Availability of essential medicines in Hungary (2017)

Availability of Essential Medicines in Hungary (2017)
Page 1 of 256 © ARETE-ZOE, LLC 2017
Availability of Essential
Medicines in Hungary
ARETE-ZOE, LLC

"We have essentially been avoiding this elephant in the room for the past twenty years, never daring to state
what we know: namely that the use of public healthcare services does not reflect the needs of society, but
rather the interests of the institutional system."
Dr. Zoltán Ónodi-Szűcs, Hungarian Secretary of State for Health (Haynes, 2017)

Executive Summary
This report analyzes availability of essential medicines as defined in the World Health Organization
(WHO) Essential List Medicines (Report of the WHO Expert Committee) in Hungary. The WHO list of essential
medicines contains most effective and safe medicines needed to meet the most important needs in health
systems and is frequently used by countries to create their own national lists. Without these drugs, some
conditions will not be able to receive optimal therapy. Availability gap represents serious public health concern.
Expert Committee of the World Health Organization selects Essential Medicines Lists in accordance with
approved procedures. The Committee evaluates the scientific evidence on the basis of the comparative
effectiveness, safety and cost–effectiveness of the medicines.
The dataset is presented as a summary and then in detail by organ class and ATC subclass as
relevant/appropriate. Focus of the following analysis is on essential medicines that are not available in Hungary,
and evaluation of the situation in the context of public health needs and global drug shortages. To this end, the
Essential List of Medicines defined by the World Health Organization (WHO) is compared to the Substitution List,
which can be found on the website of The National Institute of Pharmacy and Nutrition. Local availability is
expressed as registration, in the form of total number of licensed products, and number of marketed products,
i.e. products that were on the database. The dataset is current as of April 6, 2017. Any revisions to the database
made in the period between data download and publication of this report are not considered. Locally available
products were compared to the WHO list of essential medicines. The material is presented in graphs and
summary tabulations as listed in the table of contents. In Hungary, the most affected groups are anthelmintics,
antiprotozoals, antituberculars and antibiotics.
Essential medicines availability gap represents both public health degradation and risk of harm to
individual patients. Substitutions and second line therapies are often less effective, more toxic, or more
expensive. Improvisation and the use of less familiar medicines lead to medication errors. Mitigation of
shortages and creation of shared contingency supplies puts additional strain on understaffed hospitals. Legal
importation is often bureaucratic and burdensome, and unresponsive to therapeutic necessity. Procurement
rules forced by state budgetary practices such as just-in-time supply chain compound vulnerability to
interruptions. Attempts to obtain essential medications from alternative sources provide opportunity for the
introduction of counterfeit, falsified and substandard drugs into clinical practice. Natural market dynamics will
not make essential medicines available without specific regulatory intervention or concerted advocacy by
caregivers and patients. Europe consists of multiple small disparate national markets with complex regulatory
environment and inconsistently applied and enforced rules that often change in response to political demand.
Systematic mapping of the essential medicines availability gap within public health systems in Europe should be
conducted. The analysis has to include burden of disease, assessment of the ability of individual countries to
cope with existing and newly introduced infectious and parasitic, especially vector-borne diseases, multi-drug
resistant tuberculosis, and increased caseload due to refugees and migrants, and the ability of individual
countries to tackle mass-casualty incidents. Treatment of neglected tropical diseases, multidrug-resistant
tuberculosis and HIV/AIDS can be very expensive, especially if high numbers of people with no health insurance
are concentrated in countries that have limited resources to care for them.

About ARETE-ZOE
ARETE-ZOE, as a consultancy, provides solutions to complex problems in the high stakes and high consequence
environment of Global Pharmaceuticals, including clinical research, healthcare informatics, and public health.
We blend established, Pharma sector methodologies, innovation, and adaptations/transfers from other sectors to identify
and resolve consequential practices that pose risk and often result in avoidable patient casualty. However, we
are specifically, not a patient advocacy group but believe in optimizing organizational effectiveness and that smart business
is agile, competitive and profitable, while intrinsically safe, secure, and resilient.
We work within a global context because transnational interests influence national circumstances and choices at point of
prescription.
ARETE-ZOE provides full spectrum organizational and operational risk management consultancy. Our published materials
provide a glimpse of some aspects of our services to demonstrate both knowledge and ongoing participation within the
Pharmaceutical Industry. Our analysis and consultancy includes all channels of misuse, diversion, counterfeiting and illicit
exploitation of pharmaceuticals, medical devices, and precursor chemicals. Our advisement is to manufactures,
jurisdictional entities, insurers, legislators, litigators, patients, and health care providers.
This scope also frequently segues into the nexus of crime and terrorism as significant influencers that undermine sector
integrity differentiated from other criminal activity. Obviously, vulnerability assessment, information collection
management and intelligence production supporting decision-making for risk reduction and interventions are routinely
within the scope of our services as well as design and implementation of operational control measures.

TABLE OF CONTENTS
Executive Summary..................................................................................................................................................3
About ARETE-ZOE.....................................................................................................................................................4
Table of Contents.....................................................................................................................................................5
The Situation in Hungary.....................................................................................................................................14
Analysis and Interpretation....................................................................................................................................16
Relevance of unavailability of essential medicines for health care systems ..........................................................19
Appendices ............................................................................................................................................................20
Analysis and Interpretation: Breakdown by System Organ Class......................................................................21
Alimentary tract and metabolism ..........................................................................................................................21
Cardiovascular system ...........................................................................................................................................28
Dermatologicals.....................................................................................................................................................31
Genito-urinary products and sex hormones...........................................................................................................34
Hormones for systemic use, excluding sex hormones and insulins........................................................................35
Antiinfectives for systemic use ..............................................................................................................................36
Antineoplastic products.........................................................................................................................................48
Musculoskeletal system.........................................................................................................................................51
Nervous system .....................................................................................................................................................53
Antiparasitics.........................................................................................................................................................54
Respiratory system ................................................................................................................................................62
Sensory organs.......................................................................................................................................................63
Various...................................................................................................................................................................65
Conclusion..............................................................................................................................................................67
Abbreviations and Legend......................................................................................................................................69
APPENDIX 1 Availability of essential medicines in Hungary ............................................................................70
FIG. 1 - Summary (table): Availability of essential medicines by organ class..........................................................70
FIG. 2 – Summary (graph): Essential medicines lists by organ class........................................................................71
FIG. 3 – Summary (graph): Availability of essential medicines lists by organ class.................................................72
Alimentary Tract and Metabolism (A) ................................................................................................................73
FIG. 5 – Summary (graph): Availability of registered products (A) – National EM List............................................74

FIG. 6 – Summary (graph): Availability of registered products (A) – WHO EM List and National EM List
combined...............................................................................................................................................................75
FIG 7 – Stomatologicals (A01) and Acid related disorders (A02).............................................................................76
FIG. 8 – Drugs for functional GIT disorders (A03), antiemetics and antinauseants (A04) .......................................76
FIG. 9 – Bile and liver therapy (A05), drugs for constipation (A06), anti-diarrheals (A07)......................................77
FIG. 10 – Anti-obesity drugs (A08) and digestives incl. enzymes (A09)...................................................................77
FIG. 11 – Drugs used in diabetes (A10)...................................................................................................................78
FIG. 12 - Vitamins (A11) .........................................................................................................................................78
FIG. 13 - Mineral supplements (A12), other alimentary tract & metabolism drugs (A16) ......................................79
Blood and Blood-forming organs (B)...................................................................................................................80
FIG. 14 – Summary (graph): Availability of registered products (B) – WHO EM List and National EM List
combined...............................................................................................................................................................80
FIG 15 - Anti-thrombotic agents (B01)....................................................................................................................81
FIG 16 – Anti-hemorrhagics (B02)...........................................................................................................................81
FIG 17 – Anti-anemic preparations (B03) ...............................................................................................................82
FIG 18 – Blood substitutes and perfusion solutions (B05) ......................................................................................82
Cardiovascular system (C) ...................................................................................................................................83
FIG 19 – Summary (graph): Availability of registered products (C) – WHO EM List ................................................83
FIG. 20A – Summary (graph): Availability of registered products (C) – National EM List........................................84
FIG. 20B – Summary (graph): Availability of registered products (C) – National EM List ........................................85
FIG. 20C – Summary (graph): Availability of registered products (C) – National EM List ........................................86
FIG. 20D – Summary (graph): Availability of registered products (C) – National EM List........................................87
FIG. 21A – Summary (graph): Availability of registered products (C) – WHO EM List and National EM List
combined...............................................................................................................................................................88
FIG. 21B – Summary (graph): Availability of registered products (C) – WHO EM List and National EM List
combined...............................................................................................................................................................89
FIG. 21C – Summary (graph): Availability of registered products (C) – WHO EM List and National EM List
combined...............................................................................................................................................................90
FIG. 22 - Cardiac therapy (C01)...............................................................................................................................91
FIG. 23 - Antihypertensives (C02)...........................................................................................................................92
FIG. 24 – Diuretics (C03) and peripheral vasodilatators (C04) ................................................................................92
FIG. 25 – Vasoprotectives (C05) and beta-blocking agents (C07)............................................................................93
FIG. 26 - Calcium-channel blockers (C08) ...............................................................................................................94

