4, 10–13 Read full chapter. The plasma half-life is 8 hours and the duration of action is 4 to 6 hours. The drug is supplied as 350-mg tablets and the recommended dose is one tablet taken four times daily. The onset of action of carisoprodol is 30 minutes. Carisoprodol is also available in combination with aspirin (Soma Compound) or aspirin and codeine (Soma Compound with Codeine).
Andrew Dubin, in Practical Management of Pain (Fifth Edition), 2014. Kenneth C. Jackson, .
Read full chapter. On the other hand, all the centrally acting muscle relaxants cause sedation, and it seems likely that any muscle relaxant properties of these drugs are caused by their sedative effects. GABA, an inhibitory neurotransmitter in the central nervous system, tends to decrease neuronal activity, including the activity of the α-motor neuron that activates skeletal muscle. Valium increases the inhibitory effects of GABA in the spinal cord. The drugs commonly used to control muscle spasms act on the central nervous system and attempt to reduce excitatory input onto the α-motor neuron. Carisoprodol, for example, may affect GABA receptors in a manner similar to diazepam, whereas cyclobenzaprine may increase the inhibitory effects of serotonin in the brainstem. The actions of other centrally acting muscle relaxants are poorly understood. Diazepam (Valium) and a diverse group of drugs such as carisoprodol (Soma), cyclobenzaprine (Flexeril), and other centrally acting muscle relaxants are available to treat these conditions. Valium increases GABA-mediated inhibition of the α-motor neuron, which, in turn, causes decreased muscle activation, with subsequent relaxation of muscles that are in spasm.
Minke Reuvers, Christof Schaefer, in Drugs During Pregnancy and Lactation (Second Edition), 2007.
The driving-related skills affected by either include loss of coordination, sluggish movements, tremor, reduced visual functioning, confusion, disorientation, slowed cognition, and lack of comprehension. The former is prescribed to relax muscles and the latter is prescribed to reduce anxiety; both are dispensed in tablet form. Carisoprodol and meprobamate are both central nervous system depressants that are legally available only by prescription.
Given that most of these medications are used only to address symptoms and do not affect any structural changes to the lumbosacral area, they are perhaps best used during acute exacerbations of CLBP rather than on an ongoing basis. Read full chapter. The ideal CLBP patient for this type of intervention should also be willing to engage in an active intervention such as therapeutic exercise to address possible physical contributors to their condition. Patients with CLBP who are most likely to experience improvements with common analgesics are those without any contraindications or sensitivities to a specific medication, and without risk factors for chronicity such as psychological dysfunction, financial disincentives, or poor social support systems.
For antiepileptics used for the treatment of neuropathic pain, see Chapter 4.8. Among the myotonolytics, in the broadest sense, there are very different agents, such as baclofen, carisoprodol, quinine ethyl carbonate, chlormezanone, clostridium botulinum toxin, dantrolene, fenyramidol, mephenesin, methocarbamol, orphenadrine, pridinol, tetrazepam, tizanidine, and tolperisone.
The plasma half-life is 8 hours, and the duration of action is 4 to 6 hours. Carisoprodol is also available in combination with aspirin (Soma Compound) or aspirin and codeine (Soma Compound with Codeine). Read full chapter. The onset of action of carisoprodol is 30 minutes. The drug is supplied as 350-mg tablets, and the recommended dose is one tablet taken 4 times daily.
Wallace, in Kelley and Firestein's Textbook of Rheumatology (Tenth Edition), 2017. Polston, Mark S. Gregory R.
Signs of cognitive and psychomotor impairment in persons found to be driving under the influence of either carisoprodol or meprobamate include poor perception, impaired reaction time, confusion, disorientation, inattentiveness, slurred speech, slow responses, sleepiness, lack of coordination, and difficulty standing, walking or exiting vehicles.
From: Pain Management, 2007.
There is one case report on baclofen in which a maximum of 0.13mg/l was measured in the mother's milk following a single dose of 20mg ( Erikssons 1981 ). In one breastfeed, this would be 1.2% of the weight-related dosage for the child.
Carisoprodol is available as a 250-mg or 350-mg tablet and in combination with aspirin (soma compound) and with aspirin and codeine (soma compound with codeine). Carisoprodol dosing should not exceed four doses in a 24-hour period ( Table 41.2 ). Similar to other muscle relaxants, carisoprodol has additive sedative effects when taken with alcohol or other central nervous system (CNS) depressants.
Physiotherapeutic measures and antiphlogistics/ antirheumatics are preferable. In individual cases, the relaxant effect of low doses of the better-studied diazepam should be used in the short term. Apart from emergency treatment with dantrolene for malignant hyperthermia, the indications for using a myotonolytic should be considered very critically. Read full chapter.
Recommendation. The available experience with the use of the other older and outdated treatments in pregnancy is not sufficient for a risk assessment.
Waldman MD, JD, in Pain Review, 2009. Steven D.
