chapter
Herbal drugs
Pages 18

Induces the metabolizing enzyme CYP3A4: gingko weakly induces CYP2D6, which metabolizes alprazolam

Avoid concomitant use if possible. If the sedative action is impaired, discontinue the herb

3. Milk thistle

2. Lamivudine 3. Amprenavir 4. Saquinavir 5. Nelfinavir 6. Lopinavir 7. Efavirenz 8. Nevirapine

Blood levels of saquinavir may be ↓ by garlic and ginger. Milk thistle ↓ blood levels of indinavir. Garlic ≠ gastrointestinal side-effects of ritonavir

• Induces metabolizing enzymes (CYP3A4). Garlic and ginger ↓ blood levels of saquinavir • Unknown mechanism (milk thistle) • Induction of transport protein P-gp (St John’s wort)

Avoid concomitant use

Herbs that may ≠ blood levels of anti-HIV drugs 1. Piper longum 2. Hypoxis hemerocallidea

1. Nevirapine ≠ blood levels, with potential risk of side-effects

• Inhibits metabolizing CYP450 isoenzyme (nevirapine) • Inhibits both CYP3A4 and P-gp (Hypoxis hemerocallidea)

If either drug is introduced, monitor closely for side-effects

Herbs that may ≠ effects of drugs used in blood sugar control 1. Angelica dahurica 2. Aloe 3. Asian ginseng 4. Bai zhi 5. Garlic 6. Gingko biloba 7. Guarana 8. Karela (bitter melon) 9. Ma huang (Ephedra sinica) 10. Neem 11. Rosemary 12. Sage 13. Milk thistle

1. Tolbutamide 2. Metformin 3. Glimepiride 4. Glipizide 5. Glipizide 6. Glyburide 7. Insulin 8. Pioglitazone 9. Nateglinide 10. Repaglinide

May run the risk of low blood sugar

• ↓ absorption of sugar (aloe) • Unknown (Asian ginseng, garlic, karela, neem) • Inhibits CYP2E1 isoenzyme (bai zhi). Gingko biloba induces metabolism of tolbutamide) • May ≠ serum insulin level (rosemary ≠ insulin in rats)

Monitor blood glucose regularly when either drug is introduced. Once the blood sugar has been stabilized, avoid sudden changes of doses of either form of drug. Use alternative antidiabetic drugs metabolized less through CYP2E1 (pioglitazone, rosiglitazone, netoglitazone, repaglinide) when indicated. Avoid using longer-acting oral hypoglycaemic drugs such as glibenclamide, especially in elderly people. Report symptoms such as light-headedness, lethargy and sweating to the physician

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• ↓ absorption of metformin and

glibenclamide Avoid concomitant use. Monitor blood sugar closely if either drug is introduced

Herbs that may ≠ blood levels of antiepileptic medications or ≠ potency of antiepileptic medications 1. Piper longum 2. Piper nigrum 3. Willow 4. Valerian 5. Passion flower 6. Kava 7. Shankapushpi

1. Phenytoin 2. Carbamazepine 3. Valproate 4. Lamotrigine 5. Gabapentin

≠ phenytoin levels, which may lead to ≠ side-effects. Valerian, passion flower and kava kava may theoretically potentiate antiepileptic drugs as animal experiments have revealed antiseizure activity. Valerian constituents inhibit breakdown of GABA and enhance BZD binding, which could potentiate the effects of carbamazepine

• Inhibition of transport (P-gp) and metabolizing enzymes (CYP2C9 and CYP3A4). Piperine found in Piper nigrum (black pepper) and Piper longum ≠ bioavailability of phenytoin • Displaces from protein binding (salicylate contained in willow displaces phenytoin from binding sites) • Passion flower contains chrysin, which is a partial agonist at GABA receptors and shows antiseizure effects

Closely monitor for side effects of phenytoin if Piper nigrum is introduced. Avoid sudden withdrawal of the herb after stabilization to avoid breakthrough seizures

