Methocarbamol

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Methocarbamol
Methocarbamol.svg
Clinical data
Trade names Robaxin, Marbaxin, others
AHFS/Drugs.com Monograph
MedlinePlus a682579
License data
Pregnancy
category
  • AU:B2
Routes of
administration 		By mouth, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolism Liver
Elimination half-life 1.14–1.24 hours [2]
Identifiers
  • (RS)-2-hydroxy-3-(2-methoxyphenoxy)propyl carbamate
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.007.751 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C11H15NO5
Molar mass 241.243 g·mol−1
3D model (JSmol)
  • O=C(OCC(O)COc1ccccc1OC)N
  • InChI=1S/C11H15NO5/c1-15-9-4-2-3-5-10(9)16-6-8(13)7-17-11(12)14/h2-5,8,13H,6-7H2,1H3,(H2,12,14) Yes check.svgY
  • Key:GNXFOGHNGIVQEH-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Methocarbamol, sold under the brand name Robaxin among others, is a medication used for short-term musculoskeletal pain. [3] [4] It may be used together with rest, physical therapy, and pain medication. [3] [5] [6] It is less preferred in low back pain. [3] It has limited use for rheumatoid arthritis and cerebral palsy. [3] [7] Effects generally begin within half an hour. [3] It is taken by mouth or injection into a vein. [3]

Contents

Common side effect include headaches, sleepiness, and dizziness. [3] [8] Serious side effects may include anaphylaxis, liver problems, confusion, and seizures. [4] Use is not recommended in pregnancy and breastfeeding. [3] [4] Because of risk of injury, skeletal muscle relaxants should generally be avoided in geriatric patients. [3] Methocarbamol is a centrally acting muscle relaxant. [3] How it works is unclear, but it does not appear to affect muscles directly. [3]

Methocarbamol was developed in 1956 in the laboratories of A. H. Robins (later acquired by Pfizer). Studies were directed towards the development of propanediol derivatives which possessed muscle relaxant properties superior to those of mephenesin, which had low potency and a short duration of action. [9] It was approved for medical use in the United States in 1957. [3] It is available as a generic medication. [3] [4] It is relatively inexpensive as of 2016. [10] In 2021, it was the 123rd most commonly prescribed medication in the United States, with more than 4 million prescriptions. [11] [12]

Medical use

Methocarbamol is a muscle relaxant used to treat acute, painful musculoskeletal spasms in a variety of musculoskeletal conditions. [13] However, there is limited and inconsistent published research on the medication's efficacy and safety in treating musculoskeletal conditions, primarily neck and back pain. [13]

Methocarbamol injection may have a beneficial effect in the control of the neuromuscular spasms of tetanus. [6] It does not, however, replace the current treatment regimen. [6]

It is not useful in chronic neurological disorders, such as cerebral palsy or other dyskinesias. [3]

Currently, there is some suggestion that muscle relaxants may improve the symptoms of rheumatoid arthritis; however, there is insufficient data to prove its effectiveness as well as answer concerns regarding optimal dosing, choice of muscle relaxant, adverse effects, and functional status. [7]

Comparison to similar agents

The clinical effectiveness of methocarbamol compared to other muscle relaxants is not well-known. [13] One trial of methocarbamol versus cyclobenzaprine, a well-studied muscle relaxant, in those with localized muscle spasm found there was no significant differences in their effects on improved muscle spasm, limitation of motion, or limitation of daily activities. [13]

Contraindications

Contraindications for methocarbamol include:

Side effects

Methocarbamol is a centrally acting skeletal muscle relaxant that has significant potential adverse effects, especially on the central nervous system. [3]

Potential side effects of methocarbamol include:

While the product label states that methocarbamol can cause jaundice, there is minimal evidence to suggest that methocarbamol causes liver damage. [8] During clinical trials of methocarbamol, there were no laboratory measurements of liver damage indicators, such as serum transaminase (AST/ALT) levels, to confirm hepatotoxicity. [8] Although unlikely, it is impossible to rule out that methocarbamol may cause mild liver injury with use. [8]

