Usage
Fluphenazine + Nortriptyline is prescribed for mild to moderate mixed anxiety/depression, emotional disturbances, sleep disorders, and gastric problems associated with anxiety or depression. It is also used for various forms of neuroses (anxiety, hysteria, depression, neurasthenia, hypochondria), transient situational disturbances, and learning disturbances.
This combination medication falls under the pharmacological classifications of:
- Antipsychotic: Fluphenazine is a phenothiazine antipsychotic.
- Tricyclic Antidepressant (TCA): Nortriptyline is a TCA.
The mechanism of action involves the combined effects of Fluphenazine and Nortriptyline. Fluphenazine primarily acts as a dopamine (D2) receptor antagonist, reducing the effects of dopamine, a neurotransmitter implicated in psychosis and mood regulation. Nortriptyline inhibits the reuptake of norepinephrine and serotonin, two neurotransmitters essential for mood balance, thereby increasing their levels in the brain.
Alternate Names
This drug combination doesn’t have an international nonproprietary name (INN). It is marketed under various brand names, including:
- Amival
- Anflu
- Apresin
- Euphor
- Flutrip
- Fresh
- Monitol
- Mudibak
- Norflu
- Norzin
- Permival
- Modrin
- Motisone
- Motival
- Tripnor
How It Works
Pharmacodynamics: Fluphenazine exerts its antipsychotic effect by blocking dopamine D2 receptors in the brain. Nortriptyline’s antidepressant action is primarily due to its ability to inhibit the reuptake of norepinephrine and serotonin at nerve terminals, effectively increasing their concentrations in the synaptic cleft.
Pharmacokinetics: Both drugs are well-absorbed from the gastrointestinal tract but undergo significant first-pass metabolism in the liver. Nortriptyline has a plasma half-life ranging from 18 to 93 hours, while Fluphenazine’s half-life is approximately 15 hours. Nortriptyline is metabolized by CYP2D6 enzyme and Fluphenazine is a substrate of CYP2D6.
Mode of Action: Fluphenazine primarily acts by antagonizing dopamine D2 receptors, impacting dopaminergic neurotransmission. Nortriptyline primarily inhibits the presynaptic reuptake pumps for norepinephrine and serotonin.
Elimination: Both Fluphenazine and Nortriptyline are extensively metabolized in the liver and excreted primarily in urine.
Dosage
Standard Dosage
Adults:
One tablet (containing 0.5mg Fluphenazine and 10mg Nortriptyline) two to three times daily. The course of treatment should generally be limited to three months. Some sources suggest a total daily dose of three tablets taken in the evening or as a divided dose.
Children:
This combination is not recommended for children.
Special Cases:
- Elderly Patients: Initiate therapy with one tablet twice daily, increasing to three times daily if necessary and tolerated.
- Patients with Renal Impairment: Dosage adjustments may be necessary. Monitor renal function closely.
- Patients with Hepatic Dysfunction: Dosage adjustments may be necessary due to impaired metabolism. Closely monitor liver function.
- Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, glaucoma, prostatic hypertrophy, or history of seizures.
Clinical Use Cases
The available sources do not recommend Fluphenazine + Nortriptyline for specific medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments should be made based on individual patient response and tolerance, considering factors such as age, renal function, hepatic function, and coexisting medical conditions.
Side Effects
Common Side Effects:
Dry mouth, drowsiness, dizziness, constipation, blurred vision, nasal congestion, tachycardia, faintness.
Rare but Serious Side Effects:
Tardive dyskinesia, neuroleptic malignant syndrome, blood dyscrasias (agranulocytosis, leukopenia), sudden death, jaundice, pigmentary retinopathy, extrapyramidal symptoms, QT interval prolongation, cardiac arrhythmias.
Long-Term Effects:
Tardive dyskinesia can be a long-term side effect, particularly with prolonged use of Fluphenazine.
Adverse Drug Reactions (ADR):
Agranulocytosis, Neuroleptic Malignant Syndrome, QT interval prolongation requiring immediate medical intervention.
Contraindications
- Hypersensitivity to Fluphenazine, Nortriptyline, or any other phenothiazines or tricyclic antidepressants.
- History of epilepsy or organic brain damage.
- Blood dyscrasias.
- Severe cardiac insufficiency, heart block, arrhythmias.
- Renal or hepatic impairment.
- Concomitant use of MAOIs.
- Coma.
- Severe CNS depression.
Drug Interactions
- Alcohol, Barbiturates, Narcotics: Increased CNS depression.
