Methocarbamol, sold under the brand name Robaxin among others, is a medication used for short-term

musculoskeletal The human musculoskeletal system (also known as the human locomotor system, and previously the activity system) is an organ system that gives humans the ability to move using their muscular and skeletal systems. The musculoskeletal system provid ...

pain. It may be used together with rest, physical therapy, and

pain medication An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in so ...

. It is less preferred in

low back pain Low back pain or wiktionary:lumbago#Etymology, lumbago is a common musculoskeletal disorders, 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 var ...

. It has limited use for

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

and

cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, spasticity, stiff muscles, Paresis, weak muscles, and tremors. There may b ...

. Effects generally begin within half an hour. It is taken by mouth or

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. Common side effects include headaches, sleepiness, and dizziness. Serious side effects may include

anaphylaxis Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

, liver problems, confusion, and

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

s. Use is not recommended in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

and

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

. Because of the risk of injury, skeletal muscle relaxants should generally be avoided in geriatric patients. Methocarbamol is a centrally acting

muscle relaxant 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 therapeu ...

. How it works is unclear, but it does not appear to affect muscles directly. Methocarbamol was developed in 1956 in the laboratories of A. H. Robins (later acquired by

Pfizer Pfizer Inc. ( ) is an American Multinational corporation, multinational Pharmaceutical industry, pharmaceutical and biotechnology corporation headquartered at The Spiral (New York City), The Spiral in Manhattan, New York City. Founded in 184 ...

). 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. It was approved for medical use in the United States in 1957. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2022, it was the 126th most commonly prescribed medication in the United States, with more than 5million prescriptions. Methocarbamol is available in a

fixed-dose combination A combination drug is a combination of two or more pharmaceutical drugs as active ingredients combined into a single dosage form, typically as a ''fixed-dose combination'', with each constituent standardized to specifications of a fixed dose. Fix ...

with ibuprofen as methocarbamol/ibuprofen (sold under the brand name Summit Ultra).

Medical use

Methocarbamol is a muscle relaxant used to treat acute, painful musculoskeletal spasms in a variety of musculoskeletal conditions. 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 Tetanus (), also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'' and characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually l ...

. It does not, however, replace the current treatment regimen. It is not useful in chronic neurological disorders, such as

or other

dyskinesia Dyskinesia refers to a category of movement disorders that are characterized by involuntary muscle movements, including movements similar to tics or chorea and diminished voluntary movements. Dyskinesia can be anything from a slight tremor of t ...

s. Currently, there is some suggestion that muscle relaxants may improve the symptoms of

; 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.

Comparison to similar agents

The clinical effectiveness of methocarbamol compared to other muscle relaxants is not well known. One trial of methocarbamol versus

cyclobenzaprine 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. Common ...

, 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

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 Acidosis is a biological process producing hydrogen ions and increasing their concentration in blood or body fluids. pH is the negative log of hydrogen ion concentration and so it is decreased by a process of acidosis. Acidemia The term ac ...

and urea retention.

Side effects

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 Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

), upset stomach, flushing, mood changes, trouble urinating, itchiness, and fever. * Both

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

(fast heart rate) and

bradycardia Bradycardia, also called bradyarrhythmia, is a resting heart rate under 60 beats per minute (BPM). While bradycardia can result from various pathological processes, it is commonly a physiological response to cardiovascular conditioning or due ...

(slow heart rate) have been reported. * Hypersensitivity reactions and anaphylatic reactions are also reported. * May cause respiratory depression when combined with

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

barbiturate Barbiturates are a class of depressant, depressant drugs that are chemically derived from barbituric acid. They are effective when used medication, medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological a ...

codeine Codeine is an opiate and prodrug of morphine mainly used to treat pain, coughing, and diarrhea. It is also commonly used as a recreational drug. It is found naturally in the sap of the opium poppy, ''Papaver somniferum''. It is typically use ...

, or other muscle relaxants. * May cause urine to turn black, blue, or green. While the product label states that methocarbamol can cause

jaundice Jaundice, also known as icterus, is a yellowish or, less frequently, greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving ...

, 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 Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid con ...

( AST/

ALT Alt or ALT may refer to: Abbreviations for words * Alt account, an alternative online identity also known as a sock puppet account * Alternate character, in online gaming * Alternate route, type of highway designation * Alternating group, mathem ...

) levels, to confirm

hepatotoxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdr ...

. Although unlikely, it is impossible to rule out that methocarbamol may cause mild liver injury with use.

Elderly

Skeletal muscle relaxants are associated with an increased risk of injury among older adults. Methocarbamol appeared to be less sedating than other muscle relaxants, most notably

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."

Pregnancy

Methocarbamol is labeled by the FDA as a

pregnancy category The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does ''not'' include any risks conferred by pharmaceutical agents or their ...

