Leponex 25 mg and 100 mg tablets – clozapine for treatment-resistant schizophrenia

Leponex contains clozapine, a medicine from the group of antipsychotics used to treat mental illnesses such as psychosis. It is intended for patients with schizophrenia in whom treatment with at least two other antipsychotics has not worked or has caused severe side effects, and for people with Parkinson's disease who have severe disturbances of thinking, emotions and behaviour.

The medicine is available as 25 mg and 100 mg tablets; both strengths are scored and can be divided into equal doses. Because of the risk of agranulocytosis, treatment requires regular blood count checks.

Who is Leponex intended for and why are blood tests mandatory during treatment?

Key facts about the medicine

What is Leponex used for?

• treatment-resistant schizophrenia – when at least two previous medicines for schizophrenia did not work or caused severe side effects that could not be treated;
• severe disturbances of thinking, emotions and behaviour in people with Parkinson's disease in whom other treatments have not been successful.

How is Leponex taken and dosed?

The doctor increases the dose gradually to reduce the risk of low blood pressure, seizures and drowsiness. Tablets are swallowed with enough water. Usual dosing (PIL):

• At doses above 450 mg daily the risk of side effects, especially seizures, increases – the lowest effective dose is always used.
• If you have not taken the medicine for more than 48 hours, do not restart on your own – contact your doctor; treatment is restarted at 12.5 mg.

Special patient groups

• Children and adolescents under 16: the medicine is not intended for this group (insufficient data).
• People aged 60 and over: treatment is started at a lower dose and increased very slowly; fainting on changing position, dizziness, fast heartbeat, difficulty urinating and constipation are more common. In elderly people with dementia, antipsychotics are associated with a slightly increased mortality.
• Liver disease: the medicine must not be taken with severe liver disease or acute jaundice; with milder disorders – regular liver function tests.
• Kidney and heart disease: the medicine is contraindicated in severe disease.

Contraindications – when the medicine must not be used

• allergy to clozapine or any of the excipients;
• inability to have regular blood count checks;
• previous low white blood cell count (leukopenia, agranulocytosis), especially drug-induced (except after chemotherapy);
• previous discontinuation of Leponex due to severe side effects (agranulocytosis, heart problems);
• current or previous treatment with long-acting depot antipsychotic injections;
• bone marrow disease;
• uncontrolled epilepsy;
• acute mental illness caused by alcohol or drugs; impaired consciousness, severe drowsiness, coma; circulatory collapse;
• severe kidney, heart or liver disease, myocarditis, acute jaundice;
• paralytic ileus;
• medicines that interfere with bone marrow function or reduce white blood cells.

Warnings and precautions

• blood clots (also in the family), glaucoma, diabetes or raised blood sugar, prostate and urination problems;
• chronic constipation or anticholinergics, colon disease, abdominal surgery;
• controlled epilepsy, QT prolongation (also in the family), risk of stroke;
• weight gain and blood lipids – the doctor may monitor body weight and lipids;
• fainting or dizziness on standing – caution, risk of falls; before surgery or prolonged immobility talk to your doctor (risk of thrombosis);
• neuroleptic malignant syndrome (sudden rise in temperature and muscle stiffness) – emergency care;
• nausea, vomiting, loss of appetite – liver check; the medicine contains lactose.

Interactions with other medicines, food and drink

• must not be combined with medicines that damage bone marrow or reduce white blood cells: carbamazepine, chloramphenicol, sulphonamides (co-trimoxazole), pyrazolone analgesics (phenylbutazone), penicillamine, cytotoxic medicines, depot antipsychotic injections;
• caution and informing the doctor with: lithium, fluvoxamine, tricyclic antidepressants, MAO inhibitors, citalopram, paroxetine, fluoxetine, sertraline, other antipsychotics, benzodiazepines, narcotics, phenytoin, valproic acid, adrenaline and noradrenaline, warfarin, antihistamines, anticholinergics, Parkinson's medicines, digoxin, antiarrhythmics, omeprazole, cimetidine, erythromycin, rifampicin, ketoconazole, protease inhibitors, atropine and hormonal contraceptives;
• alcohol is not allowed; sudden changes in smoking or caffeine intake (coffee, tea, cola) can change the effect of the medicine – tell your doctor.

Pregnancy and breast-feeding

• During pregnancy the doctor weighs benefits and risks; tell them immediately if you become pregnant. Newborns of mothers who took the medicine in the last trimester may have trembling, muscle stiffness or weakness, drowsiness, agitation, breathing and feeding problems.
• Periods may normalise when switching to Leponex – adequate contraception is needed.
• Do not breast-feed while taking the medicine – clozapine passes into breast milk.

