What are muscle relaxers

Muscle relaxers are a heterogeneous group of medications acting both centrally and peripherally to relieve muscle spasms. Muscle relaxers are used to treat two different conditions: (1) spasticity from upper motor neuron syndromes as occurs in multiple sclerosis or cerebral palsy and (2) muscular pain or spasms from peripheral musculoskeletal diseases or injury such as low back pain. Although muscle relaxers have by convention been classified into one group, the Food and Drug Administration (FDA) has approved only a few muscle relaxers in this class for treatment of spasticity; the remainder are approved for treatment of musculoskeletal conditions ¹.

The muscle relaxers in current use have variable mechanisms of action, efficacy and side effects. Muscle relaxers are generally well tolerated, with the most common side effects being drowsiness and nausea.

Skeletal muscle relaxers have been in wide use for decades. Data from the Third National Health and Nutrition Examination (NHANES III) survey (1988–1994) estimated that 1% of American adults are taking muscle relaxants, often on a chronic basis ².

What do muscle relaxers do?

Muscle relaxers are a heterogeneous group of medications acting both centrally and peripherally to relieve muscle spasms. Muscle relaxers are used to treat two different conditions: (1) spasticity from upper motor neuron syndromes as occurs in multiple sclerosis or cerebral palsy and (2) muscular pain or spasms from peripheral musculoskeletal diseases or injury such as low back pain.

Spasticity, although difficult to define precisely, is a clinical condition that has been described as “a motor disorder characterized by velocity dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex, as one component of the upper motor neuron syndrome” ³. The upper motor neuron syndrome is a complex of signs and symptoms that, in addition to spasticity, can be associated with exaggerated cutaneous reflexes, autonomic hyperreflexia, dystonia, contractures, paresis, lack of dexterity, and fatigability ⁴. Spasticity from the upper motor neuron syndrome can result from a variety of conditions affecting the cortex or spinal cord. Some of the more common conditions associated with spasticity and requiring treatment include multiple sclerosis ⁵, spinal cord injury ⁶, traumatic brain injury, cerebral palsy, and post-stroke syndrome ⁷. In many patients with these conditions, spasticity can be disabling and painful with a marked effect on functional ability and quality of life ⁸.

Common musculoskeletal conditions causing tenderness and muscle spasms include fibromyalgia ⁹, tension headaches ¹⁰, myofascial pain syndrome, and mechanical low back or neck pain. If muscle spasm is present in these conditions, it is related to local factors involving the affected muscle groups. There is no hypertonicity or hyperreflexia, and the other symptoms associated with the upper motor neuron syndrome are not present. These conditions are commonly encountered in clinical practice and can cause significant disability and pain in some patients. Skeletal muscle relaxants are one of several classes of medications (including antidepressants, neuroleptics, anti-inflammatory agents, and opioids) frequently used to treat these conditions ¹¹.

How do muscle relaxers work?

Skeletal muscle relaxers have been approved for either treatment of spasticity or for treatment of musculoskeletal conditions. Drugs classified as skeletal muscle relaxers are baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine and tizanidine. Only baclofen, dantrolene, and tizanidine are approved for the treatment of spasticity ¹. These three antispasticity medications act by different mechanisms: baclofen blocks pre- and post-synaptic GABA-B (gamma-amino butyric acid B) receptors ¹², tizanidine is a centrally acting agonist of α2 receptors ¹³ and dantrolene directly inhibits muscle contraction by decreasing the release of calcium from skeletal muscle sarcoplasmic reticulum ¹⁴. Medications from other classes have also been used to treat spasticity. Diazepam, a benzodiazepine, was the first medication thought to be effective for spasticity. It acts by central blockade of GABA-A (gamma-amino butyric acid A) receptors ¹⁵. Other medications used to treat spasticity but not formally approved for this indication include other benzodiazepines, clonidine, gabapentin, and botulinum toxin ¹⁴.

The skeletal muscle relaxers carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine have been approved for treatment of musculoskeletal disorders, but not for spasticity. They constitute a heterogeneous group of medications. Cyclobenzaprine is closely related to the tricyclic antidepressants ¹⁶, carisoprodol is metabolized to meprobamate ¹⁷, methocarbamol is structurally related to mephenesin ¹⁶, chlorzoxazone is a benzoxazolone derivative ¹⁸ and orphenadrine is derived from diphenhydramine ¹⁹. The mechanism of action for most of these agents is unclear, but may be related in part to sedative effects. These drugs are often used for treatment of musculoskeletal conditions whether muscle spasm is present or not ²⁰. Although there is some overlap between clinical usage (tizanidine in particular has been studied for use in patients with musculoskeletal complaints) ²¹, in clinical practice each skeletal muscle relaxant is used primarily for either spasticity or for musculoskeletal conditions.

