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Skeletal Muscle Relaxants (Systemic)

This monograph includes information on the following:

1) Carisoprodol
2) Chlorphenesin 
3) Chlorzoxazone 
4) Metaxalone 
5) Methocarbamol
6) Orphenadrine

VA CLASSIFICATION
Carisoprodol
Primary: MS200

Chlorphenesin
Primary: MS200

Chlorzoxazone
Primary: MS200

Metaxalone
Primary: MS200

Methocarbamol
Primary: MS200

Orphenadrine Citrate
Primary: MS200

Orphenadrine Hydrochloride
Primary: AU305


Commonly used brand name(s): Antiflex6; Banflex6; Carbacot5; Disipal6; EZE-DS3; Flexoject6; Maolate2; Mio-Rel6; Myolin6; Myotrol6; Norflex6; Orfro6; Orphenate6; Paraflex3; Parafon Forte DSC3; Relaxazone3; Remular3; Remular-S3; Robaxin5; Robaxin-7505; Skelaxin4; Skelex5; Soma1; Strifon Forte DSC3; Vanadom1.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Skeletal muscle relaxant—Carisoprodol; Chlorphenesin; Chlorzoxazone; Metaxalone; Methocarbamol; Orphenadrine Citrate;

Parkinsonism therapy adjunct—Orphenadrine Hydrochloride;

Indications

Accepted

Spasm, skeletal muscle (treatment)—Skeletal muscle relaxants are indicated as adjuncts to other measures, such as rest and physical therapy, for the relief of muscle spasm associated with acute, painful musculoskeletal conditions. {01} {02} {03} {04} {05} {06} {07} {09} {11}

Parkinsonism (treatment adjunct)—Orphenadrine hydrochloride is indicated (but is rarely used) as an adjunct to physical therapy and other medications in the treatment of postencephalic, arteriosclerotic, or idiopathic parkinsonism. {11} It produces symptomatic relief of tremor. The medication may be used concurrently with reduced dosages of more potent medications in treating patients who cannot tolerate effective doses of the other medications.

Unaccepted
Methocarbamol is also FDA-approved for control of the neuromuscular manifestations of tetanus. {05} However, it has largely been replaced in the treatment of tetanus by diazepam, or, in severe cases, a neuromuscular blocking agent such as pancuronium. Such therapy is used as an adjunct to other measures, such as debridement, tetanus antitoxin, penicillin, tracheotomy, fluid and electrolyte replacement, and supportive treatment. {05}


Pharmacology/Pharmacokinetics

Table 1. Pharmacology/Pharmacokinetics



Drug
Absorption
Protein
Binding
(%)
Biotransformation
Half-
life
(hr)
Elimination
Primary (%
Excreted Unchanged)/
Secondary
Carisoprodol
    Hepatic *
{01} {02} {13} {17}
8
{02} {13} {17}
Renal (<1)
{01} {02} {17}
Chlorphenesin
Rapid; complete
{14}
  Hepatic
{14}
2.3–5
{13} {14} {17}
Renal §
Chlorzoxazone
Rapid; complete
{13} {14}
  Hepatic
{13}
1.1
{13} {14} {17}
Renal (<1)
{03} {14}
Metaxalone
    Hepatic
{14}
2–3
{14}
Renal
{14}
Methocarbamol
Rapid
{14}
  Probably
hepatic
{14}
0.9–2.2
{13} {17}
Renal/fecal
{17}
Orphenadrine
  Low
Hepatic
14 #
{13} {14} {17}
Renal/fecal
{17}
* One of the metabolites is meprobamate. {13}
 Distributed into breast milk; concentration may reach 2 to 4 times the maternal plasma concentration. {01} {02} Also, may be removed from the circulation via hemodialysis and peritoneal dialysis. {01} {02} {14}
 At least partially metabolized. {14}
§ 85% of a dose excreted within 24 hours as the glucuronide metabolite.
# For the parent compound; half-life of metabolites may range from 2 to 25 hours. {17}

Table 2. Pharmacology/Pharmacokinetics



Drug
Onset of
Action
Time to
Peak Concentration
(hr)
(single dose)
Peak
Serum Concentration
(single dose)
Duration
of Action
(hr)
Carisoprodol
0.5 hr
{17}
4 (350 mg)
{17}
4–7 mcg/mL
{14}
4–6
{01} {02} {13}
Chlorphenesin
  1–3
{17}
3.8–17 mcg/mL (800 mg)
{17}
 
Chlorzoxazone
Within 1 hr
1–2
{03} {13}
10–30 mcg/mL (750 mg)
3–4
{17}
Metaxalone
1 hr
{17}
2 (800 mg)
{17}
295 mcg/mL (800 mg)
{17}
 
Methocarbamol
       
Oral
Within 0.5 hr
{14}
2 (2 grams)
{17}
16 mcg/mL (2 grams)
{14}
 
IV (300 mg/min)
Immediate
{14}
Almost immediate
{14}
19 mcg/mL (1 gram)
{14}
 
Orphenadrine citrate *
       
Oral (extended-release tablets)
Within 1 hr
6 to 8 (100 mg)
60–120 nanograms/mL (100 mg)
12
IM
5 min
0.5 (60 mg)
   
IV
Immediate
Immediate
   
Orphenadrine hydrochloride
Within 1 hr
3 (50 mg)
110–210 nanograms/mL (100 mg)
8
* Relief of muscle spasm.
 In parkinsonism.

