Possible adverse effects of erythromycin./nThe patient, a 32-year-old woman with tonsilitis, began

Fråga: Possible adverse effects of erythromycin.

The patient, a 32-year-old woman with tonsilitis, began treatment with tablets of Abboticin (1000 mg per day) on 920428. The first day of treatment, the patient noted nausea, dizziness and eye fibrillation. On 920503, the patient reported experiencing twitches, primarily in the neck and jaw, and also noted difficulty in moving her arms, as well as a general overall swelling. She also fainted once. One 920504 the patient came in to the emergency department, where weakness in the right arm, nystagmus when looking both right and left, diplopia (primarily when looking to the right), a tendency to lowering in the Grasset test and a tendency toward right-side pronation were noted. CT was normal. The diagnosis was assessed as functional genesis and the patient was sent home. After one week, the patient noticed a yellowish tinge to the whites of her eyes and to her tongue. She also noticed right-sided subcostal pain. Liver tests (ASAT, ALAT, LD, bilirubin, gamma-GT, ALP) taken on 920507 were normal, as was a throat culture. By 920510 the patient was completely recovered.

The patient reacted in a similar way in the early 80s when treated with paracetamol and dextropropoxyphene. Her case history also mentioned that she is hypersensitive to quinoline yellow, which, according to the patient, has been verified by test. She is also allergic to penicillin and preservatives. Could the above-mentioned symptoms be side-effects of the treatment with erythromycin?

Sammanfattning: Erythromycin can cause gastrointestinal disturbances, for example nausea. Hypersensitivity reactions are rare. Cholestatic jaundice usually becomes evident clinically 10-14 days after starting therapy and is often associated with abdominal cramps and aminotransferase elevation. There are no reports of erythromycin-induced focal neurological signs, and, although it is imprudent to exclude the possibility that it could produce complications such as those in the present case, other explanations for the symptoms should be suspected.

Svar: Gastrointestinal disturbances are fairly common with erythromycin, especially large doses, but serious side-effects are rare (1). Hypersensitivity reactions have been reported in 0.5 per cent of patients taking the drug (5,7). Among the allergic reactions observed are fever, eosinophilia, and skin eruptions, which may occur alone or in combination; each disappears shortly after therapy is stopped (2). Also, maculopapular rashes, pruritus, urticaria, angio-oedema and skin rash have been described (5). A skin test with erythromycin has been found useful for diagnosis of the immediate and/or delayed type of hypersensitivity. Isolated cases of anaphylaxis have been reported (1). Reversible deafness has occurred after high doses of erythromycin (1).

Erythromycin 500 mg twice daily by mouth was given 30 minutes before food for at least 6 months to 607 patients with acne. The most common adverse effect was diarrhoea (7.2 per cent) and nausea (1.6 per cent). Dizziness occurred with a frequency of 0.2 per cent (1).

There are several previous Drugline documents (6,9) on erythromycin-induced hepatic injury. Cholestasis, cholestatic jaundice and allergic reactions are the most common side-effects of erythromycin. The incidence of cholestatic liver injury has been estimated to be 2-4 per cent in erythromycin-treated patients. Another study based on a large population estimated the incidence at less than 0.1 per cent. The incidence of hepatic injury was earlier found to be much higher with erythromycin estolate than with other salts or the base compound (6). However, recent evidence suggests that, contrary to earlier impressions, erythromycin estolate is no more likely to be implicated than the other formulations (4,8). Erythromycin estolate is no longer marketed in Sweden (6).

Symptoms of hepatotoxicity follow after about 10-20 days of treatment and are characterised initially by nausea, vomiting, and upper abdominal cramps or subcostal pain. The pain often mimics that of acute cholecystitis (2-4) and has been suggested to be due to erythromycin-induced contractions in the gastrointestinal tract with endogenous release of motilin (9). These symptoms are followed shortly thereafter by jaundice, which may be accompanied by fever, leucocytosis, eosinophilia, and elevated activities of transaminases in plasma. Biopsy of the liver reveals cholestasis, periportal infiltration by neutrophils, lymphocytes, and eosinophils, and, occasionally, necrosis of neighbouring parenchymal cells. All manifestations usually disappear within a few days after cessation of drug therapy and are rarely prolonged (2). Abdominal cramps, nausea, vomiting, and diarrhoea are dose related and occur more commonly in children and young adults (2).

An electromyographic, myasthenia-like clinical picture has been described in adult patients receiving 1.5 gram of erythromycin. The phenomenon disappeared after withdrawal of the antibiotic (3).

The files of the Swedish Adverse Drug Reaction Advisory Committee (SADRAC) contain a total of 595 adverse effects reported since 1966. There are 14 reports of neurological side-effects which were judged to be related to erythromycin treatment. Among these there were one case of muscle weakness, one case of facial paralysis, and six cases of vertigo. There were also one case of diplopia, one case of a tendency to faint, two cases of oedema, two cases of anaphylactic reaction, and 46 cases of icterus. There were 159 cases of gastrointestinal side-effects reported to SADRAC.

The documentation of adverse neurological effects is very sparse. Furthermore, there have not been any case reports at all in the literature indicating that erythromycin could cause vertigo, nystagmus or eye fibrillation. In a review on drug-induced neurological disease (10) it has been pointed out that all antibiotics are potentially neurotoxic, including undiluted penicillin. Despite this brief documentation of neurological symptoms in the literature, in view of the existing reports of liver disturbances and hypersensitivity reactions complicating the use of erythromycin, and the close time relation between erythromycin therapy and the appearance of symptoms in your patient, it seems imprudent to exclude the possibility that erythromycin could have induced the symptoms in the present case. If there is no other obvious explanation, this case should be reported to the Swedish Medical Board of Health.