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Reports of side effects associated with the use of drugs 1985

Item type Report

Authors National Drugs Advisory Board (NDAB)

Publisher National Drugs Advisory Board (NDAB)

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http://hdl.handle.net/10147/244354

Charles Lucas House, 63-64 Adelaide Road, Dublin 2.

NATIONAL DRUGS ADVISORY BOARD

(An B6rd Comhairleach Naisiunta Druganna)

Report of Side Effects

Associated with the Use of Drugs

1985

This publication is for the exclusive use of registered medical and dental practitioners nurses and pharmacists.

t

INTRODUCTION

Any drug which Is therapeutically active may be associated with side effects. These in many circumstances are tolerable because of the ultimate beneficial action of the drug.

Side effects to drugs may be defined as those effects which are:

1. Unintended 2. Unexpected and undesirable 3. Additional to the desired therapeutic one, but expected 4. Excessive in response 5. Due to relative overdose 6. Due to the chemical nature of the drug 7. Due to the drug's capacity to alter the metabolism of other drugs taken by the patient. 8. Due to lack of expected response. 9. Due to failure of absorption or a delay in elimination

10. Inexplicable

All the above side effects may occur at doses normally used in man.

Causative Factors which may be due to the Drug. 1. The basic pharmacological actions 2. The formulation, inactive ingredients and dose form 3. The chemical structure on manufacture or after storage and degradation 4. Allergenicity 5. Interaction with other drugs 6. The kinetics of the drug

Causative Factors which may be due to the patient. 1. Idiosyncrasy 2. Genetic differences 3. Concomitant illness e.g. renal or hepatic dysfunction, thyroid dysfunction, etc. 4. Age 5. Pregnancy 6. Enzyme induction or suppression 7. Concurrent therapy either prescribed or self administered.

In order that drugs for therapeutic use shou ld be given under the best and safest circumstances, it is Important that practitioners be aware of potential hazards In their use.

To help practitioners, the National Drugs Advisory Board circulates these lists of side effects reported in Ireland at yearly intervals. The compilation of such a list Is limited almost entirely by the interest and concern of doctors and dentists and pharmacists in reporting effects associated with drugs.

The practitioners are reminded of the need for cooperation In reporting of all side effects, even suspicions of drug related effects. lt is also suggested that nursing staff in hospitals and in community centres should be alerted and their assistance sought.

CONTENTS

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4-10

Drugs Affecting Central Nervous System Anaesthetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Hypnotics, Sedatives and Anticonvulsants ............................... ...... ............. ..... .. 11-13 Tranquillisers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13-16 Antidepressants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16-18 Stimulants ................ . ............... .... .................................................. 18-19 Analgesics (Central Action) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19-21 Analgesics (PeriphE,ral Action) .............. .. . . ............ . .. . . . ................................ 21 -27 Drugs acting on Peripheral Nerves .......... .. .............. . ..................................... 27-28 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

Drugs Affecting Autonomic System Parasympatholytics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29-30 Sympatholytics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30-33 Sympathomimetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33-34

Drugs Affecting Cardiovascular System Drugs acting on Heart Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Coronary Vasodilat:>rs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35-37 Peripheral Vasodilators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Antihistamines, Histamine and Related Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38-41

Drugs Affecting Haemopoietic System Antineoplastics ancl Antivirals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42-43 Haematinics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 Anticoagulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Coagulants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Blood Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Blood Substitutes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Drugs Affecting Endocrine System Affecting Pituitary Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Oestrogens-Con)unated . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 Oestrogens with Progestogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45-46 Progestogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Corticosteroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46-47 Special Hormones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • . . . . . . . 47-48

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CONTENTS (continued)

Drugs Affecting Nutrition and Metabolism Vitamin Mixtures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Thyroid and Anti-Thyroid Substances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Drugs Affecting Blood Sugar Levels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Salts and Ion Exchangers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51-54 Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54

Anti-Infective Drugs Antibiotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55-59 Synthetic Antibacterials .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59-61 Antiprotozoals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61 Anthelmlntics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 Antifungals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 Local Antiseptics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62 Ectoparasiticides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62-63 Vaccines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63-64

Diagnostic Agents Radiographic Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65

Drugs Acting Locally Affecting Gastrointestinal Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 .l\ffecting Respiratory Tree . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Affecting Skin and Mucous Membranes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66-67 Heavy Metals, Radioisotopes with Chelating Agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

Pharmaceutical Adjuncts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67

Suspected Side Effects 1985 by Systems Affected . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68-69 Sources of Side Effects 1985 ..................................... : . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Deaths Due to Suspected Side Effects 1985 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Interactions 1985 .. .. .................................................... . ....................... 72-73 Special Post Marketing Surveillance 1985 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74 Quality Defects Reported 1985 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Nomifensine Warning January 1986 ............................................................... 76 New Recommendations Concerning Use of Almitrine (Vectarion) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77 New Recommendations Concerning Sympathomimetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77-78

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COMMENTS ON SIDE EFFECTS

1. Halothane In the ten year J:eriod of 1970 to 1980 the Board received 9 reports of hepatitis (2 fatal) associated with the repeated use of halothano. This mirrors experience in other countries. Although the mechanism of action is not as yet generally accepted, the role of allergenicity is considered highly significant. lt Is recommended that where ever possible administration of halothane should not be repeated at less than 3 monthly Intervals.

A second potential source of risk from halothane lies in its cardiodepressant action, a tendency to bradycardia, and to arrhythmias which may lead to particular problems when the anaesthetic is administered to patients maintained on beta-adrenoceptor blockade. lt Is essential that anaesthetists be aware of medications used on patients coming under their cam so that appropriate precaution can be taken.

2. Carbamazepin•~ This drug Is being used more frequently in the mangement not only of epilepsy but for other conditions. lt is useful therefore to review the types of side effects for which clinicians need to be on the alert. The most Important of these concern the central nervous system with incoordination, drowsiness and ataxia, hypersensitivity reactions affecting skin, liver, blood and lung particularly, and those apparently directly related to plasma levels of carbamazepine such as the syndrome of inappropriate secretion of antidiuretic hormone.

3. Glutethimide This drug was withdrawn from the market in 1983. As has been reported in other countries its use has been associated with cases of d•3pendence.

4. Phenothiazineu The Neuroleptic Malignant Syndrome characterised by hyperthermia, semi coma to coma, muscular rigidity and autonomic disorders is generally recognised as being most frequently associated with the high potency anti psychotic drugs such as chlorpromazine, flupenthixol and trifluoperazine. lt is less commonly known that a similar adversf effect can deve op with prolonged antihistamine therapy especially with the phenothiazines, but also with some of th-d other antihistamines. Recovery is delayed with those drugs having a long half life or presented as a dep6t preparation. The reaction cnn be particularly severe in the young.

5. Benzodiazepines lt is again noteworthy that central nervous system irritability manifested as confusion, bizzare behaviour, nightmares, hallucinations, aggression, and occasionally withdrawal syndrome, etc. occurs In some individuals in association with drugs ofthis group particularly those with a short half-life, when used over prolonged periods, in association with other centrally active drugs, or in the elderly.

lt is important tl1at use of benzodiazepines should be limited to short periods of 4 to 6 weeks or less, whether the drug is intended for Insomnia or anxiety, kept to as low a dose as possible if given concomitantly with other central nervous system drugs, and used at minimal levels for the elderly.

6. Midazolam This short acting benzodiazepine has been available for about 18 months as a parenterally administered anaesthetic for short durat.on minor procedures. Particular care is required in its rate of administration and in the selection of patients for its use since lt has a significant propensity for cardiorespiratory functional depression.

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Following the adverse effect reported In 1984, a more dilute formulation was introduced. Doctors are reminded of the need to consider the conditions of use to minimise the possibility of further similar mishaps. The elderly and those with respiratory insufficiency are particularly at risk.

7. Lofepramine

8.

This drug and its active metabolite belong to the tricyclic group of anti depressants. As the side effect pattern shows the anticholinergic and cardiac reactions occur in a fashion similar to that with other trlcyclics. Although no interactions have as yet been reported it is important that practitioners regard this drug as requiring the same precautions as do other members of the group.

Nomifenaine During the first 5 of the 8 years in which this product was marketed In Ireland there was little of significance in the side effect profile observed. However by 1985 a number of unusual hypersensitivity type reactions had occurred, associated in most cases with an Interruption of treatment followed by a repeat course. The manifestations usually consisted of 'flu-like' symptoms but one case involved hepatic dysfunction and in another (1984) acute tubular necrosis and a haemolytic anaemia occurred. During 1985 a few more hypersensitivity reactions of the 'flu-like' type were reported.

The pattern of side effects was similar to that reported elsewhere and in the literature. The incidence was low(less than 1 in 1 0,000) in Ireland. Reactions tended to appear within the first 8 weeks of initial treatment, or in the first few days of reintroduction of the drug. However, ln view of the evidence of increasing hypersensitivity reactions the company, In consultation. with the National Drugs Advisory Board (and similar authorities elsewhere) decided to withdraw the product at the beginning of 1986.

9. Buprenorphine Forty-two adverse reactions were reported in association with use of this centrally acting analgesic. All but one effect followed sublingual dosage. lt is suggested that these side effects should be kept in mind when considering the need for use and the dosage against the degree of pain to be controlled.

10. Nefopam

(see notes on Intensive Surveillance)

11 . Non Steroidal Anti-Inflammatory Drugs The three drugs of this group with the highest number of side effects reported as associated with their use were diclofenac (32), indomethacin (47), and piroxicam (39).

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Diclofenac Indomethacin Piroxicam

Under 65+ Under 65+ Under 65+ 65 years 65 years 65 years

Central Nervc•us System Effects 0 6 0 2 (4 not stated) (4 not stated)

Liver Dysfunction 0 2 0 0 0

Gastrolntestinal Disorders Major 1 2 3 2 1 6 *(1) *(2) *( 1) *(2) *(6)

Minor 8 1 1 4 4

Skin Reactions 3 3 2 0 5 2 (3 not stated)

Blood Dyscraslas 4 0 2 0 4

46% 29% 37% 32% 25% 45%

·o = Bleedin!J

Usage figure~; are not available therefore no figures can be established for incidence of side effects.

Evidence of g :~stro-intestlnal bleeding was the most serious adverse effect in the older age group(> 65 years) with all three drugs. Peptic ulceration as a complication occurred in the younger age group.

lt is suggested that elderly patients receiving nonsteroidal anti-inflammatory drugs should be particularly cautioned in this respect.

12. lbuprofen Two products containing this active ingredient became available in pharmacies without prescription during 1985 for a trial period. Particular attention is being directed to side effects reported with this substance to ensure that the frequency or severity of such reactions does not change significantly with the increased opportunity of misuse. Twentythree side effects were reported during the year.

13. Oxybutynin This anticholinergic drug is used in the management of lower urinary tract dysfunction, and has been under Intensive surveillance lor 2 years. During that time 300 patients received treatment with the drug, and 9 experienced side effects, all anticholinergic in type. Four were sufficiently severe as to require that treatment be discontinued.

14. Sympathomimetic and Antihistamine Combinations During 1985, twenty-one further side effects were reported In association with sympathomimetics and antihistamine. These occurred In 7 children and 5 adults. Of the children, 3 were under the age of 1 year- 2, 3 and 9 months. Four side effects msulted from the concurrent use of an oral dose form and nasal drops. Children under the age of 2 years should not mceive these medications unless they are considered essential by the physician and particular care should be talcen to avoid concomitant use of nasal or eye drops with similar active ingredients.

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15. Tocainide This product, an antiarrhythmic was introduced on to the market in 1985 for use in patients unresponsive to conventional therapy. Two cases of white cell abnormalities occurred in patients on prolonged therapy. Both were reversible on discontinuing the drug. Nevertheless in view of this experience and that reported elsewhere the Board has limited its use to a 'named patient' basis with consultant supervision.

