Updates in Pharmacy

What’s New, What’s Gone,What’s Off-label that’s Useful….

Show of hands, please…Who has prescriptive authority?Who uses that prescriptive authority?Who likes being the first to write for a new drug on themarket?Who knows what a “Black Box” warning is?Where is that “Black Box”—who sees it?Who has a trusted relationship with a localpharmacist?Who knows if the compounding pharmacy being usedis accredited?

• How does prescriptive authority apply tonaturopathic doctors?• If NDs are “known” for using nature to cure, iswriting prescriptions something we shouldhabitually be doing?• Are we losing our medicine and becoming“green allopaths”?

Pharmacist (RPh) since 1988Naturopathic Doctor since 2004Practiced in unlicensed Virginia from 2005-2012Taught pharmacology at Bastyr this yearCurrently in private practice in SeattleGave talk (with Tish Dick-Kronenberg, ND) atAANP 2011; will offer similar class at Bastyr thisfall—”Hey, Doc—how do I get off these drugs?”NOTE: I am not anti-pharmaceutical! I am all forpracticing the principles of naturopathic medicineand following the Therapeutic Order.

Chloramphenicol• On the market since 1949• Antibacterial agent• Pulled 2012 due to bone marrow toxicity(aplastic anemia)

Propoxyphene (Darvon/Darvocet)• On the market since 1957• Pain medication• Pulled 2010 because of increased risk ofmyocardial infarction & stroke

Rosiglitazone (Avandia)• On the market since 1999• Oral hypoglycemic• Pulled 2010 in Europe and in 2011 in NewZealand because of increased risk ofmyocardial infarction & death• Still on US market despite estimated 83000heart attacks attributed to product and over13000 lawsuits• In combination with metformin (Avandamet)and glimepiride (Avandaryl)

Phosphosoda (Fleet’s Phosphosoda)• Over the counter laxative & bowel prep• Pulled 2008 due to acute phosphatenephropathy• Other oral phosphosoda agents remain onthe market by prescription only

Sibutramine (Meridia)• On the market since 1997• Appetite suppressant• Pulled 2010 due to increased risk of heartattack & stroke

Gemtuzumab ozogamicin (Mylotarg)• On the market since 2000 (acceleratedapproval from FDA)• Treatment for acute myeloid leukemia• Pulled 2010 due to increased risk of venoocclusiveliver disease & lack of clinicalbenefit

Efalizumab (Raptiva)• On the market since 2003• Treatment for psoriasis• Pulled 2009 due to increased risk ofprogressive focal leukoencephalopathy(rapidly progressive CNS infectionleading to death or severe disability; nocure known)

Peginesatide (Omontys)• On the market since March 2012• Pulled February 2013 due tocardiovascular events, anaphylaxis, death• Treatment for anemia due to chronickidney disease

Ivermectin lotion (Sklice)• For the treatment of head lice• Approved February 2012• Anti-helminthic use since 1981 (Stromectol)• Now labeled for the single use (1 treatmentonly) on dry hair for head lice in patientsgreater than 6 months of age

Ingenol mebutate gel (Picato)• For the treatment of actinic keratosis• Approved January 2012• 3-day treatment at the cost of about $600• Euphorbia peplus sap contains the substance onwhich this is based

Cysteamine hydrochloride drops (Cystaran)• For the treatment of corneal cystine crystalaccumulation due to cystinosis• Approved October 2012• In cosmetics, a hair waving/straighteningagent• To be used every hour while awake• [Cysteamine bitartrate (Proscybi) approvedApril 2013 for nephropathic cystinosis]

Ocriplasmin injection (Jetrea)• For the treatment of symptomaticvitreomacular adhesion• Approved October 2012• Dissolves proteins laminin & fibronectin,detaching vitreous from macula

Ranibizumab injection (Lucentis)• For the treatment of diabetic macular “wet” edema• Approved August 2012• Monoclonal antibody fragment from same parentmouse antibody as bevacizumab (Avastin)• Originally approved 2006 for treatment of macularedema following retinal vein occlusion; newindication• Cost is $1600 per monthly intravitreal injection vs$42 for bevacizumab which is used for certaincancers

