Usage
- Penfluridol is prescribed for the long-term management of chronic schizophrenia and other psychotic disorders, helping to alleviate symptoms such as delusions, hallucinations, and disorganized thinking. It may also be used for Tourette’s syndrome.
- Pharmacological Classification: Antipsychotic (also known as a neuroleptic), and more specifically, a diphenylbutylpiperidine derivative. It is a first-generation antipsychotic (FGA) or “typical” antipsychotic.
- Mechanism of Action: Penfluridol primarily acts as a dopamine D2 receptor antagonist in the mesolimbic dopaminergic system. This action helps reduce the excessive dopamine activity believed to contribute to the positive symptoms of schizophrenia. It also affects other neurotransmitter systems including serotonin.
Alternate Names
- International Nonproprietary Name (INN): Penfluridol
- Other Names: Flupidol, Penfluridol NHWA
- Brand Names: Semap (discontinued), Acemap
How It Works
- Pharmacodynamics: Penfluridol primarily blocks dopamine D2 receptors, reducing dopaminergic neurotransmission. This leads to a decrease in psychotic symptoms. It also exhibits some affinity for serotonin receptors, although the clinical significance is uncertain. Its long duration of action results from high lipid solubility, slow release from fatty tissues, and a prolonged elimination half-life (around 66 hours).
- Pharmacokinetics: Penfluridol is well-absorbed orally, reaching peak plasma concentrations after approximately 2 hours. It is highly lipophilic and distributes extensively throughout the body, accumulating in fatty tissues. It undergoes hepatic metabolism, primarily via CYP450 enzymes, and is excreted mainly in feces, with only a small amount eliminated in urine.
- Mode of Action: Binds to and blocks dopamine D2 receptors, leading to a reduction in dopaminergic activity. It also inhibits the release of hypothalamic and hypophyseal hormones.
Dosage
Standard Dosage
Adults:
- Initial: 20-60 mg orally once a week. This can be increased weekly by 20 mg if necessary.
- Severe/resistant cases: Up to 250 mg once a week in severe or resistant conditions.
- Maintenance: Dosages are usually in the range of 20-40 mg once a week and should be individualized.
Children:
- Not recommended for use in children due to insufficient safety and efficacy data.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 20 mg/week) and titrate cautiously due to increased sensitivity and potential for adverse effects.
- Patients with Renal Impairment: Dose adjustments are not typically required, as only a small amount of the drug is excreted unchanged in urine. Careful monitoring is still recommended.
- Patients with Hepatic Dysfunction: Use with caution and consider dose reduction, as hepatic metabolism is the primary route of elimination. Close monitoring is needed.
- Patients with Comorbid Conditions: Careful consideration and monitoring are essential, especially in patients with cardiovascular disease, epilepsy, diabetes, or hypothyroidism.
Clinical Use Cases
- Penfluridol is not generally recommended for acute management of conditions like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations due to its slow onset of action. It’s intended for long-term maintenance therapy of chronic conditions, particularly schizophrenia.
Dosage Adjustments
- Dose modifications are based on individual patient response and tolerability. Adjust according to clinical response and monitor for side effects.
Side Effects
Common Side Effects
- Drowsiness, sedation
- Extrapyramidal symptoms (EPS): Tremors, rigidity, bradykinesia, akathisia, dystonia
- Weight gain
- Anticholinergic effects: Dry mouth, constipation, blurred vision
- Nausea, vomiting
- Headache
- Dizziness
Rare but Serious Side Effects
- Tardive dyskinesia (potentially irreversible movement disorder)
- Neuroleptic malignant syndrome (NMS), a life-threatening condition
- QT interval prolongation and potentially fatal arrhythmias
- Orthostatic hypotension
- Blood dyscrasias (rare)
Long-Term Effects
- Hyperprolactinemia, leading to menstrual irregularities, sexual dysfunction, galactorrhea, and potential bone loss
- Metabolic syndrome (weight gain, dyslipidemia, hyperglycemia)
Adverse Drug Reactions (ADR)
- Neuroleptic malignant syndrome
- Tardive dyskinesia
- Severe arrhythmias
- Agranulocytosis
Contraindications
- Hypersensitivity to penfluridol
- Pre-existing CNS depression or coma
- Severe cardiovascular disease
- Parkinson’s disease without concurrent antiparkinson medication
Drug Interactions
- CNS depressants (alcohol, benzodiazepines, opioids): Increased sedation and respiratory depression
- Anticholinergic medications: Exacerbated anticholinergic effects
- Dopamine antagonists: Increased risk of EPS
- CYP450 inducers (rifampicin, phenytoin): Decreased penfluridol levels
- CYP450 inhibitors (ketoconazole, erythromycin): Increased penfluridol levels
- Type 1a antiarrhythmics, tricyclic antidepressants, some quinolone antibiotics: Increased risk of QT prolongation
- Trazodone: Additive hypotensive effects
- Lithium: Increased neurotoxicity risk
Pregnancy and Breastfeeding
- Pregnancy: Not recommended. While not assigned an FDA Pregnancy Category due to its limited use in the US currently, it’s advised to avoid use during pregnancy due to potential risks to the fetus.
