Adverse Reactions and Drug Interactions with Radiopharmaceuticals

Summary

Adverse reactions to radiopharmaceuticals are comparatively few in number. Various estimates quote an incident rate of 1 to 6 reactions per 100 000 injections. Other figures quoted are 1 in 800 for the bone-seeking radiopharmaceutical methylene diphosphonate, and 1 in 400 for the lung visualisation agent macroaggregated albumin. The very low numbers of reported adverse effects probably reflect the tiny amounts of material which are used in the formulation of radiopharmaceuticals.

Adverse reactions to radiopharmaceuticals are usually mild and transient and require little or no medical treatment. A few reactions involve respiratory or circulatory collapse or loss of consciousness. Several fatalities have been reported with the liver scanning agent ^99mTc (technetium 99m)-albumin colloid.

Clinical manifestations may be categorised under the headings of vasomotor effects i.e. faintness, pallor, diaphoresis or hypotension, and anaphylactoid effects such as nausea, dermographism, wheezing, bronchospasm, erythema and pruritus.

The most prominent group of radiopharmaceuticals that have been reported to produce adverse events are the diphosphonates, which are used for scanning the skeleton. Typical diphosphonate reactions include erythema (especially over the extremities), nausea, vomiting and malaise. The onset of reaction is usually 2 to 3 hours after injection. The second group of radiopharmaceuticals which give rise to adverse events are the colloids, which are used for liver and spleen scintigraphy. Typical colloid reactions include pallor, nausea, flush and pulse changes.

Adverse events may also occur as a result of the patient’s medication interfering with the disposition of the radiopharmaceutical. Although not usually hazardous or dangerous, such events may be so pronounced that a marked deviation in the expected pharmacokinetics may occur.

Drug interactions can be conveniently categorised under the headings of unusual handling of the radiopharmaceutical because of pharmacological action, genuine in vivo interaction between the medication and radiopharmaceutical, drug-induced disease and interaction between the radiopharmaceutical and catheters or syringes.

The most serious drug interactions are those where the patient is taking cortisone or cytotoxic agents prior to tumour scintigraphy. Other important effects occur in patients undergoing bone scanning who are receiving iron preparations. Nifedipine has been reported to produce quite severe problems in scanning, including difficulties in the radiolabelling of red cells (for cardiac scintigraphy), and other effects where the drug appears to prevent the transport of bone-seeking materials into the skeleton.

Many drugs alter hormonal status and these effects may produce marked deviations from the expected biodistribution. Diethylstilbestrol (stilboestrol), digitalis, gonadotrophins, phenothiazines and cimetidine all increase estrogen levels in high doses. In such instances gynaecomastia can occur, and it has been found that there is increased localisation of the cardiac imaging agent ^99mTc-pyrophosphate and the tumour localisation agent ⁶⁷Ga (gallium 67)-citrate in gynaecomastic breasts.

Many therapeutic drugs can cause or aggravate disease, and the disease itself may produce an unexpected biodistribution of radiopharmaceutical. An example is liver toxicity as a result of ingestion of large amounts of paracetamol (acetaminophen), aspirin, cytotoxic drugs, tetracycline and halothane. Liver disease would show up on the scintigram as a ‘cold’ area.

For both adverse reactions and drug interactions there is, at present, considerable underreporting. It is essential to report all adverse events, no matter how trivial, in order to make a proper assessment of the size of the problem and to improve diagnostic accuracy.