Pimavanserin

Before taking pimavanserin,

• tell your doctor and pharmacist if you are allergic to pimavanserin, any other medications, or any of the ingredients in pimavanserin tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: carbamazepine (Carbatrol, Tegretol, Teril, others); chlorpromazine; clarithromycin (Biaxin, in Prevpac); gatifloxacin; indinavir (Crixivan); itraconazole (Onmel, Sporanox); ketoconazole (Nizoral); certain medications for irregular heartbeat including amiodarone (Cordarone, Nexterone, Pacerone), disopyramide (Norpace), procainamide, quinidine (in Nuedexta), and sotalol (Betapace, Sorine, Sotylize); moxifloxacin (Avelox); phenytoin (Dilantin, Phenytek); rifampin (Rifadin, Rimactane, in Rifamate, in Rifater); thioridazine; or ziprasidone (Geodon). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with pimavanserin, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor what herbal products you are taking, especially St. John's wort.
• tell your doctor if you have or have ever had QT prolongation (an irregular heart rhythm that can lead to fainting, loss of consciousness, seizures, or sudden death); an irregular heartbeat; low levels of potassium or magnesium in your blood; or kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking pimavanserin, call your doctor.

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Tell your doctor if you are pregnant or plan to become pregnant.

There are no data on pimavanserin use in pregnant women. That said, the risk for major congenital malformations or miscarriage can not be assessed. In animal studies, no problems in regards to the baby's development were seen.

Pimavanserin is not approved for use in psychotic conditions related to dementia. Pimavanserin may increase the risk of death in older adults with dementia-related conditions.

Usual Adult Dose for Psychosis:

Recommended dose: 34 mg (as two 17 mg tablets) orally once a day

Comment:
-This drug does not require titration.

Use: Treatment of hallucinations and delusions associated with Parkinson's disease psychosis

• If you have an allergy to this medicine or any part of pimavanserin.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Kidney disease or liver disease.
• If you have any of these health problems: Long QTc on ECG or other heartbeat that is not normal, slow heartbeat, or low potassium or magnesium levels.
• If you are taking any drugs that can cause a certain type of heartbeat that is not normal (prolonged QT interval). There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take pimavanserin with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• This medicine may cause a type of abnormal heartbeat (prolonged QT interval). If this happens, the chance of other unsafe and sometimes deadly abnormal heartbeats may be raised. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using pimavanserin while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Take pimavanserin at the same time of day.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

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Pimavanserin acts as an inverse agonist and antagonist with high affinity for 5-HT2A receptors and low affinity for 5-HT2C and sigma 1 receptors; no affinity for 5-HT2B, dopaminergic (including D2), muscarinic, histaminergic, or adrenergic receptors, or to calcium channels.

Distribution

Vd: 2173 L

Metabolism

Primarily via CYP3A4 and CYP3A5; forms active N-desmethylated metabolite (AC-279)

Excretion

Feces (<2%); urine (<1% as unchanged drug)

Time to Peak

6 hours (median: 4 to 24 hours)

Half-Life Elimination

Pimavanserin: ~57 hours; N-desmethylated metabolite: ~200 hours

Protein Binding

~95%

Parkinson disease psychosis: Oral: 34 mg once daily

Dosage adjustment for concomitant therapy:

Strong CYP3A4 inhibitors (eg, ketoconazole): 17 mg once daily

Strong CYP3A4 inducers: 34 mg once daily; however, monitor for reduced efficacy; dosage increase may be necessary

Discontinuation of therapy: The American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (APA [Lehman 2004]; Cerovecki 2013; CPA [Addington 2005]; WFSBP [Hasan 2012]); risk for withdrawal symptoms may be highest with highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months, and the APA guidelines recommend reducing the dose by 10% each month (APA [Lehman 2004]; CPA [Addington 2005]). Continuing anti-parkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Cerovecki 2013). When switching antipsychotics, 3 strategies have been suggested: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic), overlap and taper (maintaining the dose of the first antipsychotic while gradually increasing the new antipsychotic, then tapering the first antipsychotic), and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). Evidence supporting ideal switch strategies and taper rates is limited, and results are conflicting (Cerovecki 2013; Remington 2005).

Use is not recommended; has not been studied in patients with hepatic impairment.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

Administration advice:
-May be taken with or without food

Patient advice:
-Patients should be advised to report all concurrent prescription and nonprescription medications or herbal products they are taking.
-Patients should be advised to speak to a healthcare provider if pregnant, intend to become pregnant, or are breastfeeding.