The page number in the footer is not for bibliographic referencingwww.tandfonline.com/oemd 6 S Afr Fam Pract ISSN 2078-6190 EISSN 2078-6204 © 2019 The Author(s) PRODUCT FOCUS The term “skeletal muscle relaxants” represents a broad group of drugs that are structurally and pharmacologically diverse.1 Skeletal muscle relaxants are used to treat both spasticity and local musculoskeletal spasms.1 These two conditions differ in their aetiology, with spasticity originating centrally more as a result of a motor neuron disorder, while local musculoskeletal spasms occur peripherally and more as a result of trauma or muscle strain.1 For this reason, centrally-acting (e.g. baclofen) and peripherally-acting skeletal muscle relaxants (e.g. orphenadrine, cyclobenzaprine) cannot be used interchangeably. Orphenadrine is used to relieve musculoskeletal spasm originating from painful peripheral musculoskeletal conditions.1 Mechanism of action Orphenadrine is structurally similar to diphenhydramine, but has less antihistaminic activity.2,3 It also has a less sedating effect than diphenhydramine, having a slight euphorigenic effect.4,5 The precise mechanism of action of orphenadrine is not known, but it appears to indirectly relieve muscle pain through central atropine-like effects.3It does not work directly on the muscle to relieve muscle spasm and does not affect normal muscle tone.3,5 Indications Oral orphenadrine is indicated for use in conditions involving skeletal muscle spasm, such as lower back pain and torticollis, as well as those conditions resulting from trauma, such as whiplash.5 The orphenadrine 100 mg tablets are recommended for short-term use.3 Pharmacokinetics Orphenadrine is 95% bioavailable after oral absorption.2 Time to peak concentration after oral administration is 2 to 4 hours.2 It is extensively metabolised in the liver through the cytochrome P450 (CYP450) system and the metabolites are primarily eliminated in the urine.1,3 The elimination half-life (t1/2) of orphenadrine varies between 13.2 to 20.1 hours.2 Dosing One tablet of orphenadrine 100 mg may be taken two or three times daily.5 The tablets may be taken without regard to meals.6 Efficacy Skeletal muscle relaxants have been found to be more effective than placebo when used for short-term relief of back pain.3Peak effects occur after two to four hours and can last for up to 6 hours.3 Skeletal muscle relaxants may be used in combination another with analgesics for lower back pain. They may also be used as an alternative to nonsteroidal anti-inflammatory drugs (NSAIDs) in patients who are not able to tolerate NSAIDs, or who have renal dysfunction.7 Safety of orphenadrine Adverse effects The side-effect profile of orphenadrine is mainly related to the anticholinergic effects of the drug.3 These side-effects usually occur at higher doses and may include: • Dry mouth, nausea, blurring of vision8 • Drowsiness8 • Increased intraocular pressure4 • Urinary retention4 • CNS stimulation (especially in elderly people)4 • Constipation For this reason, oral orphenadrine is contraindicated for use in patients with6: • Myasthenia gravis • Gastrointestinal (GI) obstruction • Glaucoma • Bladder obstruction or other urinary tract obstruction • Prostatic hypertrophy Oral orphenadrine should also be used with caution in patients with: • Heart failure (palpitations, tachycardia)6 • Gastro-oesophageal reflux6 • Hepatic disease, renal impairment, or renal disease6 • A history of substance abuse, due its euphoric effects (can occur at therapeutic doses)6 South African Family Practice 2019; 61(3):6-8 Open Access article distributed under the terms of the Creative Commons License [CC BY-NC-ND 4.0] http://creativecommons.org/licenses/by-nc-nd/4.0 Focus on: Orphenadrine citrate as a muscle relaxant L Steyn Amayeza Info Services References: 1. Impact Rx. Script Data – December 2018. 2. McGuiness BW. A Double-Blind Comparison in General Practice of a Combination Tablet Containing Orphenadrine Citrate and Paracetamol (‘Norgesic’) with Paracetamol Alone. J Int Med Res 1983;11:42-45. 3. Hunskaar S, Donnell D. Clinical and Pharmacological Review of the Efficacy of Orphenadrine and Its Combination with Paracetamol in Painful Conditions. J Int Med Res 1991;19:71-87. 4. Waldman HJ. Centrally Acting Skeletal Muscle Relaxants and Associated Drugs. J Pain Symptom Manage 1994;9(7):434-441. 5. Massey T, et al. Cochrane Database Syst Rev; (6):CD007402. doi:10.1002/14651858.CD007402.pub2. 6. Norflex® Gel approved package insert, September 2001. 7. Norflex® Co Tablets approved package insert, July 1992. 8. Difflam Gel [cited 22 November 2018]; Available from URL: http://www.myvmc.com/drugs/difflam-gel/. 