Plovdiv

ACCESS TO MEDICINES FOR THE TREATMENT
OF RARE DISEASES: THE BULGARIAN REALITY
Stoimenova Assena*, Manova Manoela, Petrova Guenka
Medical University, Faculty of Pharmacy, 1000 Sofia, Bulgaria,
*assena_stoimenova@mail.bg
Introduction
Table 3. Rare diseases which are present in the Positive
Drug List, Annex 1 by the ICD code
Rare diseases are life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in EU. Rare disease
Access to treatment and % of reimbursement
Orphan drugs
Most of the people in EU are actually affected by less frequently occurring diseases (1 in 100,000). The medicinal products Positive Drug List and
code name
availability
No orphan drug is designated.
No orphan drug is designated.
which are intended for the diagnosis, prevention or treatment of rare diseases are known as orphan drugs. The No orphan drug is designated.
2 orphan drugs are designated
but not available in Bulgaria.
pharmaceutical industry has little interest in developing and marketing orphan medicines (1,2,3). The patients should be availability of treatment of rare
No orphan drug is designated.
entitled to the same quality of treatment (4). In order to stimulate the R&D and bringing to the market orphan drugs the Insulin Human, Insulin Lispo, Insulin aspart, Insulin glulisine, Insulin No orphan drugs are
diseases
designated.
Glibenclamide,Gliclazide,Glipizide,Glimepiride, Metformin European Parliament and the EU Council have established Community procedure for designation of as orphan medicinal hydrochloride/ Rosiglitazone, Acarbose, Rosiglitazone, Sitagliptin Exenatide Glucagon, (100%) Repaglinide (50%) The Positive list was analyzed from the perspective of Orphan drug is designated and
availability of rare diseases in the annexes (as determined available under Annex 4.
No orphan drugs are
designated.
in www.orpha.net ) and the access of the Bulgarian No orphan drugs are
designated.
No orphan drugs are
designated.
The aim of our study is to analyze the Bulgarian regulatory policy for orphan
There are 4 annexes of the Positive as follows: 2 mg betamethasone as disodium phosphate and 5 mg betamethasone as No orphan drugs are
designated.
Annex 1: Medicinal products covered by the National 1 orphan drug is designated but
medicines and rare diseases, and it’s consistency with EU policies
not available.
healthcare fund (intended for home treatment of the Risperidone, alprazolam , Quetiapine, Olanzapine, Zuclopenthi-xol, No orphan drugs are
Flupentixol, Ziprasidone, Fluphena-zine,Haloperidol, Biperiden, Valproic designated.
Materials and methods
diseases which are covered by the health insurance Carbidopa/ Levodopa, Levodopa/Benserazide, Pramipe- Levodopa and Carbidopa
xole,Entacapone,Rasagiline, Selegiline,Cabergoline, Ropinirole, (gastroenteral use) – advanced
Apomorphine hydro-chloride (inhalation use), Biperiden idiopatic Parkinson’s disease
with severe motor fluctuations
and not reposnding to oral
Annex 2: Medicinal products covered by the hospital treatment.
Tizanidine, Tolperisone Hydrochloride, Flunarizine (25%) No orphan drugs are
The current publication reviews and analysis the following EU and Bulgarian legislation: designated.
budget (intended for hospital treatment); Interferon beta - 1 a, Interferon beta-1b (100%) Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan drugs; Diclofenac, Aceclofenac, Tolperisone Hydrochloride (25%) No orphan drugs are
Annex 3:Medicinal products intended for treatment of designated.
Commission Regulation (EC) No 847/2000 of 27 April 2000 laying down the provisions for implementation of the 1 orphan drug is designated but
diseases which are not covered by the obligatory health not available in Bulgaria.
criteria for designation of a medicinal product as an orphan medicinal product and definition of the concepts “similar insurance and are paid from the state budget No orpha n drugs are
designated.
medicinal product” and “clinical superiority. It was reviewed the Health law, Law on medicines in human medicine, Annex 4: Medicinal products intended for treatment of No orphan drugs are
designated.
Regulation No22/2005 on orphan drugs, Regulation on criteria, conditions and rules for inclusion of medicinal, rare diseases, AIDS and treatment and prophylaxis of Methylprednisolone,Prednisolone, Tobramycin, Fluorome tholone, No orphan drugs are
designated.