Elderly

Skeletal muscle relaxants are associated with an increased risk of injury among older adults. [17] Methocarbamol appeared to be less sedating than other muscle relaxants, most notably cyclobenzaprine, but had similar increased risk of injury. [16] [17] 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." [18]

Pregnancy

Methocarbamol is labeled by the FDA as a pregnancy category C medication. [6] The teratogenic effects of the medication are not known and should be given to pregnant women only when clearly indicated. [6]

Overdose

There is limited information available on the acute toxicity of methocarbamol. [5] [6] 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. [6] There are reported deaths with an overdose of methocarbamol alone or in the presence of other CNS depressants. [5] [6]

Abuse

Unlike other carbamates such as meprobamate and its prodrug carisoprodol, methocarbamol has greatly reduced abuse potential. [19] 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. [19] It is considered to have an abuse profile similar to, but weaker than, lorazepam. [19]

Interactions

Methocarbamol may inhibit the effects of pyridostigmine bromide. [5] [6] Therefore, methocarbamol should be used with caution in those with myasthenia gravis taking anticholinesterase medications. [6]

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. [6]

Pharmacology

Mechanism of action

The mechanism of action of methocarbamol has not currently been established. [3] Its effect is thought to be localized to the central nervous system rather than a direct effect on skeletal muscles. [3] It has no effect on the motor end plate or the peripheral nerve fiber. [6] The efficacy of the medication is likely related to its sedative effect. [3] Alternatively, methocarbamol may act via inhibition of acetylcholinesterase, similarly to carbamate. [20]

Pharmacokinetics

In healthy individuals, the plasma clearance of methocarbamol ranges between 0.20 and 0.80 L/h/kg. [6] The mean plasma elimination half-life ranges between 1 and 2 hours, and the plasma protein binding ranges between 46% and 50%. [6] The elimination half-life was longer in the elderly, those with kidney problems, and those with liver problems. [6]

Metabolism

Methocarbamol is the carbamate derivative of guaifenesin, but does not produce guaifenesin as a metabolite, because the carbamate bond is not hydrolyzed metabolically; [8] [6] its metabolism is by Phase I ring hydroxylation and O-demethylation, followed by Phase II conjugation. [6] All the major metabolites are unhydrolyzed carbamates. [21] [22] Small amounts of unchanged methocarbamol are also excreted in the urine. [5] [6]

Society and culture

Methocarbamol was approved as a muscle relaxant for acute, painful musculoskeletal conditions in the United States in 1957. [8] 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. [8] Methocarbamol and orphenadrine are each used in more than 250,000 U.S. emergency department visits for lower back pain each year. [23] In the United States, low back pain is the fifth most common reason for all physician visits and the second most common symptomatic reason. [24] 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. [25] The most commonly prescribed drugs for low back pain included skeletal muscle relaxants. [26] Cyclobenzaprine and methocarbamol are on the U.S. Medicare formulary, which may account for the higher use of these products. [17]

Economics

The generic formulation of the medication is relatively inexpensive, costing less than the alternative metaxalone in 2016. [27] [10]

Marketing

Generic methocarbamol 750mg tablet. Methocarbamol 750 MG Oral Tablet.jpg
Generic methocarbamol 750mg tablet.

