methocarbamol

Methocarbamol is a muscle relaxant used to treat acute, painful musculoskeletal spasms in a variety of musculoskeletal conditions.{{cite journal | vauthors = Chou R, Peterson K, Helfand M | title = Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review | journal = Journal of Pain and Symptom Management | volume = 28 | issue = 2 | pages = 140–175 | date = August 2004 | pmid = 15276195 | doi = 10.1016/j.jpainsymman.2004.05.002 | doi-access = free }} However, there is limited and inconsistent published research on the medication's efficacy and safety in treating musculoskeletal conditions, primarily neck and back pain.

Methocarbamol injection may have a beneficial effect in the control of the neuromuscular spasms of tetanus. It does not, however, replace the current treatment regimen.

It is not useful in chronic neurological disorders, such as cerebral palsy or other dyskinesias.

Currently, there is some suggestion that muscle relaxants may improve the symptoms of rheumatoid arthritis; however, there is insufficient data to prove its effectiveness or to answer concerns regarding optimal dosing, choice of muscle relaxant, adverse effects, and functional status.

The clinical effectiveness of methocarbamol compared to other muscle relaxants is not well known. One trial of methocarbamol versus cyclobenzaprine, a well-studied muscle relaxant, in those with localized muscle spasm found there were no significant differences in their effects on muscle spasm, limitation of motion, or limitation of daily activities.

Contraindications for methocarbamol include:

• Hypersensitivity to methocarbamol or any of the injection components.
• For the injectable form, suspected kidney failure or renal pathology, due to large content of polyethylene glycol 300 that can increase pre-existing acidosis and urea retention.

Methocarbamol is a centrally acting skeletal muscle relaxant that has significant potential adverse effects, especially on the central nervous system.

Potential side effects of methocarbamol include:

• Most commonly drowsiness, blurred vision, headache, nausea, and skin rash.
• Possible clumsiness (ataxia), upset stomach, flushing, mood changes, trouble urinating, itchiness, and fever.{{cite web|url=https://medlineplus.gov/druginfo/meds/a682579.html|title=Methocarbamol |website=MedlinePlus |access-date=18 April 2020}}
• Both tachycardia (fast heart rate) and bradycardia (slow heart rate) have been reported.{{cite web|url=https://www.drugs.com/sfx/methocarbamol-side-effects.html|title=Methocarbamol Side Effects: Common, Severe, Long Term|website=Drugs.com|access-date=18 April 2020}}
• Hypersensitivity reactions and anaphylatic reactions are also reported.
• May cause respiratory depression when combined with benzodiazepines, barbiturates, codeine, or other muscle relaxants.{{cite journal | vauthors = See S, Ginzburg R | title = Choosing a skeletal muscle relaxant | journal = American Family Physician | volume = 78 | issue = 3 | pages = 365–370 | date = August 2008 | pmid = 18711953 }}
• May cause urine to turn black, blue, or green.

While the product label states that methocarbamol can cause jaundice, there is minimal evidence to suggest that methocarbamol causes liver damage. During clinical trials of methocarbamol, there were no laboratory measurements of liver damage indicators, such as serum transaminase (AST/ALT) levels, to confirm hepatotoxicity. Although unlikely, it is impossible to rule out that methocarbamol may cause mild liver injury with use.

Skeletal muscle relaxants are associated with an increased risk of injury among older adults.{{cite journal | vauthors = Spence MM, Shin PJ, Lee EA, Gibbs NE | title = Risk of injury associated with skeletal muscle relaxant use in older adults | journal = The Annals of Pharmacotherapy | volume = 47 | issue = 7–8 | pages = 993–998 | date = July 2013 | pmid = 23821610 | doi = 10.1345/aph.1R735 | s2cid = 9037478 }} Methocarbamol appeared to be less sedating than other muscle relaxants, most notably cyclobenzaprine but had a similarly increased risk of injury. Methocarbamol is cited along with "most muscle relaxants" in the 2012 Beers Criteria as being "poorly tolerated by older adults, because of anticholinergic adverse effects, sedation, increased risk of fractures," noting that "effectiveness dosages tolerated by older adults is questionable."{{cite web|url=https://dcri.org/beers-criteria-medication-list/|title=Beers Criteria Medication List|website=DCRI|access-date=18 October 2020|archive-date=7 November 2020|archive-url=https://web.archive.org/web/20201107180832/https://dcri.org/beers-criteria-medication-list/|url-status=dead}}

Methocarbamol is labeled by the FDA as a pregnancy category C medication. The teratogenic effects of the medication are not known and should be given to pregnant women only when indicated.

There is limited information available on the acute toxicity of methocarbamol. Overdose is observed frequently in conjunction with CNS depressants such as alcohol or benzodiazepines and will have symptoms of nausea, drowsiness, blurred vision, hypotension, seizures, and coma. There are reported deaths with an overdose of methocarbamol alone or in the presence of other CNS depressants.

