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Australian Adverse Drug Reactions Bulletin, Vol 15, No 3

August 1996

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


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 has 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 (median 65) years), cisapride was the only suspected drug. Five of these reports described palpitations or tachycardia, one documented atrial fibrillation and one detailed bradycardia.

In 6 of the 7 cases, the arrhythmia developed within the first week of therapy (5-40 mg daily) including one case in which it appeared two hours after the first dose. In 3 of these cases, the suspected arrhythmia was the only adverse effect noted. Palpitations were accompanied by abdominal pain in one case and dyspnoea in another. Tachycardia was accompanied by tremor and hypertension in one case, and the report of bradycardia documented fatigue, nightmares and insomnia. In five cases there was a recurrence of symptoms after rechallenge. Similar cases have been reported overseas1.

There have been recent reports of an interaction between cisapride and other drugs inducing cardiac arrhythmias2 and the product information has been changed to indicate "that isolated cases of QT prolongation and/or torsades de pointes have been observed in patients receiving other medications and having preexisting cardiac disease or risk factors for arrhythmia". Cisapride is metabolised mainly by the cytochrome P4503A4 enzyme system which is inhibited by imidazoles such as itraconazole, ketoconazole and fluconazole and macrolide antibiotics such as erythromycin and clarithromycin. Therefore, coadministration of these drugs with cisapride should be avoided. ADRAC has received a report of QT prolongation and torsades de pointes in association with the concomitant use of erythromycin and cisapride. QT prolongation can also occur with high-dose cisapride alone3.

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.


  1. Olsson S, Edwards Rl. Tachycardia during cisapride treatment. BMJ 1992; 305: 748-49.
  2. Ahmad SR, Wolfe SM. Cisapnde and torsades de pointes. Lancet 1995; 345:508.
  3. Bran S, Murray WA, Hirsch IB, Palmer JP. Long QT interval during high-dose cisapride. Arch Intern Med 1995; 155: 765-68.

Oral acyclovir and neurological reactions

When used intravenously, acyclovir (Acyclo-V, Zovirax, Zyclir) 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
Encepphalopathy 5 2
Convulsions 2 2
Depression 2 -
Coma 2 1
Total No. of Reports 148 59

The reactions occurred after oral use in 29 patients whose age ranged from 19 to 86 (median: 55) years and 17 were female. Most patients (20) were taking the drug for herpes zoster (shingles). The daily dose ranged from 800 to 4000 mg but 12 patients were taking 4000 mg daily which is the recommended dose for shingles. In 28 of the patients the adverse effects resolved quickly when acyclovir was stopped.

Because acyclovir is eliminated mainly by the kidneys, adverse effects could be more common in patients with renal impairment. Of the 29 who experienced neurological symptoms, 4 were renal transplant recipients and 8 others were in renal failure. In six other patients who were elderly (69-86 years), age-related decline in renal function may have contributed to the reaction. The 11 other patients had no documented renal problems.

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.

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SSRls and genitourinary disorders

The selective serotonin reuptake inhibitors (SSRIs), fluoxetine (Lovan, Prozac, Zactin), paroxetine (Aropax 20) and sertraline (Zoloft) are associated with a variety of adverse effects. This review highlights two of the more unusual types.

Urinary symptoms

Reports to ADRAC of urinary problems in association with the SSRIs are shown in Table 2. Urinary incontinence, urinary frequency, retention and dysuria are the most commonly reported symptoms.

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 2 6 1
Dysuria 2 6 2
Other 2 7 -
Total Urinary Reports* 10 28 7

The ages of the patients involved ranged from 16 to 86 (median: 48) years with those taking fluoxetine older (median: 61 years). The majority were female (28:17). The time to onset of the symptoms ranged from days to months. There is only limited information on the outcome. About half of the reports indicated recovery after the drug was withdrawn but in the other half, the patient had not recovered at the time the report was submitted or the outcome was not stated.

Sexual dysfunction

Sexual dysfunction is a recognised effect of the SSRls 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
Total No. of Reports 620 595 347
  F M F M F M
Anorgasmia 5 - 19 1 9 -
Ejeculation Failure - 3 - 26 - 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 (median: 41) years with no difference among the 3 drugs whereas reactions affecting males have been reported more commonly for paroxetine.

The time to onset of the symptoms ranged from within 24 hours of starting the drug to 2-3 months after. Information on outcome was limited and was similar to that with urinary symptoms with about half of the reports documenting recovery after the drug was stopped. In 5 of the 103 patients, the reaction recurred on rechallenge.

Prescribers are reminded that both urinary reactions and sexual dysfunction are possible adverse effects of therapy with SSRls.

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Drugs of current interest

Please report all suspected reactions to these Drugs of Current Interest

  • Azithromycin (Zithromax)
  • Cabergoline (Dostinex)
  • Cilazapril (Inhibace)
  • Enoxacin (Enoxin)
  • Famciclovir (Famvir)
  • Fluvastatin (Lescol, Vastin)
  • Gestrinone (Dimetriose)
  • Goserelin (Zoladex)
  • Leuprorelin (lucrin)
  • Nafarelin (Synarel)
  • Pantoprazole (somac)
  • Salmeterol (Serevent)
  • Sevoflurane (Sevorane)
  • Tacrine (Cognex)
  • Ticlopidine (Ticlid)
  • Valaciclovir (Valtrex)
  • Zopiclone (Imovane)

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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:

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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