FIG. 27 - Renin-angiotensin system: ACE inhibitors (C09A) ....................................................................................94
FIG. 28 - Renin-angiotensin system: ACE inhibitors in combinations (C09B) ..........................................................95
FIG. 29 - Renin-angiotensin system: Angiotensin II antagonists (C09C)..................................................................95
FIG. 30 - Renin-angiotensin system: Angiotensin II antagonists in combinations (C09D) .......................................96
FIG. 31 - Lipid modifying agents (C10)....................................................................................................................97
Dermatologicals (D)..............................................................................................................................................98
FIG. 32 – Summary (graph): Availability of registered products (D) – WHO EM List...............................................98
FIG. 33 – Summary (graph): Availability of registered products (D) – National EM List..........................................99
FIG. 34 – Summary (graph): Availability of registered products (D) – WHO EM List and National EM List
combined.............................................................................................................................................................100
FIG. 35 - Antifungals for dermatological use (D01)...............................................................................................101
FIG. 36 - Emollients and protectives (D02), antipsoriatics (D05) and antibiotics and chemotherapeutics for
dermatological use (D06).....................................................................................................................................101
FIG. 37 – Corticosteroids for dermatological use (D07) ........................................................................................102
FIG. 38 – Antiseptics and disinfectants (D08) .......................................................................................................102
FIG. 39 – Anti-acne preparations (D10) ................................................................................................................103
Genito-urinary system and sex hormones (G) ...................................................................................................104
FIG. 40 – Summary (graph): Availability of registered products (G) – WHO EM List.............................................104
FIG. 41 – Summary (graph): Availability of registered products (G) – National EM List........................................105
FIG. 42 – Summary (graph): Availability of registered products (G) – WHO EM List and National EM List
combined.............................................................................................................................................................106
FIG. 43 - Antiinfectives and antiseptics (G01), other gynecologicals (G02)...........................................................107
FIG. 44 – Hormonal contraceptives for systemic use: Progestogens and estrogens, fixed combinations (G03AA)108
FIG. 45 – Hormonal contraceptives for systemic use: Progestogens and estrogens, sequential preparations
(G03AB)................................................................................................................................................................108
FIG. 46 –Progestogens (G03AC) and emergency contraceptives (G03AD) ............................................................109
FIG. 47 – Androgens (G03B), estrogens (G03C), progestogens (G03D) androgens and female hormones comb.
(G03E), and progestogens and estrogens comb. (G03F).......................................................................................110
FIG. 48 – Gonadotropins and other ovulation stimulants (G03G), antiandrogens (G03H) and other sex
hormones and modulators of the genital system (G03X).....................................................................................110
FIG. 49 – Urologicals (G04)...................................................................................................................................111
Hormones for systemic use, excl. sex hormones and insulins (H)......................................................................112

FIG. 50 – Summary (graph): Availability of registered products (H) – WHO EM List and National EM List
combined.............................................................................................................................................................112
FIG. 51 – Pituitary and hypothalamic hormones and analogues (H01), corticosteroids for systemic use (H02) ...113
FIG. 52 – Thyroid therapy (H03), pancreatic hormones (H04), calcium homeostasis (H05) ..................................113
Antiinfectives for systemic use (J)......................................................................................................................114
FIG. 53 – Summary (graph): Availability of registered products (J) – WHO EM List (values <4 included in table
56C)......................................................................................................................................................................114
FIG. 54 – Summary (graph): Availability of registered products (J) – National EM List.........................................115
FIG. 55A – Summary (graph): Availability of registered products (J) – WHO EM List and National EM List
combined.............................................................................................................................................................116
FIG. 55B – Summary (graph): Availability of registered products (J) – WHO EM List and National EM List
combined.............................................................................................................................................................117
FIG. 55C – Summary (table): Availability of registered products (J) – WHO EM List and National EM List
combined.............................................................................................................................................................118
FIG. 56 - Antibacterials (J01): Tetracyclines (J01A) amphenicols (J01B)................................................................120
FIG. 57 - Antibacterials (J01): Beta-lactams – penicillins (J01C)............................................................................120
FIG. 58 - Antibacterials (J01): Beta-lactams – non-penicilline (J01D)....................................................................121
FIG. 59 - Antibacterials (J01): Sulphonamides and trimethoprim (J01E) and macrolides, linkosamides and
streptogramins (J01F) ..........................................................................................................................................121
FIG. 60 - Antibacterials (J01): Aminoglycosides (J01G) .........................................................................................122
FIG. 61 - Antibacterials (J01): Quinolones (J01M).................................................................................................122
FIG. 62 - Antibacterials (J01): Other antibacterials (J01X) ....................................................................................123
FIG. 63 – Antimycotics for systemic use (J02).......................................................................................................123
FIG. 64A – Antimycobacterials (J04): Tuberculosis (J04A) ....................................................................................124
FIG. 64B – Antimycobacterials (J04) Tuberculosis (J04A) and leprosy (J04B)........................................................124
FIG. 65 – Antivirals for systemic use (J05): Nucleosides and nucleotides excl. reverse transcriptase inhibitors
(J05AB) and Protease inhibitors (J05AE) ..............................................................................................................125
FIG. 66 – Antivirals for systemic use (J05): Nucleoside and nucleotide reverse transcriptase inhibitors (J05AF),
Non-nucleoside reverse transcriptase inhibitors (J05G) and Neuraminidase inhibitors (J05AH)..........................126
FIG. 67 – Antivirals for systemic use (J05): Antivirals for treatment of HIV infections, combinations (J05AR) and
Other antivirals (J05AX) .......................................................................................................................................126
FIG. 68 – Immune sera and immunoglobulins (J06)..............................................................................................127
FIG. 69A – Vaccines (J07): Bacterial vaccines (J07A).............................................................................................128
FIG. 69B – Vaccines (J07): Bacterial vaccines (J07A) .............................................................................................128

FIG. 70A – Vaccines (J07): Viral vaccines (J07B)....................................................................................................129
FIG. 70B– Vaccines (J07): Viral vaccines (J07B).....................................................................................................129
FIG. 70C– Vaccines (J07): Viral vaccines (J07B).....................................................................................................130
FIG. 71 – Vaccines (J07): Bacterial and viral vaccines combined (J07C) ................................................................131
Antineoplastic and immunomodulating agents (L)............................................................................................132
FIG. 72A – Summary (graph): Availability of registered products (L) – WHO EM List ...........................................132
FIG. 72B – Summary (graph): Availability of registered products (L) – WHO EM List............................................133
FIG. 73 – Summary (graph): Availability of registered products (L) – National EM List.........................................134
FIG. 74A – Summary (graph): Availability of registered products (L) – WHO EM List and National EM List
combined.............................................................................................................................................................135
FIG. 74B – Summary (graph): Availability of registered products (L) – WHO EM List and National EM List
combined.............................................................................................................................................................136
FIG. 74C – Summary (graph): Availability of registered products (L) – WHO EM List and National EM List
combined.............................................................................................................................................................137
FIG. 75 - Antineoplastic agents (L01): Alkylating agents (L01A)............................................................................138
FIG. 76 - Antineoplastic agents (L01): Antimetabolites (L01B)..............................................................................138
FIG. 77 - Antineoplastic agents (L01): Plant alkaloids and other natural products (L01C) ....................................139
FIG. 78 - Antineoplastic agents (L01): Cytotoxic antibiotics & related substances (L01D) ....................................139
FIG. 79 - Antineoplastic agents (L01): Other antineoplastic agents (L01X) ...........................................................140
FIG. 80 – Endocrine therapy (L02) ........................................................................................................................141
FIG. 81 – Immunostimulants (L03) .......................................................................................................................141
FIG. 82 - Immunosuppressants (L04)....................................................................................................................142
Musculo-skeletal system (M)..............................................................................................................................143
FIG. 83 – Summary (graph): Availability of registered products (M) – WHO EM List ............................................143
FIG. 84 – Summary (graph): Availability of registered products (M) – National EM List.......................................144
FIG. 85 – Summary (graph): Availability of registered products (M) – WHO EM List and National EM List
combined.............................................................................................................................................................145
FIG. 86 – Musculoskeletal system (M): Anti-inflammatory and anti-rheumatic products (M01)..........................146
FIG 87 – Musculoskeletal system (M): Topical products for joint and muscular pain (M02), muscle relaxants
(M03) ...................................................................................................................................................................146
FIG. 88 – Musculoskeletal system (M): Anti-gout preparations (M04), drugs for the treatment of bone diseases
(M05) ...................................................................................................................................................................147
Nervous system (N).............................................................................................................................................148

