7/13/16 DISCLOSURE OBJECTIVES THINKING OUTSIDE THE BOX: NON-OPIATE PAIN MEDICATIONS AND CUSTOMIZED MEDICATION OPTIONS

Transcription

1 THINKING OUTSIDE THE BOX: NON-OPIATE PAIN MEDICATIONS AND CUSTOMIZED MEDICATION OPTIONS Dawn Ipsen, PharmD, Owner Kusler s Compounding Pharmacy Snohomish, WA dawn@kuslers.com AANP Annual Convention July 27, 2016 DISCLOSURE Compounded medications are off-label uses of FDA-approved drugs. No financial conflict of interest exists. OBJECTIVES What is pain? Types of pain and pain assessment Background behind compounded medication recommendations Topical vs. Transdermal Categories of medications to consider Treatment approach techniques Patient case example 1

2 WHAT IS PAIN? McCaffery 1968 Whatever the experiencing person says it is, existing whenever she/he says it does. Subjective International Association for the Study of Pain Unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. Complex and multi-dimensional TYPES OF PAIN Acute Pain Alarm system, useful pain Short term, self-limiting Response to tissue trauma Resolves with healing and goal is to cure Nociceptive (may be neuropathic) May become chronic TYPES OF PAIN Chronic Pain Often 3-6 months or greater Pain extending past healing; cause not present Multi-dimensional; insomnia is common component Nociceptive, neuropathic, or both Goal is to rehabilitate and improve quality of life 2

3 NOCICEPTIVE PAIN Peripheral transduction from receptors Release inflammatory mediators Examples: burns, cuts, arthritis, tendonitis, appendicitis, post-op, pancreatitis, mechanical low back Sharp, pricking, burning, dull, aching, cramping NEUROPATHIC PAIN Nervous system injury or impairment Effecting signal processing Pain that serves no purpose Examples: neuropathy, phantom limb, trigeminal neuralgia, complex regional pain syndrome (CRPS) Burning, tingling, prickling, shooting, jabbing, electric shock-like, squeezing, deep aching, spasm, cold NAME THAT PAIN 42yo male presents to your clinic with pain that is described as burning, sharp and shooting pain that radiates from his low back and down his right leg. This started 6 months ago as the result of an overly aggressive basketball game. 1. Acute or Chronic? 2. Nociceptive, Neuropathic or Both? 3

4 PAIN ASSESSMENT Pain assessment: P (provokes), Q (quality), R (radiates), S (severity), T (timeline) Pain scale: Active and at Rest PAIN ASSESSMENT Dermatome mapping show me where you hurt ASSESSMENT QUIZ True or False: It is important to assess both pain at rest and pain while active when quantifying the level of pain a person may be experiencing. 4

5 TRANSDERMAL VS. TOPICAL Topical Penetration into the skin only Superficial or localized effect Minimal systemic effects Creams, lotions, gels, ointments, liquid spray, etc. powder spray, troche, medicated lollipop, mouthwash, enema CUSTOMIZED TRANSDERMAL OPTIONS Transdermal Penetration of drug(s) through the skin into the systemic circulation Bypass 1 st -pass effect Local peripheral action Ability to combine multiple MOA in 1 delivery Less adverse effects than oral medications Lipoderm TM, Pluronic Lecithin Organogel (PLO), VanPen TM, Anhydrous Gels DRUG CATEGORIES TO CONSIDER NSAID s Muscle relaxants Anticonvulsants Tricyclic antidepressants Anesthetics Alpha-2 agonist 5

6 NSAID S Diclofenac, Ketoprofen, Piroxicam, Flurbiprofen, Ibuprofen, etc. MOA: Inhibit all cyclooxygenase (COX) activity Reduces production of prostaglandins Indications: Nociceptive pain Acute inflammation NSAID S Ibuprofen mg po Q4-6H prn; max 1200mg/day for 10 days unless directed by prescriber Diclofenac potassium 25-50mg po TID; max mg/day Piroxicam 20mg/day po as single dose or divided Side effects: Hypertention; gastrointestinal bleeding and ulcers; liver toxicity; hearing loss; worsening of asthma; rash; SJS NSAID S Evidence for Transdermal Application: Diclofenac commercially available topically Several transdermal NSAID s licensed in UK Diclofenac, ibuprofen, ketoprofen, piroxicam Ketoprofen and diclofenac have the most evidence NSAID s commonly used for peripheral analgesia by decreasing inflammation (Merry, et al. 1995) Ibuprofen can increase the absorption of other drugs ionic surfactant (J Control Release 2004 Nov 24) 6

