Chapter 20 USE OF DRUGS FOR NEUROLOGICAL DISORDER

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1 Chapter 20 USE OF DRUGS FOR NEUROLOGICAL DISORDER Sapiah S. 1, Mohd. Sufian A. 1, Norsima Nazifah S. 2, Nurul Faezah M.Y. 2, Khutrun Nada Z. 1, Md. Hanip M.R Kuala Lumpur Hospital, Kuala Lumpur, 2. Sultanah Nur Zahirah Hospital, Kuala Terengganu Introduction: In 2008, there were four major categories of neurological drugs being analysed. These include the antiepileptics (AEDs), drugs for Parkinson s disease (PD), antimigraine preparations and Central Nervous System (CNS) drugs for other nervous system disorders (drugs mainly used to treat vertigo and motor neuron disease). The later drugs were grouped together as other nervous system drugs. This year we also analysed another group of drug (Interferons-β) which is used to treat multiple sclerosis. AEDs remained the largest group of neurological drugs being dispensed with the total utilisation of DDD/1000 population/day. This can be explained by the used of AEDs for other indications, including neuropathic pain, bipolar affective disorder and generalised anxiety disorder. 1 The second largest drugs being dispensed was antiparkinson drugs (0.8784), other nervous system drugs (0.8247), interferon-β (0.0734) and antimigraine preparations (0.068). Generally there is a significant reduction in the utilisation of AEDs and antimigraine mainly in the private sector while usage in the public sector (MOH, Universities Hospitals and Armed-Forces Hospitals) showed an increment in all group of drugs. The changes in the trend of prescribing were probably contributed by the slow economic growth worldwide in 2008, which also affected Malaysia. Antiepileptics Drugs: Phenytoin was the most commonly prescribed AED with DDD/1000 population/day, followed by valproic acid, carbamazepine, and phenobarbital ( DDD/1000 population/day, DDD/1000 population/day, and DDD/1000 population/day respectively). The utilisations of these older AEDs were lower compared to 2007 due to new trend of management towards usage of new generation of AEDs. The overall dispensing trend for the new generation of AEDs showed reduction in 2008, especially for levetiracetam which showed tremendous reduction ( DDD/1000 population/day) as compared to 2007 ( DDD/1000 population/day) mainly in the private sector ( DDD/1000 population/day and DDD/1000 population/day respective years). However, gabapentin showed a slight increment in utilisation in public sector which is used mainly for neuropathic pain. The reversed trend was observed in the private sector, probably due to the introduction of pregabalin for the same indication. The utilisation of other AEDs such as vigabatrin, oxcarbazepine, ethosuximide and primidone were very low since they were used mainly by the university hospitals and private sectors. Anti-Parkinson Drugs: The five main classes of drugs used for PD are the levodopa (+ peripheral dopamine decarboxylase inhibitors), dopamine agonists (ergot and non-ergot), anticholinergics, adamantane derivatives and the catechol-o-methyltransferase inhibitors. 2 Trihexyphenidyl (Artane) was the most commonly prescribed drug for tremor in PD with It is also widely used for the prevention and treatment of drug-induced extrapyramidal syndrome (EPS). 2 Levodopa and decarboxylase inhibitor persistently remains the gold standard treatment in PD 2 with the usage of DDD/1000 population/day. In 2008, the usage of pramipexole and ropinirole were similar but a huge jump in utilisation of pramipexole was observed compared to 2007; ( DDD/1000 population/day to DDD/1000 population/day). There was remarkable reduction in piribedil; this may be due to the lack of neuroprotective effect compared with non-ergot dopamine agonist. 2 Comparing other enzyme inhibitor groups, selegiline was dispensed more frequently entacapone, DDD/1000 population/day and DDD/1000 population/day, respectively. 123

2 Anti-migraine preparations: The total utilisation of antimigraine preparation in Malaysia was DDD/1000 population/day which showed a reduction compared to utilisation in Flunarizine is the preferred drugs used for prophylaxis of migraine in Malaysia and the utilization in 2008 is DDD/1000 population/day while the usage of pizotifen is DDD/1000population/day. For drugs used in abortive migraine attack, the utilisation of sumatriptan is DDD/1000 population/day. Ergotamine and combination ergotamine utilisation in public sector is generally low but their usage is more preferred in private sector. Ergotamine combination excluding psycholeptics showed a utilisation records of DDD/1000 population/day in private sector compared to only DDD/1000 population/ day in public sector. In general, similar pattern of utilisation for antimigraine preparations can be seen in Australia whereby selective serotonin (5HT 1 ) receptor agonist ranked the highest followed by ergot alkaloids. 3 Other nervous system drugs: Other nervous system drugs: Other nervous system drugs are categorised as parasympathomimetics, antivertigo and riluzole. Parasympathomimetics drugs such as neostigmine and pyridostigmine contributed to 0.1 DDD/1000 population/day. This finding was comparable to Finland statistic at 0.19, suggestive of its low prevalence of Myasthenia Gravis worldwide. 4 In Finland and Australia, the only antivertigo drug listed is betahistine at 2.37 and 24.00, respectively. 3,4 In Malaysia, total utilisation of antivertigo is DDD/1000 population/day with betahistine ranked the highest at DDD/1000 population/day. This indicates that the other two antivertigo preparation, cinnarizine and flunarizine were mainly used for other indication such as antimigraine. Finally, riluzole which is used for motor neuron disease, it usage stands at DDD/1000 population/day in Malaysia compared to Finland and Australia stand at 0.03 and 0.10, respectively. 3,4 Interferon: The immunomodulating drugs, namely Interferon-β 1-a (Rebif) and Interferon-β 1-b (Betaferon) were used in treating Remitting-Relapsing Multiple Sclerosis (RRMS). The total utilisation were and <0.0001DDD/1000 population/day, respectively. There was an increasein utilisation of Rebif by DDD/1000 population/day from 2007 which is due to the inclusion of the drug into the MOH drug formulary. The utilisation of Betaferon was very low because it has not been listed in MOH drug formulary. Table 20.1: Use of Drugs for Neurological Disorder, in DDD/1000 population/day N02C Antimigraine preparations N03 Antiepileptics N04 Anti-parkinson drugs N07 Other nervous system drugs Table 20.2: Use of Anti-Epileptics by Drug Class, in DDD/1000 population/day N03A Antiepileptics N03A A Barbiturates and derivatives N03A B Hydantoin derivatives N03A D Succinimide derivatives < < N03A E Benzodiazepine derivatives N03A F Carboxamide derivatives N03A G Fatty acid derivatives N03A X Other antiepileptics