Products in positive list, Regulation 34/2005, The current Positive Drug List in Bulgaria.
No orphan drugs are
designated.
The above documents have been reviewed and analyzed from the perspective of their relation to diagnosis, prevention Travoprost, Latanoprost, Latanoprost/Timolol, Betaxolol, Timolol Our study is focused on Annexes 1,3 and 4 as they Moxonidine, Rilmenidine, Prazosin, Doxazosin, No orphan drugs are
and treatment of rare disease and orphan drug and their role for improving the access to adequate treatment. The Hydrochlorothiazide,Chlortalidone, Indapamide, Spironolactone, designated.
include medicinal products available for continuous out- Propranolol, Nitrendipine, Lacidipine, Verapamil, Diltiazem, Enalapril maleate, Lisinopril, Perindopril, Ramipril, Quinapril, Cilazapril, Positive list was reviewed for ICD codes that correspond to rare diseases (according to the data available in Fosinopril, Trandolapril , Moexipril hydrochloride, Zofenopril calcium, Losartan, Eprosartan, Valsartan, Candesartan, Telmisartan (25%) Methyldopa,Furosemide, Triamterene, Hydrochlorothiazide, Metoprolol tartrate, Atenolol, Bisoprolol Nebivolol, Carvedilol, www.orpha.net (3) and only the treatment of rare diseases was analyzed from the perspective of both with orphan Annex 1 contains medicinal product intended for Bisoprolol/Hydrochlorothiazide, Amlodipine (as amlodipine besilate), Felodipine, Nifedipine, Lercanidipine hydrochloride, Trandolapril/ verapamil, Enalapril maleate/Hyd rochlorithiazide, Enalapril maleate; ambulatory treatment. We have found that it contains 39 Hydrochlorthiazide, Lisinopril; Hydrochlorothiazide, Perindopril/ Indapamide, Ramipril/ hydrochlorothiazide, Quinapril/Hydrochlorothiazide, Fosinopril; Hydrochlorothiazide, Perindopril arginine/ Amlodipine, Lisinopril; Amlodipine, Losartan; ICD codes of diseases which presence allow patients to Hydrochlorothiazide, Eprosartan/ Hydrochlorothiazide, Valsartan/ Hydrochlorothiazide, Telmisartan/Hydrochlorothiazide, Aliskiren, Amlodipine/ Valsartan, Amlodipine/Atorvastatin (50%) receive symptomatic and supportive treatment. Actually Moxonidine, Rilmenidine, Prazosin, Doxazosin, Hydrochlorothiazide, No orphan drugs are
Chlortalidone, Indapamide, Spironolactone,Propranolol, Nitrendipine, designated.
for the majority of the diseases in Annex 1 there are no Lacidipine, Verapamil, Diltiazem, Enalapril maleate, Lisinopr il, Perindopril, Ramipril, Quinapril, Cilazapril, Fosinopril, Trandolapril, Moexipril hydrochloride, Zofenopril calcium, Losartan, Eprosartan, orphan drugs designated. The treatment of two diseases Valsartan, Candesartan, Telmisartan (25%) Furosemide, Triamterene, Hydrochlorothiazide, Metoprolol tartrate, Regulation on orphan drugs in the European Union
Atenolol, Bisoprolol, Nebivolol, Carvedilol, (acromegaly and pulmonary arterial hypertension) is Bisoprolol/Hydrochlorothiazide, Amlodipine (as amlodipine besilate), Felodipine, Nifedipine, Lercanidipine hydrochloride, Trandolapril/ verapamil, Enalapril maleate/ Hydrochlorithiazide, Enalapril maleate; No specific legislation was created on Community level until 22 January 2000 when the Orphan Medicinal Product covered 100% by Annex 4, but Annex 1 provided Hydrochlorthiazide, Lisinopril; hydrochlorothiazide, Perindopril/ Indapamide, Ramipril/ hydrochlorothiazide, Quinapril/Hydrochlorothiazide, Fosinopril; Hydrochlorothiazide, Perindopril arginine/ Amlodipine, Lisinopril; Amlodipin e, Losartan; Regulation (Regulation (EC) 141/2000) was published.
additional supportive treatment. The orphan drugs Hydrochlorothiazide, Eprosartan/ Hydrochlorothiazide , Valsartan/ Hydrochlorothiazide, Telmisartan/Hydrochlorothiazide, Aliskiren, Amlodipine/ Valsartan, Amlodipine/Atorvastatin (50%) Regulation (EC) 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan Levodopa and Carbidopa are reimbursed 100% for the Isosorbide dinitrate, Pentoxifylline (25%) Orphan drug is designated and
available under Annex 4.
