Pharmacists’ expertise wanted on cannabinoid drug–drug interactions

Pharmacists know patients are using cannabis or taking cannabidiol (CBD) for things like insomnia and pain—use of these products is only growing as the number different cannabinoid formulations. But little known about unintended interactions between cannabinoids medications. Right now, pharmacists other health care providers don't have system alerts that can pop up with contraindications in combination medications taking. “The most important thing do ask ‘are you a product?’ then medication reconciliation to see if having an effect on drug warfarin,” said Kent Vrana, PhD, professor chair Department Pharmacology at Penn State University College Medicine. Vrana helped develop free URL through assesses against database prescription OTC perception safe, but we kind redirected conversation yes maybe they how affect medications?” Paul Kocis, RPh, PharmD, MPH, clinical pharmacist Health Milton S. Hershey Medical Center. “It's still evolving area, which hoping contribute down road,” who drove development tool called CANNabinoid Drug Interaction Review (CANN-DIR). He resource intended both caregivers. “We want going their doctor them recognize should be telling CBD oil,” Kocis said. one over hundred plant. It metabolized by liver isoenzymes CYP2C19 CYP3A4, major players metabolism. Concomitant use moderate strong inhibitors inducers may result increased risk potentially serious adverse effects associated reduced therapeutic response CBD, respectively. For example, patient product carbamazepine, inducer, dose might not effective them. Maybe getting any benefits from after being it while. too low because inducer medication. The opposite also hold true when inhibitor, well could causing effect. Tabled 1Metabolic drug–drug enzyme substrates, inhibitors, inducersReprinted from: Brown Winterstein. Journal Clinical 2019.EnzymeMedication examplesEffect/RecommendationCYP3A4 substratesImmunosuppressants, chemotherapeutics, antidepressants, antipsychotics, opioids, benzodiazepines, z-hypnotics, statins, calcium channel blockers, othersIncreased related substrate. Avoid coadministration, reduce substrate dose, monitor toxicity. prescribing cascade new treatment effects.CYP3A4 inhibitorsStrong: Protease ketoconazole, loperamide, nefazodone Moderate: Amiodarone, verapamil, cimetidine, aprepitant, imatinibIncreased bioavailability, possible increase effects. Reduce dose.CYP3A4 inducersStrong: Enzalutamide, phenytoin Carbamazepine, topiramate, phenobarbital, rifampicin, efavirenz, pioglitazoneDecreased decrease effectiveness. Increase dose.CYP2C19 substratesAntidepressants, antiepileptics, proton pump clopidogrel, propranolol, carisoprodol, cyclophosphamide, warfarinIncreased effects.CYP2C19 Fluvoxamine, fluoxetine Other: Proton fluconazole, efavirenzIncreased inducersRifampin, phenytoin, St. John's WortDecreased dose.CYP2C8/9 substratesRosiglitazone, burprenorphine, montelukast, celecoxib, sulfonylureas, losartan, naproxen, rosuvastatin, valsartan, Open table tab common warfarin, used treat prevent blood clots, well-known example. Cannabinoid warfarin metabolized, either reducing its effectiveness leading toxicity, such bleeding. safety profile comes largely data FDA-approved, prescription-only cannabidiol, Epidiolex (Greenwich Biosciences), first-ever containing CBD. indicated two rare severe forms epilepsy ages 2 years older. trial results showed was dose-related increases function tests, specifically, elevations AST, ALT total bilirubin, injury. interacts several antiepileptic same disorders, fact. doses diazepam, clobazam, stiripentol, will likely need toxicity patients. Elevations enzymes seem occur more readily coadministration valproic acids, well. Given lack information specific interactions, it's area where pharmacist's expertise needed. accessible this example that's important,” Saswat Kabisatpathy, Avant Pharmacy Wellness Center Charlotte, NC. “I think obligation our educated topic.” past few years, Kabisatpathy has hosted continuing education webinar personnel he's always flooded questions end presentation. “This goes show lot knowledgeable be.” encourages talk cannabis. systems check resources fingertips,” he opportunities within consultation patient's use. discussion smoking, Another key component products. opportunity during conversation. “And say ‘yes,’ pharmacists, educate those emphasize potential offer resources,” teams doing reconciliations, make sure noted profile. Medication therapy management platforms dispensing ways identify In follow-up conversations patients, they've noticed differences since let communicate physician, CANN-DIR, accessed www.cann-dir.psu.edu/#/. “All based FDA Kocis. link included, suggestion Pennsylvania cannabis-dispensing consulted project. emphasized general reference educational resource, substitute professional medical advice, diagnosis, treatment. identification practicing medicine,” noted. A disclaimer opening page site states clearly. business model here, harm reduction freely available,” Vrana. host regulation cannabis-derived products, here: www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#relatedinfo What cannabis?The plant contains 554 compounds. These compounds, active chemicals, include 113 cannabinoids, tetrahydrocannabinol (THC) (CBD).“As look pharmacological actions expected responses, name label help us, instead knowing whether THC type, hybrid type,” Kari Franson, BCPP, associate dean Southern California.Although research, body. binds receptors body, while interact indirectly receptors. chemical responsible psychoactive quality cannabis, antinausea analgesic no properties, inflammation. Other compounds plant, terpenes flavonoids, play synergistic role cannabis—what's “entourage effect.”Fiona Oxsher, cofounder manager LKN Extractions, learning body's endocannabinoid system—which discovered 2002—helps us understand work.The controls person's stress, one's mood, appetite, energy balance, more. Oxsher explained bodies been increasingly void environment, food eat, factors. Plants way saturate system—the CB1 CB2 receptors, specifically—she said.Cannabinoids present rosemary, echinacea, kava, plants. “But highest percentage cannabinoids,” Oxsher. (CBD). “As California. Although effect.” Fiona work. Cannabinoids Δ-8 THC, dangerous synthetic productΔ-8 tetrahydrocannabinol, product—a substance found sativa plant—that's quickly gaining popularity among consumers. received hundreds event reports involving warning public risks use.Saswat NC, concerns what actually labeled process behind making product. Additional chemicals needed convert hemp, into contaminated heavy metals. addition, there many states—although some banned sale THC.Here 5 THC: 1.Δ-8 evaluated approved safe marketed put risk.2.FDA THC–containing products.3.Δ-8 intoxicating effects.4.Δ-8 often involve harmful create concentrations claimed marketplace.5.Δ-8 kept out reach children pets.More www.fda.gov/consumers/consumer-updates/5-things-know-about-delta-8-tetrahydrocannabinol-delta-8-thc THC. Here pets. More Full- versus broad-spectrum productsFull spectrum full complement minor cannabinoids—these phytochemicals. On hand, alternative full-spectrum products; everything THC.Hemp marijuana fall under federal designations. Hemp variety grown specifically fiber industrial purposes. 2018 Farm Bill legalized production hemp extracts. less than 0.3% Cannabis greater considered Schedule I DEA federally illegal. Full What's difference cannabis?Cannabis scientific abundant contained