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Kava (Piper methysticum G. Forst)
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Kava/Drug Interactions:- ACE inhibitorsACE inhibitors: Kava has diuretic properties and may have additive effects when taken with angiotensin-converting enzyme (ACE) inhibitors, such as benazepril, captopril, lisinopril, quinapril, or ramipril.
- AlcoholAlcohol: Animal studies have demonstrated marked increases in alcohol's hypno-sedative effects when taken with kava (115). However, this effect has not been confirmed in healthy human volunteers (104).
- AnalgesicsAnalgesics: Kava may have additive sedative effects when taken concomitantly with the opioid analgesics oxycodone and propoxyphene.
- AnestheticsAnesthetics: Kava may prolong the sedative action of anesthesia due to presumed MAOI-like action. While numerous anecdotal reports have circulated, there is a lack of clinical research that confirms this interaction (116). Anesthesiologists may recommend that patients stop taking kava 2-3 weeks prior to surgery.
- Antianxiety drugsAntianxiety drugs: Theoretically, kava may have additive effects when taken with antianxiety drugs. Kava has been shown to have anxiolytic-like effects (117; 99).
- Antineoplastic agentsAntineoplastic agents: Kava may participate in pharmacokinetic interactions with anticancer drugs (118).
- Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): The pyrone constituents of kava have been found to have weak MAO-inhibitory properties in vitro (119). Therefore, there may be an additive effect when used concomitantly with MAO-inhibitory agents, including phenelzine (Nardil®) and tranylcypromine (Parnate®). This effect has not been confirmed in humans.
- Antidepressant agents, selective serotonin reuptake inhibitors (SSRIs)Antidepressant agents, selective serotonin reuptake inhibitors (SSRIs): Kava may cause excessive drowsiness when taken with SSRIs, such as fluoxetine, fluvoxamine, paroxetine, or sertraline. Use cautiously in patients with endogenous depression due to purported sedative activity of kava resin and the pyrones dihydrokawain and dihydromethysticin (1; 114).
- Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Racemic kavain, present in kava preparations, has been shown to have antiplatelet effects due to cyclooxygenase inhibition and inhibition of thromboxane synthesis (94). Effects on platelets have not been reported in humans and clinical relevance is not clear.
- BenzodiazepinesBenzodiazepines: Kava may cause adverse neurological effects and excessive perioperative sedation. Such a reaction may be due to benzodiazepine and antidepressant activities on noradrenergic and/or serotonergic pathways that may potentiate benzodiazepine and induction anesthetic potency (109).
- Buspirone and opipramolBuspirone and opipramol: Kava-Kava LI150 has been used in the acute treatment of out-patients suffering from generalized anxiety disorder (GAD) (57). Therefore, kava may cause additive effects when taken concomitantly with these or other agents with similar effects.
- CNS depressantsCNS depressants: Kava may potentiate CNS depressants, including barbiturates and benzodiazepines (120). Lethargy and disorientation were reported in a 54 year-old man taking kava in combination with alprazolam (105). Kavalactones have been shown to potentiate the effects of CNS depressants, such as ethanol, benzodiazepines, low-potency neuroleptics, beta-blockers, and barbiturates in animals with concurrent use being potentially toxic (115; 121).
- ContraceptivesContraceptives: Theoretically, kava may interact with contraceptives, as the herb may decrease uterine tone (1).
- Cytochrome P450 metabolized agentsCytochrome P450 metabolized agents: Preliminary evidence suggests that kava may significantly inhibit multiple cytochrome P450 enzymes such as cytochrome P450 2C9 inhibitors, cytochrome P450 2D6 inhibitors, and cytochrome P450 3A(4,5,7) inhibitors (122; 123; 124).
- DiureticsDiuretics: Because kava has diuretic properties, it should not be taken with diuretic drugs, such as acetazolamide, amiloride, or furosemide.
- Dopamine antagonistsdopamine agonistsDopamine antagonists, dopamine agonists: Kava has been reported to antagonize the effect of dopamine and elicit extrapyramidal effects (39; 96; 63). Therefore, it may interfere with the effects of dopamine or dopamine agonists and exacerbate the extrapyramidal effects of dopaminergic antagonists such as droperidol, haloperidol, risperidol, and metoclopramide. Kava (Piper methysticum) increases 'off' periods in Parkinson patients taking levodopa and can cause a semicomatose state when given concomitantly with alprazolam (113).
- Gastrointestinal agents, miscellaneousGastrointestinal agents, miscellaneous: Theoretically, kava may interact with gastrointestinal agents, as gastrointestinal upset has been reported as an infrequent adverse event in trials (6; 79; 53).
- Hepatotoxic agentsHepatotoxic agents: More than 30 cases of liver damage have been reported, including hepatitis (27; 28; 29), cirrhosis, and fulminant liver failure (30; 31), and there have also been reports of death (32; 33). Concomitant use with other potentially hepatotoxic drugs, such as anabolic steroids, amiodarone, methotrexate, acetaminophen (Tylenol®), or antifungals like ketoconazole, is generally not advised.