Herbs that may Ø plasma levels of antiepileptic drugs or Ø seizure threshold 1. Borage oil 2. Ginkgo biloba 3. Evening primrose oil 4. Plantain 5. Sage 6. Shankapushpi 7. Guarana, cola (contain caffeine) 8. Volatile oils, e.g. rosemary, sage, hyssop, fennel

1. Valproate 2. Carbamazepine

↓ valproate and carbamazepine levels and may precipitate seizures. Evening primrose oil and borage oil contain gamolenic acid, which is reported to ↓ seizure threshold. Report of tonic-clonic seizures in subjects without a prior history of epilepsy after using essential oils transdermally and orally

• Unknown mechanism (ginkgo biloba ↓ valproate levels) • ↓ seizure threshold (evening primrose oil, shankhapushpi) • Plantain ↓ absorption of valproate • Caffeine is known to ↓ seizure threshold and exacerbate seizures in animals. Volatile oils contain epileptogenic compounds (e.g. cineole, camphor, fenchone), which can be absorbed through the skin during aromatherapy. Sage is known to cause seizures in large doses

Avoid concomitant use if possible. Avoid eating plantains 30 minutes before and after carbamazepine. Avoid concomitant use of St John’s wort, especially in patients with poor seizure control. Avoid driving and work with machinery if either drug is introduced

3. Ashwagandha 4. Asian ginseng 5. Broom 6. Cascara 7. Dan shen (Salvia mitiorrhiza) 8. Devil’s claw 9. Echinacea 10. Ginger 11. Ginkgo biloba 12. Ginseng 13. Ginseng (Siberian) 14. Hawthorn 15. Kyushin 16. Liquorice 17. Plantain 18. Oleander 19. Rhubarb 20. Squill 21. Uzara root

3. Ouabain 4. Deslanoside

cardiac glycosides. May give rise to falsely ≠ or ↓ digoxin levels

• Contains cardiac glycosides or cardioactive substances (adonis, broom, devil’s claw, ginger, hawthorn, oleander, squill) • Lowers serum potassium (aloe, cascara, liquorice, rhubarb) • Interferes with digoxin assay using fluorescence polarization immunoassay (ashwagandha, ginseng and Siberian ginseng falsely elevate, Asian ginseng and dan shen ≠ or ↓ levels) • Inhibits P-gp (echinacea, ginkgo biloba) • ≠ levels due to unknown mechanism (ginseng)

Avoid the concomitant use of herbs that contain cardiac glycosides with these drugs. Monitor serum potassium, and administer potassium supplements orally if indicated. Take drugs 1 hour before or 2 hours after herbal products. Avoid taking ashwagandha and Asian ginseng at least a week before digoxin assay

Herbs that may Ø cardiac glycoside levels 1. Guar gum 2. Senna 1. Digoxin 2. Digitoxin

3. Ouabain 4. Deslanoside

May lower therapeutic effect • May lower the absorption of these drugs (guar gum, senna) • Induces P-gp (St John’s wort)

Avoid concomitant use. Monitor for worsening of therapeutic effects if the herb is introduced. If used concomitantly, take herbs at least 1 hour before and after these drugs

Herbs that may ≠ antibiotic blood levels 1. Piper nigrum and Piper longum

1. Amoxicillin 2. Cefotaxime 3. Rifampicin 4. Erythromycin 5. Telithromycin

≠ blood levels of these antibiotics • Attributed to inhibition of metabolism and of P-gp, e.g. Piper longum

Be aware that toxic effects of antibiotics may occur, particularly when the prescriber/dispenser is unaware of the intake of herbal medicines

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5. Yohimbine

3. Penicillin 4. Tetracycline

• Unknown mechanism (dandelion ↓ ciprofloxacin levels in rats; khat ↓ absorption and thus blood levels of ampicillin and amoxicillin, possibly due to the formation of a tannin-antibiotic complex; guar gum ↓ absorption of penicillin) • Other mechanism (yohimbine chelates tetracyclines). Fennel extracts are considered to chelate with ciprofloxacin