7 NSAID S Evidence for Transdermal Application Somberg JC, Molnar J. American Journal of Therapeutics. 2015(22): A retrospective study of 2,177 patients in 3 groups Cream I: Flurbiprofen 20%, Tramadol 5%, Clonidine 0.2%, Cyclobenzaprine 4%, Bupivicaine 3% Cream II: Flurbiprofen 20%, Baclofen 2%, Clonidine 0.2%, Gabapentin 10%, Lidocaine 5% Voltaren gel Pain decreased by 35%-37% vs. 19% Voltaren gel Adverse effects <2% for both compounded creams MUSCLE RELAXANTS Baclofen, Cyclobenzaprine, Guaifenesin MOA: Baclofen Gaba-b receptor agonist; muscle relaxant and anti-spastic properties Cyclobenzaprine Structurally related to TCA s Indications: Trigeminal neuralgia Nociceptive pain Fibromyalgia MUSCLE RELAXANTS Baclofen: For spasticity 5mg po TID; may increase by 15mg/day q3 days; max 80mg/day (divided) Cyclobenzaprine: For muscle spasm 5mg po TID; may increase to 10mg po TID for up to 2-3 weeks Side effects: Drowsiness; constipation; nausea; dry mouth; dizziness; cardiac changes; edema; abnormal liver function 7

8 MUSCLE RELAXANTS Evidence: Barton, et al Adjunct with carbamazepine and phenytoin for TMJ (Baker, et al. 1985) ANTICONVULSANTS Gabapentin, Carbamazepine MOA: Gabapentin block glutamate (NMDA calcium channel) Carbamazepine - Block sodium channels AMPA Effects GABA ANTICONVULSANTS Indications: 1 st line for neuropathic pain Post-herpetic neuralgia Diabetic peripheral neuropathy Trigeminal neuralgia Mixed neuropathic pain Phantom limb Spinal cord injury Combo therapy only? 8

9 ANTICONVULSANTS Evidence for transdermal application 2014 retrospective study of Gabapentin 6% in 23 patients. 20/23 benefited from topical 11/23 clinically meaningful pain reduction (>30%) 2008 retrospective study Gabapentin 2%-6% cream in 35 women with vulvodynia. Pain scores decreased by average 4.77 points 80% demonstrated at least 50% improvement in pain scores. ANTICONVULSANTS Gabapentin 300mg day 1, 300mg BID day 2, 300mg TID day 3; may increase to 1,800mg/day (divided TID) Carbamazepine 100mg BID day 1, may increase by 100mg q12h prn pain control; max 1,200mg/day ANTICONVULSANTS Side effects: Gabapentin: Peripheral edema, nausea/vomiting, viral illness, ataxia, dizziness, nystagmus, somnolence, hostile behavior, fatigue, fever, SJS Carbamazepine: Hypotention, pruritus, rash, constipation, nausea/vomiting, xerostomia, asthenia, ataxia, dizziness, somnolence, blurred vision, nystagmus, AV block, CHF, SJS, metabolic imbalance, bone marrow depression, liver toxicity, angioedema 9