Methocarbamol without other ingredients is sold under the brand name Robaxin in the U.K., U.S., Canada [28] and South Africa; it is marketed as Lumirelax in France, Ortoton in Germany and many other names worldwide. [29] 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. [30] [31] However, in Spain the tradename Robaxisal is used for the paracetamol combination instead of Robaxacet.[ citation needed ] These combinations are also available from independent manufacturers under generic names.[ citation needed ]

Research

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 muscles spasms associated with rib fractures. [32] [33] [34] However, methocarbamol was less useful in the treatment of acute traumatic pain in general. [35]

Long-term studies evaluating the risk of development of cancer in using methocarbamol have not been performed. [5] [6] There are currently no studies evaluating the effect of methocarbamol on mutagenesis or fertility. [5] [6]

The safety and efficacy of methocarbamol has not been established in pediatric individuals below the age of 16 except in tetanus. [5] [6]

Related Research Articles

<span class="mw-page-title-main">Back pain</span> Area of body discomfort

Back pain is pain felt in the back. It may be classified as neck pain (cervical), middle back pain (thoracic), lower back pain (lumbar) or coccydynia based on the segment affected. The lumbar area is the most common area affected. An episode of back pain may be acute, subacute or chronic depending on the duration. The pain may be characterized as a dull ache, shooting or piercing pain or a burning sensation. Discomfort can radiate to the arms and hands as well as the legs or feet, and may include numbness or weakness in the legs and arms.

An antispasmodic is a pharmaceutical drug or other agent that suppresses muscle spasms.

<span class="mw-page-title-main">Lorazepam</span> Benzodiazepine medication

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy-induced nausea and vomiting. It is also used during surgery to interfere with memory formation and to sedate those who are being mechanically ventilated. It is also used, along with other treatments, for acute coronary syndrome due to cocaine use. It can be given orally, transdermal, intravenously (IV), or intramuscularly When given by injection, onset of effects is between one and thirty minutes and effects last for up to a day.

A muscle relaxant is a drug that affects skeletal muscle function and decreases the muscle tone. It may be used to alleviate symptoms such as muscle spasms, pain, and hyperreflexia. The term "muscle relaxant" is used to refer to two major therapeutic groups: neuromuscular blockers and spasmolytics. Neuromuscular blockers act by interfering with transmission at the neuromuscular end plate and have no central nervous system (CNS) activity. They are often used during surgical procedures and in intensive care and emergency medicine to cause temporary paralysis. Spasmolytics, also known as "centrally acting" muscle relaxant, are used to alleviate musculoskeletal pain and spasms and to reduce spasticity in a variety of neurological conditions. While both neuromuscular blockers and spasmolytics are often grouped together as muscle relaxant, the term is commonly used to refer to spasmolytics only.

<span class="mw-page-title-main">Cramp</span> Pathological, often painful, involuntary muscle contraction

A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity; while generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the affected muscle. A cramp usually goes away on its own over a period of several seconds or (sometimes) minutes. Cramps are common and tend to occur at rest, usually at night. They are also often associated with pregnancy, physical exercise or overexertion, age, in such cases, cramps are called idiopathic, because there is no underlying pathology. In addition to those benign conditions cramps are also associated with many pathological conditions.

Colloquially known as "downers", depressants or central depressants are drugs that lower neurotransmission levels, or depress or reduce arousal or stimulation in various areas of the brain. Depressants do not change the mood or mental state of others. Stimulants, or "uppers", increase mental or physical function, hence the opposite drug class from depressants are stimulants, not antidepressants.

<span class="mw-page-title-main">Low back pain</span> Medical condition

Low back pain or lumbago is a common disorder involving the muscles, nerves, and bones of the back, in between the lower edge of the ribs and the lower fold of the buttocks. Pain can vary from a dull constant ache to a sudden sharp feeling. Low back pain may be classified by duration as acute, sub-chronic, or chronic. The condition may be further classified by the underlying cause as either mechanical, non-mechanical, or referred pain. The symptoms of low back pain usually improve within a few weeks from the time they start, with 40–90% of people recovered by six weeks.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<span class="mw-page-title-main">Carisoprodol</span> Muscle relaxant medication

Carisoprodol, sold under the brand name Soma among others, is a medication used for musculoskeletal pain. Use is only approved for up to three weeks. Effects generally begin within half an hour and last for up to six hours. It is taken orally.

