Baclofen (Systemic)
VA CLASSIFICATION
Primary: MS200
Secondary: CN103
Commonly used brand name(s): Apo-Baclofen; Lioresal; Novo-Baclofen; Nu-Baclofen; PMS-Baclofen.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Formssection(s).
Category:
Antispastic analgesic (in trigeminal neuralgia)—
Indications
Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.
Accepted
Spasticity (treatment)—Baclofen is indicated to relieve the signs and symptoms of spasticity caused by multiple sclerosis, spinal cord diseases, or spinal cord injury . It is especially useful in relieving flexor spasms and concomitant pain, clonus, and muscular rigidity . Baclofen may also improve bowel and bladder function in some patients with spinal lesions; however, it may not improve spastic stiff gait or manual dexterity.
[Neuralgia, trigeminal (treatment)]—Baclofen is used to reduce the number and severity of attacks of trigeminal neuralgia in patients who are not able to tolerate, or who have become refractory to the effects of, carbamazepine. In some patients, baclofen may provide additional benefit when used concurrently with carbamazepine.
Unaccepted
Baclofen should not be used in patients who require spasticity to sustain upright posture or balance in locomotion, or to obtain increased function .
Baclofen may not be effective, and is not recommended, in the treatment of patients with cerebrovascular accident, parkinsonism, cerebral palsy, or trauma-induced cerebral lesions .
Baclofen is not indicated in the treatment of skeletal muscle spasm caused by rheumatic disorders .
1 Not included in Canadian product labeling.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
213.66
Mechanism of action/Effect:
The precise mechanism of action of baclofen has not been fully determined. It acts mainly at the spinal cord level to inhibit the transmission of both monosynaptic and polysynaptic reflexes, possibly by hyperpolarization of primary afferent fiber terminals resulting in antagonism of the release of putative excitatory transmitters (i.e., glutamic and aspartic acids). Actions at supraspinal sites may also be involved .
Other actions/effects:
Baclofen has general central nervous system (CNS)–depressant actions .
Absorption:
Rapid and extensive but subject to interpatient variation . Also, the rate and extent of absorption may decrease with increasing doses .
Protein binding:
Low (30%) .
Biotransformation:
Hepatic; only about 15% of a dose is metabolized .
Half-life:
2 to 4 hours .
Onset of action:
Highly variable; may range from hours to weeks.
Time to peak concentration:
Within 2 hours ..
Peak serum concentration
500 to 600 nanograms per mL (nanograms/mL) (2.34 to 2.81 micromoles/L) following a 40-mg single dose; concentration remains above 200 nanograms/mL (0.94 micromoles/L) for 8 hours.
Therapeutic serum concentration
80 to 400 nanograms/mL (0.37 to 1.87 micromoles/L).
Elimination:
Renal; 70 to 85% of a dose is excreted unchanged within 24 hours. Small amounts may also be excreted via the feces. About 40% of a dose is usually excreted within 6 hours, and excretion is usually complete within 3 days; however, with chronic use the rate of excretion is subject to interpatient variation.
Precautions to Consider
Pregnancy/Reproduction
Pregnancy—
Studies have not been done in humans .
Some studies in rats have shown that baclofen increases the incidence of omphaloceles (ventral hernias) and incomplete sternebral ossification in the fetus when given in doses approximately 13 times the maximum recommended human dose (MRHD) . However, these abnormalities did not occur in studies using mice or rabbits. Also, studies in rabbits have shown that baclofen causes an increased incidence of unossified phalangeal nuclei of forelimbs and hindlimbs in the fetus when given in doses approximately 7 times the MRHD . In addition, some studies in mice have shown that baclofen causes a reduction in fetal birth weight with consequent delays in skeletal ossification when given in doses 17 times or 34 times the MHRD .
Breast-feeding
Baclofen is distributed into breast milk . However, problems in humans have not been documented .
Pediatrics
No information is available on the relationship of age to the effects of baclofen in pediatric patients . Safety and efficacy in children up to 12 years of age have not been established .
Geriatrics
Geriatric patients may be especially at risk for the development of CNS toxicity, leading to hallucinations, confusion or mental depression, other psychiatric disturbances, or incapacitating sedation, during baclofen therapy. Also, elderly patients are more likely to have age-related renal function impairment, which may require a reduction of dosage in patients receiving baclofen.
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.
Antidepressants, tricyclic (concurrent use with baclofen may result in pronounced muscle hypotonia; caution is recommended )
Antidiabetic agents, oral or
Insulin (baclofen may increase blood glucose concentrations; dosage adjustments of these medications and/or of baclofen may be necessary during and after concurrent therapy )
Antihypertensives or
Other hypotension-producing medications (concurrent use with baclofen may increase the risk of hypotension; dosage adjustment of the antihypertensive agent may be needed )
Carbidopa and levodopa (concurrent use with baclofen may result in mental confusion, hallucinations, or agitation )
» CNS depression–producing medications, other (see ) or
» Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline (concurrent use may result in increased CNS-depressant and hypotensive effects; caution is recommended and dosage of one or both agents should be reduced )
Neuromuscular blocking agents (concurrent use with neuromuscular blocking agents may enhance the effects of baclofen )
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 physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) and
Alkaline phosphatase and
Aspartate aminotransferase (AST [SGOT]) (values may be increased)
Glucose, blood (concentration may be increased)
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).
Risk-benefit should be considered when the following medical problems exist
Cerebral lesions or
Cerebrovascular accident (increased risk of CNS, respiratory, or cardiovascular depression; ataxia; and psychiatric disturbances such as hallucinations, euphoria, and mental excitation, confusion, or depression)
Diabetes mellitus (baclofen may increase blood glucose concentrations )
Epilepsy (baclofen may cause deterioration of seizure control, electroencephalographic [EEG] changes)
Psychiatric disorders, pre-existing (increased risk of baclofen-induced psychiatric disturbances)
» Renal function impairment (baclofen may accumulate; reduction in dosage may be required)
Sensitivity to baclofen
Caution is required in geriatric patients, who may be especially susceptible to baclofen-induced CNS toxicity and who are more likely than younger adults to have renal function impairment.