C medication. The

teratogenic Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology caused by ...

effects of the medication are not known and should be given to pregnant women only when indicated.

Overdose

There is limited information available on the acute toxicity of methocarbamol. Overdose is observed frequently in conjunction with CNS depressants such as

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

s and will have symptoms of nausea, drowsiness, blurred vision,

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

, seizures, and coma. There are reported deaths with an overdose of methocarbamol alone or in the presence of other CNS depressants.

Abuse

Unlike other carbamates such as

meprobamate Meprobamate—marketed as Miltown by Wallace Laboratories and Equanil by Wyeth, among others—is a carbamate derivative used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the benz ...

and its prodrug

carisoprodol Carisoprodol, sold under the brand name Soma among others, is an oral medication used for musculoskeletal pain. Effects generally begin within half an hour and last for up to six hours. Common side effects include headache, dizziness, and s ...

, methocarbamol has greatly reduced abuse potential. Studies comparing it to the benzodiazepine

lorazepam Lorazepam, sold under the brand name Ativan, Tavor among others, is a benzodiazepine medication. It is used to treat anxiety (including anxiety disorders), insomnia, severe agitation, active seizures including status epilepticus, alcoh ...

and the antihistamine

diphenhydramine Diphenhydramine, sold under the brand name Benadryl among others, is an antihistamine and sedative. Although generally considered sedating, diphenhydramine can cause paradoxical central nervous system stimulation in some individuals, particula ...

, along with placebo, find that methocarbamol produces increased "liking" responses and some sedative-like effects; however, at higher doses

dysphoria Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation. In psychiatry Intense states of distress and uneas ...

is reported. It is considered to have an abuse profile similar to, but weaker than,

Interactions

Methocarbamol may inhibit the effects of pyridostigmine bromide. Therefore, methocarbamol should be used with caution in those with

myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision, ...

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.

Pharmacology

Mechanism of action

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 In organic chemistry, a carbamate is a category of organic compounds with the general Chemical formula, formula and Chemical structure, structure , which are formally Derivative (chemistry), derived from carbamic acid (). The term includes orga ...

Pharmacokinetics

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 In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

problems, and those with

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

problems.

Metabolism

Methocarbamol is the

derivative of

guaifenesin Guaifenesin, also known as glyceryl guaiacolate, sold under the brand name Mucinex, among others, is an expectorant medication taken by mouth and marketed as an aid to eliminate sputum from the respiratory tract. Chemically, it is an ether of ...

, but does not produce guaifenesin as a

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

, 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. Small amounts of unchanged methocarbamol are also excreted in the urine.

Society and culture

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 Orphenadrine (sold under many brand names) 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 ...

are each used in more than 250,000 U.S. emergency department visits for lower back pain each year. In the United States, low back pain is the fifth most common reason for all physician visits and the second most common symptomatic reason. 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. The most commonly prescribed drugs for low back pain included skeletal muscle relaxants.

Cyclobenzaprine 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. Common ...

and methocarbamol are on the U.S. Medicare formulary, which may account for the higher use of these products.

Economics

It is relatively inexpensive as of 2016. The generic formulation of the medication is relatively inexpensive, costing less than the alternative

metaxalone Metaxalone, sold under the brand name Skelaxin, is a muscle relaxant medication used to relax muscles and relieve pain caused by strains, sprains, and other musculoskeletal conditions. Its exact mechanism of action is not known, but it may be due ...

in 2016.

Marketing

Methocarbamol without other ingredients is sold under the brand name Robaxin in the U.K., U.S., Canada and South Africa; it is marketed as Lumirelax in France, Ortoton in Germany and many other names worldwide. In combination with other active ingredients it is sold under other names: with

acetaminophen Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...

(paracetamol), under trade names Robaxacet and Tylenol Body Pain Night; with

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...

as Robax Platinum; with

acetylsalicylic acid Aspirin () is the Generic trademark, genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions ...

as Robaxisal in the U.S. and Canada. However, in Spain the tradename Robaxisal is used for the paracetamol combination instead of Robaxacet. These combinations are also available from independent manufacturers under generic names.

Research

Although

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

s 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 fracture A rib fracture is a break in a rib bone. This typically results in chest pain that is worse with inspiration. Bruising may occur at the site of the break. When several ribs are broken in several places a flail chest results. Potential complicat ...

s. However, methocarbamol was less useful in the treatment of acute traumatic pain in general. 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

References

{{Portal bar , Medicine Carbamates Catechol ethers Drugs with unknown mechanisms of action Muscle relaxants Secondary alcohols Veterinary drugs Glycerols 2-Methoxyphenyl compounds Wikipedia medicine articles ready to translate