+ Herbal Products and Dietary Supplements Amber Frick, PharmD

+ Patient Case 1 One of your regular patients comes to pick up his Coumadin. In the checkout area, you see ginkgo supplements, green tea, and St. John’s Wort in his basket.

What general counseling point for herbal products is inappropriate? 1. Just because this product is considered natural, doesn’t mean it is safe. 2. There is not a lot of evidence on the effectiveness of herbal products. 3. You should avoid using herbal products, because there is not enough evidence for their use, and they can be dangerous. 4. Herbal products are not FDA- approved so caution should be taken when using these products.

+ When should a patient not take herbal medications?

+ Labels DSHEA 1994: “This product is not intended to diagnose, cure, or prevent any disease.”

+ Herbal Resources Certifications United States Pharmacopeia (USP) National Sanitation Foundation (NSF) International Consumer Lab Natural Medicines Comprehensive Database/Natural Standard National Center for Complementary and Alternative Medicine

Which one of these herbal products are you most concerned will interact with his warfarin and will promptly caution him on? 1. Ginkgo supplements 2. Green Tea 3. St. John’s Wort 4. All of the above

+ Drug Interactions The G’s… HerbalDocumented InteractionsPotential Interactions Garlic OCs: decreased effectiveness Warfarin: increased INR Saquinavir: 50% decrease in levels Induction of CYP3A4 and CYP2D6 Ginger Antiplatelet drugs: additive effects at high dosages (> 4 g daily) Antihyperglycemic drugs: additive effects (avoid) Gingko Antiplatelet drugs: additive effect Trazodone: case report of coma Seizure threshold lowering drugs: may precipitate seizures (avoid) Antihypertensives: additive effects Hydrochlorothiazide: case report of paradoxical hypertension Ginseng Antihyperglycemic drugs: lowered BG levels in type 2 DM (monitor) Phenelzine: case report of headache, tremor, and mania Anticoagulant and antiplatelet drugs: unpredictable effect Antipsychotics and immunosuppressants: interference Inhibition of CYP2D6 (not clinically significant) Green Tea Decongestants: additive stimulant effect Sedatives: antagonism Anticoagulants and antiplatelet drugs: additive effects at high dosages (> 4 g daily) Warfarin: antagonism

+ Drug Interactions … and St. John’s Wort HerbalDocumented InteractionsPotential Interactions St. John’s Wort CYP3A4 substrates: decreased drug levels and effects OCs and hormone therapy: decreased activity Antidepressants: increased risk of serotonin syndromes with nefazodone, sertraline, and paroxetine Protease inhibitors and nonnucleoside reverse transcriptase inhibitors: decreased serum levels Cyclosporine: decreased blood levels and case reports of transplant graft rejection Photosensitizing agents: contraindicated 5-HT 1 agonists, dextromethorphan, meperidine, pentazocine, and tramadol: increased risk of serotonin syndrome Amiodarone: decreased levels and effect Fexofenadine: toxicity (monitor)

+ Patient Case 2 A patient asks for help in finding a natural product he heard about that might help with his muscle pain. He is taking Crestor 10 mg, lisinopril 20 mg, and aspirin 81 mg daily. What is the remedy he is looking for, and how would he use it? What is one major counseling point? Do you feel comfortable recommending it? If not, what additional information would you need from the patient?

What is your next course of action? 1. Treat the patient. 2. Refer the patient. 3. Request more information.

+ CoQ10 Cardiovascular protectant and general antioxidant Statin-associated effects Dose Statin-associated effects: 100 mg daily for 30 days Other: 100 mg 1 to 3 times daily Adverse Effects: GI distress Anorexia Headache Irritability Dizziness Procoagulant effects

+ Patient Case 3 A patient has been told to start fish oil for his triglycerides. He has picked up three bottles and asks which one is best. Which of the following fish oil products is best? How much fish oil do you recommend? What is one major counseling point?

Which product do you recommend? A B C 1. A 2. B 3. C

+ Fish Oil Triglyceride reduction agent, cardiovascular protectant, and anti- inflammatory Dose Based on the amount of omega-3 (EPA and DHA) Cardiac protection: 1 g daily Triglyceride lowering: 3 to 5 g daily Adverse effects Belching Fishy halitosis GI distress Bleeding Increased risk: ≥ 4 g daily Concomitant anticoagulant: ≤ 3 g daily.

+ Patient Case 4 A patient approaches you to ask about a natural product he heard he could try for “dribbling” when urinating. He is 59 years-old and wants to use something over-the-counter before going to see a physician. What is the remedy he is looking for? When can he expect relief? What is one major counseling point? Do you feel comfortable recommending it? If not, what additional information would you need from the patient?

What is your next course of action? 1. Treat the patient. 2. Refer the patient. 3. Request more information.

+ Saw Palmetto BPH treatment 5-alpha-reductase inhibitor Adverse effects GI complaints Bleeding Prostate cancer

+ Patient Case 5 A patient, who looks fatigued, asks about using a natural product for recovering from traveling. She just returned from a international flight for a business trip and needs to return to her normal daytime work schedule. What is the remedy she is looking for, and how would she use it? What is one major counseling point? Do you feel comfortable recommending it? If not, what additional information would you need from the patient?

What is your next course of action? 1. Treat the patient. 2. Refer the patient. 3. Request more information.

+ Melatonin Insomnia treatment and “jet lag” prevention Dose Synthesized melatonin Insomnia: 0.3 to 5 mg before bedtime Jet lag: 2 to 5 mg in the evening of the arrival day at destination and at bedtime for the following 2 to 5 days Adverse effects N/V Headache Tachycardia Dysthmia and worsening of depressive symptoms Morning “hangover” efffect Drug interactions MAOIs Tricyclic antidepressants BZDPs Valproate Oral contraceptives Caffeine Verapamil Nifedipine Immunosuppressants Cancer chemotherapy

+ Take Home Points Increased herbal use Evidence of safety and efficacy Comparative effectiveness “Natural” versus “safe” USP standards Health promotion and disease prevention Clear communication

+ What is your recommendation? A patient comes to your pharmacy and is noticeably distressed. She went to the physician’s office one week ago, where she was diagnosed with diabetes. Rather than take medicine right away, she opted to attempt to make lifestyle modifications. Also, one of her friends told her about konjac glucomannan, but she would like your opinion before trying it. What do you do next? What is your advice regarding konjac glucomannan?