Innovative Management of Pain Through Compounding. Shawn Needham R.Ph.

Innovative Management of Pain Through Compounding Shawn Needham R.Ph.

Disclosure Shawn Needham is a compounding pharmacist and does have interest in a compounding pharmacy Compounded pharmaceuticals are not FDA approved

Objectives Discuss the benefits of topically applied medications for pain to treat neuropathy Discuss the role of Low Dose Naltrexone (LDN) to help patients stay off opioids Discuss options for treating opioid induced constipation

What is compounding Mixing of ingredients (medications)for a specific patient, based on a prescription. Involves the Triad relationship; prescriber, patient, and pharmacist. Drug manufactures do not have this advantage. Pharmacists have compounded for over 3000 years. Drug companies have been established for a little of 100 years. Compounding pharmacists solve unique problems for prescribers that drug companies cannot.

Low Dose Naltrexone (LDN) Synthesized in 1963 Within a certain dosage window opioid antagonists like LDN can exert a paradoxical analgesic effect Mono therapy with out opioids, ultra low dose has been used in conjunction with opioids Similar to Naloxone but absorbed better orally and a longer half life

LDN History Naltrexone was FDA approved in 1984 to treat opioid addiction and alcohol withdrawal 50-100mg LDN is typically 1/10 that dose Most common dose 4.5mg At lower doses exhibit an anti-inflammatory effect which have not been reported at higher doses

LDN How it Works? Competitive antagonist at opioid receptor Immune modulation via the opioid receptor Opioid induced hyperanalgesia Paradoxical response to opiods causes? NMDA receptor, upregulation of receptors? Exact mechanism unknown but theory is opposite of hyperanalgesia caused by opioids Glial cells- When activated causes inflammatory response in brain (cytokines). Contributes to maintenance of persistent pain LDN may be a glial cell modulator, works as antiinflammatory independent of opioid receptor

LDN in Chronic Pain Fibromyalgia- Does not commonly respond to typical anti-inflammatories yet there may be an inflammatory component. Double blind study showed 57% of patients exhibited 1/3 rd less pain with 4.5mg LDN nightly

LDN How does it Work? Blocks glial cells which activate inflammation Dextro-naltrexone the stereo isomer has no effect on opioid receptor yet posses antiinflammatory properties Erythrocyte Sedmentation Rate (ESR)- Patients with elevated ESR tend to respond better to LDN, LDN does not lower ESR though

LDN other mechanisms Blocking opioid receptor Small and transient opioid blockage causes upregulation of endogenous opioids and down regulation of opioid receptors Opioid rebound effect can enhance endogenous analgesia

LDN dosing 0.5mg po qhs increase by 0.5mg weekly until effect or side effects- vivid dream or sleep disturbances Not SR capsule- must be immediate release Most common dose is 4.5mg Do not use in patients taking opioids- withdrawal Side effect insomnia, use lower dose

Why Low Doses? Complete opioid blockage would have a negative outcome for chronic pain? Paradoxical hyper analgesia effect of low dose morphine Dose is 1/10 th of typical dose use to produce analgesia Dose of naltrexone is 1/10 th of dose to treat substance abuse

LDN 50mg dosage available commercially FDA approved to treat substance abuse Pharmaceutical company looking for approval of 4.5mg dosage Many patients obtain 50mg tablet and divide it up into 10 doses

LDN.. Accuracy of dosing Convenience Not one size fits all Compounded capsule Cost varies by region $35 per month Much less than many other treatments for chronic pain

LDN.. Low side effects No ulcers, renal insufficiency, heart attacks or clotting factors, seen with NSAIDS No withdrawal symptoms

LDN Vivid dreams, dose related and immediate, better over time Headaches, withdrawal? Tachycardia, withdrawal? Anxiety, withdrawal? No liver toxicity, even at higher doses No abuse potential!!!

LDN other diseases of inflammation Chrohn s 80% success rate Multiple Sclerosis

LDN

LDN Conference 2018 July 7 th Glasgow University, Live stream available www.ldnresearchtrust.org

Why Use Topical Pain Medications? High concentration in affected area Lower systemic drug levels ie side effects Less potential for drug to drug interactions Easier to titrate without side effects Less potential for abuse- Non narcotic Ketamine is a controlled substance

Percutaneous Absorption Physiochemical factors Solubility Particle size Partition coefficient Lipid content Dermal factors Hydradation Site of application Pathological

Dermal Factors Hydration increases absorption Lipid content is important for lipid soluble compounds- Lipid content in the strateum corneum is inversely proportional to age Site of application- behind ear, genitilia, forehead and scalp better for systemic absorption Local effects apply to fatty areas to act as depot Pathological factors- burn patients, non-intact skin

What We Can Control Hydration- Well hydrated, after showering Site of application systemic effects or local effects? Penetration enhancers ie DMSO, Occlussion, solubilized Particle size- Mixed with appropriate technique