Tafluprost ophthalmic solution (Zioptan)• For the treatment of elevated intraocularpressure• Approved February 2012• Another prostaglandin analogue likelatanoprost (Xalatan)

Beclomethasone dipropionate nasal spray (Qnasl)• For the treatment of seasonal and perennialallergic rhinitis• Approved March 2012• Prodrug of beclomethasone, on market since1972• “Dry” nasal spray

Aclidinium bromide powder for inhalation(Tudorza Pressair)• For the maintenance treatment ofbronchospasm associated with chronicobstructive pulmonary disease• Approved July 2012• Anticholinergic; long-acting muscarinic blockersimilar to tiotropium (Spiriva)

Ivacaftor (Kalydeco)• For the treatment of cystic fibrosis with theG551D mutation in the CFTR gene• Approved January of 2012• This genetic mutation accounts for 4-5% of CF• Currently being evaluated in genetic mutationF508del, which accounts for 70% CF cases• Vertex (manufacturer, along with CFF) is tomake drug available at no cost to US familieswith no insurance and household income lessthan $150000 per year

Lucinactan (Surfaxin)• For the treatment of respiratory distresssyndrome in premature infants• Approved March 2012• Designed to decrease duration and risk ofmechanical ventilation in children under 2years of age diagnosed with acute respiratoryfailure

Prednisone delayed release tablets (Rayos)• For the treatment of certain inflammatorydiseases, including arthritis, COPD, asthmaand psoriatic conditions• Approved July of 2012• Delayed release version of 1940s “miracledrug”

Icosapent ethyl (Vascepa)• For the treatment of hypertriglyceridemia• Approved July 2012• Ethyl ester of eicosapentanoic acid• Dose is 4g daily

Taliglucerase alfa (Elelyso)• For the treatment of Gaucher disease• Approved May 2012• Plant-derived enzyme; recombinantglucocerebrosidase from transgenic carrot cells• First plant-made pharmaceutical to gainapproval by FDA

Linaclotide (Linzess)• For the treatment of irritable bowel syndromewith constipation and chronic idiopathicconstipation• Approved August 2012• Forecasted to be blockbuster in sales by 2021• Lubiprostone (Amitiza) only otherIBS/constipation drug on the market• Tegaserod (Zelnorm) pulled from market in2002 due to increased risk of heart attack &stroke

Pancrelipase tablets (Viokace)• For the treatment of exocrine pancreaticinsufficiency due to chronic pancreatitis orpancreatectomy• Approved March 2012• Other pancrelipase products include brandsCreon, Zenpep, Pancreaze, Pertzye, Ultresa

Pancrelipase delayed release capsules (Ultresa)• For the treatment of exocrine pancreaticinsufficiency due to cystic fibrosis or otherconditions• Approved March 2012• Delayed release option

Linagliptin + metformin (Jentadueto)• For the treatment of type II diabetes• Approved February 2012• Tradjenta (2011) + Glucophage (1994) in 1 pill

Mifepristone (Korlym)• For the control of hyperglycemia in adults withendogenous Cushing’s syndrome• Approved February 2012• Abortion agent (RU486) with new indication(Mifeprex approved in US in 2000)

Lorcaserin HCl (Belviq)• For the chronic management of weight loss• Approved June 2012• Schedule IV controlled drug withhallucinogenic activity• Serotonin receptor agonist• First weight loss drug approved since 1999• Only two remain on market—orlistat (Xenicalby prescription, Alli over-the-counter) &phentermine (Fastin)

Phentermine + topiramate extended release capsules(Qsymia)• For the treatment of chronic weight management• Approved July 2012• Topamax (anticonvulsant approved 1996) + Fastin(appetite suppressant approved 1959) together in 1pill• Remember phen-fen (phentermine +fenfluramine)? Numerous deaths due topulmonary hypertension & heart valve problems.Fenfluramine pulled from market after $13 billionpaid out in legal damages. Topiramate’s patentexpired 2009.