List of muscle relaxers

• Baclofen (Lioresal, Baclosan)
• Carisoprodol (Soma, Carisoma, Sodol)
• Chlorzoxazone (Parafon Forte, Remular)
• Cyclobenzaprine (Flexeril)
• Dantrolene (Dantrium)
• Methocarbamol (Marbaxin, Robaxin)
• Metaxalone (Skelaxin)
• Orphenadrine (Flexon, Norgesic, Norflex)
• Tizanidine (Zanaflex)

Baclofen

Baclofen is a centrally acting muscle relaxant commonly prescribed for spasticity in patients with multiple sclerosis. Baclofen is sometimes prescribed for other uses; ask your doctor or pharmacist for more information. Baclofen is a gamma-amino butyric acid (GABA) derivative that acts as an agonist of the GABA B receptor, thereby activating potassium channels and reducing calcium conductance leading to hypotonia and muscle relaxation. Baclofen acts primarily at the level of the spinal cord, inhibiting synaptic reflexes. Baclofen reduces the number and severity of muscle spasms and relieves pain, clonus and muscle rigidity due to spasticity. Baclofen is indicated primarily for treatment of spasticity from spinal cord injuries and multiple sclerosis. Baclofen has been used off label as adjunctive therapy to help with alcohol abstinence and withdrawal.

Baclofen was approved for use in the United States in 1977 and is widely used with several million prescriptions filled yearly.

Baclofen is available in various generic forms as well as under the brand names of Lioresal and Remular in tablets of 10 or 20 mg and in formulations for intrathecal injections of 0.5 mg/mL. The recommended adult dose for spasticity is 10 to 20 mg orally three to four times daily at evenly spaced intervals. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take baclofen exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. Baclofen must be taken regularly for a few weeks before its full effect is felt. The dose should be increased and tapered gradually.

Continue to take baclofen even if you feel well. Do not stop taking baclofen without talking to your doctor, especially if you have taken large doses for a long time. Your doctor probably will want to decrease your dose gradually.

The most common side effects of baclofen are nausea, drowsiness, confusion, dizziness and fatigue.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Baclofen special precautions

Before taking baclofen:

• tell your doctor and pharmacist if you are allergic to baclofen or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially muscle relaxants, sleeping pills, tranquilizers, and vitamins.
• tell your doctor if you have or have ever had kidney disease, epilepsy, ulcers, a stroke, a rheumatic disease, cerebral palsy, Parkinson’s disease, or a psychiatric condition.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking baclofen, call your doctor immediately.
• you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how baclofen affects you.
• remember that alcohol can add to the drowsiness caused by this drug.

Baclofen side effects

Baclofen may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• drowsiness
• dizziness
• weakness
• confusion
• upset stomach

If you experience either of the following symptoms, call your doctor immediately:

• difficulty breathing
• seizures

Baclofen may cause other side effects. Call your doctor if you have any unusual problems while you are taking baclofen.

Carisoprodol

Carisoprodol is a centrally acting muscle relaxant that has been in use for more than fifty years. Carisoprodol is a carbamate derivative similar to meprobamate. Carisoprodol mechanism of action as a muscle relaxant is unknown, but it is a sedative and may act centrally by modifying perception of pain without affecting pain reflexes. Carisoprodol is recommended for treatment of acute, painful disorders caused by strains, sprains, and other muscle injuries and is used with rest, physical therapy, and other measures to relax muscles and relieve pain and discomfort.

Carisoprodol is available by prescription only and is classified as a Schedule IV agent, meaning that it has low potential for abuse and physical or psychological dependence and has an accepted medical usefulness.

Carisoprodol is available in 250 and 350 mg tablets in generic formulations and under the trade names of Soma, Carisoma, Sodol and Vanadom. Fixed combinations of carisoprodol with aspirin or codeine are also available. The recommended adult dosage is 250 to 350 mg three to four times daily for 2 to 3 weeks. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take carisoprodol exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Carisoprodol may cause an upset stomach. Take carisoprodol with food or milk.