16. Theophylline Products containing theophylline are being used increasingly in the management of bronchospasm. Twenty-four side effects were reported during 1985. In 3 patients interactions with ketoconazole were recorded, with reduced efficacy of theophylline. The other system with significant adverse effects was the central nervous system with hallucinations, agitation and nightmares as examples of effects often associated with plasma levels of drug higher than are desired.

17. Suloctodil During 1984 and 1985 reports appeared in the literature concerning hepatic adverse reactions associated with the use of suloctodil, a peripheral vasodilator. The National Drugs Advisory Board investigated the details of the various cases reported. Initially the Board felt that the regular monitoring of liver function would be sufficient to detect the early phases of hepatotoxicity but subsequent information suggested that the development of the reaction might progress too rapidly. The company in consultation with the National Drugs Advisory Board, and similar bodies in other countries withdrew the product in the latter part of 1985.

18. Dinoprostone Intravaginal dinoprostone for Induction of labour at term was introduced a number of years ago. Its use has been satisfactory and free of major problems in patients kept under close observation during the treatment. An adverse event occurred in 1985. One of the problems with any Induction agent is the precipitation of uterine hypertonus in which the sustained strong contraction may force the foetal head against the bony margin of the unprepared cervical canal and vagina. Fracture of the foetal skull with tentorial tears and intracranial haemorrhage led to the loss of the baby. Unfortunately the mother developed other complicating sequelae of uterine hypertonus with an amniotic fluid embolus, an intravascular coagulopathy and cerebral haemorrhage, from which she died. Fortunately such cases are a rare experience in countries in which the product has been used extensively. The event however underlines the need for close objective monitoring of uterine activity and foetal wellbeing at all t imes from introduction of the vaginal product to delivery of the infant.

19. Almitrine A number of cases of peripheral neuropathy including one in Ireland , have been reported In association with the use of this product in the management of irreversible chronic obstructive airways disease with respiratory insufficiency. Since the condition itself Is associated with the development of neuropathy it is difficult to attribute such events solely to the use of almitrine. Nonetheless investigation carried out as a consequence suggested the need for revision of dosage regime to take account of possible accumulation of drug with prolonged use. The product Is under special monitoring of use.

20. Anti-infectives The results of a special study of pseudomembraneous colitis carried out by a large general hospital were reported to the Board. In a hospital setting it is common for patients to have multiple antibiotic therapy, usually broad spectrum antibiotics often with an additional anti-infective with activity against unusual or resistant microorganism such as pseudomonas. Of the 24 patients with pseudomembraneous colitis who were studied only 7 had a single antibiotic.

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The remaining 17 received anything from 2 to 6 with an average of 3. While it is often the case that ttospitalised patients are suffering from complicated multiple infections and the chances of cross infection are high in the wards, it might be well to review anti-infective therapy regularly on the wards to avoid unnecessary continuation of therapy or duplication of agents affecting the same range of micro-organisms.

21. Piperazine Attention should be drawn to the side effects associated with the use of this anthelmintic in the adult as well as the child. Of parti<;ular concern are those affecting the central nervous system.

22. Radio-opaquE· Contrast Media Twenty nine rEtports were received of adverse effects associated with use of these agents in radiography. Many of these were serious and even life threatening requiring emergency measures for recovery.

23. Dyes The reported E1xperiences with tartrazine as an allergen have alerted physicians to the possibility of similar reactions from other azeo dyes used not only in medicines but also in comestibles. While the substance is rare which exerts no J allergenicity cllrtain substances used frequently such as colourants should be extensively investigated before use or attempts mad•3 to avoid dyes altogether.

24. Tardive dyskinesia As a result of reports received in the previous year 1984, the National Drugs Advisory Board now requires that this potential risk t•e brought to the attention of prescribers of all anti-psychotic drugs and major tranquillisers. A special warning is now included in the literature for such products:-

Tardive dyskinesia, a syndrome characterised by involuntary dyskinetic improvement may develop in patients on antipsychotic therapy and occasionally even in those who have discontinued such treatment. Those at particular risk include the elderly, females, and patients on high dosage or prolonged therapy, i.e. with a high total cumulative dose. Nonetheless the syndrome can develop without such factors being involved. The syndrome may be irreversible, or only slowly reversed. Fine vermicular movements of the tongue are reported to be an early sign and if the medication is discontinued the syndrome may not progress.

In an attempt to minimise the possibility of the development of such a syndrome, major tranquill iser therapy should be reserved for these patients for whom it is essential, the dosage used should be the lowest commensurate with optimal benefit and duration of treatment should not extend beyond that necessary for the patient.

There is no known treatment for tardive dyskinesia. The antipsychotic drug may mask it, as may anticholinergic agents. Although the latter do not predispose to tardive dyskinesia, they should not be used routinely to mask the parkinsonian ottects of anti-psychotic drugs as they may mask the early signs of tardive dyskinesia.

25. Reyes Syndrome This syndrome, first described in 1963, comprises an acute encephalopathy associated with hypoglycaemia, hyperammonctemia, elevated transaminase, and fatty changes in the liver and in muscle. lt has been reported after upper respiratory tract Infections with a variety of common viruses including the agents for influenza and varicella, herpes simplex, adenovirus, and Coxsackie virus.

it may occur in children and adolescents but its true incidence is difficult to determine because of confusion with other diseases having signs of encephalopathy and liver disorder, and the possibility of missing cases through failure to apply the accepted diagnostic criteria. However, the condition is rare, and at least in some countries, becoming even rarer. At presnnt its incidence is estimated to be about 1:100,000 of the population at r isk.

8

A few papers have been published over the last few years suggesting that the Ingestion of aspirin, given for the relief of the upper respiratory tract infection, might play a role in the development of the syndrome. Two prospective studies were commenced, one In the United States and one in the United Kingdom, neither of which are complete. However, preliminary reports may be interpreted as supporting to some extent a relationship between Reye's Syndrome and aspirin ingestion.

In Ireland a few patients with A eye's Syndrome have been reported over the past five years, but aspirin ingestion did not occur in all cases.

Despite the relative rarity of Reye's Syndrome and the absence of evidence clearly linking Ingestion of aspirin with development of the syndrome, the pharmaceutical companies have agreed with the National Drugs Advisory Board to take certain precautionary measures as follows:-

1. All paediatric dose forms of aspirin will be confined to pharmacies, available on prescription only.

2. All Aspirin containing preparations will carry an additional warning on the pack:-"This product should not be given to children, particularly those under twelve years of age, without medical advice".

The Board requests that doctors, when prescribing aspirin for children, bear In mind the possibility of a complication of this type even If it is remote, and report any suspicions to the National Drugs Advisory Board.

lt would be appreciated if doctors and pharmacists remind patients and parents not to use aspirin, or any medicine, unnecessarily for their children.

During 1985 the National Drugs Advisory Board received 976 reports of adverse reactions from which 2020 side effects were recorded.

As in previous years just over 30% of the effects were associated with drugs affecting the central nervous system and just under 30% were associated with anti-Infective drugs.

Fourteen deaths were reported in association with the administration of drugs. Three of these were the result of accidental overdose. Two (a mother and infant) were consequent to an undetected and excessive reaction to prostaglandin E2 use. The Malignant Neuroleptic Syndrome associated with the use of major tranquillisers resulted in another death possibly as a result of additive toxicity. One death from liver failure underlines the importance of regular monitoring of liver function in patients on prolonged therapy with non sterlodal anti-inflammatory agents.

Eighteen drug interactions were reported in 1985. Additive toxicity occurred in six Instances, two with alcohol (1 fatal), two with central nervous system depressants (1 fatal), one associated with two drugs both, myocardial depressants, and one with sympathominetics administered concomitantly in three different medications.

Cimetidine, by inhibiting hepatic microsomal activity accentuated the toxic responses of two drugs given concurrently. The efficacy of oestrogen/ progestogen combinations was decreased by concurrently used phenobarbitone and penicill in, while theophylline efficacy was lowered by concurrent ketoconazole administration. Displacement from protein binding likely accounted for the increased anti-coagulant effect of warfarin with Indomethacin. The occurence of hyponatraemia with captoprll and amiloride used together emphasises the importance of avoiding such a combination.

9

Forty-four percent of the reports received came from general practitioners, 13% from pharmacists and 27% from hospitals. Pharmacists also reported 26 quality defects.

The Board would like to express its appreciation of the co-operation of doctors and pharmacists in reporting side effects to medicines, and alsCt quality defects.

The Board particularly requests that medical and pharmacy practitioners report any suspicions with regard to medicines which they are usin;J. This would greatly assist the Board in carrying out its surveillance functions limited as they are by curtailment of staffing.

10

SIDE-EFFECTS JANUARY- DECEMBER 1985

No. of No. of Drug Act ion Approved Name Reaction CaRS CaRS ----- -----

Drugs Affecting Central Nervous System

Anaesthetics Halothane Interaction with Propranolol Interaction (Bradycardia 0

(Heart Block 0

Hypnotics, Sedatives and Alcohol Interaction with Disulf~ram Anticonvulsant.s Interaction Cardiac Arrest 1 1

Hypotension 1 0 Nausea 1 0 Sweating - Excessive 1 0 Tremor 1 0 Vomiting 1 0

Interaction Interaction w1th Phentermine (Agitat1on 1 0 (Ataxia 1 0 (Paraesthesia 1 0

Carbamazepine Abnormal liver Function Tests 1 0 Angioneurotic Oedema 1 0 Ataxia 2 0 DermatitiS 1 0 Drowsiness 1 0 Eye Irritation 1 0 Inappropriate Antidiuretic 4 0

Hormone Secretion Syndrome Leucopenia 1 0 Nausea 2 0 Photosensitivity 1 0 Rash 4 0 Speech Slurred 1 0 Systemic lupus Erythematosus 1 0 Toxic Erythema 1 0 Vision - Blurred 1 0 Vomiting 2 0

Glutethimide Drug Dependence 0

11

SIDE-EFFECTS JANUARY - DECEMBER 1985

No. of No. of Drug Action Approved Name Reaction Cases c .... ---- ---


Hypnotics, Sed.ativu and Nitrazepam Aplastic Anaemia 1 0 Antlconvulsants Nightmares 1 0

Phenobarbitone Atax1a 0 Claw Hand 0 Dupuytren's Contracture 0

Interaction Interaction with Ethinyloestradiol plus Levonorgestrel 0

(Breakthrough Bleeding 0 (Rash

Phenytoin Angioneurotic Oedema 1 0 Anorexia 1 0 Cervical Lymphadenopathy 1 0 Conjunctivitis 1 0 Erythema 2 0

Interaction Interaction with Cimetidine 1 0 (Peripheral Neuropathy)

0 lethargy 1 Low Serum Folate 1 0 Pruntus 1 0 Rash 2 0 Visual Disturbance 1 0

Sod1um Valproate Ataxia 1 0 (Congenital Abnormality 1 0 (lumbar Myelocele (Congenital Abnormality) (Spina Bifida)

0

Dermatitis - Exfoliative 1 0 Drowsiness 1 0 Hypertonia 1 0 leucopenia 1 0 Nausea 1 0 Vomiting 1 0

12


No. of No. of Drug Action Approved Name Reaction Cases CaMS

----


Hypnotics, Sedatives and Temazepam Gastric Upset 1 0 Anticonvulsants Hallucinations 1 0

Insomnia 2 0 Nervousness 1 0 Restlessness 1 0

Thiopentone Rash 0

Triazolam Backache 1 0 Epileptic Attack 1 0 Headaches 1 0

Interaction Interaction with Amitriptyline (Confusion 1 0 (Disorientation 1 0 (Dyspepsia 1 0 (Somnambulism 1 0 Muscle Spasm 1 0

Triclofos Appetite Loss 1 0 Hypertonia 1 0 Hypotonia 1 0 Periorbital Oedema 1 0

Tranquillisers Alprazolam Dizziness 0 Epileptic Attack 0

Bromazepam Emotional Lability 1 0 Grand Mal Attack 1 0

Chlordiazepoxide with Drowsiness 0 Amitriptyline

Chlorpromazine Cardiorespiratory Arrest 1 1 Dysphagia 1 0 Erythema 1 0

13


No. of No. of Drug Action Approved Name Reaction Cases Cases


Tranquillisers Chlorpromazine Euphoria 1 0 Extrapyramidal Disorder 1 0 Hypotension 1 0 Leucopenia 1 0 Lupus Erythematosus 1 0 Malignant Neuroleptic Syndrome 1 0 Photosensitivity 1 0

Clobazam Ataxia 1 0 Drowsiness 1 0 Speech Slurred 1 0 Urinary Retention 1 0

Clorazepate Drowsiness 0 Oculogyric Crisis 0

Diazepam Aggression 1 0 Confusion 1 0 Drowsiness 1 0 Emotional Upset 1 0 Rash 1 0 Syncope 1 0

Flunitrazepam Nightmares 0

Flupenthixol Cardiorespiratory Arrest 1 1 Dysphagia 1 0 Euphoria 1 0 Extrapyramidal Disorder 1 0 Malignant Neuroleptic Syndrome 1 0 Muscle Spasm of Jaw 1 0

Fluphenazine Amnesia 0 Erythema 0 Extrapyramidal Disorder 0 Hypotension 0 Lupus Erythematosus 0

14


No. of No. of Drug Action Approved Name Reaction Cases c ....