FIG. 89A – Summary (graph): Availability of registered products (N) – WHO EM List...........................................148
FIG. 89B – Summary (graph): Availability of registered products (N) – WHO EM List...........................................149
FIG. 90A – Summary (graph): Availability of registered products (N) – National EM List .....................................150
FIG. 90B – Summary (graph): Availability of registered products (N) – National EM List......................................151
FIG. 90C – Summary (graph): Availability of registered products (N) – National EM List......................................152
FIG. 91A – Summary (graph): Availability of registered products (N) – WHO EM List and National EM List
combined.............................................................................................................................................................153
FIG. 91B – Summary (graph): Availability of registered products (N) – WHO EM List and National EM List
combined.............................................................................................................................................................154
FIG. 91C – Summary (graph): Availability of registered products (N) – WHO EM List and National EM List
combined.............................................................................................................................................................155
FIG. 91D – Summary (graph): Availability of registered products (N) – WHO EM List and National EM List
combined.............................................................................................................................................................156
FIG. 92 – Anesthetics (N01): General anesthetics (N01A).....................................................................................157
FIG. 93 – Anesthetics (N01): Local anesthetics (N01B) .........................................................................................157
FIG. 94 – Analgesics (N02): Opioids (N02A)..........................................................................................................158
FIG. 95 – Analgesics (N02): Other analgesics and antipyretics (N02B) and antimigraine products (N02C) ...........158
FIG. 96 – Antiepileptics (N03)...............................................................................................................................159
FIG. 97 – Anti-Parkinson drugs (N04) ...................................................................................................................160
FIG. 98 – Psycholeptics (N05): Antipsychotics (N05A) ..........................................................................................161
FIG. 99 – Psycholeptics (N05): Anxiolytics (N05B) ................................................................................................162
FIG. 100 – Psycholeptics (N05): Hyponotics and sedatives (N05C) .......................................................................162
FIG. 101 – Psychoanaleptics (N06): Antidepressants (N06A)................................................................................163
FIG. 102 – Psychoanaleptics (N06): Psychostimulants, agents used for ADHD and nootropics (N06B) and anti-
dementia drugs (N06D)........................................................................................................................................164
FIG. 103 – Other nervous system drugs (N07): Parasympathomimetics (N07A), drugs used in addictive
disorders (N07B), anti-vertigo preparations (N07C) and other (N07X).................................................................164
Antiparasitic products, insecticides and repellents (P)......................................................................................165
FIG. 104 – Summary (graph): Availability of registered products (P) – WHO EM List and National EM List
combined.............................................................................................................................................................165
FIG. 105 – Antiparasitics, insecticides and repellents (P): Antiprotozoals (P01), anthelmintics (P02) and
ectoparasiticides (P03).........................................................................................................................................165
FIG. 106 – Antiparasitics, insecticides and repellents (P): Antiprotozoals (P01), anthelmintics (P02) and
ectoparasiticides (P03).........................................................................................................................................166

Respiratory system (R).......................................................................................................................................167
FIG. 107 – Summary (graph): Availability of registered products (R) – WHO EM List and National EM List
combined.............................................................................................................................................................167
FIG. 108 – Summary (graph): Availability of registered products (R) – WHO EM List and National EM List
combined.............................................................................................................................................................168
FIG. 109 – Respiratory system (R): Nasal preparations (R01) ...............................................................................169
FIG. 110 – Respiratory system (R): Throat preparations (R02) and drugs for obstructive airway diseases (R03)..169
FIG. 111 – Respiratory system (R): Cough and cold preparations (R05)................................................................170
FIG. 112 – Respiratory system (R): antihistamines for systemic use (R06) and other respiratory system
products (R07)......................................................................................................................................................170
Sensory organs (S) ..............................................................................................................................................171
FIG. 113 – Summary (graph): Availability of registered products (S) – WHO EM List and National EM List
combined.............................................................................................................................................................171
FIG. 114 – Ophthalmologicals (S01): Antiinfectives (S01A)...................................................................................172
FIG. 115 – Ophthalmologicals (S01): Antiinflammatory agents (S01B), Antiinflammatory angents and
antiinfectives in combination (S01C), antiglaucoma preparations and miotics (S01E) .........................................173
FIG. 116 – Ophthalmologicals (S01): Mydriatics and cycloplegics (S01F), decongestants and antiallergics
(S01G), local anesthetics (S01H), and diagnostic agents (S01J) ............................................................................174
Various (V)..........................................................................................................................................................175
FIG. 117 – Summary (graph): Availability of registered products (V) – WHO EM List and National EM List
combined.............................................................................................................................................................175
FIG. 118 – Various (V): All other therapeutic products (V03)................................................................................176
FIG. 119 – Various (V): Diagnostic agents (V04), all other non-therapeutic products (V07) and contrast media
(V08) ....................................................................................................................................................................177
APPENDIX 2 Essential medicines (WHO EML) not registered in Hungary ...................................................178
FIG. 120 - Alimentary tract and metabolism (A)...................................................................................................178
FIG. 121 - Blood and blood forming organs (B).....................................................................................................178
FIG. 122 - Cardiovascular system (C) ....................................................................................................................178
FIG. 123 - Dermatologicals (D)..............................................................................................................................179
FIG.124 - Genito-urinary system and sex hormones (G).......................................................................................179
FIG. 125 - Systemic hormonal preparations, excl. sex hormones and insulins (H)................................................179
FIG. 126 - Antiinfectives for systemic use (J) ........................................................................................................180
FIG. 127 - Antineoplastic and immunomodulating agents (L)...............................................................................181

FIG. 128 - Musculo-skeletal system (M) ...............................................................................................................181
FIG. 129 - Nervous system (N)..............................................................................................................................181
FIG 130 - Antiparasitic products, insecticides and repellents (P)..........................................................................182
FIG. 131 - Respiratory system (R) .........................................................................................................................183
FIG. 132 - Sensory organs (S)................................................................................................................................183
FIG. 133 - Various (V) ...........................................................................................................................................183
APPENDIX 3 Essential medicines unavailable in Hungary (not registered)....................................................184
FIG. 134 - Alimentary tract and metabolism (A)...................................................................................................184
FIG. 135 - Blood and blood forming organs (B).....................................................................................................185
FIG. 136 - Cardiovascular system (C) ....................................................................................................................186
FIG. 137 - Dermatologicals (D)..............................................................................................................................187
FIG. 138 - Genito-urinary system and sex hormones (G)......................................................................................188
FIG. 139 - Antiinfectives for systemic use (J) ........................................................................................................189
FIG. 140 - Antineoplastic and immunomodulating agents (L)...............................................................................193
FIG. 141 - Musculo-skeletal system (L).................................................................................................................194
FIG. 142 - Nervous system (N)..............................................................................................................................195
FIG. 143 - Antiparasitic products, insecticides and repellents (P).........................................................................196
African Trypanosomiasis (Sleeping Sickness).........................................................................................................197
FIG. 144 - Respiratory system (R) .........................................................................................................................199
FIG. 145 - Sensory organs (S)................................................................................................................................200
FIG. 146 - Various (V) ...........................................................................................................................................201
APPENDIX 4 – Shortages of essential medicines in Hungary by system organ class.......................................202
FIG. 147 – Alimentary tract and metabolism (A) ..................................................................................................202
FIG. 148A – Blood and blood forming organs (B)..................................................................................................203
FIG. 148B – Blood and blood forming organs (B)..................................................................................................204
FIG. 148C – Blood and blood forming organs (B)..................................................................................................205
FIG. 148D – Blood and blood forming organs (B) .................................................................................................206
FIG. 149A – Cardiovascular system (C) .................................................................................................................207
FIG. 149B – Cardiovascular system (C) .................................................................................................................208
FIG. 149C – Cardiovascular system (C)..................................................................................................................209
FIG. 150 – Dermatologicals (D).............................................................................................................................210
FIG. 151 – Genito-urinary system and sex hormones (G) .....................................................................................211