Carisoprodol was approved for use in the United States in 1959 and is widely used with more than 10 million prescriptions filled yearly.

Common side effects include dizziness, drowsiness and headache. Overdose can cause progressive obtundation, coma, neuromuscular rigidity, myoclonus and seizures.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Carisoprodol special precautions

Before taking carisoprodol:

• tell your doctor and pharmacist if you are allergic to carisoprodol, meprobamate (Equanil, Meprospan, Miltown, Neuramate), any other medications, or any of the ingredients in carisoprodol tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially medications for allergies, coughs, or colds; muscle relaxants; sedatives; sleeping pills; tranquilizers; and vitamins.
• tell your doctor if you have or have ever had kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking carisoprodol, call your doctor.
• talk to your doctor about the risks and benefits of taking carisoprodol if you are 65 years of age or older. Older adults should not usually take carisoprodol because it is not as safe or effective as other medications that can be used to treat the same condition.
• you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how carisoprodol affects you.
• remember that alcohol can add to the drowsiness caused by this drug.

Carisoprodol side effects

Carisoprodol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• drowsiness
• dizziness
• clumsiness
• headache
• fast heart rate
• upset stomach
• vomiting
• skin rash

If you experience any of the following symptoms, call your doctor immediately:

• difficulty breathing
• fever
• weakness
• burning in the eyes

Carisoprodol may cause other side effects. Call your doctor if you have any unusual problems while you are taking carisoprodol.

Chlorzoxazone

Chlorzoxazone is a centrally acting muscle relaxant commonly used for low back pain caused by muscle strains and sprains. Chlorzoxazone has been linked to rare instances of acute liver injury, a few of which have been fatal. Chlorzoxazone acts centrally rather than directly on muscles to relieve muscle spasms, either through its sedative effects or other unknown mechanisms. Chlorzoxazone is indicated for therapy of low back pain and muscle spasms, in combination with physical therapy, analgesics (such as aspirin or acetaminophen), and rest, although its overall efficacy is considered only fair.

Chlorzoxazone was approved for use in the United States in 1958 and is still widely used.

Chlorzoxazone is available in various generic forms as well as under the brand names of Parafon Forte and Remular in tablets of 250 or 500 mg. The usual recommended dose in adults is 250 to 750 mg orally three to four times daily, reducing the dose to lowest effective level once a response occurs. Chlorzoxazone is typically given for 1 to 4 weeks only. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take chlorzoxazone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Common side effects of chlorzoxazone include dizziness, drowsiness, headache, fatigue and tremor.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Chlorzoxazone special precautions

Before taking chlorzoxazone:

• tell your doctor and pharmacist if you are allergic to chlorzoxazone or any other medications.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially sedatives, sleeping pills, tranquilizers, and vitamins.
• tell your doctor if you have or have ever had liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking chlorzoxazone, call your doctor.
• talk to your doctor about the risks and benefits of taking chlorzoxazone if you are 65 years of age or older. Older adults should not usually take chlorzoxazone because it is not as safe or effective as other medications) that can be used to treat the same condition.
• you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• ask your doctor about the safe use of alcohol during your treatment with chlorzoxazone. Alcohol can make the side effects of this medication worse.

Chlorzoxazone side effects

Chlorzoxazone may cause side effects. Your urine may turn purple or red; this effect is not harmful. Tell your doctor if any of these symptoms are severe or do not go away:

• upset stomach
• drowsiness
• dizziness
• lightheadedness
• weakness

If you experience any of the following symptoms, call your doctor immediately:

• skin rash or itching
• yellowing of the skin or eyes
• stomach pain

Chlorzoxazone may cause other side effects. Call your doctor if you have any unusual problems while you are taking chlorzoxazone.

Cyclobenzaprine

Cyclobenzaprine is a centrally acting muscle relaxant closely related to the tricyclic antidepressants. Despite its similarity to tricyclic antidepressants, there is little evidence that cyclobenzaprine causes liver injury. Cyclobenzaprine is a tricyclic antidepressant derivative that relaxes skeletal muscle by an unknown mechanism of action. Cyclobenzaprine is also a central nervous system depressant, and its efficacy may be related to its sedative effects. Cyclobenzaprine is used with rest, physical therapy, and other measures to relax muscles and relieve pain and discomfort caused by strains, sprains, and other muscle injuries.