Be aware. Discontinue the herb during the course of antibiotic therapy. Penicillins should be taken on an empty stomach

Herbs that may Ø immunosuppressant effects 1. Astralagus 2. Echinacea 3. Liquorice 4. Milk thistle 5. Neem 6. Sea buckthorn

1. Ciclosporin 2. Azathioprine 3. Methotrexate 4. Tacrolimus 5. Daclizumab 6. Cyclophosphamide

Possibility of graft rejection • ↓ blood level; unknown mechanism (astralagus). • Other mechanisms:alkyl amides from echinacea modulate tumour necrosis factor alpha mRNA expression in human monocytes/macrophages via the cannabinoid type 2 receptor • Unknown mechanism (milk thistle is known to ↓ cyclosporine levels; neem ↓ effects of azathioprine, prednisolone and daclizumab; sea buckthorn may ↓ effect of cyclophosphamide) • Induces metabolizing enzymes, CYP3A4 and P-gp (St John’s wort ↓ ciclosporin and tacrolimus levels)

Avoid concomitant use of the herb

2. Geum chiloense 3. Liquorice

2. Azathioprine 3. Ciclosporin 4. Prednisolone

≠ plasma ciclosporin levels 6-8-fold

• Unknown mechanism (black cohosh) • Inhibits metabolizing enzymes. Glycyrrhizin present in liquorice inhibits the metabolizing enzyme of prednisolone, 11 beta-hydroxysteroid dehydrogenase, which converts the active metabolite to an inactive form. ↓ clearance of prednisolone in healthy individuals

Be aware. Advice is to avoid echinacea with immunosuppressants

Herbs that may Ø effects of anticancer medication 1. Aloe 2. Soy/soya 3. Red clover 4. Kava kava 5. Ginseng 6. Garlic 7. Echinacea 8. Beta-carotene 9. Quercetin

1. Cisplatin 2. Tamoxifen

Lower the anticancer activity of these drugs. Most oncolytic drugs have a narrow therapeutic window

• Red clover and soya contain oestrogenic isoflavonoids. Unknown mechanism with aloe • Induces the metabolizing enzyme (soy induces CYP isoenzymes that metabolize tamoxifen)

It is best to avoid the concomitant use of herbs with hormonal effects (includes dong quai, chasteberry, black cohosh) in patients with hormone-dependent cancers, e.g. breast cancer

Herbs that may ≠ effects of anticancer medication 1. Black cohosh 2. Caffeine 3. Evening primrose oil 4. Scutellaria baicalensis 5. Starflower (borage)

1. Docetaxel 2. Paclitaxel 3. Doxorubicin 4. Tamoxifen 5. Cisplatin 6. Vinorelbine

≠ cytotoxic properties • Unknown mechanism (black cohosh). Caffeine ≠ cytotoxic effects of cisplatin; wogonin present in Scutellaria enhances etoposide-induced apoptosis. Gamolenic acid found in evening primrose oil and borage potentiated the in vitro toxicity of paclitaxel and vinorelbine, attributed to an unsaturated fatty acid as modulators of tumour cell chemosensitivity

Be aware and avoid concomitant use

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4. Ephedra 5. Ginseng 6. Parsley 7. Shepherds purse 8. Verbena (vervain) 9. Capsicum

3. Moclobemide

effects such as psychosis and hallucinations with Asian ginseng. Headache, tremulousness and manic episodes have been reported with ginseng and phenelzine

• Unknown mechanism (anise, Asian ginseng) • Inhibits metabolism of ephedra (MAOIs inhibit the metabolism of ephedra)

Avoid concomitant use

Herbs that may Ø effects of diuretics 1. Aloe 2. Dandelion 3. Elder 4. Liquorice 5. Nettle 6. Rhubarb