9. Norflex® Tablets approved package insert, February 1985. Visit w w w.nor f lexgel.co.za to f ind out more. THE RANGE FOR EFFECTIVE RELIEF FROM PAINFUL MUSCULAR CONDITIONS WHICH OCCUR DUE TO EVERYDAY ACTIVIT Y2,3,4,5 * Refers to the Norflex Oral Range So uth Africa’s #1 Muscle relaxan t b ra nd PRES CRIBE D 1 RANGETHE Relieves ANYDAY painful muscular conditions, ANY TIME2,3,4 Scheduling status: S2 Proprietary name (and dosage form): NORFLEX CO Tablets. Composition: Each tablet contains 35 mg Orphenadrine citrate and 450 mg Paracetamol. Pharmacological classification: A.2.9 (Other analgesics). Reference number: B 1098 [Act 101/1965]; Scheduling status: S2 Proprietary name (and dosage form): NORFLEX Tablets. Composition: Each tablet contains 100 mg Orphenadrine citrate. Pharmacological classification: Category: A.2.10 (Centrally active muscle relaxants). Reference number: H 1612. [Act 101/1965]. Scheduling status: S1 Proprietary name and dosage form: NORFLEX Gel. Composition: Each 100g contains: Benzydamine hydrochloride 3,0g. Pharmacological classification: A3.1 Antirheumatics (anti-inflammatory) agents. Registration number: 32/3.1/0547. Name and business address of applicant: iNova Pharmaceuticals (Pty) Ltd. Reg. No.: 1952/001640/07. 15E Riley Road, Bedfordview. Tel. No.: 011 087 0000. www.inovapharma.co.za. For full prescribing information, refer to the package insert as approved by the SAHPRA (South African Health Products Regulatory Authority). Further information is available on request from iNova Pharmaceuticals. IN3061/19. oral can be co-prescribed with 4 Anti-inflammatory6 Analgesic6,7 Local Anaesthetic8 Skeletal Muscle Relaxant*7,9 S Afr Fam Pract 2019;61(3):6-88 The page number in the footer is not for bibliographic referencingwww.tandfonline.com/oemd 8 Long-term use Safety and efficacy of long-term use of orphenadrine has not been established.6 It is recommended that periodic blood, urine, and liver function tests should be performed if orphenadrine is used long term.4Chronic use of orphenadrine 100 mg should be tapered slowly before discontinuation.3 Use in the elderly Careful consideration should be taken in recommending orphenadrine to people over 65 years of age, due to the increased risk of anticholinergic side-effects, drowsiness and the associated increased risk for falls.3 Drug interactions Although metabolised by CYP450, orphenadrine being a minor substrate and weak inhibitor, is less likely to be involved in drug interactions.3 Increased CNS depression may occur when orphenadrine is taken with other CNS depressants, including alcohol.1 Conclusion Skeletal muscle relaxants, including orphenadrine are usually recommended for short term use in the treatment of painful musculoskeletal conditions.3,6 They are recommended for use in conjunction with other non-drug measures, such as rest and physical therapy.6 If orphenadrine preparations are used in combination with other analgesics such as paracetamol, contraindications and precautions for each individual ingredient should be taken into account.4 References: 1. Fudin J, Raouf M. Practical Pain Management. A Review of Skeletal Muscle Relaxants for Pain Management. Vol 16, Issue 5.[updated 11 April 2017; cited 5 June 2019] Available from: https://www. practicalpainmanagement.com/treatments/rehabilitation/applying-kinesiology -multi-prong-approach-pain-management 2. Orphenadrine citrate. In: Medicines Complete. Greenwood Village  (CO): Truven Health Analytics; publication year [5 June 2019]. Available from: www. micromedexsolutions.com. Subscription required to view. 3. Witenko C, Moorman-Li R, Motycka C, Duane K, Hincapie-Castillo J, Leonard P, Valaer C. Considerations for the appropriate use of skeletal muscle relaxants for the management of acute low back pain. P T. 2014 Jun;39(6):427-35. PubMed PMID: 25050056; PubMed Central PMCID: PMC4103716.  Available from: https:// www.ncbi.nlm.nih.gov/pmc/articles/PMC4103716/ 4. AHFS® Drug Information. Online via Medicines Complete. Orphenadrine citrate.© Copyright, 1959-2019, Selected Revisions January 1, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814. 5. Package Insert. Norflex®. iNova Pharmaceuticals (Pty) Ltd. 21 Feb 1985. 6. Prescribers’ Digital Reference (PDR). Orphenadrine citrate - Drug Summary. ©2019. Available from: https://www.pdr.net/drug-summary/ Orphenadrine-Citrate-Extended-Release-Tablets-orphenadrine-citrate-1580 7. See S, Ginzburg R. Choosing a Skeletal Muscle Relaxant.American Family Physician. 2008  Aug  1;78(3):365-370. Available from: https://www.aafp.org/ afp/2008/0801/p365.html 8. Australian Product Information-Norflex (orphenadrine citrate) tablets. iNova Pharmaceuticals (Australia) Pty Limited. 3 Oct 2018. Available from: http://www. guildlink.com.au/gc/ws/ia/pi.cfm?product=iapnorfx11018