<span class="mw-page-title-main">Back injury</span> Damage or wear to bones, muscles or other tissues of the back

Back injuries result from damage, wear, or trauma to the bones, muscles, or other tissues of the back. Common back injuries include sprains and strains, herniated discs, and fractured vertebrae. The lumbar spine is often the site of back pain. The area is susceptible because of its flexibility and the amount of body weight it regularly bears. It is estimated that low-back pain may affect as much as 80 to 90 percent of the general population in the United States.

<span class="mw-page-title-main">Cyclobenzaprine</span> Muscle relaxant medication

Cyclobenzaprine, sold under several brand names including, historically, Flexeril, is a muscle relaxer used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth.

<span class="mw-page-title-main">Orphenadrine</span> Muscle relaxant drug

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.

<span class="mw-page-title-main">Chlorzoxazone</span> Muscle relaxant

Chlorzoxazone (INN) is a centrally acting muscle relaxant used to treat muscle spasm and the resulting pain or discomfort. It can also be administered for acute pain in general and for tension headache. It acts on the spinal cord by depressing reflexes. It is sold under the brand names Lorzone, Paraflex and Muscol and in combination form as Parafon Forte, a combination of chlorzoxazone and acetaminophen (paracetamol). Possible side effects include dizziness, lightheadedness, malaise, nausea, vomiting, and liver dysfunction. When used with acetaminophen it has added risk of hepatotoxicity.

<span class="mw-page-title-main">Mephenesin</span> Muscle relaxer & antidote for strychnine poisoning

Mephenesin (INN), also called myanesin, is a centrally acting muscle relaxant. It can be used as an antidote for strychnine poisoning. Mephenesin however presents with the major drawbacks of having a short duration of action and a much greater effect on the spinal cord than the brain, resulting in pronounced respiratory depression at clinical doses and therefore a very low therapeutic index. It is especially dangerous and potentially fatal in combination with alcohol and other depressants. Mephenesin was the inspiration for the synthesis of a derivative of 1,3-propanediol, meprobamate, by Bernard Ludwig and Frank Berger, the first tranquilizer to see widespread clinical use. Mephenesin is no longer available in North America but is used in Italy and a few other countries. Its use has largely been replaced by the related drug methocarbamol, which is better absorbed.

<span class="mw-page-title-main">Eperisone</span> Antispasmodic and muscle relaxant drug

Eperisone is an antispasmodic drug.

<span class="mw-page-title-main">Hydrocodone/paracetamol</span> Combination pain relief drug

Hydrocodone/paracetamol is the combination of the pain medications hydrocodone and paracetamol (acetaminophen). It is used to treat moderate to severe pain. It is taken by mouth. Recreational use is common in the United States.

<span class="mw-page-title-main">Neck pain</span> Medical condition

Neck pain, also known as cervicalgia, is a common problem, with two-thirds of the population having neck pain at some point in their lives.

<span class="mw-page-title-main">Thiocolchicoside</span> Chemical compound

Thiocolchicoside is a muscle relaxant with anti-inflammatory and analgesic effects. Its mechanism of action is unknown, but it is believed to be act via antagonism of nicotinic acetylcholine receptors (nAchRs). However, it also appears to be a competitive antagonist of GABAA and glycine receptors. As such, it has powerful convulsant activity and should not be used in seizure-prone individuals.

<span class="mw-page-title-main">Chlorphenesin carbamate</span> Muscle relaxant drug

Chlorphenesin carbamate is a centrally acting muscle relaxant used to treat muscle pain and spasms. Chlorphenesin carbamate is no longer used for this purpose in most developed nations due to the availability of much safer spasmolytics such as benzodiazepines.

An analgesic adjuvant is a medication that is typically used for indications other than pain control but provides control of pain (analgesia) in some painful diseases. This is often part of multimodal analgesia, where one of the intentions is to minimize the need for opioids.

References

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  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 "Methocarbamol Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists.
  4. 1 2 3 4 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 1093. ISBN   9780857113382.
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  9. ↑ Analytical Profiles of Drug Substances and Excipients, pp. 373
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