Physicochemical characteristics:
Molecular weight—
    Carisoprodol: 260.34 {12}
    Chlorphenesin carbamate: 245.66 {12}
    Chlorzoxazone: 169.57 {12}
    Metaxalone: 221.26 {12}
    Methocarbamol: 241.25 {12}
    Orphenadrine citrate: 461.51 {12}
    Orphenadrine hydrochloride: 305.85

Mechanism of action/Effect:

Skeletal muscle relaxant—Precise mechanism of action has not been determined. {01} {02} {03} {04} {05} {06} {09} {17} {18} These agents act in the central nervous system (CNS) {13} {17} {18} rather than directly on skeletal muscle. {01} {02} {03} {04} {05} {06} {09} {13} {18} Several of these medications have been shown to depress polysynaptic reflexes preferentially. {03} {13} {17} {18} The muscle relaxant effects of most of these agents may be related to their CNS depressant (sedative) effects. {01} {02} {03} {04} {05} {06} {17} {18} Carisoprodol blocks interneuronal activity in the descending reticular formation and in the spinal cord. {01} {02} Chlorzoxazone acts primarily at the spinal cord level and at subcortical areas of the brain. {13} Orphenadrine has analgesic activity, which may contribute to its skeletal muscle relaxant properties. {09}

Parkinsonism therapy adjunct—Orphenadrine has mild anticholinergic actions, which produce its beneficial effect in parkinsonism.


Other actions/effects:

Orphenadrine also has anticholinergic properties. {09}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other carbamate derivatives (for example, carbromal, meprobamate, mebutamate, or tybamate) may be sensitive to carisoprodol also. {01}

Pregnancy/Reproduction

Pregnancy—

Carisoprodol, chlorzoxazone, and methocarbamol

Problems in humans have not been documented.



Chlorphenesin

Studies have not been done in either animals or humans.



Metaxalone

Although studies in humans have not been done, studies in rats have not shown that metaxalone causes adverse effects in the fetus. {04}



Orphenadrine

Problems in humans have not been documented.

Studies in animals have not been done. {09}

Orphenadrine citrate—FDA Pregnancy Category C. {09}


Breast-feeding

Carisoprodol:

Carisoprodol is distributed into breast milk in concentrations that may reach 2 to 4 times the maternal plasma concentrations; {01} {02} use by nursing mothers may cause sedation and gastrointestinal upset in the infant.



Chlorphenesin, chlorzoxazone, metaxalone, methocarbamol, and orphenadrine:

It is not known whether these medications are distributed into breast milk. However, problems in humans have not been documented. {04} {05} {06} {07} {14}


Pediatrics


Carisoprodol:

Although appropriate studies with carisoprodol have not been performed in the pediatric population, {01} the medication has been used in children. {14} Pediatrics-specific problems that would limit the use of carisoprodol in these patients have not been documented.



Chlorphenesin, metaxalone, methocarbamol, and orphenadrine:

No information is available on the relationship of age to the effects of these medications in pediatric patients. Safety and efficacy have not been established. {04} {05} {06} {07} {09} {10}



Chlorzoxazone:

This medication has been used in children. Pediatrics-specific problems that would limit use of chlorzoxazone in these patients have not been documented.



Geriatrics


No information is available on the relationship of age to the effects of skeletal muscle relaxants in geriatric patients. However, elderly males are more likely to have age-related prostatic hypertrophy and may therefore be adversely affected by orphenadrine's anticholinergic activity. Also, elderly patients are more likely to have age-related renal function impairment, which may require that parenteral methocarbamol not be used at all and that other skeletal muscle relaxants be used with caution.


Dental


Orphenadrine:

The peripheral anticholinergic effects of orphenadrine may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.


Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.


For all skeletal muscle relaxants
» Alcohol or
» CNS depression–producing medications, other (See Appendix II )    (concurrent use with a skeletal muscle relaxant may result in additive CNS depressant effects; caution is recommended and dosage of one or both agents should be reduced {01} {02} {03} {05} {06} {07})


For orphenadrine (in addition to the interaction listed above)
Anticholinergics or other medications with anticholinergic action (See Appendix II )    (anticholinergic effects may be intensified when these medications are used concurrently with orphenadrine because of orphenadrine"s secondary anticholinergic activity)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results

For metaxalone:
Copper sulfate urine sugar tests    (false-positive test results may occur, possibly because of the presence of an unknown reducing substance; results of tests using glucose oxidase are not affected {04})


For methocarbamol:
5-Hydroxyindoleacetic acid (5-HIAA), in urine, determinations     (values may be falsely increased when the nitrosonaphthol reagent is used )


Vanillylmandelic acid (VMA), in urine, determinations    (values may be falsely increased when the Gitlow screening method is used; no error occurs when the quantitative procedure of Sunderman is used)

With physiology/laboratory test values

For metaxalone
Cephalin flocculation tests    (elevations may occur without concurrent changes in other liver function tests {04})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Table 3. Medical considerations/Contraindications



The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance).
Legend:
I=Carisoprodol
II=Chlorphenesin
III =Chlorzoxazone


