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Skeletal Muscle Relaxants Therapeutic Class Review (TCR) December 3, 2012

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Skeletal Muscle Relaxants Therapeutic Class Review (TCR) December 3, 2012 Skeletal Muscle Relaxants Therapeutic Class Review (TCR) December 3, 2012 Please Note: This clinical document has been retired. It can be used as a historical reference. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage or retrieval system without the express written consent of Magellan Rx Management. All requests for permission should be mailed to: Magellan Rx Management Attention: Legal Department 6950 Columbia Gateway Drive Columbia, Maryland 21046 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. This material is not intended to be relied upon as medical advice for specific medical cases and nothing contained herein should be relied upon by any patient, medical professional or layperson seeking information about a specific course of treatment for a specific medical condition. All readers of this material are responsible for independently obtaining medical advice and guidance from their own physician and/or other medical professional in regard to the best course of treatment for their specific medical condition. This publication, inclusive of all forms contained herein, is intended to be educational in nature and is intended to be used for informational purposes only. Send comments and suggestions to [email protected]. Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2007–2012 Magellan Rx Management. All Rights Reserved. FDA-APPROVED INDICATIONS Drug Manufacturer Indications baclofen generic For the alleviation of signs and symptoms of spasticity (Lioresal)1 resulting from multiple sclerosis (MS), particularly for the relief of flexor spasms, concomitant pain, clonus, and muscular rigidity baclofen Metacel For the treatment of spasticity resulting from MS, (Ozobax™)†2 particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity May also be of some value in patients with spinal cord injuries and other spinal cord diseases carisoprodol (Soma)3 generic, Meda carisoprodol compound or generic carisoprodol and aspirin4 chlorzoxazone5 (Parafon Forte generic DSC) As an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful chlorzoxazone6 (Lorzone™) Vertical musculoskeletal conditions cyclobenzaprine (Flexeril)7 generic cyclobenzaprine Hudson Scientific, (Cyclotens™, Fexmid)8,9,10 Casper cyclobenzaprine ER (Amrix)11 generic dantrolene sodium (Dantrium)*12 generic For the control of clinical spasticity resulting from upper motor neuron disorders such as spinal cord injury, stroke, cerebral palsy, or multiple sclerosis metaxalone generic As an adjunct to rest, physical therapy, and other measures (Skelaxin)13 for the relief of discomfort associated with acute, painful musculoskeletal conditions methocarbamol (Robaxin)14 generic As an adjunct to rest, physical therapy, and other measures methocarbamol/aspirin15 generic for the relief of discomfort associated with acute, painful musculoskeletal conditions orphenadrine citrate16 generic As an adjunct to rest, physical therapy, and other measures orphenadrine compound or generic, for the relief of discomfort associated with acute, painful orphenadrine/aspirin/ Poly Pharmaceuticals musculoskeletal conditions caffeine (Norgesic Forte)17,18 Symptomatic relief of mild to moderate pain of acute musculoskeletal disorders tizanidine (Zanaflex)19 generic, For the acute and intermittent management of increased Acorda/Covis muscle tone associated with spasticity † Ozobax is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders. * Oral Dantrium is also indicated preoperatively to prevent or attenuate the development of signs of malignant hyperthermia in known, or strongly suspect, malignant hyperthermia susceptible patients who require anesthesia and/or surgery. Skeletal Muscle Relaxants Review – December 2012 Page 2 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2007–2012 Magellan Rx Management. All Rights Reserved. OVERVIEW Skeletal muscle relaxants are FDA-approved to treat two different types of conditions: muscular pain or spasms from peripheral musculoskeletal conditions and spasticity from upper motor neuron syndromes. Both conditions affect patients' mobility and affect independence in activities of daily living and work. Spasticity is a condition in which muscles are continuously contracted causing stiffness or tightness which may interfere with movement and speech. It is usually caused by damage to the portion of the