Orap

Patient Information Leaflet

Orap 4 mg tablets

Pimozide
Please read all of this leaflet carefully before you start taking this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Orap is and what it is used for
2. What you need to know before taking Orap
3. How to take Orap
4. Possible side effects
5. How to store Orap
6. Contents of the pack and other information

1. What Orap is and what it is used for

Orap contains pimozide, which belongs to a group of medicines called “Antipsychotics
(major tranquilizers or neuroleptics) derived from diphenylbutylpiperidine”.
Orap is indicated in the following cases:

• particularly as a maintenance therapy in long-term antipsychotic treatment of chronic and acute psychotic patients who are sensitive to the specific antipsychotic effects of neuroleptics;
• as initial treatment in outpatients or recently hospitalized or readmitted patients, provided that psychomotor agitation, aggressiveness, or particularly severe anxiety states are not the predominant symptoms of the clinical picture;
• in borderline cases between schizophrenic and neurotic forms (e.g. paranoid and schizoid states) leading to difficulties in social relationships.

Consult your doctor if you do not feel better or if you feel worse.

2. What you should know before taking Orap

DO NOT take Orap

• if you are allergic to pimozide or any of the other ingredients of this medicine (listed in section 6);
• if you are in a coma from any cause;
• if you have been diagnosed with endogenous depression (a condition characterized by low mood not attributable to specific causes) and Parkinson’s disease (a degenerative brain disorder affecting functions such as balance and movement);
• if you are pregnant, suspect you may be pregnant, or are planning a pregnancy (see section “Pregnancy and breastfeeding”);
• if you have clinically significant heart diseases such as recent acute myocardial infarction, decompensated heart failure, or arrhythmias (abnormal heart rhythms) treated with antiarrhythmic drugs;
• if you suffer from QTc interval prolongation (a disorder affecting the heart's electrical activity);
• if you have a family history of arrhythmia or torsades de pointes (abnormal heart rhythms);
• if you have untreated hypokalaemia (low potassium levels in the blood).

Also, do not take Orap with the following medicines (see section “Other medicines and Orap”):

• medicines that prolong the QTc interval;
• medicines that inhibit an enzyme called CYP3A4, such as:
  • azole derivatives used for systemic antifungal therapy (ketoconazole, itraconazole, miconazole, and fluconazole); however, Orap may be used in combination with topical formulations of these medicines (creams, lotions, vaginal suppositories);
  • macrolide antibiotics (erythromycin, clarithromycin, or troleandomycin);
  • some medicines used to treat AIDS (protease inhibitors);
  • some antidepressants (nefazodone, amitriptyline, maprotiline, sertraline, paroxetine, citalopram, and escitalopram);
  • other antipsychotic medicines (chlorpromazine, sertindole);
  • some medicines acting on the heart (quinidine, disopyramide, procainamide, amiodarone, sotalol, and bepridil);
  • some antihistamines (astemizole and terfenadine);
  • a medicine used for certain digestive problems (cisapride);
  • an antimalarial medicine (halofantrine);
  • an antibiotic (sparfloxacin).
    If you are taking any of these or other medicines, inform your doctor, who will assess which medicines can be used together with Orap (see also section “Interactions”). Orap is contraindicated in states of aggression and psychomotor agitation (see section “Warnings and Precautions”). High-dose Orap should not be used in asthenia (reduced muscular strength) or neuroses.

Warnings and precautions
Talk to your doctor or pharmacist before taking Orap.
Use Orap with caution:

• if you have cardiovascular diseases or a family history of QT prolongation. Your doctor will prescribe certain tests before starting treatment;
• if you or someone in your family has a history of blood clots (thrombosis), as medicines like this may increase the risk of clot formation;
• if you suffer from epilepsy. Your doctor will monitor you closely;
• if you are elderly, as you may be more sensitive to Orap;
• if you have liver (hepatic insufficiency) or kidney (renal insufficiency) problems, due to the risk of medicine accumulation;
• if you have conditions that may be worsened by the anticholinergic effects of pimozide;
• if you are a patient with risk factors for stroke (sudden loss of blood flow to the brain);
• if you engage in intense physical exercise;
• if you go to very hot places or do not drink enough fluids.

Please note that:

• hypotension may very rarely occur (see section “Possible side effects”).
• Orap is metabolized in the liver by certain enzymes. Some individuals have a variation in one of these enzymes. If Orap is metabolized slowly, your doctor may consider adjusting the dose.

SPECIAL WARNINGS
Increase in psychomotor activity
Clinical studies indicate that Orap is ineffective or only minimally effective in treating agitation, excitement, and severe anxiety.

Liver diseases (hepatic disorders)
Inform your doctor if you have liver disease, as regular monitoring may be necessary during Orap therapy.

Extrapyramidal symptoms
As with all other neuroleptics, extrapyramidal symptoms may occur (see section “Possible side effects”). These include slow, rigid, or jerky limb movements; unusual involuntary posture of the neck, face, eyes, mouth, or tongue; or abnormal facial expressions. Your doctor may consider initiating therapy with Orap to help resolve these effects.