Cyclobenzaprine, structurally related to first-generation tricyclic antidepressants, inhibits the reuptake of norepinephrine in the locus coeruleus and inhibits descending serotonergic pathways in the spinal cord. Baclofen also acts by inhibiting the release of substance P in the spinal cord. The latter effect may have an inhibitory effect on alpha motor neurons in the spinal cord, resulting in decreased firing and a reduction in mono- and polysynaptic spinal reflexes. Baclofen activates GABA-B receptors in the brain and reduces the release of excitatory neurotransmitters in both the brain and spinal cord. Carisoprodol, a precursor of the sedative-hypnotic meprobamate, is believed to produce muscle relaxation by blocking interneuronal activity in the descending reticular formation and spinal cord. Tizanidine acts as a weak agonist at alpha-2 adrenergic receptors, and enhances presynaptic inhibition at spinal motor neurons. Skeletal muscle relaxants such as cyclobenzaprine (Flexeril), chlorzoxazone (Paraflex), carisoprodol (Soma), methocarbamol (Robaxin, Robaxisal), tizanidine (Zanaflex), and baclofen (Lioresal) are believed to exert their mechanism of action primarily within the brain and in some cases spinal motor neurons.
Carisoprodol is a precursor of meprobamate (Miltown and Equanil), and meprobamate is one of the three primary metabolites produced by hepatic biotransformation.
Cohen MD, in Essentials of Pain Medicine (Third Edition), 2011. Julie H.Y. Steven P. Huang MD, MBA, .
dantrolene for malignant hyperthermia. Myotonolytics are relatively contraindicated during pregnancy, and should be reserved for very special indications – e.g. Read full chapter. Physiotherapeutic measures and anti-inflammatory agents or antirheumatics are preferable. Exposure to the myotonolytics mentioned does not require either a termination of the pregnancy or invasive diagnostic procedures. In certain cases, the tension-releasing action of the better-studied diazepam can be used.
C.D. Ciccone PT, PhD, FAPTA, in Orthopaedic Physical Therapy Secrets (Third Edition), 2017.
Hanson, in Principles of Addiction, 2013. David J.
Withdrawal symptoms are similar to those seen in withdrawal from barbiturates and include restlessness, anxiety, insomnia, anorexia, and vomiting. Severe withdrawal symptoms have included agitation, hallucinations, seizures, and, rarely, death. Carisoprodol is a precursor of meprobamate (Miltown and Equanil), and meprobamate is one of the three primary metabolites produced by hepatic biotransformation. Because of this potential for physical dependency, carisoprodol should be tapered rather than abruptly discontinued following long-term use. Idiosyncratic adverse effects include weakness, speech disturbances, temporary visual loss, ataxia, and transient paralysis. Meprobamate dependency secondary to carisoprodol usage has been reported with associated drug-seeking behavior and withdrawal symptoms.
Alcohol also increases the sleepiness, disorientation, incoherence, and confusion that meprobamate can cause. Read full chapter. The use of other central nervous system depressants can also contribute to impairment. Alcohol increases the sedation and mental confusion that can be produced by carisoprodol.
CYP1C19 inducers such as rifampin or St. It is metabolized in the liver to meprobamate, a Schedule IV medication with abuse potential. John's wort increase exposure to meprobamate. Read full chapter. 113 Meprobamate binds to GABA A receptors, which results in further sedation. Doses start at 250 mg, as often as four times per day, with a maximum dose of 1400 mg per day. Carisoprodol in animal studies has shown muscle relaxation through altered interneuronal activity in the spinal cord and in the descending reticular formation of the brain. CYP1C19 inhibitors such as omeprazole or fluvoxamine may increase carisoprodol levels and decrease meprobamate. It is contraindicated in patients with a history of acute intermittent porphyria.
Christof Schaefer, in Drugs During Pregnancy and Lactation (Second Edition), 2007.
72–74 With regard to oral agents for spasticity associated with multiple sclerosis, several controlled studies have shown benefit for oral baclofen. There is robust evidence supporting the use of intrathecal baclofen in spinal cord injury (SCI) related–spasticity. 75 In comparative-effectiveness studies between oral baclofen and tizanidine, the results have been mixed. 75 For tizanidine, most, but not all studies have demonstrated efficacy. Read full chapter.
There are anecdotal reports of normal pregnancy outcomes, but also of withdrawal syndromes (especially convulsions) after bacolofen treatment during pregnancy. There are five case reports on intrathecal baclofen therapy; three patients were treated throughout the whole pregnancy. In two cases, 20–80mg was taken orally throughout the whole pregnancy. All five newborns were healthy and did not show withdrawal symptoms ( Roberts 2003, Munoz 2000 ). The other newborn showed hyperirritability and respiratory problems ( Moran 2004 ). Baclofen, carisoprodol, chlormezanone, clostridium botulinum toxin, dantrolene, fenyramidol, mephenesin, methocarbamol, orphenadrine, pridinol, quinine ethylcarbonate, tetrazepam, tizanidine, and tolperisone are available for treating muscle tension. Again there were no malformations, but both children suffered from withdrawal – one with seizures on day 7 ( Ratnayaka 2001 ).
