Generic Olanzapine: Health Authority Opportunity or Nightmare?

A. Aleksander Araszkiewicz; Katarzyna Szabert; Brian Godman; Magdalena Wladysiuk; Corrado Barbui; Alan Haycox

Disclosures

Expert Rev Pharmacoeconomics Outcomes Res. 2008;8(6):549-555. 

In This Article

Abstract and Introduction

Abstract

Pressures to contain pharmaceutical expenditure have led to increased prescribing and dispensing of generic drugs in addition to low prices for generics. Atypical antipsychotics are prescribed for schizophrenia leading to resource pressures with their higher acquisition costs than typical antipsychotics. Drug costs can be reduced once multiple sources are available. However, this must be balanced against possible efficacy, safety and compliance concerns given the high cost of relapses for patients with schizophrenia. Generic clozapine has been launched. There was an increase in relapse rates with early formulations in the USA. However, this has not been the case with more recent formulations. Despite this, there could be patient and physician concerns when additional generic atypicals, such as olanzapine are available, reducing potential savings. A retrospective survey of patients prescribed Zyprexa®, generic olanzapine or both, over an extensive period was undertaken in Poland to help address these concerns given the difficulties with conducting randomized clinical trials with generics in complex situations. The survey showed similar effective doses of olanzapine in all groups. Relapse rates were similar in patients before and after switching to generic olanzapine, and no untoward side effects were seen in any patient prescribed generic olanzapine. Consequently, generic olanzapine should be welcomed with savings redirected to improving compliance or funding new premium priced drugs that can reduce relapses in refractory patients. This should give reassurance to health authorities to continue their reforms where pertinent to optimize resources by increasing availability of generics.

Introduction

Pressures to contain pharmaceutical expenditure are growing across Europe as expenditure on health, particularly pharmaceuticals, has risen more rapidly than other components of public services in recent years.[1] This is set to continue unless addressed, with demographic changes leading to greater prevalence of chronic diseases, instigation of stricter clinical targets and the continued launch of expensive new drugs.[2,3,4,5,6,40]

European governments and health authorities have introduced successive reforms to try and address these pressures to ensure continued comprehensive healthcare, including funding new innovative drugs, without prohibitively increasing taxes or insurance premiums.[5,7,8] Measures introduced throughout Europe include reforms and initiatives to enhance generic prescribing and dispensing[9,10,11] with generic medicines now accounting for over half the medicines dispensed in Europe,[41] as well as measures to engineer low prices for generics.[11]

However, there are certain cases where generic prescribing and generic substitution is not appropriate and drugs should be prescribed by brand name with 'no substitution' indicated.[12,13] This is where differences in formulations could lead to loss of disease control or adverse effects. Examples in major mental health illnesses include lithium; where the British National Formulary advises that any change in formulation should be treated in the same way as initiating treatment in view of possible severe toxicity.[13,14]

There have also been reports of relapses and increased side-effects when patients with depression have been switched from original brand selective serotonin reuptake inhibitors to generics, for example, relapses with generic fluoxetine[15] and citalopram[16] as well as increased side-effects with different formulations of paroxetine.[17] There have also been reports of increased relapses when patients with schizophrenia have been switched from Clozaril® to generic clozapine produced by Zenith Goldline pharmaceuticals[18,19] (now IVAX). This can have significant resource implications with the cost of a relapse in schizophrenia up to 55-times greater than the acquisition cost of Clozaril[20] As a result, various authors have cautioned against the prescribing of generic drugs in patients with schizophrenia[21]

However, recently Healy and colleagues in the USA did not find any bioavailability issues, or differences in clinical parameters - such as inpatient stay - in community patients switched from Clozaril to generic clozapine produced by Mylan pharmaceuticals.[22] This is despite following patients for 1 year post-switching. In Canada, Alessi-Severeni and colleagues found no differences in physician visits or hospitalizations when switching outpatients from Clozaril to generic clozapine.[23] In the UK, Paton found no changes in dosing requirements or Clinical Global Impression scores in patients switched to generic clozapine (Zaponex®).[24] In the UK, Bazire and colleagues similarly also found no unexpected relapses or patient complaints over a 6-month period when patients were switched from Clozaril to generic clozapine produced by Denfleet.[25] Consequently, a number of authors have questioned whether any problems actually exist regarding generic clozapine.[25]

The availability of generic olanzapine should benefit governments and health authorities with atypical antipsychotics increasingly prescribed for the management of schizophrenia[26,27,28] despite recent studies suggesting no differences in effectiveness with first-generation antipsychotics and considerably lower costs[29] This represents a growing drug cost burden to the authorities in view of their significantly higher acquisition costs versus first-generation antipsychotics.[27,30,31]

However, there is likely to be uncertainty regarding the effectiveness, safety and compliance with generic olanzapine, especially if each formulation is a different color and tablet shape, as well having different packaging to the originator brand, and different formulations can be dispensed each time. This builds on the concerns with generic drugs for patients with schizophrenia[18,19,20,21] as well as concerns with generic selective serotonin reuptake inhibitors.[15,16,17] There may also be concerns with compliance if patients receive different olanzapine formulations each time they present a prescription to the community pharmacist. This is the situation in Poland, with patients required to pay any difference in price between the reimbursed price for olanzapine and the current product price, which is similar to most EU countries.[10,13,32,33,42] Alongside this, some generic manufacturers do provide additional discounts to pharmacists in Poland to preferentially dispense their branded generic, which can distort copayment levels in practice and the formulation dispensed. This activity by generic manufacturers is again seen in other European countries.[33,34,35,36]

One way to address physician and patient concerns with generic drugs, such as generic olanzapine, will be to stipulate that generic manufacturers must conduct similar efficacy and safety studies to original brand manufacturers for a product license. However this requirement was abolished in the 1980s to encourage a greater number of generics and resultant price competition[37] in view of the costs involved. In addition, in the case of generic olanzapine in Poland, it will be extremely difficult to construct a randomized clinical trial that replicates the different formulations being dispensed in pharmacies with decisions dictated by patients and community pharmacists.

Another way to address possible physician and patient concerns will be to conduct retrospective studies in countries where generic olanzapine is already available, and where there are similar market dynamics to other European countries. Poland provides this opportunity with generic olanzapine available since 2003. In addition, as previously stated patients pay the difference in price between the current reimbursed price for olanzapine and the current product price.

The aim of the retrospective review of patients' notes is to ascertain whether the availability of generic olanzapine is associated with an increase in prescribed doses, side-effects and/or relapse rates in practice versus Zyprexa® (brand name of the original olanzapine). In addition, this article aims to ascertain the extent of potential savings as generic prices fall. Generic risperidone is also available in Poland. However, this study concentrates on olanzapine as there have been supply problems with generic risperidone. This is now resolved with 14 branded generic risperidone formulations currently available in Poland, and will be the subject of future retrospective analyses.

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