Where do you get most of your information about medications?

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1 DRUG ACTION AND RLS Jacquelyn Bainbridge, Pharm.D., FCCP Professor Pei Shieen Wong, Pharm.D., BCPS University of Colorado Anschutz Medical Campus, Skaggs School of Pharmacy and Pharmaceutical Sciences, Department of Clinical Pharmacy and Department of Neurology

2 QUESTION Where do you get most of your information about medications? a. Doctor/Physician s Assistant b. Nurse c. Pharmacist d. Internet RLS website e. Family/Friend f. Internet Other websites

3 HOW DRUGS AND THE BODY INTERACT v Pharmacokinetics: What the body does to the drug (liberation, absorption, distribution, metabolism, excretion) v Pharmacodynamics: What the drug does to the body (treats disease, side effects, etc.)

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5 LIBERATION v The release of the drug from its dosage form Extended release formulations release a small amount of the drug over a long period of time

6 ABSORPTION v The movement of a drug into the bloodstream v Drug can be delivered via tablets, patches, injections etc. v Factors that affect absorption: Food, ph, other medications, or disease v Tmax- the time after administration of a drug when the maximum plasma concentration is reached

7 METABOLISM v The chemical conversion of drugs into compounds that are easier to eliminate v Certain organs, such as the liver, possess enzymes that metabolize drugs. These metabolites may be inactive or have a pharmacologic effect of their own v Some medications can cause these enzyme to work more efficiently, therefore eliminating the drug more quickly (enzyme induction) v Others can slow the enzymes down resulting in the drug staying longer in the body (enzyme inhibition)

8 EXCRETION/ELIMINATION v The removal of the substances from the body v Organs involved Kidney, lungs, intestines v Half life- the time required for serum concentrations to decrease by one-half after absorption and distribution are complete

9 HALF-LIFE v It takes approximately 5 half lives to completely remove a drug from the body v Example: 100 mg of Drug X with a half life of 5 hours After 5 hours, 50 mg is left After 10 hours, 25 mg is left After 15 hours, 12.5 mg is left After 20 hours, 6.25 mg is left After 25 hours, mg is left (50% gone) (75% gone) (87.5% gone) (93.75% gone) (96.875% gone)

10 HALF-LIFE

11 STEADY STATE v The situation where the overall intake of a drug is in equilibrium with its elimination v It takes approximately 4-5 half lives to reach steady state

12 HALF-LIFE AND DOSING v Half life is also used to determine how often a drug needs to be taken v Drug X Half life: 5 hours v Want max steady state concentration of 20mg/L and a minimum steady state of 10mg/L v Minimum concentration is ½ of the maximum, which is one half life, due to drug accumulation this medication would most likely be dosed, depending on the drug, every 12 hours (every 2 to 3 half lives) v Usually, medications with a longer half-life are dosed less frequently v Drugs that are designed to be extended release are not interchangeable with immediate release preparations

13 QUESTION Have you been on combination therapy, with a dopamine agonist in conjunction with another drug with a different mechanism of action? a. Yes b. No c. Not sure

14 RLS TREATMENT: DOPAMINERGICS v Requip (ropinirole) 0.25mg daily week 1 (typical starting dose for RLS) and increase to relief of symptoms (max dose 3 mg/daily) v Take 1-3 hours before bedtime (Half life: 6 hrs, Tmax: 1 hr) v Requip XL once-a-day dosage form of ropinirole v Absorption-High fat meal can delay Tmax by 2.5 hours v Metabolized by the liver (interactions) Warfarin-may increase INR Ciprofloxacin-may increase ropinirole exposure Anti-psychotics-decrease effectiveness of anti-psychotic v FDA approved for RLS and both are available as generic

15 DOPAMINERGICS v Mirapex (pramipexole) Generic or Brand name 0.125mg-1.5mg daily for RLS v Take 2-3 hours before bedtime (Half life: 8 hrs, Tmax: IR: 2 hrs, ER: 6 hrs) v Mirapex ER - considered for severe RLS, given once daily v Absorption- Food can delay Tmax by 1-2 hours v Dose adjustments in those with kidney problems v FDA approved for RLS

16 DOPAMINERGICS v Sinemet (carbidopa/levodopa) 25/100mg IR given 30 to 60 minutes before bedtime and may repeat once (if awaken within 2 hours) 50/200mg CR 1-2 tabs 1 hour before bedtime v Controlled Release (CR) may be best in RLS Half life: 1-2 hrs, Tmax: IR: 30 min, CR: 2 hrs v Absorption- Food can delay/reduce absorption Can take with low protein snack to avoid GI issues v Metabolism- Liver Numerous drug interactions. Consult with a pharmacist before starting. v Not FDA approved for RLS

17 DOPAMINERGICS v Neupro Patch (Rotigotine) 1-3mg daily for RLS Patch size 5,10,15 cm 2 v Half life: 5-7 hours, Tmax: hrs, detected in the serum at 3 hrs v Drug is slowly released throughout the day v Absorption- Food has no effect v No dose adjustments for liver/kidney problems v FDA approved for RLS

18 Non-Dopaminergics NEURONTIN (GABAPENTIN) v mg before bedtime (half life: 5-7 hrs, Tmax: 2hrs) Can add morning and afternoon doses v Absorption- Food can increase rate/extent of absorption Avoid taking with antacids (separate by 2 hours) v Dose adjustments in those with kidney problems v Naproxen may reduce effectiveness v Not FDA approved for RLS

