Table 2.
Case reports of herb–drug interactions in individual patients
| Patient description [reference] | Herb supplement Latin name (common use) | Affected drug | Concomitant medications | Signs or symptoms of possible interaction | Plausible mode of interaction | Probability scale 37 |
|---|---|---|---|---|---|---|
| 58‐year‐old man with a history of phalangeal fracture 42 | Ginkgo biloba (improve cognitive function) | Sodium aescinate | Cefuroxime | Elevated serum creatinine and blood, urea and nitrogen (BUN) levels | CYP2C9 and 3A4 inhibition | Probable (5) |
| 56‐year‐old man with a history of orthotopic liver transplantation 43 | Curcuma longa (anti‐inflammatory and liver protection) | Tacrolimus | Steroids, IV immunoglobulin, rituximab, sofosbuvir/ribavirin | Abdominal distention, scrotal and peripheral oedema, increased creatinine | CYP3A4/5 inhibition | Probable (7) |
| 50‐year‐old Caucasian man with monophasic synovial sarcoma 44 | Diosmin (blood disorders) | Trabectedin | Epirubicin, ifosfamide | Rhabdomyolysis, increase serum myoglobin, creatinine phosphokinase and liver function | CYP3A4 inhibition | Probable (5) |
| 52‐year‐old white, woman, with a history of major depressive disorder, hypertension and dyslipidaemia 45 | Celery root (menopause) | Venlafaxine | SJW | Confusion and speech abnormalities | CYP2D6 inhibition | Possible (4) |
| 49‐year‐old man without a family history had partial seizures with a secondarily generalization since he was age 27 years. 46 | Noni juice (Tahitian Noni Original Bioactive Beverage) | Phenytoin | Lamotrigine, lorazepam, clobazam | Low phenytoin level in blood | CYP2C9 induction | Highly probable (9) |
| 44‐year‐old white man generalized tonic–clonicseizure disorder 47 | Ginseng (improve mental and physical performance) | Lamotrigine | Deer antler velvet, sildenafil, hydrocortisone cream | DRESS syndrome (pruritic rash on more than 50% of his body, eosinophilia, myalgias, and elevated liver enzymes) | UGT2B7 inhibition | Probable (5) |
| 35‐year‐old woman with a history of depression 48 | Centella asiatica and Fucus vesiculosus(rash, eczema, psoriasis and other skin infections) | Venlafaxine | None | Progressive dyspnoea over the previous, New York Heart Association(NYHA) functional class III, myalgia, and dry cough | CYP2D6 slow metabolizer or CYP2D6 inhibition by Centella asiatica | Possible (3) |
| 56‐year‐old woman Caucasian patient diagnosed witha temporal–parietal glioblastoma WHO IV 49 | Bu Zhong Yi Qi Wan (promotes physical strength) | Temozolomide | Dexamethasone, pantoprazol, levetiracetam, mirtazapine, valaciclovir | Grade II thrombopenia and elevated liver enzymes | Unknown | Probable (5) |
| 78‐year‐old Hispanic, man, renal transplant patient 50 | Pneumus boldus(mild dyspepsia and spastic gastrointestinal complaints) | Tacrolimus | mycophenolate, metoprolol, simvastatin, tamsulosin, aspirin, lisinopril, amlodipine, calcium carbonate, omeprazole, and insulin | Asymptomatic | Unknown | Probable (6) |
| 44‐year‐old obese man (body mass index: 53 kg m –2 ) with stage‐III (ISS) IgG‐κ multiple myeloma 51 | Flor‐Essence (anticancer) | Busulfan | Bortezomib, melphalan | GI toxicities, including Grade 3 nausea,vomiting, diarrhoea and oesophagitis | Unknown | Possible (2) |
| 82‐year‐old woman with a history of hypertension, hypothyroidism, gastritis, atrial fibrillation 52 | Artemisia absinthium (sore throat) | Warfarin | Nebivolol, valsartan hydrochlorothiazide, levothyroxine and esomeprazole | abdominal pain and black, tarry stool | Unknown | Possible (4) |
