Project Title ANNEX 1 by tyndale


									                                                    ANNEX 1 - List of Pharmaceuticals from the UN List
Abbreviations used in the table;
@EC – European union. Usually recommendation by the Committee for Proprietary Medicinal Products of the European Communities

Mono Component Products
(2) Number of countries that have taken some sort of regulatory action
(3) Number of countries that have banned the product
(4) Number of countries that have made some restriction on the product
       Pharmaceutic       # of    Bann     Restri    Excerpts of WHO comments (5)
       al (1)             count   ed (3)   cted
                          ries             (4)
1      Phenacetin         42      41       1         An aniline derivative. An antipyretic gained recognition as an analgesic. Habitual use was first implicated as the cause of
                                                     methaemoglobinaemia and chronic haemolysis. Abusive use is also associated with cumulative renal damage. Suggested
                                                     to also have a carcinogenic potential. Withdrawn in many countries but may remain available in others. (Beta
                                                     ethoxylacetanilide and bucetin are analogue of phenacetin)
2      Aminophenazo       38      36       2         Pyrazolone derivative. Used as an anti-inflammatory agent and analgesic. Use associated with bone marrow depression
       ne                                            and agranulocytosis and claimed to have carcinogenic potential. Proprietary preparations containing this ingredient may
                                                     remain available.
3      Metamizole         39      27       12        Pyrazolone derivative with analgesic, antipyretic and anti-inflammatory activity. Its use has been associated as with some
       sodium                                        other pyrazolones, with serious sometimes fatal adverse reactions, notably cases of blood dyscrasias including
                                                     agranulocytosis, which led to its withdrawal by some regulatory authorities. Although preparations are prohibited in certain
                                                     countries they remain widely available in others.
4      Phenformin         28      24       4         A biguanide with oral hypoglycaemic activity. Its use has been associated with incidences of lactic acidosis and clinical
       (and related                                  studies have conclusively demonstrated that the hazards of phenformin treatment outweighed the benefits. Preparations
       Biguanide                                     containing phenformin were withdrawn in several countries and their use restricted in others. Elsewhere proprietary
       buformin)                                     preparations containing this drug may remain available. Related biguanide buformin, has been associated with lactic
                                                     acidosis and has been subjected to similar restrictions as phenformin.
5      Chloroform         26      23       3         Formerly widely used in pharmaceutical preparations as a solvent and preservative as well as for its anaesthetic and
                                                     flavouring properties. Has shown positive results in carcinogenicity screening programmes. This has led to considerable
                                                     restrictions in its use in pharmaceutical preparations. While many pharmaceutical preparations have been reformulated to
                                                     exclude this substance, it may still be incorporated in toothpastes and other specified products in some countrie, subject to
                                                     statutorily imposed concentration limits.
6      Clioquinol    (A   31      23       8         A halogenated hydroxyquinoline derivative. Used for the treatment of amoebic dysentery and simple diarrhea. Has been
       halogenated                                   associated with cases of sub-acute myelo-optic neuropathy (SMON). Has been phased out by the major manufacturer on
       hydroxyquinolin                               grounds of obsolescence between 1983 and 1985. No adequately controlled evidence was ever generated to demonstrate
       e derivative)                                 that clioqunol is effective in bacterial or viral diarrhea. However products containing clioquinol and related halogenated
                                                     hydroxyquinolones continue to be used in some tropical and sub-tropical countries where amaoebiasis remains endemic.
                                                     Other amoebocides are preferred in the WHO Model List of Essential Drugs.
7      Oxyphenbutazo      32      21       11        A pyrazolone derivative with anti-inflammatory, analgesic and antipyretic activity. Used for the treatment of rheumatic
       ne                                            disorders. It is one of the active metabolites of phenylbutazone and has a similar spectrum of activity including an
                                                     association with serious and sometimes fatal adverse reactions, notably cases of aplastic anaemia and agranulocytosis.