1. Bendroflumethiazide 2. Bumetanide 3. Chlortalidone 4. Hydrochlorothiazide 5. Indapamide 6. Furosemide 7. Torasemide

Low body potassium, which may give rise to lethargy and muscle weakness

• ≠ potassium loss from the gut (aloe, liquorice) • Possess diuretic properties (dandelion, elder, nettle, rhubarb)

Avoid concomitant use. Provide potassium supplements orally. Use a potassium-sparing diuretic such as spironolactone or amiloride

Herbs that may ≠ effects of diuretics 1. Couchgrass 2. Ginkgo biloba 3. Ginseng 4. Guar gum 5. Comfrey

1. Bendroflumethiazide 2. Bumetanide 3. Chlortalidone 4. Hydrochlorothiazide 5. Torasemide

Poor blood pressure control and diuresis

• Unknown (ginkgo biloba ↓ effect of thiazide diuretics; ginseng) • ↓ absorption ( guar gum has been shown to ↓ absorption of bumetanide)

Avoid concomitant use of the herb if blood pressure control is poor

2. Piper longum/Piper nigrum 3. Black cohosh 4. Capsicum 5. Cowslip 6. Ginkgo biloba 7. Gingseng 8. Hawthorn 9. Indian snakeroot 10. Liquorice (Glycyrrhiza glabra) 11. Parsley

(atenolol, acebutolol, bisoprolol, carvedilol, esmolol, labetolol, metoprolol, nadolol, nebivolol, pindolol, sotalol, timolol) 2. Calcium channel blockers (amlodipine, diltiazem, felodipine, isradipine, lacidipine, nicardipine, nifedipine, nimodipine, nisoldipine, verapamil) 3. ACE inhibitors and angiotensin II receptor blockers (captopril, lisinopril, enalapril, verapamil, losartan , candesartan)

bradycardia and hypotension. May worsen cough associated with ACE inhibitors

• Betel nut causes bradycardia and hawthorn ↓ blood pressure through unknown mechanisms. Piperine, a constituent of black pepper and other species (e.g. Piper nigrum), ≠ bioavailability of propranolol. Indian snakeroot was found to contain a ‘reserpine’-like constituent • Inhibits the metabolizing enzymes. Piper longum inhibits CYP1A1 and CYPA2, which metabolize propranolol. Ginkgo inhibits metabolism of nifedipine, nicardipine (CYP3A4) and propranolol (CYP1A2) enzymes. Gingseng inhibits CYP3A4 and ≠ nifedipine levels. Goldenseal inhibits losartan’s metabolizing enzyme. Grapefruit inhibits the metabolizing enzyme (CYP3A4) of felodipine, nicardipine, nifedipine, nisoldipine or nitrendipine. Grapefruit juice may also inhibit the metabolism of verapamil and losartan • Unknown (black cohosh) • Other mechanisms (capsicum depletes substance P; cowslip has demonstrated hypotensive properties in animals)

Inform physicians if either drug is introduced. Avoid sudden changes of the herb dose. Monitor PR and blood pressure closely if either drug is introduced. Discontinue the herb if side-effects worsen. Use alternative antihypertensive medications if possible (e.g. replace beta-blockers and calcium channel blockers with ACE inhibitors or angiotensin II receptor blockers if bradycardia is worsened, and replace ACE inhibitors with angiotensin II receptor blockers if cough is worsened)

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(liquorice) 4. Ma huang 5. Sage 6. Yohimbe

• Causes peripheral vasoconstriction (broom) • Contains vasoconstrictive alkaloids (ephedrine). Ma huang (a constituent of slimming pills, decongestants and antiasthma drugs) contains ephedrine • Pseudoaldosteronism (glycyrrhizin causes pseudaldosteronism and antagonises the effect of ACE inhibitors) • Yohimbe bark contains yohimbine, which is a presynaptic alpha-2 adrenoceptor agonist (and possibly an MAOI)

Avoid concomitant use

Herbs that may ≠ effect of anti arrhythmic medication 1. Adonis 2. Guarana 3. Liquorice 4. Milk thistle 5. Scopolia 6. Squill