Testosterone gel (Bio-T-Gel)• For the treatment of hypogonadism• Approved February 2012• Other topical forms of testosterone on marketsince 2000 or earlier

Estradio valerate; estradiol valerate + dienogest(Natazia)• For the treatment of heavy menstrual bleeding• Approved March 2012• Oral contraceptive 2010• Pharma’s version of bHRT: esterified form ofnatural 17-beta-estradiol + progesterone and 19-nortestosterone derivatives marketed to postmenopausalwomen for treatment of climactericsymptoms. Adverse effects include breakthroughbleeding, mastalgia, headache, abdominal pain,hypertension, thrush, migraine, weight gain,increase in endometrial thickness andmetrorrhagia

Mirabegron (Myrbetriq)• For the treatment of overactive bladder• Approved June 2012• First of its kind—activates β3 adrenergicreceptors in detrusor muscle, leading toincreased capacity of bladder through musclerelaxation

Avanafil (Stendra)• For the treatment of erectile dysfunction• Approved April 2012• Cousin to sildenafil (Viagra), tadalafil (Cialis),vardenafil (Levitra)

Rotigotine transdermal system (Neupro)• For the treatment of Restless Legs Syndrome• Approved April 2012• Dopamine agonist for use in Parkinson’s (2007)• New indication for RLS

Gabapentin enacarbil (Horizant)• For the treatment of postherpetic neuralgia• Approved June 2012• Prodrug of gabapentin (Neurontin 1994), greaterbioavailability• Approval denied 2010 for the use in restless legsyndrome due to concerns about increased cancerrisk in some animal studies—gabapentin ofconcern, too, but benefit in seizure control (notrestless leg syndrome) determined to outweighrisk of cancer• Approved for RLS in 2011 and PHN in 2012.

Pregabalin (Lyrica)• For the treatment of neuropathic painassociated with spinal cord injury• Approved June 2012 for this indication• Approved 2004 for neuropathic pain; 2007 forfibromyalgia

Teriflunomide (Aubagio)• For the treatment of multiple sclerosis• Approved September 2012• Active metabolite of leflunomide, a pyrimidinesynthesis inhibitor used as a DMARD for RA• Teriflunomide is for relapsing/remitting MS

Perampanel (Fycompa)• For the treatment of partial-onset seizures withor without secondarily generalized seizures• Approved October 2012• Non-competitive AMPA glutamate receptorantagonist

Oxcarbazepine extended release tablets (OxtellarXR)• For the adjunctive therapy of partial seizures inadults and in children 6 years to 17 years of age• Approved October 2012 in this form• Extended release form of Trileptal, which hasindications for epilepsy (2000) andbipolar/mood disorder (2009)• Structurally similar to carbamazepine(Tegretol); watch for suicidal ideation

Methylphenidate HCl (Quillivant XR)• For the treatment of Attention DeficitHyperactivity Disorder• Approved September 2012• The extended release version of Ritalin (1955;Ritalin LA 2002; Concerta 2008; Covidien 2013)• Once daily dosing in liquid form

Elvitegravir, cobicistat, emtricitabine, tenofovirdisoproxil fumarate (Stribild)• For the treatment of HIV-1 infection• Approved August 2012• “The Quad”• For initial treatment of newly diagnosed HIV• Single pill taken once daily

Vismodegib (Eviredge)• For the treatment of basal cell carcinoma• Approved January 2012• Hedgehog pathway inhibitor

Regorafenib (Stivarga)• For the treatment of previously treated patientswith metastatic colorectal cancer• Approved September 2012• Expanded use February 2013 to treat patientswith advanced gastrointestinal stromal tumorsthat cannot be surgically removed and are nolonger responsive to imatinib and sunitinib

Enzalutamide (Xtandi)• For the treatment of metastatic castrationresistantprostate cancer• Approved August 2012• For patients who previously received docetaxel• Androgen receptor antagonist with 5-foldhigher affinity than bicalutamide (Casodex)

Abiraterone (Zytiga)• For the treatment of metastatic castrationresistantprostate cancer• Approved December 2012• To be used in conjunction with prednisone inmen who have/have not been treated withchemotherapy previously