| 56‐year‐old Caucasian man with a history of progressive abdominal pain due to liposarcoma with a retroperitoneum mass (5 × 8 cm) 53 | Chokeberry juice (anticancer) | Trabectedin | Peg‐granulocyte colony stimulating factor | Rhabdomyolysis, G4 pancytopenia, elevated liver enzymes | CYP3A4 inhibition | Possible (4) |
| 16‐year‐old child with nephrotic syndrome 54 | Berberine (diarrhoea) | Tacrolimus | Prednisone | Renal toxicity | CYP3A4/5 inhibition | Possible (4) |
| 52‐year‐old woman with a history of severe psoriasis 55 | Red clover (menopausal flushing) | Methotrexate | Not mentioned | Severe vomiting and epigastric pain | Probably OAT3 inhibition | Possible (4) |
| 23‐year‐old Japanese woman with multiple sclerosis 56 | Lutein and melilot supplements (indigestion and other GI tract problems) | Interferon β‐1b | Not mentioned | Jaundiced palms, elevated alanine transaminase, periventricular and juxtacortical hyperintense signal lesions | Unknown | Probable (5) |
| 41‐year‐old woman with disorganized schizophrenia 57 | SJW (depression) | Clozapine | Not mentioned | Increased disorganization and tension | CYP3A4 induction | Probable (6) |
| 56‐year‐old white Caucasian man with a history of HIV+ 58 | Ginseng‐based oral lozenges (sexual disability) | Raltegravir plus lopinavir/ritonavir | Aspirin, esomeprazole, trimethoprim/sulfamethoxazole | Generalized pruritus, scratching lesions, increased transaminase, visible jaundiced skin and mucous membranes | CYP3A4 inhibition | Probable (6) |
| 71‐year‐old Ecuadorean‐American woman with a history of complete left knee arthroplasty 33 | Himalayan goji juice (cleanse body) | Warfarin | Ezetimibe, lisinopril, famotidine, meclizine, alprazolam, and diphenhydramine | Ecchymosis, epistaxis, and one episode of haematochezia, elevated INR | CYP2C9 inhibition | Probable (7) |
| 41‐year‐old man diagnosed with HIV 59 | Ginkgo biloba (improve cognitive function) | Efavirenz | Zidovudine, lamivudine | Increased viral load at 1350 copies ml–1 | CYP3A4 induction | Probable (6) |
| 61‐year‐old man with a T3N1M0 (stage IIIA) squamous cell carcinoma of the lung 60 | Echinacea (common cold and flu) | Etoposide | Cisplatin, omeprazole, enalapril, hydrocodone/ paracetamol, prochlorperazine, ondansetron, vitamins B12, E, D, B17 and C | Seizure‐like activity, grade 4 thrombocytopenia | Unknown | Possible (2) |
| 85‐year‐old man with a history of hypertension, old anterior wall myocardial infarctio nand atrial fibrillation 61 | SJW (depression) | Warfarin | Not mentioned | Upper gastrointestinal bleeding, increased INR | Possibly additive clotting effect | Probable (6) |
| 46‐year‐old African American woman with a history of stage 1 sarcoidosis, uterine fibroids, anaemia, cardiomyopathy and depression 62 | Cranberry juice (constipation) | Warfarin | Not mentioned | Increased INR | Unknown | Highly probable (10) |
| 71‐year‐old man with aortic valve and mitral valve replacement 63 | Sheng Mai‐yin (improvement of peripheral circulation) | Warfarin | Not mentioned | Consciousness disturbance – right hemiplegia and active pupils, increased INR | CYP2C9 induction, downregulates plasminogen inhibitor 1 (PAI‐1), tissue factor pathway inhibitor, coagulation factorXIII, A1, and, coagulation factor II (thrombin) receptor (F2R). | Probable (8) |
| 71‐year‐old Caucasian man with a history of atrial flutter, hypertension, hyperlipidemia, diabetes mellitus, erectile dysfunction and hypothyroidism 64 | Bee pollen granules (general wellbeing) | Warfarin | Hydrochlorothiazide, lisinopril, levothyroxine, simvastatin, glyburide, metformin, vardenafil, aspirin, multivitamin and amlodipine | Elevated INR | CYP2C9 inhibition | Probable (5) |