IV=Metaxalone
V =Methocarbamol
VI=Orphenadrine

I
 
II
 
III
 
IV
 
V
 
VI
 
Except under special circumstances, these medications should not be used when the following medical problems exist:
 
           
» Achalasia or
         
» Bladder neck obstruction or
         
» Glaucoma, or predisposition to, or
         
» Myasthenia gravis or
         
» Peptic ulcer, stenosing, or
         
» Prostatic hypertrophy or
         
» Pyloric or duodenal obstruction
         
(anticholinergic actions detrimental in these conditions)
           
» Hemolytic anemia, or history of, especially if drug-induced
(may be induced by metaxalone)
     
   
» Porphyria, acute intermittent, known or suspected

       
 
» Renal function impairment or disease
(for parenteral dosage form only—polyethylene glycol 300 vehicle is nephrotoxic and may cause increased urea retention and acidosis in these patients)
       

 
Risk-benefit should be considered when the following medical problems exist:
 
           
Allergic reaction to the medication considered for use, history of






Allergies or history of
   
     
Cardiac disease or arrhythmias or
         
tachycardia
         
(orphenadrine may cause tachycardia)
           
CNS depression
(may be exacerbated)






Drug abuse or dependence, history of
(psychological dependence and abuse reported rarely)

         
Epilepsy
(for parenteral dosage form only—may increase risk of seizures)
       

 
Hepatic function impairment
(metabolized in liver)


   

» Hepatic function impairment or disease
(metabolized in liver; also, potentially hepatotoxic)
   

   
Renal function impairment
(excreted via kidneys)






» Renal function impairment, severe
(excreted via kidneys)
     
   

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


For metaxalone
Liver function tests    (recommended periodically during prolonged metaxalone therapy, especially if the patient has pre-existing hepatic function impairment or disease {04})


For methocarbamol
Renal function determinations    (recommended if parenteral therapy lasts 3 days or more because the polyethylene glycol 300 vehicle may be nephrotoxic)


For orphenadrine
Blood count and
Liver function tests and
Renal function tests    (recommended during prolonged therapy since the safety of continuous long-term use has not been established {09} {10})




Side/Adverse Effects

Table 4. Side/Adverse Effects *



The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Legend:
I=Carisoprodol
II=Chlorphenesin
III=Chlorzoxazone


IV=Metaxalone
V=Methocarbamol
VI=Orphenadrine

I
 
II
 
III
 
IV
 
V
 
VI
 
Medical attention needed
 
           
Anticholinergic effects, specifically:
Decreased urination
 





L
Increased intraocular pressure (eye pain)





L
Cardiovascular effects, specifically:
Fast heartbeat —with orphenadrine, anticholinergic activity may contribute to this effect
L
U
U
U
U
L
Pounding heartbeat
 
U
U
U
U
U
L
Slow heartbeat—with parenteral dosage form only




L
U
Thrombophlebitis (local pain, tenderness, heat, redness, swelling at site of affected vein)—with parenteral administration only




R
U
Central nervous system effects, specifically:
Convulsions
 
U
U
U
U
R
U
Fainting—with carisoprodol, may also be caused by orthostatic hypotension
L
U
U
U
R
L
Hallucinations —orphenadrine's anticholinergic activity may contribute to this effect
U
U
U
U
U
R
Mental depression
 
L
U
U
U
U
U
Gastrointestinal bleeding (bloody or black, tarry stools; vomiting of blood or material that looks like coffee grounds)
U
R
R
U
U
U
Hematologic effects, specifically:
Agranulocytosis (fever with or without chills; sores, ulcers, or white spots on lips or in mouth; sore throat)
U
R
R
U
U
U
Anemia (unusual tiredness or weakness)
U
U
R
U
U
U
Anemia, aplastic [pancytopenia] (shortness of breath, troubled breathing, tightness in chest, and/or wheezing; sores, ulcers, or white spots on lips or in mouth; swollen and/or painful glands; unusual bleeding or bruising; unusual tiredness or weakness)
R
U
U
U
U
R
Anemia, hemolytic (troubled breathing, exertional; unusual tiredness or weakness)
U
U
U
R
U
U
Leukopenia (usually asymptomatic; rarely, fever or chills, cough or hoarseness, lower back or side pain, painful or difficult urination)
R
R
U
R
R
U
Thrombocytopenia (usually asymptomatic; rarely, unusual bleeding or bruising; black, tarry stools; blood in urine or stools; pinpoint red spots on skin)
U
R
U
U
U
U
Hepatotoxicity (yellow eyes or skin)
U
U
R
R
U
U
Hypersensitivity reactions, specifically:
Anaphylactic or anaphylactoid reaction (changes in facial skin color; skin rash, hives, and/or itching; fast or irregular breathing; puffiness or swelling of the eyelids or around the eyes; shortness of breath, troubled breathing, tightness in chest, and/or wheezing)—with carisoprodol, anaphylactic shock with sudden, severe decrease in blood pressure and collapse has also occurred
R
R
R
R
U
U
Angioedema (hive-like swellings, large, on face, eyelids, mouth, lips, and/or tongue)
L
U
R
U
U
U
Bronchospastic allergic reaction (shortness of breath, troubled breathing, tightness in chest, and/or wheezing)
L
U
U
U
U
U
Conjunctivitis and nasal congestion (stuffy nose and red or bloodshot eyes)
U
U
U
U
L
U
Dermatitis, allergic (skin rash, hives, itching, and/or redness)—with carisoprodol, fixed drug eruptions with cross-sensitivity to meprobamate have also been reported; with chlorzoxazone, petechial rashes and ecchymoses have also been reported
L
R
R
R
L
U
Eosinophilia
 