Cyclobenzaprine comes as a tablet and an extended-release capsule to take by mouth. The recommended dosage in adults is 5 to 10 mg three times daily for 3 to 4 weeks. Cyclobenzaprine is available in tablets of 5 and 10 mg in multiple generic forms and under the trade names of Flexeril, Flexamid and Amrix. Extended release capsules of 15 and 30 mg are also available. The extended-release capsule is usually taken with or without food once a day. Swallow the extended-release capsules whole; do not chew or crush them. If you are not able to swallow the extended-release capsule whole, mix the contents of the capsule with applesauce. Eat the mixture right away and swallow without chewing. After you eat the mixture, take a drink, and swish and swallow to make sure that you have received all the medication.

Cyclobenzaprine is usually administered for limited periods of time. Do not take cyclobenzaprine for more than 3 weeks without talking to your doctor. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take cyclobenzaprine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Cyclobenzaprine was approved for use in the United States in 1977 and it remains widely used with more than 10 million prescriptions filled yearly.

Common side effects include sleepiness, dry mouth, dizziness and headache.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for the missed one.

Cyclobenzaprine special precautions

Before taking cyclobenzaprine:

• tell your doctor and pharmacist if you are allergic to cyclobenzaprine, any other medications, or any of the ingredients in cyclobenzaprine tablets or capsules. Ask your pharmacist for a list of the ingredients.
• tell your doctor if you are taking the following medications or have stopped taking them within the past two weeks: monoamine oxidase (MAO) inhibitors, including isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate). Your doctor will probably tell you not to take cyclobenzaprine if you are taking one of these medications.
• tell your doctor and pharmacist what other prescription and nonprescription drugs, vitamins, nutritional supplements and herbal products you are taking or plan to take. Be sure to mention any of the following: medications for allergies, coughs, or colds; barbiturates such as butabarbital (Butisol), phenobarbital, and secobarbital (Seconal); bupropion (Aplenzin, Forfivo XL, Wellbutrin, Zyban); meperidine (Demerol); sedatives; sleeping pills; selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Selfemra, in Symbyax), fluvoxamine (Luvox), paroxetine (Brisdelle, Paxil, Pexeva), and sertraline (Zoloft); selective serotonin and norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine (Khedezla, Pristiq), duloxetine (Cymbalta), levomilnacipran (Fetzima), milnacipran (Savella) and venlafaxine (Effexor); tranquilizers; tricyclic antidepressants (TCAs) such as amitriptyline, amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); tramadol (Conzip, Ultram, in Ultracet); verapamil (Calan, Covera HS, Verelan, in Tarka); or any other medication for depression, mood, anxiety, or thought disorder. Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with cyclobenzaprine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor if you are recovering from a recent heart attack, or if you have an overactive thyroid gland. heart failure (condition in which the heart is unable to pump enough blood to the other parts of the body), or an irregular heartbeat, heart block, or other problems with the electrical impulses of your heart. Your doctor will probably tell you not to take cyclobenzaprine.
• tell your doctor if you have increased pressure in the eye or glaucoma, difficulty urinating, or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking cyclobenzaprine, call your doctor immediately.
• talk to your doctor about the risks and benefits of taking cyclobenzaprine if you are 65 years of age or older. Older adults should not usually take cyclobenzaprine because it is not as safe or effective as other medications that can be used to treat the same condition.
• you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how cyclobenzaprine affects you.
• ask your doctor about the safe use of alcoholic beverages while you are taking cyclobenzaprine. Cyclobenzaprine can make the effects of alcohol worse.

Cyclobenzaprine side effects

Cyclobenzaprine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dry mouth
• dizziness
• nausea
• constipation
• heartburn
• extreme tiredness

If you experience any of the following symptoms, call your doctor immediately:

• skin rash
• hives
• swelling of the face or tongue
• difficulty breathing or swallowing
• irregular or fast heart rate
• chest pain

Cyclobenzaprine may cause other side effects. Call your doctor if you have any unusual problems while you are taking cyclobenzaprine.

Dantrolene

Dantrolene, a muscle relaxant, is used to treat chronic spasticity or muscle spasms associated with spinal cord injuries, stroke, multiple sclerosis, cerebral palsy, or other conditions. Dantrolene differs from other commonly used muscle relaxants in acting peripherally on muscle, rather than centrally on the spinal cord or brain. Dantrolene can cause acute liver injury which can be severe and even fatal (see Important Warning).