1. Quinidine 2. Amiodarone 3. Adenosine 4. Procainamide

May cause ≠ adverse effects of quinidine and amiodarone. ≠ risk of prolonged Q-T interval on ECG

• Additive inotropic effects of the constituent cardiac glycosides of the herb (adonis and squill) • Inhibits metabolizing enzymes (grapefruit juice inhibits CYP3A4, which metabolizes amiodarone and quinidine; milk thistle inhibits the metabolizing enzyme of amiodarone (CYP3A4) • Unknown (liquorice, scopolia)

Avoid concomitant use. Monitor for side-effects of amiodarone if the herb is introduced. Inform physicians if used concomitantly. Monitor Q-T interval

Herbs that may Ø effect of antiarrhythmic medication

1. Guar gum 1. Adenosine ↓ blood levels and therapeutic effects

• Unknown Be aware

biloba 3. Scopolia 4. Yohimbine

amitriptyline, nortriptyline, clomipramine) 2. SSRIs (e.g. fluvoxamine fluoxetine, paroxetine) 3. Venlafaxine 4. Trazodone

and side-effects such as dryness of the mouth, retention of urine and tachycardia. ≠ sedation

• Broom contains cardioactive alkalamines such as sparteine • Inhibits metabolizing enzymes • Anticholinergic properties (hyoscine present in scopolia may worsen sideeffects of TCAs-additive antimuscarinic effects) • Yohimbine alone can cause hypertension, but lower doses cause hypertension when combined with TCAs • Unknown mechanism (ginkgo ≠ sedative effects of trazodone) • St John’s wort inhibits the uptake of serotonin and thereby ≠ serotonin levels

Avoid concomitant use. An SSRI may be a better alternative to be used with broom

Herbs that may ≠ effects of antipsychotic medication 1. Betel nut 2. Caffeine 3. Ephedra 4. Ginkgo biloba 5. Hops 6. Kava kava 7. Valerian

1. Phenothiazines (e.g. chlorpromazine, promazine, levomepromazine, pericyazine, pipotiazine, fluphenazine, perphenazine, trifluphenazine) 2. Clozapine 3. Lithium 4. Haloperidol 5. Risperidone

Worsening of side-effects such as slowness, stiffness and tremor. ≠ blood levels. A single case report of priapism induced by a ginkgo-risperidone combination. Hyperthermia

• Unknown mechanism (betel nut worsens the side-effects of flupentixol and fluphenazine). Ginkgo may ≠ haloperidol effects. Kava kava ≠ side-effects of haloperidol and risperidone • Inhibits metabolizing enzymes (caffeine inhibits CYP1A2, which metabolizes clozapine). Inhibition of CYP by ginkgo ≠ alpha-1 effects of risperidone. Valerian may worsen the sedative properties of haloperidol. Hops and phenothiazine have been associated with hyperthermia in dogs • Worsens the cardiovascular effects of phenothiazines (ephedra)

Be aware. Discontinue the herb if the side-effects of these drugs ≠

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4. Plantain (Plantain orata, Plantain psyllium) 5. Ispaghula (psyllium)

(e.g. chlorpromazine, promazine, levomepromazine, pericyazine, pipotiazine, fluphenazine, perphenazine, trifluphenazine) 3. Clozapine

and psyllium. ↓ effects of phenothiazines. Herbal diuretics contained in a mixture of juniper, buchu, horsetail, corn silk, bearberry, parsley, bromelain and paprika caused lithium toxicity

• Unknown mechanism (caffeine) • Contains dopamine agonists (chaste tree) • Induction of metabolizing enzymes (green tea may induce CYP1A2, which metabolizes clozapine) • ↓ absorption from the gut (plantain, psyllium and ispaghula may ↓ absorption of lithium, or preparations may have high a sodium content in the form of sodium bicarbonate to aid their dispersal in water before ingestion). Herbal diuretics are weak compared with their allopathic counterparts. This may be due to diuresis or other factors, e.g. enzyme inhibition