10 TRICYCLIC ANTIDEPRESSANTS Amitriptyline, Desipramine and others MOA: Blocks re-uptake of norepinephrine & serotonin Effects on NMDA receptors, glutamate, sodium, potassium, calcium channels Indications: Peripheral diabetic neuropathy Post herpetic neuralgia Headache Facial pain Myofacial pain TRICYCLIC ANTIDEPRESSANTS Amitriptyline: 10-25mg po HS; may increase weekly to max mg/day Desipramine: mg/day po (single or divided doses) Nortriptyline: 25mg po TID-QID or single daily dose; max 150mg/day Side effects: Sedation; Weight gain; constipation; dry mouth; dizziness; headache; blurred vision; EKG changes; Liver toxicity; depression TRICYCLIC ANTIDEPRESSANTS Tricyclic and tetracyclic antidepressants (TCAs) Insomnia/ Orthostatic QTc Gastrointestinal Sexual dysfunction Drug Anticholinergic Drowsiness Agitation hypotension prolongation* toxicity Weight gain 1+ (all TCAs see ) Amitriptyline to 4+ Amoxapine ND Clomipramine Desipramine ND Doxepin Imipramine Maprotiline ND Nortriptyline ND Protriptyline to 4+ Trimipramine ND Gastrointestinal forms of anticholinergic side effects include: dry mouth, constipation, epigastric distress, decreased esophagogastric tone. Refer to "Anticholinergic" data for frequency rankings. * Risk of QTc prolongation or torsades de pointes is also elevated with advanced age, female sex, heart disease, congenital long QT syndrome, hypokalemia or hypomagnesemia, elevated serum drug concentrations (eg, drug overdose, interacting drugs, organ failure) and combination of drugs with QTc prolonging effects. Refer to topic on acquired long QT syndrome. Up To Date;

11 TRICYCLIC ANTIDEPRESSANTS Evidence for Transdermal Application: Retrospective study Somberg JC, Molnar J, et al. American Journal of Therapeutics 2015(22): Amitriptyline 4%, Baclofen 2%, Bupivicaine 2%, Clonidine 0.2%, Gabapentin 6%, Ketamine 10%, Pentoxifylline, Tranilast +/- Nifedipine 2% in Topical Cream 208 patients Reduction in pain scores 35%-40% Excellent or good effect reported 70%-82% Reduction in oral pain medications 35% Avoidance of pain specialist referral 53% TRICYCLIC ANTIDEPRESSANTS Evidence for Transdermal Application: A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA Barton DL, Wos EJ, et al. Support Care Cancer 2011(19): Amitriptyline 4%, Baclofen 1%, Ketamine 2% in PLO vs. placebo up to 4gm BID 208 patients Well tolerated and no detectable blood levels Statistically significant improvement in neuropathy TRICYCLIC ANTIDEPRESSANTS Evidence for Transdermal Application: Topical amitriptyline, ketamine, and lidocaine in neuropathic pain caused by radiation skin reaction: a pilot study Uzaraga I, Gerbis B, et al. Support Care Cancer 2012 (20): Prospective, single-arm, cohort pilot study Compliance and effects 4ml of AKL in PLO TID through treatment Significantly reduced pain, both short and long term 11

12 TRICYCLIC ANTIDEPRESSANTS Evidence for Transdermal Application: Topical amitriptyline and ketamine in neuropathic pain syndromes: and open label study Lynch ME, Clark AJ, et al. The Journal of Pain, Vol. 6, No 10 (October), 2005: study subjects Amitriptyline 2% / Ketamine 1% in proprietary base Up to 4ml TID Decreased pain scores at 6 months (34%) and 12 months (37%) Minimal adverse effects and minimal systemic absorption ANESTHETICS Lidocaine, Tetracaine, Benzocaine, Bupivacaine, Prilocaine, others MOA: Decreased ionic flux through nerve membrane Stabilizing nerve cell membrane potential Blocks initiation and conduction of nerve impulse Indications: Post herpetic neuralgia Diabetic neuralgia Burn Generalized pain ANESTHETICS Lidocaine 5% extended release topical patch Apply up to 3 patches topically at one time, for up to 12 hours within a 24-hour period. Usually only 1 patch applied at a time. Side effects: Hypotension; nausea; cardiac arrest; cardiac dysrhythmia 12

13 ANESTHETICS Evidence for Transdermal Application: Commercially available as patch Uzarage, et al study Lidocaine absorption study dependent on concentration, time of application, salt vs. base, and solvents used (Akerman, et al. 1979) The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized double-blind, vehicle-controlled, 3-week efficacy study with use of the neuropathic pain scale. Galer BS, et al. Clin J Pain 2002(18): ALPHA-2 AGONIST Clonidine MOA: Reduces sympathetic CNS outflow Inhibit glutamate Inhibit substance P Activate serotonin ALPHA-2 AGONIST Indications: Neuropathic pain Synergistic with other agents Prevent NMDA antagonist problems Hyperalgesia CRPS diagnosis Evidence for Transdermal Application: Following nerve injury, sympathetic stimulation can excite primary afferent fibers via alpha-adrenoceptors (McLachlan, et al. 1993) 13