R
U
U
U
U
U
Erythema multiforme (fever with or without chills; muscle cramps or pain; skin rash; sores, ulcers, or white spots on lips or in mouth)
R
U
U
U
U
U
Fever, allergic
 
L
R
U
U
L
U
Stinging or burning of eyes
 
L
U
U
U
U
U
Medical attention needed only if continuing or bothersome
 
           
Anticholinergic effects (dryness of mouth [more frequent], confusion, difficult urination, constipation, unusually large pupils, blurred or double vision, weakness)





L
Central nervous system effects, specifically:
Blurred or double vision or any change in vision —with orphenadrine, anticholinergic activity may also contribute to this effect
R
U
U
U
M
L
Clumsiness or unsteadiness
 
R
U
U
U
U
U
Confusion—with orphenadrine, anticholinergic activity may also contribute to this effect, especially in elderly patients
U
L
U
U
U
L
Dizziness or lightheadedness—with carisoprodol, orthostatic hypotension may also contribute to this effect
L
L
M
M
M
L
Drowsiness
 
M
L
M
M
M
L
Headache
 
L
R
L
M
L
L
Muscle weakness
 
U
R
U
U
L
R
Nystagmus (uncontrolled movements of eyes)
U
U
U
U
L
U
Stimulation, paradoxical (excitement, nervousness, restlessness, irritability, trouble in sleeping)
L
R
L
M
U
L
Trembling
 
L
U
U
U
U
L
Flushing or redness of face
 
L
U
U
U
L
U
Gastrointestinal irritation, specifically:
Abdominal or stomach cramps or pain
 
L
R
L
M
U
L
Constipation—with orphenadrine, anticholinergic activity may contribute to this effect
U
U
L
U
U
L
Diarrhea
 
U
U
L
U
U
U
Heartburn
 
U
U
L
U
U
U
Hiccups
 
L
U
U
U
U
U
Nausea or vomiting
 
L
R
L
M
L
L
Pain or peeling at place of injection
 




L
U
* Differences in frequency of occurrence may reflect either lack of clinical-use data or actual pharmacologic distinctions among agents (although their pharmacologic similarity suggests that side effects occurring with one may occur with the others, except for those caused by anticholinergic activity, which is specific for orphenadrine). M = more frequent; L = less frequent; R = rare; U = unknown.
 A causal association has not been established.
 Usually reported with too-rapid intravenous administration.

Note: Rarely, an idiosyncratic reaction to carisoprodol may occur within minutes or hours following the first dose of the medication. Reported symptoms include agitation, ataxia, confusion, disorientation, dizziness, euphoria, extreme weakness, speech disturbances, temporary loss of vision or other vision disturbances, and transient quadriplegia. Symptoms usually subside within several hours, but in some cases, supportive and symptomatic therapy, including hospitalization, may be necessary. {01} {02}
Psychological dependence and abuse have occurred very rarely with carisoprodol. Signs of abstinence have not been reported with clinical usage; however, in one study abrupt withdrawal of 100 mg per kg of body weight (mg/kg) per day of carisoprodol (5 times the recommended daily dose) produced withdrawal symptoms including abdominal cramps, insomnia, chills, headache, and nausea. {01} {02}




Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Carisoprodol {01}
To decrease absorption—Emptying the stomach via induction of emesis or gastric lavage.

Specific treatment—Administering respiratory assistance, CNS stimulants, and pressor agents cautiously, if necessary.

To enhance elimination—Removing carisoprodol from the body via induction of diuresis, osmotic (mannitol) diuresis, peritoneal dialysis, or hemodialysis.

Monitoring—Monitoring urinary output.

Taking care to prevent overhydration.

Monitoring the patient for relapse due to incomplete gastric emptying and delayed absorption, and administering additional treatment as required.

Supportive care—Administering supportive treatment of observed symptoms.


Chlorphenesin:
To decrease absorption—Emptying the stomach via institution of saline catharsis or gastric lavage.

Supportive care—Administering supportive therapy of observed symptoms.



Chlorzoxazone {03}:
To decrease absorption—Emptying the stomach via induction of emesis or gastric lavage.

Specific treatment—Administering oxygen and artificial respiration for respiratory depression and plasma volume expanders or vasopressors for hypotension.

Supportive care—Administering supportive treatment of observed symptoms.

Note: Cholinergic medications and analeptic medications are of no value in chlorzoxazone overdose and should not be used.




Metaxalone:
Experience with overdose causing major toxicity is extremely limited {04}.

To decrease absorption—Emptying the stomach via induction of emesis or gastric lavage {04}.

Supportive care—Administering supportive treatment of observed symptoms {04}.



Methocarbamol:
To decrease absorption—Emptying the stomach via induction of emesis or gastric lavage (if administered orally).

To enhance elimination—The usefulness of forced diuresis or hemodialysis in treating overdose has not been determined.