Be aware. Caffeine withdrawal may precipitate lithium toxicity, so avoid sudden caffeine withdrawal. Avoid concomitant use if possible

Herbs that may interact with melatonin

1. Ashwagandha 2. Celery 3. Chamomile 4. German chamomile 5. Goldenseal 6. Hops 7. Kava kava 8. Valerian

1. Melatonin May cause ≠ sedation Unknown mechanism Be aware

2. Caffeine 3. Capsicum 4. Dan shen 5. Ephedra 6. Green tea 7. Guarana 8. Squill

may potentiate side-effects. Ephedra, caffeine, squill and green tea may worsen tachycardia and palpitation

• Inhibition of CYP 450 enzymes (Piper longum, dan shen) • Additive sympathetic stimulation (caffeine, ephedra, green tea, guarana) • May ≠ absorption (capsicum) • Unknown mechanism (squill)

Inform physicians if either drug is introduced. Avoid sudden changes of the herb dose. Discontinue the herb if side-effects worsen

Herbs that may interfere with general anaesthetic medication

1. Black cohosh 2. Kava kava 3. Ginkgo 4. Ginseng 5. Garlic 6. Goldenseal 7. Ma huang 8. Echinacea 9. Aloe 10. Ephedra 11. Sage 12. Sassafras 13. Valerian 14. Wild carrot

Anaesthetic medication, including drugs used in premedication, induction, maintenance of anaesthesia, muscle relaxation, analgesia (intra-and postoperative), bleeding and recovery

These effects are attributed to herbs that may have sedating properties (e.g. valerian, kava kava) or cause ≠ bleeding (e.g. garlic, ginger, gingko), or those that may cause changes in blood pressure (often unpredictable), e.g. black cohosh, ma huang, ephedra. Also mentioned are herbs that may interfere with healing (e.g. echinacea). Aloe vera ↓ prostaglandin synthesis and inhibits aggregations of platelets, while sevoflurane inhibits thromboxane A2 formation, resulting in ≠ blood loss

Herbal preparations are known to: • ≠ intra-and postoperative bleeding • ≠ CNS effects of drugs used in anaesthesia • cause unpredictable changes in blood pressure and PR • cause unpredictable effects on the excretions of drugs used during anaesthesia

The American Society of Anaesthesiologists has recommended that all herbal medications be stopped 2-3 weeks prior to an elective surgical procedure. Employ stringent measures related to discontinuing ginkgo, ginseng and garlic because of ≠ risk of bleeding. Discontinue black cohosh 2 weeks before surgery. Inform the anaesthetist before the procedure

Herbs that may interact with phosphodiesterase inhibitors use for impotence

1. Squill 1. Sildenafil 2. Tadalafil 3. Vardenafil

≠ blood levels of the drug, leading to serious vasodilatation. ≠ risk of cardiac arrhythmia

• Inhibits CYP3A4, which metabolizes these drugs (grapefruit juice) • Unknown mechanism (squill)

Avoid concomitant use. Avoid the combination of grapefruit juice and nitrates with these medications

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3. Lovastatin

(goldenseal), with ≠ risk of sideeffects (e.g. muscle pain due to rhabdomyolysis)

• Possibly through inhibition of P-gp. Also through the inhibition of CYP3A4. Goldenseal inhibits CYP3A4

Avoid concomitant use. Report muscle pain to physicians. Suitable alternatives are pravastatin, rosuvastatin and fluvastatin, which interact less with P-gp. Pravastatin and rosuvastatin are mainly excreted unchanged, and fluvastatin (CYP2C9) is not metabolized through CYP3A4

Herbs that may interfere with ACh receptor antagonists

1. Areca nut 1 Procyclidine (used to control extrapyramidal – parkinsonian – with antipsychotic medications)

Caused severe rigidity and jaw tremor. This is an established and clinically significant interaction