                                                     Many national drug regulatory authorities consider that more recently introduced drugs offer a safer alternative for most, if
                                                     not all, patients requiring anti-inflammatory agents. Although widely withdrawn it remains available in some countries.
                                                     Restricted indications include ankylosing spondylitis and acute attacks of gout.

8    Oxyphenisatine     20     20      --       Widely used as a laxative. Associated with acute and chronic liver disease. This association is considered by some, but not
     acetate                                    all, national drug regulatory authorities to warrant the withdrawal from the market preparations containing oxiphenisatine
                                                and its derivatives. (Triacetyldiphenolisatin is a derivative of oxyphenisatine)
9    Methapyrilene      19     19      --       An antihistamine with moderate sedative activity. Incorporated in many OTC sleeping aids. It was identified as a carcinogen
                                                in rats and, although there was no direct evidence that it constitutes a health hazard to man, it was withdrawn in many
10   Tetracycline       18     13      5        Antibiotic. All tetracyclines accumulate in the developing bones and teeth of the foetus of young children which can result i n
     (paediatric)                               retarded bone growth and dental staining. Preparations intended specifically for children have been withdrawn in some
                                                countries, whereas in others warnings are required on the label advising against administration of tetracyclines to young
                                                children and pregnant women. Non-paediatric dosage forms remain in the WHO Model List of Essential Drugs.
11   Alclofenac         13     13      --       A phenylacetic acid derivative with analgesic, antipyretic and anti-inflammatory activity. Introduced for the treatment of
                                                rheumatic disorders. Use was associated with a high incidence of adverse effects, mainly skin rashes and a urinary
                                                metabolite was reported to have mutagenic activity. The drug remains on the market in at least three countries with highly
                                                evolved regulatory authorities.
12   Phenolphthalei     @EC    @EC     1        Has been widely used as a laxative. It has been associated with adverse effects, notably skin reactions, potassium loss and
     n                  + 13   +12              atonia. This has led to the withdrawal of phenolphthalein from pharmaceutical preparations in several countries. Elsewhere
                                                it remains available in OTC preparations.
13   Phenylbutazon      36     12      26       A pyrazolone derivative with anti-inflammatory, analgesic and antipyretic activity. Used for the treatment of rheumatic
     e                                          disorders. Its use was subsequently associated with serious and sometimes fatal adverse reactions, notably cases of
                                                aplastic anaemia and agranulocytosis. Many national drug regulatory authorities consider that more recently introduced
                                                drugs offer a safer alternative for most, if not all patients requiring anti-inflammatory agents, Phenylbutazone has thus been
                                                either withdrawn at national level or retained with rigorously restricted indications for patients unresponsive to other therapy.
14   Practolol          14     11      3        A beta-adrenoreceptor antagonist. Introduced for the treatment of angina and cardiac dysrhythmias. Long-term use had
                                                been associated wit h serious delayed idiosyncratic reactions (oculo-mucocutaneous syndrome) and this led to the
                                                withdrawal of oral preparations by the major manufacturer on a worldwide basis. Intravenous preparations remain available
                                                in many countries for the emergency treatment of selected cardiac dysrhythmias.
15   Benzylpenicillin   11     11      --       Topical preparations intended for use on the skin have been associated with allergic rashes and are in general no longer
     sodium (topical                            acceptable. However, topical preparations for specialized use, in particular in the eye and on open wounds, are available in
     preparations)                              many countries. Injectable preparations of benzylpenicllin are included in the WHO Model List of Essential Drugs.
16   Somatropin         14     10      4        Used in the treatment of hypopituitary dwarfism. It became known that Creutzfeldt-Jakob disease, a potentially fatal form of
     (pituitary-                                brain degeneration resulting from a slow neurotropic viral infection, had developed in several patients who had received
     derived)                                   preparations of somatropin. This led to the withdrawal of these preparations in many countries. More efficient purification
                                                procedures greatly reduced the risk of viral contamination, but products containing pituitary derived somatropin have been
                                                largely superseded by biosynthetically-manufactured preparations produced using recombinant techniques.
