Current perspectives in herbal and conventional drug interactions based on clinical manifestations

Surana, Ajaykumar Rikhabchand; Agrawal, Shivam Puranmal; Kumbhare, Manoj Ramesh; Gaikwad, Snehal Balu

doi:10.1186/s43094-021-00256-w

Future Journal of Pharmaceutical Sciences

Table 1 Herb-drug interactions (HDIs) of some herbs with possible mechanism, outcome and level of HDIs

From: Current perspectives in herbal and conventional drug interactions based on clinical manifestations

Herb	Drug	Possible mechanism	HDI outcome	Level of HDIS	References
Danshen	Warfarin	Additive effect	Potentiated anticoagulant effect	+++	[19,20,21]
Danshen	Midazolam	CYP3A4 induction	Decreased F of midazolam	++	[22]
Echinacea	Caffeine	CYP1A2 inhibition	Decreased CL/F of caffeine	++	[24, 25]
	Midazolam	CYP3A4 induction	Increased CL and decreased F of midazolam	+	[24, 25]
	Tolbutamide	CYP2C9 inhibition (weakly)	Reduces CL/F of tolbutamide	+	[24, 25]
Garlic	Saquinavir	P-gp induction	Increased CL and decreased F of saquinavir	+++	[27, 28]
	Warfarin	Additive effect	Increased anticoagulant effect	++	[29, 30]
	Chlorzoxazone	CYP2E1 inhibition	Decreased serum 6-hydroxychlorzoxazone/chlorzoxazone ratio	++	[31, 32]
	Fluindione	P450 inhibition	Decreased INR level	++	[33]
Ginkgo biloba	Tolbutamide	CYP2C9 inhibition	Decreased AUC of tolbutamide	+	[35]
	Midazolam	CYP3A inhibition	Decreased AUC and C_max of midazolam	++	[36]
	Nifedipine	CYP3A inhibition	C_max of nifedipine was doubled	+++	[37]
	Omeprazole	CYP2C19 induction	Decreased C_max of omeprazole and increased C_max of 5-hydroxyomeprazole	+	[38]
	Talinolol	P-glycoprotein inhibition	Increased C_max and AUC of talinolol	++	[39]
	Fexofenadine	P-gp-mediated efflux inhibition	Increased AUC and C_max of fexofenadine	+++	[40]
	Ibuprofen	Additive effects	Increase anticoagulant effect	+++	[96]
	Diuretic (thiazide)	Agonism	Increased blood pressure	+++	[41]
	Valproic acid	CYP2C19 induction	Fatal seizure	++	[42]
	Antipsychotic drug (risperidone)	CYP2D6 and CYP3A4 inhibition	Increased C_max of risperidone and causes priapism	++	[43]
	Efavirenz	CYP3A4 and P-gp induction	Virologic failure associated with decreased efavirenz blood concentration	++	[44]
	Trazodone	CYP3A4 induction	Enhancement of GABAergic activity leading to coma	++	[45]
Goldenseal	Debrisoquine	CYP2D6 inhibition	Decreased debrisoquine urinary recovery ratios (DURR)	+++	[48, 49]
	Midazolam	CYP3A4/5 inhibition	Increased AUC and C_max of midazolam	+++	[48, 50]
	Cyclosporin A	CYP3A4 inhibition	Increased blood concentration of cyclosporin A	++	[48, 51]
Green tea	Folic acid	Carrier-mediated absorption inhibition	Decreased F of folic acid	+++	[53, 54]
	Simvastatin	CYP3A4 inhibition	Increased AUC and C_max of simvastatin	+++	[55, 56]
	Warfarin	Antagonism effect	Decreased anticoagulant effect	++	[57, 58]
Kava	Benzodiazepine (Alprazolam)	Additive effect on GABA receptors	Increased benzodiazepine effect	+++	[60,61,62]
	Chlorzoxazone	CYP2E1 inhibition	Decreased 6-hydroxychlorzoxazone/chlorzoxazone serum ratios	+++	[48]
	Dopamine	Dopamine antagonism	Reduced dopamine efficacy	++	[63]
Liquorice	Omeprazole	CYP3A4 induction	Decreased plasma concentrations of omeprazole	++	[65]
Liquorice	Midazolam (benzodiazepines)	CYP3A4 induction	Decreased plasma concentrations of midazolam	++	[66]
Milk thistle	Metronidazole	P-gp & CYP3A4 induction	Decreased blood concentration of metronidazole	++	[68]
	Losartan	CYP2C9 inhibition	Increased AUC of losartan.	++	[69]
	Talinolol	P-gp inhibition	Increased AUC and C_max, and decreased CL/F of talinolol	++	[70]
St. John’s wort	Amitriptyline	CYP3A4 and P-gp induction	Decreased blood concentration of amitriptyline	++	[72,73,74,75,76,77]
	Atorvastatin	CYP3A4 and P-gp induction	Reduced efficacy of atorvastatin	+	[72, 73, 78]
	Cyclosporine	CYP3A4 and P-gp induction	Cyclosporine exhibits a relatively small therapeutic window	++	[72, 73, 79,80,81,82]
	Digoxin	CYP3A4 and P-gp induction	Decreased blood concentration of digoxin	++	[72, 73, 83, 84]
	Methadone	CYP3A4 and P-gp induction	Decreased blood concentration of methadone	+++	[72, 73, 85]
	Alprazolam	CYP3A4 induction	Decreased blood concentration of alprazolam	+++	[72]
	Imatinib	CYP3A4 induction	Decreased blood concentration of imatinib	+++	[72, 86, 87]
	Indinavir	CYP3A4 induction	Decreased blood concentration of indinavir	+++	[72, 88]
	Irinotecan	CYP3A4 induction	Decreased blood levels of SN-38	+++	[72, 89]
	Nevirapine	CYP3A4 induction	Decreased blood concentration of nevirapine	++	[72, 90]
	Chlorzoxazone	CYP2E1 induction	Increase in hydroxylchlorzoxazone/chlorzoxazone serum ratio	++	[31, 32]
	Bupropion	Additive effects	Orofacial dystonia	+++	[91,92,93,94]
	Buspirone	Additive effect on 5-HT reuptake	Hypomanic episode, serotonin syndrome	+++	[94]

P-gp P-glycoprotein, F Bioavailability, AUC area under the plasma drug concentration-time curve, C_max maximum plasma concentrations, CL total renal clearance, CL/F oral clearance
+Mild HDI
++Moderate HDI
+++Major HDI

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