| 58‐year‐old Mexican man with a history of type 2 diabetes mellitus, osteoarthritis, hyperlipidaemia, hypertension, and degenerative disc disease of the spine 65 | Prickly pear cactus (diabetes) | Glipizide |
Metformin, rosuvastatin, fenofibrate, aspirin, lisinopril, gabapentin, tramado1, nabumetone and nitroglycerin |
Hypoglycaemic | Unknown | Probable (8) |
| 26‐year‐old man with chronic myeloid leukaemia 34 | Panax ginseng (improve mental and physical performance) | Imatinib | Not mentioned | Right upper quadrant pain, elevated liver enzymes | CYP3A4 and P‐glycoprotein inhibition | Probable (5) |
| 79‐year‐old man with atrial fibrillation and metastatic bladder carcinoma 66 | Grifron‐Pro Maitake D –fraction (immunoinstimulant) | Warfarin | diltiazem, hydromorphone, tamsulosin, prednisolone ophthalmic suspension, simvastatin and eszopiclone | Elevated INR | Unknown | Possible (4) |
| 59‐year‐old black man with hyperlipidaemia 67 | SJW (insomnia) | Rosuvastatin | Not mentioned | Increased total and low‐density lipoprotein cholesterol | CYP2C9 and CYP2C19 induction via PXR activation | Possible (3) |
| 53‐year‐old Sri Lankan woman with unipolar depression 68 | Arthiritis QR, Cholesterol QR, Triphala churna, Yogaraja Guggulu, Mentat, Rumalaya, Decoction‐1, Decoction‐2 (backache) | Sertraline | Not mentioned | Moderate and severe depression | Unknown | Probable (6) |
| 40‐year‐old man with generalized anxiety disorder and dream disorders 69 | Valeriana officinalis L. and Passiflora incarnata L. (anxiety and insomnia) | Lorazepam | Not mentioned | Handshaking, dizziness, throbbing and muscular fatigue | Synergistic effect only | Possible (3) |
| 52‐year‐old woman with essential hypertension and a minor ischemic stroke 70 | Nattokinase (stroke) | Aspirin | Not mentioned | Vertigo and unsteady gait, high blood pressure, cerebral microbleed | Unknown | Doubtful (0) |
| 47‐year‐old man with HIV‐1 infection 71 | Efamol tablets, rheum frangula tablets and colayur syrup (laxative intestinal cleaners) | Lopinavir, ritonavir | Stavudine, lamivudine and tenofovir | Diarrhoea, toxic lopinavir plasma level | CYP3A4 and CYP2D6 inhibition | Probable (8) |
| 36‐year old woman with stage IV adenocarcinoma of lung 72 | Ginseng, Fomes fomentarius, Inonotus obliquus, Phellinus linteus (improve mental and physical performance) | Gefitinib | Not mentioned | Increased shortness of breath | CYP3A4/5 induction | Probable (5) |
| 61‐year‐old man with a history of primary hypercholesterolemia 73 | Green tea (fat and weight loss) | Simvastatin | Amlodipine | Elevated liver enzymes, increase simvastatin lactone levels | Unknown | Probable (7) |
| 80 year‐old Chinese woman with a history of diabetes mellitus, hypertension, cerebrovascular accident and atrial fibrillation 74 | Lycium barbarum L or goji berry (promote longevity) | Warfarin | Nifedipine, glibenclamide, metformin, lorazepam | Increased INR, | Probably CYP2C9 inhibition and/or additive anticoagulation | Highly probable (9) |
| 77‐year‐old Japanese man with a history of hypertension and hyperuricemia 75 | Arejin and Daiokanzo‐to (chronic allergic rhinitis and constipation) | Enalapril | Nifedipine, famotidine, brotizolam and terazosin | Mild anaemia, liver dysfunction, mildly elevated creatine kinase (CK) level, and severehypokalaemia and hypochloraemia. | Probably via inhibition of renal 11‐beta‐hydroxysteroid dehydrogenase | Probable (7) |
| 70‐year‐old woman with history of a mechanical mitral valve placement and an episode of atrial fibrillation 76 | Matricaria chamomilla (pedal oedema) | Warfarin | Amiodarone, digoxin, synthroid, lendronate, metoprolol and a calcium–vitamin D supplement | Elevated INR, dyspnoeic on exertion, bilateralpedal oedema and ecchymoses in her perineal area, across her lower abdomen and over her left hip | Probably synergistic anticoagulation | Possible (3) |