- Anticholinergics: Additive anticholinergic effects.
- Dopamine Agonists: Decreased efficacy of Fluphenazine.
- Guanethidine, Guanadrel: Enhanced hypotensive effects.
- Lithium: Increased lithium levels and potential for toxicity.
- Antiarrhythmics (e.g., Amiodarone, Procainamide, Sotalol, Dofetilide): Increased risk of QT prolongation and arrhythmias.
- Antidepressants (e.g., SSRIs, TCAs): Increased risk of QT prolongation and serotonin syndrome.
- CYP2D6 Inhibitors (e.g., Celecoxib): Increased Fluphenazine levels.
- CYP450 Inducers/Inhibitors: Alterations in metabolism of both drugs.
Pregnancy and Breastfeeding
Fluphenazine + Nortriptyline is generally avoided during pregnancy, especially the first and third trimesters, due to potential risks to the fetus. The safety in human pregnancy has not been established. Use during breastfeeding is not recommended as both drugs can be excreted in breast milk and potentially cause adverse effects in infants.
Drug Profile Summary
- Mechanism of Action: Fluphenazine: Dopamine D2 receptor antagonist. Nortriptyline: Inhibits norepinephrine and serotonin reuptake.
- Side Effects: Dry mouth, drowsiness, dizziness, constipation, extrapyramidal symptoms, tardive dyskinesia, neuroleptic malignant syndrome, QT prolongation.
- Contraindications: Hypersensitivity, epilepsy, blood dyscrasias, severe cardiac insufficiency, renal/hepatic impairment, MAOI use.
- Drug Interactions: Alcohol, CNS depressants, anticholinergics, dopamine agonists, lithium, antiarrhythmics, antidepressants, CYP2D6 inhibitors.
- Pregnancy & Breastfeeding: Avoid during pregnancy and breastfeeding.
- Dosage: Adults: 1 tablet (0.5mg/10mg) two to three times daily. Elderly: Start with 1 tablet twice daily.
- Monitoring Parameters: Mental status, extrapyramidal symptoms, cardiac function (ECG, QTc interval), liver function tests, renal function tests, blood counts.
Popular Combinations
The available sources primarily focus on the combination of Fluphenazine and Nortriptyline. No other popular combinations are mentioned.
Precautions
- Pre-existing medical conditions (glaucoma, prostatic hypertrophy, cardiovascular disease) should be carefully considered.
- Patients should be monitored for extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome.
- Caution should be exercised in elderly patients due to increased sensitivity to side effects.
- Alcohol should be avoided due to additive CNS depressant effects.
- The drug may impair alertness, so caution is advised when driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Fluphenazine + Nortriptyline?
A: Adults: One tablet (0.5mg Fluphenazine and 10mg Nortriptyline) two to three times daily. Elderly patients should start with a lower dose. This combination is not recommended for children.
Q2: What are the common side effects?
A: Common side effects include dry mouth, drowsiness, dizziness, constipation, blurred vision, and nasal congestion.
Q3: What are the serious side effects?
A: Serious side effects include tardive dyskinesia, neuroleptic malignant syndrome, blood dyscrasias, and QT prolongation.
Q4: What are the contraindications?
A: Contraindications include hypersensitivity, epilepsy, blood dyscrasias, severe cardiac insufficiency, renal/hepatic impairment, and MAOI use.
Q5: Can this medication be used during pregnancy or breastfeeding?
A: It’s generally avoided during pregnancy and breastfeeding due to potential risks.
Q6: What are the major drug interactions?
A: Major drug interactions include alcohol, CNS depressants, anticholinergics, dopamine agonists, lithium, antiarrhythmics, and antidepressants.
Q7: What is the mechanism of action?
A: Fluphenazine blocks dopamine D2 receptors. Nortriptyline inhibits norepinephrine and serotonin reuptake.
Q8: How long should treatment typically last?
A: Treatment is typically limited to three months. If the patient does not respond after four weeks, an alternative treatment should be considered.
Q9: Are there any specific monitoring parameters for this combination?
A: Yes. It’s crucial to monitor mental status, extrapyramidal symptoms, cardiac function (ECG, QT interval), and liver and kidney function. Regular blood counts are also necessary.
Q10: What should patients be advised regarding lifestyle while taking this medication?
A: Patients should avoid alcohol and be cautious when driving or operating machinery due to potential drowsiness and impaired alertness. They should also inform their doctor about any other medications, supplements, or herbal remedies they are taking.