17   Astemizole         13     10      3        Histamine H1-receptor antagonist. Serious cardiovascular adverse reactions have been reported when used concomitantly
                                                with imidazole antifungals and macrolide antibiotics.
18   Terfenadine        15     9       6        Histamine H1-receptor antagonist. Serious cardiovascular adverse reactions have been reported when used concomitantly
                                                with imidazole antifungals and macrolide antibiotics.
19   Cisapride          14     9       5        Rare but serious heart complications, arrhythmias including sudden death.
20   Halogenated        12     9+      2+       Oxyquinoline, broxyquinoline, clioquinol, diiodohydroxyquinoline. Halogenated hydroxyquinolines are structurally related to
     hydroxyquinolin           (1pae   (1topi   clioquinol. Banned/withdrawn due to neurological disorders.
     e derivatives             )       cal)
21   Thenalidine        9      9       --       A piperidine antihistamine. Introduced for the management of dermatologic and allergic conditions. Its use has been
                                                associated with severe nutropenia. The drug has been withdrawn in many countries. It is apparently still available, however,
                                                in some combination products.
22   Tienilic acid      9      9       --       A diuretic. Use has been associated with hepatotoxicty some which have been fatal, which led to the withdrawal of the drug
                                                in most countries in which it was marketed.

23   Sulfaguanidine    10   8+      1    Sulfonamide anti-infective agent for the treatment of bacterial infections. The importance of sulfonamides has subsequently
                            (1pae        decreased as a result of increasing bacterial resistance and their replacement by antibiotics which are generally more active
                            )            and less toxic. The sulfonamides are known to cause serious adverse effects such as renal toxicity sometimes fatal
                                         exfoliative dermatitis and erythema multiforma and dangerous adverse reactions affecting blood formation such as
                                         agranulocytosis and haemolytic and aplastic anaemia. Although sulfaguanidine, which is poorly absorbed from the
                                         gastrointestinal tract, is no longer recommended in some countries, it continues to be used in others for the treatment of
                                         local intestinal infections, including bacterial dysentery, and for pre-operative bowel preparation. Other sulfa drugs include
                                         sulfacarbamide, sulfadimidine, sulfamerazine sodium, sulfamethiazole, sulfamethoxypyridazine, sulfanilamide,
                                         sulfathiazole, sulfisomidine, topical sulfonamides etc.
24   Diphenoxylate     9    8       1    Used in the symptomatic treatment of acute and chronic diarrhea to reduce intestinal motility. Has been associated with
     (paediatric)                        central nervous system toxicity, particularly in children. The WHO recommends that diphenoxylate should not be used for
                                         the management of diarrhea in children and many countries have since withdrawn products containing this product
                                         indicated for paediatric use. (Difenoxin is the principal metabolite of diphenoxylate – banned from paediatric formulations
                                         from 4 countries)
25   Erythromycin      9    8       1    Macrolide antibiotic for the treatment of gram-positive infections. Its use has been associated with a higher incidence of
     estolate                            hepatic toxicity than that seen with other salts and esters of erythromycin. This led to its withdrawal by some regulatory
                                         authorities whereas others required the addition of a warning in the product information. Evidence that the estolate ester is
                                         more hepatotxic than other salts have subsequently been disputed. It has been claimed to be the most effective ester for
                                         treatment of Legionnaire’s disease and preparations remain widely available.
26   Mibefradil        8    8       --   Calcium channel blocking agent. Serious drug interactions and serious adverse reactions.
27   Bismuth salts     14   7       7    Used in OTC preparations for the treatment of dyspepsia. Prolonged intake of high doses of bimuth subgallate was
                                         associated with cases of encephalopathy. Similar association involving the subnitrate salt became evident. Preparations
                                         containing bismuth salts have since either been withdrawn or subjected to restrictive regulatory action in many countries.