61 Another randomized, placebo-controlled trial found cyclobenzaprine to be more effective than both placebo and clonazepam in patients with TMD. Three separate randomized trials evaluating cyclobenzaprine in patients with cervical and lumbar spinal muscle spasm demonstrated efficacy in short-term follow-up. 62. Numerous studies conducted over many years have evaluated various skeletal muscle relaxants in conditions associated with muscle pain ( Table 18-4 ). A meta-analysis review found that cyclobenzaprine is more effective than placebo for LBP associated with muscle spasm, especially in the first 4 days of treatment. 58–60 In two of these studies, 59, 60 cyclobenzaprine was superior to diazepam.
The greatest impairment was found among those whose combined use of carisoprodol and meprobamate led to high blood concentrations of those drugs. Driving behaviors that were observed included extreme weaving, striking other vehicles and fixed objects, and hit-and-run accidents of which the driver appeared to be unaware. Similarly, among persons involved in driving under the influence cases who were found to be positive for carisoprodol and/or meprobamate and in which no other drugs were detected, impairment included slow reflexes, disorientation, sleepiness, poor balance, poor coordination, and slurred speech.
64 Another double-blind, placebo-controlled trial reported a significant improvement in subjective feedback in TMD treated with meprobamate. 65. 63 Yet in a more recent multicenter, randomized, double-blind, placebo-controlled, parallel-group study, carisoprodol was found to provide significant pain relief in patients with acute, painful muscle spasm of the lower back when compared to placebo. In a double-blind, placebo-controlled trial evaluating carisoprodol treatment in TMD, no difference was found between treatment and control groups.
Recommendation. There is also insufficient experience on the use of the other drugs while breastfeeding – some of them are therapeutically out of date, and a mild sedation of the breastfed child is conceivable.
Wolff, in Evidence-Based Management of Low Back Pain, 2012. Malanga, Erin T. Gerard A.
Following the use of chlormezanone during pregnancy, a fulminating hepatitis with a liver transplant and the birth of a healthy child has been reported ( Bourliere 1992 ).
The effects of carisoprodol begin within 30 min of ingestion and continue for as long as 4–6 h. However, single doses of meprobamate can impair divided attention, slow reflexes, increase reaction time, and impair coordination. Single doses of carisoprodol (700 mg) do not appear to effect cognitive or psychomotor performance. The effects of meprobamate last much longer.
66, 67 Another placebo-controlled study found tizanidine to be effective for patients with painful muscle spasm following lumbar disk surgery. Two randomized, double-blind studies performed in patients with acute lumbar and cervical paravertebral muscle spasm found that tizanidine provided comparable pain relief to diazepam, but was associated with increased spinal mobility. 68 Studies determining efficacy of tizanidine for treating TTH have yielded conflicting results, with some, 69, 70 but not all, 71 demonstrating efficacy.
Howard J. Waldman, in Pain Management, 2007. Katherine A. Waldman, .
Muscle relaxants are mostly used for acute LBP or acute exacerbations of CLBP, rather than prolonged CLBP. Diazepam is indicated for UMN muscle spasticity and local painful musculoskeletal spasm, as well as anxiety. The primary indications for cyclobenzaprine, metaxolone, methocarbamol, and carisoprodol are acute painful musculoskeletal conditions. Because the true mechanism of action on muscle spasm is unknown, the sedating side effects are often used to improve sleep. 16 Baclofen and tizanidine are indicated for spasticity associated with UMN disorders, but are frequently used off-label for painful musculoskeletal conditions.
At steady-state conditions in one woman using carisoprodol 2100mg/d, on average 0.9mg/l was found in her milk plus 11.6mg/l of the active metabolite meprobamate. The relative dose would be 4%. The child was unremarkable, but was only partly breastfed ( Nordeng 2001 ). No general conclusions for tolerance could be drawn from this.
Meprobamate dependency secondary to carisoprodol use has been reported with associated drug-seeking behavior and withdrawal symptoms. Idiosyncratic adverse effects include weakness, speech disturbances, temporary visual loss, ataxia, and transient paralysis. Carisoprodol is a precursor of meprobamate (Miltown and Equanil), and meprobamate is one of the three primary metabolites produced by hepatic biotransformation. Because of this potential for physical dependency, carisoprodol should be tapered rather than abruptly discontinued following long-term use. Severe withdrawal symptoms have included agitation, hallucinations, seizures, and, rarely, death. Withdrawal symptoms are similar to those seen in withdrawal from barbiturates and include restlessness, anxiety, insomnia, anorexia, and vomiting.
Several states within the United States have begun listing carisoprodol as a controlled substance in their state formularies. 11-16 Substance abuse is problematic with carisoprodol, probably as a consequence of meprobamate formation. Meprobamate is well known to produce phenomena that result in physical and psychological dependence. Read full chapter. It should also be cautiously tapered as opposed to immediay discontinued following long-term use. Carisoprodol is converted in the liver to meprobamate (Miltown), an intravenous (IV) controlled substance. However, carisoprodol is not considered a controlled substance at the federal level. Because of the dependence potential, carisoprodol use should be avoided.Carisoprodol