Family Medicine Pharmacotherapy Update: What s here and what s coming. Sarah Amering, PharmD, BCACP 4 March 2018

Transcription

1 Family Medicine Pharmacotherapy Update: What s here and what s coming Sarah Amering, PharmD, BCACP 4 March 2018

2 Objectives Provide a brief overview of primary care related new drug approvals in 2017 and select drugs in the pipeline for 2018 Identify current and new medications for the treatment of major depressive disorder Review non-opioid pain pharmacotherapy Discuss the terms brand name drug, generic drug, and biosimilar

3 New Drugs in 2017

4 New Drugs in 2017

5 Steglatro (ertugliflozin) Pharmacologic category Sodium-glucose cotransporter 2 (SGLT2) Inhibitor

6 Steglatro (ertugliflozin) Dosing 5 mg once daily May increase to 15 mg if required ADRs Genital candidiasis (females 9-12%, males 4%) HA, weight loss, urinary frequency, hypoglycemia Warnings Hypotension Ketoacidosis Acute renal injury Drug interactions Caution with sulfonylureas

7 Steglatro (ertugliflozin) VERTIS SU Noninferior to SU + weight loss, bp lowering - Genitourinary infections VERTIS MULTIFACTORIAL Similar to DPP4 A1C lowering (sitagliptin) Superior lowering when combined with DPP4 Diabetes Ther (2018) 9: 193;Diabetes Obes Metab. 2018;1 10

8 Ozempic (semaglutide) GLP-1 receptor agonist

9 Ozempic (semaglutide) Dosing Initial 0.25 mg weekly x 4 weeks, then increase to 0.5 mg weekly. Max dose of 1 mg weekly. ADRs Increase lipase, amylase Nausea Increase HR Warnings Thyroid tumors Drug-drug interactions Antidiabetic agents

10 Ozempic (semaglutide) Efficacy Vs sitagliptin A1C -1.6% vs -0.5% (P< ) Vs exenatide ER A1C -1.5% vs 0.9% (P< ) Vs glargine A1C -1.64% vs -0.83% (P < ) Lancet Diabetes Endocrinol.2017 May;5(5): , Diabetes Care 2017 Dec; dc , Lancet Diabetes Endocrinol.2017 May;5(5):

11 New insulins Insulins Admelog (insulin lispro) Rapid acting insulin Follow-on product Fiasp (insulin aspart) More rapid acting insulin Onset of appearance in bloodstream 2.5 minutes vs 5.2 minutes Peak effect in 1.5 to 2.2 hrs vs 1-3 hrs with Novolog Duration 5-7 hrs vs 3-5 hrs

12 ADHD

13 Mydayis (mixed salts of a single-entity amphetamine)

14 ODTs Adzenys ER (amphetamine) ER ODT ODT extended release Do not substitute mg per mg with other amphetamine products Indicated for 6 and older Cotempla XR-ODT (methylphenidate) ODT dosage form Only approved for ages 6-17

15 Allergy/Asthma/COPD

16 Odactra (house dust mite allergen Indications extract) House dust mite-induced allergic rhinitis confirmed by in vitro testing for IgE antibodies to Dermatophagoides farinae or D. pteronyssinus or skin testing 1 st dose in office Once daily Avoid missed doses

17 Eucrisa (crisaborole) Pharmacologic category: PDE4 inhibitor for atopic dermatitis Indications Atopic dermatitis in patients 2 years Well-tolerated in clinical studies Burning or stinging on application No head to head studies with CCS

18 Trelegy Ellipta (fluticasone/umeclidinium/vilanterol) Pharmacologic category CCS/Anticholinergic/LABA Indications Maintenance in those already receiving LABA/CCS requiring additional treatment FULFIL study Vs budesonide/formoterol Mean change in baseline FEV ml vs -29 ml Reduction in exacerbation rate 35% (95%CI 14-51)

19 Lonhala Magnair (glycopyrrolate) COPD Pharmacologic category Long acting muscarinic antagonist Nebulized solution DPI already exists (Seebri) Via MAGNAIR nebulizer system Portable/battery operated Dosing BID

20 Infectious disease

21 Xepi (ozenoxacin) Pharmacologic category Topical quinolone abx Indications Impetigo in those 2 years old ADRs Post-marketing: rosacealike face eruption, seborrheic dermatitis Cost??? Dosing Apply thin layer twice daily x 5 days

22 Solosec (secnidazole) Pharmacologic category Nitroimidazole antiprotozoal Indications Bacterial vaginosis Dosing 2 gram single dose ADRs HA, Nausea, DH, vulvovaginal candidiasis Drug-drug interactions Live attenuated bacterial vaccines Cost ~$300.00

23 New treatments for Major Depressive Disorder

24 Wagner G, et.al. Efficacy and safety of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants for major depressive disorder in adults: A systematic review and network meta-analysis. Journal of Affective Disorders. 228(2018)1-12.

