What is Zypadhera?
Zypadhera consists of a powder and a solvent for the preparation of a prolonged release suspension for injection. It contains the active substance olanzapine. "Extended release" means that the active ingredient is released slowly over a few weeks after the injection.
What is Zypadhera used for?
Zypadhera is used to maintain symptomatic improvement in schizophrenic patients already stabilized by an initial treatment with olanzapine taken by mouth. Schizophrenia is a mental illness characterized by various symptoms, including disconnected thinking and speech, hallucinations (auditory or visual perception of things or non-existent people), suspicious behavior and illusions.
The medicine can only be obtained with a prescription.
How is Zypadhera used?
Zypadhera is given as a deep intramuscular injection (in the buttock) by a doctor or nurse who practices this type of injection. In rare cases, patients receiving Zypadhera may experience symptoms of an overdose of olanzapine after injection if the medicine is accidentally injected into a vein. The overdose symptoms include sedation (drowsiness) and delirium (confusional state). Since patients must be monitored by specialized personnel at least for the three hours following the injection against the possible onset of these symptoms, the injection must be carried out at facilities equipped to deal with any cases of overdose. Patients who experience symptoms of overdose should continue to be monitored until symptoms disappear. Zypadhera should not be injected into a vein or under the skin.
Zypadhera is given at doses of 150 or 210 mg every two weeks, or at doses of 300 or 405 mg every four weeks. The dose depends on the dose of olanzapine previously taken by the patient by mouth. Patients should be closely monitored for possible relapse symptoms during the first or first two months of treatment, possibly adjusting the dose.
Zypadhera is not recommended for patients over 65 years of age. However, patients between the ages of 65 and 75 or patients with kidney or liver problems may use Zypadhera if an effective and well tolerated dose of olanzapine by mouth has been identified. In patients where the breakdown of olanzapine may occur slowly, for example because they suffer from moderate liver problems, it may be necessary to use a low initial dose.
How does Zypadhera work?
The active substance of Zypadhera is olanzapine, an antipsychotic drug called "atypical" as it differs from the old antipsychotics available since the 1950s. Olanzapine binds to various different receptors present on the surface of nerve cells in the brain, thus interrupting the transmission of signals between brain cells operated by "neurotransmitters", which are chemical substances that allow nerve cells to communicate with each other. It is thought that the therapeutic effect of olanzapine is due to the fact that it blocks the receptors of neurotransmitters 5-hydroxytrypamine (also called "serotonin") and dopamine. Because these neurotransmitters are involved in schizophrenia, olanzapine helps to normalize brain activity and reduce disease symptoms.
Olanzapine has been authorized in the European Union (EU) since 1996 and is available as tablets, orodispersible tablets (ie those that dissolve in the mouth) and in fast-acting injectable formulations in Zyprexa, Zyprexa Velotab and other medicines. The olanzapine contained in Zypadhera is presented in the form of "pamoate" salt which makes it less soluble. As a result, the active ingredient is released slowly over more than four weeks after the Zypadhera injection.
What studies have been carried out on Zypadhera?
As olanzapine is already authorized in the EU under the name Zyprexa, the company used some of the data related to Zyprexa to support the use of Zypadhera.
Zypadhera has been the subject of two main studies conducted on schizophrenic adults. The first study examined the initial treatment of schizophrenia while the second examined the maintenance of the response to olanzapine treatment:
- the initial treatment study compared the effect of three doses of Zypadhera compared to a placebo (dummy injections) on 404 patients. The main measure of effectiveness was the change in symptoms measured after eight weeks via a standard scale for the evaluation of schizophrenia;
- the maintenance treatment study compared the effect of four doses of Zypadhera versus olanzapine taken by mouth on 1065 patients. Three doses of Zypadhera were "high" (300 and 150 mg every two weeks, and 405 mg every four weeks) while one was "low" (45 mg every four weeks). All patients who participated in this study had been stabilized by other treatments for schizophrenia and had been taking olanzapine by mouth for at least six weeks at the start of the study. The main efficacy parameters consisted of the time elapsed until the worsening of symptoms and the number of patients with worsening symptoms over 24 weeks.
What benefit has Zypadhera shown during the studies?
In the initial schizophrenia treatment study, Zypadhera was more effective than placebo. Symptom scores were around 100 points at the beginning of the study but in Zypadhera-treated patients they had decreased by about 25 points after eight weeks, compared with about 9 points for patients treated with placebo. The effectiveness of Zypadhera was greater than with placebo starting from the second week of treatment.
In the study on the maintenance of the response to treatment with olanzapine, Zypadhera was as effective as olanzapine taken by mouth: in 10% of patients treated with Zypadhera every two weeks there was a worsening of symptoms compared to 7% of patients treated with olanzapine by mouth. The "high" doses of Zypadhera have been shown to be more effective in preventing a worsening of symptoms than the "low" dose.
What is the risk associated with Zypadhera?
The most common side effects of Zypadhera (ie seen in more than 1 patient in 10) are weight gain, drowsiness and increased levels of prolactin (a hormone). For the full list of all side effects reported with Zypadhera, see the Package Leaflet.
Zypadhera should not be used in patients who may be hypersensitive (allergic) to olanzapine or any of the other ingredients. Zypadhera cannot be used in patients at risk of narrow-angle glaucoma (hypertension in the eye).
Why has Zypadhera been approved?
The Committee for Medicinal Products for Human Use (CHMP) noted that Zypadhera is effective both in the initial treatment of schizophrenia and in maintaining the response obtained. However, it should be noted that prolonged-release injections are not suitable as an initial treatment since the reduction in symptoms begins no earlier than a week, while the patient may need a rapid control of symptoms. In the case of prolonged release injection it is also not possible to interrupt the treatment, for example in the case of side effects. The Committee therefore decided that Zypadhera's benefits are greater than its risks in the maintenance treatment of adult patients with schizophrenia sufficiently stabilized during an acute treatment with oral olanzapine and recommended the granting of the marketing authorization for Zypadhera.
What measures are being taken to ensure the safe use of Zypadhera?
The company of Zypadhera is committed to providing an education program for doctors, nurses and pharmacists, as well as a card for patients from all Member States, to remember how to use the medicine safely, including information on what to do before and after each injection, the differences between Zypadhera and other injectable olanzapine-based medicines and recommendations on how to monitor patients.
More information on Zypadhera:
On 19 November 2008, the European Commission issued a marketing authorization valid for Zypadhera, valid throughout the European Union, to Eli Lilly Nederland BV.
For the full EPAR for Zypadhera, click here.
Last update of this summary: 10-2008.