| 55‐year‐old Indian woman with a node‐positive 4‐cm grade 3 invasive ductal carcinoma 77 | Betel quid (CNS stimulant) | Doxorubicin, cyclophosphamide, paclitaxel | Docetaxel, 5‐fluorouracil and methotrexate | Grade IV mucositis, dysuria, mouth pain, and furunculosis. | Sensitization of normal tissues to the cytotoxic chemotherapy | Probable (5) |
| 57‐year‐old man with prosthetic mitral valve due to rheumatic heart disease 78 | Commiphora molmol (acute bronchitis) | Warfarin | Not mentioned | Decreased INR | Unknown | Possible (3) |
| 48‐year‐old woman with a cadaveric renal allograft 79 | Thüringen 9‐ Kräutertee (not indicated) | Cyclosporine | Mycophenolate mofetil, pravastatin, valsartan and hydrochlorothiazide | Decreased cyclosporine level, rhabdomyolysis | Unknown | Possible (4) |
| 37‐year‐old Armenian man with a cadaveric renal transplant 79 | Chamomile Tea (dyspepsia, nausea, vomiting) | Cyclosporine | Azathioprineand Mycophenolate mofetil | Decreased cyclosporine level | Unknown | Probable (7) |
| 33‐year‐old man with a cadaveric renal transplant 79 | Wild fruit tea drink (not indicated) | Cyclosporine | Mycophenolate mofetil | Increased cyclosporine level | Unknown | Possible (4) |
| 55‐year‐old man with a history of cerebrovascular accident following coronary artery bypass and seizure disorder 80 | Ginkgo supplement (improve cognitive function) | Valproic acid and phenytoin | Not mentioned | Seizure disorder leading to death while swimming | Indirect inhibition of glutamate decarboxylase and glycine activities and CYP2C19 induction | Probable (7) |
| 35‐year‐old woman with a left thigh haemangioma 81 | Aloe vera (leg pain) | Sevoflurane | Propofol, fentanyl, and rocuronium, Cefazolin, morphine | Perioperative bleeding | Probably additive inhibition of cyclooxygenase activity | Possible (3) |
| 57‐year‐old kidney transplant 82 | SJW (depression) | Cyclosporine | Prednisolone | Decrease cyclosporine concentration | CYP3A4 and P‐gp induction | Highly probable (9) |
| 61‐year‐old man with atrial fibrillation and chronic rheumatic heart disease 83 | Quilinggao (to quench internal heat) | Warfarin | Digoxin, simvastatin, furosemide and potassium chloride | gum bleeding and epistaxis, elevated INR | Inhibition of platelet function | Probable (5) |
| 28‐year‐old woman a recipient of a live‐donor allograft due to end‐stage renal disease attributed to hypertensive nephrosclerosis 84 | Rice fermented with red yeast, beta‐sitosterol, danshen root (Salvia mitorriza), and garlic bulb (Allium sativum)(to lower cholesterol) | Cyclosporine and/or diltiazem | azathioprine, prednisone, enalapril and famotidine | Increased serum creatine phosphokinase rhabdomyolysis | Unknown | Possible (3) |
| 61‐year‐old Chinese woman with a history of recurring atrial fibrillation, hypertension, hypercholesterolaemia and tricuspid regurgitation 85 | L. barbarum L. (blurred vision) | Warfarin | Benazepril, atenolol, digoxin and fluvastatin | Elevated INR | Probably CYP2C9 inhibition and/or additive anticoagulation | Probable (6) |
| 67‐year‐old Caucasian woman with a history of hypertension 86 | Boldo‐fenugreek (to help liver and stimulate digestion) | Warfarin | Metoprolol | Increased bleeding time | Inhibition of thromboxane A2 | Probable (5) |
CYP, Cytochrome P450; GI, gastrointestinal; HIV, human immunodeficiency virus; INR, international normalized ratio; IV, intravenous; PXR, pregnane X receptor; SJW, St John's wort; UGT, uridine‐5′‐diphospho‐glucuronosyltransferase