FIG. 152 – Systemic hormonal preparations, excl. sex hormones and insulins (H)...............................................212
FIG. 153A – Antiinfectives for systemic use (J) .....................................................................................................213
FIG. 153B – Antiinfectives for systemic use (J) .....................................................................................................214
FIG. 153C – Antiinfectives for systemic use (J) .....................................................................................................215
FIG. 153D – Antiinfectives for systemic use (J).....................................................................................................216
FIG. 153E – Antiinfectives for systemic use (J)......................................................................................................217
FIG. 153F – Antiinfectives for systemic use (J)......................................................................................................218
FIG. 153G – Antiinfectives for systemic use (J).....................................................................................................219
FIG. 153H – Antiinfectives for systemic use (J).....................................................................................................220
FIG. 153I – Antiinfectives for systemic use (J) ......................................................................................................221
FIG. 154A – Antineoplastic and immunomodulating agents (L)............................................................................222
FIG. 154B – Antineoplastic and immunomodulating agents (L)............................................................................223
FIG. 154C – Antineoplastic and immunomodulating agents (L)............................................................................224
FIG. 154D – Antineoplastic and immunomodulating agents (L) ...........................................................................225
FIG. 154E – Antineoplastic and immunomodulating agents (L)............................................................................226
FIG. 154F – Antineoplastic and immunomodulating agents (L) ............................................................................227
FIG. 154G – Antineoplastic and immunomodulating agents (L) ...........................................................................228
FIG. 155 – Musculo-skeletal system (L) ................................................................................................................229
FIG. 156A – Nervous system (N)...........................................................................................................................230
FIG. 156B – Nervous system (N)...........................................................................................................................231
FIG. 156C – Nervous system (N) ...........................................................................................................................232
FIG. 156D – Nervous system (N)...........................................................................................................................233
FIG. 156E – Nervous system (N) ...........................................................................................................................234
FIG. 157 – Antiparasitic products, insecticides and repellents (P) ........................................................................235
FIG. 158 – Respiratory system (R) ........................................................................................................................236
FIG. 159 – Sensory organs (S) ...............................................................................................................................237
FIG. 160 – Various (V)...........................................................................................................................................238
FIG. 161 – Number of products in shortage by inclusion in EMLs.........................................................................239
BIBLIOGRAPHY...............................................................................................................................................240

The Situation in Hungary
The World Health Organization (WHO) considers 427 drugs essential for health system, 301 are
registered in Hungary and 121 (28%) are unavailable due to no registration. All 346 active ingredients listed in
the Substitution List are available in at least one formulation. The two lists partially overlap: 83 ATC codes are
included in both lists. Summary comparison of the WHO EML and the National Substitution List by system organ
class is available in Appendix 1, Figure 1. The worst affected systems are antiparasitics (81% of the WHO EML
unavailable), dermatologicals (48%), Various (43%), Genito-urinary system (42%) and antiinfectives (30%). The
data is presented in detail in Appendix 1. The worst affected therapeutic groups are antimalarial medications,
anthelmintics, second-line antituberculars, antibiotics, dermatologicals and antidotes. Significant number of
essential medicines unavailable locally overlaps with medicines that are in periodic or chronic global shortage,
and those for the treatment of disorders that are uncommon in the area. Examples of the most significant global
shortages of essential medicines are presented in the context of local availability gap. Hungary is a small market
with low price levels and complex regulatory environment and inconsistently applied and enforced rules.
Alternative sources of registered medications currently include parallel import from other EU countries.
Attempts to obtain essential medications from alternative sources provide opportunity for the introduction of
counterfeit, falsified and substandard drugs into clinical practice. In April 2017, the Minister of Human Resources
Zoltán Balog discussed the complex situation in Hungarian healthcare industry in thorough detail. The interview
was published in The Budapest Times. Minister Balog, who has been leading the ministry since 2012, stressed
the importance of structural changes in healthcare in order to make the system economically feasible without
sacrificing health of the population. The new ministry employs about 3.000 staff members and integrates health
and healthcare, education, family and social affairs, health and pension insurance as well as some research
institutions. Some of the priorities of the government are the integration of the Roma minority and the
improvement of German-Hungarian relations (Mainka, 2017). According to PharExec, vast majority of
stakeholders agree that Hungarian system remains severely underfinanced even when compared to its
neighbors in Central and Eastern Europe. The system is perceived as overburdened, inefficient, and worse than
it used to be. Hungarian pharmaceutical industry enjoys a good reputation due to its ability to offer the same
products as in more advanced economies, due to its contribution to the national economy, and investment in
innovation. The sector employs over 14.000 people and delivers 5% of national GPD. As of 2016, the highest
sellers in Hungary are Novartis, Egis, Sanofi-Aventis, Roche, Gedeon-Richter, Pfizer, TEVA, Johnson & Johnson,
MSD Corp., and AbbVie. Under the previous government, in 2011, the industry had to put up with 30% drop in
pharmaceutical spending, in addition competitive taxation and a blind-bidding mechanism, measures that
collectively led to decrease in prices of medicines. Local manufacturing was also affected by decreased
consumption in its traditional markets because of the Russian invasion in Ukraine. As in other post-communist
states, chronic underfinancing is a major problem of Hungarian healthcare system. Communist legacy manifests
in a passive and paternalistic relationship between doctors and their patients, and many believe that this
obligation to improve health literacy of the population belongs to the pharmaceutical industry. Hungarian health
insurance system accounts for all health situations, from outpatient care and drug reimbursement to hospital
stay, including innovative oncology therapies (Pharmaceutical Executive Editors, 2017).

• Of the 427 essential drugs, 301 are registered in Hungary, and 121 (30%) are unavailable.
Detailed breakdown of registered, marketed and unavailable essential medicines can be
found in Summary table and Summary graph in Appendix 1.
• Most affected classes are antiparasitic medications, dermatologicals, drugs against
tuberculosis and HIV/AIDS, and antibacterials. Full breakdown of registered and marketed
essential medications can be found in Appendix 1.
• The reason for local unavailability is the fact that these drugs are not registered locally. For
list of essential medicines, that are unavailable in Hungary, refer to Appendix 2.
• Unavailable essential medicines overlap with drugs that are chronic or periodic shortage
globally.
• Many essential medicines that are not available locally are only needed in limited amounts in
specific situations, making them economically unattractive for businesses to pursue local
registration and marketing.

Analysis and Interpretation
Global concern: Drug shortages of essential medicines have existed for more than a decade. The issue
affects all countries around the globe, developed and developing alike, not just Hungary. Essential medicines,
with a few exceptions, are off-patent generic formulations that are relatively inexpensive to buy but not
necessarily easy to make. Generic status of these medicines leaves them open to competition and reduces
return on investment. In manufacturing practice, inexpensive generic formulations are less likely to be
emphasized because of competition over equipment and prioritization of products that provide higher return on
investment. Market prices are pushed down further by hospital procurement systems that have to prioritize low
cost over any other criteria at all times. In clinical practice, essential medicines are difficult or impossible to
replace. Proprietary solutions are usually less effective, more toxic, and/or more costly. Pharmaceutical industry
has experienced profound change since the 1980s. The current geography of pharmaceutical manufacturing and
markets is the result of long-term trends: industry consolidation through acquisition and mergers, globalization,
and outsourcing of key operations to low cost regions. Physical location of manufacturing does not necessarily
correlate with corporate headquarters; in fact, many raw materials are now produced solely in Asia. Essential
medicines most affected by global shortages are parenteral nutrition components, sterile injectable drugs,
antibacterials, and front line tuberculosis therapy, drugs for the treatment of HIV/AIDS, immune sera and
immunoglobulins, tuberculin, vaccines, oncology drugs, anesthetics, sedatives, anti-malarial drugs, and anti-
parasitic medications. Additional concerns include sudden price hikes following acquisition and consequent
rebranding of generic products, as well as for profit adulteration (heparin).
Local impact: In addition to limited global availability of these drugs, it may be difficult for Hungary to
find a supplier for other reasons as well. The main reasons are low profit margin, low price level for
pharmaceuticals due to authorized reimbursement rates as cost controls, and monetary inducements to
prescribe more expensive medicines. Reduced incident rate for demand as originally developed, however, is
relevant for contemporary combination therapies, which makes unavailability more problematic.
Pharmaceutical manufacturers tend to prioritize bigger markets where detailed contractual obligations apply.
Complex regulatory environment, inconsistent and unpredictable enforcement, administration overresponsive
to political pressures, and complicated procurement compound the problem. Some essential medicines are
available in other EU countries from which they could be obtained through parallel import. Only two essential
medicines, IMPLANON (etonorgestrel) and OKRIDO (prednisolone) are available through the EU centralized
registration process (European Commission, 2017), which means all the other unavailable essential medicines
have to be acquired through a more byzantine acquisition path. EudraPharm (EudraPharm, 2017) database has
been established to fulfil Articles 57(1)(l) and 57(2) of Regulation (EC) No 726/2004. EudraPharm is intended to
be a source of information on all medicinal products for human or veterinary use that have been authorised in
the European Union (EU) and the European Economic Area (EEA) and information on clinical trials. The database,
however only includes data entered by Portugal and the European Commission.
Root causes: Main causes of global drug shortages are consolidation of the industry, lack of competition
due to suppliers exiting the market, and monopolization. Additional causes identified in various industry
analyses are low profit margin, production issues, and raw material availability. In addition, regulatory actions