Dantrolene is a lipid soluble diphenylhydantoin analogue that inhibits muscle contractions by decreasing the release of calcium from the sarcoplasmic reticulum in target tissue. Dantrolene is used for the treatment of chronic spasticity and treatment for and prophylaxis against malignant hyperthermia (based upon its ability to block calcium release, which is the initiating event in malignant hyperthermia). Dantrolene was approved for use in the United States in 1974 and is still commonly used for spasticity.

Dantrolene is available as capsules of 25, 50 and 100 mg in several generic forms and under the commercial name Dantrium. Dantrolene usually is taken once a day at first and then increased gradually to two to four times a day. In adults, the recommended initial dose for spasticity is 25 mg daily, with subsequent increases to a dose of 25 to 100 mg three times daily. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take dantrolene exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor. If you cannot swallow capsules, empty the contents into fruit juice and mix well just before taking the dose.

Dantrolene is also available in parenteral formulations for therapy of acute episodes of malignant hyperthermia; the recommended initial dose being 1 mg/kg intravenously. For prophylaxis against hyperthermia, dantrolene is given orally in doses of 4 to 8 mg/kg daily.

Common side effects include weakness, nausea, drowsiness, fatigue and dizziness.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for the missed one.

Dantrolene special precautions

Before taking dantrolene:

• tell your doctor and pharmacist if you are allergic to dantrolene or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially diazepam (Valium); estrogen; medications for seizures, allergies, colds, or coughs; sedatives; sleeping pills; tranquilizers; and vitamins.
• tell your doctor if you have or have ever had liver, heart, rheumatic, or lung disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking dantrolene, call your doctor immediately.
• you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how dantrolene affects you.
• remember that alcohol can add to the drowsiness caused by this drug.
• you should plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Dantrolene may make your skin sensitive to sunlight.

Dantrolene side effects

Dantrolene may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• muscle weakness
• drowsiness
• dizziness
• diarrhea
• fatigue
• difficulty swallowing

In addition to the symptoms mentioned in the IMPORTANT WARNING section, if you experience the following symptom, call your doctor immediately:

• seizures

Dantrolene may cause other side effects. Call your doctor if you have any unusual problems while you are taking dantrolene.

Metaxalone

Metaxalone is a centrally acting skeletal muscle relaxant that has been in use for more than 40 years. Metaxalone acts centrally as a skeletal muscle relaxant, but its efficacy and precise mechanism of action are not well documented. Metaxalone was approved for use in the United States in 1962 and it remains a widely used muscle relaxant. Current indications include the treatment of pain and discomfort from acute musculoskeletal conditions and muscle spasms caused by strains, sprains, and other muscle injuries, in combination with rest, physical therapy, and other measures.

Metaxalone comes as a tablet to take by mouth. The recommended dosage is 800 mg orally three to four times daily. Metaxalone is available by prescription only in 400 and 800 mg tablets in generic forms as well as under the commercial name Skelaxin. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take metaxalone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Sparse data are available regarding metaxalone safety. Side effects are not common, but can include drowsiness, dizziness, headache, nausea, and dry mouth.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Metaxalone special precautions

Before taking metaxalone:

• tell your doctor and pharmacist if you are allergic to metaxalone, any other medications, or any of the ingredients in metaxalone tablets. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially medications for seizures, allergies, colds, or coughs; pain medications; sedatives; tranquilizers; and vitamins.
• tell your doctor if you have or have ever had kidney disease, liver disease, seizures, or a blood disorder.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while taking metaxalone, call your doctor immediately.
• talk to your doctor about the risks and benefits of taking metaxalone if you are 65 years of age or older. Older adults should not usually take metaxalone because it is not as safe or effective as other medications that can be used to treat the same condition.
• you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how metaxalone affects you.
• remember that alcohol can add to the drowsiness caused by this drug.

Metaxalone side effects

Metaxalone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• drowsiness
• dizziness
• upset stomach
• vomiting
• headache
• nervousness

If you experience any of the following symptoms, call your doctor immediately:

• severe skin rash
• difficulty breathing
• yellowing of the skin or eyes
• unusual bruising or bleeding
• unusual tiredness or weakness
• seizures

Metaxalone may cause other side effects. Call your doctor if you have any unusual problems while you are taking metaxalone.