Supportive care—Administering supportive treatment of observed symptoms.



Orphenadrine:
To decrease absorption—Emptying the stomach via induction of emesis or gastric lavage (if administered orally).

To enhance elimination—Maintaining a high-volume urinary output.

Institution of hemodialysis or peritoneal dialysis may be of some benefit if the serum concentration exceeds 4 mcg per mL.

Supportive care—Administering intravenous fluids and circulatory support as required. Administering supportive treatment of observed symptoms.


Note: Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



Patient Consultation

Table 5. Patient Consultation



As an aid to patient consultation, refer to Advice for the Patient, Skeletal Muscle Relaxants (Systemic) or Orphenadrine (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Legend:
I=Carisoprodol
II=Chlorphenesin
III=Chlorzoxazone


IV=Metaxalone
V=Methocarbamol
VI=Orphenadrine

I
 
II
 
III
 
IV
 
V
 
VI
 
Before using this medication
 
           
»Conditions affecting use, especially:
Sensitivity to the muscle relaxant considered for use, history of, and, for carisoprodol, sensitivity to other carbamate derivatives






Breast-feeding—Carisoprodol distributed into breast milk and may cause sedation and gastrointestinal upset in the infant; problems in nursing infants have not been reported with other skeletal muscle relaxants

         
Other medications, especially other CNS depression–producing medications






Other medical problems, especially:
Acute intermittent porphyria (known or suspected)

         
Conditions that may be adversely affected by anticholinergic activity
         
Hemolytic anemia, or history of
     
   
Hepatic function impairment or disease






Renal function impairment or disease






Proper use of this medication
 
           
Tablets may be crushed and mixed with food or liquid for ease of administration
   


 
» Proper dosing






Missed dose: Taking if remembered within an hour or so; not taking if remembered later; not doubling doses






»Proper storage






Precautions while using this medication
 
           
Regular visits to physician to check progress during prolonged therapy






»Avoiding use of alcohol or other CNS depressants during therapy unless prescribed or otherwise approved by physician






»Caution if any of the following occur:
           
Blurred vision or other vision problems

     

Clumsiness or unsteadiness

     
 
Dizziness or lightheadedness






Drowsiness






Faintness

     

Muscle weakness
         
Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with dentist if dry mouth continues for more than 2 weeks
         
Diabetics: May cause false-positive urine sugar tests
     
   
Side/adverse effects
Signs and symptoms of potential side effects, especially:
Allergic reactions






Anticholinergic effects

 

 

 

 

 

Blood dyscrasias
 




Convulsions

 

 

 

 
*

 
Fainting


 

 

 
*

Fast heartbeat


 

 

 

 

Gastrointestinal bleeding

 

 


 

 

 
Hallucinations

 

 

 

 

 

Hepatotoxicity

 

 

 


 

 
Mental depression


 

 

 

 

 
Pounding heartbeat

 

 

 

 

 

Slow heartbeat
        *
 
Medication may color urine orange or reddish purple
   
     
Medication may color urine black, brown, or green, especially if allowed to stand
       
 
* For parenteral administration only.

CARISOPRODOL

Summary of Differences


Pharmacology/pharmacokinetics:
Physicochemical characteristics—Molecular weight: 260.34.

Biotransformation—Hepatic; one metabolite is meprobamate.

Half-life—8 hours

Onset of action—0.5 hour.

Time to peak concentration—4 hours (350-mg single dose).

Peak serum concentration—4–7 mcg per mL.

Duration of action—4–6 hours.

Elimination—Renal, <1% as unchanged carisoprodol. Carisoprodol is dialyzable.



Precautions:
Cross-sensitivity and/or related problems—May occur with other carbamate derivatives.

Breast-feeding—Distributed into breast milk in significant quantities; may cause sedation and gastrointestinal upset in the nursing infant.

Medical considerations/contraindications—

Should not be used in patients with known or suspected acute intermittent porphyria.

Caution also recommended in patients with a history of drug abuse or dependence.



Side/adverse effects:
Idiosyncratic reactions may occur shortly after first dose.

Psychological dependence and abuse reported very rarely.

Also may cause orthostatic hypotension, fast heartbeat, mental depression, clumsiness or unsteadiness, fever (allergic), stinging or burning of eyes, angioedema, bronchospastic allergic reaction, blurred vision, and flushing.



Oral Dosage Forms

CARISOPRODOL TABLETS USP

Usual adult and adolescent dose
Skeletal muscle relaxant
Oral, 350 mg four times a day. {01} {02}


Usual pediatric dose
Skeletal muscle relaxant
Children up to 5 years of age: Dosage has not been established.

Children 5 to 12 years of age: Oral, 6.25 mg per kg of body weight four times a day. {20}


Strength(s) usually available
U.S.—


350 mg (Rx) [Soma{01}] [Vanadom{15}][Generic]{15}

Canada—


350 mg (Rx) [Soma{02}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a well-closed container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CHLORPHENESIN

Summary of Differences


Pharmacology/pharmacokinetics:
Physicochemical characteristics—Molecular weight: 245.66.

Absorption—Rapid; complete.

Biotransformation—Hepatic; at least partially metabolized.

Half-life—2.3–5 hours

Time to peak concentration—1–3 hours.

