Medical Information

Nuplazid is a selective 5-HT2A receptor inverse agonist primarily used to treat psychotic hallucinations and delusions associated with Parkinson's disease. Its mechanism of action is unique and requires caution in its interaction with CYP3A4 modulators.

1. Effect of action

(1) Mechanism of receptor action

By selectively antagonizing and reverse exciting 5-HT2A receptors, regulating dopaminergic neurotransmission, improving psychiatric symptoms without exacerbating motor disorders.

(2) Clinical efficacy characteristics

During the 6-week treatment, the frequency of hallucinations/delusions can be significantly reduced, with an onset time of about 2-4 weeks and no significant impact on cognitive function.

(3) Pharmacokinetics

Oral bioavailability is about 50%, and high-fat meals can increase AUC by 50%. It is necessary to take medication during meals to ensure stable blood drug concentration.

2. Drug interactions

(1) CYP3A4 inhibitor

Strong inhibitors (such as itraconazole) can increase the exposure of pimavanserin by 4 times, and should be avoided in combination or reduced by 50%.

(2) CYP3A4 inducer

Levofloxacin and other strong inducers can reduce drug concentration by 70%, and the efficacy needs to be monitored and dosage adjustments considered.

(3) Other psychotropic drugs

Combination therapy with dopamine antagonists may exacerbate extrapyramidal reactions and should be administered at least 12 hours apart.

(4) QT interval prolonging drugs

Avoid co administration with class I/III antiarrhythmic drugs as their synergistic effect may induce apical torsion ventricular tachycardia.

3. Indications for discontinuation of medication

(1) Insufficient therapeutic effect

If there is no significant improvement in symptoms after 6 weeks of continuous treatment, it is recommended to consider discontinuing the medication and changing the treatment plan to avoid the accumulation of adverse reactions caused by ineffective medication.

(2) Serious adverse reactions

When QT interval prolongation, consciousness disorders, or severe motor disorders occur, medication should be stopped immediately and electrocardiogram monitoring should be performed for at least 72 hours.

4. Reduction plan

(1) Standard reduction process

It is recommended to reduce the dosage by 50% every 2 weeks, from 34mg/d to 17mg/d and then to discontinuation, with a total reduction period of no less than 4 weeks to reduce the risk of rebound.

(2) Adjustment for long-term medication users

For those who have been taking medication for more than 1 year, the reduction period should be extended to 8 weeks, during which the recurrence of psychiatric symptoms should be evaluated weekly.