against manufacturers that fail to comply with good manufacturing practice and occasional import bans may
force significant investment in modernization of production or business decision to exit the market. Business
decisions to discontinue products for which there is low or unpredictable demand and reallocation of resources
to prioritize products with higher return on investment compound the problem. This creates conditions that are
exploited by counterfeiters. U.S. Government Accountability Office (GAO) Report to Congress (2016) highlighted
the fact that many manufacturers had a long history of manufacturing compliance failures, and that declining
number of suppliers was more likely to lead to shortage of drugs on the market. In addition, due to low profit
margins of generic drugs, and especially sterile injectable formulations, manufacturers were less likely to
increase production to meet market demand (United States Government Accountability Office, 2016). Due to
the fact that natural market forces are unlikely to reduce the shortfall, government intervention may be
necessary to ensure supply availability. Canadian report on drug shortages identified additional causes of
increased demand: new indication for a generic drug, changes in guidelines, or disease outbreaks often result in
inability of production to keep pace, especially if the manufacturing process is lengthy and complicated by
multiple sourcing of raw materials. Business decisions to discontinue certain drugs or reallocation of resources
and production capacity have the same effect. Regulatory requirements, import bans and expenses required to
remedy them are another common cause of drug shortages and discontinuations. Additional problems include
the fact that many manufacturers are located in countries that have less stringently enforced safety and
regulatory standards. Quality controls become more challenging because raw materials may be imported from a
third party. Finally, communication of upcoming shortages is essential to mitigate their impact (The Multi-
stakeholder steering Committee on drug shortages in Canada, 2017). Major drug producing countries like China
are not spared, either. According to survey conducted in Shaanxi province, 8 traditional Chinese medicines and
87 types of biologicals and chemicals were reported to be in short supply, most of them essential medicines. The
main determinants identified by the authors were low prices, low market demand, Good Manufacturing Practice
(GMP) issues, materials issues, and regulatory hurdles for imported drugs (Yang et al., 2016).
Counterfeit, falsified and substandard medications: Whilst producers of counterfeit products mainly
focus on lifestyle drugs and common drugs of abuse that are easy to sell through illicit channels, such as erectile
dysfunction medications, benzodiazepines, steroids or anti-obesity drugs, essential medicines are now also
increasingly found on the black market (Ossola, 2015). Europol in its 2016 report on counterfeiting in the
European Union considers fake pharmaceuticals a major hazard (Europol, 2015). The most common findings are
cancer drugs, anti-infectives such as treatments for HIV/AIDS (Safe Medicines, 2017), tuberculosis, or common
antibiotics, and anti-malarials (Kelesidis, & Falagas, 2015), but also diabetes medications and others. Although
counterfeit anti-infective and anti-parasitic drugs are traditionally a problem in Africa and Asia (Almuzaini,
Choonara, & Sammons, 2013), they are now reaching Europe as well. Security and integrity of pharmaceutical
supply chain in Europe made significant progress due to Falsified Medicines Directive and obligatory safety
features on pharmaceutical packaging. However, many of these measures have yet to be implemented
(European Medicines Agency, 2017). Currently, the main concerns in U.S. and European hospital supply chains
are cancer drugs (Europol, 2017) and (Campbell, 2017). In 2012, counterfeit bevacizumab reached U.S. cancer
patients (FDA, 2017), and in 2014, EMA warned against counterfeit Herceptin (Johnson, 2014).

Consequences: Essential medicines availability gap represents both public health degradation and risk of
harm to individual patients. Substitutions and second line therapies are often less effective, more toxic, or more
expensive. Improvisation and the use of less familiar medicines lead to medication errors. Mitigation of
shortages and creation of shared contingency supplies puts additional strain on understaffed hospitals.
However, unavailability inflicts social stress from patients’ and physicians’ frustration, anger and feeling of
helplessness. Drug unavailability makes it impossible to follow evidence-based practice guidelines, and force
consequential decisions to prioritize certain group of people over another. Public health concerns arise due to
inability to prevent and treat contagious diseases such as tuberculosis. Significant resources have to be
dedicated to overseeing and managing the situation at government and supranational level. Legal importation is
often bureaucratic and burdensome, and unresponsive to therapeutic necessity. Procurement rules forced by
state budgetary practices such as just-in-time supply chain compound vulnerability to interruptions. Attempts to
obtain essential medications from alternative sources provide opportunity for the introduction of counterfeit,
falsified and substandard drugs into clinical practice. Natural market dynamics will not make essential medicines
available without specific regulatory intervention or concerted advocacy by caregivers and patients.
Suggested solution: Europe consists of multiple small disparate national markets with complex
regulatory environment and inconsistently applied and enforced rules that often change in response to political
demand. Systematic mapping of the essential medicines availability gap within public health systems in Europe
should be conducted. The analysis has to include burden of disease, assessment of the ability of individual
countries to cope with existing and newly introduced infectious and parasitic, especially vector-borne diseases,
multi-drug resistant tuberculosis, and increased caseload due to refugees and migrants, and the ability of
individual countries to tackle mass-casualty incidents. Needs analysis has to include definition of treatment
standards for specific conditions and availability of essential medicines at national level in line with these
guidelines. Although national registrations in Europe should be available through EudraPharm, the database
does not contain the necessary data to be useful. Shortages in Europe are poorly mapped at supranational level.
Treatment of neglected tropical diseases, multidrug-resistant tuberculosis and HIV/AIDS can be very expensive,
especially if high numbers of people with no health insurance are concentrated in countries that have limited
resources to care for them. The last mile obstructions may be due to social upheaval that obstructs the access to
the point of need. Analysis and solution development must extend beyond simply connecting the dots in the
logistical framework. The objective shall be to identify needs that require supranational coordination and
solution, such as a shared procurement system for essential medicines that are needed in low and unpredictable
amounts, and the definition of requirements for transnational emergency stockpiles. The objective shall be to
identify opportunities to optimize established information management systems that emphasize the reduction
of these gaps in essential medicines availability necessary to enable pooling demand, regionally shared
procurement of essential medicines, and their supply on as needed basis for both national domestic populations
and for uninsured/transient populations.

Relevance of unavailability of essential medicines for health care systems
Clinical Practitioners
Inability to follow evidence-based guidelines forces the use of alternatives.
Alternative and second line therapies are often less effective, more toxic, or more expensive.
Improvisation and use of less familiar products leads to medication errors.
Off-label use of familiar drugs affects treatment outcome, and introduces additional liabilities.
Frustration, anger, feeling of helplessness strains professional relationships and stalls collaboration.
Consequential decisions have to be made to prioritize certain group of people over another.
Pharmacists
Mitigation of shortages and communication with hospitals and practitioners adds to staff workload
Not all products can be adequately replaced
Search for legal import options is bureaucratic and labor intensive, slow, and labor intensive
Expensive and rarely used alternative treatment options introduce additional potential liabilities
Individual Patients
Postponed non-emergency surgeries and procedures, affecting quality of life and ability to work
Adverse outcomes caused by improvisation, errors, and efficacy/toxicity of alternative treatments
Direct treatment costs, indirect costs caused by prolonged treatment, disability and time off work
Isolation due to major public health threats (tuberculosis)
Self-medication with drugs from illicit sources may lead to deleterious health consequences.
Hospital administration
Mitigation of shortages and creation of contingency plans is labor intensive, puts additional strain on staff
Triage guidelines institutionalize discrimination, often in favor of vulnerable groups.
Contingency plans and alternative treatment options are often less effective, more toxic and more expensive.
Search for legal import options is bureaucratic and labor intensive, and often to slow
Counterfeit, substandard and falsified products are a concern when less familiar distributors have to be used.
Public officials and State Administration
Unavailability of essential medicines represents public health issue and poses risk for individual patients.
Mitigation of shortages leads to trade-offs between GMP and other requirements and ensuring access.
Inability to prevent and treat contagious diseases forces introduction of unpopular measures such as isolation
Cost of treatment of certain diseases can increase dramatically
Supranational organizations or joint task forces may have to be established to mitigate the situation successfully
Significant dedicated resources including external consultants and diversion of staff from other tasks.

Appendices
• Appendix 1: Availability of Essential Medicines in Hungary shows summary tables that compare the
World Health Organization Essential Medicines List (WHO EML) with the National Substitution List (NL)
by system organ class. The graphs are color-coded for easier orientation: WHO EML products are
marked blue, NL products are green, and products included in both lists are yellow. Number of
registrations include number of individual drug forms including package sizes and dosage forms rather
than a single registration number. This is because different dosage forms may have different indications.
Drugs are categorized by ATC Code; that means some active ingredients are listed in all relevant forms
and system organ classes.
• Appendix 2: Essential Medicines (WHO EML) not registered in Hungary lists active ingredients including
ATC codes that are currently not registered in Hungary by system organ class.
• Appendix 3: Essential Medicines Unavailable in Hungary: Main Indications details main indications for
essential medicines that are unavailable in Hungary.
• Appendix 4: Shortages of Essential medicines in Hungary by System Organ Class details duration of
shortage of drugs listed in the WHO EML.