Ziv-aflibercept (Zaltrap)• For the treatment of metastatic colorectalcancer• Approved August 2012• To be used in conjunction with 5-fluorouracil,leucovorin, and irinotecan in patients resistantto or experiencing progression of disease postoxaliplatin therapy

Pazopanib (Votrient)• For the treatment of soft tissue sarcoma• Approved April 2012• Tyrosine kinase inhibitor for use in renal cellcarcinoma (2009); new indication for soft tissuesarcoma• May cause severe or life-threatening liverdamage

Glucarpidase (Voraxaze)• For the treatment of toxic plasma methotrexateconcentrations in patients with impaired renalfunction• Approved January 2012• Single injection; $22,500 per 1ml vial• Derived from genetically modified E. coli

Pertuzumab (Perjeta)• For the first-line treatment of HER2+ metastaticbreast cancer• Approved June 2012• First of its kind: HER dimerization inhibitor—binding to HER2 inhibits dimerization of HER2to other HER receptors, slowing tumor growth

Paclitaxel protein-bound particles for injectablesuspension (Abraxane)• For the treatment of non-small cell lung cancer• Approved October 2012• Taxol was the original, approved 1992 forovarian cancer & 1994 for breast cancer; thisversion is albumin-bound, originally approved2005 for metastatic breast cancer• New indication

Bosutinib (Bosulif)• For the treatment of Ph+ chronic myelogenousleukemia• Approved September 2012• Tyrosine kinase inhibitor

Vincristine sulfate liposome injection (Marqibo)• For the treatment of Ph- acute lymphoblasticleukemia• Approved August 2012• Lipid-encapsulated vincristine designed tocirculate in blood longer, accumulate in tumor,be released over longer period of time at tumorsite• Original, Oncovin, approved 1963

Omacetaxine mepesuccinate (Synribo)• For the treatment of chronic or acceleratedphase chronic myeloid leukemia• Approved October 2012• For use in CML resistant/intolerant to two ormore tyrosine kinase inhibitors

Carfilzomib (Kyprolis)• For the treatment of multiple myeloma• Approved July 2012• Selective proteasome inhibitor• Cost is $10,000 for 28-day cycle• Fast-tracked out of Phase 2b trials

Tbo-filgrastim (Neutroval)• For the reduction in the duration of severechemotherapy-induced neutropenia• Approved August 2012• Filgrastim (Neupogen 2009); same indicationsand adverse effects

Fentanyl sublingual spray (Subsys)• For the treatment of breakthrough cancer pain• Approved January of 2012• IV anesthetic Sublimaze (1960s), patchDuragesic (1990s), buccal soluble film Onsolis(2009), lollipop Actiq & buccal tablet Fentora(2011)

• Ibuprofen with itraconazole or terbinafine inDMSO topically for nail fungus• Cimetidine topically for warts• Ketamine, gabapentin, clonidine oramitriptyline with NSAID and guaifenesintopically for neuropathic pain (guaifenesin ismuscle relaxant when used topically)• Phenytoin topically to enhance wound healing

• Atropine, ketoconazole, biotin in vaginalsuppository form for vulvodynia• Carbidopa/chromium/5-HTP in a lollipop forweight loss• Betahistine 8mg bid for tinnitus & vertigo• Dextromethorphan mixed with opioid orally toreduce tolerance

• Low dose naltrexone (1.5-4.5mg) orally forneuropathy, autoimmune diseases,fibromyalgia, autism, PTSD, PCOS• Clonidine for use in hot flashes, migraineheadaches, restless legs syndrome (RLS),attention-deficit/hyperactivity disorder(ADHD), sleep apnea, smoking cessation,Tourette's syndrome, withdrawal from alcoholand narcotics

• Pharmacy Compounding Centers of America(PCCA)• Pharmacy Compounding Accreditation Board(PCAB)• Setting uniform standards of “sound practices,processes, facilities, equipment and personnel”• Not absolutely necessary, but nice

• SSRIs for generalized anxiety disorder,premature ejaculation, migraine headaches,diabetic neuropathy, fibromyalgia,neurocardiogenic syncope• Any SSRI or SNRI (other than Prozac orLexapro) to adolescents• Wellbutrin (bupropion) for weight loss, adultADD/ADHD, RLS/PLMD, sexual dysfunction,bipolar depression, depression of Parkinson’s;Zyban (bupropion) for depression!