- Breastfeeding: Not recommended as it is excreted in breast milk and can cause adverse effects in nursing infants.
Drug Profile Summary
- Mechanism of Action: Dopamine D2 receptor antagonist.
- Side Effects: Drowsiness, EPS, weight gain, anticholinergic effects, tardive dyskinesia, NMS, QT prolongation.
- Contraindications: CNS depression, coma, severe cardiovascular disease, hypersensitivity.
- Drug Interactions: CNS depressants, anticholinergics, CYP450 inducers/inhibitors.
- Pregnancy & Breastfeeding: Avoid use.
- Dosage: 20-60 mg/week initially, up to 250 mg/week; adjust based on response.
- Monitoring Parameters: Weight, EPS, ECG (for QT interval), prolactin levels, complete blood count (CBC), liver function tests.
Popular Combinations
- There are no firmly established, routinely recommended drug combinations with penfluridol. Concomitant use with other antipsychotics or medications should be carefully considered due to potential drug interactions and additive side effects.
Precautions
- General Precautions: Evaluate baseline ECG, liver and renal function. Monitor for EPS, NMS, and other adverse effects. Patient education regarding side effects and adherence is crucial.
- Specific Populations: See “Dosage - Special Cases.”
- Lifestyle Considerations: Advise patients to avoid alcohol and other CNS depressants. Driving may be impaired due to sedation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Penfluridol?
A: Initial dose is typically 20-60mg once weekly for adults. This can be adjusted up to a maximum of 250mg weekly, based on individual response and tolerability. Not recommended for children.
Q2: How long does it take for Penfluridol to start working?
A: Penfluridol has a slow onset of action. Noticeable improvement may take several weeks to become apparent.
Q3: What are the most common side effects of Penfluridol?
A: Drowsiness, extrapyramidal symptoms (EPS, such as tremors and stiffness), weight gain, and anticholinergic effects (dry mouth, constipation).
A: Neuroleptic malignant syndrome (NMS), tardive dyskinesia, severe arrhythmias, and blood dyscrasias.
Q5: Can Penfluridol be used during pregnancy or breastfeeding?
A: It is generally not recommended due to potential risks to the fetus or nursing infant.
Q6: Does Penfluridol interact with other medications?
A: Yes, it can interact with several medications, including other antipsychotics, CNS depressants, and drugs metabolized by CYP450 enzymes. Provide a comprehensive medication list to the prescribing physician.
Q7: How is Penfluridol administered?
A: Orally, usually once a week as a tablet.
Q8: What should I monitor in patients taking Penfluridol?
A: Monitor for EPS, NMS, weight changes, ECG changes (QT interval), prolactin levels, and other potential adverse effects. Monitor metabolic parameters for dyslipidemia and hyperglycemia.
Q9: Is Penfluridol suitable for the rapid treatment of acute psychotic episodes?
A: No, due to its slow onset of action. It is more suited for long-term maintenance treatment.
Q10: What should patients know about taking Penfluridol?
A: They should be informed about potential side effects, the importance of adhering to the prescribed dosing schedule, and to avoid alcohol and other CNS depressants. They should also report any new or worsening symptoms to their healthcare provider.