No orphan drugs are
medicinal products sets up criteria for orphan drug designation in EU and describes the incentives in the Acenocoumarol, Sotalol hydrochloride, Metoprolol tartrate, Atenolol designated.
No orphan drugs are
Introduction part which are implemented to encourage the research, development and marketing of orphan drugs 32 rare diseases are included in Annex 3 and their Acenocoumarol, Quinidine sulphate, Propafenone, Amiodarone, Sotalol designated.
hydrochloride, Metoprolol tartrate, Atenolol (50%) Propranolol, Verapamil (25 %) (4). The main requirements of Regulation (EC) 141/2000 are described in Table 1: treatment is covered 100% by the state budget. Most of No orphan drugs are
Acenocoumarol, Quinidine sulphate, Propafenone, Amiodarone, Sotalol designated.
hydrochloride, Metoprolol tartrate, Atenolol (50%) Commission Regulation (EC) No 847/2000 is defining the concepts “similar medicinal product” and “clinical them are various kinds of malignant diseases, syndromes Pentoxifylline, Nicergoline, Naftidrofuryl, Naftidrofuryl hydrogen No orphan drugs are
oxalate, Tolperisone Hydrochloride (25%) designated.
superiority” and it is intended to assist potential sponsors, the Committee for Orphan Medicinal Products, and etc. treated with supportive and symptomatic drugs. Ranitidine, Famotidine, Omeprazole, Lansoprazole, Esomeprazole, No orphan drugs are
designated.
competent authorities in the interpretation of Regulation (EC) No 141/2000. This regulation specifies the criteria for There are no orphan drugs designated for 14 diseases. For Budenoside, Sulfasalazine, Mesalazine (50%) No orphan drugs are
designated.
designation and definitions such as “significant benefit” for the purpose of implementation of art. 3 of Regulation 11 diseases there are orphan drugs are designated, but Methylprednisolone, Prednisolone, Prednisone (50%) No orphan drugs are
designated.
No orphan drugs are
No141/2000; “active substance”, “similar medicinal product”, “similar active substance” for the purposes of either not available in Bulgaria nor not reimbursed and Sulfasalazine, Methylprednisolone, Prednisolone, designated.
Methylprednisolone,/Lidocaine, Prednisone, Etanercept, Adalimumab, Tetrazepam (50%) implementation of article 8 of Regulation (EC) No 141/2000, “clinically superior” etc.
therefore not affordable for the Bulgarian patients. Chloroquine , Diclofenac, Aceclofenac, Meloxicam, Ibuprofen, Dexetoprofen, Etoricoxib, Nimeulide (25%) Regulation (EC) No 141/2000 and Commission Regulation (EC) No 847/2000 provide the legislative frame for Patients, suffering form 7 diseases have access to orphan orphan drugs and rare diseases setting up the Community procedure for designation of orphan drugs and incentives Treatment of 6 rare diseases is covered with Annex 4 Table 4. Rare diseases which are present in the PDL, annex
The treatment of rare diseases and the improvement of quality of life of the affected by rare disease people in EU (acromegaly, galactosemia, N-acetyl-alpha-D- 3 by the ICD code-100% reimbursed
depends not only on legislation available but on development and implementation of common strategies, in Europe. galactosaminidase deficiency, cystic fibrosis, pulmonary Rare disease
Available reimbursed local
Orphan drugs availability
Rare diseases are one of the priorities in the current EU Public Health Program running till 2013 and the oriented in arterial hypertension, acute respiratory distress syndrome treatment
No orphan drugs are designated. Access to local treatment
3 main fields: improving recognition and visibility on rare diseases, supporting policies on rare diseases in Member and Turner syndrome). For two of the diseases Methylprednisolone, Tramadol, Dihydro codeine, Morphine,Fentanyl, Pethidine states and developing European cooperation, coordination and regulation for rare diseases. It was created Orphanet, (acromegaly and pulmonary arterial hypertension) the No orphan drugs are designated. Access to local treatment
Eurordis and several networks of clinical centers cooperating to develop information services or to coordinate their drugs received orphan designation are reimbursed – Tropisetron , Methylprednisolone, Tramadol, Dihydro codeine, Morphine, Fentanyl, Pethidine hydrochloride clinical activities (5). In addition, an EU Rare Disease Task Force was established. pegvisomant and sidlenafil and iloprost respectively. Tegafur, EU designation date: 20/12/2007, authorized in
Bulgaria, but not reimbursed.