19 Non-Dopaminergics HORIZANT (GABAPENTIN ENACARBIL) v Prodrug of gabapentin v Extended release tablet designed to last 24 hours v Moderate to severe primary RLS 600 mg once daily with food at 5PM (terminal half life 5-6 hours of gabapentin) 1200 mg had no additional benefit v Not interchangeable with other gabapentin products v Absorption- Food can delay the time to maximum blood concentration and increase amount of drug available to the body Tmax: 7 hrs v Dose adjustments in those with kidney problems v FDA approved for RLS

20 Non-Dopaminergics LYRICA (PREGABALIN) v mg min before bedtime v > mg divided at 2 pm and before bedtime (Half life: 6 hrs, Tmax: 1.5hrs) v Absorption- Food can increase Tmax to 3 hrs Avoid taking with antacids (separate by 2 hours) v Dose adjustments in those with kidney problems v Naproxen may reduce effectiveness v Not FDA approved for RLS

21 Non-Dopaminergics TEGRETOL/CARBATROL (CARBAMAZEPINE) v 600-1,500 mg a day (divided into 2 or 3 doses) (Half life: 2-9 hrs, Tmax: 3-13hrs) v Absorption- Food has no effect v Metabolism- Liver Numerous drug interactions. Consult with a pharmacist before starting Induces its own metabolism therefore the dose is increased gradually v Dose adjustments in kidney disease v Not FDA approved for RLS v Additionally opioids are listed in the guidelines

22 AUGMENTATION v Main complication of long-term dopaminergic treatment of RLS Sinemet, Mirapex, Requip Neupro patch lower rate of augmentation Case reports of occurrence with tramadol v Defined as worsening of RLS symptoms that occurs after starting a medication to treat RLS v Generally occurs within the first six months of starting therapy v Symptoms occur earlier in the day, at least two hours earlier than prior to the initiation of drug therapy v Temporal relationship exists between: daily medication symptom intensity daily medication symptom intensity v Sensations spread to previously uninvolved parts of the body v RLS symptoms while awake occur for the first time or are worse than before

23 AUGMENTATION TREATMENT v First consider/remove other factors Example: changes in lifestyle, iron deficiency, v Adjusting the timing or dose v Switching to a different medication class v Drug holiday v Combination of agents with different mechanisms of action

24 QUESTION If you have taken Neupro, was it prior to the product withdrawal/reformulation? a. Yes b. No c. Not sure

25 NEUPRO PATCH (ROTIGOTINE) v 1-3mg patch once daily 1 mg patch: 1 inch in diameter (2.25 cm) 2mg patch : 1 ¼ inches (3.15 cm) 3 mg patch : 1 ½ inches (3.85 cm) v Rotate site each day to avoid irritation Don t use same site for 14 days

26 NEUPRO PATCH (ROTIGOTINE) v Precautions Apply to clean, dry, healthy skin (do not apply to red, irritated, or injured skin) Do not place patch underneath tight clothing or waistband If you need to shave the area - do so 3 days prior Avoid creams, lotions, ointments, oils and powders to the skin area where the patch will be placed v Warnings Sulfite sensitivity not sulfonamide or sulfate sensitivity Seen more frequently in asthma patients

27 NEUPRO PATCH (ROTIGOTINE) v Open the pouch and pull the patch out v Hold it with protective liner on top v Bend the edges away from you to open up the s shaped cut v Pull off half of the protective liner v DO NOT touch the sticky side

28 NEUPRO PATCH (ROTIGOTINE) v Apply to the chosen area v PRESS firmly for 30 seconds with your hand (you need the heat from you hand to activate the adhesive) v DO NOT use any other heat sources (ie., hair dryer) v Wash your hands with soap and water after handling the patch v Do not touch your eyes before washing your hands v Dispose of the patch by folding the sticky side inwards before discarding in the trash v Keep the medication away from children or pets

29 NEUPRO PATCH (ROTIGOTINE) v Commercial Plans - Tier 3, unrestricted v Medicare Part D will require a prior authorization Prior authorization may not be required in the future v Medicaid-varies by each state CO/UT-$3 v Copay card available at Will cover up to $65 resulting in a copay of $10 for most commercial plans Also can be used for cash paying customers ($65 savings) Good for 12 months v This information changes on a regular basis and may vary by state

30 NEUPRO PATCH (ROTIGOTINE) v Patient Assistance Program Provide Neupro to qualifying patients at a reduced price Government-funded insurance programs are excluded from this patient assistance Program will begin Monday August 6 th

31 QUESTION If you have taken any medication via patch (for pain, or nicotine cessation, etc.) did you have any of the following: a. Skin REACTION due to the medication b. Skin IRRITATION due to the patch/ adhesive

32 CONCLUSION v RLS is a common, under diagnosed treatable condition that can have significant negative effects on quality of life v Medications for RLS should be taken as prescribed and follow the pattern of the symptoms v Drug interactions can occur with prescription and over the counter medications v Always talk to your health care practitioner and pharmacist about all the medications you are taking or have question about

33 Q & A DRUG ACTIONS AND RLS Webinar Series 2015 RESTLESS LEGS SYNDROME FOUNDATION 3006 Bee Caves Rd. Suite D206 Austin, TX (512) info@rls.org