Table II.
Case Reports and Case Series Reporting Interactions Between St John’s Wort and Prescribed Drugs
| Prescribed drug (reference) | SJW extract, dosage/duration | Sex (M/F)/age (years) | Clinical result of interaction | Possible mechanism | Comment |
|---|---|---|---|---|---|
| Adrenergic vasopressors (ephedrine 50 mg and phenylephrine 1 mg, bolus) (107) | NR, 6 months | F/23 | Decreased responsiveness to vasopressors | Unknown (SJW might theoretically reduce the expression of adrenergic receptors) | The possibility that the anesthetic alone may have caused hypotension cannot be ruled out |
| Anesthetics (fentanyl, propofol, sevoflurane in O2, and N2O) (110) | Extract standardized to 0.3% hypericin, 500–1,000 mg tid for 3 months | F/21 | Delayed emergence | Unknown | The American Society of Anesthesiologists advises that the use of SJW should be discontinued 2 or 3 weeks before surgery |
| Bupropion (110) | NR, 300 mg once a day for several years | F/58 | Persistent orofacial dystonia | Additive effect on 5-HT reuptake | It is not recommended to use SJW in combination with 5-HT reuptake inhibitors or 5-HT ligands |
| Buspirone and fluoxetine (96) | NR | F/42 | Hypomanic episode, with prominent anxious features and underlying depression | Additive effect on 5-HT signaling | The cases were complicated by the concomitant use of fluoxetine (one case) or Ginkgo biloba (both cases) |
| Buspirone (95) | Hypericum 2000 plus®—3 capsules daily for 2 months | F/27 | Serotonin syndrome | Additive effect on 5-HT signaling | |
| Cyclosporine (47) | NR, 300 mg bid | F/61 | Lowering of blood cyclosporine levels; rejection episode | Induction of CYP3A4 and/or P-glycoprotein | Physicians should be aware of this interaction (which causes acute rejection episode) when treating patients with cyclosporine |
| Cyclosporine (47) | NR, 300 mg tid | F/54 | Lowering of blood cyclosporine levels | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (48) | NR | 30 patients, NR | Lowering of blood cyclosporine levels (47%) | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (49) | NR | 10 patients, NR | Lowering of blood cyclosporine levels (49%); rejection episode in 1 patient | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (50) | Extract, 300 to 900 mg daily | 5 patients, NR | Lowering of blood cyclosporine levels | Induction of CYP3A4 and/or P-glycoprotein | |
| Tea: NR | |||||
| Cyclosporine (51) | NR | F/mid-20s | Lowering of blood cyclosporine levels (75%) | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (52) | LI 160, 300 mg tid for 3 weeks | NR/61 | Lowering of plasma cyclosporine levels to 95 g/L; rejection episodes | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (52) | LI 160, 300 mg tid for 3 weeks | NR/63 | Lowering of blood cyclosporine levels to 87 g/L; rejection episode | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (53) | Extract standardized to 0.3% hypericin, 300–600 mg/daily for 2 months | F/29 | Lowering of blood cyclosporine (from 250–300 to 155 ng/mL): moderate to severe refection episode | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (54) | Jarsin® 300 mg/daily for 4 weeks | F/55 | Lowering of blood cyclosporine, (from 131 to 74 ng/mL) | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (55) | NR, 2× 900 mg/day for 2 weeks | M/63 | Lowering of blood cyclosporine levels; rejection episode | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (56) | NR, for 3 days | F/38 | Lowering of blood cyclosporine (from 147 to 39.7 ng/mL) | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (57) | Extract standardized to 0.3% hypericin | F/44 and M/29 | Lowering of blood cyclosporine; acute rejection episode in M/29 | Induction of CYP3A4 and/or P-glycoprotein | |
| F/44, 600–900 mg/daily for 6 months | |||||
| M/29, 300–600 mg/daily for 30 days | |||||
| Cyclosporine (58) | NR, for 2–5 weeks | 3 patients, NR | Lowering of blood cyclosporine (<100 ng/mL) | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (59) | Neuroplant®, 300 mg tid for 5 years | F/55 | Lowering of blood cyclosporine (81 ng/mL) | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (60) | NR, 300 mg bid for 26 days | M/58 | Lowering of blood cyclosporine levels (from 200 to 67 µg/L) | Induction of CYP3A4 and/or P-glycoprotein | |
| Cyclosporine (61) | Herbal tea mixture containing SJW, NR | M/57 | Lowering of blood cyclosporine levels (from from 100–130 to 70 µg/L) | Induction of CYP3A4 and/or P-glycoprotein | |
| Eletriptan (119) | NR, for 1 month | F/28 | Serotonin syndrome | Additive effect on 5-HT signaling | The patient also took fluoxetine, which probably predisposed the patient to develop the syndrome precipitated by subsequent use of eletriptan |