Peak serum concentration—3.8–17 mcg per mL (800-mg single dose).

Elimination—Renal; 85% of a dose excreted within 24 hours as the glucuronide metabolite.



Side/adverse effects:
Gastrointestinal bleeding reported, but causal relationship not established.

Also may cause fever (allergic), agranulocytosis, leukopenia, or thrombocytopenia.



Additional Dosing Information
The safety of administering chlorphenesin for longer than 8 weeks has not been established.


Oral Dosage Forms

CHLORPHENESIN CARBAMATE TABLETS

Usual adult and adolescent dose
Skeletal muscle relaxant
Oral, 800 mg three times a day initially; may be decreased to 400 mg four times a day or less, as required to maintain the desired response. {13}


Usual pediatric dose
Safety and efficacy have not been established. {13}

Strength(s) usually available
U.S.—


400 mg (Rx) [Maolate{15}{16}]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


CHLORZOXAZONE

Summary of Differences


Pharmacology/pharmacokinetics:
Physicochemical characteristics—Molecular weight: 169.57.

Absorption—Rapid; complete.

Biotransformation—Hepatic.

Half-life—1.1 hours.

Onset of action—Within 1 hour.

Time to peak concentration—1–2 hours.

Peak serum concentration—10–30 mcg per mL (750-mg single dose).

Duration of action—3–4 hours.

Elimination—Renal; <1% as unchanged chlorzoxazone.



Precautions:
Medical considerations/contraindications: Also should be used with caution in patients with allergies (or history of).



Side/adverse effects:
Also may cause agranulocytosis, gastrointesinal bleeding, angioedema, anemia, diarrhea, heartburn, and constipation.

Hepatotoxicity reported, but causal association not established.



Additional Dosing Information
Discontinuation of chlorzoxazone therapy is recommended if symptoms of hepatotoxicity or sensitivity (e.g., skin rash, hives, or itching) occur. {03}


Oral Dosage Forms

CHLORZOXAZONE TABLETS USP

Usual adult and adolescent dose
Skeletal muscle relaxant
Oral, 250 to 750 mg three or four times a day; usually 500 mg three or four times a day initially and increased or decreased as determined by patient response. {03}


Usual pediatric dose
Skeletal muscle relaxant
Oral, 20 mg per kg of body weight or 600 mg per square meter of body surface, in three or four divided doses; {20} or 125 to 500 mg three or four times a day, according to the child's age and weight. {19}


Strength(s) usually available
U.S.—


250 mg (Rx) [Paraflex{03}] [Remular-S{15}][Generic]{15}


500 mg (Rx) [EZE-DS{15}] [Parafon Forte DSC{03} (scored)] [Relaxazone{15}] [Remular{15}] [Strifon Forte DSC{15}][Generic]{15}

Canada—
Not commercially available.

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Preparation of dosage form:
Single dose—Tablets may be crushed and mixed with food or liquid for ease of administration.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


METAXALONE

Summary of Differences


Pharmacology/pharmacokinetics:
Physicochemical characteristics—Molecular weight 221.26.

Biotransformation—Hepatic.

Half-life—2–3 hours

Onset of action—1 hour.

Time to peak concentration—2 hours (800-mg single dose).

Peak serum concentration—295 mcg per mL (800-mg single dose).

Elimination—Renal.



Precautions:
Laboratory value alterations—

May interfere with copper sulfate urine sugar test results.

May cause liver function test abnormalities.

Medical considerations/contraindications—Also should not be used in patients with hemolytic anemia or a history of hemolytic anemia, especially if drug-induced.

Patient monitoring—Liver function tests recommended during prolonged therapy.



Side/adverse effects:
Also may cause hemolytic anemia and hepatotoxicity.



Additional Dosing Information
Discontinuation of metaxalone therapy is recommended if signs of hepatotoxicity occur.


Oral Dosage Forms

METAXALONE TABLETS

Usual adult and adolescent dose
Skeletal muscle relaxant
Oral, 800 mg three or four times a day. {04}


Usual pediatric dose
Safety and efficacy have not been established. {04}

Strength(s) usually available
U.S.—


400 mg (Rx) [Skelaxin{04} (scored)]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


METHOCARBAMOL

Summary of Differences


Pharmacology/pharmacokinetics:
Physicochemical characteristics—Molecular weight: 241.25.

Absorption—Rapid.

Biotransformation—Probably hepatic.

Half-life (elimination)—0.9–2.2 hours.


Onset of action——
Oral: Within 0.5 hour.

Intravenous: Immediate.



Time to peak concentration—
Oral: 2 hours (2-gram single dose).

Intravenous: Almost immediate.



Peak serum concentration—
Oral: 16 mcg per mL (2-gram single dose).

Intravenous: 19 mcg per mL (1-gram single dose).



Elimination—
Renal and fecal.




Precautions:
Laboratory value alterations—Urinary 5-Hydroxyindoleacetic acid (5-HIAA) values may be falsely increased (with nitrosonaphthol reagent).

Urinary vanillylmandelic acid (VMA) values may be falsely increased (with the Gitlow screening method).

Medical considerations/contraindications—

Parenteral dosage form should not be used in patients with renal function impairment or disease because the polyethylene glycol 300 vehicle is nephrotoxic.

Parenteral dosage form also should be used with caution in patients with epilepsy.