25 Eligibility criteria Methods Adult population Active comparator or placebo Outcomes Efficacy Harms Minimum duration 6 weeks Double-blinded, RCT Sample 100

26 Results

27 Levomilnacipran No direct comparison studies No statistically significant differences

28 Vilazodone Only one headto-head with citalopram No statistically significant differences

29 Vortioxetine Direct comparison Duloxetine Paroxetine Venlafaxine XR No statistically significant differences

30 Safety analysis Vilazodone Similar rates of ADRs/discontinuations Vs. Citalopram: more diarrhea (26.5% vs 10.6%, RR %CI ) and vomiting (6.6% vs 1.8%, RR 3.76, 95%CI )

31 Safety analysis Vortioxetine vs duloxetine Similar rates of ADRs/discontinuation Less dry mouth (RR 0.40, 95%CI ), decreased appetite (RR %CI ), sexual dysfunction (RR 0.67, 95%CI ), and fatigue (RR 0.44, 95%CI ) Vs paroxetine More nausea (37.5% vs 16.7%, RR 2.25, 95%CI )

32 Discussion No substantial differences However very few direct comparison trials Tailor treatment to the individual

33 Non-opioid options Courtesy: Pixbay

34 Musculoskeletal pain NSAIDs Naproxen, ibuprofen, ketoprofen OTC/Rx Use for short duration (acute flare) Equally efficacious Patient specific

35 NSAID Diclofenac Rx Oral Topical Gel, solution, transdermal patch Systemic absorption from gel: 3-10% of dose Plasma concentration from patch: ng/ml Vs mcg/ml from oral

36 NSAID Celecoxib COX-2 selective Noninferior to IBU and naproxen for cardiovascular safety Meloxicam More COX-2 activity but still COX-1 as well Indomethacin May also affect central serotonergic pathways

37 NSAID ADRs GI ulceration and bleeding Misoprostol or HD PPI reduces GI bleed by 25-75% when used concurrently Reduce GFR Adequate hydration Na and H20 retention -> Increase BP As much as 5-10 mmhg with chronic use

38 NSAID Clinical Pearls Great for musculoskeletal pain But not fibromyalgia pain Monitor renal function Caution in those with uncontrolled HTN Use acutely for short term treatment Concern regarding oxidative stress in joint spaces Cartilage destruction??

39 Neuropathic pain TCAs SNRIs NSRIs Anticonvulsants Gabapentinoid Non-gabapentin-type Vanilloid receptor agonists Cannabinoids

40 TCAs Agents Combined NNT (evidence) for at least 30% pain reduction Common ADRs Comments Amitriptyline, nortriptyline, desipramine 3.6 (95%CI ) Anticholinergic, cardiovascular, mood changes, appetite changes (weight gain), arrhythmia Caution: serotonin syndrome with other agents Suicidality warning

41 SNRIs Agents Combined NNT (evidence) for at least 30% pain reduction Common ADRs Comments Duloxetine Venlafaxine 6.4 (95%CI ) Nausea, dry mouth, HA, drowsiness, fatigue, weakness, abdominal pain, constipation, appetite/weight changes Venlafaxine: sweating, dose-related BP increase Caution: serotonin syndrome with other agents Suicidality warning

42 NSRIs Agents Combined NNT (evidence) for at least 30% pain reduction Common ADRs Comments Milnacipran Presumed similar to SNRIs Dizziness, sweating, palpitations, nausea, increased HR, HTN, migraine, dry mouth Caution: serotonin syndrome with other agents Suicidality warning

43 Agents Anticonvulsants- Gabapentanoid Combined NNT (evidence) for at least 30% pain reduction Common ADRs Comments Gabapentin 6.3 (95% CI ) Pregabalin 7.7 (95%CI ) Dizziness, drowsiness, mood changes, lower extremity edema, weight gain, cognitive slowing, abuse liability Avoid in advanced CHF or renal failure, suicidality warning Pregabalin: risk of addiction

44 Anticonvulsants- Non-gabapentanoid Agents Combined NNT (evidence) for at least 30% pain reduction Common ADRs Comments Carbamazepine Lamotrigine Vigabatrin Small/short studies, not available Dizziness, drowsiness, ataxia, nausea, cognitive slowing, rash, blood cell dyscrasias, SIADH/hyponat remia (CBZ ADRs generally dose related Suicidality warnings

45 Agents Combined NNT (evidence) for at least 30% pain reduction Vanilloid receptor agonists Common ADRs Comments Capsaicin 0.25%- 0.75% topical solution/ cream 8% topical patch Patch: (95%CI ) Localized erythema, local pain or itching, transient hypertension (patch), blisters, nausea (patch), localized swelling, nasal congestion Solution or cream must be applied at least TID for best effectiveness

46 Agents Combined NNT (evidence) for at least 30% pain reduction Cannabinoids Common ADRs Comments Dronabinol Nabilone Medical cannabis Mixed NNT 14 (95%CI, 8-45) (neuropathic pain) Tachycardia, vasodilation, euphoria, dizziness, drowsiness, depersonalization, hallucination, nervousness, abdominal pain, nausea, weakness, abuse liability Paranoia associated with medical cannabis and dronabinol

47 Definitions Brand Example: Neurontin A drug marketed under a proprietary, trademark-protected name Generic Example: Gabapentin A medication created to be the same as an existing approved brand-name drug in dosage form, safety, strength, route of administration, quality and peformance Biosimilar Example: Basaglar (insulin glargine) A biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product

48 Brand name product Have undergone FDA approval via NDA process Center for Drug Evaluation and Research Drug company conducts all research and submits to CDER for review Lengthy and expensive process

49 Generic product Dosage form Strength Route Bioequivalent Active ingredient Indications Kinetics

50 Generic product Exactly the same? Slight variability One study demonstrated 3.5% difference in absorption No more than what occurs between batches of branded products

51 Biosimilar Highly similar No meaningful difference Purity Chemical identity Bioactivity Safety Purity Potency

52 Interchangeable product Met additional requirements Produce same clinical results as reference product No difference when switching between reference product and interchangeable

53 Questions