Unlike other carbamates such as meprobamate and its prodrug carisoprodol, methocarbamol has greatly reduced abuse potential. Studies comparing it to the benzodiazepine lorazepam and the antihistamine diphenhydramine, along with placebo, find that methocarbamol produces increased "liking" responses and some sedative-like effects; however, at higher doses dysphoria is reported. It is considered to have an abuse profile similar to, but weaker than, lorazepam.{{cite journal | vauthors = Preston KL, Wolf B, Guarino JJ, Griffiths RR | title = Subjective and behavioral effects of diphenhydramine, lorazepam and methocarbamol: evaluation of abuse liability | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 262 | issue = 2 | pages = 707–720 | date = August 1992 | doi = 10.1016/S0022-3565(25)10815-X | pmid = 1501118 }}

Methocarbamol may inhibit the effects of pyridostigmine bromide. Therefore, methocarbamol should be used with caution in those with myasthenia gravis taking anticholinesterase medications.

Methocarbamol may disrupt certain screening tests as it can cause color interference in laboratory tests for 5-hydroxy-indoleacetic acid (5-HIAA) and in urinary testing for vanillylmandelic acid (VMA) using the Gitlow method.

The mechanism of action of methocarbamol has not currently been established. Its effect is thought to be localized to the central nervous system rather than a direct effect on skeletal muscles. It does not affect the motor end plate or the peripheral nerve fiber. The efficacy of the medication is likely related to its sedative effect. Alternatively, methocarbamol may act via inhibition of acetylcholinesterase, similarly to carbamate.{{cite web| work = PubChem |title= Methocarbamol|url=https://pubchem.ncbi.nlm.nih.gov/compound/4107|access-date=6 July 2020| publisher = U.S. National Library of Medicine }}

In healthy individuals, the plasma clearance of methocarbamol ranges between 0.20 and 0.80 L/h/kg. The mean plasma elimination half-life ranges between 1 and 2 hours, and the plasma protein binding ranges between 46% and 50%. The elimination half-life was longer in the elderly, those with kidney problems, and those with liver problems.

Methocarbamol is the carbamate derivative of guaifenesin, but does not produce guaifenesin as a metabolite, because the carbamate bond is not hydrolyzed metabolically; its metabolism is by Phase I ring hydroxylation and O-demethylation, followed by Phase II conjugation. All the major metabolites are unhydrolyzed carbamates.Methocarbamol. In: DRUGDEX System [intranet database]. Greenwood Village, Colorado: Thomson Healthcare; c1974–2009 [cited 2009 Feb 10].{{cite journal | vauthors = Bruce RB, Turnbull LB, Newman JH | title = Metabolism of methocarbamol in the rat, dog, and human | journal = Journal of Pharmaceutical Sciences | volume = 60 | issue = 1 | pages = 104–106 | date = January 1971 | pmid = 5548215 | doi = 10.1002/jps.2600600120 }} Small amounts of unchanged methocarbamol are also excreted in the urine.

Methocarbamol was approved as a muscle relaxant for acute, painful musculoskeletal conditions in the United States in 1957. Muscle relaxants are widely used to treat low back pain, one of the most frequent health problems in industrialized countries. Currently, there are more than 3 million prescriptions filled yearly. Methocarbamol and orphenadrine are each used in more than 250,000 U.S. emergency department visits for lower back pain each year.{{cite journal | vauthors = Friedman BW, Cisewski D, Irizarry E, Davitt M, Solorzano C, Nassery A, Pearlman S, White D, Gallagher EJ | title = A Randomized, Double-Blind, Placebo-Controlled Trial of Naproxen With or Without Orphenadrine or Methocarbamol for Acute Low Back Pain | journal = Annals of Emergency Medicine | volume = 71 | issue = 3 | pages = 348–356.e5 | date = March 2018 | pmid = 29089169 | pmc = 5820149 | doi = 10.1016/j.annemergmed.2017.09.031 }} In the United States, low back pain is the fifth most common reason for all physician visits and the second most common symptomatic reason.{{cite journal | vauthors = Chou R, Huffman LH | title = Medications for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline | journal = Annals of Internal Medicine | volume = 147 | issue = 7 | pages = 505–514 | date = October 2007 | pmid = 17909211 | doi = 10.7326/0003-4819-147-7-200710020-00008 | s2cid = 32719708 }} In 80% of primary care visits for low back pain, at least one medication was prescribed at the initial office visit and more than one third were prescribed two or more medications.{{cite journal | vauthors = Cherkin DC, Wheeler KJ, Barlow W, Deyo RA | title = Medication use for low back pain in primary care | journal = Spine | volume = 23 | issue = 5 | pages = 607–614 | date = March 1998 | pmid = 9530793 | doi = 10.1097/00007632-199803010-00015 | s2cid = 23664539 }} The most commonly prescribed drugs for low back pain included skeletal muscle relaxants.{{cite journal | vauthors = Luo X, Pietrobon R, Curtis LH, Hey LA | title = Prescription of nonsteroidal anti-inflammatory drugs and muscle relaxants for back pain in the United States | journal = Spine | volume = 29 | issue = 23 | pages = E531–E537 | date = December 2004 | pmid = 15564901 | doi = 10.1097/01.brs.0000146453.76528.7c | s2cid = 72742439 }} Cyclobenzaprine and methocarbamol are on the U.S. Medicare formulary, which may account for the higher use of these products.