Tranquillisers Fluphenazine Parkinson's Syndrome 1 0 Vomiting 1 0

Fluphenazine with Glossitis 0 Nortriptyline

Flurazepam Drowsiness 0

Haloperidol Dystonia 3 0

Lorazepam Ataxia 2 0 Confusion 3 0 Disorientation 1 0 Dizziness 1 0 Drowsiness 1 0 Speech Slurred 1 0 Syncope 1 0 Visual Disturbance 1 0 Withdrawal Syndrome 1 0

Meprobamate with Aspirin Diarrhoea 1 0 with Ethoheptazine Nausea 1 0

Pruritus 1 0 Rash 1 0 Vision Blurred 1 0

Midazolam Cardiac Respiratory Failure 1 1 Coma 1 0 Hypertension 1 0 Respiratory Depression 1 0 Restlessness 1 0 Tachycardia 1 0

Prazepam Abdominal Pain 1 0 Lethargy 1 0 Oedema of Hands 1 0 Tongue Oedema 1 0 Urticaria 1 0

15




Tranquillisers Perphenazine Oculogyric Crisis 0

Prochlorperazine Eye Pain 0

Thiorldazine Drug Overdose 1 1 Dystonia 1 0 Hypotension 3 0 Neutropenia 1 0

Trifluoperazine Cardiac Arrest 1 Dysphagia 0 Euphoria 0 Malignant Neuroleptic Syndrome 0

Trifluoperazine with Alopecia 0 Tranylcypromine

Interaction Interaction with Dothiepin (Death due to probable overdose)

Antidepressants Amitriptyline Bronchospasm 0 Grand Mal Attack 0

Interaction Interaction with Triazolam (Confusion 0 (Disorientation 0 (lack of Awareness 0 (Somnambulism 0

Amitriptyline with Drowsiness 2 0 Chlordiazepoxide

Clomipramlne Anorexia 1 0 Hypotension 1 0 Paraesthesia 1 0 Tremor 1 0

16



--------


Antidepressants Dothiepin Angioneurotic Oedema Constipation

1 0 1 0

Enlarged Parotid Glands 1 0 Insomnia 1 0 Rash 1 0 Sweating Excessive 1 0 Urticaria 1 0 Visual Disturbance 1 0 Weakness 1 0

Imipramine Irritability 1 0 Withdrawal Syndrome 1 0

Lithium Bradycardia 1 0 Photosensitivity 1 0

Lofepramine Chest Pain 1 0 Constipation 1 0 Dry Mouth 1 0 Headache 1 0 Hypomania 1 0 Insomnia 1 0 Muscle Spasm 1 0 Nightmares 1 0 No Response to Drug 1 0 Tachycardia 1 0 Urinary Retention 1 0

Mianserin Delirium 1 0 Drowsiness 3 0 Exacerbation of Depression 1 0 Irritability 1 0 Nightmares 2 0 Polyuria 1 0

Nomifensine Cerebrovascular Accident 0 Myalgia 0 Nausea 0

17



-----

Drugs Affecting tCentral Nervous System

Antidepressants Nomifensine Pyrexia 0 Shivering 0

Nortriptyline with Glossitis 0 Fluphenazine

Tranylcypromine with Trifluoperazine

Alopecia 0

Interaction Interaction with Dothiepin (Death due to probable overdose)

Trazodone Asthenia 1 0 Erythema 1 0 Hyperactivity 1 0 Palpitations 1 0 Pruritus 1 0 Urticaria 2 0

Trimipramine Agitation 1 0 Ataxia 1 0 Drowsiness 2 0 Insomnia 1 0 Nightmares 1 0

Stimulants Caffeine with Dizziness 2 0 Ascorbic Acid with Dyspnoea 1 0 Brompheniramine with Headache 1 0 Paracetamol Hypertension 1 0

Rash 1 0 Restlessness 1 0

Caffeine with Aspirin Vomiting 0

Diethylpropioi'J Erythema 0 Rash 0

18


No. of No. of Drug Action Approved Name Reaction Cases Cases ----------------------- -----------------Drugs Affecting Central Nervous System

Stimulants Phentermine

Interaction

Analgesics -(Central Action)

Buprenorphine

Codeine

Codeine with Dicyclomine with Potassium Chloride

19

Insomnia

Interaction with Alcohol (Agitation (Ataxia (Paraesthesia Nausea

Confusion Dehydration Disorientation Dizziness Drowsiness Enuresis Fear Gastric Stasis Gastric Upset Hallucinations Headache Insomnia Lethargy Malaise Nausea Oral Aphthous Ulceration Sweating - Excessive Syncope Tremor Vomiting Weakness

Drug Abuse Drug Dependence Withdrawal Symptoms

Erythema Rash

2

1 1 1 1

1 1 1 4 1 1 1 2 1 1 4 1 1 1 5 1 1 1 3 9 1

1 1 1

0

0 0 0 0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0

0 0




Analgesics - Dextromethorphan Dizziness 0 (Central Action) Ught Headedness 0

Tinnitus 0

Dihydrocodeine Lack of Efficacy 0 Weakness 0

Dihydrocodeine with Paracetamol Urticaria 0

Ethoheptazine with Diarrhoea 1 0 Aspirin with Nausea 1 0 Meprobamate Pruritus 1 0

Rash 1 0 Vision - Blurred 1 0

Meptazinol Dizz10ess 1 0 Dyspepsia 1 0 Nausea 2 0 Pallor 6 0 Sweating Excessive 6 0

Nefopam Agitation 1 0 Hallucinations 1 0 Hyperexcitation 1 0 Hysteria 1 0 Light Headedness 1 0 Nausea 5 0 Restlessness 1 0 Shivering 1 0 Syncope 1 0 Thirst 1 0 Vertigo 1 0 Vomiting 1 0

Pentazocine with Dizziness 1 0 Paracetamol Malaise 1 0

Vomiting 1 0

20


No. of No. of Drug Action Approved Name Reaction c .... Cases

------ -- -- ------


Analgesics Pholcodlne Anaphylaxis 0 (Central Action) ConjunctivitiS 0

Urticaria 0

Pholcodine with Carbinoxamine wtth AnaphylaxiS 0 Ephedrine Urticaria 0

Analgesics - Aspirin Amnesia 1 0 (Peripheral Action) No Response to Drug 1 0

Reyes Syndrome 2 1

Aspirin with CaHeine Vomitmg 0

Aspirin with Ethoheptazlne Diarrhoea 1 0 with Meprobamate Nausea 1 0

Pruntus 1 0 Rash 1 0 VIsion - Blurred 1 0

Asptrin with Bronchospasm 1 0 Methocarbamol Drowsiness 1 0

Nausea 1 0 Purpura 1 0 Rash 1 0 Urticaria 1 0

Asp1nn w1th Sodium Bicarbonate Asthma 0

Diclofenac Anaemia 1 0 Aplastic Anaemia 1 0 Bone Marrow Hypoplasia 1 0 ?Cerebrovascular Accident 1 0 Confusion 1 0 Constipation 1 0 Dyspepsia 1 0 Dyspnoea 1 0 Erythema Nodosum 1 0 Ep1gastric Pain 1 0

21




Analgesics Oiclofenac Gastritis 1 0 (Peripheral Action) Gastrointestinal Haemorrhage 1 0

Hepatitis 2 1 Hypochromic Anaemia 1 0 Injection Site Fibrosis 1 0 Jaundice 2 0 Liver Failure 1 1 Macrocytosis 1 0 Melaena 2 0 ?Myocardial Infarct 1 0 Nausea 1 0 Oedema - Ankles 1 0 Pancytopenia 1 0 Petechiae 2 0 Rash 2 0 Urticaria 1 0 Visual Dis1Urbance 1 0 Vomiting 1 0

Oiflunisal Pruritus 1 0 Urticaria 1 0

Fenbufen Bullae - Lips 1 0 Dyspepsia 2 0 Erythema 1 0 Erythema Multiforme 1 0 Mouth Ulcers 1 0 Nausea 1 0 Pruritus 2 0 Purpura 1 0 Rash 8 0 Urticaria 2 0 Vomiting 1 0

Floctafenine Agranulocytosis 0

Flurbiprofen Angioneurotic Oedema 2 0 Asthenia 1 0

22




Analgesics Flurbiprofen Dyspnoea 1 0 (Peripheral Action) Gastritis 2 0

Haematemesis 1 0 Hypotension 1 0 Sweating Excessive 1 0 Syncope 1 0 Tachycardia 1 0 Vomiting 1 0

lbuprofen Alopecia 1 0 Anaemia 1 0 Anorexia 1 0 Bronchospasm 1 0 Diarrhoea 1 0 Depression 1 0 Duodenal Ulcer 1 0 Dry Mouth 1 0 Dyspepsia 1 0 Fatigue 1 0 Gastric Ulcer 1 0 Gastritis 1 0 Haemoly1ic Anaemia 1 0 Headache 1 0 Nausea 2 0 Periorbital Oedema 1 0 Pruritus 1 0 Rash 1 0 Stricture of Bile Duct 1 0 Thrombocy1openia 1 0 Vision - Blurred 1 0 Urticaria 1 0

Indomethacin Abnormal Liver Function Tests 1 0 Angioneurotic Oedema 1 0 Anxiety 1 0 Anxiety Neurosis 1 0 Bizarre Behaviour 4 0 Confusion 4 0 Decreased Renal Function 1 0

23



Drugs Affecting C:entral Nervous System

Analgesics Indomethacin Diabetes Mellltus 1 0 (Peripheral Action) Diarrhoea 1 0

Dizziness 1 0 Drowsiness 1 0 Dyspepsia 1 0 Exacerbation of Cardiac Failure 1 0 Gastrointestinal Bleeding 1 0 Haematemesis 1 0 Haemolytic Anaemia 1 0 Headache 2 0 Hepatitis 2 1

Interaction Interaction with Warfarin (Haematemesis 1 0 (Prolonged Prothrombin Time 1 0 Jaundice 2 0 Liver Failure 1 1 Malaise 1 0 Nausea 5 0 Nightmares 1 0 Oedema of Ankles 1 0 Perforated Duodenal Ulcer 1 0 Perforation of Gastrointestinal Tract 1 0 Positive Coomb's Test 1 0 Psoriasis 1 0 Thrombocytopenia 1 0 Vertigo 1 0 Vomiting 2 0

Ketoprofen Dermatitis - Exfoliative 0 Nausea 0

Mefenamic Acid Angioneurotic Oedema 1 0 Asthenia 1 0 Diarrhoea 2 0 Drug Eruption 1 0 Dyspnoea 1 0 Erythema 2 0

