Diosmin - Provigil (Modafinil) Interaction

Interaction Details

Modafinil is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, diosmin might inhibit the metabolism of CYP3A4 substrates.
Laboratory research is conflicting with respect to the effects of diosmin on CYP3A4. Some research suggests that diosmin does not affect CYP3A4 activity. However, other research suggests that diosmin alters the metabolism of carbamazepine, a CYP3A4 substrate. Laboratory and animal research show that oral administration of diosmin for 7 days prior to oral administration of carbamazepine increases plasma concentrations of carbamazepine, decreases the clearance of carbamazepine, and decreases the formation of carbamazepine's active metabolite. Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of carbamazepine 200 mg increases blood levels of carbamazepine by approximately 58% and decreases carbamazepine clearance by 42%. It is speculated that diosmin reduces the metabolism of carbamazepine by inhibiting CYP3A4. Diosmetin, a metabolite of diosmin, may also inhibit CYP3A4.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Bedada SK, Neerati P. Modulation of CYP3A enzyme activity by diosmin and its consequence on carbamazepine pharmacokinetics in rats. Naunyn Schmiedebergs Arch Pharmacol. 2018;391(2):115-21.
• Burkina V, Zlabek V, Halsne R, Ropstad E, Zamaratskaia G. In vitro effects of the citrus flavonoids diosmin, naringenin and naringin on the hepatic drug-metabolizing CYP3A enzyme in human, pig, mouse and fish. Biochem Pharmacol. 2016;110-111:109-16
• Bedada SK, Boga PK. Influence of diosmin on the metabolism and disposition of carbamazepine in healthy subjects. Xenobiotica. 2017;47(10):879-84.

Interaction Details

Modafinil is classified as belonging to the following category: P-Glycoprotein Substrates

Theoretically, diosmin might increase levels of drugs that are substrates of P-glycoprotein (P-gp).
Preliminary laboratory research suggests that diosmin inhibits P-gp. Additionally, pharmacokinetic research in healthy male subjects shows that taking diosmin (Venex) 500 mg daily for 10 days prior to oral administration of fexofenadine 120 mg increases blood levels of fexofenadine, a P-gp substrate, by approximately 49% and decreases the apparent oral clearance of fexofenadine by 41%. The time taken to reach maximum plasma concentration, the half-life, and the apparent renal clearance of fexofenadine are not affected. For this reason, it is speculated that diosmin inhibits P-gp in the intestine, but not in the kidney or liver.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Yoo HH, Lee M, Chung HJ, Lee SK, Kim DH. Effects of diosmin, a flavonoid glycoside in citrus fruits, on P-glycoprotein-mediated drug efflux in human intestinal Caco-2 cells. J Agric Food Chem. 2007 Sep 5;55(18):7620-5.
• Bedada SK, Boga PK, Kotakonda HK. The effect of diosmin on the pharmacokinetics of fexofenadine in healthy human volunteers. Xenobiotica. 2017;47(3):230-35.

Modafinil Overview

• Modafinil is used to treat excessive sleepiness caused by narcolepsy (a condition that causes excessive daytime sleepiness) or shift work sleep disorder (sleepiness during scheduled waking hours and difficulty falling asleep or staying asleep during scheduled sleeping hours in people who work at night or on rotating shifts). Modafinil is also used along with breathing devices or other treatments to prevent excessive sleepiness caused by obstructive sleep apnea/hypopnea syndrome (OSAHS; a sleep disorder in which the patient briefly stops breathing or breathes shallowly many times during sleep and therefore doesn't get enough restful sleep). Modafinil is in a class of medications called wakefulness promoting agents. It works by changing the amounts of certain natural substances in the area of the brain that controls sleep and wakefulness.

Diosmin - More Interactions

Diosmin interacts with 839 drugs

Interaction Rating Key

These severity listings are for informational use only. Never start, stop or otherwise change your therapy before speaking with your provider.