain antiarrhythmics, antipsychotics, and some antibiotics): both fluphenazine and nortriptyline can independently prolong the QT interval, and combining with other QT-prolonging drugs significantly increases the risk of dangerous heart rhythm disturbances.
• Other central nervous system depressants (alcohol, barbiturates, opioids, other sedatives): additive sedation and central nervous system depression.
• Other anticholinergic medicines: additive anticholinergic effects (dry mouth, constipation, urinary retention, confusion), given nortriptyline's own atropine-like properties.
• Metoclopramide and other dopamine-blocking antiemetics: combining with fluphenazine increases the risk of extrapyramidal symptoms and tardive dyskinesia.
• CYP2D6-metabolized drugs: both components are metabolized via pathways that can compete with other CYP2D6-metabolized medicines, potentially raising blood levels of either agent when combined with other drugs sharing this pathway.

Common side effects

• Drowsiness, sedation
• Dry mouth
• Blurred vision
• Constipation
• Dizziness, particularly on standing (orthostatic hypotension)
• Headache

Serious side effects (require prompt medical attention)

• Tardive dyskinesia: repetitive, involuntary movements of the face and body, associated with the fluphenazine component; risk increases with duration of treatment and total cumulative dose, and the condition can be irreversible; report any unusual movements to your doctor promptly.
• Cardiac arrhythmia and QT prolongation: palpitations, dizziness, fainting - both components can affect heart rhythm, and the combination requires particular cardiac caution.
• Neuroleptic malignant syndrome (rare): high fever, muscle rigidity, altered consciousness, autonomic instability - a rare but potentially fatal reaction associated with the fluphenazine component.
• Blood disorders (rare): unusual bruising or bleeding, signs of infection, which may indicate reduced blood cell counts.
• Increased risk of suicidal thoughts, particularly in young people starting antidepressant treatment - monitor mood changes closely, especially in the first weeks of treatment.

Pregnancy

Published data on fluphenazine use during pregnancy (several hundred reported pregnancies) have not shown an increased risk of malformations; data specific to this exact combination in human pregnancy are more limited. This combination should be used during pregnancy only if a doctor determines the benefit outweighs the potential risk, given the combined tricyclic and antipsychotic exposure involved.

Breastfeeding

Both fluphenazine and nortriptyline are excreted in breast milk in small amounts; use during breastfeeding should be discussed with a healthcare professional, given the potential for sedation or other effects in the nursing infant.

• Cardiovascular caution: both components can affect cardiac conduction; use with great caution in patients with myocardial insufficiency, severe atherosclerosis, or any history of cardiac rhythm problems, and only under close medical supervision.
• Tardive dyskinesia: monitor regularly for early signs, particularly with prolonged use; the dose should be periodically reviewed to the lowest effective level.
• Elderly patients: use with extreme caution, given a high risk of sedation, confusion, falls from orthostatic hypotension, and pronounced anticholinergic effects in this population.
• Suicide risk: monitor for worsening depression or emerging suicidal thoughts, particularly in the early weeks of treatment or with dose changes, especially in younger patients.
• Do not stop this medicine abruptly; gradual dose reduction under medical supervision is required to avoid withdrawal effects.
• Use with caution in patients with glaucoma, urinary retention, epilepsy, or hepatic or renal impairment.

Overdose of this combination is potentially serious, given the combined tricyclic antidepressant and antipsychotic components, and can cause severe anticholinergic effects (dry mouth, dilated pupils, urinary retention, confusion), cardiac arrhythmias, seizures, profound sedation or coma, and dangerously low blood pressure; tricyclic antidepressant overdose in particular carries a significant risk of life-threatening cardiac toxicity. Suspected overdose is a medical emergency requiring immediate treatment; do not attempt home management, and seek emergency care or contact a poison control center immediately.

Store at room temperature, protected from light and moisture, as directed on the product label. Keep out of reach of children, and store securely given the seriousness of overdose with tricyclic antidepressants.

• Elderly: Use with extreme caution at a reduced starting dose, given significantly increased risk of sedation, confusion, falls, cardiac effects, and anticholinergic toxicity in this population.
• Cardiovascular disease: Use only with great caution and close monitoring, given the combined QT-prolonging and cardiac effects of both components; contraindicated in severe cardiovascular disease.
• Hepatic or renal impairment: Use with caution, given hepatic metabolism and renal excretion of both components.

Treatment duration is individualized based on clinical response, typically continued for at least several months once an adequate response is achieved, similar to standard antidepressant treatment courses, with periodic reassessment of the ongoing need for the antipsychotic component given the tardive dyskinesia risk associated with prolonged use. Discontinuation should always be gradual, under medical supervision.

Drug Class: Piperazine phenothiazine (fluphenazine) combined with a tricyclic antidepressant (nortriptyline)

Nortriptyline works by blocking the reuptake of noradrenaline (and, to a lesser extent, serotonin) at nerve synapses, increasing the availability of these mood-regulating neurotransmitters in the brain, which helps relieve depressive symptoms over several weeks of treatment. Fluphenazine works mainly by blocking dopamine D2 receptors; at the low dose used in this combination, this contributes an anti-anxiety and mild antipsychotic effect that helps address the agitation, tension, or mild psychotic features that can accompany depression, complementing nortriptyline's core antidepressant action.

This combination is not established for use in children, and is not recommended in this age group, given the combined tricyclic antidepressant and antipsychotic exposure and limited pediatric safety data for this specific combination.