Capecitabine,Methylpredni-solone, Tramadol, Other 2 drugs received orphan designation but not available
Bulgarian legislation on orphan drugs and rare diseases and
in Bulgaria.
The available but not reimbursed orphan drugs in Bulgaria
are: Paclitaxel, EU designation date: 31/10/2006 and
Gemcitabine,Methyl-prednisolone, Tramadol, Cisplatin, EU designation date: 08/06/2007.
transposition of EU legislation of orphan drugs in Bulgaria
Another 14 m edicinal products are designated as orphan
products but not available in Bulgaria.
2 orphan drugs are available in Bulgaria - Imatinib mesilate,
EU designation date: 20/11/2001and Nilotinib hydrochloride
For its 7 5000 000 population (official data as of 2004) the patients suffering from rare diseases is estimated 400 - Conclusions
monohydrate, marketing authorization date: 19/11/2007.
One more orphan drug is designated but not available in
Bulgaria.
450 000 people. There are 6 medical management centers in the country for diagnosis and treatment of rare diseases 2 orphan drugs are designated but not available in Bulgaria
Palonosetron,Tropisetron,Methylprednisolone, (Picoplatin, EU designation date:06/12/2007 and Amrubicin
hudrochloride, EU designation date: 02/04/2008).
in Bulgaria (6). The national legislation on orphan drugs comprises of several laws and regulations (6) presented in Although the Bulgarian legislation concerning rare Table 2. The Health law outlines the genetic examinations and prenatal tests which are aimed to limit the incidence disease and orphan drugs is harmonized with the EU No orphan drugs are designated. Access to local treatment
Ondasetron,Granisetron,Palonosetron,Tropiset ron, Methylprednisolone, Tramadol, Dihydro of rare diseases in the country. The Law on medicines refers to Regulation (EC) 141/2000 and sets up the conditions policies, Bulgarian patients with rare diseases have codeine, Morphine, Fentanyl, Pethidine hydrochlorid for marketing authorization of orphan drugs, their pricing and reimbursement. These drugs are included into the access to very few of the orphan drugs authorized in EU 2 orphan drugs are designated but not available in Bulgaria
(Ranprinase, EU designation date: 29/03/2001 and NGR-
Positive list and are covered by the Health insurance fund or the state budget. and the majority of the drugs covered are intended for human tumour necrosis factor, EU designation date:
03/06/2008).
symptomatic and supportive treatment. Only several Topotecan, Cisplatin, Bleomycin, Paclitaxel, One orphan drug is available and reimbursed in Bulgaria -
Paclitaxel, EU designation date:18/12/2006. Another 9
rare diseases could be treated with the reimbursed medicinal products received orphan designation but not
available in Bulgaria.