                                         However, in some countries preparations containing bismuth subsalicylate, which retains a place in the management of
                                         dyspepsia, have been exempted from this restriction. Additionally colloidal bismuth subcitrate is widely used in the
                                         treatment of gastritis and peptic ulcer disease.
28   Nialamide         7    7       --   A monoamine oxidase inhibitor (MAOI) for the treatment of depressive illness. Potentially serious interactions with foods
                                         containing tyramine have inspired much restrictive regulatory action. MAOI still retains a place in serious depressive illness
                                         although there is no international consensus on which compounds should be preferred. (Other MAO inhibitors include
                                         iproniazid, isocarboxazid, tranylcypromine)
29   Amfepramone       7    7       --   A phenethylamine derivative. Controlled under Schedule IV of the 1971 Convention of Psychotropic Substances. It remains
     (hydrochloride)                     available in many countries with highly evolved drug regulatory authorities as an aid to weight reduction. Some regulatory
                                         authorities have banned these products due to the lack of evidence of their value in long-term management of obesity and
                                         the potential for abuse and dependency.
30   Methaqualone      7    7       --   A quinazolone derivative. A sedative-hypnotic drug. It is widely abused and is associated with severe withdrawal symptoms.
                                         Is controlled under Schedule IV of the 1971 Convention of Psychotropic Substances.
31   Phentermine       7    7       --   A sympathomimetic amine used as an anorexic agent. It retains a place in the treatment of obesity. However, since it has
                                         been subjected to abuse and because dependence can occur, it is controlled under Schedule IV of the 1971 Convention on
                                         Psychotropic Substances. (chlorphentermine was introduced for the treatment of obesity. Associated cases of pulmonary
                                         hypertension led to its withdrawal in some countries)
32   Strychnine and    7    7       --   Has no demonstrated therapeutic value and there is no justification for its presence in any medication.
33   Trovafloxacin     8    6       2    Fluoroquinolone antibiotic. Risks of serious liver toxicity. (Also alatrofloxacin has been rejected registration in some
     mesilate                            countries due to serious and unpredictable liver injuries)
34   Furazolidone      8    6       2    A nitrofuran derivative with antibacterial and antiprotozoal activity. It was shown to have carcinogenic potential following
                            (2pae        long-term administration to experimental animals. However, the relevance of this to short term therapy has not been
                            )            established. The risk-benefit assessment varies and furazolidone remains widely available in many countries.

35   Amfetamine        7    6   1    Potent central stimulant. Use had been widely discouraged due to abuse of their euphoric effect and their limited field of
                                     usefulness. Have a place in the treatment of narcolepsy and in hyperkinetic syndrome in children. They are no longer
                                     recommended for use in obesity or depressive illness. It is controlled under Schedule II of the 1971 Convention of
                                     Psychotropic Substances. (dexamphetamine)
36   Amineptine        7    6   1    Antidepressant. Potential for risk of abuse and dependence.
37   Cyclamates   in   7    6   1    Non nutritive sweetening agents. Demonstrated to have carcinogenic potential in experimental animals at very high and
     drugs                           long sustained doses. Some countries have consequently banned their use as food additives, whereas in others they
                                     remain available for this purpose. Most countries, however, continue to allow their use in small quantities in pharmaceutical
38   Dantron           7    6   1    An anthroquinone derivative. Had been widely used as a laxative. Studies have shown that administration of high doses is
                                     associated with the development of intestinal and liver tumors in rodents.
39   Tolcapone         7    6   1    Reports of hepatotoxicity and unfavourable risk/benefit balance.
40   Dihydrostrepto    6    6   --   A derivative of the aminoglycoside antibiotic streptomycin with similar antibacterial activity. Used in the treatment of
     mycin                           tuberculosis and gram-negative infection. Preparations for systemic use had been widely withdrawn due to unfavourable
                                     risk/benefit ratio. Known to cause severe ototoxicity. Oral preparations remains available in some countries .
