CHLORZOXAZONE
ACTIONS/CLINICAL PHARMACOLOGY:
Chlorzoxazone is a centrally-acting agent for painful musculoskeletal
conditions. Data available from animal experiments as well as human study
indicate that chlorzoxazone acts primarily at the level of the spinal cord and
subcortical areas of the brain where it inhibits multisynaptic reflex arcs
involved in producing and maintaining skeletal muscle spasm of varied etiology.
The clinical result is a reduction of the skeletal muscle spasm with relief of
pain and increased mobility of the involved muscles. Blood levels of
chlorzoxazone can be detected in people during the first 30 minutes and peak
levels may be reached, in the majority of the subjects, in about 1 to 2 hours
after oral administration of chlorzoxazone. Chlorzoxazone is rapidly metabolized
and is excreted in the urine, primarily in a conjugated form as the glucuronide.
Less than one percent of a dose of chlorzoxazone is excreted unchanged in the
urine in 24 hours.
INDICATIONS AND USAGE:
. chlorzoxazone is indicated as an adjunct to rest, physical
therapy, and other measures for the relief of discomfort associated with acute,
painful musculoskeletal conditions. The mode of action of this drug has not been
clearly identified, but may be related to its sedative properties. Chlorzoxazone
does not directly relax tense skeletal muscles in man.
CONTRAINDICATIONS:
. chlorzoxazone is contraindicated in patients with known
intolerance to the drug.
WARNINGS:
Serious (including fatal) hepatocellular toxicity has been reported rarely in
patients receiving chlorzoxazone. The mechanism is unknown but appears to be
idiosyncratic and unpredictable. Factors predisposing patients to this rare
event are not known. Patients should be instructed to report early signs and/or
symptoms of hepatotoxicity such as fever, rash, anorexia, nausea, vomiting,
fatigue, right upper quadrant pain, dark urine, or jaundice. Chlorzoxazone
should be discontinued immediately and a physician consulted if any of these
signs or symptoms develop. Chlorzoxazone use should also be discontinued if a
patient develops abnormal liver enzymes (eg. AST, ALT, alkaline phosphatase and
bilirubin). The concomitant use of alcohol or other central nervous system
depressants may have an additive effect.
Usage In Pregnancy: The safe use of . chlorzoxazone has not been
established with respect to the possible adverse effects upon fetal development.
Therefore, it should be used in women of childbearing potential only when, in
the judgment of the physician, the potential benefits outweigh the possible
risks.
PRECAUTIONS:
. chlorzoxazone should be used with caution in patients with
known allergies or with a history of allergic reactions to drugs. If a
sensitivity reaction occurs such as urticaria, redness, or itching of the skin,
the drug should be stopped.
If any signs or symptoms suggestive of liver dysfunction are observed, the drug
should be discontinued.
DRUG INTERACTIONS:
The concomitant use of alcohol or other central nervous system depressants may
have an additive effect.
(See Also WARNINGS)
ADVERSE REACTIONS:
Chlorzoxazone containing products are usually well tolerated. It is possible in
rare instances that chlorzoxazone may have been associated with gastrointestinal
bleeding. Drowsiness, dizziness, lightheadedness, malaise, or overstimulation
may be noted by an occasional patient. Rarely, allergic-type skin rashes,
petechiae, or ecchymoses may develop during treatment. Angioneurotic edema or
anaphylactic reactions are extremely rare. There is no evidence that the drug
will cause renal damage. Rarely, a patient may note discoloration of the urine
resulting from a phenolic metabolite of chlorzoxazone. This finding is of no
known clinical significance.
OVERDOSAGE:
Symptoms: Initially, gastrointestinal disturbances such as nausea, vomiting, or
diarrhea together with drowsiness, dizziness, lightheadedness or headache may
occur. Early in the course there may be malaise or sluggishness followed by
marked loss of muscle tone, making voluntary movement impossible. The deep
tendon reflexes may be decreased or absent. The sensorium remains intact, and
there is no peripheral loss of sensation. Respiratory depression may occur with
rapid, irregular respiration and intercostal and substernal retraction. The
blood pressure is lowered, but shock has not been observed.
Treatment: Gastric lavage or induction of emesis should be carried out, followed
by administration of activated charcoal. Thereafter, treatment is entirely
supportive. If respirations are depressed, oxygen and artificial respiration
should be employed and a patent airway assured by use of an oropharyngeal airway
or endotracheal tube. Hypotension may be counteracted by use of dextran, plasma,
concentrated albumin or a vasopressor agent such as norepinephrine. Cholinergic
drugs or analeptic drugs are of no value and should not be used.
DOSAGE AND ADMINISTRATION:
Usual Adult Dosage: One caplet three or four times daily. If adequate response
is not obtained with this dose, it may be increased to 1 1/2 caplets (750 mg)
three or four times daily. As improvement occurs dosage can usually be reduced.
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