14 ALPHA-2 AGONIST Evidence for Transdermal Application: Randomized control trial of topical clonidine for treatment of painful diabetic neuropathy. Campbell CM, Kipnes MS, et al. Pain Sep; 153(9): Randomized, double-blind, placebo-controlled, parallelgroup, multicenter Nociceptive response tested 0.1% clonidine gel vs. placebo TID x 12 weeks Significantly reduced foot pain in patients with functional nociceptive response. EVIDENCE BASED MEDICINE PLEASE Which of the following lists of medications appear to have some, if limited, evidence based medicine supporting their use as a possible transdermal treatment for pain? A) Cyclobenzaprine, baclofen B) Gabapentin, amitriptyline, clonidine C) None of the above D) All of the above TREATMENT APPROACH Acute vs. Chronic Look closely at oral (traditional) therapies both current and past Analyze current medication and supplement list Lifestyle and Supplement considerations Look for 3+ different MOA s for best results with compounded transdermal therapies Patient counseling Fair expectations Proper application and dosing Who, What, When, Where, How and Why 14

15 DERMATOMES Helpful for medication application Apply where it hurts? Where is the source or cause of the pain? PAIN A COMPLICATED MATTER bending treatment worried burning lasts aches day bothering Shooting stabbing medicine dull feels sleep pain radiating Gets worse when stiffness cramping walking working gnawing sharp sciatic head knees better support pulsating PATIENT CASE EXAMPLE 49 yo female referred by local pain specialist MD for pharmacy consult Fell off foot ladder 3 years prior Shattered right heel and ankle extending up into tibia and fibula 3 surgeries since injury No work, no hobbies, can t drive longer than 1 hr. 15

16 PATIENT CASE EXAMPLE Aggravators: standing, walking, weight bearing pressure Alleviators: include elevation and rest Allergies: sulfa s, oxycodone, codeine, hydrocodone Concomitant medical conditions: depression, anxiety, fibromyalgia PATIENT CASE EXAMPLE (CONT.) Medications, supplements, over-thecounters, etc. Sertraline 100mg tid Bupropion SR 150mg bid Atenolol 25mg am Clonazepam 0.5mg bid Gabapentin 600mg tid Baclofen prn Methocarbamol prn Multivitamin Omega fish oil Chromium picolonate B complex Calcium Acacia berry Vitamin D 20,000IU daily OTC s creams and medications barely help Arnica gel is useful Medical Marijuana helps PATIENT CASE EXAMPLE (CONT.) Pain scores: Active: 7-9 (primarily 7); Rest: 5-6 Subjective description: Stiff, painful, freezing cold areas and burning areas, falls asleep, nerve firing, intense dull pain, burning, bone-on-bone grinding, pressure pain on heel, shoots up leg, arthritic 16

17 PATIENT CASE QUESTIONS Acute or chronic? Nociceptive, neuropathic or both? Medications for transdermal therapy to consider? PATIENT CASE EXAMPLE (CONT.) Plan: Ketoprofen 10%, Gabapentin 10%, Amitriptyline 2%, Baclofen 2% in Lipoderm cream 1-2 pumps to affected area 3-4 times daily. PATIENT CASE EXAMPLE (CONT.) 1 week pharmacist follow-up: Dizzy/floating feeling first couple doses Settled at 1 pump BID 40% reduction of pain during activity 80% reduction of pain during rest Her quality of life and daily activities have greatly improved!! Patient is very pleased with outcome! 17

18 SUMMARY THOUGHTS Improving lives one patient at a time Be a patient advocate Listen to what patients have to say Know what is important to your patient What are their pains, what are their joys This is their journey and you can have a positive impact along the way! THANK YOU! Dawn Ipsen, PharmD Kusler s Compounding Pharmacy 700 Avenue D, Suite 102 Snohomish, WA (360) dawn@kuslers.com 18