Methocarbamol, sold under the brand name Robaxin among others, is a medication used for short-term musculoskeletal pain. It may be used together with rest, physical therapy, and

pain medication An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). I ...

. It is less preferred in low back pain. It has limited use for

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

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, stiff muscles, weak muscles, and tremors. There may be problems with sens ...

. 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 nutrie ...

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

anaphylaxis Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

, liver problems, confusion, and

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

s. Use is not recommended in

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

and

breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that bre ...

. Because of 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 therap ...

. How it works is unclear, but it does not appear to affect muscles directly.

History and culture

Methocarbamol was developed in 1956 in the laboratories of A. H. Robins (later acquired by

Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfize ...

). Studies were directed towards the development of

propanediol Propanediol may refer to any of four isomeric organic chemical compounds: Non-geminal diols (glycols) *1,2-Propanediol Propylene glycol ( IUPAC name: propane-1,2-diol) is a viscous, colorless liquid, which is nearly odorless but possesses a f ...

derivatives which possessed muscle relaxant properties superior to those of

mephenesin Mephenesin ( INN) 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 co ...

, 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 ...

. It is relatively inexpensive as of 2016. In 2020, it was the 127th most commonly prescribed medication in the United States, with more than 4million prescriptions.

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 is 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 ...

. 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 ...

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

; 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.

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 the brand name Flexeril, among others) is a medication used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth. Use is not recommended for mor ...

, 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.

Contraindications

There are few contraindications to methocarbamol. They include: * Hypersensitivity to methocarbamol or to 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 process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describe ...

and urea retention.

Side effects

Methocarbamol is a centrally acting skeletal muscle relaxant that has significant 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 is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

), 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 sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, ...

(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), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, ...

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

, 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 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 abnormal heme meta ...

, 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

aminotransferase 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 c ...

( 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, mathema ...

) levels, to confirm

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

. 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 similar increased risk of injury. Methocarbamol is cited along with "most muscle relaxants" in the 2012

Beers Criteria The Beers Criteria for Potentially Inappropriate Medication Use in Older Adults, commonly called the Beers List, are guidelines published by the American Geriatrics Society (AGS) for healthcare professionals to help improve the safety of prescribi ...

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. The related ...

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

Overdose

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

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

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

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

, 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 be ...

and its prodrug

carisoprodol 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. ...

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

lorazepam Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety disorders, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and che ...

and the antihistamine

diphenhydramine Diphenhydramine (DPH) is an antihistamine and sedative mainly used to treat allergies, insomnia, and symptoms of the common cold. It is also less commonly used for tremor in parkinsonism, and nausea. It is taken by mouth, injected into ...

, 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 Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. This increases the amount of the acetylcholine or butyrylcholine in the sy ...

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 has no effect on 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 formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formall ...

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 The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

problems, and those with

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

problems.

Metabolism

Methocarbamol is the

derivative of

guaifenesin Guaifenesin, also known as glyceryl guaiacolate, is an expectorant medication that aids in the elimination of sputum from the respiratory tract. Chemically it is an ether of guaiacol and glycerine. It is often used in combination with other ...

, 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, ...

, 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 i ...

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 the brand name Flexeril, among others) is a medication used for muscle spasms from musculoskeletal conditions of sudden onset. It is not useful in cerebral palsy. It is taken by mouth. Use is not recommended for mor ...

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

Economics

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, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...

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

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used for treating pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus ar ...

as Robax Platinum; with

acetylsalicylic acid Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat ...

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 substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...

s are a typically first line in treatment of 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. 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 has not been established in pediatric individuals below the age of 16 except in

References

External links

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