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Australian Adverse Drug Reactions Bulletin, Vol 18, No 1

February 1999

Prepared by the Adverse Drug Reactions Advisory Committee (ADRAC) and the Office of Medicine Safety Monitoring (OMSM) of the TGA.

Contents

Angiotensin II receptor antagonists ? New drugs ...

Losartan, marketed in late 1997 as the potassium salt (Cozaar), was the first of the angiotensin II receptor antagonists (ARAs) approved for the treatment of hypertension in Australia. It was followed by irbesartan (Avapro, Karvea) in mid 1998 and more drugs of this class are expected to be marketed. To November 1998 ADRAC has received 230 reports of suspected adverse reactions associated with losartan and 133 reports in association with irbesartan. Most reports (84%) implicated the ARA as the only suspected drug. Ages ranged from 25 to 93 (median: 67) years and 68% were over the age of 60. The onset of the reaction was in the first few weeks in most cases and recurrence of symptoms was documented on rechallenge in 24 reports.

More Commonly Reported Reactions with ARAs
Adverse Effect Number of Reports
with Losartan
(Total = 230)
Number of Reports
with Irbesartan
(Total = 133)
Rash/pruritus 37 21
Psychiatric disturbances 33 19
Cough 23 14
Arrhythmias 20 9
Headache 19 14
Musculoskeletal pain 17 8
Fatigue 15 2
Angioedema 17 7
Dizziness/vertigo 14 10

... with some old problems

The more commonly reported reactions are listed in the table. Skin reactions and neuropsychiatric disturbances comprised the largest groups of reports. Neuropsychiatric problems included insomnia (14 reports), depression (10), confusion (9), nightmares (6), and agitation (5).

Of particular interest are reports of cough and angioedema. The clinical characteristics were remarkably similar to those seen with ACE inhibitors. There were 37 reports of cough which was sometimes described as persistent and dry. As with ACE inhibitors, the 24 reports of angioedema described swelling of the neck, face or tongue. Over half (19) of the reports of cough documented similar problems associated with previous use of an ACE inhibitor. Time to onset varied but was mostly in the first month. Most patients recovered after the drug was stopped but three reports described recurrence of cough on rechallenge.

Early expectations were that problems such as cough and angioedema associated with the ACE inhibitors would be avoided with this new class of antihypertensive agent. However, this appears not to be so.

.... and some new problems

Two other effects in association with ARAs which have come to ADRAC's attention are hepatotoxicity and hyperglycaemia. There have been 14 reports of hepatic dysfunction with losartan. Seven of these described abnormal liver function tests while the other 7 described hepatitis or jaundice. For irbesartan, there has been one report of cholestatic hepatitis, one of jaundice, and one of abnormal liver function tests.

In addition, there have been 3 reports received which have described irregularities in glycaemic control with losartan. In 2 reports there was an increase in blood sugar levels soon after patients with diabetes started losartan, and in the other report a patient developed an acute onset of hyperosmolar diabetes mellitus within a month of an increase in the dose of losartan.

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Allergic reactions with echinacea

The complementary medicine echinacea is derived from several species of this flowering plant and has become increasingly popular in recent years, particularly for the prophylaxis and treatment of cold and flu symptoms. Between July 1996 and November 1998 ADRAC has received 37 reports of suspected adverse drug reactions in association with echinacea. Over half of these (21) described allergic-like effects including bronchospasm (9 reports), dyspnoea (8), urticaria (5), chest pain (4) and angioedema (3).

Of the 21 patients, ages ranged from 3 to 58 (median 31) years. Twelve of 18 patients for whom medical histories were available had a history of asthma (7) and/or allergic rhinitis/conjunctivitis/hayfever (5). Echinacea was the only suspected cause in 19 of the 21 cases. Onset ranged from within 10 minutes of the first dose to "a few months", although all but two cases occurred within 3 days of starting treatment. At the time of reporting, 17 of the patients had recovered, 2 had not yet recovered and the outcome was unknown in the other 2 cases.

ADRAC is concerned that these reports suggest that individuals with asthma and hayfever may be predisposed to developing allergic reactions to echinacea. Patients presenting with allergic symptoms should be questioned about ingestion of herbal and other complementary products as part of the usual drug history. In any further reports of these problems, ADRAC is interested in obtaining as much detail as possible including the trade name and preparation of echinacea used.