Tardive dyskinesia
As with all antipsychotic medicines, tardive dyskinesia may occur in some patients receiving long-term treatment or after discontinuation of the medicine. This syndrome is characterized mainly by involuntary rhythmic movements of the tongue, face, mouth, or jaw. Symptoms may be permanent in some patients. The syndrome may be masked when treatment is resumed, when the dose is increased, or when switching to another antipsychotic. In such cases, your doctor will advise you to discontinue treatment.

Neuroleptic Malignant Syndrome (NMS)
A potentially fatal condition called Neuroleptic Malignant Syndrome has been reported during treatment with antipsychotic medicines. Clinical manifestations of this syndrome include: hyperthermia (fever), muscle rigidity, acinesia (marked reduction in movement of a muscle or the entire body), autonomic dysfunction (pulse and blood pressure irregularities, sweating, tachycardia, arrhythmias); and altered mental status, which may progress to stupor and coma. Treatment of NMS consists of immediately discontinuing antipsychotic medicines and other non-essential drugs, and initiating intensive symptomatic therapy (special care must be taken to reduce hyperthermia and correct dehydration). If your doctor considers it essential to restart antipsychotic treatment, you will be closely monitored.

Seizures
Use Orap with caution, as with other antipsychotics, if you have a history of seizures or other conditions that may lower the seizure threshold. In addition, generalized tonic-clonic seizures (seizures characterized by loss of consciousness and generalized muscle contractions) have been reported in association with Orap.

Body temperature regulation
Antipsychotic agents have been associated with impaired ability of the body to reduce body temperature. Caution is advised when pimozide is prescribed to patients who may be exposed to conditions that increase body temperature, such as intense physical exercise, exposure to high heat, concomitant administration of anticholinergic drugs, or tendency to dehydration.

Endocrine effects
Hormonal effects of neuroleptic antipsychotic medicines include (see section “Possible side effects”):

• hyperprolactinaemia (increased levels of the hormone prolactin), which may cause galactorrhoea (discharge of a milky or serous fluid from one or both nipples);
• gynaecomastia (development of breasts in males);
• oligomenorrhoea or amenorrhoea (menstrual cycle disturbances);
• breast swelling and erectile dysfunction.

Other medicines and Orap
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Orap may enhance:

• the effects of alcohol;
• the action of antihypertensive and blood pressure-lowering medicines;
• the action of medicines acting on the central nervous system.

Orap may alter the effects of antiparkinsonian medicines.
Do not take Orap concomitantly with the following medicines:

• medicines that prolong the QT interval, such as certain antiarrhythmics (used to normalize heart rhythm) of class Ia (quinidine, disopyramide, procainamide) and class III (amiodarone, sotalol);
• some antihistamines (for allergy treatment);
• other antipsychotic medicines;
• some antimalarial medicines (quinine and mefloquine);
• antibiotic medicines (moxifloxacin);
• medicines causing electrolyte imbalances;
• diuretic medicines, particularly those that may cause hypokalaemia (low potassium levels in the blood).

This list is indicative and not exhaustive.
Orap and beverages
Do not consume grapefruit juice during Orap therapy.
Orap and alcohol
Avoid consuming alcohol during treatment, as Orap enhances the effects of alcohol.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before taking this or any other medicine.
Pregnancy
Orap is contraindicated during pregnancy. If in doubt, contact your doctor.
The following symptoms have been observed in newborns of mothers who took conventional or atypical antipsychotics, including Orap, during the third trimester (the last three months of pregnancy): tremor, muscle rigidity and/or weakness, drowsiness, agitation, breathing difficulties, and feeding problems. Contact your doctor if your baby shows any of these symptoms.
Breastfeeding
Do not breastfeed while taking Orap, as small amounts of Orap may pass into breast milk. If in doubt, contact your doctor.
Driving and using machines
Avoid driving vehicles and performing tasks requiring full alertness. This product, like similar medicines, may cause sedation and drowsiness.

3. How to take Orap

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Take your daily dose of Orap in the morning as a single administration.
Do not drink grapefruit juice during treatment with Orap.
The initial dose for an adult is 1-2 mg per day (depending on body weight and severity of
symptoms). Your doctor may adjust the dose until the optimal daily dose is reached.
Please note that your doctor may:

• modify the dose, determining the most appropriate pimozide dosage for you;
• gradually increase the dose by 2-4 mg at intervals of no less than one week, up to a maximum daily dose of 20 mg. Generally, the optimal maintenance dose ranges between 1 and 8 mg per day.

Your doctor will monitor you to ensure you are treated with the lowest effective dose.
Also keep in mind that:

• when switching from an ongoing neuroleptic therapy to Orap, it is advisable to gradually reduce the dose of the previously used medicine rather than stopping it abruptly.
• after starting treatment, some time may pass before symptoms disappear and the medicine takes effect.
• after prolonged use of Orap, your doctor may consider a gradual discontinuation of the medicine, as symptoms of transient dyskinesia (movement disorders) may occur.

