ADVERSE REACTION NEWSLETTER 1996:3
NATIONAL DRUG MONITORING CENTRES-DRUG SAFETY ISSUES

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INDEX

y WHO CENTRE INFORMATION
Malaysia Czech Republic

y NATIONALLY CIRCULATED INFORMATION
Australia Canada Denmark Finland Ireland Japan New Zealand Philippines Sweden United Kingdom

y REGULATORY DECISIONS
Germany USA

y LITERATURE REFERENCES
Canada Denmark Netherlands

WHO CENTRE INFORMATION

Malaysia

The Uppsala Monitoring Centre was recently informed that Dr Anis Bin Ahmad is the new person in charge of activities at the national centre in Malaysia. The previous head, Dr Ahmad bin Mahmud has moved to another division within the Ministry of Health.

Czech Republic

Dr Dana ?tolbova was recently appointed head of the national drug monitoring centre in the Czech Republic. Her telephone number is +42-2-67082599.

NATIONALLY CIRCULATED INFORMATION

Australia

ADRAC Bulletin Vol 15, No 3. August 1996

Cisapride and cardiac arrhythmias


Cisapride (Prepulsid) is a substituted benzamide which is indicated for management of gastrointestinal motility disorders including reflux oesophagitis. Up to July 1996, ADRAC had received 170 reports in association with the drug. Of these, 9 reports describe possible cardiac arrhythmias and in 7 (4 male, 3 female, age range 46-69 years), cisapride was the only suspected drug.
Prescribers should be aware that cisapride may interact with other drugs to induce cardiac arrhythmias and in isolated cases, it may induce early onset arrhythmias even in the absence of other drugs or known risk factors.

Oral acyclovir and neurological reactions

When used intravenously, acyclovir is well recognised to cause neurological adverse reactions but these may also occur with oral use. Table 1 shows the more severe neurological and psychiatric reactions which have been reported to ADRAC in association with both IV and oral acyclovir. A few of the reactions were described as "Acute brain syndrome".

Table 1
Neurological Reactions with Acyclovir

Oral IV
Hallucinations 11 9
Confusion 8 5
Agitation/aggression 7 2
Encephalopathy 5 2
Convulsions 2 2
Depression 2 0
Coma 2 1
Total No of Reports 148 59

Neurological and/or psychiatric symptoms are occasionally associated with oral acyclovir therapy and the ADRAC reports suggest that patients with impaired renal function are at particular risk.

SSRIs And Genitourinary Disorders

The selective serotonin reuptake inhibitors (SSRIs), fluoxetine, paroxetine and sertraline are associated with a variety of adverse effects.
Urinary reactions
Reports to ADRAC of urinary problems in association with the SSRIs are shown in Table 2. The age of the patients involved ranged from 16 to 86 years with those taking fluoxetine older. The majority were female. The time to onset of the symptoms ranged from days to months. About half of the reports indicated recovery after the drug was withdrawn.


Table 2
Urinary Reactions in Association with the SSRIs

Fluoxetine Paroxetine Sertraline
Total No of Reports 620 595 347
Incontinence 3 9 4
Frequency/Urgency 3 8 2
Retention 3 6 1
Dysuria 2 6 2
Other 2 7 -
Total Urinary Reports 10 28 7
Sexual Dysfunction
Sexual dysfunction is a recognised effect of the SSRIs and ADRAC data in Table 3 show that it is an effect common to all 3 members of the class which are marketed in Australia.

Table 3 Reports of Sexual Dysfunction with SSRIs
Fluoxetine Paroxetine Sertraline
Tot No of Reports 620 595 347
F M F M F M
Anorgasmia 5 - 19 1 9 -
Ejaculation Failure - 3 - 26 7 7
Impotence - 5 - 7 - 4
Libido Decreased 2 2 12 6 5 4
Libido Increased 1 2 2 - - -
Priapism - - 4 - - -
Total Reports of Sexual Dysfunction 11 8 24 37 11 11

The age of the patients affected ranged from 18 to 70 years with no difference among the 3 drugs whereas reactions affecting males have been reported more commonly for paroxetine.
Prescribers are reminded that both urinary reactions and sexual dysfunction are possible adverse effects of therapy with SSRIs.