Patient monitoring—Renal function determinations recommended if parenteral therapy lasts 3 days or more.



Side/adverse effects:
Parenteral dosage form also reported to cause convulsions, fainting, slow heartbeat, muscle weakness, nystagmus, and facial flushing, especially when given too rapidly.

Parenteral dosage form may also cause pain or peeling of skin at injection site and thrombophlebitis.

Also may cause fever (allergic), conjunctivitis and nasal congestion, and leukopenia.

May be more likely than other muscle relaxants to cause blurred or double vision.



Additional Dosing Information

For parenteral dosage forms only
The injection may be given intravenously or intramuscularly. Subcutaneous administration is not recommended. {05}

The polyethylene glycol 300 vehicle in the parenteral dosage form may be nephrotoxic. {05}

The medication may be administered intravenously undiluted at a rate not to exceed 3 mL (300 mg) per minute. It may also be given as an intravenous infusion in sodium chloride injection or 5% dextrose injection. {05}

The patient should lie down during and for at least 10 to 15 minutes following intravenous administration. {05}

Extravasation should be avoided, since the injection is hypertonic and may cause thrombophlebitis. {05}

The manufacturer's labeling should be consulted for special directions for use in tetanus. {05}

Not more than 5 mL (500 mg) should be given intramuscularly into each gluteal region at one time. The injections may be repeated at 8-hour intervals, if necessary. {05}


Oral Dosage Forms

METHOCARBAMOL TABLETS USP

Usual adult and adolescent dose
Skeletal muscle relaxant
Initial: Oral, 1.5 grams four times a day for the first forty-eight to seventy-two hours of therapy. For severe conditions, 8 grams a day may be administered initially. {06} {07}

Maintenance: Oral, 750 mg every four hours; 1 gram four times a day; or 1.5 grams three times a day. {06}


Note: If used as adjunctive therapy in the treatment of tetanus—Via nasogastric tube, up to 24 grams a day depending on patient response. {05}


Usual pediatric dose
Safety and efficacy have not been established.

Strength(s) usually available
U.S.—


500 mg (Rx) [Carbacot{15}] [Robaxin{06}][Generic]{15}


750 mg (Rx) [Carbacot{15}] [Robaxin-750{06}][Generic]{15}

Canada—


500 mg (OTC) [Robaxin{07} (scored)]


750 mg (OTC) [Robaxin-750{07} (scored)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Preparation of dosage form:
For administration via nasogastric tube—Crush tablets and suspend in water or saline solution.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

METHOCARBAMOL INJECTION USP

Usual adult and adolescent dose
Skeletal muscle relaxant
Intramuscular or intravenous, 1 to 3 grams a day for three days. Following a drug-free interval of forty-eight hours, the course may be repeated if necessary. {05}


Note: If used as adjunctive therapy in the treatment of tetanus—Intravenous, 1 or 2 grams by direct intravenous injection. An additional 1 or 2 grams may be administered by intravenous infusion, so that a total initial dose of up to 3 grams is administered. This regimen should be repeated every six hours until therapy via a nasogastric tube can be instituted.


Usual adult prescribing limits
Total adult dosage should not exceed 3 grams per day. Also, the medication should not be administered for more than three consecutive days except in the treatment of tetanus. {05}

Usual pediatric dose
Skeletal muscle relaxant
Safety and efficacy in children up to 12 years of age have not been established for conditions other than tetanus.


Note: If used as adjunctive therapy in the treatment of tetanus—Intravenous, 15 mg per kg of body weight every six hours. {05}


Strength(s) usually available
U.S.—


100 mg per mL (1 gram per 10-mL single-dose ampul or vial) (Rx) [Carbacot{15}] [Robaxin{05}] [Skelex{15}][Generic]{15}

Canada—


100 mg per mL (1 gram per 10-mL single-dose vial) (OTC) [Robaxin{08}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

Preparation of dosage form:
For intravenous infusion—Dilute with sodium chloride injection or 5% dextrose injection; 10 mL (1 gram) of medication should be diluted to not more than 250 mL of infusion. After dilution, the injection should not be refrigerated. {06}


ORPHENADRINE

Summary of Differences


Category:
Hydrochloride salt indicated to relieve tremor in parkinsonism.


Pharmacology/pharmacokinetics—



Physicochemical characteristics—Molecular weight—
Orphenadrine citrate—461.51.

Orphenadrine hydrochloride—305.85.



Mechanism of action (parkinsonism therapy adjunct)—
Has anticholinergic activity.



Protein binding—
Low.



Biotransformation—
Hepatic.



Half-life—
14 hours (parent compound; half-life of metabolites may range from 2 to 25 hours).



Onset of action—


Orphenadrine citrate—
Oral (extended-release tablets)—Within 1 hour.

Intramuscular—5 minutes.

Intravenous—Immediate.



Orphenadrine hydrochloride—
Oral—Within 1 hour.




Time to peak concentration—


Orphenadrine citrate—
Oral (extended-release tablets)—6–8 hours (100-mg single dose).

Intramuscular—0.5 hour (60-mg single dose).

Intravenous—Immediate.



Orphenadrine hydrochloride—
Oral—3 hours (50-mg single dose).