Use in elderly patients
In treating elderly patients, dosage must be carefully determined by the doctor, who will consider whether a reduction of the above-mentioned doses is necessary.
Use in slow metabolizers
In slow metabolizers (individuals who eliminate drugs more slowly at the liver level), it is recommended that the dose should not exceed 4 mg per day and that doses should not be increased more frequently than every 14 days.
If you take more Orap than you should
In case of accidental ingestion/overdose of Orap, contact your doctor immediately or go to the nearest hospital.
If an overdose occurs, you will be monitored until normal heart rhythm is restored.
Possible signs of overdose include:

• unusual muscle stiffness;
• inability to move or to remain still;
• irregular heartbeat (such as risk of cardiac arrhythmias, possibly associated with QT interval prolongation and ventricular arrhythmias, including torsades de pointes).

If you stop taking Orap
If you have any questions about how to use this medicine, consult your doctor or pharmacist.
Orap treatment may only be stopped on the advice of your doctor.
If treatment is to be discontinued, gradual withdrawal is recommended, especially if you have been taking a high dose of the medicine, and only under medical guidance.
Stay in contact with your doctor if you should stop treatment suddenly.
The following symptoms may occur with abrupt discontinuation of Orap:

• nausea;
• vomiting;
• temporary muscle spasms and insomnia.

4. Possible side effects

Like all medicines, Orap can cause side effects, although not everyone experiences them.
Below is a list of side effects that have been reported.

Very common side effects (may affect more than 1 in 10 people):

• dizziness
• somnolence (drowsiness)
• hyperhidrosis (excessive sweating compared to normal)
• nocturia (frequent need to urinate during the night)

Common side effects (may affect up to 1 in 10 people):

• anorexia
• insomnia
• headache
• tremor
• lethargy (pathological state of deep sleep)
• blurred vision
• constipation
• dry mouth
• vomiting
• overactivity of sebaceous glands
• pollakiuria (frequent urination of small amounts of urine)
• erectile dysfunction
• prostration (state of extreme physical and mental exhaustion)
• depression
• agitation
• restlessness
• extrapyramidal disorder (abnormalities in movement coordination or involuntary muscle movements)
• akathisia (a psychomotor syndrome characterized by inability to sit still)
• hypersalivation (excessive salivation)
• muscle rigidity
• bradykinesia (difficulty initiating and performing movements)
• cogwheel rigidity
• dyskinesia (movement disorder)
• dystonia (motor disorder leading to unnatural postures)
• dysarthria (motor speech disorder)
• oculogyration (involuntary rotary eye movements)
• muscle spasms
• amenorrhea (temporary absence of menstrual periods)
• facial edema (swelling of the face)

Very rare side effects (may affect up to 1 in 10,000 people):

• hyperglycemia (in patients with pre-existing diabetes), (increased blood sugar levels)
• hyperprolactinemia (increased levels of the hormone prolactin)
• hyponatremia (low sodium concentration in the blood)
• decreased libido
• neuroleptic malignant syndrome (NMS)
• generalized seizures
• tardive dyskinesia (movement disorder)
• torsade de pointes
• ventricular fibrillation
• ventricular tachycardia
• urticaria
• pruritus (itching)
• rash
• neck rigidity
• glycosuria (presence of sugar in the urine)
• galactorrhea (discharge of a milky or serous fluid from one or both nipples)
• gynaecomastia (development of breasts in men)
• neonatal withdrawal syndrome
• extrapyramidal symptoms
• hypothermia (reduction of body temperature below 35°C)
• QT interval prolongation on electrocardiogram
• abnormal electroencephalogram
• weight gain

Not known: frequency cannot be estimated from the available data

• blood clots (thrombi) in the veins, particularly in the legs (symptoms include swelling, pain and redness of the legs), which may travel through blood vessels to the lungs causing chest pain and breathing difficulties.

If you notice any of these symptoms, contact your doctor immediately.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, inform your doctor or pharmacist.
You can also report side effects directly via the national reporting system at the following website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Orap

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the word
Exp. The expiry date refers to the last day of that month.
The expiry date refers to the product in its original, unopened packaging stored correctly.
Store below 30°C.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Orap contains

• The active substance is pimozide. One tablet contains 4 mg of pimozide.
• The other components are calcium hydrogen phosphate dihydrate, maize starch, microcrystalline cellulose, povidone K30, talc, hydrogenated vegetable oil, yellow iron oxide, indigotine sodium disulfonate, aluminium lake.

Description of the appearance of Orap and pack contents
20 tablets for oral use

Marketing Authorisation Holder and Manufacturer
Eumedica N.V./S.A.
Chemin de la Nauwelette 1
BE-7170 Manage
Belgium

Manufacturer
Lusomedicamenta Sociedade Técnica Farmacêutica S.A.
Estrada Consiglieri Pedroso, 69-B
Queluz de Baixo
PT-2730-055 Barcarena
Portugal
or
Eumedica N.V./S.A.
Chemin de la Nauwelette 1
BE-7170 Manage
Belgium