Canada

Canadian Adverse Drug Reaction Newsletter, Vol 6, No 3, July 1996

Cisapride and arrhythmia

Cisapride monohydrate (Prepulsid® - first marketed in Canada in 1990). It is well documented in the product monograph that concomitant administration of cisapride with drugs that inhibit the cytochrome P450 enzyme system, has resulted in elevated cisapride plasma concentrations and a prolonged QT interval. Therefore, the use of ketoconazole, itraconazole and fluconazole, as well as the macrolide antibiotics, such as erythromycin and clarithromycin, are contraindicated with cisapride, because they interfere with its cytochrome P450 mediated metabolism. In addition, serious ventricular arrhythmias and torsade de pointes associated with QT prolongation have been observed in patients with pre-existing cardiac disease or risk factors for arrhythmia while taking cisapride in combination with other medication. Reference: WHO SIGNAL No 2, 1992
WHO ADR Newsletter 1995:1, 1996:2

Midazolam

Midazolam (Versed®), available in Canada since October 1987, is a short-acting benzodiazepine with several indications. One use is as an intravenous agent for patients requiring "conscious sedation" before and during short endoscopic or diagnostic procedures.
Points to consider:
*Midazolam dosage and rate of injection should be individualized as the duration of action and the effect (both desired effect sedation; and adverse effect respiratory depression) may vary from person to person. Conscious sedation can easily lead to anaesthesia, at which time the patient is highly vulnerable to asphyxation or aspiration.
*Opioid agonists and other sedatives, may cause respiratory depression. Concomitant use will have a synergistic effect and is likely to put patients at risk, especially if the dosage of both agents is not reduced. Patients over 55 years of age or debilitated patients need specific attention:
*An initial dose of 1-1.5 mg of midazolam is recommended.
*If there has been premedication with narcotic or other CNS depressant: reduce the dose by 30 %.

Clarithromycin and tooth discolouration and smell alteration

Clarithromycin, a semi-synthetic macrolide antibiotic that is structurally and pharmacologically related to erythromycin, was approved in Canada in May 1992. Clarithromycin is reported to be better tolerated than erythromycin, although gastrointestinal distress is still a common adverse effect. For example, abnormal taste, abdominal discomfort or pain, diarrhoea, nausea and vomiting are reported to occur in 2 to 3 % of patients taking clarithromycin.
The Canadian Adverse Drug Reaction Monitoring Program has recently received four reports of adult patients experiencing tooth discolouration and five reports of adult patients reporting alterations of the sense of smell suspected to be associated with the use of clarithromycin.
Tooth discolouration:
The onset time of the tooth discolouration after initiation of therapy varied from 4 to 10 days. Three of the reports did not mention any concomitant drugs taken by the patient. The tooth discolouration appears to be temporary; of the four patients experiencing tooth discolouration, two patients recovered after cleaning by dentist and a third patient intended to consult a dentist. The fourth patient had not yet recovered at the time of reporting.
Alteration of the sense of smell:
Of the five reports of adult patients reporting alterations of the sense of smell following the use of clarithromycin, three reports described a loss of smell and taste. In two of these cases, the outcomes were not reported and in the third case, the loss of the smell and taste persisted for at least 3 weeks. The remaining two cases described an alteration of smell and taste. In both cases, the patients had not yet recovered at the time of reporting. In one case, the reaction persisted 10 weeks after stopping clarithromycin.
Canadian Adverse Drug Reaction Newsletter, Vol 6, No 8, October 1996.

