Herb-drug interactions: Caution patients when changing supplements

Ms. X, age 41, has a history of bipolar disorder and presents with extreme sleepiness, constipation with mild abdominal cramping, occasional dizziness, and "palpitations." Although usually she is quite articulate, Ms. X seems to have trouble describing her symptoms and reports that they have been worsening over 4 to 6 days. She is worried because she is making mistakes at work and repeatedly misunderstanding directions. Ms. X has a family history of hyperlipidemia, heart disease, and diabetes, and she has been employing a healthy diet, exercise, and use of supplements for cardiovascular health since her early 20s. Her medication regimen includes lithium, 600 mg, twice a day, quetiapine, 1,200 mg/d, a multivitamin and mineral tablet once a day, a brand name garlic supplement (garlic powder, 300 mg, vitamin C, 80 mg, vitamin E, 20 IU, vitamin A, 2,640 IU) twice a day, and fish oil, 2 g/d, at bedtime. Lithium levels consistently have been 0.8 to 0.9 mEq/L for the last 3 years. Ms. X describes no changes in her diet or prescription medications, but mentions that the brand name garlic supplement she takes was out of stock early last week, so she bought another brand of garlic supplement, consisting of oil capsules. Ms. X says, "I made sure the dose was exactly the same, since you told me not to change doses without check ing with you first!" You review the bottle she brought with her and see that it contains garlic oil with "allien equivalent to 300 mg of garlic powder" and 60 mg of vitamin C with rose hips, vitamin E, 20 IU, vitamin A, 2,200 IU, and piperine, 20 mg. Factors of drug-supplement interactions Because an interaction is possible doesn't always mean that a drug and an offending botanical cannot be used together. With awareness and planning, possible interactions can be safely managed (Table 1). Such was the case of Ms. X, who was stable on a higher-than-usual dosage of quetiapine (average target is 600 mg/d for bipolar disorder) because of presumed moderate enzyme induction by the brand name garlic supplement. Ms. X did not want to stop taking this supplement when she started quetiapine. Although garlic is listed as a possible moderate cytochrome P450 (CYP) 3A4 inducer, there is conflicting evidence. (1) Ms. X's clinician advised her to avoid changes in dosage, because it could affect her quetiapine levels. However, the change in the botanical preparation from dried, powdered garlic to garlic oil likely removed the CYP3A4 enzyme induction, leading to a lower rate of metabolism and accumulation of the drug to toxic levels. Drug metabolism. Practitioners are increasingly aware that St. John's wort can significantly affect concomitantly administered drug levels by induction of the CYP isoenzyme 3A4 and more resources are listing this same possible induction for garlic. (1) However, what is less understood is the extent to which different preparations of the same plant possess different chemical profiles (Table 2, page 40). Clinical studies with different garlic preparations--dried powder, aqueous extracts, deodorized preparations, oils--have demonstrated diverse and highly variable results in tests of effects on CYP isoenzymes and other metabolism activities. (2) There also is contradictory evidence between in vitro and in vivo studies, with 1 in vitro study of garlic extract demonstrating marked CYP3A4 effects up to 30%, while another study using a water-soluble, aged garlic extract noted little or no effects. (3) Box The function of P-glycoprotein P-glycoprotein is known as a multi-drug resistance protein because it is involved in resistance mechanisms for a number of drugs. P-glycoprotein is involved in drug transport in the gut where it functions as an efflux pump, sending toxins and other xenobiotics, such as drugs, back into the intestinal lumen. It functions similarly as a component of the blood-brain barrier. When P-glycoprotein is inhibited, bioavailability of orally administered drugs goes up and penetration across the blood-brain barrier increases; inducement of P-glycoprotein results in lower blood levels of the target drug. …