Multiple Sclerosis ABC R Avonex 1 Betasteron 1 Copaxone glatiramer acetate Rebif 1 Name Interferon 1 Betaseron Extavia Interferon 1 Avonex Interferon 1 Rebif Efficacy Dose 250 mcg 8 mil international units SC every other day DOES NOT require refrigeration TITRATION Starting dose 0 0625 mg 62 5 g Starting dose week 1 2 increase by 25 every 2 weeks Ending dose Week 7 0 25 mg Dose 30 mcg 6mil IU IM once weekly Available as 0 5 mL 4 per package Refrigerate RT for 7 days Dose 22 or 44 mcg SQ 3 x weekly Refrigerate room temperature for 30 days Administration Step 1 attach vial to needle Step 2 attach needle vial to syringe Step 3 push in plunger Step 4 pull back plunger to take in proper dose Step 5 remove vial from needle syringe and inject SC Hand weakness may make admin difficult Autoinjector A needle depth adjuster to let you know how deeply the needle will go under your skin important for people with less body fat one step loading so you don t have to unscrew the plunger from the needle A non slip rubber grip and a side release button for added control a visual signal to let you know that your injection is complete A safety feature so the Rebiject II cannot be activated until it is pressed against your skin and the release button is pressed Interferon 1 vs 1 does NOT appear to be a difference in clinical efficacy 1 has idential AA sequence of a natural compound and is glycosylated may lead to stability and higher biological potency weekly dosing less injection site reactions MOA in MS unknown Development of neutralizing antibodies nABs frequency 1 1 clinical effect unclear May develop AXB against agent switch to another interferon Another agent Gray area But if s sx switch tx MOA cytokines mediate antiviral antiproliferative immunomodulatory activities ALL Interferons Warnings ADE Warnings Liver dysfunction severe leucopenia thrombocytopenia pregnancy lactation not for use during rate in relapse during 3rd trimester but rate post partum severe depression also a 3 s sx of MS ADE injection site redness swelling flu like symptoms Advil non daily Tylenol L dysfunction Less common tachycardia depression thyroid dysfunction necrosis rare Monitoring Counseling points Baseline Blood counts Inj technique Body temperature of agent Platelets LFTs At 1 month then q 3 months for 1 year then every 6 months thereafter will inj Site reactions Inj site irritation rotate site apply cold packs before after hydrocortisone cream long term use skin thinning Flu like symptoms APA NSAIDs before after inj last 24 hours transient 1 3 months taper to full dose over 1 2 months Drug MOA Dose Storage ADE Place in therapy 1 Glatiramer Acetate Copaxone ABC R Review Mimics myelin basic protein 20 mg SC injection daily REFRIGERATE RT up to 10 transient chest tightness flushing and dyspnea angina 1 week s sx avoid in CAD angina CHF not CI but needs CLOSE monitoring MI angina attack or copaxone ADE Rebif interferon beta 1a Avonex interferon beta 1a Under the skin 3 times per week Into the muscle Once per week Betaseron interferon Copaxone glatiramer beta 1b Under the skin Every other day Extavia interferon beta 1b Under the skin Every other day acetate Under the skin Every day Route of injection Dosing frequency Number of injections per year Prefilled preassembled syringes Auto injector available Storage 156 YES OR 52 YES OR YES YES Store in refrigerator NO Store in refrigerator at room temp up to 30 days at room temp up to 7 days Store at room temp OR refrigerate and use within 3 hours if already reconstituted YES Store at room temp OR refrigerate and use within 3 hours if already reconstituted YES Store in refrigerator at room temp up to 1 week Protect from Light YES NO NO 182 NO YES 182 NO 365 YES OR YES 2 Drug Natalizumab Tysabri Dose 300 mg IV infusion q4 weeks Place in Therapy Patients with inadequate response unable to tolerate other MS therapy greater relapse reduction vs interferons 12mg m2 administered as brief 5 15 min infusion q3m MAX lifetime does 140mg m2 Patients with worsening relapse disease Patients with worsening SPMS whether or not relapses are occurring 0 5 mg PO once First ORAL therapy for daily relapsing MS MOA Attaches to VLA 1 and blocks activated lymphocytes from crossing BBB Anthracenedione family Induces DNA cross links and strand breaks leading to apoptosis immunomodulator blocks lymphocyte capacity to egress from lymph nodes reduces the lymphocyte count in peripheral blood ADE BBW Progressive multifocal leukoencephalopathy PML Screening test JCV assay used to determine if a patient has antibodies to the JC virus AXB more likely to develop PLM 1 10 000 chance of developing PLM Warning cardiotoxicity BM suppression secondary malignancy ADE Nausea alopecia menstrual irregularities URI UTI leucopenia blue green secretions Headache infections diarrhea back pain LFT elevation cough HTN macular edema QT prolongation Avoid live vaccines during and 2 months after Birth control during at 2 months after Monitor Infections infusion related reactions LFTs D C if or jaundice develops Neutralizing antibody testing CBC LFTs LVEF before does Hold if 50 S sx of CHF Baseline CBC CV 6 hrs post 1st dose for bradycardia w hourly HR BP EKP b4 1st dose at end of observation period Ophthalamologic exam baseline 3 4m PFTs LFTs VZV AxB fetal risk BC during 2m after FDA review of PT death after first fingolimod dose Dec 2011 occurred w I 24 hours after 1st dose of fingolimod pt underwent post dose monitoring cause of death unknown but potentially CV related Labeling revised with stronger CV warnings and recommendations CI in pts with preexisting heart conditions stroke or on class Ia or III antiarrhythmic meds Quinidine procainamide disopyramide amiodarone bretylium sotalol ibutilide azimilide dofetilide and dronedarone Label change Apr 2014 Posterior reversible encephalopathy syndrome added to warnings and precautions of safety labeling rare cases of PRES reported symptoms sudden onset of severe headache altered mental status visual disturbances and seizure may be reversible but also may evolve into ischemic stroke or cerebral hemorrhage Mitoxantrone Novantrone Fingolimod Gilenya Fingolimod 3 Drug Teriflunomiade Aubagio 7 14mg PO once Dose daily MOA Pyrimidine synthesis inhibitor active metabolite of leflunomide DMARD for RA Place in Therapy FDA approved for relapsing MS Decrease relapse rates disability progression MRI evidence Dimethyl Fumurate Tecfidera Alemtuzumab Lemtrada Nicotinic acid receptor agonist