Cefaclor-associated serum sickness-like reaction

Serum sickness was first described by von Pirquet in 1905 following the use of antidiptheria horse serum. It is characterized by fever, arthralgia, skin eruptions, lymphadenopathy, nephritis, edema and neuritis.
A similar condition, known as serum sickness-like reaction (SSLR), has been recognized in association with a variety of drugs including: penicillin, sulfonamides, thiouracils, hydantoins, p-aminosalicylic acid, phenylbutazone, thiazides and streptomycin. Cases of SSLR have also been reported following the use of cefaclor, a second generation cephalosporin. In contrast to classic serum sickness, signs and symptoms of SSLR involving cefaclor appear to be confined primarily to findings including erythema multiforme or other skin manifestations accompanied by arthritis or arthralgia, with or without fever.
81 cases were reported in association with the use of cefaclor. Many of the case reports described the skin rashes and joint complaints associated with the SSLR. SSLR associated with cefaclor appears to occur more frequently in children.
While SSLR is appropriately described in the product monograph, the wide use of cefaclor has prompted the Canadian Adverse Drug Reaction Monitoring Program to remind health care professionals of the occurrence of this reaction, particularly in young patients.

Denmark

Ugeskr læger 158/34, August 1996.

Omeprazole and vision disturbances

The Danish Sundhetsstyrelsen has received three ADR reports of omeprazole and vision disturbances. They concern two women aged 58 and 46 years and a 79-year-old man, who were all given omeprazole 20mg daily. After one to two weeks of treatment the two women experienced adverse reactions including decrease in the peripheral visual field. They both recovered within a few days after withdrawal of the drug. The course was slightly different for the man; after taking omeprazole for two months he started to complain about yellow vision and visual impairment. After withdrawal, the yellow vision disappeared but the visual acuity did not totally go back to the level he had before starting omeprazole treatment. Reference: WHO ADR Newsletter 1994:2 and 1994:3

Finland

Tabu, Vol 4, No 4, April 1996

Alendronate and oesophageal damage

Several cases of potential oesophageal damage associated with alendronate consumption were reported in the UK. Similar cases have been observed in the USA. No case of this kind have been reported to the National Agency for Medicines in Finland.
A tablet swallowed dry, or with little water immediately before lying down, will tend to stick to the oesophagus. A sufficient quantity of water is to be taken with the tablet, and the patient is to remain upright after taking the tablet.

Ireland

Irish Medicines Board Drug Safety Newsletter, No 2, May 1996.

ACE inhibitors

The Irish Medicines Board reminds prescribers that concomitant use of ACE inhibitors and antidiabetic medicines (insulin, oral hypoglycaemic agents) may cause an increased blood glucose lowering effect with the risk of hypoglycaemia.

Calcium channel blockers

(Calcium Antagonists)
The Irish Medicines Board, following review and evaluation of the data at national level and by the EU CPMP (Committee for Proprietary Medicinal Products), recommends the following:
* Regarding ischaemic heart disease, their use should be restricted to the prophylaxis of stable angina. Use is contraindicated in patients with unstable angina.
* Prescribers are reminded that treatment of hyperten-sion with short-acting nifedipine may induce an abrupt fall in blood pressure as well as tachycardia, which could lead to a detrimental outcome.

Vitamin A - Products

High dietary intake of Vitamin A appears to be teratogenic.
Vitamin supplements are frequently taken by patients without medical advice. Health care professionals are requested to remind patients who are pregnant or likely to become pregnant of the potential risks associated with high doses of Vitamin A (from both dietary and supplementary sources).

