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Drug Interactions between Lescol XL and nitisinone

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

fluvastatin nitisinone

Applies to: Lescol XL (fluvastatin) and nitisinone

MONITOR: Coadministration with inhibitors of CYP450 2C9 may increase the plasma concentrations of fluvastatin. According to the prescribing information, fluvastatin is primarily metabolized by CYP450 2C9 (approximately 75%) and, to a much lesser extent, by CYP450 2C8 and 3A4 (approximately 5% and 20%, respectively). When a single 40 mg oral dose of fluvastatin was administered on day 4 of treatment with the moderate CYP450 2C9 inhibitor fluconazole (400 mg orally on day 1 and 200 mg on days 2 to 4) in 12 healthy study subjects, mean fluvastatin peak plasma concentration (Cmax), systemic exposure (AUC) and elimination half-life (t1/2) increased by 44%, 84% and 80%, respectively, compared to administration with placebo. Fluconazole is also a moderate CYP450 3A4 inhibitor, which may have contributed to the interaction. In a similar study conducted by the same investigators, fluconazole had no significant effect on the pharmacokinetics of a single 40 mg oral dose of pravastatin.

MANAGEMENT: Caution is advised when fluvastatin is prescribed with CYP450 2C9 inhibitors. The lowest starting dosage of fluvastatin is recommended, then titrated as needed based on clinical response and tolerance. Alternatively, pravastatin is not metabolized by CYP450 2C9 and may be a reasonable substitute for fluvastatin. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed.

References (4)
  1. (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
  2. Kantola T, Backman JT, Niemi M, Kivisto KT, Neuvonen PJ (2000) "Effect of fluconazole on plasma fluvastatin and pravastatin concentrations." Eur J Clin Pharmacol, 56, p. 225-9
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."

Drug and food interactions

Moderate

nitisinone food

Applies to: nitisinone

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References (32)
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  3. Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
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  5. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
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  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
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  18. Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

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