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):
Electroencephalogram (EEG) and clinical state determinations (increased or periodic monitoring recommended for epileptic patients because baclofen may cause deterioration of seizure control and EEG changes in these patients)
Side/Adverse Effects
Note: Chronic administration of baclofen to female rats has caused a dose-related increase in the incidence of ovarian cysts and in enlarged and/or hemorrhagic adrenal glands .
Many of the CNS, visual, and genitourinary side effects listed below may be symptoms associated with the underlying spastic disease rather than baclofen-induced .
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:
Those indicating need for medical attention
Incidence less frequent or rare
Bloody or dark urine
chest pain
CNS toxicity (visual and auditory hallucinations; mental depression or other mood changes; ringing or buzzing in ears)
dermatitis, allergic (skin rash or itching)
ovarian cysts —up to 5% of the female population using baclofen
syncope (fainting)
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
CNS effects (drowsiness [up to 63%]; dizziness or lightheadedness [up to 15%]; weakness [up to 15%]; confusion [up to 11%])
muscle weakness —may be caused by CNS effect or become apparent if baclofen-induced reduction of muscle tone unmasks existing paresis
nausea —4 to 12%
Incidence less frequent or rare
CNS effects (clumsiness, unsteadiness, trembling, or other problems with muscle control; false sense of well-being; headache [up to 8%]; muscle pain; numbness or tingling in hands or feet; slurred speech or other speech problems; trouble in sleeping [up to 7%]; unexplained muscle stiffness; unusual excitement; unusual tiredness [up to 4%])
constipation —2 to 6%
difficult or painful urination or decrease in amount of urine
fluid retention (swelling of ankles; weight gain)
frequent urge to urinate or uncontrolled urination —2 to 6%
gastrointestinal irritation (abdominal or stomach pain or discomfort; diarrhea)
loss of appetite
low blood pressure —up to 9%
pounding heartbeat
sexual problems in males
stuffy nose
Those indicating need for medical attention and/or reinstitution of therapy if they occur after medication is abruptly discontinued
Convulsions
hallucinations, visual and auditory
increased spasticity
mood or mental changes such as paranoid ideation or manic psychosis
unusual nervousness or restlessness
Overdose
For specific information on the agents used in the management of baclofen overdose, see in monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see ).
Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Acute and chronic
CNS toxicity (blurred or double vision; convulsions; miosis; mydriasis; severe muscle weakness; strabismus)
respiratory depression (shortness of breath or unusually slow or troubled breathing)
vomiting
Treatment of overdose
To decrease absorption—May include emptying the stomach by induction of emesis and/or gastric lavage .
Specific treatment—Administration of atropine has been recommended to increase ventilation, heart rate, blood pressure, and core body temperature. See the package insert or in monograph.
Supportive care—May include maintaining adequate respiratory exchange. Respiratory stimulants should not be used. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Baclofen (Systemic) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to baclofen
Use in the elderly—Increased risk of adverse CNS effects
Other medications, especially other CNS depression–producing medications
Proper use of this medication
» Proper dosing
Missed dose: Taking if remembered within an hour or so; not taking if not remembered within an hour; not doubling doses
» Proper storage
Precautions while using this medication
» Checking with physician before discontinuing medication; gradual dosage reduction is necessary
» Avoiding alcohol or other CNS depressants
» Caution if drowsiness, dizziness, visual disturbances, or impaired coordination occur
Diabetics: May increase blood sugar concentrations
Side/adverse effects
Convulsions, hallucinations, mood or mental changes, increased spasticity, seizures, or unusual nervousness or restlessness may occur following abrupt withdrawal
Signs and symptoms of potential side effects, especially bloody or dark urine, chest pain, CNS toxicity, allergic dermatitis, and syncope
General Dosing Information
Side effects may be minimized by initiating therapy with low doses, which should be increased gradually until the desired response is obtained.
If the desired response is not achieved after a reasonable trial period, the medication should be slowly withdrawn .
Lower doses may be required in patients with renal function impairment .
Convulsions, hallucinations, other psychiatric disturbances, and exacerbation of spasticity have occurred following abrupt withdrawal of baclofen; gradual reduction of dosage over a period of 1 to 2 weeks or more is recommended before the medication is discontinued .
Oral Dosage Forms
Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.
BACLOFEN TABLETS USP
Usual adult and adolescent dose
Antispastic and
[Analgesic (in trigeminal neuralgia)]
Oral, 5 mg three times a day initially, then increased by increments of 5 mg per dose every three days until the desired response is achieved .
Note: A smoother response may be achieved in some patients if the total daily dose is given in four divided doses.
Usual adult prescribing limits
80 mg daily .
Note: Higher doses may be required in some patients.
Usual pediatric dose
Safety and efficacy have not been established.
Strength(s) usually available
U.S.—
10 mg (Rx) [Lioresal (scored)][Generic]
20 mg (Rx) [Lioresal (scored)][Generic]
Canada—
10 mg (Rx) [Apo-Baclofen] [Lioresal (scored)] [Novo-Baclofen] [Nu-Baclofen] [PMS-Baclofen]
20 mg (Rx) [Apo-Baclofen] [Lioresal (scored)] [Novo-Baclofen] [Nu-Baclofen] [PMS-Baclofen]
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F) . Store in a well-closed container .
Auxiliary labeling:
• May cause drowsiness .
• Avoid alcoholic beverages .
Professional Information
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