Published: March 1999

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Parenteral Gold and Acute Vasodilatory Reactions

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Prescriber Update 18: 39-41
March 1999

Medsafe Editorial Team

Two acute cardiovascular reactions following sodium aurothiomalate injection (Myocrisin™) have been reported to the Centre for Adverse Reactions Monitoring. Such reactions involve weakness, flushing, hypotension, tachycardia and palpitations. Very rarely myocardial infarction and stroke may follow.
The likelihood and severity of such a reaction is increased by concomitant ACE inhibitor therapy. The frequency of this reaction with or without an ACE inhibitor is not known. Aurothiomalate should be administered to those on an ACE inhibitor only where there is ready access to emergency measures for resuscitation. The patient should be observed after administration, and any vasodilatory reaction should be treated the same as anaphylaxis. Patients who develop a vasodilatory reaction should have their medication changed.

Acute vasodilatory reactions may occur with aurothiomalate

The March and June 1998 meetings of the Medicines Adverse Reactions Committee each considered a case of acute vasodilatory reactions with sodium aurothiomalate injection (Myocrisin™). The first report was of severe hypotension in a woman who had been receiving injections of sodium aurothiomalate for 30 years. She was also taking the ACE inhibitor, enalapril. The second case was fatal. The patient was taking a non-steroidal anti-inflammatory agent (NSAID) and had recently started receiving aurothiomalate injections. She had cardiac arrest 3.5 hours after the injection, apparently without early signs of an adverse effect. Defibrillation and cardiopulmonary resuscitation (CPR) restored cardiac rhythm, but she did not regain consciousness and died 2 days later. In this case, since there were no early symptoms, the cardiac arrest may have been coincidental.

MNG Dukes in Meyler’s Side Effects of Drugs¹ states that:

Acute vasodilatory (nitritoid) reactions may occur in a minority of patients on parenteral gold, especially sodium aurothiomalate. A few minutes after injection, the patient experiences weakness, flushing, hypotension, tachycardia, palpitations, sweating and sometimes syncope. Very rarely indeed, myocardial infarction and stroke follow.

Reactions may be life-threatening with concomitant ACE inhibitor

Several cases of such reactions have been published in the literature. Healey and Backes² report four cases in patients who had been receiving monthly injections of sodium aurothiomalate for at least 2 years. Each had recently commenced therapy with one of the ACE inhibitors. One patient was subsequently able to tolerate aurothioglucose (this product is oil-based and not marketed in New Zealand), two continued sodium aurothiomalate after the ACE inhibitor was withdrawn and the other experienced no adverse reaction with aurothiomalate at a reduced dose of 25mg.

Two other cases are described in more detail. In one case³ the woman had been receiving concomitant lisinopril for 12 months without incident, except for a brief occurrence of paraesthesiae, when she experienced a severe vasodilatory reaction. Five to ten minutes after receiving an injection of aurothiomalate she became dizzy, flushed and nauseated. She then collapsed with no blood pressure or pulse and stopped breathing. Recovery followed administration of CPR, intravenous adrenaline and hydrocortisone. Another patient⁴ received fortnightly sodium aurothiomalate 50mg and daily captopril for 31 weeks without incident, but then developed a vasodilatory reaction from which she rapidly recovered. Subsequent administration of aurothiomalate resulted in confusion, profuse sweating and a drop in blood pressure within 30 minutes of the dose, followed by loss of consciousness with respiratory insufficiency. The patient died without regaining consciousness.

ACE inhibitors may unmask a hypersensitivity reaction

Acute vasodilatory reactions with sodium aurothiomalate can occur without co-administration of ACE inhibitors. In such cases the reaction is usually mild although it may be frightening. It rarely occurs after the first year of use. With concomitant use of ACE inhibitors the reaction may become life-threatening. It appears that ACE inhibitors contribute to the reaction by unmasking a hypersensitivity reaction through potentiation of kinins. (See article on resensitisation to bee and wasp venom) A related issue, also associated with the action on kinins, is that of the angioedema that occurs with ACE inhibitors.⁵ In some cases angioedema develops within the first week of therapy but for others the first episode may be up to 4 years after commencement of treatment. Some have many episodes before diagnosis.

Treat any vasodilatory reaction as for anaphylaxis

No data are available on the frequency of acute vasodilatory reactions following the administration of aurothiomalate injection to patients taking ACE inhibitors. Clinicians should be aware that these reactions may occur and that they may be life-threatening. Unfortunately it is not possible to provide precise guidance for patient management. Patients who are receiving an ACE inhibitor and aurothiomalate injections should be warned of the risk of an acute vasodilatory reaction, and a decision should be reached with the patient whether the benefit gained from the treatment is worth the risk of developing the reaction. Aurothiomalate should be administered where there is ready access to emergency measures for resuscitation, and the patient should be monitored for blood pressure, heart rate and respiratory rate. If a vasodilatory reaction develops it should be treated in the same way as anaphylaxis. There should be a change of medication in any patient who develops a vasodilatory reaction.

References

1. Dukes MNG. Metals (Section editor P Folb). In Dukes MNG (Ed). Meyler's Side Effects of Drugs 13^th Edn. 1996: Amsterdam, Elsevier, p. 590.
2. Healey LA, Backes MB. Nitritoid reactions and angiotensin-converting enzyme inhibitors. New Eng J Med 1989;321:763.
3. Ching DWT, McClintock AD. Nitritoid reaction in a patient on ACE inhibitor and Myocrisin treatments. Aust NZ J Med 1997;27:343.
4. Tilelli JA, Heinrichs MM. Adverse reactions to parenteral gold salts. Lancet 1997;349:853.
5. Pillans PI, Coulter DM, Black P. Angioedema and urticaria with angiotensin converting enzyme inhibitors. Eur J Clin Pharmacol 1996;51:123-6.