brain or spinal cord that controls voluntary movement. Spasticity is a major health concern and can be associated with a number of disease entities such as spinal cord injury, multiple sclerosis, traumatic brain injury, cerebral palsy, and stroke. Symptoms may include hypertonicity, clonus, exaggerated deep tendon reflexes, muscle spasms, scissoring, and fixed joints. The degree of spasticity varies from mild muscle stiffness to severe, painful, and uncontrollable muscle spasms. Spasticity may cause decreased range of motion, contractures, sleep disorders, and impaired ambulation. Common musculoskeletal conditions associated with muscle spasms include low back pain, neck pain, tension headaches, and myofascial pain syndrome. Hypertonicity and hyperreflexia are not present as with upper motor neuron syndromes. These conditions can cause significant disability and pain. The 2005 Multiple Sclerosis Council for Clinical Practice Guidelines for spasticity management in multiple sclerosis included the oral skeletal muscle relaxant agents baclofen and tizanidine, as effective first-line treatment options.20 Generally, skeletal muscle relaxants are administered orally. Baclofen can be administered intrathecally, and orphenadrine can be administered either intravenously (IV) or intramuscularly (IM). Only the oral agents are included in this review. Skeletal Muscle Relaxants Review – December 2012 Page 3 | Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2007–2012 Magellan Rx Management. All Rights Reserved. PHARMACOLOGY Drug Mechanism of Action baclofen . Inhibits monosynaptic and polysynaptic reflexes at the spinal level by (Lioresal, Ozobax)21,22 hyperpolarization of afferent terminals . Additionally acts at supraspinal sites . Has general central nervous system (CNS) depressant properties carisoprodol (Soma)23 . In animals, it produces muscle relaxation by blocking interneuronal activity in the descending reticular formation and spinal cord. carisoprodol compound or . Carisoprodol, in animals, produces muscle relaxation by blocking interneuronal carisoprodol and aspirin24 activity in the descending reticular formation and spinal cord. Aspirin is a non-narcotic analgesic with anti-inflammatory activity. Inhibition of prostaglandin biosynthesis appears to account for most of its anti-inflammatory and for at least part of its analgesic properties. chlorzoxazone25, 26 . Acts primarily at the spinal cord level and subcortical areas of the brain, inhibiting multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm of varied etiology cyclobenzaprine (Flexeril, . Relieves skeletal muscle spasm of local origin without interfering with muscle function Fexmid)27, 28 . Ineffective in muscle spasm due to CNS disease cyclobenzaprine ER (Amrix)29 dantrolene sodium . In isolated nerve-muscle preparation, dantrolene produced relaxation by affecting (Dantrium)30 contractile response of the skeletal muscle at a site beyond the myoneural junction and directly on the muscle itself. In skeletal muscle, dantrolene dissociates the excitation-contraction coupling, probably by interfering with the release of calcium from the sarcoplasmic reticulum. Does not appear to directly affect the CNS; the extent of its indirect effect is unknown metaxalone (Skelaxin)31 . May be caused by general CNS depression methocarbamol (Robaxin)32 . The drug has no direct action on the contractile mechanism of striated muscle, the motor endplate, or the nerve fiber. methocarbamol/aspirin33 . May be caused by general CNS depression . Methocarbamol has no direct action on the contractile mechanism of striated muscle, the motor endplate, or the nerve fiber. Aspirin is a non-narcotic analgesic with anti-inflammatory activity. Inhibition of prostaglandin biosynthesis appears to account for most of its anti-inflammatory and for at least part of its analgesic properties. orphenadrine citrate34 . Acts centrally at the brain stem . Does not directly relax tense skeletal muscles . Possesses anticholinergic actions orphenadrine compound . Orphenadrine acts centrally at the brain stem. or . Orphenadrine does not directly relax tense skeletal muscles. orphenadrine/aspirin/ . Orphenadrine possesses anticholinergic actions. caffeine (Norgesic Forte)35,36 . Aspirin is a non-narcotic analgesic with anti-inflammatory activity. Inhibition of prostaglandin biosynthesis appears to account for most of its anti-inflammatory and for at least part of its analgesic properties. Caffeine increases levels of intracellular cyclic-AMP. tizanidine (Zanaflex)37
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