Mefloquine

Mefloquine is an anti-malarial agent used in the treatment and prevention of malaria due to Plasmodium Falciparum.
The Irish Medicines Board would like to remind physicians of the following when prescribing mefloquine for patients.
Contraindications It should not be used in the following situations:
1. Prophylactic use in patients with a history of or existing psychoses or epilepsy
2. Prophylactic use in patients with renal insufficiency or severe impairment of liver function
3. Use in patients with a known hypersensitivity to mefloquine or related compounds
4. Concomitant use with halofantrine

Minocycline

The Irish Medicines Board recommends the following:
A- Treatment of acne with minocycline should be limited where possible to a maximum duration of six months.
B- Treatment could be continued beyond six months if there is a satisfactory response and if liver function and ANF are monitored.
C- Minocycline is contraindicated in patients with a history of or existing hepatic dysfunction.
D- In common with other tetracyclines, increases in liver function tests and rarely hepatitis and acute liver failure have been reported.

Japan

Information on Adverse Reactions to Drug in Japan, No 135, January 1996

Carteolol hydrochloride eye drop and bronchial asthma

Beta-adrenergic blocker eye drops are currently used as the drugs of first choice in the treatment of glaucoma and ocular hypertension. The Beta-blockers approved as eye drop preparations include timolol maleate, carteolol hydrochloride, befunolol hydrochloride and betaxolol hydrochloride.
Caution must be observed not only with respect to local ocular adverse reactions but against systemic adverse reactions as well since Beta-blocker instillations applied to the eyes are absorbed and distributed systemically to tissues.
Recently, bronchial asthma which occurred following the use of carteolol hydrochloride instillation in patients with a past history of bronchial asthma has been reported. The precautions in the package insert have accordingly been amended. By means of a brief review of some of the reported cases, the Pharmaceutical Affairs Bureau is cautioning physicians against the potential risk of asthma associated with the use of Beta-blocker eye drops.

Blood disorders associated with antiulcer drugs -proton pump inhibitors

It is known that blood disorders such as leucopenia appear in rare cases in patients receiving proton pump inhibitors which inhibit gastric acid secretion and which are used for treatment of gastric and duodenal ulcers. Safety concerns about this problem are stated in the current Precautions of their package inserts.
Development of two or more blood disorders, and the appearance of pure red cell aplasia associated with proton pump inhibitor medication have recently been documented. Physicians must be careful concerning blood disorders in patients in whom the use of such drugs is considered. Further, patients given such drugs must also be carefully followed and if any abnormality is confirmed, appropriate measures should be instituted, e.g. withdrawal of the medication.
The proton pump inhibitors in use in Japan are omeprazole and lansoprazole.

New Zealand

Prescriber update, No 12 July 1996

Contraceptives and cervical dysplasia

In a 5 year prospective study the New Zealand Contraception and Health Study Group examined the relative risk of cervical dysplasia in users of OCs, IUDs or injections of depot medroxyprogesterone (Depo-ProveraR).
6262 women aged 20-39 years using either of the above mentioned contraceptive methods and without smear tests positive for dysplasia since the past 6 weeks to 12 months were recruited.
The study did not find significant differences in the incidence of cervical dysplasia in the groups of women using the three contraceptive methods. However, a positive association was defined with number of sex partners and current cigarette smoking. The Most important risk factor was number of sex partners.

Top ten ADRs to moclobemide

The Intensive Medicines Monitoring Program (IMMP) includes, in 25% of the country's population, prescriber event monitoring (PEM) which involves routine follow-up of prescriptions to seek reports of any adverse events. In the rest of the country adverse event data relies on intensified spontaneous reporting.
Below is a table showing the numbers of the ten most commonly reported ADR to moclobemide.

All NZ PEM regions
ADR No/Rate/1000 No/Rate/1000
Nausea/Vomit 67/4.9 43/10.1
Sleep disorder 49/3.6 37/8.7
Headache 46/3.4 33/7.7
Fatigue, malaise 41/3.0 34/8.0
Anxiety/agit. 36/2.7 29/6.8
Diarrhoea 20/1.5 10/2.3
Extrapyr.eff. 19/1.4 7/1.6
Dizziness/Hypotension 17/1.3 12/2.8
Dry mouth 15/1.1 14/3.8
Stimulation/Hypomania 13/1.0 12/2.8

Adverse reactions of current concern

A list of adverse reactions of current concern was first initiated in December 1994.
There are two reasons for this list:
A- To raise the level of awareness of these adverse reactions.
B- To evoke reports so that more information may be gathered and appropriate action taken.

