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Australian Adverse Drug Reactions Bulletin, Vol 16, No 4

November 1997

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


SSRIs and neonatal disorders ......

The selective serotonin reuptake inhibitors (SSRIs) fluoxetine (Erocap, Lovan, Prozac, Zactin), fluvoxamine (Luvox), paroxetine (Aropax) and sertraline (Zoloft) are now the most widely used class of antidepressants in the Australian community. With this increasing use has come a relatively large number of reports to ADRAC (fluoxetine, 803; fluvoxamine, 5; paroxetine, 887; sertraline, 1243) including reports of effects on the neonate.

...... withdrawal reactions

Four reports to ADRAC describe withdrawal reactions in neonates whose mothers had taken SSRIs throughout their pregnancies. One case, in which the mother had taken fluoxetine, involved a three day old baby who developed tachypnoea, irritability, jitteriness, fever, anorexia, cyanosis and possible fitting. The second case, in which the mother had taken sertraline, concerned the smaller of a set of twins, who, at three days, became jittery and unsettled. The third case describes a baby who was treated for irritability and rapid breathing for two days after birth to a mother who had taken sertraline. The fourth case involved a mother who had taken fluoxetine and whose baby had a good Apgar score at birth but then became lethargic and fed poorly. The effects in all four cases appeared to resolve spontaneously.

...... breast milk transfer

A further four reports relate to probable breast milk transfer. In one report, a 5 month old breast fed baby whose mother was taking fluoxetine for post-partum depression, was found to have hyperglycaemia and glycosuria which resolved after the cessation of breast feeding. A second report describes a breast fed baby who became agitated, unsettled and had difficulty feeding while its mother was taking paroxetine. The outcome is unknown in this case. The third report describes a 5 month old baby who became agitated for a few days when her mother began taking sertraline for post-partum depression. This settled spontaneously while the mother continued with the drug. In the fourth report, a breast feeding mother took sertraline for about three months from the time her baby was 10 days old. During this time, the baby was somnolent, with low muscle tone, hearing problems and suspected developmental difficulties. When the mother discontinued the drug, the baby's condition improved dramatically and is now considered normal.

These reports suggest that adverse reactions to SSRIs can occur in neonates, through either placental or breast milk transfer. Practitioners should consider this possibility when prescribing to depressed patients who are pregnant or breastfeeding.

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Boxed warnings

Prescribers may have noticed that during the past 2 years, a "boxed" safety warning has been included in the product information (PI) for a small number of drugs available on the Australian market. These drugs are associated with specific safety problems, whose clinical importance or severity are considered to have a critical impact on patient welfare. Special care should always be taken with a drug with a boxed warning. The content of the warning will be succinct and designed to draw the attention of the prescriber to information within the main body of the PI. The boxed warning will be applied in full to all advertisements and to brand name reminders in the form "see warning". A sample boxed warning appears below

Drug X: Drug X has caused severe hepatic injury in some patients. The hepatic dysfunction is reversible in most cases if the suspected drug is ceased when symptoms first appear.

Laboratory monitoring with calcitriol - an update

In the February Bulletin, ADRAC drew attention to the problem of hypercalcaemia in association with calcitriol (Rocaltrol).1 In that article, it was pointed out that the product information for calcitriol had a precaution concerning serum calcium monitoring. This involved twice weekly determinations of serum calcium early in therapy with at least weekly determinations for the first 12 weeks and monthly determinations thereafter. The product information has now been changed so that laboratory monitoring is specified according to the indication for use. For osteoporosis, the indication for which ADRAC has received most reports, the current recommendation for serum calcium monitoring is as follows:

  • at the commencement of therapy, at 2-4 weeks, and thereafter at 2 to 3 monthly intervals.


  1. ADRAC. Calcitriol and hypercalcaemia. Aust Adv Drug React Bull 1997; 16: 2.

Fatal outcomes after sumatriptan

In 1993, ADRAC drew attention to the problem of chest pain associated with the use of sumatriptan. Subsequently, ADRAC has received 3 reports documenting a fatal outcome.

  • A 44 year old woman developed chest pain and died suddenly after taking sumatriptan orally (dose not stated) during an episode of migraine. She had a long history of recurrent migraine, commenced sumatriptan seven months previously and in that period she had received three prescriptions each for 12 tablets. She had no history of symptoms of ischaemic heart disease. Post mortem examination established that she had suffered an acute myocardial infarction resulting in pulmonary oedema.
  • A 57 year old woman who had a history of severe hypertrophic obstructive cardiomyopathy, hypertension, and long term smoking and who was recovering from a stroke, complained of migraine which was relieved by a pethidine injection. A few days later the headache returned and she was treated with sumatriptan 100mg orally as she had found this to be effective in the past. Ninety minutes later she developed dull constant left-sided chest pain and atrial flutter. Her chest pain responded to glyceryl trinitrate but six hours later she was found unconscious in respiratory arrest and unresponsive ventricular fibrillation.
  • A 58 year old woman had a long history of migraine for which she had been taking methysergide prophylactically for 7 years. During her annual 'break' from methysergide she experienced a migraine headache and took sumatriptan (dose not stated). She then developed chest pain and vomiting and died suddenly 3 hours later. She had recently been diagnosed as having rheumatic mitral stenosis and autopsy revealed ischaemic heart disease although she had not complained of chest pain in the past.

Although there were significant confounding features, these 3 reports describe fatal outcomes following the onset of chest pain in women who had taken sumatriptan orally some hours earlier. None had complained of chest pain previously and in two cases there was evidence of myocardial ischaemia/infarction. The product information states that serious coronary events, hypotension and arrhythmias have been reported in connection with the use of sumatriptan. Prescribers should be aware that sumatriptan is contraindicated in any patient with heart disease or uncontrolled hypertension.


  1. ADRAC. Sumatriptan and chest pain. Aust Adv Drug React Bull; 1993: 12: 3.

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Drugs of current interest

Please report all suspected reactions to these Drugs of Current Interest

  • Acarbose(Glucobay)
  • Alendronate (Fosamax)
  • Cilazapril (Inhibace)
  • Dicloxacillin (Diclocil)
  • Eformoterol (Foradile)
  • Famciclovir (Famvir)
  • Fexofenadine (Telfast)
  • Fluvastatin (Lescol, Vastin)
  • Fluvoxamine (Luvox)
  • Losartan potassium (Cozaar)
  • Meropenem (Merrem)
  • Nefazodone (Serzone)
  • Olanzapine (Zyprexa)
  • Sevoflurane (Sevorane)
  • Topiramate (Topamax)
  • Valaciclovir (Valtrex)
  • Venlafaxine (Efexor)

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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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