- Hormonal agentsHormonal agents: Theoretically, kava may interact with contraceptives, as the herb may decrease uterine tone (1).
- Mood stabilizersMood stabilizers: Kava may have additive effects when taken with mood stabilizers, such as antidepressants or antianxiety agents. The pyrone constituents of kava have been found to have weak MAO inhibitory properties in vitro (119). Kava may cause excessive drowsiness when taken with SSRIs, such as fluoxetine, fluvoxamine, paroxetine, or sertraline, and kava has been shown to have anxiolytic-like effects (117; 99).
- Neurologic agentsNeurologic agents: The extrapyramidal side effects caused by neuroleptic agents may be reduced by kava special extract WS 1490 (125).
- Renally eliminated drugsRenally eliminated drugs: Theoretically, kava may increase the side effects of renally eliminated drugs, as there has been a case report of rhabdomyolysis in a 29 year-old man who consumed an herbal combination of kava, ginkgo, and guarana (95). It is unclear if renal failure occurred. The causal role of kava in this case is unclear. Acute urinary retention secondary to kava ingestion has also been reported (112).
- SedativesSedatives: Kava may potentiate CNS depressants, including barbiturates and benzodiazepines (120). Lethargy and disorientation were reported in a 54 year-old man taking kava in combination with alprazolam (105). Kavalactones have been shown to potentiate the effects of CNS depressants, such as ethanol, benzodiazepines, low-potency neuroleptics, beta-blockers, and barbiturates in animals with concurrent use being potentially toxic (115; 121).
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Kava/Herb/Supplement Interactions:- AnalgesicsAnalgesics: Kava may have additive sedative effects when taken concomitantly with the herbs and supplements that act as opioid analgesics.
- AnestheticsAnesthetics: Kava may prolong the sedative action of anesthesia due to presumed MAOI-like action. While numerous anecdotal reports have circulated, clinical research is lacking (116). Anesthesiologists may recommend patients to stop taking kava 2-3 weeks prior to surgery.
- Antidepressant agents, monoamine oxidase inhibitors (MAOIs)Antidepressant agents, monoamine oxidase inhibitors (MAOIs): The pyrone constituents of kava have been found to have weak MAO-inhibitory properties in vitro (119). Therefore, there may be an additive effect when used concomitantly with MAO-inhibitory agents, including chromium, ephedra, evening primrose oil, fenugreek, Ginkgo biloba, hops, St. John's wort, tyrosine, valerian, yohimbe, 5-HTP (5-hydroxytryptophan), DHEA (dehydroepiandrosterone), DLPA (DL phenylalanine), SAMe (S-adenosylmethionine), vitamin B6, and homeopathic remedies, including Aurum Metallicum, Kali Bromatum, and sepia. This has not been confirmed in humans.
- Antidepressants, selective serotonin reuptake inhibitors (SSRIs)Antidepressants, selective serotonin reuptake inhibitors (SSRIs): Kava may cause excessive drowsiness when taken with SSRIs. Use cautiously in patients with endogenous depression due to purported sedative activity of kava resin and the pyrones dihydrokawain and dihydromethysticin (1; 114).
- AntineoplasticsAntineoplastics: An increasing number of cancer patients are using complementary and alternative medicines (CAM) in combination with their conventional chemotherapeutic treatment (126). Considering the narrow therapeutic window of oncolytic drugs, this CAM use increases the risk of clinically relevant herb-anticancer drug interactions. Kava may participate in pharmacokinetic interactions with herbs and supplements with potential anticancer effects (118).
- Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Racemic kavain, present in kava preparations, has been shown to have antiplatelet effects due to cyclooxygenase inhibition and inhibition of thromboxane synthesis (94). Effects on platelets have not been reported in humans and clinical relevance is not clear.
- AnxiolyticsAnxiolytics: Theoretically, kava may have additive effects when taken with antianxiety agents. Kava has been shown to have anxiolytic-like effects (117; 99).
- ContraceptivesContraceptives: Theoretically, kava may interact with contraceptives, as the herb may decrease uterine tone (1).
- Cytochrome P450 metabolized herbs and supplementsCytochrome P450 metabolized herbs and supplements: Preliminary evidence suggests that kava may significantly inhibit multiple cytochrome P450 enzymes such as cytochrome P450 2C9 inhibitors, cytochrome P450 2D6 inhibitors, and cytochrome P450 3A(4,5,7) inhibitors (122; 123).
- DiureticsDiuretics: Kava has diuretic properties and may have additive effects with herbs and supplements with similar properties.