Methylprednisolone, Tramadol, Dihydro codeine, Morphine, Fentanyl, Pethidine HCl Table 1. Main requirements of Regulation (EC) 141/2000
Table 2. Bulgarian legislation concerning rare diseases/orphan drugs
No orphan drugs are designated. Access to local treatment
Triptorelin,Goserelin, Leuprorelin, Buserelin, Orphan drugs are reimbursed for 10 rare diseases and Ondasetron,Granisetron Palonosetron, Tropisetron, Cyproterone, Methylpred- Requirements
other treatment is covered 100 % for another 28 nisolone, Tramadol, Dihydro codeine, Morphine, Fentanyl, Pethidine hydrochloride Law/regulation
Scope of the document
Relation to rare diseases/orphan drugs
No orphan drugs are designated. Access to local treatment
Article 3. Criteria for designation
Includes the criteria for orphan drug designation. Health law
• Chapter 4 “Health protection of specific populations”, section
Article 4. Committee for Orphan
COMP is set within EMEA with the following tasks: to examine any application for the 2 “Reproductive health”, paragraph 127 (2),p.5 requires prenatal
diseases. For another 39 rare diseases there are partially Tropisetron, Methylprednisolone, Tramadol, Dihydro codeine, Morphine, Fentanyl, Pethidine hydrochloride Medicinal Products (COMP)
designation of a medicinal product as an orphan product, to advise the Commission on the diagnostics and prophylaxis of genetic diseases. establishment and development of a policy on orphan medicinal products for the European • Chapter 4 “Health protection of specific populations”, section
reimbursed supportive and symptomatic treatment. Interferon alfa, Interferon alfa -2a, Sorafenib,
1 orphan drug is available and reimbursed in Bulgaria -
Sorafenib tosylate. Everolimus is orphan drug which is not
Union, to assist the Commission in liaising internationally on matters relating to orphan 4 “Genetic health and genetic examinations”, paragraph 137-144
reimbursed but available in Bulgaria. Temsirolimus is
medicinal products and to assist the Commission in preparation of detailed guidelines. requires treatment prophylaxis and diagnostics of genetic diseases, Tropisetron, Vincristine, Methylprednisolone, orphan drug, registered via the centralized proc edure
(marketing authorization date: 19/11/2007). 17 drugs are
Article 5. Procedure for designation
After submission of application by the sponsor to EMEA, together with required received orphan designation but are not available in Bulgaria
and removal from the register
documentation, the COMP gives opinion about the designation within 90 days of the receipt Law on medicinal Marketing authorization of medicinal • Chapter 3 “Marketing authorization”,, paragraph 25
Epirubicin, Bleomycin, Etoposide, Ondasetron 3 drugs received orphan designation but are not available in
of the valid application. The designated medicinal product is entered in the Community products in human products, licensing of pharmaceutical (1): reference to Regulation (EC) 141/2000 regarding the
Register of Orphan Medicinal Products. Each year, the sponsor submits to EMEA a report on medicine
manufacturers, wholesalers, retailers, criteria for orphan drug and paragraph 25 (2) which is
Table 5. Rare diseases which are present in the Positive Drug List,
Bulgaria.
the state of development of the designated product. reference to Regulation 762/2004 with regard to marketing classification, pharmacovigilance, state authorization of orphan drugs. annex 4 by the ICD code
Lomustine, Methylpredni-solone, Tramadol, Dihydro codeine, Morphine,Fentanyl, Incentives for the sponsors
Article 6. Protocol assistance
The sponsor of an orphan medicinal may, prior to the submission of an application for the Chapter 3 “Marketing authorization”, paragraph 27,
Ibritumomab tiuxetan, Rituximab, Ondasetron, No orphan drugs are designated. Access to local treatment
marketing authorization request advice from the EMEA on the conduct of the various tests regarding the proof of orphan drug designation required as and clinical trials necessary to demonstrate the quality, safety and efficacy of the medicinal submission documentation for marketing authorization. Liposomal Cytarabine,Cladribine, Methyl- • Chapter 12 “Pricing of medicinal products”, paragraph
prednisolone, Tramadol, Dihydro codeine, Morphine, Fentanyl, Pethidine hydrochloride Article 7. Community marketing
The person responsible for placing an orphan medicinal product on the market may request 262, (4), p.4: orphan drugs are part of the “positive” list (the
Rare disease name
Available reimbursed
Orphan drug availability and affordability
1 orphan drug is designated and available under the
authorization
the authorization to be granted with the provisions of Centralized Procedure without having centralized procedure Cladribine (subcutaneous use), EU
local treatment
to justify that the medicinal product qualifies under Part B of the Regulation. Reductions of marketing authorization date: 14/04/2004. The drug is not
the fees payable to EMEA are offered to the sponsors. Regulation No22/2005
Regulates the criteria for orphan drug designation and Pegvisomant (marketing authorization date 13/12/2002) is reimbursed
reimbursed in Bulgaria.
requirements for orphan drug designation which are orphan drug.
Article 8. Market exclusivity
Where a marketing authorization in respect of an orphan medicinal product is granted, the 2 orphan drugs are designated but not available in Bulgaria.
Community and the Member States shall not, for a period of 10 years, accept another application for a marketing authorization, or grant a marketing authorization or accept an Regulation No 34 as of Lays down the provisions for
According to Regulation 34/2005, article 2, (1),p.4 the No orphan drugs are designated.