Analysis and Interpretation: Breakdown by System Organ Class
The dataset is presented as a summary and then in detail by organ class and ATC subclass as
relevant/appropriate. Focus of the following analysis is on essential medicines that are not available in the
Hungary, and evaluation of the situation in the context of public health needs and global drug shortages. To this
end, the Essential List of Medicines defined by the World Health Organization (WHO) is compared to the
Substitution List, which can be found on the website of The National Institute of Pharmacy and Nutrition. The
Substitution List defines interchangeability of essential marketed products in regards to bioavailability and
intended use according to approved Summary of Product Characteristics (SPC). Parenteral formulations are not
included on this list, because bioequivalence studies are not required for them as long as the conditions
specified in Directive CPMP/EWP/QWP/1401/98 are met. Compounded drugs can be issued if no alternative is
available ("Országos Gyógyszerészeti és Élelmezés-egészségügyi Intézet", 2017). Substitution List can therefore
be treated as the National List of Essential Medicines; bearing in mind, it does not include parenteral
formulations. Information on indications as listed in this section and in Appendix 3 was extracted from the
current product labels as approved by the FDA and the MHRA and from Doctors Without Borders Essential
Medicines guide (Pilon, 2016). U.S. labels were obtained from the NIH U.S. National Library of Medicine
("DailyMed", 2017).
Alimentary tract and metabolism
There are 34 medicines listed on the World Health Organization list of Essential Medicines (WHO EML),
of which 26 are currently approved for marketing and available to patients. As of April 6, 2017, 8 (24%) were
unavailable in Hungary. The NL lists 38 ATC codes in total. Thirteen (13) medicines are included in both lists.
Detailed information on the availability of essential medicines for the treatment of alimentary tract ailments and
metabolism can be found in Figures 4-13, Appendix 1. List of unavailable essential medicines can be found in
Appendix 2, Figure 120. Overview of main indications of unavailable essential medicines is detailed in Appendix
3, Figure 134. Finally, products included in WHO EML that are in shortage, including duration of this shortage,
can be found in Appendix 4, Figure 147.
Anticholinergic agents: Hyoscine (scopolamine) hydrobromide:
• Hyoscine injection (400 and 600 microgram/ml) is used as a surgery premedication to control bronchial,
nasal, pharyngeal and salivary secretions, to prevent bronchospasm and laryngospasm and to block
cardiac vagal inhibiting reflexes during induction of anesthesia and intubation.
• Hyoscine transdermal patch (1mg/72 hours) is indicated for the prevention of motion sickness that
manifests as nausea and vomiting and vertigo.
Hyoscine hydrobromide is also widely used off-label in clozapine-induced hypersalivation due to its
anticholinergic properties. Shortages of hyoscine hydrobromide makes other choices difficult (Kasmi, 2014).
Hyoscine hydrobromide tablets are currently in shortage internationally due to a problem with the ingredient.
The only manufacturer of this product is Bayer; therefore, there is no alternative source available. Hyoscine
hydrobromide patches should be back in supply commencing February 2017. Alternatives to hyoscine

hydrobromide include pirenzepine, trihexyphenidyl, propantheline, atropine, amisulpiride or moclobemide
(Dixon, 2017). Hyoscine, as an anticholinergic agent, can also be used as an alternative or adjunct to atropine for
the treatment of pesticide and nerve agents poisoning. Rapid administration of very large doses of atropine is
required for the treatment of nerve-agent exposed casualties (Marrs, Maynard, Sidell, & Marrs, 2007).
Quantities of anticholinergic drugs required in a mass casualty situation may not always be readily available
especially in facilities with just-in-time management of medication supply chains.
Drugs against constipation: Docusate sodium
• Docusate sodium (capsule 100 mg, and oral liquid 50 mg/5 ml) is used for long-term management of
constipation as a stool softener. Oral formulations are considered essential in palliative care (Pilon,
2016)
• Docusate sodium is also used as an adjunct in abdominal radiological procedures
Stool softeners should be used in palliative care in addition to stimulant laxatives, including opioid-
induced constipation. There is sufficient evidence to support the use of laxatives in palliative care patients in
them management of functional constipation. However, there is insufficient evidence to support one laxative
over another (International Association for Hospice and Palliative Care (IAHPC), 2013).

Paromomycin: Aminoglycoside antibiotic, antiprotozoal
• Paromomycin injection (solution for intramuscular injection 750 mg/ml) is used for the treatment of
visceral leishmaniosis. This formulation is on the WHO EML (Pilon, 2016).
• Paromomycin oral formulations (capsule 250 mg) is used for the treatment of acute and chronic
intestinal amoebiasis caused by Entamoena histolytica. Other indications include cryptosporidiosis (C.
parvum and C. hominis) and tapeworm infestation (T. saginatta, T. solium, D. latum, D. caninum). Oral
formulations are used as an adjunct therapy in hepatic coma.
• Paromomycin topical formulations (ointment) are indicated for the treatment of cutaneous
trichomoniasis and cutaneous leishmaniasis.
Aminoglycoside paromomycin is an aminoglycoside antibiotic that was discovered in the 1950s and first
approved for the treatment of visceral leishmaniosis in 2006. Paromomycin is effective against Gram-negative
and Gram-positive bacteria, some protozoa including Cryptosporidium spp. and Leishmania spp. and also
cestodes. Paromomycin does not affect normal intestinal flora. Dientamoeba fragilis is frequently (up to 30%)
detected in human stool, originally believed to be a-pathogenic. Persistent infestation may be associated with
clinical symptoms. Eradication of these protozoa can be a therapeutic challenge. The drugs tested in previous
studies included erythromycin, doxycycline, metronidazole, clioquinol, iodoquinol, diphetarsone and
paromomycin. Paromomycin was found to be consistently effective in the eradication of D. fragilis in adult
patients and can be recommended as first-line treatment (van Hellemond, Molhoek, Koelewijn, Wismans, & van
Genderen, 2012). Cryptosporidium parvum causes opportunist infections of humans and animals, including
cattle, sheep, deer, horses, buffaloes and cats. C. parvum and C. hominis are responsible for outbreaks of water-
borne diarrhea in immunocompetent individuals and traveler diarrhea and is especially problematic in patients
with HIV/AIDS. The symptoms range from asymptomatic carriage and self-limiting diarrhea in immune-
competent individuals to persistent, high-volume watery diarrhea in immunocompromised patients. Of the
many drugs screened for the treatment of cryptosporidiosis, only paromomycin and nitazoxanide demonstrated
significant clinical benefit (Farthing, 2006).
Corticosteroids
• Hydrocortisone foam enema, supplied in an aerosol can filled with expanding foam, is used for the
treatment of ulcerative colitis, proctosigmoiditis and granular proctitis.
First-line treatment for mild to moderate proctitis and proctosigmoiditis includes topical or oral
aminosalicylates alone or in combination, or a topical corticosteroid (hydrocortisone) alone or in combination
with oral prednisolone (National institute for Clinical and Healthcare Excellence (NICE), 2013). Mild to moderate
distal colitis may be treated with topical meslamine, oral aminosalicylates, or topical corticosteroids. Category A
evidence exists for all stated interventions ("Ulcerative Colitis in Adults | American College of Gastroenterology",
2017). Topical aminosalicylates are more effective than topical steroids in achieving symptomatic, histological or
endoscopic remission. Topical steroids should be prescribed to patients who have inadequate response to
aminosalicylates or are allergic to them (Harbord et al., 2017).