- Dopamine antagonists and dopamine agonistsDopamine antagonists and dopamine agonists: Kava has been reported to antagonize the effect of dopamine and elicit extrapyramidal effects (39; 96; 63). Therefore, it may interfere with the effects of dopamine or dopamine agonists and exacerbate the extrapyramidal effects of dopaminergic antagonists.
- Gastrointestinal herbs and supplementsGastrointestinal herbs and supplements: Theoretically, kava may interact with gastrointestinal agents, as gastrointestinal upset has been reported as an infrequent adverse event in trials (6; 79; 53).
- Hepatotoxic herbs and supplementsHepatotoxic herbs and supplements: More than 30 cases of liver damage have been reported, including hepatitis (27; 28; 29), cirrhosis, and fulminant liver failure (30; 31), and there have also been reports of death (32; 33). Therefore, concomitant use with other potentially hepatotoxic agents is generally not advised.
- MelatoninMelatonin: Theoretically, kava and melatonin taken concomitantly may have additive sedative effects.
- Hormonal herbs and supplementsHormonal herbs and supplements: Theoretically, kava may interact with contraceptives, as the herb may decrease uterine tone (1).
- Mood stabilizersMood stabilizers: Kava may have additive effects when taken with mood stabilizers, such as antidepressants or antianxiety agents. The pyrone constituents of kava have been found to have weak MAO-inhibitory properties in vitro (119). Kava may cause excessive drowsiness when taken with SSRIs, and kava has been shown to have anxiolytic-like effects (117; 99).
- Neurologic herbs and supplementsNeurologic herbs and supplements: The extrapyramidal side effects caused by neuroleptic agents may be reduced by kava special extract WS 1490 (125). However, there is controversy in this area because other laboratory and animal studies suggest a potential interaction with dopamine or dopamine agonists, which may lead to the exacerbation of the extrapyramidal effects of dopaminergic antagonists.
- Renally eliminated herbs and supplementsRenally eliminated herbs and supplements: Theoretically, kava may increase the side effects of renally eliminated drugs, as there has been a case report of rhabdomyolysis in a 29 year-old man who consumed an herbal combination of kava, ginkgo, and guarana (95). It is unclear if renal failure occurred. The causal role of kava in this case is unclear. Acute urinary retention secondary to kava ingestion has also been reported (112).
- SedativesSedatives: Kava may potentiate CNS depressants, including barbiturates and benzodiazepines (120). Kavalactones have been shown to potentiate the effects of CNS depressants (115; 121). It is unclear to what extent kava might act additively or synergistically with other purported sedative herbs, such as calamus, calendula, California poppy, catnip, capsicum, celery, couch grass, elecampane, ginseng (Siberian), gotu kola, German chamomile, goldenseal, hops, dogwood, lemon balm, sage, St. John's wort, sassafras, scullcap, shepherd's purse, stinging nettle, valerian, wild carrot, wild lettuce, withania root, or yerba mansa.
- St. John's wortSt. John's wort: In a telephone survey, one woman reported nausea, diaphoresis, muscle cramping, weakness, and elevated pulse and blood pressure after a single dose of an herbal combination of kava, St. John's wort (Hypericum perforatum), and valerian (127).
- ValerianValerian: In a telephone survey, one woman reported nausea, diaphoresis, muscle cramping, weakness, and elevated pulse and blood pressure after a single dose of an herbal combination of kava, St. John's wort, and valerian (Valeriana officinalis) (127).
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Kava/Food Interactions:- Tyramine/tryptophan-containing foods/beveragesTyramine/tryptophan-containing foods/beverages: Tyramine or tryptophan-containing foods may pose a risk of hypertensive crisis if eaten while taking kava, due to the monoamine oxidase inhibitory (MAOI) activity of kava found in vitro (119) However, this interaction has not been reported in humans.
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Kava/Lab Interactions:- Lymphocyte countLymphocyte count: Chronic heavy use of kava has been associated with decreased lymphocyte counts (62; 93).
- Red blood cell volume, platelet sizeRed blood cell volume, platelet size: Chronic heavy use of kava has been associated with increased red blood corpuscle volume and reduced platelet size (62). It is not clear if poor nutrition or iron deficiency coincides with chronic kava use, thus confounding these findings.
- Serum albumin, total proteinSerum albumin, total protein: Chronic heavy use of kava has been associated with decreased albumin and total protein (62). Causality is unclear and may be due to poor nutrition in chronic kava users or hepatic damage.
- Serum bilirubinSerum bilirubin: Chronic heavy use of kava has been paradoxically associated with decreased bilirubin (62).
- Serum transaminasesSerum transaminases: Kava use has been associated with elevations of liver function tests in animals and humans (62; 93; 23; 24).
- Urine red blood cellsUrine red blood cells: Hematuria of unclear etiology has been reported anecdotally with kava use, although scientific data are scant (62).
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Copyright © 2011 Natural Standard (www.naturalstandard.com)
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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
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