No orphan drugs are designated. Access to local treatment
application to extend an existing marketing authorization, for the same therapeutic indication, 25.11.2005
treatment of rare diseases is paid by the Ministry of health. in respect of a similar medicinal product. This period may be reduced to six years if the Cytarabine Methyl-prednisolone, Tramadol, Article 9. Other incentives
Medicinal products designated as orphan medicinal products shall be eligible for incentives 3 orphan drug are available (Heparin sodium, EU designation date:
made available by the Community and by the Member States to support research into, and the Regulation on criteria, Lays down the provisions for inclusion Regulates the inclusion of drugs into a positive list, including
22/05/2006 and Levofloxacin EU designation date: 23/09/2008 and
No orphan drugs are designated. Access to local treatment
development and availability of, orphan products and in particular aid for research for small- conditions and rules for of medicinal products into the Positive the drugs for the treatment of rare diseases.
Mannitolum, EU designation date: 07/11/2005) but not reimbursed. 13
inclusion of medicinal list.
orphan drugs are designated but not available.
Vincristine, Fludarabine phosphate, Methyl-prednisolone, Tramadol, Dihydro c odeine, products in PDL
2 orphan drugs are available and reimbursed (Sildenafil citrate, marketing
Morphine, Fentanyl, Pethidine hydrochloride authorization date: 28/10/2005 and Iloprost, marketing authorization date:
Pamidronic acid, Interferon alfa, Interferon 1 orphan drug is designated, available via the centralized
16/09/2003). 3 other orphan drugs are available via centralized procedure
alfa-2a, Bortezomib, Ondasetron Granisetron, procedure but not reimbursed (3-(4´amnioisoindoline-I´-
but not reimbursed (Bosentan, marketing authorization date: 15/05/2002,
one)-1-piperidine-2,6-dione, marketing authorization date:
Bibliography
Sitaxentan sodium, marketing authorization date: 10/08/2006 and
14/06/2007). Another 4 drugs received orphan designation
Ambrisentan, marketing authorization date: 21/04/2008).
codeine, Morphine, Fentanyl, Pethidine HCl but not available in Bulgaria.
Another 6 orphan products are designated but not available.
2 orphan drugs are available and reimbursed - Dasatinib, EU
Dasatinib, Ondasetron, Granisetron,
designation date:23/12/2005 and Nelarabine, marketing
One orphan drug is designated but not available (Sinapultide, EU
Tropisetron, Vincristine, Nelarabine,
authorization date: 22/08/2007. Imatinib mesilate is available
designation date: 29/07/2004).
but not reimbursed in Bulgaria (EU designation date:
26/08/2005). Mercaptopurine received orphan designation in
o4/2009 and is available but not reimbursed in Bulgaria. 4
1. Communication from the Commission to the European Parliament , the Council, the European Economic and Social Committee and the orphan drugs are designated but not available in Bulgaria.
No orphan drug is designated.
The orphan drug Cladribine is available and reimbursed.
One more orphan dr ug is designated but not available.
Committee of the Regions on rare diseases: Europe’s challenges Cladribine, Methylpredni-solone, Tramadol,
Dihydro codeine, Morphine,Fentanyl,
2. “Orphan drugs and rare diseases at a glance”, Doc. Ref. EMEA/290072/2007, European Medicines Agency Imatinib, Nilotinib, Dasatinib, Mitomycin,
1 orphan drug is available and reimbursed (Dasatinib,
EU marketing authorization date: 20/11/2006). Another
Tropisetron, Methylprednisolone, Tramadol, 3 orphan drug are designated but not available in
4. Regulation (EC) 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products Bulgaria.
No orphan drugs are designated. Access to local treatment
5. Ségolène Aymé , J. Schmidtke “Networking for rare diseases: a necessity for Europe ”, Bundesgesundheitsblatt - Gesundheitsforschung – Gesundheitsschutz, vol.50, number 12, December 2007, 1477-1483 codeine, Morphine, Fentanyl, Pethidine HCl Deferasirox, Deferiprone, Deferoxamine
1 orphan drug is available and reimbursed – Deferasirox. 2
6. Ministry of health. National Program for rare diseases (2009-2013) (genetic, malformations and non heredity diseases), MoH Bulgaria orphan drugs are designated but not available in Bulgaria .
1 orphan drug is designated, available but not reimbursed
(pegylated factor VIIa). 1 orphan drug is not available in BG

Source: http://conf2009.raredis.org/posters/Poster%2044%20-%20Asena%20Stoimenova.pdf