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Update on visual field constriction with vigabatrin

In August 1997 ADRAC reported on visual field defects occurring in association with the antiepileptic drug, vigabatrin (Sabril).1 At that time, ADRAC had received 5 reports of this problem. To November 1998, ADRAC has received a total of 100 reports in association with vigabatrin. Of these, 43 describe visual field constriction, which was symptomatic in 30 cases. Ages of the patients involved (M: 31, F: 12) ranged from 9 to 69 years with a median of 40 years. Daily doses ranged from 0.5 to 4.5 g with a median of 2.5 g. Time to onset ranged from less than a month to over 6 years but most (38) cases had a time to onset of greater than 2 years. Only one of the patients was reported as having recovered symptomatically but this was shown to be incomplete on visual testing.

It was recently estimated that 10-20% of patients on long-term vigabatrin will develop visual field constriction.2 ADRAC recommends that all individuals taking vigabatrin should have special visual testing consisting of a Humphries automated visual field test out to 60° performed at regular intervals.

References

  1. ADRAC. Visual field defects with vigabatrin. Aust Adv Drug React Bull 1997; 16: 11.
  2. Appleton RE. Guideline may help in prescribing vigabatrin. BMJ 1998; 317: 1322.

Withdrawal of tolcapone

Tolcapone (Tasmar) was registered in Australia last year and is the first of a new class of drugs for the treatment of Parkinson's disease. It acts by selective and reversible inhibition of catechol-O-methyl transferase, thus reducing the metabolism of concomitantly administered levodopa. This can lead to an improvement in symptomatic response and may allow a reduction in the daily dose of levodopa. Following overseas reports of serious and unpredictable hepatotoxicity including 3 fatalities, its registration has been withdrawn in Australia. The drug has also been suspended in Canada and Europe.

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Drugs of current interest

Please report all suspected reactions to these Drugs of Current Interest

  • Acarbose (Glucobay)
  • Alendronate (Fosamax)
  • Atorvastatin (Lipitor)
  • Carvedilol (Dilatrend, Kredex)
  • Citalopram (Cipramil)
  • Diclofenac/misoprostol (Arthrotec)
  • Dicloxacillin (Diclocil, Distaph)
  • Dolasetron (Anzemet)
  • Donepezil (Aricept)
  • Fexofenadine (Telfast)
  • Fluvoxamine (Luvox)
  • Irbesartan (Avapro, Karvea)
  • Losartan (Cozaar)
  • Montelukast (Singulair)
  • Naratriptan (Naramig)
  • Nefazodone (Serzone)
  • Nicorandil (Ikorel)
  • Olanzapine (Zyprexa)
  • Sildenafil (Viagra)
  • Tiagabine (Gabitril)
  • Tiludronate (Skelid)
  • Topiramate (Topamax)
  • Tramadol (Tramal)
  • Trovafloxacin (Trovan)
  • Zafirlukast (Accolate)
  • Zolmitriptan (Zomig)

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What to report?

(you do not need to be certain, just suspicious!)

ADRAC encourages the reporting of all suspected adverse reactions to medicines, including vaccines, OTC medicines, herbal, traditional or alternative remedies. ADRAC particularly requests reports of:

  • ALL suspected reactions to new drugs (see drugs of current interest)
  • ALL suspected drug interactions
  • Suspected reactions causing
    • Death
    • Admission to hospital or prolongation of hospitalisation
    • Increased investigations or treatment
    • Birth defects

For blue cards

Reports of suspected adverse drug reactions are best made by using a prepaid reporting form ("blue card") which is available from the website or from the Office of Medicines Safety Monitoring (02 6232 8744).

Reports can also be submitted electronically, by clicking on "Report a problem" on this website, by fax: 02 6232 8392, or email: ADR.Reports@tga.gov.au.

ISSN 0812-3837

© Commonwealth of Australia 1999

All correspondence to be addressed to: The Secretary, ADRAC, PO Box 100, Woden ACT 2606

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Content last updated: Wednesday, 24 March 1999

Web page last updated: Monday, 21 February 2011

URL: http://www.tga.gov.au/hp/aadrb-9902.htm