Drug Interaction Report

MONITOR: Coadministration with human growth hormone may decrease the plasma concentrations of drugs that are metabolized by CYP450 3A4. Data from an interaction study performed in growth hormone deficient adults suggest that growth hormone (somatropin) administration can increase the clearance of compounds known to be metabolized by cytochrome P450 isoenzymes, especially CYP450 3A4. The clinical significance is unknown.

MANAGEMENT: Caution is advised when human growth hormone is used concurrently with drugs that are known CYP450 3A4 substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever human growth hormone is added to or withdrawn from therapy.

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.