• Procyclidine is an antimuscarinic agent, i.e. antagonizes the effects of ACh in one set of ACh receptors. Thus, herbal products used culturally with effects similar to ACh, e.g. areca nut, will produce enhanced effects at other – nicotinic – receptors to produce adverse effects

Avoid chewing betel nut (also found in prepared ‘pan masala’)

Herbs that may Ø effects of antidepressant medications 1. St John’s wort 1. TCAs (e.g. amitrypty-

line, nortryptiline, clomipramine) 2. SSRIs (e.g. fluvoxamine, fluoxetine) 3. Venlafaxine

Low blood amitriptyline levels (20%). May potentially ↓ therapeutic effects. Nortriptyline levels may be ↓ by 50%. St John’s wort ≠ sedative effects (weakness, lethargy, fatigue, slow movements, incoherence) of SSRIs

• Due to induction of metabolizing CYP3A4 enzyme and P-gp transport proteins • St John’s wort inhibits uptake of serotonin and thereby ≠ serotonin levels

Avoid concomitant use

2. Caffeine 3. Ephedra 4. Ginkgo biloba 5. Hops 6. Kava kava 7. Valerian

(e.g. chlorpromazine, promazine, levomepromazine, pericyazine, pipotiazine, fluphenazine, perphenazine, trifluphenazine) 2. Clozapine 3. Lithium 4. Haloperidol 5. Risperidone

slowness, stiffness and tremor. ≠ blood levels. A single case report of priapism induced by a ginkgo-risperidone combination. Hyperthermia

• Unknown mechanism (betel nut worsens the side-effects of flupentixol and fluphenazine). Ginkgo may ≠ haloperidol effects. Kava kava ≠ side-effects of haloperidol and risperidone • Inhibits metabolizing enzymes (caffeine inhibits CYP1A2, which metabolizes clozapine). Inhibition of CYP by ginkgo ≠ alpha-1 effects of risperidone. Valerian may worsen the sedative properties of haloperidol. Hops and phenothiazine have been associated with hyperthermia in dogs • Worsens the cardiovascular effects of phenothiazines (ephedra)

Be aware. Discontinue the herb if the side-effects of these drugs ≠

Herbs that may Ø effects of antipsychotic medication 1. Caffeine 2. Chaste tree 3. Green tea 4. Plantain

1. Lithium 2. Phenothiazines (e.g. chlorpromazine, promazine, levomepromazine, pericyazine, pipotiazine, fluphenazine, perphenazine, trifluphenazine) 3. Clozapine

↓ blood lithium levels with ↓ clinical effects. ↓ effects of phenothiazines

• Unknown mechanism (caffeine) • Contains dopamine agonists (chaste tree) • Induction of metabolizing enzymes (green tea may induce CYP1A2, which metabolizes clozapine) • ↓ absorption from the gut (plantain may ↓ absorption of lithium)

Be aware. Caffeine withdrawal may precipitate lithium toxicity, so avoid sudden caffeine withdrawal. Avoid concomitant use if possible

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4. German chamomile 5. Goldenseal 6. Hops 7. Kava kava 8. Valerian

sedation • Unknown mechanism Be aware

Herbs that may ≠ risk of theophylline side-effects 1. Piper longum 2. Caffeine 3. Capsicum 4. Dan shen 5. Ephedra 6. Green tea 7. Guarana 8. Squill

1. Theophylline ≠ plasma level of theophylline and may potentiate side-effects Ephedra, caffeine, squill and green tea may worsen tachycardia and palpitation

• Inhibition of CYP450 enzymes (Piper longum, dan shen) • Additive sympathetic stimulation (caffeine, ephedra, green tea, guarana) • May ≠ absorption (capsicum) • Unknown mechanism (squill)

Inform physicians if either drug is introduced. Avoid sudden changes of the herb dose. Discontinue the herb if side-effects worsen