41   Triacetyldiphen   6    6   --   Derivative of oxyphenisatine.
42   Thalidomide       12   5   7    Not withstanding the highly potent teratogenic action, this drug retains a place in the treatment of reactional lepromatous
                                     leprosy and several serious dermatological conditions. In many countries, the competent authorities have granted
                                     exemption for licensing requirements to enable doctors to obtain limited supplies of thalidomide under strict controlled
                                     circumstances for use in named patients. Arrangements have also been made by some national drug regulatory authorities
                                     for thalidomide to be used in institutions concerned with the treatment of leprosy.
43   Benzyl alcohol    8    5   3    Antimicrobial agent in pharmecutical preparations. Following the death of neonates after parenteral administration many
                                     countries warned against the use of such preparations in neonates. This decision is not applicable for the use of benzyl
                                     alcohol as a preservative in other circumstances or its use in topical preparations and no country has placed a total ban on
                                     the compound.
44   Amaranth          5    5   --   A colouring agent in foods and pharmaceutical products, Positive findings in carcinogenicity tests have been reported. It has
                                     been withdrawn by some national regulatory authorities because of uncertainty regarding its safety, but elsewhere it
                                     remains widely used.
45   Azaribine         5    5   --   An antineoplastic agent. Introduced for the treatment of severe, recalcitrant, disabling arthritis. Thromboembolic and
                                     thrombotic reactions have been reported.
46   Canthaxanthin     5    5   --   Naturally occurring carotenoid. Widely used as a food colouring agent. It has been included in oral ‘artificial suntan’
                                     preparations. Also available in preparations used in the treatment of certain photodermatoses. It has been associated w ith
                                     crystalline deposits in the retina. Reported functional changes relating to dark adaptation have been of marginal significanc e
                                     and largely reversible. It has led to the withdrawal of suntan preparations containing cathaxanthin by several regulatory
                                     authorities. Preparations for treatment of photodermatoses remain available in some but not all of these countries.
47   Chlormadinone     5    5   --   A synthetic progestogen, Has been associated with an increased incidence of mammary tumours in beagle bitches which
     acetate                         led to its withdrawal by several regulatory authorities. The validity of the beagle bitch model as a predictor of carcinogeni city
                                     of steroid contraceptives has been contested by many national regulatory authorities. Chlormadinone remains available i n
                                     some countries.
48   Grepafloxacin     5    5        A fluoroquinoline. In 4 countries the drug was voluntarily withdrawn after the observation of severe cardiovascular events.
49   Hexestrol         5    5   --   Hexestrol is a stilbene derivative. See 61
50   Propyphenazon     5    5   --   A pyrazolone derivative with anti-inflammatory, analgesic and antipyretic activity. Introduced for the treatment of rheumatic
     e                               disorders. Structurally related to the aminophenzones and has been associated with severe blood dyscrasias. Does not
                                     produce potentially carcinogenic nitrosamines and has therefore been used as a replacement drug for aminophenazone. In
                                     certain countries products containing propyphenzone have now been restricted in their indications, whereas in others they

                                             are still available sometimes as OTC preparations.
51     Triazolam          @EC    5    @EC    A benzodiazepine derivative with sedative and hypnotic activity. Introduced for the management of insomnia. It is controlled
                          + 15        + 10   under Schedule IV of the 1971 Convention of Psychotropic Substances. There were reports of a reversible complex of
                                             symptoms including paranoia, depersonalization, nightmares, suicidal tendency and hyperaestheisa in patients receiving
                                             the drug. The basis for this decision was successfully contested by the manufacturer and the drug was reregistered in early
                                             1990 with a revised product information. However, concern was regenerated elsewhere that higher doses are associated
                                             with an unacceptable incidence of unwanted effects and the manufacturer has eventually withdrawn 0.5mg tablets on a
                                             worldwide basis. In 1991 the issue of the safety of triazolam was again reopened by reports of retrograde amnesia and
                                             depression among patients taking the decreased recommended dosages. The product information has been revised by the
                                             US FDA to include more rigorous cautions regarding dosage.