Peak serum concentration—


Orphenadrine citrate—
Oral (extended-release tablets)—60–120 nanograms per mL (100-mg single dose).

Orphenadrine hydrochloride: Oral—110–210 nanograms per mL (100-mg single dose).




Elimination—
Renal and fecal.




Precautions:
Dental—May cause dryness of mouth.

Medical considerations/contraindications—

Also should not be used in patients with medical conditions in which anticholinergic actions are detrimental.

Also should be used with caution in patients with cardiac disease or arrhythmias, especially tachycardia.

Patient monitoring—Blood count and hepatic and renal function tests recommended during prolonged therapy.



Side/adverse effects:
Also may cause side effects typical of anticholinergics and aplastic anemia.

Also may cause hallucinations, syncope, confusion (especially in the elderly), and blurred or double vision; anticholinergic as well as CNS actions may contribute to these effects.



Additional Dosing Information
The safety of continuous long-term administration of orphenadrine has not been established.


Oral Dosage Forms

ORPHENADRINE CITRATE EXTENDED-RELEASE TABLETS

Usual adult and adolescent dose
Skeletal muscle relaxant
Oral, 100 mg two times a day, in the morning and evening. {09} {10}


Usual pediatric dose
Safety and efficacy have not been established. {09} {10}

Strength(s) usually available
U.S.—


100 mg (Rx) [Norflex{09}][Generic]{15}

Canada—


100 mg (OTC) [Norflex{10}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight, light-resistant container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


ORPHENADRINE HYDROCHLORIDE TABLETS

Usual adult and adolescent dose
Skeletal muscle relaxant
and Parkinsonism therapy adjunct
Oral, 50 mg three times a day. {11}


Note: Smaller doses may suffice if other antiparkinson medications are being administered concurrently.


Usual adult prescribing limits
Up to 250 mg a day.

Usual pediatric dose
Dosage has not been established.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—


50 mg (OTC) [Disipal{11}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

ORPHENADRINE CITRATE INJECTION USP

Usual adult and adolescent dose
Skeletal muscle relaxant
Intramuscular or intravenous, 60 mg every twelve hours as needed. {09} {10}


Usual pediatric dose
Safety and efficacy have not been established. {09}

Strength(s) usually available
U.S.—


30 mg per mL (Rx) [Antiflex{15}] [Banflex{15}] [Flexoject{15}] [Mio-Rel{15}] [Myolin{15}] [Myotrol{15}] [Norflex{09}] [Orfro{15}] [Orphenate{15}][Generic]{15}

Canada—


30 mg per mL (OTC) [Norflex{10} (sodium bisulfite)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light. Protect from freezing.



Revised: 08/11/1995



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. Carisoprodol (Soma, Wallace). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 2613.
  1. Carisoprodol (Soma, Horner). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 30th ed. Ottawa: Canadian Pharmaceutical Association, 1995: 1255.
  1. Chlorzoxazone (Paraflex, Parafon Forte DSC, McNeil). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 1471.
  1. Metaxalone (Skelaxin, Carnrick). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 847-8.
  1. Methocarbamol Injection (Robaxin, Robins). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 2014-5.
  1. Methocarbamol Tablets (Robaxin, Robaxin-750, Robins). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 2015.
  1. Methocarbamol Tablets (Robaxin, Robaxin-750, Whitehall-Robins). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 30th ed. Ottawa: Canadian Pharmaceutical Association, 1995: 1181.
  1. Methocarbamol Injection (Robaxin, Whitehall-Robins). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 30th ed. Ottawa: Canadian Pharmaceutical Association, 1995: 1181.
  1. Orphenadrine citrate (Norflex, 3M). In: PDR Physicians' desk reference. 49th ed. 1995. Montvale, NJ: Medical Economics Data Production Company, 1995: 1386.
  1. Orphenadrine citrate (Norflex, 3M). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 30th ed. Ottawa: Canadian Pharmaceutical Association, 1995: 909.
  1. Orphenadrine hydrochloride (Disipal, 3M). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 30th ed. Ottawa: Canadian Pharmaceutical Association, 1995: 410.
  1. Fleeger CA, editor. USP dictionary of USAN and international drug names 1995. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1994: 123, 144, 146, 419, 423, 488.
  1. Drug evaluations subscription. Volume I. Chicago: American Medical Association, Summer 1992: 4:6-4:10.
  1. McEvoy GK, editor. AHFS Drug information 95. Bethesda, MD: American Society of Health-System Pharmacists, 1995: 891-5, 899-903.
  1. Red book 1995. Montvale, NJ: Medical Economics Company, 1995: 126, 143, 160, 163, 175, 238, 241, 312, 321, 330, 337, 356, 401, 458.
  1. Personal communication, Manufacturer representative, Upjohn, via telephone 6/29/95.
  1. Elenbaas JK. Central acting oral skeletal muscle relaxants. Am J Hosp Pharm 1980; 37: 1313-23.
  1. Waldman HJ. Centrally acting skeletal muscle relaxants and associated drugs. J Pain Symptom Manage 1994; 9: 434-41.
  1. Chlorzoxazone (Paraflex, McNeil). In: PDR Physicians' desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data Production Company, 1994: 1362.
  1. Shirkey HC. Pediatric drug handbook. Philadelphia: W. B. Saunders, 1977: 168-9.
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