Herbs that may Ø effect of theophylline 1. St John’s wort 2. Royal jelly

1. Theophylline ↓ theophylline levels and risk of therapeutic failure

• Due to activation of metabolizing CYP1A2 enzymes, which metabolize theophylline

Discontinue St John’s wort if the therapeutic effects of theophylline ↓

Herbs that may interact with phosphodiesterase inhibitors used for impotence

1. Grapefruit juice 2. Squill

1. Sildenafil 2. Tadalafil 3. Vardenafil

≠ blood levels of the medication, leading to serious vasodilatation. ≠ risk of cardiac arrhythmia

• Inhibits CYP3A4, which metabolizes these drugs (grapefruit juice) • Unknown mechanism (squill)

Avoid concomitant use. Avoid the combination of grapefruit juice and nitrates with these medications

2. Goldenseal

2. Simvastatin 3. Lovastatin

(grapefruit juice) and lovastatin (goldenseal) with ≠ risk of sideeffects (e.g. muscle pain due to rhabdomyolysis)

• Possibly through inhibition of P-gp. Also through inhibition of CYP3A4 (grapefruit juice). Goldenseal inhibits CYP3A4

Avoid concomitant use. Report muscle pain to physicians. Suitable alternatives are pravastatin, rosuvastatin and fluvastatin, which interact less with P-gp. Pravastatin and rosuvastatin are mainly excreted unchanged, while fluvastatin (CYP2C9) is not metabolized through CYP3A4

Herbs that may Ø effects of lipid-lowering agents 1. St John’s wort 1. Atorvastatin

2. Simvastatin 3. Lovastatin

↓ blood levels and lipid-lowering effect

• Induction of metabolizing CYP3A4 enzymes, which metabolize simvastatin

Avoid concomitant use if possible. Monitor response to simvastatin closely. Avoid sudden changes of the herb dosage

Herbs that may interfere with oral contraceptive medication

1. St John’s wort 2. Red clover 3. Saw palmetto

1. Oral contraceptives Failure of contraception. Theoretically, saw palmetto could interfere with oral contraception and hormone replacement therapy

St John’s wort preparations induce metabolizing CYP3A4 enzymes and glycoprotein drug transporters of these medications

Avoid concomitant use. Use an alternative contraceptive methods (barrier methods) if the herb is introduced

Herbs that may cause additive hepatotoxicity

1. Echinacea 1. Hepatotoxic drugs, e.g. anabolic steroids 2. amiodarone 3. Methotrexate 4. Ketoconazole

Risk of additive hepatotoxicity • Use of echinacea for over 8 weeks can cause hepatotoxicity

Be aware and use drugs with a potential to cause hypertonicity cautiously, monitoring clinically and biochemically for any early signs of hepatic dysfunction

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Probable mechanism of interaction Precautions

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MISCELLANEOUS HERBAL DRUGS

4. Sage

3. Androgens (e.g. finasteride, flutamide) 4. Thyroid replacement therapy

interfere with thyroid therapy. Saw palmetto interferes with male hormones and oestrogencontaining therapies

• Additive/antagonistic hormonal effects. Kelp is a source of iodine. Sage may increase TSH levels

Be aware

Herbs that may Ø absorption of co-administered drugs 1. St John’s wort 2. Saw palmetto

1. Iron ↓ absorption of co-administered iron

• Due to tannic acid content Be aware and separate oral intake by at least 2 hours

Herbs that may interfere with drugs used in the treatment of migraine

1. Feverfew 1. Antimigraine drugs, e.g. sumatriptan

≠ risk of episodes of tachycardia and hypertension (may be dangerous)

The parthenolide constituent of feverfew has been shown to inhibit the release of serotonin and prostaglandins. Sumatriptan is an SSRI

Avoid concomitant use

Herbs that may interfere with drugs used in the treatment of Alzheimer’s disease

1. Donepezil 2. Galantamine 3. Memantine

May be ≠ anticholinergic effects Sage possesses some anticholinergic effects, such as that on sweating

Be aware