This list is as follows:
Medicine Adverse Prescriber
Reaction Update reference
Clozapine myocarditis No.7, Dec 1994
Flucloxacillin cholestatic hepatitis No.7, Dec 1994
Non-sedating anti-histamines cardiac effect No.7, Dec 1994
Oral contraceptives venous thromboembol No.11, Feb 1996
Roxithromycin cardiac arrhythmias No.11, Feb 1996
Terbinafine haematological reactions No.8, May 1995
Tiaprofenic acid cystitis No.8, May 1995

Royal Jelly

Health professionals are reminded of the potential danger to their patients of consuming the nutritional supplement Royal Jelly, especially in those known to the asthma. Information on adverse reactions to royal jelly was published in Prescriber Update No.4, March 1994.

Intensive Medicine Monitoring programme

The medicines currently being monitored are:
Medicine ProprietaryName Indication/Action
Copper IUCD Multiload Cu IUCD
Formotero Foradil potent long-acting, B2-agonist
Omeprazole Losec proton pump, inhibitor
Salmeterol Serevent potent long acting, B2-agonist
Sumatriptan Imigran selective 5HT1-like, receptor agonist
Moclobemide was removed from the list of monitored medicines on 1 April because a sufficient cohort had been accumulated - around 13600 patients in November 1995.

Philippines

SIGNALS in Adverse Drug Reactions Monitoring, Vol 1, No 8, August 1996.

Disulfiram - alcohol reaction

This well known clinical phenomenon include the symptoms of flushing, sweating, palpitations, dyspnea, hyper-ventilation, increased pulse, fall in BP, nausea and vomiting.
Disulfiram-like reactions may occur with many other drugs and are divided into three categories:
1- Clinically significant reactions are noted with the use of drugs such as cephalosporins, chlorpropamide, tolbutamide, procarbazine and organic solvents like dimethylformamide, trichloroethylene and N-butyraldoxine.
2- Possible reactions, though quite rare have been reported with drugs like griseofulvin and metronidazole.
3- Potential reactions may develop with drugs and chemicals that inhibit aldehyde dehydrogenase to varying extents.

SIGNALS in Adverse Drug Reaction Monitoring Vol 1, No 7, July 1996

Mefenamic acid

Mefenamic acid is used as an analgesic with anti-inflammatory properties and antipyretic effect. A 33-year-old female was admitted to hospital with the impression of thrombocytopenia. One week prior to admittance she consulted a private practitioner and was given unrecalled doses of mefenamic acid. 5 days prior to admittance she developed petechiae over her extremities and unexplained bleeding. Her condition worsened. She was treated with platelet transfusion and recovered.

Sweden

Information from the Medical Products Agency, Vol 7, No 4, September 1996.

Lamotrigine - serious skin reaction

LamictalR (lamotrigine) was approved in January 1994 as additional treatment of partial and general epilepsy and in November 1995 as monotherapy. Skin reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are known rare adverse reactions (<1/1000).
The MPA has received seven cases of serious skin reactions (4 SJS and 3 TEN). Internationally there has been about 115 such cases, the reactions have in almost all cases occurred within the first 4-6 weeks of treatment. In a majority of the cases the recommended gradual increase of dosage had been exceeded and many patients were concomitantly taking sodium valproate which inhibits the metabolism of lamotrigine.
The MPA gives the following recommendations:
*Slowly increase the dosage
*Cautiousness when co-administrating sodium valproate
*Inform the patient to contact physician if any skin reaction occurs
*Report all cases of serious skin reactions ASAP
*Serum tests should be taken and sent to the MPA when a reaction occurs.