24




Analgesics Mefenamic Acid Exacerbation of Asthma 1 0 (Peripheral Action) Gastritis 1 0

Haematemesis 1 0 Hypotension 1 0 Pruritus 2 0 Rash 7 0 Sweating Excessive 1 0 Syncope 1 0 Tachycardia 1 0 Vomiting 1 0 Urticaria 1 0

Naproxen Angioneurotic Oedema 1 0 Diarrhoea 1 0 Dizziness 1 0 Dyspepsia 2 0 Epigastric Pain 1 0 Excaberation of Duodenal Ulcer 1 0 Gastrointestinal Haemorrhage 1 0 Gastritis 3 0 Haematuria 1 0 Nausea 2 0 Periorbital Oedema 1 0 Pruritus 1 0 Rash 1 0 Thrombocytopenia 1 0 Thrombocytopenia Purpura 1 0 Vomiting 3 0

Nabumetone Anorexia 1 0 Dizziness 1 0 Epigastric pain 1 0 Gastritis 2 0 Nausea 1 0 Testicular Swelling 1 0

Paracetamol Haematemesis 1 0 No Response to Drug 1 0 Urticaria 1 0

25




Analgesics Paracetamol with Dizziness 2 0 (Peripheral Action) Ascorbic Acid with Dyspnoea 1 0

Brompheniramlne with Headache 1 0 Caffeine Hypertension 1 0

Rash 1 0 Restlessness 1 0

Paracetamol with Dihydrocodeine Urticaria 0

Paracetamol with Muscle Spasm 0 Metoclopramide Tremor 0

Paracetamol wi th Orphenadrine Syncope 2 0

Paracetamol with Dizziness 1 0 Pentazocine Malaise 2 0

Vomiting 1 0

Paracetamol with Phenylpropanolamine with Phenyltoloxamine Bullae 0

Piroxicam Abdominal Pain 1 0 Anorexia 1 0 Anxiety Neurosis 1 0 Aplastic Anaemia 3 0 Bone Marrow Hypoplasia 1 0 Dizziness 1 0 Drowsiness 1 0 Dyspepsia 1 0 Fluid Retention 1 0 Gastritis 1 0 Haematemesis 5 0 Hyperexcltation 1 0 Light Headedness 1 0

26




Analgesics Piroxicam Melaena 1 0 (Peripheral Action) Nausea 3 0

Nightmares 1 0 Pancytopenia 1 0 Photosensitivity 1 0 Pruritus 1 0 Purpura 1 0 Rash 4 0 Reactivation of Duodenal Ulcer 1 0 Reflux Oesophagitis 1 0 Tremor 1 0 Urticaria 2 0 Vision - Blurred 1 0 Vomiting 1 0

Salicylic Acid with Betamethasone (Topical) Sweating - Excessive 0

Tetrahydrofurfuryl Salicylate (Topical) Pruritus 0

Tiaprofenic Acid Dizziness 0 Gastritis 0 Nausea 0 Vomiting 0

Tolmetin Rash 0

Drugs Acting on Peripheral Nerves

Atracurium Cardiac Arrest

Bupivacaine Bradycardia 3 0 Hypotension 10 0 Lack of Efficacy 10 0 No Response to Drug 2 0 Penile Engorgement 1 0

27




Drugs Acting on Lignocaine Agitation 1 0 Peripheral Nerves Erythema 2 0

Irritability 2 0 Paraesthesia 1 0 Shivering 1 0

Lignocaine with Adrenaline Erythema 1 0 Fear 1 0 Hypotension 1 0 Sweating Excessive 1 0

Pancuronium Interaction with Pirenzipine Interaction (Tachycardia) 0

Miscellaneous Amantadine Angioneurotic Oedema 0 Pruritus 0

Biperiden Dry Mouth 0

Disulfiram Interaction with Alcohol

Interaction (Antabuse Reaction 0 (Cardiac Arrest 1

Methocarbamol with Bronchospasm 0 Aspirin Drowsiness 0

Nausea 0 Purpura 0 Rash 0 Urticaria 0

Orphenadrine Lack of Efficacy 0

Orphenadrine with Paracetamol Syncope 2 0

28



Drugs Affecting Autonomic System

Parasympatholytic& Atropine with Aggression 0 Diphenoxylate Disorientation 0

Dicyclomine Cyanosis 1 0 Dyspnoea 1 0 Vomiting 1 0

Dicyclomine with Codeine Erythema 1 0 with Potassium Chloride Rash 1 0

Dicyclomine with Doxylamine with Pyridoxine Congenital Upper Limb Deformity 0

Emepronium Visual Disturbance 0

Hyoscine Angioneurotic Oedema 1 0 Pharyngitis 1 0 Urticaria 1 0

lpratropium Bronchospasm 1 0

lsopropramide with Diphenylpyraline with Paraesthesia 0 Phenylpropanolamine Tremor 0

Oxybutynin Anticholinergic Reaction 1 0 Dizziness 1 0 Dry Mouth 1 0 Elevated Amylase 1 0 Eye Dryness 1 0 Malaise 1 0 Parotid Duct Blockage 1 0 Parotitis 1 0 Taste Perversion 1 0


Drug Action Approved Name


Parasympatholytics

Sympatholytics

Pirenzlpine Interaction

Poldine

Atenolol

Atenolol with Chlorthalldone

30

Reaction

Interaction with Pancuronlum (Tachycardia) Parotid Gland Enlarged

Visual Disturbance

Arrhythmia Bradycardia Bronchospasm ConjunctivitiS Diabetes Mellitus Dry Mouth Dyspepsia Ery1hema Headache Hypotens1on Impotence Insomnia Nausea Oral Monilia Peripheral Neuropathy Peripheral Vasoconstriction Pruritus Rash Stomatitis Taste Perversion Temporary Vision Loss

Constipation Hypotens1on Leg Cramps Paraesthesia Vasospasm Syncope

No. of No. of Cases Cases

1 1 2 1 1 1 2 1 2 1 1 1 1 1 1 1 1 1 1 1 1

1 1 1 1 1 1

0 0

0

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0

0 0 0 0 0 0




Sympatholytics Clonidine Biliary Cirrhosis 1 0 Rash 1 0

Ergometrine Albuminuria 2 0 Hypotension 3 0

Hydralazine Anaphylaxis 1 0 Dizziness 1 0 Fear 1 0 Vision Blurred 0

Labetalol Erythema 1 0 Pruritus 1 0 Rash 1 0

Methyldopa Abnormal Liver Function Tests 3 0 Anaemia 1 0 Anorexia 1 0 Ataxia 1 0 Clonic Limb Spasm 1 0 Drowsiness 1 0 Epigastric Pain 1 0 Haemolytic Anaemia 1 0 Jaundice 3 0 Nausea 1 0 Weight Loss 1 0

Metoprolol Bronchospasm 1 0 Drowsiness 1 0 Euphoria 1 0 Fatigue 1 0 Fluid Retention 1 0 Hyperactivity 1 0 Lassitude 1 0 Pulmonary Oedema 1 0

Metoprolol with Hydrochlorothiazide Hypotension 0

31


No. of No. of Drug Action Approved Name Reaction Cues Cases

Drugs Affecting ALltonomic System

Sympatholytjcs Minoxidil Ecchymoses 1 0 Haematoma Lt. Leg Muscle 1 0 Muscle Strain 1 0

Oxprenolol Interaction w1th Salbutamol

Interaction (Lack of EHicacy of Salbutamol) 0

Propranolol Ankle Oedema 1 0 Conjunctivitis 1 0 Dry Mouth 1 0 Dyspepsia 1 0 Dyspnoea 1 0 Fluid Retention 1 0 Hallucinations 1 0

lnteract1on Interaction with Halothane (Bradycardia 1 0 (Heart Block 1 0 Lassitude 1 0 Nausea 1 0 Necrosis of finger tips 1 0 Raynaud's Syndrome 1 0 Vomiting 1 0 Weight Gain 1 0

Sotaloi w1th E.C.G. Changes 1 0 Hydrochlorothiazide Fluid Retention 1 0

Hypokalaemia 1 0 Vertigo 1 0

Tertatolol Chest Pain 0 Myocardial Infarction 0

Timolol with Agitation 0 Bend rofluazide Anaphylaxis 0

Bradycardia 0

32



---- --- ----


Sympatholytics Timolol with Bronchospasm 3 0 Bendrofluazide Erythema 1 0

Fluid Retention 1 0 Hypokalaemia 1 0 Pruritus 1 0 Rash 1 0 Shock 1 0 Syncope 1 0

Sympathomimetic.s Butethamate with Ephedrine Oculogyric Crisis 1 0

Carbuterol Tremor 0

Ephedrine with Carbinoxamine with Anaphylaxis 0 Pholcodine Urticaria 0

Ephedrine with Excitability 1 0 Gualphenesin with Insomnia 1 0 Theophylline Palpitations 1 0

Ephedrine Nasal Drops Interaction Pseudoephedrine & Triprolidine with Orciprenaline (Cerebral Irritation 1 0 Interaction (Hypertension 1 0

(Hypertonia 1 0 (Screaming Episodes 1 0

Naphazoline with Methylene Blue (Eyedrops) Conjunctival Dark Blue Staining 0

Phenylpropanolamine Bullae 1 0 with Diphenylpyrallne Paraesthesia 1 0 with lsopropamide Tremor 1 0

Phenoxybenzamlne Nausea 0 Vomiting 0

33




Sympathominetics Pseudoephedrine Nightmares 0 Urticaria 0

Pseudoephedrine with Ataxia 2 0 Trlprolidine Confusion 1 0

Drowsiness 1 0 Emotional Upset 1 0 Erythema Multiforme 1 0 Hysteria 1 0 Insomnia 1 0 irritability 1 0 Malignant Neuroleptic Syndrome 1 0 Paraesthesia 1 0

Salbutamol Allergic Reaction 1 0 Angioneurotic Oedema 1 0 Cerebrallrntatlon 1 0 Drowsiness 1 0 Inco-ordination 1 0

Interaction Interaction with Oxprenolol (Lack of Efficacy of Salbutamol) 1 0 Paraesthesia 1 0 Tremor 3 0 Urticaria 1 0 Vasospasm 1 0

Salbutamol with Tartrazine Allergic Reaction 1 0

Terbutaline Dyspepsia 1 0 Emotional Upset 1 0 Exacerbation of Asthma 1 0 Headache 1 0 Palpitations 1 0 Sweating - Excessive 1 0 Tremor 1 0

Tolbuterol Tremor 2 0

34



---- ----- -----

Drugs Affecting Cardiovascular System

Drugs Acting on Amiodarone Angioneurotic Oedema 1 0 Heart Muscle Confusion 1 0

Fat1gue 1 0 Hallucinations 1 0 Insomnia 1 0 Photophobia 1 0 Photosensitivity 1 0 Rash 2 0

Digoxin Bradycardia 1 0 Death Due to Accidental Overdose 1 0 No Response to Drug 1 0

Flecainide Ventricular Tachycardia 0

Mexiletlne Palpitations 0

Quinidine Thrombocytopenia 0

Tocainide Agranulocytosis 1 0 Bradycardia 1 0 Carcinoma of Bladder 1 0 Dizziness 2 0 Hypotension 1 0 Neutropenia 1 0 Tremor 1 0

Coronary Vasodilators Aminophylline Dyspepsia 1 0 Gynaecomastia 1 0 Malaise 1 0 Nausea 1 0 Pruritus 2 0 Rash 1 0 Vomiting 3 0

Felodipme Myocardial Infarction 0

35


No. of No. of Drug Action Approved Name Reaction Ca.ses Cases

------- -- --------------------------Drugs Affecting Cardiovascular System

Coronary Vasodilator• Glyceryl Trlnitrate Headache 1 0 Lack of Efficacy 1 0 Local Allergic React1on 1 0 Pruritus 1 0

lsosorbide Dinitrate Bradycardia 1 0 Headache 6 0 Hypotension 1 0 Nausea 1 0 Rash 1 0 Sweating - Excessive 1 0

Nicardipine Incomplete Bundle Branch Block 1 0 Palpitations 1 0 Unifocal Ventricular Ectopics 1 0

Nifedipine Agitation 1 0 Anaemia 1 0 Bradycardia 1 0 Coldness 1 0 Conjunctivitis Discharge 1 0 Constipation 1 0 Duodenitis 1 0 Dyspepsia 1 0 Exacerbation of Angina 1 0 Fluid Retention 1 0 Flushing 1 0 Headache 5 0 Haematemesis 1 0 Impotence 3 0 insomnia 1 0 Leg Cramps 1 0 Melaena 1 0 Muscle Spasm 1 0 Paraesthesia 1 0 Pulmonary Oedema 1 0 Shivering 1 0 Vomiting 1 0 Weakness 1 0

36


No. of No. of Drug Ac1ion Approved N• m• R .. ction Cues c ....

