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Australian Adverse Drug Reactions Bulletin, Vol 14, No 1

February 1995

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

Contents

Serious arrhythmias with intravenous erythromycin

The product information for intravenous erythromycin mentions the possibility of cardiac arrhythmias occurring but states that causality has not been proven. Recently the Committee received four reports of serious arrhythmias, two of them fatal, in connection with intravenous administration of erythromycin. The case summaries of these are outlined here.

A 15 year old diabetic girl was taking multiple herbal remedies (including 'golden seal root', Korean ginseng, and Siberian ginseng) when she developed an acute lower respiratory tract infection (thought to be due to Mycoplasma). This, together with poor compliance with her usual diabetic therapy (insulin and diet) resulted in diabetic ketoacidosis. She was admitted to hospital for management of her diabetes and intravenous antibiotic administration. Intravenous insulin, amoxycillin and erythromycin were prescribed together with oral paracetamol and sucralfate. Three and a half hours after completion of a one hour infusion of erythromycin lactobionate 600 mg she developed ventricular tachycardia. Resuscitation measures were unsuccessful and she died.

A 58 year old woman with atypical lobar pneumonia of unknown aetiology (possibly psittacosis) was hospitalised for intravenous antibiotic therapy. She was treated initially with intravenous doxycycline 100 mg daily but after two days her condition deteriorated and she required ventilation and inotrope support. Her myocardial function was described as 'severely depressed' and it was unclear whether this was due to myocarditis or myocardial infarction. After the addition of a number of drugs including morphine, midazolam, adrenaline, dopamine, heparin and sucralfate, intravenous erythromycin lactobionate was also commenced with 1 gram being infused over 30 minutes. Within 30 minutes of completion of this first dose she experienced the onset of multifocal ventricular ectopic beats which progressed to ventricular tachycardia requiring cardioversion, lignocaine and amiodarone. Further ventricular ectopic beats (without ventricular tachycardia) were noted after the next dose (reduced to 750 mg) of erythromycin. These responded to lignocaine. Subsequent doses were reduced to 500 mg and no further arrhythmias were recorded, suggesting that this patient's ventricular arrhythmias might have been dose related.

A 77 year old man with controlled hypertension and chronic renal failure treated with recurrent dialysis was admitted to hospital for treatment of a chest infection. His usual therapeutic regimen including atenolol, nifedipine, prochlorperazine and ranitidine was continued in hospital. Initial treatment with intravenous cefotaxime was followed by three days of oral cephalexin therapy. At this time it was decided to recommence intravenous cefotaxime and initiate intravenous erythromycin therapy. Over a 10 minute period one gram each of erythromycin and cefotaxime were administered intravenously. This was followed by ventricular fibrillation and cardiac arrest which failed to respond to prolonged resuscitation measures. The fact that he had tolerated intravenous cefotaxime at the same dose level previously suggests that the intravenous erythromycin had a causal role in this patient's demise.

A 49 year old diabetic woman with controlled hypertension was hospitalised for treatment of atypical pneumonia and associated pulmonary oedema. Her usual therapeutic regimen of diet, insulin and enalapril were continued and intravenous antibiotic therapy was initiated with ceftriaxone and erythromycin 1 g every 6 hours. The first dose of erythromycin 1 g was infused over two hours and runs of ventricular tachycardia were noted. Care was taken to reduce the dose and infusion rate for subsequent treatments with erythromycin (500 mg over 3 hours) and no further runs of ventricular tachycardia were reported.

These four cases all illustrate that intravenous infusion of high doses of erythromycin can be followed closely (within minutes to hours) by serious ventricular arrhythmias. There have also been recent reports of similar reactions in association with intravenous erythromycin occurring elsewhere. These include a report of torsades de pointes which developed in two elderly females and a report of fatal cardiac toxicity which developed in two preterm neonates.1,2 Despite several confounding features in these cases the reports serve as a reminder that potentially life threatening arrhythmias may be associated with intravenous erythromycin. Extra care is required when high doses are given by the intravenous route and the rate of the infusion is of particular importance.

References

  1. Gitler B, Berger LS, Buffa SD. Torsades de pointes induced by erythromycin. Chest 1994; 105: 368-72
  2. Gouyon JB, Benoit A, Bétremieux P, et al. Cardiac toxicity of intravenous erythromycin lactobionate in preterm infants. Ped Infect Dis J 1994; 13: 840-41.