Driving and using machines

• Leponex has a strong effect on psychophysical abilities. Driving and using machines are not permitted during treatment.

Possible side effects

• Very common (more than 1 in 10): drowsiness, dizziness, increased salivation, severe constipation, fast heartbeat.
• Common (up to 1 in 10): signs of infection (fever, sore throat – urgent blood test), seizures, fainting, increased white blood cells and eosinophils, weight gain, blurred vision, headache, tremor, stiffness, restlessness, ECG changes, high blood pressure, nausea, vomiting, dry mouth, loss of bladder control, fatigue, sweating, slurred speech.
• Uncommon (up to 1 in 100): agranulocytosis, neuroleptic malignant syndrome, fainting on standing, stuttering.
• Rare (up to 1 in 1,000): myocarditis, pericarditis, pneumonia, pancreatitis, circulatory collapse, difficulty swallowing, hepatitis, raised blood sugar and diabetes, thromboembolism, delirium, anaemia, pauses in breathing during sleep.
• Very rare and not known: cardiomyopathy, cardiac arrest, bowel obstruction, fulminant liver necrosis, kidney inflammation, heart attack, atrial fibrillation, sepsis, bowel perforation or ischaemia, megacolon, rhabdomyolysis, DRESS syndrome, restless legs syndrome.

Overdose, missed dose and stopping treatment

• Overdose: tell a doctor immediately or call an ambulance; symptoms include drowsiness, loss of consciousness, coma, confusion, hallucinations, convulsions, increased salivation, low blood pressure, fast or irregular heartbeat, shallow breathing.
• Missed dose: take it as soon as you remember; if it is time for the next one, skip it. Do not take a double dose. If you have not taken the medicine for more than 48 hours, ask your doctor for advice.
• Stopping treatment: do not stop on your own – sweating, headache, nausea, vomiting, diarrhoea and return of symptoms may occur; gradual reduction by 12.5 mg over 1–2 weeks is recommended.

Related information

Leponex is used only under the supervision of a psychiatrist, with regular blood count checks according to the schedule set by the doctor. For questions about treatment and monitoring, contact your doctor; always read the enclosed leaflet.

Composition, pack and manufacturer

• Active substance: clozapine 25 mg or 100 mg per tablet.
• Excipients: lactose monohydrate, maize starch, magnesium stearate, colloidal anhydrous silica, povidone, talc.
• Appearance: 25 mg – round yellow tablets about 6.3 mm in diameter, marked "CLOZ" and "L/O" by the score line; 100 mg – round yellow tablets about 10 mm in diameter, marked "CLOZ" and "Z/A".
• Pack: carton with 5 blisters of 10 tablets (50 tablets).
• Marketing authorisation holder: Viatris Healthcare d.o.o., Bulevar Mihajla Pupina 115a, Belgrade; manufacturers: McDermott Laboratories (Mylan Dublin), Ireland; Mylan Hungary Kft., Komárom, Hungary; Madaus GmbH, Troisdorf, Germany.
• Authorisation numbers: 515-01-05038-21-001 (25 mg) and 515-01-05039-21-001 (100 mg) of 03.11.2022 (renewals).

Storage

• This medicine does not require any special storage conditions.
• Keep out of the sight and reach of children.
• Do not use after the expiry date; return unused medicines to a pharmacy that collects them.

Frequently asked questions

How often are blood tests done during treatment with Leponex?

Before starting, then weekly for the first 18 weeks, afterwards at least monthly, and for another 4 weeks after stopping treatment. The medicine may only be taken if the blood cell count is normal.

Why is constipation important with clozapine?

Severe constipation is a very common side effect and, if untreated, can lead to serious complications such as bowel obstruction. Tell your doctor about bowel problems so they can be treated in time.

Do smoking and coffee affect Leponex?

Yes. Sudden changes in smoking or in drinking caffeinated beverages can change the effect of the medicine. Tell your doctor if you smoke, how much coffee, tea or cola you drink and if you plan to change these habits.

What if I miss the medicine for two days?

If you have not taken Leponex for more than 48 hours, do not continue at your usual dose – seek your doctor's advice as soon as possible. When treatment is restarted after a two-day break, the starting dose is 12.5 mg.

Sources

• ALIMS – Patient leaflet Leponex 25 mg and 100 mg tablets (PIL, Serbian, 25 mg authorisation)
• ALIMS – SmPC Leponex 25 mg (Serbian)
• ALIMS – Patient leaflet Leponex (PIL, Serbian, 100 mg authorisation)
• ALIMS – SmPC Leponex 100 mg (Serbian)

Date sources were checked: 25.10.2026.