----- ---- ---- ---Drugs Affecting Cardiovascular System

Coronary Vasodilators Theophylline Abdominal Pain 1 0 Agitation 1 0 Allergic React1on 1 0 Diarrhoea 1 0 Dyspepsia 1 0 Dyspnoea 1 0 Exacerbation of Asthma 1 0 Hallucinations 1 0

Interaction Interaction w1th Ketoconazole (Asthma - Uncontrolled 1 0 (Lack of Efficacy of Theophylline due to Ketoconazole 0

Interactions Interaction with Ketoconazole (Reduced Efficacy of Theophylline (due to Ketoconazole 2 0 leg Cramps 1 0 Nausea 2 0 Nightmares 1 0 Palpitations 1 0 Sweating Excessive 1 0 Syncope 1 0 Tachycardia 1 0 Tremor 1 0 Vomtting 2 0

Theophylline with Excitability 1 0 Ephedrine with Insomnia 1 0 Guaiphenesin Palpitations 1 0

Verapamil Arrhythmia 1 0 Bradycardia 1 0 Conjunctivitis 1 0 Dizziness 1 0 E.C.G. Changes 1 0 No Response to Drug 1 0 Periorbital Oedema 1 0 Pruritus 1 0 Rash 2 0

37




Peripheral Vasodilators Cinnarizine Fatigue 0

Dipyridamole Chest Pain associated with Dysphagia 1 0 Dysphagia 1 0 Thrombocytopenia 1 0 Vomiting 1 0

Flunarizine Fatigue 0 Headache 0 Parkinsonism 0

Ketanserin Pyrexia 1 0 Thrombocytopenia 1 0 Thrombophlebitis 1 0 Ventricular Fibrillation 1 0

Suloctidil Hepatomegaly 1 0 Jaundice 1 0 Positive Coombs Test 1 0 Splenomegaly 1 0

Antihistamines, Histamine and Bromphenlramine Dizziness 2 0 Related Substance:~ with Ascorbic Acid with Dyspnoea 1 0

Caffeine with Paracetamol Headache 1 0 Hypertension 1 0 Rash 1 0 Restlessness 1 0

Carbinoxamine with Anaphylaxis 1 0 Ephedrine with Pholcodine Urticaria 1 0

Chlorpheniramine Convulsions in Newborn Infant 0

Cimetidlne Agranulocytosis 0 Angioneurotic Oedema 0 Fissure of Tongue 0

38


No. of No. of Drug Action Approved Name Reaction CaMS Cases - --Drugs Affecting Cardiovascular System

Antihistamines, Histamine and Cimetidine Gastrointestmal Haemorrhage 1 0 Related Substances GynaecomaS1ia 2 0

Interaction Interaction w1th Metoclopramide (lack of Efficacy of Cimetldlne) 1 0

Interaction Interaction with Phenytoin (Peripheral Neuropathy) 1 0

Interaction Interaction with Warfarin (Prolonged Prothrombin Time) 1 0 Tinnitus 1 0 No Response to Drug 1 0 Pharyngitis 1 0 Pyrex la 1 0 Tonsillitis 1 0 Urticaria 2 0

Diphenhydramine with Confusion 1 0 Ammonium Chloride Dermographism 1 0

Hallucmations 1 0 Urt1caria 1 0

Diphenhydramine with Drowsmess 0 Sodium Citrate Hallucinations 0

Diphenylpyraline wrth lsopropamide with Paraesthesia 1 0 Phenylpropanolamine Tremor 1 0

Doxylamine with Dicyclomme with Pyridoxine Congenital Upper limb Deformity 1 0

Metoclopramide Anaphylaxis 1 0 Breast Enlorgement 1 0 Chest Pain 1 0 Exacerbation of Parkmson's Disease 1 0

39


No. of No. of Drug Action Approved Name Reaction Case$ Cases ---- --- -- -- -- -- ----Drugs Affecting Cardiovascular System

Antihistamines, Hisbtmine and Metoclopramide Extrapyramidal Disorder 1 0 Related Substances Galactorrhoea 2 0

Grand Mal Attack 1 0 No Response To Drug 1 0 Oculogyric CriSIS 4 0 Pruritus 1 0 Raised Serum Prolactin 1 0 Speech Slurred 1 0 Urticaria 1 0

Metoclopramide with Spasm 0 Paracetamol Tremor 0

Phenlramlne Dlzzmess 1 0 Syncope 1 0

Phenyltoloxamine with Paracetamol with Phenylpropanolamine Bullae 1 0

Promethazine Hyperactivity 1 0

Ranit1dme Exacerbation of Nausea 1 0 Hypotension 2 0 Nausea 1 0 Pruritus 1 0 Rash 2 0 Vomiting 2 0

Terfenadine Exacerbation of Urtlcana 1 0 Nausea 1 0 Vomiting 1 0

Trlprolldlne with Ataxia 2 0 Pseudoephedrine Confusion 1 0

Drowsiness 1 0 Emotional Upset 1 0 Erythema Mulllforme 1 0 Hyster ia 1 0 Insomnia 1 0

40


Drug Action Approved Name


Antihistamine, Histamine and Interaction Related Substances

Triprolidine with Pseudoephedrine

41

Reaction

Interaction with Ephedrine Nasal Drops with Orciprenaline (Cerebral Irritation (Hypertension (Hypertonia (Screaming Episodes

Irritability Malignant Neuroleptic Syndrome Paraesthesia


1 1 1 1

0 0 0 0

0 0 0


No. of No. of Drug Action Approved Name Reaction Ca.es Cases

Drugs Affecting Haemopoietic System

Antineoplaatics and Acyclovir Dysphagia 1 0 Antivirala lips Cracked 1 0

Nausea 2 0 Oral Monilia 1 0 Rash 1 0 Tonsillitis 1 0

Asparagmase Abnormal Liver Function Tests 1 0 Cerebral Haemorrhage 1 0 Jaundice 1 0 ?Perforation of Ileum 1 0 Prolonged Prothrombin Time 1 0

Azathioprine Anaemia 0 Leucopenia 0 Thrombocy1openia 0

Chlorambucil Brain Damage 1 0 Dlzzrness 1 0 Focal Epilepsy 1 0 Hallucinations 1 0 Light Headedness 1 0 Nausea 1 0 Psychosis 1 0 Syncope 1 0

Cytosine Arabinoside Conjunctivitis 0 Pyrexia 0 Scleritis 0

ldoxuridine Ery1hema 2 0

Mrtomycin - C Pruritus 0 Rash 0

Streptozotocin Anorexia 1 0 Malaise 1 0

42


No. of No. of Drug Action Approved Name Reaction Cues Cases --- -------- -----Drugs Affecting Haemopoietic System

Antineoplastics and Streptozotocin Nausea 2 0 Antivirals Vomiting 2 0

Vindesine Alopecia 9 0 Anaemia 7 0 Leucopenia 4 0 Nausea 11 0 Neuropathy 2 0 Thrombocytopenia 2 0 Vomiting 11 0

Haematinics Ferrous Fumarate Lack of Efficacy 0

Ferrous Fumarate with FolicAc1d Nausea 0

Folic ACid Angioneurotic Oedema 0 Pruritus 0 Rash 0

Folic Acid w1th Cyanacobalamln with Diarrhoea 1 0 Ferrous Gluconate Nausea 1 0

Hydroxocobalamin Prcrexia 0 Rgor 0

Iron Dextran Back Pain 2 0 Hallucinations 1 0 Headache 3 0 Myalgia 3 0 Neck StlHness 2 0 Pyrex la 2 0

43


Drug Action Approved Name Reaction No. of No. of Cases Cases

Drugs Affecting Haemopoietic System

Anticoagulants Heparin Anaphylaxis 2 1 Injection Site Inflammation 1 0 Lack of Efficacy 2 0 Rash 1 0

Warfarin Interaction with Cimetidine

Interaction (Prolonged Prothrombin Time) 0

Interaction Interaction with Indomethacin (Haematemesis 1 0 (Prolonged Prothrombin Time 1 0 Subarachnoid Haemorrhage 1 0

Coagulant.s Sodium Tetradecyl Arthralgia 1 0 Chest Pain 1 0 Fatigue 1 0 Hypotension 1 0

Blood Proteins Gamma Globulin Lack of Efficacy 0

Blood Substitutes Dextran Flushing 0

44


No. of No. of Drug Act ion Approved Name Reaction Cases Cases

Drugs Affecting Endocrine System

Affecting Pituitary Gland Felypressin with Erythema 1 0 Prilocaine Fear 1 0

Hypertension 1 0 Sweating - Increased 1 0

Gonadorelin Anaphylaxis 0

Oxytocin Dizziness 1 0 Floating Sensation 1 0 Headache 1 0

Somatostatln Drowsiness 1 0 Fatigue 1 0 Loss of Appetite 1 0

Oestrogens Oestrogens Conjugated Headache 0 Nausea 0 Oedema 0

Oestrogens with Progestogens Ethinyloestradlol with Headache 0 Desogestrel Migraine 0

Paraesthesia 0

Ethinyloestradiol with Abdominal Pain 1 0 Levonorgestrel Dizziness 1 0

Headache 2 0 Hypertension 1 0

Interaction Interaction with Phenobarbitone (Breakthrough Bleeding) 1 0 Leg Pain 1 0 Migraine 2 0 Nausea 1 0 Unintended Pregnancy 1 0

45

....... -------------


No. of No. of Drug Action Approved Name Reaction Cues c ....