Methocarbamol

Methocarbamol is a commonly used, centrally acting muscle relaxant. Methocarbamol is a guaifenesin derivative and acts centrally as a muscle relaxant by an unknown mechanism. Methocarbamol was approved for use in the United States in 1957, and currently more than 3 million prescriptions are filled yearly. Methocarbamol is used with rest, physical therapy, and other measures for the relief of acute, painful musculoskeletal conditions caused by strains, sprains, and other muscle injuries.

Methocarbamol comes as a tablet to take by mouth. Methocarbamol is available in 500 and 750 mg tablets in several generic formulations, both alone and in combination with other drugs and under the brand names of Robaxin and Marbaxin. The recommended dosage is 1500 mg orally three to four times daily at first, then it may be changed to three to six times a day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take methocarbamol exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

The most common side effects of methocarbamol are drowsiness blurred vision, headache, nausea and skin rash.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Methocarbamol special precautions

Before taking methocarbamol:

• tell your doctor and pharmacist if you are allergic to methocarbamol, any other medications or any of the ingredients in methocarbamol tablets. Ask your doctor or pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: medications for seizures, depression, colds, or coughs; sedatives; and tranquilizers.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking methocarbamol, call your doctor.
• talk to your doctor about the risks and benefits of taking methocarbamol if you are 65 years of age or older. Older adults should not usually take methocarbamol because it is not as safe or as effective as other medications that can be used to treat the same condition.
• you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how methocarbamol affects you.
• talk to your doctor about the safe use of alcohol during your treatment with this medication. Alcohol can make the side effects of methocarbamol worse.

Methocarbamol side effects

Methocarbamol may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• drowsiness
• dizziness
• upset stomach
• blurred vision
• fever
• black, blue, or green discoloration of urine

If you experience either of the following symptoms, call your doctor immediately:

• rash
• itching

Methocarbamol may cause other side effects. Call your doctor if you have any unusual problems while you are taking methocarbamol.

Orphenadrine

Orphenadrine is a centrally acting muscle relaxant that works by changing the way your body senses muscle pain. Orphenadrine is a centrally acting, nonopiate analgesic and muscle relaxant that has been in clinical use for more than 50 years. Orphenadrine is a methyl derivative of diphenhydramine (a commonly used antihistamine), but its mechanism of action in causing analgesia and skeletal muscle relaxation is not well defined. Orphenadrine has anticholinergic activity and may act centrally on pain perception. Orphenadrine is currently used with rest, physical therapy, and other measures for the treatment of acute, painful musculoskeletal conditions to relieve pain and discomfort caused by strains, sprains, and other muscle injuries. Orphenadrine can be given orally or parenterally. Orphenadrine was approved for use as a muscle relaxant in the United States in 1957 and it is still in wide use.

Orphenadrine comes as a tablet and an extended-release (long-acting) tablet to take by mouth. Orphenadrine is available in multiple generic forms as standard and extended release tablets of 100 mg. Orphenadrine is also available under commercial names such as Norgesic, Norflex, Deenar, Banflex, Disipal and X-Otag. The recommended dosage is 100 mg twice daily. Try to take orphenadrine at around the same times every day. Orphenadrine extended-release, swallow the extended-release tablets whole, do not split, chew, or crush them. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take orphenadrine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Orphenadrine is also available in parenteral formulations under the names of Flexoject and Myolin. The parenteral dose recommendation is 60 mg either intravenously or intramuscularly twice daily.

The most common side effects are those typical of anticholinergics including drowsiness, dry mouth, diaphoresis, flushing, confusion and visual disturbances. Orphenadrine also has a potential for abuse and fatal overdoses have been reported.

What should I do if I forget a dose?

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Orphenadrine special precautions

Before taking orphenadrine:

• tell your doctor and pharmacist if you are allergic to orphenadrine,any other medications, or any of the ingredients in orphenadrine tablets or extended-release tablets.
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: amantadine (Symadine, Symmetrel), fluphenazine (Prolixin), haloperidol (Haldol), medications for colds or allergies, medications for depression, perphenazine (Trilafon), prochlorperazine (Compazine), promethazine (Phenergan), sedatives, sleeping pills,and trifluoperazine (Stelazine). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had glaucoma; myasthenia gravis; ulcers; a urinary tract or intestinal blockage; an enlarged prostate; an irregular heartbeat; or liver, kidney, or heart disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking orphenadrine, call your doctor.
• talk to your doctor about the risks and benefits of taking orphendrine if you are 65 years of age or older. Older adults should not usually take orphenadrine because it is not as safe as other medications that can be used to treat the same condition.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking orphenadrine.
• you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how orphenadine will affect you.
• ask your doctor about the safe use of alcohol while you are taking this medication. Alcohol can make the side effects of orphenadrine worse.