| Loperamide (122) | NR | F/39 | Brief episode of acute delirium (disoriented, agitated, confused state) | Unknown | If confirmed, such interaction is potentially dangerous |
| Nefazodone (97) | NR, 300 mg tid for 3 days | F/84 | Nausea, vomiting, headache | Additive effect on 5-HT reuptake | The syndrome could be fatal particularly in the elderly |
| Nevirapine (87) | NR, for several months | 5 M/range from 34 to 53 | Decreased plasma concentration of nevirapine | Induction of CYP (CYP3A4) | SJW may render ineffective nevirapine treatment |
| Oral contraceptive (67) | NR | F/NR | Changed menstrual bleeding | Induction of CYP3A4 | Physicians should be aware of this interaction. Changes in the pharmacokinetic of oral contraceptive pills can result in reduced efficacy and increased breakthrough bleeding |
| Oral contraceptive (67) | NR | 8 F/range from 23 to 31 | Intermenstrual bleeding | Induction of CYP3A4 | |
| OC: ethinylestradiol desogestrel (47) | NR | F/NR | Intermenstrual (breakthrough) bleeding | Induction of CYP3A4 | |
| OC: ethinylestradiol desogestrel (47) | NR | F/NR | Intermenstrual (breakthrough) bleeding | Induction of CYP3A4 | |
| OC: ethinylestradiol desogestrel (47) | NR | F/44 | Intermenstrual (breakthrough) bleeding | Induction of CYP3A4 | |
| OC, Valette® (70) | NR, 1,700 mg daily for 3 months | F/36 | Unwanted pregnancy | Induction of CYP3A4 | |
| Paroxetine (98) | NR, 600 mg/day for 10 days | F/50 | Nausea, weakness, fatigue, groggy, and lethargic state | Additive effect on 5-HT reuptake | The syndrome could be fatal particularly in the elderly |
| Phenprocoumon (47) | NR | F/75 | Increased “Quick-Wert test” (indicating decreased anticoagulant effect) | Induction of CYP3A4 and possibly other CYP isoforms | The decreased plasma levels of phenprocoumon could be clinically relevant |
| Prednisone (65) | NR | F/36 | Maniac episode | Unknown | A clinical trial did not confirm this interaction (66) |
| Sertraline (97) | NR | F/78 | Dizziness, nausea, vomiting, headache | Additive effect on 5-HT reuptake | The syndrome could be fatal particularly in the elderly |
| Sertraline (97) | NR | M/64 | Nausea, epigastric pain, anxiety | Additive effect on 5-HT reuptake | |
| Sertraline (97) | NR, 300 mg bid for 2 days | M/82 | Nausea, vomiting, anxiety, confusion | Additive effect on 5-HT reuptake | |
| Sertraline (97) | NR, 300 mg tid for 2 days | M/79 | Nausea, anxiety, feelings of restlessness, and irritability | Additive effect on 5-HT reuptake | |
| Sertraline (100) | Dosage unclear: for 5 weeks | M/28 | Manic episode | Additive effect on 5-HT reuptake | |
| Tacrolimus (62) | Neuroplant®—600 mg/daily for 1 month | M/65 | Decreased tacrolimus levels | Induction of CYP3A4 | Physicians should be aware of this interaction (which causes acute rejection episode) |
| Theophylline (114) | Extract standardized to 0.3% hypericin, 300 mg/daily for 2 months | F/42 | Decreased theophylline levels | Induction of CYP2E1 and CY3A4 | A clinical trial did not confirm this interaction (115) |
| Tibolone (73) | NR: infusion 2 g/daily for 10 weeks | F/57 | Acute hepatitis | Unknown | In absence of evidence of a potential role for concomitant medication, an interaction between SJW and tibolone was suspected as likely case of liver damage |
| Tryptophan (112) | NR | M/19 | Serotonin syndrome (agitation, anxiety, tremors) | Additive effects (tryptophan may increase central serotonin levels) | The case was complicated by the use of an unknown antitussive drug |
| Venlafaxine (99) | Tincture, 200 gtt tid; usual dose 160 daily | M/32 | Serotonin syndrome | Additive effect on 5-HT reuptake | The syndrome could be fatal particularly in the elderly |
| Warfarin (67) | NR | F/79 | Decreased INR (from 2.5–3.8 to 1.7) | Induction of CYP3A4 and possibly other CYP isoforms | The decreased plasma levels of warfarin could be clinically relevant |
| Warfarin (67) | NR | M/65 | Decreased INR (from 2.4–3.6 to 2.0–2.1) | Induction of CYP3A4 and possibly other CYP isoforms | |
| Warfarin (67) | NR | M/76 | Decreased INR (from 2.6 to 1.1) | Induction of CYP3A4 and possibly other CYP isoforms | |
| Warfarin (67) | NR | F/61 | Decreased INR (INR before treatment not available; INR after 1.2) | Induction of CYP3A4 and possibly other CYP isoforms | |
| Warfarin (67) | NR | F/84y | Decreased INR (from 2.9–3.6 to 1.5) | Induction of CYP3A4 and possibly other CYP isoforms | |
| Warfarin (67) | NR | F/56 | Decreased INR (from 2.6 to 1.5) | Induction of CYP3A4 and possibly other CYP isoforms | |
| Warfarin (67) | NR | F/85 | Decreased INR (from 2.1–4.1 to 1.5) | Induction of CYP3A4 and possibly other CYP isoforms |
NR not reported, bid twice daily, CYP cytochrome, INR international normalized ratio, tid three times daily, OC oral contraceptive, SJW St John’s wort, 5-HT 5-hydroxytryptamine