Drug Interactions between brentuximab and Mevacor
This report displays the potential drug interactions for the following 2 drugs:
- brentuximab
- Mevacor (lovastatin)
Interactions between your drugs
lovastatin brentuximab vedotin
Applies to: Mevacor (lovastatin) and brentuximab
MONITOR: Brentuximab vedotin can cause peripheral neuropathy, and concurrent use of other agents that are also associated with this adverse effect can potentiate the risk. The peripheral neuropathy associated with brentuximab vedotin treatment is cumulative and primarily sensory, but cases of peripheral motor neuropathy have also been reported. In premarketing clinical trials, 54% of patients experienced neuropathy of any grade. Of these patients, 49% had complete resolution, 31% had partial improvement, and 20% had no improvement. A total of 51% of patients who reported neuropathy had residual neuropathy at the time of their last evaluation.
MONITOR: Coadministration of brentuximab vedotin with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Serious cases of hepatotoxicity, some fatal, have occurred in patients treated with brentuximab vedotin. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and typically occurred after the first dose or after a rechallenge. Preexisting liver disease and elevated baseline liver enzymes may also increase the risk.
MANAGEMENT: The potential for increased risk and/or severity of peripheral neuropathy and hepatotoxicity should be considered when brentuximab vedotin is used with other drugs that are also associated with these adverse effects. Patients should be closely monitored for symptoms of neuropathy such as burning, tingling, pain, numbness, or weakness. Liver enzymes and bilirubin should be measured before and during treatment, especially in patients with underlying hepatic disease or marked baseline transaminase elevations. Patients experiencing new, worsening, or recurrent neuropathy or hepatotoxicity may require a delay, change in dosage, or discontinuation of brentuximab vedotin in accordance with the product labeling. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice.
References
- (2011) "Product Information. Adcetris (brentuximab vedotin)." Seattle Genetics Inc
Drug and food interactions
lovastatin food
Applies to: Mevacor (lovastatin)
GENERALLY AVOID: Coadministration with grapefruit juice may significantly increase the plasma concentrations of lovastatin and simvastatin and their active acid metabolites. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. When a single 60 mg dose of simvastatin was coadministered with 200 mL of double-strength grapefruit juice three times a day, simvastatin systemic exposure (AUC) increased by 16-fold and simvastatin acid AUC increased by 7-fold. Administration of a single 20 mg dose of simvastatin with 8 ounces of single-strength grapefruit juice increased the AUC of simvastatin and simvastatin acid by 1.9-fold and 1.3-fold, respectively. The interaction has also been reported with lovastatin, which has a similar metabolic profile to simvastatin. Clinically, high levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death.
ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.
Coadministration with green tea may increase the plasma concentrations of simvastatin. The mechanism of interaction has not been established, but may involve inhibition of organic anion transporting polypeptide (OATP) 1B1- and/or 2B1-mediated hepatic uptake of simvastatin by catechins in green tea. The interaction was suspected in a 61-year-old man who experienced muscle intolerance during treatment with simvastatin while drinking an average of 3 cups of green tea daily. He also experienced similar muscle intolerance (leg cramps without creatine phosphokinase elevation) during treatments with atorvastatin and rosuvastatin while drinking green tea. Pharmacokinetic studies performed during his usual green tea intake demonstrated an approximately two-fold higher exposure to simvastatin lactone (the administered form of simvastatin) than that observed after stopping green tea intake for a month. He was also able to tolerate simvastatin after discontinuing green tea consumption. The authors of the report subsequently conducted two independent studies to assess the effect of different green tea preparations on simvastatin pharmacokinetics. One study was conducted in 12 Italian subjects and the other in 12 Japanese subjects. In the Italian study, administration of a single 20 mg dose of simvastatin following pretreatment with 200 mL of a hot green tea standardized infusion 3 times daily for 14 days (estimated daily intake of 335 mg total catechins and 173 mg epigallocatechin-3-gallate (EGCG), the most abundant and biologically active catechin in green tea) was found to have no significant effect on mean peak plasma concentration (Cmax) or systemic exposure (AUC) of simvastatin lactone and simvastatin acid relative to administration with water. However, green tea increased simvastatin lactone AUC (0-6h) by about two-fold in 3 of the study subjects. In the Japanese study, administration of a single 10 mg dose of simvastatin following pretreatment with 350 mL of a commercial green tea beverage twice daily for 14 days (estimated daily intake of 638 mg total catechins and 322 mg EGCG) did not affect mean simvastatin lactone Cmax or AUC to a statistically significant extent compared to administration with water, but increased mean simvastatin acid Cmax and AUC by 42% and 22%, respectively. Similar to the first study, green tea increased simvastatin lactone AUC (0-6h) by two- to three-fold in 4 of the study subjects. Although not studied, the interaction may also occur with lovastatin due to its similar metabolic profile to simvastatin.
MANAGEMENT: Patients receiving therapy with lovastatin, simvastatin, or red yeast rice (which contains lovastatin) should be advised to avoid the consumption of grapefruit and grapefruit juice. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are metabolized by other enzymes and may be preferable alternatives in some individuals. 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. Also, patients should either refrain from the use of oat bran and pectin, or separate the administration times by at least 2 to 4 hours if concurrent use cannot be avoided. Caution may be advisable when coadministered with green tea or green tea extracts. Dosing reduction of the statin and/or limiting consumption of green tea and green tea products may be required if an interaction is suspected.
References
- Richter WO, Jacob BG, Schwandt P (1991) "Interaction between fibre and lovastatin." Lancet, 338, p. 706
- (2002) "Product Information. Mevacor (lovastatin)." Merck & Co., Inc
- (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
- Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
- Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
- Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
- Thompson PD, Clarkson P, Karas RH (2003) "Statin-associated myopathy." JAMA, 289, p. 1681-90
- Neuvonen PJ, Backman JT, Niemi M (2008) "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin Pharmacokinet, 47, p. 463-74
- Werba JP, Giroli M, Cavalca V, Nava MC, Tremoli E, Dal Bo L (2008) "The effect of green tea on simvastatin tolerability." Ann Intern Med, 149, p. 286-7
- Werba JP, Misaka S, Giroli MG, et al. (2014) "Overview of Green Tea Interaction with Cardiovascular Drugs." Curr Pharm Des
- Roth M, Timmermann BN, Hagenbuch B (2011) "Interactions of green tea catechins with organic anion-transporting polypeptides." Drug Metab Dispos, 39, p. 920-6
- Knop J, Misaka S, Singer K, et al. (2015) "Inhibitory effects of green tea and (-)-epigallocatechin gallate on transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-glycoprotein." PLoS One, 10, e0139370
lovastatin food
Applies to: Mevacor (lovastatin)
MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.
MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.
References
- (2001) "Product Information. Pravachol (pravastatin)." Bristol-Myers Squibb
- (2001) "Product Information. Zocor (simvastatin)." Merck & Co., Inc
- (2001) "Product Information. Lescol (fluvastatin)." Novartis Pharmaceuticals
- (2001) "Product Information. Lipitor (atorvastatin)." Parke-Davis
- (2002) "Product Information. Altocor (lovastatin)." Andrx Pharmaceuticals
- (2003) "Product Information. Crestor (rosuvastatin)." AstraZeneca Pharma Inc
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2010) "Product Information. Livalo (pitavastatin)." Kowa Pharmaceuticals America (formerly ProEthic)
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.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Further information
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