3 Table 20.3: Use of Anti-Epileptics by Drug Class and Agents, in DDD/1000 population/day N03A A N03A A02 N03A A03 N03A B N03A B02 N03A D N03A D01 N03A E N03A E01 N03A F N03A F01 N03A F02 N03A G N03A G01 N03A G04 N03A X N03A X09 N03A X11 N03A X12 N03A X14 N03A X16 Barbiturates and derivatives Phenobarbital Primidone Hydantoin derivatives Phenytoin Succinimide derivatives Ethosuximide Benzodiazepine derivatives Clonazepam Carboxamide derivatives Carbamazepine Oxcarbazepine Fatty acid derivatives Valproic acid Vigabatrin Other antiepileptics Lamotrigine Topiramate Gabapentin Levetiracetam Pregabalin Public Private Total Public Private < Total Public Private Total Public < < Total < < Public Private Total Public Private Total Public Private Total Public Private Total Public < < Private < Total Public Private Total Public Private Total Public Private Total Public Private Total Public < Private Total

4 Table 20.4: Use of Anti-Parkinson by Drug Class, in DDD/1000 population/day N04A Anticholinergic agents N04A A Tertiary amines N04A C Ethers of tropine or tropine derivatives N04B Dopaminergic agents N04B A Dopa and dopa derivatives N04B B Adamantane derivatives N04B C Dopamine agonists N04B D Monoamine oxidase B inhibitors N04B X Other dopaminergic agents Table 20.5: Use of Anti-Parkinson by Drug Class and Agents, in DDD/1000 population/day N04A A N04A A01 N04A A04 N04A C N04A C01 N04B A N04B A02 N04B A03 N04B B N04B B01 N04B C N04B C01 N04B C02 N04B C04 N04B C05 N04B C08 Tertiary amines Trihexyphenidyl Procyclidine Ethers of tropine or tropine derivatives Benzatropine Dopa and dopa derivatives Levodopa and decarboxylase inhibitor Levodopa, decarboxylase inhibitor and COMT inhibitor Adamantane derivatives Amantadine Dopamine agonists Bromocriptine Pergolide Ropinirole Pramipexole Piribedil Public Private Total Public Private < < Total Public Total Public Private Total Public Private Total Public Private Total Public Private < Total Public - - Total - - Public Private Total Public Private Total Public Private Total

5 N04B D Monoamine oxidase B inhibitors Public N04B D01 Selegiline Private Total N04B X Other dopaminergic agents Public N04B X02 Entacapone Private Total Table 20.6: Use of Antimigraine Preparations by Drugs Class, in DDD/1000 population/day N02C Antimigraine preparations N02C A Ergot alkaloids N02C C Selective serotonin (5HT 1 ) agonists N02C X Other antimigraine preparations Table 20.7: Use of Antimigraine Preparations by Drugs Class and Agents, in DDD/1000 population/day N02C A Ergot alkaloids Public - < N02C A02 Ergotamine Private Total Public N02C A52 Ergotamine, combinations excl. psycholeptics Private Total N02C C Selective serotonin (5HT1) agonists Public N02C C01 Sumatriptan Private Total N02C X Other antimigraine preparations Public N02C X01 Pizotifen Private Total Public - - N02C X02 Clonidine Private < Total < Table 20.8: Use of Other Nervous System Drugs by Drug Class, in DDD/1000 population/day N07A Parasympathomimetics N07A A Anticholinesterases N07C Antivertigo preparations N07C A Antivertigo preparations N07X Other nervous system drugs N07X X Other nervous system drugs

6 Table 20.9: Use of Other Nervous System Drugs by Drug Class and Agents, in DDD/1000 population/day N07A A Anticholinesterases Public N07A A01 Neostigmine Private Total Public N07A A02 Pyridostigmine Private Total Public - - N07A A03 Distigmine Total - - N07C A Antivertigo preparations Public N07C A01 Betahistine Private Total Public N07C A02 Cinnarizine Private Total Public N07C A03 Flunarizine Private Total N07X X Other nervous system drugs Public - < N07X X02 Riluzole Private Total Table 20.10: Use of Interferons by Drug Class and Agents, in DDD/1000 population/day L03A B Interferons Public L03A B07 Interferon beta-1a Private Total Public - < L03A B08 Interferon beta-1b Private < < Total < < References: 1. Epilepsy Council, Malaysian Society of Neurosciences. Malaysian Consensus Guidelines on the Management of Epilepsy Malaysian Parkinson s Disease Association (MPDA). Malaysian Consensus on Parkinson s Disease Australian Government Department of Health and Ageing. Australian Statistics on Medicines Finnish Statistic on Medicine WHO Collaborating Centre for Drug Statistics Methodology, Guidelines for ATC Classification and DDD Assignment Oslo