Orphenadrine side effects

Orphenadrine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dry mouth
• drowsiness
• dizziness or lightheadedness
• upset stomach
• vomiting
• constipation
• difficulty urinating
• blurred vision
• headache

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately:

• fast or irregular heartbeat
• fainting
• confusion
• hallucinations
• skin rash

Orphenadrine may cause other side effects. Call your doctor if you have any unusual problems while you are taking orphenadrine.

Tizanidine

Tizanidine is a commonly used muscle relaxant that has been linked to rare instances of acute liver injury, a few of which have been fatal. Tizanidine is an imidazoline derivative and is a centrally acting muscle relaxant used for therapy of acute muscle spasms and chronic spasticity. The mechanism by which tizanidine causes skeletal muscle relaxation is not well known; it appears to act at the level of spinal cord pain reflexes, most likely through activity as a central alpha-adrenergic agonist which results in an decrease in activity of motor neurons. Tizanidine was approved for use in the United States in 1996 and currently several million prescriptions are filled yearly. The current indications are limited to short-term management of spasticity and increased muscle tone caused by multiple sclerosis (MS, a disease in which the nerves do not function properly and patients may experience weakness, numbness, loss of muscle coordination and problems with vision, speech, and bladder control), stroke, or brain or spinal injury.

Tizanidine comes as a tablet and a capsule to take by mouth. Tizanidine is available in several generic forms as well as under the brand name of Zanaflex in tablets and capsules of 2, 4 or 6 mg. The recommended dose in adults is 2 to 6 mg orally three to four times daily. Tizanidine is usually taken consistently either always with or always without food two or three times a day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take tizanidine exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Tizanidine capsules may be opened and sprinkled on soft foods such as applesauce. Talk to your doctor before opening the capsules because the effects of the medication when used in this manner may be different than when swallowing the capsule whole.

The medication in the capsule is absorbed differently by the body than the medication in the tablet, so one product cannot be substituted for the other. Each time you have your prescription filled, look at the tablets or capsules in the bottle and make sure that you have received the right product. If you think you received the wrong medication, talk to your doctor or pharmacist right away.

Your doctor will probably start you on a low dose of tizanidine and gradually increase your dose, depending on your response to this medication.

Do not stop taking tizanidine without talking to your doctor. If you suddenly stop taking tizanidine, your heart may beat faster and you may have increased blood pressure or tightness in your muscles. Your doctor will probably decrease your dose gradually.

Common side effects include tiredness, drowsiness, dizziness, muscular weakness, dry mouth and occasionally hypotension.

What should I do if I forget a dose?

If your doctor has told you to take tizanidine regularly, take the missed dose as soon as you remember it. However, if it is almost time for your next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Tizanidine special precautions

Before taking tizanidine:

• tell your doctor and pharmacist if you are allergic to tizanidine or any other medications.
• tell your doctor if you are taking ciprofloxacin (Cipro) or fluvoxamine. Your doctor will probably tell you not to take tizanidine if you are taking either of these medications.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: acyclovir (Zovirax); amiodarone (Cordarone, Pacerone); baclofen; cimetidine (Tagamet); clonidine (Catapres, Catapres-TTS); dantrolene (Dantrium); diazepam (Valium); famotidine (Pepcid, Pepcid AC); medications for anxiety, seizures, or high blood pressure; mexiletine (Mexitil); oral contraceptives (birth control pills); propafenone (Rythmol); fluoroquinolones such as gemifloxacin (Factive), levofloxacin (Levaquin), moxifloxacin (Avelox), norfloxacin (Noroxin), and ofloxacin (Floxin); ticlopidine (Ticlid); sedatives; sleeping pills; tranquilizers; verapamil (Calan, Covera, Isoptin, Verelan); and zileuton (Zyflo). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Other medications may also interact with tizanidine, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• tell your doctor if you have or have ever had kidney or liver disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking tizanidine, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking tizanidine.
• you should know that this medication may make you drowsy. Do not drive a car or operate machinery until you know how this medication affects you.
• remember that alcohol can add to the drowsiness caused by this medication.
• you should know that tizanidine may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking tizanidine. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up. Tizanidine can decrease muscle tone, so be careful when walking or doing other activities where you rely on your muscle tone to help with your posture or balance.