Oestrogens with Ethmyloestradlol with Breakthrough Bleeding 0 Progestogens Norethisterone Headache 0

Interaction Interaction with Penicillin (Unintended Pregnancy) 0

Oestrogens with Cerebral Infarction 1 0 Progestogens (Unclassified) Headache 1 0

Paraesthesia 2 0 Right Hemiplegia 1 0 Speech Slurred 1 0

Progestrogens Dydrogesterone Palpitations 1 0

Corticosteroids Beclomethasone (Inhalation) Oral Moniliasis 0

Betamethasone Diabetes Mellitus 0

Betamethasone (Topical) Dermatitis - Exacerbated 0

Betamethasone with SaNcylic Acid (Topical) Sweating - Excessive 1 0

Prednisolone Anal Moniliasis 1 0 Cushings Syndrome 1 0 Fluid Retention 1 0 Gastrolntestinal Upset 1 0 Haematemesis 1 0 Intestinal Moniliasis 1 0 Oral Moniliasis 1 0 Purpura 1 0

46


No. of No. of Drug Action Approved N•me Re•ction c .... Cases

--- - - -----Drugs Affecting Endocrine System

Corticosteroids Prednisone Fluid Retention - Increased 0

Triamcinolone Oral Moniliasis 0

Special Hormones Bromocriptine Disorientation 1 0 Drowsiness 1 0 Hypotenston 1 0 Syncope 3 0

Captopril (Acute Exacerbation of Mild Renal (Insufficiency 1 0 Chest Pain 1 0 Eye Irritation 1 0

Interaction Interaction with Amiloride and Hydrochlorothtazide (Hyponatraemia 1 0 (Malaise 1 0 (Nausea 1 0 Loss of Libido 1 0 Malaise 1 0 Nail Dystrophy 3 0 Nausea 3 0 No Response to Drug 1 0 Normochromtc and Normocyttc Anaemta 1 0 Pemphigoid Reaction - Drug Related 1 0 Pruritus 1 0 Taste Perversion 2 0 Thrombocytopenia 1 0

Clomiphene Angioneurotic Oedema 0 Urticaria 0

Dinoprostone Bizzare Sensation 0 Dizztness 0 Headache 0

47


No. of No. of Drug Action Approved Name Reaction Cues Cues ---- - - --


Special Hormones Olnoprostone (Amniotic Fluid Embolus 1 0 In mother- (Coagulopathy 1 0

(HypertoniC Utenne Contractions 1 0 (lntercranlal Haemorrhage 1 0

In baby of (Fractured Skull 1 0 above mother - (Intracranial Haemorrhage 1 1

Enalapril Dehydration 1 0 Hypotension 1 0 Pulmonary Congest1on 1 0 Raised Creatinine Level 1 0 Raised Potassium level 1 0 Raised Urea level 1 0

Misoprostll Haematemesis 0

Pancreozymin Epigastric Pain 1 0 Nausea 1 0 Tachycardia 1 0

Prostaglandin Ez Diarrhoea 1 0 Erythema 1 0 Nausea 1 0

48


Drug Action Approved Name Reaction - --------

Drugs Affecting Nutrition and Metabolism

Vitamin Mixtures Ascorbic Acid

Ascorbic Acid with Bromphenlramine with CaHeme w1th Paracetamol

Etretlnate

Inositol

lsotretinoin

Diarrhoea

Dizziness Dyspnoea Headache Hypertension Rash Restlessness

?Abnormal Sperm Petech1ae

Ataxia Dizziness Drowsiness Faintness Paresthesia

Urticaria

P-Amino-Benzoic Acid with Angioneurotic Oedema Padimate Erythema

Pruntus

Pyridoxine with Dicyclomlne with Doxylamine Congenital Upper Limb Deformity

Vitamin 8

Vitamin 8 Complex

Vitamin Mixtures

49

Diarrhoea

Urticaria

Bullae Diarrhoea Urticaria Vomiting


2 1 1 1 1 1

1

1 1 3

0

0 0 0 0 0 0

0 0

0 0 0 0 0

0

0 0 0

0

0

0

0 0 0 0


No. of No. of Drug Action Approved Name Reaction Cases c .... ----- -----Drugs Affecting Nutrition and Metabolism

Thyroid and Antithyroid Carbimazole Urticaria 2 0 Substances

Thyroxine Tachycardia 1 0

Drugs Affecting Blood Chlorpropamide Hypoonatraemfa 0 Sugar Levels

Dextrose AnaphylactiC Shock 0

Metformin Diarrhoea 1 0 Flushing 1 0

Salts and Ion Exchangers Ammonium Chloride with Chloroform with Confusion 0 Diphenhydramine Visual Hallucinations 0

Ammonium Chloride Dermographism 1 0 with Diphenhydramine Urticaria 1 0

Potassium Chloride Confusion 1 0 with Bendrofluaz•de Hypokalaemia 1 0

Sweating Increased 1 0 Syncope 1 0

Potassium Chloride Electrolyte Changes 1 0 with Bumetamfde Hyperuricaemia 1 0

Potassium Chloride with Erythema 0 Codeine with Dicyclomlne Rash 0

Potassium Chloride with Frusemide Nausea 0

Sodium Citrate with Drowsiness 0 Diphenhydramine Hallucinations 0

50


No. of No. of Drug Act ion Approved N•me Re•ction c .... c .... ------ ------Drugs Affecting Nutrition and Metabolism

Diuretics Acetazolamide Agranulocytosis 1 0 Aplastic Anaemia 1 0 Diarrhoea 1 0 Haematemesis 1 0 Marrow Hypoplasia 1 0 Melaena 1 0 Nausea 1 0 Thrombocytopenia 1 0 Vomiting 1 0

Amiloride Dizziness 1 0 Hirsutism 1 0 Nausea 1 0 Syncope 1 0

Amiloride w1th Dehydration 1 0 Hydrochlorothiazide Hyperglycaemia on drugs 1 0

Hypoglycaemia oH drugs 1 0 Hypotension Postural 1 0

Interaction Interaction with Captopril (Hyponatraemia 1 0 (Malaise 1 0 (Nausea 1 0 Raised Blood Urea 1 0 Raised Creatinine 1 0

Bendrofluazide Hypokalaemia 1 0

Bendrofluazide with Confusion 1 0 Potassium Chloride Hypokalaemia 1 0

Sweating - Increased 1 0 Syncope 1 0

Bendrofluazide with Agitation 0 Timolol Anaphylaxis 0

Bradycardia 0

51


No. of No. of Drug Action Approved Name Reaction Cases Cases --- --- --

Drugs Affecting N utririon and Metabolism

Diuretics Bendrofluazide with Bronchospasm 3 0 Timolol Erythema 1 0

Fluid Retention 1 0 Hypokalaemia 1 0 Pruritus 1 0 Shock 1 0 Syncope 1 0 Rash 1 0

Bumetanide with Potassium Chloride Electrolyte Changes 1 0

Chlorthalidone Dizziness 1 0 Hyperglycaemia 1 0 Hypokalaemia 1 0 Weakness 1 0

Chlorthahdone with Constipation 1 0 Atenolol Fluid Retention 1 0

Hypotension 1 0 Leg Cramps 1 0 Paraesthesia 1 0 Syncope 1 0 Vasospasm 1 0 Vomiting 1 0

Frusemide Depression 1 0 Insomnia 1 0 Lassitude 1 0 Palpitations 1 0 Raised Blood Urea 1 0 Tremor 1 0

Frusemide with Potassium Chlonde Nausea 0

Hydrochlorothiazide with Metoprolol Hypotension 0

52


No. of No. of Drug Action Approved Neme Reectlon Ceses c ....


Diuretics Hydrochlorothiazide E.C.G. Changes 1 0 with Sotalol Hypokalaemia 1 0

Vertigo 1 0

Hydrochlorothiazide Dizziness 1 0 with Trlamterene Gout 1 0

Photosensitivity 1 0 Stomatitis 1 0 Weakness 1 0

Hydroflumethiaztde with Spironolactone Gynaecomastla 3 0

lndapamide Chest Pain 1 0 Drowsiness 1 0 Gout 1 0 Hypokalaemia 3 0 Hypotension 1 0 Lethargy 1 0 Peripheral Vascular Failure 1 0 Syncope 1 0

Metolazone Constipation 1 0 Hypokalaemia 1 0 Nausea 1 0

Metolazone wtth Abdominal Pain 0 Trlamterene Leg Cramps 0

Lethargy 0 Malaise 0

Piretanide Fatigue 0 Hypokalaemia 0

Polythlazlde Gout 0

53




Diuretics Spironolactone Nausea 1 0 Vomiting 1 0

Xipamide Hypotension 2 0 Impotence 1 0

Miscellaneous Almitrine Numbness 0 Paraesthesia 0 Urticaria 0

Amino-Acids Anaphylactic Shock 0

Clavulanic Acid Diarrhoea 1 0 with Amoxycillin D1plopia 1 0

Dizziness 1 0 Headache 2 0 Nausea 3 0 Nystagmus 1 0 Pruritus 2 0 Rash 1 0 Vomiting 3 0

Penicillamine Myasthenia Grav1s 0

Streptokinase Abnormal Liver Function Tests 0 Eosinophilia 0

54


No. of No. of Drug Action App,.oved Name Reaction Cases Cases

Anti-Infective Drugs

Antibiotic. Amoxycillln Allergic Reaction 1 0 Angioneurotic Oedema 1 0 Candidiasis 1 0 Diarrhoea 6 0 Erythema 1 0 No Response to Drug 1 0 Pseudomembraneous Colitis 5 0 Pyrexia 1 0 Rash 2 0 Stevens Johnson Syndrome 1 0 Vomiting 1 0

Amoxyclllln with Diplopia 1 0 Clavulanlc Acid Diarrhoea 1 0

Dizziness 1 0 Headache 2 0 Nausea 3 0 Nystagmus 1 0 Pruritus 2 0 Rash 1 0 Vomiting 3 0

Ampicillin Angioneurotic Oedema 3 0 Candidiasis 2 0 Diarrhoea 16 0 Erythema 1 0 Hallucinations 1 0 Injection Site Pain 6 0 No Response to Drug 1 0 Photosensitivity 1 0 Proctitis 1 0 Pruritus 1 0 Pseudomembraneous ColitiS 12 0 Rash 6 0 Syncope 6 0 Urticaria 1 0 Vomiting 7 0

55



-----Anti-Infective Drugs

Antibiotics Ampicillin with Anaphylactic Shock 12 0 Cloxacillin Injection Site Pain 14 0

Vomiting 2 0

Cefotaxime Abnormal Liver Function Tests 1 0 Diarrhoea 10 0 Pseudomembraneous Colitis 11 0 Syncope 1 0

Ceftazidime Haematuria 1 0 Raised Creatinine 1 0 Renal Failure 1 0 Renal Insufficiency 1 0

Cefurozime Allergic Vasculitis 1 0 Diarrhoea 4 0 Pseudomembraneous Colitis 4 0 Purpura 1 0 Rash 1 0

Cephaiexin Anaphylactic Shock 1 0 Angioneurotic Oedema 2 0 Candidiasis 1 0 Diarrhoea 1 0 Nausea 1 0 Rash 2 0 Tongue Oedema 1 0 Vomiting 2 0

Cephrad1ne Diarrhoea 3 0 Hallucmat1ons 5 0 Pseudomembraneous Colitis 3 0

Chloramphenicol Diarrhoea 0 Pseudomembraneous Cohtis 0

Chloramphenicol Allergic ConjunctiVItis 1 0 (Eye Ointment) Allergic React1on 2 0

56


No. of No. of Drug Action Approved Name Reaction Cases Ca.ses


Antibiotics Cloxacillin Diarrhoea 2 0 Haematuria 1 0 Joint Swelling 1 0 Pseudomembraneous Colitis 2 0 Purpura of Gastrointestinal Tract 1 0 Purpura of Skin 1 0 Vasculftis 1 0

Doxycycline Nausea 1 0 Oesophagitis 1 0 Vomiting 1 0

Ethambutol Hepatitis 1 0

Erythromycin Abdominal Pain 1 0 Abnormlil liver Function Tests 1 0 Diarrhoea 3 0 Dysphagia 1 0 Gastrolntestlnal Upset 1 0 Hallucinations 1 0 Hepatitis 1 0 Nausea 1 0 Pseudomembraneous Colitis 1 0 Rash 1 0 Vomiting 4 0

Flucloxacillin Bronchospasm 1 0 Diarrhoea 2 0 Dyspnoea 1 0

Interaction Interaction with Tetanus Vaccine (Recurrence of Injection Site Swelling) 1 0 Pruritus 1 0 Pseudomembraneous Colitis 1 0 Urticaria 1 0

Gentamicin Diarrhoea 5 0 Haematuria 1 0

57


No. of No. of Drug Action Approved Name Reaction CaMs CaMs

-- --Anti-Infective Drugs

Antibiotics Gentamicin Pseudomembraneous Colitis 5 0 Raised Creatinine 1 0 Renal Failure 1 0

Gramicidin with Neomycin with Polymixin (Eye Ointment) Anaphylaxis 0

Minocycllne Angioneurotic Oedema 1 0 Diarrhoea 1 0 Nausea 1 0 Photosensitivi1y 2 0 Vertigo 14 0 Vomiting 1 0

