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Australian Adverse Drug Reactions Bulletin, Vol 15, No 1
Prepared by the Adverse Drug Reactions Advisory Committee (ADRAC) and the Office of Medicine Safety Monitoring (OMSM) of the TGA.
ADRAC has previously drawn attention to the problem of severe thrombocytopenia in association with the use of quinine and its salts to treat muscle cramps. Less well known is the fact that quinine can also cause the haemolytic uraemic syndrome (HUS), a rare but potentially life threatening condition.
Since 1979 the Committee has received four such reports of HUS involving 3 females and one male, aged 35 to 63 years. Three cases occurred soon after the ingestion of one dose of quinine as therapy for muscular cramps. Two of these patients had experienced nausea, diarrhoea and vomiting with previous treatment. The other patient had developed HUS with two previous exposures to quinine, although the association was unrecognised at the time. In the fourth case the patient had taken the drug for one to two weeks without prior exposure.
All four reports documented rapid onset of intravascular haemolysis associated with acute oliguric renal failure requiring haemodialysis. Disseminated intravascular coagulation was also documented in two of the cases with the added complication of retroperitoneal haemorrhage in one patient. Quinine dependent red cell agglutinating antibodies were documented in one of the reports. Two of the patients made a full recovery but the other two still required dialysis at the time of reporting.
Quinine sensitivity is now a well established cause of HUS and the reports received by ADRAC have many features in common with overseas case reports published in recent years.1,2 Quinine should never be prescribed or administered to a patient who has had any adverse reaction to it previously, and its use in the treatment of muscle cramps should be carefully considered. It should also be remembered that quinine is present in tonic water and 'bitter lemon' beverages and patients who have had a reaction to quinine should avoid these. Two of the patients referred to in overseas reports developed HUS after a second exposure to quinine in such beverages.
- Gottschall JL, Elliot W, Lianos E et al. Quinine-induced immune thrombocytopenia associated with hemolytic uremic syndrome: a new clinical entity. Blood 1991; 77: 306-310.
- Aster RH. Quinine sensitivity: a new cause of the hemolytic uremic syndrome. Ann Intern Med 1993; 119: 243-244.
Terbinafine (Lamisil) is a new antifungal drug with activity against infections due to dermatophytes (e.g. "ringworm") and Candida albicans. It was first marketed in Australia in late 1993 and since that time ADRAC has received 168 reports documenting a total of 323 suspected adverse reactions to terbinafine, and these are grouped in the figure below. ADRAC is concerned by the number and nature of these reports, considering that the drug is often used for minor conditions and for a prolonged period.
There are two prominent groups of adverse reactions. Those reactions involving the gastrointestinal tract (GIT) (87 reports) include nausea (14 cases), abdominal pain (8), mouth ulceration (5), and in particular, taste perversion or loss which is described in 29 reports. In many of these cases, the taste disturbance had not recovered at the time the report was submitted (21 cases). Reports involving the skin (106 reactions) include many eruptions suggestive of hypersensitivity or photosensitivity: the reactions described include a variety of rashes, urticaria, erythema multiforme and eczema.
Other serious adverse drug reactions including blood dyscrasias (especially affecting white cells) have been the subject of concern in some other countries, and to date ADRAC has received 2 reports describing suspected neutropenia (both recovered) and 1 case of agranulocytosis (not recovered at the time of the report). Finally, there are 11 adverse hepatic reactions involving 5 reports of abnormal hepatic function, 4 reports of jaundice and 2 reports of hepatitis. While all the above reactions are mentioned in the product information, the potentially wide usage of terbinafine has prompted this early overview in order to encourage careful prescribing and close monitoring of its adverse effects.
Withdrawal syndromes have long been recognised with the opioids and benzodiazepines but are rarely reported with other drugs. Fluoxetine (Prozac), paroxetine (Aropax) and sertraline (Zoloft) are antidepressant drugs belonging to the class of selective serotonin reuptake inhibitors (SSRI's). To date the Committee has received 26 reports of withdrawal symptoms in connection with the use of these drugs as summarised in the table below.
|Total Reports||Reports of withdrawal (%)||Daily dose (mg)||Half-life|
|Fluoxetine||578||5 (0.5)||20-40||2-3 days|
|Paroxetine||406||22 (5.4)||20-40||~1 day|
|Sertraline||242||7 (2.9)||50-100||26 hours|
The age (range 23 to 68 years) and sex distribution (23 females and 9 males) probably reflect usage. In those reports which included the information, duration of therapy ranged from several weeks to months and onset of the reaction was within the first week (usually in the first couple of days) after ceasing therapy. In 8 cases the symptoms abated on recommencing the drug but recurred in 3 of these after the drug was again stopped. One patient experienced withdrawal symptoms in connection with sertraline and later, also with paroxetine.
The symptoms most commonly reported on withdrawal were dizziness (15 reports) and nausea (10). Anxiety, headache (both 5 reports), agitation, insomnia, increased sweating, tremor and vertigo (4 of each), hallucinations, and depersonalisation (3 of each) were also described. There was a total of 51 different symptoms documented in the reports with a wide range of other neurological and psychiatric symptoms including amnesia, ataxia, blurred vision, confusion, dysarthria, delirium, fatigue, hyperacusis, hypertonia, meningism, mood swings, neurosis, nervousness, nightmares, paraesthesia, rigors, sensory disturbance, tinnitus, and twitching. There was also a report of a neonatal withdrawal reaction. Eighteen of the patients had recovered at the time of reporting and there were no fatalities.
Interestingly, paroxetine accounted for the majority of reports and its shorter elimination half-life in addition to the fact that it lacks active metabolites are possibly pertinent in this context. In contrast, fluoxetine has a longer half-life and its active metabolite, norfluoxetine has a half-life of 6-9 days.
Prescribers should be aware that drugs in this class have the potential to produce withdrawal symptoms if therapy is ceased abruptly. When a decision is made to terminate therapy, gradual reduction of the dose may be necessary particularly for drugs with a shorter elimination half-life.
A total of 29 reports describing palpitations, arrhythmias or chest pain associated with loratadine (Claratyne) have been forwarded to ADRAC. Many of these cases involve relatively young fit individuals who developed a rapid onset of the reaction after only one or two doses. The Committee believes there may be a signal in this cluster of cases and urges reporting health professionals to include electrocardiographic (ECG) results whenever these are available.
Please report all suspected reactions to these Drugs of Current Interest
- Azithromycin (Zithromax)
- Clarithromycin (Klacid)
- Enoxacin (Enoxin)
- Famciclovir (Famvir)
- Gabapentin (Neurontin)
- Goserelin (Zoladex)
- Lamotrigine (Lamictal)
- Lansoprazole (Zoton)
- Leuprorelin (Lucrin)
- Nafarelin (Synarel)
- Paroxetine (Aropax 20)
- Pantoprazole (Somac)
- Piperacillin/tazobactam (Tazocin)
- Pravastatin (Pravachol)
- Salmeterol (Serevent)
- Sertraline (Zoloft)
- Tacrine (Cognex)
- Terbinafine (Lamisil)
- Ticlopidine (Ticlid)
- Vigabatrin (Sabril)
- Zopiclone (Imovane)
(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
- 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.
© Commonwealth of Australia 1999
All correspondence to be addressed to: The Secretary, ADRAC, PO Box 100, Woden ACT 2606