Vitamins
• Ergocalciferol (oral formulations) is indicated for the prevention of rickets and osteomalacia.
• Nicotinamide (oral formulation) is indicated for the treatment of pellagra.
• Riboflavin (oral formulations) is indicated for the prevention of vitamin B2 deficiency.
Injectable vitamins for parenteral nutrition registered in Hungary:
• Calcitriol (Calcijex 2 mcg/ml, AbbVie Kft.);
• Thiamine (COCARBOXYLASE JELFA 25 mg/ml, Jelfa SA and VITAMIN B1-ZENTIVA 10 mg and 50 mg,
Zentiva HU Kft.);
• Combination thiamine + cyanocobalamin + pyridoxine (NEUROBION 100 mg/100ml, Merck Kft. and
MILGAMMA N, Wörwag Pharma GmbH&Co.KG);
• Pyridoxine (VITAMIN B6 EGIS 25 mg/ml, Egis Gyógyszergyár Zrt.);
• Ascorbic acid (CEBION 100 mg/ml, Merck Selbstmedikation GmbH and VITAMIN C EGIS 100 mg/ml, Egis
Gyógyszergyár Zrt.) and
• Alfa-tocopherol (VITAMIN E 30 mg, Pharmamagist Kft.).
The term Vitamin D is used for ergocalciferol (calciferol, vitamin D2), cholecalciferol (vitamin D3),
dihydrotachysterol, alfacalcidol (1α-hydroxycholecalciferol), and calcitriol (1,25-dihydroxycholecalciferol).
Vitamin D is necessary for the absorption of calcium and phosphates from intestines and for normal bone
calcification. It is available as an oral solution, capsules and tablets. Recommended daily allowance for
nutritional supplementation is 600 IU (15 mcg)/day for adults. For prophylaxis and treatment of osteoporosis,
800-1000 IU (20-25 mcg)/day are recommended. 12.000 to 500.000 IU (0.3 – 12.5 mg)/day are required for
Vitamin-D resistant rickets. For hypoparathyroidism, 50.000 – 200.000 (0.625-5mg)/day is used in addition to
oral calcium supplements. Because of potential toxicity, all patients receiving pharmacological doses of vitamin
D should be closely monitored for plasma calcium concentrations ("ERGOCALCIFEROL : British National
Formulary", 2017). Other forms of vitamin D (A11CC) are available in Hungary.
The clinical manifestation of pellagra includes a tetrad of symptoms: photosensitive dermatitis and
diarrhea, with cognitive impairment and eventually death. This vitamin deficiency responds to treatment with
nicotinic acid. Pellagra was widespread in 19th century Europe and in the 1920s it became epidemic in the
American South. Hungarian-born physician Joseph Goldberger of the United States Public Health Service
eventually solved the problem through dietary modification. Pellagra results from inadequate consumption of
nicotinic acid, tryptophan or both. Pellagra develops in malnourished individuals or secondary to isoniazid
treatment. Isoniazid-induced pellagra may occur despite pyridoxine supplementation. HIV/AIDS patients also
develop pellagra-like state due to decreased tryptophan levels. The symptoms can become life-threatening
because the disease is often unrecognized. Dietary-induced pellagra can occur in adults with sensitization to
multiple foodstuffs on a severely restrictive diet or those with anorexia nervosa. Secondary pellagra occurs due
to interference with niacin absorption or processing, such as prolonged diarrhea, chronic alcoholism, dialysis,
ulcerative colitis, liver cirrhosis, malignant carcinoid tumors, or Hartnup syndrome (Hegyi, 2017).

Riboflavin is a water-soluble vitamin naturally present in many foods. Riboflavin is an essential
component of coenzymes flavin mononucleotide (FMN, riboflavin-5’-phosphate) and flavin adenine dinucleotide
(FAD). These coenzymes are essential in cellular energy production, growth and development, in metabolism of
lipids, xenobiotics and steroids, conversion of aminoacid tryptophan to niacin (utilizing FAD) conversion of
vitamin B6 to the coenzyme pyridoxal 5’-phosphate (utilizing FMN). Riboflavine also helps maintain normal
levels of homocysteine. Bacteria in large intestine produce riboflavin after ingestion of vegetable-based foods.
Riboflavin deficiency caused by inadequate intake is extremely rare in the developed world. The symptoms of
ariboflavinosis include dermatitis, hyperemia and edema of the mouth and throat, angular stomatitis, cheilosis,
hair loss, itchy and red eyes, reproductive problems, degeneration of the liver and nervous system, and anemia
and cataracts. Riboflavin deficiency usually occurs in combination with other dietary deficiencies in severely
malnourished individuals ("Office of Dietary Supplements - Riboflavin", 2017). Combinations of vitamin B-
complex (A11D, A11E) are available in Hungary although it may be challenging to find the right supplement in
cases of an isolated deficiency of niacin or riboflavin ("Országos Gyógyszerészeti és Élelmezés-egészségügyi
Intézet", 2017).
Minerals
• Sodium fluoride (topical formulation) is used for prophylaxis of dental caries.
Sodium fluoride is safe and effective in preventing and controlling dental caries. Topically applied
fluoride inhibits the demineralization of sound enamel and facilitates its remineralization. Fluoride also inhibits
the metabolic activity of cariogenic bacteria. Fluoride ingested in salt or drinking water acts topically due to its
presence in saliva and gingival mucosa. To maximize the beneficial effect of fluoride in the toothpaste, rinsing
after brushing should be minimized (American Academy of Pediatric Dentistry, 2017). Proliferation of alternative
truth and conspiracy websites throughout Eastern Europe can have significant impact on human behavior. One
example of such prolific medical hoax is the meme on the dangers of water fluoridation due to fluoride toxicity.
It is widely believed that governments add fluoride in water to maintain the populace in the state of slavish
obedience (Thea, 2017).
Shortages: There are no current significant global shortages of hyoscine hydrobromide, docusate
sodium, paromomycin, hydrocortisone rectal foam, sodium fluoride, oral ergocalciferol, riboflavin or
niacin products. However, parenteral nutrition components, including vitamins, are in chronic shortage
worldwide. Major shortages include calcium gluconate, cyanocobalamin inj., magnesium sulfate inj.,
multi-vitamin infusion, trace elements inj. and others ("ASPEN | Parenteral Nutrition Component
Shortages Update", 2017). Shortages of parenteral nutrition components, including multivitamins and
trace elements, are forcing rationing of existing supplies. These medicines are irreplaceable for
premature infants and infants born with congenital anomalies. Shortages and unavailability have been
associated with adverse outcomes, such as lactic acidosis or Wernicke encephalopathy from thiamine
deficiency or impaired pulmonary or skeletal development due to inadequate supply of vitamins A and D
(Hanson et al., 2012). Detailed overview of drug shortages of essential medicines for the treatment of
alimentary system and metabolism in Hungary and their duration is available in Figure 147, Appendix 4.
Current product shortages in Hungary involve ranitidine, omeprazole, loperamide, multienzymes,
metformin, glibenclamide and gliclazide. Alternatives were available to replace products in shortage.

Thirty medicines for the treatment of blood and blood-forming organs are listed on the WHO EML. Of these, 27
are currently approved for marketing and available to patients. As of April 6, 2017, 3 (10%) were not registered
in Hungary. The NL lists 5 ATC codes in total. Two (2) medicines are included in both lists. Detailed information
on the availability of essential medicines for the treatment of blood and blood—forming organs can be found in
Figures 14-18, Appendix 1. List of unavailable essential medicines can be found in Appendix 2, Figure 121.
Overview of main indications of unavailable essential medicines is detailed in Appendix 3, Figure 135. Finally,
products included in WHO EML that are in shortage, including duration of this shortage, can be found in
Appendix 4, Figure 148A-D.
Magnesium sulfate: Anticonvulsant
• Magnesium sulfate (i.v. or i.m. injection) is used for the treatment of severe preeclampsia and
eclamptic seizures. Other uses include hypomagnesemia, Torsades de Pointes, and preterm labor (off-
label).
Magnesium sulfate is available as an injection or solution for infusion and its main uses include the
treatment of hypomagnesemia, treatment and prevention of seizures associated with pre-eclampsia and
eclampsia, and Torsades de Pointes. It is also used off-label as a tocolytic to stop preterm labor. Magnesium
sulfate is strongly recommended for the prevention of eclampsia in women with severe pre-eclampsia in
preference to other anticonvulsants. The quality of evidence is categorized as high for severe eclampsia and
moderate for eclampsia (WHO recommendations for prevention and treatment of pre-eclampsia and eclampsia,
2011). Magnesium sulfate is classified by the Food and Drug Administration (FDA) as pregnancy category D,
meaning it can only be used in life-threatening emergencies when no safer alternative is available. The risks
associated with use longer than 5-7 days include fetal skeletal demineralization, hypocalcaemia and
hypermagnaesemia that may result in skeletal abnormalities in neonates. ("MgSO4 (magnesium sulfate) dosing,
indications, interactions, adverse effects, and more", 2017). Magnesium sulfate is recommended for the
treatment of serious arrhythmias such as salvos of rapid ventricular tachycardia with Torsade de Pointes,
especially in the presence of hypokalemia or hypokalemia and hypomagnesaemia ("9.5.1.3 Magnesium: British
National Formulary", 2017). According to NICE guideline for the treatment of eclampsia and severe eclampsia,
hypertensive disorders during pregnancy complicate up to 7% of all pregnancies in the United Kingdom and
continue to be major cause of maternal death. The guideline defines pre-eclampsia as new hypertension
presenting after 20 weeks of pregnancy with significant proteinuria; severe pre-eclampsia as pre-eclampsia with
severe hypertension and/or with symptoms, biochemical or hematological impairment; and eclampsia as a
convulsive condition associated with pre-eclampsia. The aim is to keep blood pressure (BP) below 150/100 mm
Hg. Oral preparations of choice include nifedipine and labetalol, followed by volume expander Hartmann’s
solution, i.v. hydralazine and labetalol, and magnesium sulfate for eclampsia and severe pre-eclampsia
(Eclampsia and severe pre-eclampsia - Clinical Guideline, 2017). Severe pre-eclampsia and eclampsia are rare but
potentially life-threatening complications of pregnancy. In Pakistan, just like in other low-and-middle-income
countries, magnesium sulfate is critically underutilized. International recommendation has been adequately
translatedinto local policies and guidelines, in practice, these guidelines are not implemented with fidelity. The
medicine is often unavailable in hospitals. In addition, health staff was reluctant to use the medicine when
indicated. Low price of the drug, in addition to narrow indication and small market, were the main reasons for
unavailability/secondary shortage (Bigdeli, Zafar, Assad, & Ghaffar, 2013).

