Kava and Levodopa Oral Inhalation: Interaction Details

a) A 27-year-old Aboriginal Australian male presented three times following heavy kava use with symptoms of severe choreoathetosis of the limbs, trunk, neck, and facial musculature, and athetosis of the tongue. Level of consciousness was not impaired. Symptoms resolved within 12 hours of intravenous diazepam on each occasion. Acute rheumatic fever was excluded, cerebrospinal fluid and computed tomography of the brain was normal, and urinary drug screen was negative. The only abnormalities found in hematological and biochemical tests were a serum alkaline phosphatase of 162 international units/liter (IU/L) (normal: 35-135 IU/L) and serum gamma-glutamyltransferase of 426 IU/L (normal less than 60 IU/L). These were attributed to kava use. The patient did not drink alcohol ¹.

b) A 76-year-old female with idiopathic Parkinson's disease of 17 years' duration treated for 8 years with levodopa 500 milligrams (mg) and benserazide 125 mg was prescribed kava extract (Kavasporal Forte(R)) 150 mg twice daily for complaints of inner tension. Within 10 days, she noted a pronounced increase in her daily "off" periods both in terms of duration and number. Within 2 days of discontinuing the kava product, symptoms had returned to her normal baseline ².

c) A 63-year-old female experienced sudden and acute forceful involuntary oral and lingual dyskinesias on the fourth day of self-initiated therapy with kava extract (Kavasporal Forte(R)) 150 mg three times daily. She was treated successfully in the emergency room with biperiden 5 mg intravenously. She denied taking any other medications in the months preceding this event ².

d) A 22-year-old female took kava extract (Laitan(R)) 100 mg once for anxiety and nervousness. Within four hours she experienced oral and lingual dyskinesias, tonic rotation of the head, and painful twisting trunk movements. She was treated successfully with biperiden 2.5 mg intravenously. She denied taking any other medications in the months preceding this event ².

e) A 28-year-old male experienced acute involuntary neck extension with forceful upward deviation of the eyes within 90 minutes of taking kava extract (Laitan(R)) 100 mg. Symptoms resolved spontaneously within 40 minutes. This man had a history of acute dystonic reactions following exposure to promethacin (50 mg) and fluspirilene (1.5 mg), which had responded to biperiden 5 mg intravenously 9 and 12 years previously ².

f) In mice, kava extracts antagonized apomorphine-induced hyperreactivity to external stimuli. The number of hyperreactive mice after apomorphine 20 milligrams/kilogram (mg/kg) intraperitoneal administration was 6/6 in the saline treated group versus 0/6 in the group treated with kava resin (120 mg/kg) (p less than 0.005) or aqueous kava extract (p less than 0.001) ³.

g) Kava reversibly inhibited MAO(B) in intact platelets (IC50 1.2 micromole (mcmol)) in venous blood of healthy subjects. The constituents of kava evaluated individually were found in the following order of potency: desmethoxyangonin greater than (+)-methysticin greater than yangonin greater than (+)-dihydromethysticin greater than (+)-dihydrokavain greater than (+)-kavain. The percent inhibition of MAO (B) activity in nondiluted platelet homogenates was 98.2 +/- 0.8% with (-)-deprenyl versus 66.7 +/- 4.4% with (+)-methysticin ⁴.