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Class: Skeletal Muscle Relaxants, Miscellaneous
VA Class: MS200
CAS Number: 341-69-5

Medically reviewed by Last updated on March 2, 2020.


Centrally acting skeletal muscle relaxant.110 120 121 122 125

Uses for Orphenadrine

Muscular Conditions

Used alone or in combination with aspirin and caffeine as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute, painful musculoskeletal conditions.120 121 122

If pharmacologic therapy is required for acute low back pain (usually a benign and self-limiting condition105 106 108 ), experts state that an NSAIA or skeletal muscle relaxant may be considered.109 Skeletal muscle relaxants may provide small improvements in pain relief, but are associated with a high incidence of adverse effects (e.g., CNS effects).104 106 107 108 109 Use with caution after weighing risks against benefits.104 106 107 108

Various skeletal muscle relaxants appear to have comparable efficacy for low back pain relief.103 104 106 108

Orphenadrine Dosage and Administration


Administer orally or by IV or IM injection.120 121 122

Oral Administration

Administer extended-release tablets orally twice daily (once in the morning and once in the evening).120

Administer fixed-combination tablets (with aspirin and caffeine) orally 3 or 4 times daily.122

IV Administration

Place patient in supine position during and for 5–10 minutes following IV injection.a (See CNS Effects under Cautions.) To minimize adverse reactions, assist patient from recumbent position after the drug is administered.a

Rate of Administration

Administer IV over about 5 minutes.a


Available as orphenadrine citrate; dosage expressed in terms of the salt.120 121 122


Muscular Conditions
Extended-release Tablets

100 mg twice daily.120

Fixed-combination Tablets

25–50 mg (in combination with aspirin 385–770 mg and caffeine 30–60 mg) 3 or 4 times daily.122

Parenteral Therapy
IV or IM

60 mg every 12 hours.121

Cautions for Orphenadrine


  • Glaucoma.120 121

  • Pyloric or duodenal obstruction.120 121

  • Stenosing peptic ulcers.120 121

  • Prostatic hypertrophy or obstruction of the bladder neck.120 121

  • Cardiospasm (megaesophagus).120 121

  • Myasthenia gravis.120 121

  • Known hypersensitivity to orphenadrine or any ingredient in the formulation.120 121



CNS Effects

Transient episodes of lightheadedness, dizziness, or syncope reported.120 121

Performance of activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle) may be impaired.120 121

Sensitivity Reactions

Sulfite Sensitivity

Injectable formulation contains sodium bisulfite, which can cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals.100 121

Overall prevalence of sulfite sensitivity in the general population unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.100 121

General Precautions

Adequate Patient Monitoring

Safety of continuous therapy not established.120 121 Perform periodic blood, urine, and liver function tests during prolonged orphenadrine therapy120 121

Cardiac Effects

Possible tachycardia and palpitation; may be associated with increased dosages.120 121 Use with caution in patients with tachycardia, cardiac decompensation, coronary insufficiency, or cardiac arrhythmias.120 121

Use of Fixed Combinations

When orphenadrine is used in fixed combination with aspirin and caffeine, consider the cautions, precautions, and contraindications associated with each agent in the combination.122

Specific Populations


Category C.120

Not known whether the drug can cause fetal harm or affect reproductive capacity.120 121 Use during pregnancy only if potential benefits outweigh potential risks, particularly during early pregnancy.120 121


Not known whether orphenadrine is distributed into milk; use with caution.a

Pediatric Use

Safety and efficacy not established.120 121

Geriatric Use

Because of risk of injury, skeletal muscle relaxants should generally be avoided in geriatric patients.111

Common Adverse Effects

Dry mouth, tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased intraocular pressure, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness.120 121

Orphenadrine Pharmacokinetics



Readily absorbed following oral administration.a



Distribution not fully characterized in humans.a In animals, detected in all organs, especially those with greatest perfusion (e.g., lungs).a

Orphenadrine may cross the placenta; not known whether distributed into milk.a



Almost completely metabolized to at least 8 metabolites; however, metabolic fate not fully determined.a

Elimination Route

Eliminated principally in urine as metabolites and, in small amounts, as unchanged drug.a


