DENZAPINE Tablet Ref.[49997] Active ingredients: Clozapine

Denzapine 25 mg Tablets

UK: Denzapine Official Recommendations

As a consequence of a recent European regulatory initiative, the Denzapine Summary of Product Characteristics (SmPC) has been harmonised across Europe. The SmPC states that blood monitoring should be carried out in accordance with national-specific official recommendations. These are reproduced below.

The Denzapine Monitoring Service (DMS) was developed in order to manage the risk of agranulocytosis associated with clozapine. It is available 24 hours a day. When a monitoring service is not used, evidence suggests a mortality rate from agranulocytosis of 0.3%¹. This is compared to a mortality rate when clozapine is used in conjunction with a Monitoring Service, of 0.01%².

The Denzapine Monitoring Service provides centralised monitoring of leucocyte and neutrophil counts which is a mandatory requirement for all patients in the UK and Ireland who are treated with Denzapine. The use of Denzapine is restricted to patients who are registered with the Denzapine Monitoring Service. In addition to registering their patients, prescribing physicians must register themselves and a nominated pharmacist with the Denzapine Monitoring Service. All Denzapine-treated patients must be under the supervision of an appropriate specialist and supply of Denzapine is restricted to hospital and retail pharmacies registered with the Denzapine Monitoring Service. Denzapine is not sold to, or distributed through wholesalers.

The patient’s white cell count with a differential count must be monitored:

• At least weekly for the first 18 weeks of treatment
• At least at 2 week intervals between weeks 18 and 52
• After 1 year of treatment with stable blood counts (green range), patients may be monitored at least at 4 week intervals
• Monitoring must continue throughout treatment and for at least 4 weeks after discontinuation

If the blood result of a patient taking Denzapine is below the normal range (See Section 4.4), Britannia will contact the physician and pharmacist registered to the patient on the Denzapine Monitoring Service to inform them.

The Denzapine Monitoring Service maintains a database which includes all patients who have developed abnormal leucocyte or neutrophil findings and who should not be re-exposed to Denzapine or any other brand of clozapine.

Prescribers and pharmacists should adhere to brand prescribing and dispensing of clozapine in order to prevent the disruption to effective monitoring that may be caused if patients switch brands.

Furthermore, in order to protect patient safety, at any one time patients should only be prescribed one brand of clozapine and only registered with the monitoring service connected to that brand.

Advice on Monitoring Clozapine Blood Levels

Blood clozapine level monitoring is advised in certain clinical situations such as when a patient ceases smoking or switches to e-cigarettes, when concomitant medicines may interact to increase clozapine blood levels, where poor clozapine metabolism is suspected, when a patient has pneumonia or other serious infection and in the event of onset of symptoms suggestive of toxicity (see section 4.4).

For further information regarding Denzapine and the Denzapine Monitoring Service please call 0333 200 4141 (UK)

¹ De la Chapelle A, et al. Clozapine-induced agranulocytosis: a genetic and epidemiologic study. Hum Genet, 1977. 37: p. 183-194.

² Denzapine Monitoring Service, data on file.

Denzapine can cause agranulocytosis. Its use should be limited to patients:

• with schizophrenia who are non-responsive to or intolerant of antipsychotic drug treatment, or with psychosis in Parkinson’s disease when other treatment strategies have failed (see section 4.1)
• who have initially normal leucocyte findings (white blood cell count of ≥3500/mm³ (≥3.5 × 10⁹/L), and an absolute neutrophil count (ANC) of ≥2000/mm³ (≥2.0 × 10⁹/L)), and
• in whom regular white blood cell (WBC) counts and absolute neutrophil counts (ANC) can be performed as follows: weekly during the first 18 weeks of therapy, at least every 2 weeks between weeks 18 and 52, and at least every 4 weeks thereafter throughout treatment. Monitoring must continue throughout treatment and for 4 weeks after complete discontinuation of Denzapine (see section 4.4).

Prescribing physicians should comply fully with the required safety measures. At each consultation, a patient receiving Denzapine must be reminded to contact the treating physician immediately if any kind of infection begins to develop. Particular attention should be paid to flu-like complaints such as fever or sore throat and to other evidence of infection, which may be indicative of neutropenia (see section 4.4).

Denzapine must be dispensed under strict medical supervision in accordance with official recommendations (see section 4.4).

Myocarditis

Clozapine is associated with an increased risk of myocarditis which has, in rare cases, been fatal. The increased risk of myocarditis is greatest in the first 2 months of treatment. Fatal cases of cardiomyopathy have also been reported rarely (see section 4.4).

Myocarditis or cardiomyopathy should be suspected in patients who experience persistent tachycardia at rest, especially in the first 2 months of treatment, and/or palpitations, arrhythmias, chest pain and other signs and symptoms of heart failure (e.g. unexplained fatigue, dyspnoea, tachypnoea) or symptoms that mimic myocardial infarction (see section 4.4).

If myocarditis or cardiomyopathy are suspected, Denzapine treatment should be promptly stopped and the patient immediately referred to a cardiologist (see section 4.4).

Patients who develop clozapine-induced myocarditis or cardiomyopathy should not be re-exposed to clozapine (see section 4.3 and 4.4).