Ingredients in Compounded Topicals Gabapentin Sodium channel blocker 6-10% apply tid Ketoprofen Nsaid 10-20% apply tid

Ingredients continued Dexamethasone Corticosteroid use short term only 0.2% apply tid Morphine sulfate Mu Agonist 10-30mg q4 hours

Ketamine Ingredients continued NMDA Ca Channel receptor blocker 10% apply tid Capsacian Inhibits substance p 0.025-2% apply tid- start low, burns, 14 days Amitriptyline Norepinephrine and serotonin reuptake inhibitor 2-10% apply tid

How to Start Sometimes multiple ingredients needed targeted for different types of pain Ie inflammation equals NSAID Neuropathy equals gabapentin Each therapy should be titrated to maximum dose Many pain gels were compounded to maximize insurance billing, not because the ingredient was necessary

Where to Apply Location of pain Site of original injury Dermatome Trigger point locations Combination of sites

Dermatomes

Trigger Points

Patient EH Case Study Football player with right knee pain after an acute injury. After examination, physician decides to start transdermal therapy. Start with Ketoprofen 10% and dexamethasone 0.2% transdermal gel apply a pea sized amount to affected area 3-4 times daily for a maximum of 3 weeks

Pain is better Follow up 2 weeks Continue therapy for another week Prescribe ketoprofen 10% transdermal gel to start using in one week

Patient MJ 42 yo female with cyclical migraines HRT therapy may help History of car accident causing neck and shoulder pain Is migraine caused by other source of pain? Start Ketoprofen/Gabapentin 10/6% gel apply pea sized amount 3-4 times daily to affected shoulder and neck area

Follow up Patient follow up 2 weeks later, symptoms better but not completely resolved Increase ketoprofen to 20% and add lidocaine 2% Other options add Ketamine, use magnesium topical for a muscle relaxant.

Patient JN Bone cancer with mets to liver, hospice patient Difficulty in swallowing Injections cause pain, anxiety Feeling aches and pains in joints and all over Start Neurocam (Ketoprofen, piroxicam, amitriptyline, baclofen, cyclobenzaprine and gabapentin) Apply a pea sized amount to areas of pain 3-4 times daily

Patient MC 56 yo male with diabetes and diabetic neuropathy in feet Start Gabapentin 6% gel Apply to affected areas of feet 2-3 times daily Patient follow up in 2 weeks reports symptoms better but not resolved increase gabapentin to 10% Add nifedipine 0.2%

Patient NM 49yo Female with recent diagnosis of fibromylagia Cycles are becoming more irregular Gained 15 pounds over last year, mostly around the middle Hair is thinning, Decreased libido, Decreased energy Depression, recently started citalopram Recent diagnosis of high cholesterol, started atorvastatin Feeling aches and pains especially around neck and shoulder area Check hormones!! Start Ketoprofen/gabapentin 10/6%, apply to shoulder and neck area 3-4 times daily Patient is currently taking levothyroxine 0.1mg tablet Hormone levels come back, testosterone level 17 (15-70), TSH 2.9(2-5), Free T4 1.5 (0.7-2)and Free T3 2.5 (2.3-4.5)

Patient NM cont. Free level testosterone 0.1 (0.2-5) Testosterone is not just for men Total testosterone vs Free testosterone Low thyroid and testosterone levels mimic each other TSH vs Free T3 vs T4 Treatment: Testosterone 2mg topical cream apply once daily Add T3(Liothyronine) SR 15mcg capsule po qam Recheck Free Testosterone, Free T3, Free T4 and TSH in 8 weeks Dhea? Supports adrenal function, converts to testosterone Progesterone? Helps support sleep, normalize cortisol, night sweats

Patient NM cont. 8 weeks later, Free Testosterone 5.1, Free T3 4.6, Free T4 1.5, TSH 0.25 No symptoms of high testosterone ie oily skin or acne No symptoms of hyperthyroid Timing of dose? Half life? Feels much better- increased libido, cholesterol is lower, pain levels are decreased, losing weight, more energy Stop atorvastatin? Causing pain and fatique? Stop citalopram? Causing decreased libido? Treat problems not symptoms Order correct labs and interpret appropriately, optimal levels Treat patient, not lab levels

Naloxone use for opioid induced constipation (OIC) Opioid receptor antagonist like naltrexone Not absorbed orally Has been combined with commercially available products to avoid abuse (injection/inhalation) and to treat OIC Blocks affects of mu receptors in gut to decrease constipation side effect without being absorbed systemically to prevent relief of pain Hospice has used for years Commercially available analogs are $$$$$$, not covered by insurance, high tier copays

Naloxone use for opioid induced constipation (OIC) dosing.. Starting dose is 2mg qhs in an SR capsule May need to increase BID or 4mg qhs depending on GI transit time Monitor for effects of opioid withdrawal- rare, higher doses?