Drug-grapefruit juice interaction cases

Information in the PI is typically based on the studies submitted by a drug s manufacturer. The FDA has also utilized spontaneous adverse event case reports as a tool in the evaluation of drug-grapefruit juice interaction labeling. Other sources of data that contribute to labeled information include studies or case reports from the medical literature. 

To identify case reports containing information on drug and grapefruit juice interaction, the Adverse Event Reporting System (AERS) (2) database... 

Many drugs will cause adverse effects if the dose is excessive but some cause adverse effects at the correct dose in certain individuals. This can be due to an increased sensitivity of the patient because of genetic or other factors (see pp. 29-31). There may also be side effects which are not apparent at low or therapeutic doses but which become more important at higher doses. Occasionally, unexpected and serious adverse effects occur in a few patients. Sometimes this is due to an interaction between two drugs or between a drug and a food constituent such as occurred with the drug terfenadine (used to treat hay fever) and grapefruit juice (see case note, pp. 33-4). 

Lee M, Min DI. Determination of sildenafil citrate in plasma by high-performance liquid chromatography and a case for the potential interaction of grapefruit juice with sildenafil citrate. Ther Drug Monit 2001 23(l) 21-26. 

These predictions are as yet unconfirmed, but it would certainly be prudent to monitor sirolimus levels closely if these drugs are used concurrently. What should be remembered is that the extent of the inhibitory effects of these drugs is not identical, so that very marked effects like those observed with ketoconazole may not occur, nevertheless the interaction may still be clinically important. Grapefruit juice also inhibits CYP3A4 (potentially raising sirolimus levels), and in this case the manufacturers recommend that concurrent use should be avoided. - ... 

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