Losartan - two years on the market

Loasartan was launched in Sweden in September 1994. Until June '96 about 14-15000 patients have been exposed to the drug and during this period the MPA has received 59 case reports describing 69 adverse reactions. Most commonly reported ADRs were: exanthema (9), coughing (5), vomiting (4), myalgia (4), dizziness (4) and diarrhoea (3).
In the latest international safety update from the manufacturer (September 1995), there is a discussion about angioedema in association with losartan. In the data sheets in Sweden (FASS) this ADR will be added. Three cases of respiratory disorders (dyspnoea, broncho-spasm and coughing) in association with losartan were described in the Information from MPA No 4 19951. Since then the MPA has received another nine cases describing respiratory disorders, including bronchial asthma and asthma aggravated (one case of each). Many of the patients had been transferred to losartan due to drug induced coughing from ACE inhibitors. Some studies1,2 though show that the incidence of dry cough is lower for losartan compared to ACE inhibitors.
References: 1) WHO ADR Newsletter 1995:4
2) Lacourcière Y et al. Effects of modulators of the renin-angiotensin-aldosterone system on cough. J Hypertens 1994;12:1387-93
3) Goldberg AI et al. Safety and tolerability of losartan. Am J Cardiol 1995;75:793-5.

United Kingdom

Current Problems in Pharmacovigilance Vol 22, July 1996

Alendronate sodium (Fosfamax®) and oesophageal reactions.

Alendronate sodium is a bisphosphonate used for the treatment of osteoporosis in post-menopausal women. Between September 1995 and March 1996 the MCA received 116 spontaneous reports of 197 adverse reactions. Of these, 10 involved the oesophagus: oesophageal reflux 4, oesophagitis 4, and oesophageal ulceration 2. Approximately 9,000 patients have been treated with alendronate sodium in the UK.
In order to minimise the risk of oesophageal reactions:
*Alendronate sodium should be taken with a full glass of plain water, immediately after getting up in the morning.
*Patients should not lie down for at least 30 minutes after taking the tablets and until after their first food of the day.
*Patients should be specifically instructed not to take the tablets at bedtime or before getting up in the morning.
Alendronate sodium should not be prescribed for patients with abnormalities of the oesophagus or with other factors that delay oesophageal emptying. It should be used with caution in patients with upper gastrointestinal problems.
The frequency of upper gastro-intestinal adverse reactions appears to be greater when alendronate sodium is used in conjunction with non-steroidal anti-inflammatory drugs and aspirin.
See also: Finland above.

Mefloquine (Lariam®) and neuropsychiatric reactions

Mefloquine has been available in the UK since 1989 for the prevention and treatment of malaria.
The overall frequency of adverse reactions, with a prophylactic use of mefloquine has been reported in Lancet 1993;341:1299-1303 Steffen R et al., to be 19%. This is similar to the frequency for chloroquine but less than that for the combination of chloroquine and proguanil.
Some of the observed neuropsychiatric reactions are depression and suicidal ideation, anxiety, panic, confusion, hallucinations, paranoid delusions and convulsions.
In order to minimise the occurrence of neuropsychiatric reactions and to prevent premature discontinuation of anti-malaria prophylaxis the MCA recommend that:
*Prophylactic mefloquine is contraindicated in patients with a history of neuropsychiatric disturbance including depression or convulsions.
*Patients should be informed about the adverse reactions that may occur in association with mefloquine and advised that, if these occur, they should seek medical advice on alternative anti-malaria prophylaxis before their next dose is due.
No malaria prophylaxis is completely effective and patients should be advised that chemo-prophylaxis should always be used in conjunction with measures to prevent mosquito bites. Patients taking any anti-malarial should be advised of the importance of finishing the course. They should be informed about the potential for serious side-effects and advised to seek medical advice if these occur.