Approximately 14 hours.a





20–25°C in tight, light-resistant containers.120



20–25°C.121 Protect from light; do not use if precipitation occurs.121


  • Centrally acting skeletal muscle relaxant.110 120 121 122 125

  • Precise mechanism of action not known.120 121 Does not directly relax skeletal muscle;120 121 therapeutic action may be related to analgesic properties.120 121

  • May reduce skeletal muscle spasm, possibly through an atropine-like central action on cerebral motor centers or on the medulla.a

  • Exhibits postganglionic anticholinergic, antihistaminic, and local anesthetic properties.a

Advice to Patients

  • Potential to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known.120 121

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.120 121

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.120 121

  • Importance of informing patients of other important precautionary information.120 121 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Orphenadrine Citrate


Dosage Forms


Brand Names



Tablets, extended-release

100 mg*

Orphenadrine Citrate Extended-release Tablets



30 mg/mL*

Orphenadrine Citrate Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Orphenadrine Citrate Combinations


Dosage Forms


Brand Names




25 mg with Aspirin 385 mg and Caffeine 30 mg*

Orphenadrine Citrate, Aspirin, and Caffeine Tablets

50 mg with Aspirin 770 mg and Caffeine 60 mg*

Orphenadrine Citrate, Aspirin, and Caffeine Tablets

Orphengesic Forte


AHFS DI Essentials™. © Copyright 2021, Selected Revisions March 2, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.


Only references cited for selected revisions after 1984 are available electronically.

100. Food and Drug Administration. Sulfiting agents; labeling in drugs for human use; warning statements. [21 CFR Part 201] Fed Regist. 1986; 51:43900-5.

103. See S, Ginzburg R. Skeletal muscle relaxants. Pharmacotherapy. 2008; 28:207-13.

104. van Tulder MW, Touray T, Furlan AD et al. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev. 2003; :CD004252.

105. Roelofs PD, Deyo RA, Koes BW et al. Non-steroidal anti-inflammatory drugs for low back pain. Cochrane Database Syst Rev. 2008; :CD000396.

106. Chou R, Qaseem A, Snow V et al. Diagnosis and treatment of low back pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007; 147:478-91.

107. Institute for Clinical Systems Improvement. Health care guideline: adult acute and subacute low back pain. 15th ed. Bloomington, MN; 2012 Jan. From the ICSI website

108. Toth PP, Urtis J. Commonly used muscle relaxant therapies for acute low back pain: a review of carisoprodol, cyclobenzaprine hydrochloride, and metaxalone. Clin Ther. 2004; 26:1355-67.

109. Qaseem A, Wilt TJ, McLean RM et al. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017; 166:514-530.

110. Friedman BW, Cisewski D, Irizarry E et al. A Randomized, Double-Blind, Placebo-Controlled Trial of Naproxen With or Without Orphenadrine or Methocarbamol for Acute Low Back Pain. Ann Emerg Med. 2018; 71:348-356.e5.

111. Spence MM, Shin PJ, Lee EA et al. Risk of injury associated with skeletal muscle relaxant use in older adults. Ann Pharmacother. 2013 Jul-Aug; 47:993-8.

112. Friedman BW, Irizarry E, Solorzano C et al. A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain. Ann Emerg Med. 2019;

113. Friedman BW, Dym AA, Davitt M et al. Naproxen With Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain: A Randomized Clinical Trial. JAMA. 2015; 314:1572-80.

120. Sandoz. Orphenadrine citrate extended-release tablets prescribing information. Princeton, NJ: 2017 July.

121. Actavis. Orphenadrine citrate injection prescribing information. Parsiappy, NJ: 2016 July.

122. Galt. Orphengesic Forte (orphenadrine citrate, aspirin, and caffeine tablets 50 mg/770 mg/60 mg) prescribing information. Atlanta, GA: 2018 Sept.

123. Katzenschlager R, Sampaio C, Costa J et al. Anticholinergics for symptomatic management of Parkinson's disease. Cochrane Database Syst Rev. 2003; :CD003735.

124. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014 Apr 23-30; 311:1670-83.

125. 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 Mar-Apr;19(2):71-87.

a. AHFS Drug Information 2020. Snow EK, ed. Metaxalone. Bethesda, MD: American Society of Health-System Pharmacists; 2020.