Tizanidine side effects

Tizanidine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• dizziness
• drowsiness
• weakness
• nervousness
• depression
• vomiting
• tingling sensation in the arms, legs, hands, and feet
• dry mouth
• constipation
• diarrhea
• stomach pain
• heartburn
• increased muscle spasms
• back pain
• rash
• sweating

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• nausea
• extreme tiredness
• unusual bleeding or bruising
• lack of energy
• loss of appetite
• pain in the upper right part of the stomach
• yellowing of the skin or eyes
• unexplained flu-like symptoms
• seeing things or hearing voices that do not exist
• slow heartbeat
• changes in vision

Tizanidine may cause other side effects. Call your doctor if you have any unusual problems while taking tizanidine.

1. Chou R, Peterson K. Drug Class Review: Skeletal Muscle Relaxants: Final Report [Internet]. Portland (OR): Oregon Health & Science University; 2005 May. Introduction. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10693[↩][↩]
2. Dillon C, Paulose-Ram R, Hirsch R. et al. Skeletal Muscle Relaxant Use in the United States: Data from the Third National Health and Nutrition Examination Survey (NHANES III). Spine. 2004;29(8):892–896.[↩]
3. Lance JW. Symposium synopsis. In: Feldman RG, Young RR, Koella WP, eds. Spasticity: disordered motor control. Chicago: Yearbook Medical; 1980:485–494[↩]
4. Young RR. Spasticity: a review. Neurology. 1994;44(11 Suppl 9):S12–20[↩]
5. Andersson PB, Goodkin DE. Current pharmacologic treatment of multiple sclerosis symptoms. West J Med. 1996;165(5):313–317[↩]
6. Burchiel KJ, Hsu FP. Pain and spasticity after spinal cord injury: mechanisms and treatment. Spine. 2001;26(24 Suppl):S146–160.[↩]
7. Barnes MP. Medical management of spasticity in stroke. Age Ageing. 2001;30(Suppl. 1):13–16.[↩]
8. Anonymous Spasticity. Lancet. 1989;2(86788679):1488–1490.[↩]
9. Leventhal LJ. Management of fibromyalgia. Ann Intern Med. 1999;131(11):850–858.[↩]
10. Redillas C, Solomon S. Prophylactic pharmacological treatment of chronic daily headache. Headache. 2000;40(2):83–102.[↩]
11. Cherkin DC, Wheeler KJ, Barlow W. et al. Medication use for low back pain in primary care. Spine. 1998;23(5):607–614[↩]
12. Davidoff RA. Antispasticity drugs: mechanisms of action. Ann Neurol. 1985;17(2):107–116.[↩]
13. Wagstaff AJ, Bryson HM. Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997;53(3):435–452[↩]
14. Kita M, Goodkin DE. Drugs used to treat spasticity. Drugs. 2000;59(3):487–495.[↩][↩]
15. Cook JB, Nathan PW. On the site of action of diazepam in spasticity in man. J Neurol Sci. 1967;5(1):33–37.[↩]
16. Preston EJ, Miller CB, Herbertson RK. A double-blind, multicenter trial of methocarbamol (Robaxin) and cyclobenzaprine (Flexeril) in acute musculoskeletal conditions. Todays Ther Trends. 1984;1(4):1–11[↩][↩]
17. Reeves R, Carter O, Pinkofsky H. Carisoprodol (Soma): abuse potential and physician unawareness. J Addict Dis. 1999;18:51–56.[↩]
18. Azoury FJ. Double–blind study of Parafon Forte and Flexeril in the treatment of acute skeletal muscle disorders. Curr Ther Res. 1979;26:189–197[↩]
19. Gold RH. Orphenadrine citrate: Sedative or muscle relaxant? Clin Ther. 1978;1(6):451–453.[↩]
20. Cherkin DC, Wheeler KJ, Barlow W. et al. Medication use for low back pain in primary care. Spine. 1998;23(5):607–614.[↩]
21. Smith HS, Barton AE. Tizanidine in the management of spasticity and musculoskeletal complaints in the palliative care population. Am J Hosp Palliat Care. 2000;17(1):50–58[↩]