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Australian Adverse Drug Reactions Bulletin, Vol 19, No 2

June 2000

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

Contents

Celecoxib: early Australian reporting experience

Celecoxib (Celebrex) is the first in the class of COX-2 inhibitors to be marketed in Australia. From the start of marketing in October 1999 to April 2000, ADRAC has received 919 reports of suspected adverse reactions.

Celecoxib reporting profile chart
Adverse Reaction Profile for Celecoxib
(The chart shows the proportion of reaction terms in the various categories. Numbers of more common terms are shown. Where more than one term within a category was mentioned in a report, each term was counted.)

The figure opposite shows the profile of reporting based on the 869 reports where celecoxib was the only suspected drug. Relatively minor gastrointestinal adverse reactions (nausea, abdominal pain, dyspepsia, diarrhoea) have been mentioned commonly. There have been relatively few reports of serious upper or lower gastrointestinal adverse reactions (31 and 28 reports respectively). This is consistent with clinical trial comparisons of celecoxib with the more conventional NSAIDs naproxen and diclofenac.1 Some patients do develop GI ulcers or bleeds while taking celecoxib. It is uncertain at this stage whether this reflects a background rate for these problems or whether the drug is being used in preference to other NSAIDs in a high-risk group of patients.

There have been nine reports which describe either acute renal failure or worsening of chronic renal failure. Consistent themes in these reports were that the patients were elderly (59; 70 to 94 years) and that in six of the reports, the patients were taking both an ACE inhibitor and a diuretic at the time the celecoxib was started. It appears that celecoxib shares the propensity of the conventional NSAIDs to worsen renal function in patients taking the combination of these 3 drug classes (the "triple whammy").2

Several other types of reactions appear to be prominent with celecoxib:

  • There is a high proportion of rashes/urticaria but few reports of serious reactions such as Stevens Johnson syndrome (1 report) or erythema multiforme. (2)
  • About 5% of the reports have mentioned other forms of allergy including face or tongue oedema, and angioedema (7) and anaphylactoid reaction (3). There are also reports of asthma or aggravation of asthma.
  • Peripheral oedema has been described often; eleven reports described varying degrees of hypertension.
  • Dizziness and headache have been reported commonly.
  • Celecoxib sometimes increases the INR in patients taking warfarin and this has been reported to ADRAC 7 times.

In its first months of marketing, celecoxib has generated a large number of reports to ADRAC. Apart from the gastrointestinal tract, its adverse effect profile appears similar to that of a conventional NSAID.

References

  1. Celecoxib, approved product information
  2. ADRAC, Thomas MC. Diuretics, ACE inhibitors and NSAIDs - the triple whammy. MJA 2000; 172: 184-5.

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Zanamivir and respiratory effects

Zanamivir (Relenza) is a drug which was developed in Australia for treatment of influenza. It was marketed last year but was not used in significant numbers of patients until the recent Northern Hemisphere winter. In the US, there were several reports of deterioration in respiratory function or bronchospasm in patients who used zanamavir with asthma or chronic airways disease.

In Australia, there has been a report of bronchospasm and dyspnoea in a non-smoker with no past history of asthma and 2 other reports which described wheeze or dyspnoea.

In these instances, it is difficult to exclude confidently the underlying influenza as a cause of these symptoms. Zanamivir may be used more widely this winter and prescribers should be aware of the possibility of bronchospasm or decline in respiratory function, especially in patients with asthma or chronic airways disease.

Overall, ADRAC received 22 reports last year in association with zanamivir. Most reports described minor reactions such as headache, rashes, nausea, vomiting and diarrhoea.

Alert! Interactions with St John's Wort

The possibility that the complementary medicine, St John's wort (Hypericum perforatum) interacts with newer antidepressants has been known for some time.

Earlier this year, a series of articles indicated that the herb also interacts with indinavir and cyclosporin, and has the potential to interact with other HIV drugs, anticonvulsants, digoxin, warfarin and oral contraceptives. This prompted the TGA to issue an Alert and an accompanying Information Sheet on the issue. These two documents can be found on the TGA website.

Valaciclovir: renal impairment and neuropsychiatric reactions

Valaciclovir (Valtrex) is an antiviral drug used for treatment of various herpes infections. It is a prodrug of aciclovir. ADRAC has received 69 reports of adverse reactions with the majority being minor reactions such as headache (16 reports), nausea (14), rashes (12), and dizziness (9). Another group of reactions are neuropsychiatric effects and there are 13 reports of more severe reactions describing hallucination (7 cases), confusion (6), delirium (3), ataxia (2), dysarthria (2), convulsions, psychosis and stupor (1 each).

Of these 13 reports, all but one occurred in patients with chronic renal failure or age-related renal impairment. This is consistent with the product information for Valtrex which indicates that neurological reactions are more likely in patients with renal impairment, and gives advice about dosage adjustment.

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Drugs of current interest

Please report all suspected reactions to these Drugs of Current Interest

  • Acamprosate (Campral)
  • Candesartan (Atacand)
  • Celecoxib (Celebrex)
  • Clopidogrel (Iscover, Plavix)
  • Donepezil (Aricept)
  • Entacapone (Comtan)
  • Eprosartan (Teveten)
  • Gelatin succinylated (Gelofusine)
  • Leflunomide (Arava)
  • Montelukast (Singulair)
  • Naltrexone (ReVia)
  • Orlistat (Xenical)
  • Quetiapine (Seroquel)
  • Raloxifene (Evista)
  • Repaglinide (NovoNorm)
  • Sildenafil (Viagra)
  • Telmisartan (Micardis/Pritor)
  • Tramadol (Tramal)
  • Zafirlukast (Accolate)
  • Zanamavir (Relenza)

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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 2000

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

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