Oxytetracycline Monilia 0 Vaginal Candidiasis 0

Penicillin Ang1oneurot1c Oedema 2 0 Aplastic Anaemia 1 0 Diarrhoea 1 0 Exfoliative Dermatitis 1 0 Hypoalbuminaemla 1 0

Interaction (Interaction with Ethlnyloestrad1ol (with Norethisterone (Unintended Pregnancy) 1 0 Nausea 1 0 Petechiae 1 0 Pulmonary Oedema 1 0 Rash 3 0

Penicillin Subconjunctival Haemorrhage 0 Urticaria 0

Plperacillin Diarrhoea 1 0 Pseudomembraneous Colitis 1 0

58


Ho. of Ho. of Drug Action Approved Name Reaction c .... Cases

---- -- ----Anti-Infective Drugs

Antibiotics Pivampiclllin Pruritus 1 0 Rash 1 0 Urticaria 2 0

Pivamplcillln w1th Abdommal Pain 1 0 Pivmeclllinan Nausea 1 0

Pruritus 1 0 Rash 1 0 VIsion Blurred 1 0

Sodium Fusldate Erythema 0 Urticaria 0

Streptomycin Erythema 0

Tetracycline Abdominal Pain 1 0 Angioneurotic Oedema 2 0 Dizziness 1 0 ?Herpes Zoster 1 0 Impaired Concentration 1 0 Moniliasis 1 0 Nausea 1 0 No Response to Drug 1 0 Paraesthesia 1 0 Pruritus 3 0 Rash 5 0 Urticaria 2 0 Vagmal Candidiasis 1 0

Synthetic Antibacterials Clofazlmine lcthyosis 0

Nalidixic Acid Nausea 0 Paresis 0

Nitrofurantom Diarrhoea 0 Nausea 0

59


No. of No. of Drug Action Approved Name Reaction Cases Cues ----- --- ---- ---Anti-Infective Drugs

Synthetic Antibacterials Nitrofurantoin Paraesthesia 1 0 Peripheral Neuropathy 1 0 Pseudomembraneous Colitis 1 0 Rash 1 0 Urticaria 1 0 Vomiting 1 0

Sulphadiazine w1th Sulphadimidine Erythema 0

Sulphametopyrazine Anorexia 1 0 Rash 1 0

Sulphasaiazine Abdominal Pain 0 Agranulocytosis 0 Photosensitivity 0

Trtmethoprim Anaphylaxis 1 0 Muscle Pain 1 0 Pruritus 1 0 Rash 2 0 Stevens Johnson Syndrome 1 0 Tremor 1 0 Urticaria 3 0 Vomiting 1 0

Trimethoprim with Abdominal Pain 1 0 Sulphamethoxazole Agranulocytosis 1 0

Alopecia 1 0 Anaphylactic Shock 1 0 Anaphylaxis 2 0 Angioneurotic Oedema 5 0 Anorexia 1 0 Balanitis 1 0 Candidiasis 2 0 Conjunctivitis 2 0 Diarrhoea 4 0 Dyspepsia 1 0

60


No. or No. of Drug Action Approved Name Reaction Cases Cases

--- ------


Synthetic: Antibac:terials Trimethoprim w1th Erythema 6 0 Sulphamethoxazole Erythema Mull1forme 2 0

Headache 2 0 Leucopenia 1 0 Mouth Ulcers 2 0 Nausea 7 0 Neutropenia 1 0 Palpitations 1 0 Paraesthesia 1 0 Periorbital Oedema 1 0 Pruritus 6 0 Pseudomembraneous Colitis 4 0 Pyrexla 2 0 Rash 23 0 Algor 1 0 Stridor 1 0 Sweating - Increased 1 0 Thrombocytopenia 1 0 Urt1caria 5 0 Vomiting 3 0

Antiprotozoals Chloroquine Depress1on 0

Metronidazole Angioneurotic Oedema 1 0 Bradycardia 1 0 Diarrhoea 5 0 Migraine 1 0 Nausea 2 0 Photosensitivity 1 0 Pseudomembraneous ColitiS 5 0 Pulmonary Oedema 1 0 Rash 1 0 Vomiting 1 0 Urticaria 2 0

Praz.iquantel Asthenia 1 0 Pyrexla 1 0 Rigors 1 0 Sweating Increased 1 0

61


No. of No. of Drug Action Approved Name Reaction Cases Cases - --- -----Anti-Infective Drugs

Anthelmintics Levamlsole Diarrhoea 1 0 Headache 1 0

Piperazine Abdominal Pain 1 0 Anxiety 1 0 Chest Tightness 1 0 Diarrhoea 1 0 Drowsiness 1 0 Dyspnoea 1 0 Nausea 1 0 Tachycardia 1 0

Antifungals Clotrimazole Lack of Efficacy 0 (Topical) Urticana 0

Ketoconazole Confusion 1 0 Dtsorientatton 1 0

Interaction Interaction wtth Theophylline (Asthma Uncontrolled 1 0 (lack of Efficacy of Theophylline (due to Ketoconazole 0

Interactions Interactions with Theophylline (Reduced Efficacy of Theophylline (due to Ketoconazole 2 0 Neutropenia 1 0 Pruritus 1 0

Local Antiseptics Benzoyl-Peroxide (Topical) Rash 2 0

Ectoparasitieides Benzoyl-Benzoate Angioneurotic Oedema 1 0 (Topical) Cyanosis 1 0

Urticaria 1 0

62



----


Ectoparasiticides Benzene Hexachloride Candidiasis 1 0 (Topical) Nasal Congestion 1 0

Nausea 2 0 Pyrexia 1 0 Rash 1 0

Vaccines Cholera Vaccine Injection Site Swelling 0 Rash 0

Oiphthena with Convulsions 0 Pertussis with Cyanosis 0 Tetanus Vaccene Pyrexia 0

Syncope 0

Diphthena with Injection S1te Pa1n 0 Tetanus Vaccine Injection Site React1on 0

Injection Site Swelling 0 Malaise 0 Pyrexia 0

Hepatitis - B Vaccine Injection Site Inflammation 1 0 Injection Site Pain 4 0 Injection Site Swelling 1 0 Rash 1 0

Measles Vaccene Convulsions 1 0 Exacerbation of Epilepsy 1 0 Irritability 2 0 Pyrex la 1 0 Rash 1 0

Rubella Vaccine Headache 1 0 Lymphadenopathy 1 0 Pyrex1a 1 0

63


No. of No. of Drug Action Approved Name Reaction Cases Cases ----- ---


Vaccines Tetanus Vaccine Injection S1te Swelling 1 0

Interaction Interaction with Flucloxacillin (Recurrence of Injection Site Swelling) 0

Typhoid Vaccine Injection Site Swelling 1 0 Rash 1 0

64


No. of No. of Drug Action Approved Name Reaction c .... c ....

-------- - - - -Diagnostic Agents

Radiographic Agents lopamidol Abnormal Cerebrospinal Fluid 0 Headache 0 Hyperpyrexia 0 Hypotension 0 Leucocytosis 0 Respiratory Arrest 0 Rigors 0

Meglumlne Dtatrizoate Asthma 1 0 with Sodium Diatrlzoate Bronchospasm 1 0

Collapse 1 0 Hypotension 2 0 Pyrexla 1 0 Respiratory Arrest 1 0 Vomiting 2 0

Meglumine loxaglate Angioneurotic Oedema 1 0 Erythema 1 0 Hypotension 1 0 Nausea 3 0 Rash 1 0 Vomiting 1 0

Sod1um lothalamate Acute Renal Failure 1 0 Anaphylactic Shock 1 0 Post-Injection Abscess 1 0 Pulmonary Oedema 1 0 Thrombocytopenia 1 0

---

65


No. of No. of Drug Action Approved N•me Ae.ction Cues Cues --- -------Drugs Acting Locally

Affecting Gastrolnteatinal Bismuth Potassium Citrate Diarrhoea 0 Tract

Carbenoxolone Generalised Oedema 0

Danthron Urticaria 0

Dlphenoxylate with Aggression 1 0 Atropine Disorientation 1 0

Domeridone Diplopia 1 0 Dystonia 1 0 Oculogyric Crisis 1 0 Peripheral Neuropathy 1 0

Sodium Bicarbonate with Aspirin Asthma 0

Sucralfate Psoriasis 0

AHectlng Reapirat,)ry Tree Acetylcysteine Atrial Fibrillation 1 0 Coagulopathy 1 0 Hypotension 1 0 Paroxysmal Atrial Tachycardia 1 0 Periorbital Oedema 1 0 Thrombocytopenia 1 0 Urticaria 1 0

Guaiphenesin Excitation 1 0 Insomnia 1 0 Palpitations 1 0

AHecting Skin and Padimate Angioneurotic Oedema 0 Mucous Membrane Erythema 0

66


No. of No. of Drug Action ApJ)n)ved Name Reaction Cases Cases

Drugs Acting Locally

Affecting Skin and Padimate w1th Angioneurotic Oedema Mucous Membranes P-Amlnobenzoic Acid Erythema 1 0

Pruritus 3 0

Heavy Metals, Radioisotopes Copper with Chetating Agents (I.U D)

Erythema Multlforme 0

Sodium Aurothiomalate Collapse 0

Pharmaceutical Adjuncts

Amaranth Allergic Reaction 0

Azo Dyes Dermatitis-Generalised 0

Methylene Blue Conjunctival Staming 0

Polyurethane (Topical) Erythema 0 Skin Eruption 0

Tartrazine Allerg1c Reaction 0

67

SUSPECTED SIDE-EFFECTS FOR 1985 BY SYSTEM AFFECTED

Drugs Affecting Central Nervous System No. of Side Effects No. of Deaths

Anaesthetics 2 0 Hypnotlcs, Sedatives and Anticonvulsants 83 1 Tranquillisers 88 5 Antidepressants 66 1 Stimulants 16 0 Analgesics (Centra Action) 62 0 Analgesics (Perlph«3ral Action) 279 3 Drugs Acting on Peripheral Nerves 41 1 Miscellaneous 14 1 -

Totals 651 11

Drugs Affecting Autonomic System No. of Side Effects No. of Deaths

Parasympatholytics 27 0 Sympatholytics 106 0 Sympathomlmetics 52 0

Totals 185 0

Drugs Affecting Cardiovascular System No. of Side Effects No. of Deaths

Drugs Acting on Heart Muscle 23 1 Coronary Vasodilutors 94 0 Peripheral Vasodilators 16 1 Antihistamines, Histamine and Related Substances 88 0

Totals 221 2

Drugs Affecting ltaemopoletie System No. of Side Effects No. of Deaths

Antlneoplastlcs and Antivirals 83 0 Haematlnlcs 22 0 Anticoagulants 9 2 Coagulants 4 0 Blood Proteins 1 0 Blood Substitutes 1 0

Totals 121 2

68

SUSPECTED SIDE-EFFECTS FROM 1985 BY SYSTEM AFFECTED

Drugs Aftecting Endocrine System No. of Side Eftects No. of Deaths

Affecting Pituitary Gland 11 0 Oestrogens 3 0 Oestrogens wuh Progestogens 23 0 Progestogens 1 0 Cortlcosteroids 14 0 Spec1al Hormones 51 2

Totals = 103 2

Drugs AftectJng Nutrition and Metabolism No. of Side Eftects No. of Duths

Vitamin Mixtures 28 0 Thyroid and Anti-Thyroid Substances 3 0 Drugs Affecting Blood Sugar Levels 4 0 Salts and Ion Exchangers 15 0 Diuretics 68 0 M1scellaneous 22 0

Totals = 140 0

Anti-Infective Drugs No. of Side Eftects No. of Deaths

AntlbiOtJCS 317 0 Synthet1c Antibacterial& 129 0 Antlprotozoals 26 0 Anthelmlntlcs 10 0 Antlfungals 10 0 Local Ant1sept1cs 2 0 EctoparasitiCides 9 0 Vaccines 31 0