• Lamictal (lamotrigine) as monotherapy, or forbipolar II, treatment-resistant bipolar disorder,treatment-resistant depression• Topamax (topiramate) or Trileptal(oxcarbazepine) for bipolar disorder• Neurontin (gabapentin) for bipolar disorder,diabetic neuropathy, complex regional painsyndrome, ADD, RLS, trigeminal neuralgia,periodic limb movement disorder of sleep(PLMD), migraine headaches, alcoholwithdrawal

• Glucophage (metformin) for use in gestationaldiabetes, PCOS, HIV lipodystrophy• Keppra XR (levetiracetam) for migraines,neuropathic pain, bipolar disorder, anxietydisorders, and substance abuse/addictions,seizures associated with traumatic brain injuryand/or tumor• Adderall (dextroamphetamine + amphetamine)for use in depression, “study drug”, appetitesuppressant

1. Re-establish the basis for health2. Stimulate the healing power of nature3. Tonify weakened systems4. Correct structural integrity5. Prescribe specific natural substances for pathology6. Prescribe pharmacological substances for pathologyPharmaceutical intervention to halt or palliate disease process7. Prescribe surgery, suppressive measures, radiation, and chemo

1. Re-establish the basis for health2. Stimulate the healing power of nature3. Tonify weakened systems4. Correct structural integrity5. Prescribe specific natural substances for pathology6. Prescribe pharmacological substances for pathologyPharmaceutical intervention to halt or palliate disease process7. Prescribe surgery, suppressive measures, radiation, and chemo

1. First Do No Harm primum non nocere2. Identify and Treat the Cause tolle causam3. The Healing Power of Nature vis medicatrixnaturae4. Doctor as Teacher docere5. Treat the Whole Person tolle totum6. Prevention/Wellness7. “Don’t tell me what to think!”

• http://www.centerwatch.com/drug-information/fda-approvals/• www.Rxlist.com• http://en.wikipedia.org/wiki/List_of_withdrawn_drugs• http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm319905.htm• http://en.wikipedia.org/wiki/Chloramphenicol• http://www.medicinenet.com/propoxyphene/article.htm• http://www.gibbonslaw.com/UserFiles/Image/1193175381.pdf• http://www.latimes.com/news/nationworld/nation/la-122001fda,0,4840718,full.story• http://www.citizen.org/Page.aspx?pid=2366#rr6• http://articles.mercola.com/sites/articles/archive/2012/02/11/leading-causes-of-death-cost-for-useconomy.aspx• Introduction to Compounded Medication Alternatives, Natalie Gustafson, PharmD; presentation toOANP, June 15, 2010• http://diabetes.emedtv.com/metformin/metformin-uses.html• http://www.crazymeds.us/pmwiki/pmwiki.php/Meds/Keppra-XR• http://www.crazymeds.us/pmwiki/pmwiki.php/Meds/LamictalApprovedAndOffLabelUses• http://consumerreports.org/cro/2012/05/off-label-use-of-clonidine/index.htm• http://www.aafp.org/afp/2003/0801/p498.html• http://www.amcp.org/data/jmcp/contemporary%20subject-559-568.pdf• http://adderall.legalview.com/articles/off-label-use-of-adderall-poses-increasing-threat/173925/• http://www.crazymeds.us/pmwiki/pmwiki.php/Meds/WellbutrinApprovedAndOffLabelUses• http://www.cancer.gov/cancertopics/druginfo/fda-regorafenib• http://www.ncbi.nlm.nih.gov/pubmed/11827562• Manufacturers websites of individual agents• Wikipedia.com• http://www.ahrp.org/cms/content/view/861/56/

Thank YOU!In health,Christie Fleetwood, ND, RPh