     Combination Products
82     Hormonal           15     15   15     High dose eostrogen/progesterone preparations for pregnancy testing has been associated with birth defects.
83     Mercuric           8      8    8      Mercuric derivatives were formerly widely available in topical anti-infective preparations. The hazards associated with their
       derivatives                           use, including hypersensitivity and allergy, outweigh any therapeutic benefit and such preparations have been withdrawn in
       (topical)                             many countries. Systemic absorption has resulted in chronic mercury poisoning and acrodynia (pink disease) in children.
84     Barbiturates in    7      7           Have been extensively used as sedative-hypnotic drugs. Their use in the treatment of sleep disorders and anxiety has been
       combination                           largely superseded by the benzodiazepines since barbiturates have a greater liability for abuse and development of
                                             tolerance and withdrawal syndrome, lower therapeutic index and a higher incidence of drug interactions and adverse effects
                                             possibly including carcinogenic, mutagenic and teratogenic effects. Although many preparations containing barbiturates
                                             remain available, some regulatory authorities have severely restricted their and withdrawn product licences for combination
                                             products containing these substances. Eg. Combinations with analgesics, anti-rheumatics, other barbiturates, anti-
                                             asthmatics etc.
                                             Barbiturates include heptabarb, hexobarbital, vinbarbital amobarbital, aprobarbital, barbital, Phenobarbital,
                                             secobarbital, pentobarbital etc.
8      Anorectic drugs    @EC    5    @EC    Amphetamine like – amfepramone, clobenzorex, fenbutrazate, fenproporex, mazindol, mefenorex, cathine
       (Anorectic         +6          +1     (norpseudoephedrine), phendimetrazine, phenmetrazine, phentermine and propylhexedrine, benfluorex,
       drugs         in                      benzfetamine, metamphetamine, methylphenidate
       combination)                          Serotonergi compounds – dexfenfluramine, fenfluramine, levofenfluramine
                                             Other anorectic agents and those drugs used in anoretic preparations include pemoline, pipradol, cathine
                                             Drugs used in appetite suppressants - Hyoscine methonitrate, meprobamate, phenylpropanolamine
                                             ‘Anti-obesity’ drugs. The Committee of Proprietary Medicinal Products recommends the inclusion of a boxed warning in the
                                             Summary Product Characteristics that clearly sets out the risks of pulmonary hypertension that is associated with anorectic
                                             agents. The committee concluded the risk-benefit balance is favourable provided that the products are used under strict
                                             supervision by specialist in carefully selected patients.
86     Antidiarrhoeal     6      6    --     The list concerned is very long. Eg. The aminoglycoside antibiotics – streptomycin, kanamycin and neomycin, non-
       combinations                          absorbable sulfonamides (i.e. sulfaguanidine, succinylsulfathiazole, phthalylsulfahiazole) and halogenated
                                             hydroxyquinolines (Eg. Clioquinol, broxyquinoline, chlorquinandol). There is no satisfactory evidence that they are effective.
                                             They have occasionally been associated with severe adverse reactions and some promote the emergence of bacterial
                                             resistance. The WHO recommends that they should not be used for the management of diarrhea in children.
87     Pyrazolones in     9      4    5      Pyrazolone derivatives, which include aminophenzone, metamizole sodium, phenylbutazone and propyphenazone have
       combination                           been associated with serious adverse effects. Since safer alternatives are widely available some regulatory authorities have
                                             withdrawn or severely restricted all pharmaceutical preparations containing pyrazolone derivatives. Other pyrazolone
                                             derivatives include kebuzone, mofebutazone, phenazone, azapropazone, bumadizone, suxibuzone


To top