Electrolytes (B05BB01)
Of the total number of 17 electrolyte products registered in Hungary, five are currently in shortage (see
Figure 148B). The system is vulnerable to disruption due to very low number products on the market and a
limited number of suppliers. All electrolyte products (B05BB01) manufactured by TEVA Gyógyszergyár zrt. are
currently in shortage in Hungary (see Figure 148 C).
Red Blood cells and fresh frozen plasma
According to Hungarian National Blood Transfusion Service (HNBTS), there are 5 regional blood centers
and 23 local blood banks in Hungary. Collection of blood takes place in the local blood banks, whilst the
production of blood products takes place in the regional centers. Laboratory tests are performed centrally in
Budapest and Debrecen. Approximately 400.000 donations a year cover national needs. Hungarian National
Blood Transfusion Service (HNBTS) is a member of the European Blood Alliance (EBA). EBA is an association of
non-profit blood establishments with members from 25 countries throughout the European Union and
European Free Trade Area. Proportionate increase in the production of plasma for transfusion and fractionation
in each member state is one of the goals of EBA (EBA Annual Report 2015, 2017).
Shortages: Magnesium sulfate injectable products are currently in shortage in the USA. According to
ASHP (2017), American regent has had magnesium sulfate unavailable since late 2012. Fresenius Kabi
has the product on shortage due to increased demand, and Pfizer has been experiencing manufacturing
delays. Another manufacturer, X-Gen, has magnesium sulfate injection available ("ASHP | Drug
Shortages | Current shortages", 2017). Parenteral nutrition and mineral components have been
experiencing chronic and repeated shortages for almost a decade. The American Society for Parenteral
and Enteral Nutrition (A.S.P.E.N.) developed parenteral nutrition considerations that should be taken
into account when developing hospital contingency plans. Current information on shortages can be
found on the website of national authorities, However, due to global nature of pharmaceutical supply
chains and manufacturing, global shortages are likely to manifest locally as well. Oral supplements or
enteral electrolytes should be provided whenever possible. Stockpiling products makes the situation
worse for everyone else. Significant current global shortages include concentrated calcium gluconate,
concentrated magnesium additives, concentrated phosphate, concentrated potassium and
concentrated sodium ("ASPEN | Parenteral Nutrition Electrolyte and Mineral Product Shortage
Considerations", 2017).

Cardiovascular system
Twenty-five (25) medicines for the treatment of cardiovascular system are listed on the WHO EML. Of
these, 20 are currently approved for marketing and available to patients. As of April 6, 2017, 5 (20%) were not
registered in Hungary. The NL lists 81 ATC codes in total. Thirteen (13) medicines are included in both lists.
Detailed information on the availability of essential medicines for the treatment of cardiovascular system can be
found in Figures 19-31, Appendix 1. List of unavailable essential medicines can be found in Appendix 2, Figure
122. Overview of main indications of unavailable essential medicines is detailed in Appendix 3, Figure 136.
Finally, products included in WHO EML that are in shortage, including duration of this shortage, can be found in
Appendix 4, Figure 149A-C.
Vasopressors
• Ephedrine (solution for injection) is used in spinal anesthesia during delivery, to prevent hypotension.
Other uses include the treatment of shock unresponsive to fluid replacement.
The effects of spinal anesthesia on blood pressure, and its ability induce severe hypotension, is known
since the 1920s (Ockerbald & Dillon, 1927). Hypotension is the most common and most serious adverse effect of
spinal anesthesia during caesarean delivery with incidence greater than 80%. A variety of strategies are used to
prevent maternal hypotension: a lateral uterine displacement, intravenous fluid preload, gravity (leg raising),
compression devices and prophylactic vasopressors. Prophylactic intramuscular administration of ephedrine is
very controversial because its systemic absorption and peak effect are difficult to predict. Intravenous route is
more effective and controllable. The incidence of hypotension can still be high despite high doses. Ephedrine is
the vasopressor of choice in obstetric anesthesiology. Ephedrine has mixed α- and β-adrenoreceptor activity; it
maintains arterial pressure mainly by increases in cardiac output and heart rate as a result of its predominant
activity on β1-adrenoreceptors (Kol et al., 2009).
Diuretics
• Amiloride (oral formulation) is used as a potassium-conserving diuretic.
Amiloride is a potassium-conserving diuretic that can be used alone. More often, however, it is
combined with thiazides to conserve potassium during periods of vigorous diuresis or maintenance therapy.
Main uses include congestive heart failure, hypertension and hepatic cirrhosis with ascites.
Vasodilators, antianginal agents, antihypertensives
• Isosorbide dinitrate (5mg tablet) is used for the treatment of acute angina and as an adjunct therapy in
left congestive heart failure.
• Hydralazine (powder for injection) is used for the acute management of severe pregnancy-induced
hypertension.
• Hydralazine (oral formulations) - acute management of severe pregnancy-induced hypertension.

• Nitroprusside (powder for infusion) is used for immediate reduction of blood pressure during
hypertensive crisis in adult and pediatric patients. Other uses include controlled hypotension during
surgery in order to reduce bleeding, and the treatment of acute heart failure to reduce left ventricular
end-diastolic pressure.
Combination of isosorbide dinitrate and hydralazine is recommended in the management of chronic
heart failure. The guideline still recommends these drugs for some patients in specific situations (Scottish
Intercollegiate Guidelines Network (SIGN), 2016) and (Chronic heart failure: National clinical guideline for
diagnosis and management in primary and secondary care, 2010). Sodium nitroprusside is an arterial and
venous vasodilator that has been used in clinical practice for over four decades. Sodium nitroprusside reacts
with sulfhydryl groups physiologically present in plasma, releasing nitric oxide, and causing rapid vasodilation.
Nitric oxide then acutely lowers blood pressure. Cyanide anion release may result in potential cyanide
accumulation and toxicity. Main uses currently include cardiac surgery, hypertensive crises, heart failure,
vascular surgery and pediatric surgery. Nitroprusside is often replaced by newer agents with more favorable
safety profile. Nitroprusside causes arterial and venous dilatation, reduces afterload, decreases ventricular filling
pressures and lowers the systemic blood pressure. It also increases cardiac output without lowering the heart
rate. Nitroprusside is indicated in situations when rapid onset is required, in combination with accuracy of
titration to target blood pressure (Belani, Hottinger, Kozhimannil, Prielipp, & Beebe, 2014). In December 2016,
Special Committee on Aging, United States Senate, published report Sudden Price Spikes in Off-Patent
Prescription Drugs: The Monopoly Business Model that Harms Patients, Taxpayers, and the U.S. Health Care
System (U.S. Senate). Special investigation into abrupt and dramatic price increases of prescription drugs
centered on four companies – Turing Pharmaceuticals, Retrophin, Inc., Valeant Pharmaceuticals International,
and Rodelis Therapeutics. These firms acquired decades old off-patent affordable medicines and then suddenly
raised their prices astronomically. The Committee closely examined a business model that these four companies
used, provided case studies, explored the influence of investors, assessed the impact of price hikes on patients,
payers, providers, hospitals and governments, and discussed potential responses. The business model involved
acquisition of off-patent sole-source drugs over which they could exercise de facto monopoly pricing power, and
then impose and protect astronomical price increases. The central elements of this business model are the
acquisition of a sole-source drug, for which there is only one manufacturer and therefore there is no immediate
competition, and the fact that the drug is considered the gold standard so physicians cannot stop prescribing it.
Additional elements of this business model identified by the report were small market, not attractive to
competition and dependent population incapable of organizing effective opposition. Closed distribution
through specialty pharmacies were intended to prevent competition from entering the market. Lastly, the
companies engaged in price gouging not justified by R&D or other costs. Of the case studies included in this
report, two involved essential medicines: Turing’s Daraprim (pyrimethamine) for the treatment of
toxoplasmosis, and Valeant’s Nitropress (nitroprusside) used for acute hypertensive crises in emergency
medicine (U.S. Senate. Special Committee on Aging United States Senate, 2016).

Availability of essential medicines in Hungary (2017)

Availability of essential medicines in Hungary (2017)

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