Totals 534 0

Diagnostic Agents No. of Side Efteets No. Deaths

Rad•ograph•c Agents 29 0 Totals "" 29 0

Drugs Acting Locally No. of Side Eftects No. of Duths Affectmg Gastrointestmal Tract 11 0 Affecting Respiratory Tree 10 0 Affecting Respiratory Tree 10 0 AffectJng Skin and Mucous Membranes 7 0 Heavy Metals, Radaolsotopes wath Chelatlng Agents 2 0 -- -

Totals = 30 0

Pharmaceutical Adjuncts 6 0 -Totals 6 0

69

General PractitionE·rs Dentists Hospital PharmaciHts Retail Pharmacists Clinics, Health Cer tres etc. Company Reports Patients Reports Intensive Drug Mo1itoring Hospitals - Generul Hospitals - Childffms Hospitals - Maternity Hospitals - Psychiatric Hospitals- SpeciE I

Total No. of Side Effects Reports Total No. of Side Effects Total No. of Deaths Total No. of Interactions Quality Defects Roports Total No. of Repo-ts

SOURCES OF SIDE-EFFECTS- 1985

70

No. of Reports

429 4

12 114 33

119 9

23 199

11 4 7

12

976 2020

14 18 26

1002

0~ of Total

43.95% .41%

1.23% 11.68% 3.38%

12.19% .92%

2.36% 20.39%

1.13% .41%

.72% 1.23%

DEATHS DUE TO SUSPECTED SIDE-EFFECTS - 1985

Acetazolamide

Alcohol

Aspirin

Chlorpromazine or Flupenthlxol or Trifluoperazine

Diclofenac or Indomethacin

Dig ox m

Dinoprostone - Mother

Dinoprostone - Baby

Heparin

Ketanserin

Midazolam

Thioridazine

Tranylcypromine with Trifluoperazine

Warfarin

71

Aplastic Anaemia

Interaction with Disulfiram Cardiac Arrest

Reyes Syndrome

Cardiorespiratory Arrest due to either of drugs

Hepatitis and Liver Failure

Accidental Overdose

Uterine followed by Amniotic Fluid Embolus and Coagulopathy and Intracranial Haemorrhage

Fractured Skull followed by Intracranial Haemorrhage

Anaphylaxis

Ventricular Fibrillation

Cardiac Respiratory Failure

Drug Overdose

Interaction with Dothlepin Probable Overdose

Subarachnoid Haemorrhage

1

1

INTERACTIONS 1985

Alcohol with Disulfiram (1 x case)

Alcohor with Phentormine (1 x case)

Amitriptyline with 1 riazolam (1 x case)

Captopril with Am loride and Hydrochlorothiazide (1 x case)

Cimetldlne with Metoclopramide (1 x case)

Cimetidine wrth Phenytoin (1 x case)

Cimetidine with Warfarin (1 x case)

Oothiepln with Tranylcypromrne and Trifluoperazine (1 x case)

Ephedrine Nasa Drops with Orciprenallne with Pseudoephedrire and Triprolidine (1 x case)

72

Cardiac Arrest and Death Hypotension Nausea Sweating Excessive Tremor Vomiting

Agitatron Ataxia Paraesthesia

Confusion Disorientation Dyspepsra Somnambullsm

Hyponatraemia Malaise Nausea

Lack of Efficacy of Cimetrdine

Peripheral Neuropa1hy

Prolonged Prothrombin Time

Death due to Probable Overdose

Cerebral Irritation Hypertenison Hypertonia Screaming Episodes

INTERACTIONS 1985

Ethinyloestradlol and Levonorgestrel with Phenobarbitone (1 X case)

Ethmyloestradlol and Nore1hlsterone with Penicillin (1 x case)

Flucloxacilhn with Tetanus Vaccine (1 x case)

Halothane with Propranolol (1 X case)

lmdomethacm wi1h Warfarin (1 x case)

Ketoconazole with Theophylline (1 x case)

Ketoconazole with Theophylline (2 X cases)

Oxprenolol with Salbutamol (1 x case)

Pancuronium with Plrenzipine (1 x case)

73

Breakthrough Bleeding

Unintended Pregnancy

Recurrence of Injection S1te Swelling

Bradycardia with Heart Block

Haematemesis Prolonged Prothrombm Time

Asthma - Uncontrolled Lack of Efficacy of Theophylline

Reduced Efficacy of Theophylline

Lack of Eff1cacy of Salbutamol

Tachycardia

SPECIAL POST MARKETING SURVEILLANCE 1985

AMIODARONE

The National Drugs Advisory Board received reports of 9 side effects during 1985 assoc1ated with the use of this antiarrhythmia agent, us·3 of which Is restricted to consultant supervision. Allergic reactions and photosensitivity were the most frequent. The incide1ce of side effects was 8% of patients treated.

CAPTOPRIL

During 1985, this drug use of which was previously restricted (5 years) to consultant superv1s1on, became more widely available for use provided dosage did not exceed 150 mg daily and there were no renal complications.

Thirteen side eflects have been reported subsequently. Attentton is drawn to several of these. ( 1) Drug Interaction leading to hyponatraemia was associated the use of Captopril with a thiazide dturetic and a potassium saving diuretic. 11 is Important that amtloride, spironolactone or triamterene should not be used wtth Captopril.

(2) An acute ex3cerbalton of chronic renal insufficiency the patient recovered on discontinUing Captopril. However, the event underline:; the need to investigate renal function before beginntng Captopril. Should any degree of insufficiency be present the patl•mt should be referred for consultant management if Captopril is to be used.

IBUPROFEN

A product conlatntng this acttve ingredient has now been available for over one year tn pharmacies wtthout prescription. One of the Bonrd's concerns before approving this change in 'status' had been the possibtltty of concurrent use of the agent with non ste ·oidal anti-inflammatory drugs available on prescnptlon without the doctor or pattent being aware.

During 1985, 10 reports were received by the Board, of 23 side effects. Only 1 report was made by a pharmactst and relattng to the product available without prescription.

The Board would like the special assistance of doctors and pharmactsts in reporttng any stde effects which come to their attention ass•>ciated with lbuprofen and In Identifying the product used.

MEPTAZINOL

During 1985, 16 side effects were reported with Meptazinol. almost all related to pallor and sweattng.

NEFOPAM

During 1985, Nefopam was associated with 16 reported side effects; 6 Involved nausea and vomiting and 6 cerebral Irritation with hallucinations, agitation, etc. There appeared to be no evident assoctation with age. The Board has records of use of the drug lrt 350 patients.

74

QUALITY DEFECTS REPORTED 1985

Tot1l Number Defects Defects Cluaot Number Detect. Physlc•l Description oescriptlon Chemlal

Prep1r1tlon of Reports Proved Cont.lner ChlrKteristics Microblologlul Particle Chlr1cteristics LAbelling

Large Volume Parenterals 1

Small Volume Parenterals 1

Tablets 12 9 7 2

Capsules 4 3 3

Suspension 6 6 1 3 2

Topical Cream, etc. 2 2 1

Four reported defects proved on assay to be of proper quality and the side eHects were due to the drug substance.

75

JANUARY 1986

WARNING

NOMIFENSINE (Merital)

This andldepr~ssant, an isoquinoline denvative unrelated to either trlcycllc or monoamine oxidase inhibitor antidepressants, hns been on the market in Ireland for about nine years.

During that time reports have appeared In the literature of various forms of hypersensitivity associated w1th the use of Nomifensine. Generally thse have appeared with the first eight weeks of introduction of treatment or in the first few days to beginning a second course of the drug. The features of these reactions varied, but included an influenza-like syndrome, alveolitis, acute Intravascular haemolysis, hepatitis, nephropathy or vasculitis. Almost all cases recovered unless the syndrome was allowed to progress with continued drug Ingestion.

Fortunately tht' incidence of such reactions Is low (1 in 1 O,OOO). In Ireland there have been f1ve hypersensitivity react1ons in the past four years; all five patients were receiving over 100 mgs of Nomitensine daily, three of these occurred in patients In whom treatment had been interrupted tor a significant interval. Four of the patients recovered completely after cessation of drug; the fifth, an elderly patient on multiple therapy, died.

Although then3 have been few problems in Ireland, the incidence of hypersensitivity reactions occurring in some other countries was ristrg, possibly in part due to more widespread use and to the frequency w1th which treatment was stopped and restarted.

The company concerned, Hoechst (Ireland) Limited with its principal, and with the agreement of The National Drugs Advisory Board di3Cided to withdraw Marital from the market as a safety precaution, following appropriate notification to medical practitiorers and pharmacists.

Unless its us3 Is essential, patients hitherto on Marital (Nomlfensine) should now have been transferred to other suitable treatment.

A. SCOTT, Medical Director, National Drugs Advisory Board

76

NEW RECOMMENDATIONS CONCERNING USE OF ALMITRINE (Vectarion)

1. Dosage should be adjusted on the basis of the patient's weight, the seventy of the blood gas abnormality and the inc1dence of adverse reactions.

Thus

(i) For patients less than 50 kg body we1ght the dose is generally 1 tablet dally

(11) For patients with severe changes In blood gases short periods of dosing with 3-4 tablets daily may be required

(iii) Persistent Paraesthesia In general an initial interval of three months treatment should be followed by a one month Interruption of treatment then cycles of two months on treatment and 1 month off treatment

Persistent evidence of peripheral neuropathy or a weight loss of 5% or more should be regarded as an indication to discontinue treatment.

NEW RECOMMENDATIONS CONCERNING SYMPATHOMIMETICS

The drugs hsted below are acceptable as oral or topical nasal decongestants in the dose ranges/ strengths indicated:

Phenylpropanolamtne

Phenylephrine

Pseudoephedrine

Ephedrine

A. ORAL PREPARATIONS MAXIMUM RECOMMENDED DAILY DOSE

Adults

25 mg q.i.d. 50 mg b.d. 1n slow release form

10 mg q.1.d. 20 mg b.d. in slow release form

60 mg t.i.d.

Not recommended as decongestant

77

Children 2-12 years in age-related doses

6 25- 20 mg q .i .d

2 75 - 7 5 mg q .1 d

15-45 mg t.i.d.

Not recommended as decongestant

NEW RECOMMENDATIONS CONCERNING SYMPATHOMIMETICS

B. TOPICAL NASAL PREPARATIONS

STRENGTH

Adults Children

Oxymetazollne 0.05% 0.25%

Xylometazoline 0.1% 0.05%

Phenylphrine 0.5% 0.25%

Tramazoline 0.15% Not recommended

Ephedrine Not recommended Not recommended

2. Topical Na~ aJ Preparations available 0. T.C. should not be used for more than 5-7 consecutive days without a doctors advice. A lnbel statement to this effect is necessary.

3. For oral pr•Jducts available O.T.C. the following cautionary statement is acceptable: "If symptoms persist consult your doctor".

4. ALL sympathomimetic containing preparations, both topical and oral, should carry the label statements: "If you are receiving medication, or are under a doctors care, consult him before using".

5. All sympathomimetic containing preparations should contain in their data sheet the following statement: "The physician or pharmacist should reassure himself that sympathomimetic containing preparations are not simultaneously administered by several routes i.e. orally and topically (nasal, aural and eye preparations)".

ADDITIONAL RECOMMENDATIONS FOR USE IN CHILDREN

6. Use of all sympathomimetic containing products in children under 2 years old should be on a doctors advice only. for oral p1·oducts available O.T.C. a label statement to this effect will be necessary. Topical nasal preparations Intended for paediatric use i.e. in infants and children under 2 years, should be supplied in unit dose dispensers only and on prescription only.

7. The following statement should be added to the data sheet: " When considering use in infants and young children under 2 years old great caution should be exercised. Serious side effe :;ts, including malignant neuroleptic syndrome, hypertension, cerebral irritation with screaming attacks, muscula.- rigidity and convulsions have been reported in this age group".

78

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