It is relatively inexpensive as of 2016. The generic formulation of the medication is relatively inexpensive, costing less than the alternative metaxalone in 2016.{{cite book | vauthors = Robbins LD |title=Management of Headache and Headache Medications |date=2013 |publisher=Springer Science & Business Media |isbn=978-1-4612-2124-1 |page=PT147 |url=https://books.google.com/books?id=Bmh3BQAAQBAJ&dq=Methocarbamol+inexpensive&pg=PT147 }}{{cite book | vauthors = Fine PG |title=The Hospice Companion: Best Practices for Interdisciplinary Care of Advanced Illness |date=2016 |publisher=Oxford University Press |isbn=978-0-19-045692-4 |page=PT146 |url=https://books.google.com/books?id=I7NjDQAAQBAJ&dq=Methocarbamol+cost&pg=PT146 }}

File:Methocarbamol 750 MG Oral Tablet.jpg

Methocarbamol without other ingredients is sold under the brand name Robaxin in the U.K., U.S., Canada{{cite web|title=ROBAXIN product appearance in Canada|url=https://ctchealth.ca/product/robaxin-500mg/|access-date=13 December 2021|website=ctchealth.ca|date=13 July 2021 }} and South Africa; it is marketed as Lumirelax in France, Ortoton in Germany and many other names worldwide.{{cite web|title=Methocarbamol|url=https://www.drugs.com/international/methocarbamol.html|website=Drugs.com|access-date=12 May 2018}} In combination with other active ingredients it is sold under other names: with acetaminophen (paracetamol), under trade names Robaxacet and Tylenol Body Pain Night; with ibuprofen as Robax Platinum; with acetylsalicylic acid as Robaxisal in the U.S. and Canada.{{cite web | title = New Drugs and Indications Reviewed at the May 2003 DEC Meeting | publisher = ESI Canada | url = http://www.esi-canada.com/aboutus/news/health_newsflashes/volume5_issue9_newdrugsmay2003.pdf | access-date = 14 November 2008 | url-status = dead | archive-url = https://web.archive.org/web/20110710201457/http://www.esi-canada.com/aboutus/news/health_newsflashes/volume5_issue9_newdrugsmay2003.pdf | archive-date = 10 July 2011 }}{{cite web | title = Tylenol Body Pain Night Overview and Dosage | publisher = Tylenol Canada | url = http://www.tylenol.ca/adult-pain-relief/tylenol-body-pain-night | format = website | access-date = 23 April 2012 | url-status = dead | archive-url = https://web.archive.org/web/20120331074351/http://www.tylenol.ca/adult-pain-relief/tylenol-body-pain-night | archive-date = 31 March 2012 }} However, in Spain the tradename Robaxisal is used for the paracetamol combination instead of Robaxacet.{{citation needed|date=April 2020}} These combinations are also available from independent manufacturers under generic names.{{citation needed|date=April 2020}}

Although opioids are typically first-line treatments in severe pain, several trials suggest that methocarbamol may improve recovery and decrease hospital length of stay in those with muscle spasms associated with rib fractures.{{cite journal | vauthors = Patanwala AE, Aljuhani O, Kopp BJ, Erstad BL | title = Methocarbamol use is associated with decreased hospital length of stay in trauma patients with closed rib fractures | journal = American Journal of Surgery | volume = 214 | issue = 4 | pages = 738–742 | date = October 2017 | pmid = 28088301 | doi = 10.1016/j.amjsurg.2017.01.003 }}{{cite journal| vauthors = Deloney L, Smith M, Carter C, Privette A, Leon S, Eriksson E |date=January 2020 |title= 946: Methocarbamol reduces opioid use and length of stay in young adults with traumatic rib fractures |journal=Critical Care Medicine |volume=48 |issue=1 |page=452 |doi=10.1097/01.ccm.0000633320.62811.06 |issn=0090-3493|doi-access=free }}{{cite journal| vauthors = Smith M, Deloney L, Carter C, Leon S, Privette A, Eriksson E |date=January 2020|title=1759: Use of methocarbamol in geriatric patients with rib fractures is associated with improved outcomes |journal=Critical Care Medicine |volume=48 |issue=1 |page=854 |doi=10.1097/01.ccm.0000649332.10326.98 |issn=0090-3493|doi-access=free }} However, methocarbamol was less useful in the treatment of acute traumatic pain in general.{{cite journal | vauthors = Aljuhani O, Kopp BJ, Patanwala AE | title = Effect of Methocarbamol on Acute Pain After Traumatic Injury | journal = American Journal of Therapeutics | volume = 24 | issue = 2 | pages = e202–e206 | date = 2017 | pmid = 26469684 | doi = 10.1097/mjt.0000000000000364 | s2cid = 24284482 }}

Long-term studies evaluating the risk of development of cancer in using methocarbamol have not been performed. There are currently no studies evaluating the effect of methocarbamol on mutagenesis or fertility.

The safety and efficacy of methocarbamol have not been established in pediatric individuals below the age of 16 except in tetanus.

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