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Psychiatric effects of vigabatrin

Vigabatrin is a recently introduced anticonvulsant which is recommended as add-on therapy for the treatment of epilepsy not satisfactorily controlled by other antiepileptic drugs. The drug acts by dose dependent enzyme inhibition of g-aminobutyric acid-transaminase (GABA-T) resulting in increased brain concentrations of the inhibitory neurotransmitter, GABA.

ADRAC received its first adverse reaction report involving vigabatrin in October 1993, and to November 1994, 21 reports have been collected. Twelve of these describe psychiatric symptoms. Ages of the patients involved ranged from 4 to 66 years (median: 36) and 8 were female.

The most commonly reported adverse reactions, documented in 6 reports, were marked behavioural changes such as agitation, aggression, inappropriate behaviour, mood swings and temper tantrums. Other symptoms included depression (4 reports), paranoia (3), hallucinations (2), suicidal ideas (2), apathy (1) and nightmares (1). Although other drugs were being taken in these cases, in each instance the adverse reaction began soon after vigabatrin was commenced and resolved after the drug was ceased. Prescribers should be aware that psychiatric symptoms, which may be severe and often feature an aggressive aspect, seem to be important adverse effects of vigabatrin and subside soon after the drug is withdrawn.

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Bronchospasm and NSAIDs over the counter

The Committee has commented previously on first dose reactions1 and also severe hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs).2 It is sometimes assumed that over the counter (OTC) medications are completely safe yet although serious reactions to these drugs are rare, they do occur. Two recent reports, related to naproxen in this instance, but known to occur with other NSAIDs (some are also available OTC), highlight the problem.

A 44 year old woman had been taking a tetracycline/nystatin combination for two weeks for 'gastrointestinal thrush' when she developed dysmenorrhoea for which she took a single dose of Naprogesic (naproxen sodium). One minute after ingestion of the tablet she experienced nausea, fever, rigors, palpitations, urticaria, oedema of the tongue and bronchospasm. Following treatment with subcutaneous adrenaline and intramuscular promethazine she recovered fully.

In a similar case a 17 year old woman, described as a 'stable asthmatic' (well controlled on salbutamol, beclomethasone and theophylline), used Naprogesic for treatment of dysmenorrhoea. Within one hour she experienced the onset of periorbital oedema followed by intense bronchospasm. The reporter commented that this patient had a history of aspirin sensitivity.

Altogether, ADRAC has received 209 reports describing bronchospasm (148 reports) or anaphylactoid reaction (61 reports) in association with NSAIDs, including aspirin. In almost all of the reports, the NSAID was the only suspected drug cause. In the majority of cases the onset of symptoms occurred within two hours of the NSAID dose. Many patients required hospital treatment for the reaction and a number of cases documented a history of previous reactions to aspirin or other drugs. The majority had recovered at the time of reporting.

The above cases highlight that severe hypersensitivity reactions with NSAIDs can occur following OTC use. They also demonstrate the need for patient awareness of drug toxicity or cross sensitivity, especially with regard to a previous reaction to aspirin or another NSAID.

References

  1. ADRAC. One ADRAC meeting ..... first dose reactions. Aust Adv Drug React Bull 1992: 11: 6
  2. ADRAC. Severe hypersensitivity reactions to NSAIDs. Aust Adv Drug React Bull 1993; 12: 2.

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Drugs of current interest

Please report all suspected reactions to these Drugs of Current Interest

  • Amlodipine (Norvasc)
  • Clarithromycin (Klacid)
  • Enoxacin (Enoxin)
  • Finasteride (Proscar)
  • Gabapentin (Neurontin)
  • Gestrinone (Dimetriose)
  • Itraconazole (Sporanox)
  • Ketorolac (Toradol)
  • Lamotrigine (Lamictal)
  • Lansoprazole (Zoton)
  • Leuprorelin (Lucrin)
  • Loratadine (Claratyne)
  • Moclobemide (Aurorix)
  • Nicotine patch (Nicabate, Nicorette, Nicotinell, Prostep)
  • Nizatidine (Tazac)
  • Paroxetine (Aropax 20)
  • Piperacillin/tazobactam (Tazocin)
  • Pravastatin (Pravachol)
  • Roxithromycin (Biaxin, Rulide)
  • Salmeterol (Serevent)
  • Sertraline (Zolof)
  • Terbinafine (Lamisil)
  • Tiaprofenic acid (Surgam)
  • Ticlopidine (Ticlid)
  • Vigabatrin (Sabril)
  • 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: 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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