Restricted indication for sotalol

In view of information now available, eg. Waldo, AL et al. Lancet 1996:348;7-12 and Julian, DG et al. Lancet 1982:(i);1142-7, the use of sotalol should be limited to the treatment of ventricular arrhythmias or prophylaxis of supraventricular tachyarrhythmias. It should no longer be used for angina, hypertension, thyrotoxicosis or for secondary prevention after myocardial infarction. Evidence is lacking that sotalol has a favourable benefit to risk profile in comparison to alternative beta-blockers available for the treatment of these conditions. When stopping sotalol, the dose should be reduced gradually.

Inhaled nitric oxide - Unlicensed: responsibility for use rests with the prescriber

Over the past few years inhaled nitric oxide has been used to reduce pulmonary hypertension, although it is not licensed for this or any other purpose. Unlike other vasodilators, it can improve ventilation/perfusion matching without causing significant systemic hypotension. However, there are a number of concerns regarding its use, eg:
*A high concentration of nitric oxide can cause acute pulmonary oedema and methaemoglobinaemia, which can be fatal.
*Other potential side-effects include central nervous system toxicity, altered platelet function, reduced effectiveness of pulmonary surfactant, and possible interference with immune function. Neonates may be at particular risk.
Further work is needed to address these concerns. Doctors are reminded that they are entirely responsible for any adverse consequences of using an unlicensed medicine.

Amphotericin intravenous and anaphylaxis

*Anaphylaxis occurs rarely with any intravenous amphotericin product.
*A test dose is advisable before commencing the first infusion of amphotericin.
*A small amount of drug should be infused over about 10 minutes and the patient carefully observed for about 30 minutes.
*Prophylactic antipyretics or hydrocortisone should only be used in patients who have previously experienced acute adverse reactions (in whom continued treatment with amphotericin is essential).
The product information has been updated to reflect these recommendations.

Griseofulvin: contraceptive precautions

Griseofulvin induces abnormal segregation of chromosomes following cell division and is a potential teratogen. To prevent congenital abnormalities both men and women taking griseofulvin should use contraception.
Men: As sperm may be affected, men should take precautions to avoid fathering children during treatment and up to six months after griseofulvin has been stopped.
Women: Women should not become pregnant during treatment or within one month of stopping griseofulvin. As griseofulvin may reduce the effectiveness of oral contraceptives, additional contraceptive precautions should be taken.

REGULATORY DECISIONS

Germany

Bundesinstitute für Arzneimittel und Medizinprodukte 7/96

Anthraquinone containing laxatives

The anthraquinone containing laxatives andira, cassia, rhamnus, rheum and aloe should only be used for short periods, and not for any other indications. This is due to the risk of too strong effect, which causes diarrhoea, interfering with the normal intestinal functions, changes in water and salt balance which can cause severe adverse reactions in the cardiac and circulatory system.
This restriction will be valid from the 1st of November 1996.

USA

Dexfenfluramine labeling to be updated

The US FDA has requested that Interneuron Pharmaceuticals, Inc., and Wyeth-Ayerst Laboratories, manufacturer and distributor respectively of the appetite suppressant dexfenfluramine (Redux), update the drug`s labelling to inform doctors and patients about the increased risk of primary pulmonary hypertension, a rare but serious and life-threatening lung disorder.

LITERATURE REFERENCES

Canada

Postmarketing surveillance in Canada. W.C Appel, PhD Drug Information Journal 1996; Vol 30: 655-659.

Denmark

Serotonin syndrome: Definitions and cause. Laier G. Nord J Psychiarty 1996; 50: 249-260.

Netherlands

Can adverse drug reactions be detected earlier? A comparison of reports by patients and professionals. T C G Egberts, M Samulders, F H P de Koning, R H B Meyboom, H G M Leufkens BMJ 1996; 313: 530-531

Taste loss to terbinafine: a case-control study of potential risk factors.
B Stricker, M. Van Riemsduk, M C J M Sturkenboom and J P Ottervanger. Br J Clin Pharmacol 1996; 42: 313-318

last updated 961104