baclofen (Rx)

>10%

Oral solution/tablets

• Drowsiness (10-63%)
• Dizziness (5-15%)
• Weakness (5-15%)
• Nausea (4-12%)
• Confusion (1-11%)
• Intrathecal H4
• Hypotonia (2.4-34.7%)
• Somnolence (5.7-20.9%)

1-10%

Oral solution/tablets

• Hypotension (0-9%)
• Headache (4-8%)
• Insomnia (2-7%)
• Constipation (2-6%)
• Urinary frequency (2-6%)
• Fatigue (2-4%)

Intrathecal

• Convulsion (0.5-10%)
• Urinary retention (0.9-8%)
• Dizziness (1.7-8%)
• Paresthesia (2.1-6.7%)
• Nausea and vomiting (1.4-7.3%)
• Headache (1.6-10.7%)
• Constipation (0.2-5.1%)
• Pruritus (4%)
• Hypotension (0.2-4%)
• Pain (0.6-4%)
• Accidental injury (0.2-3.5%)
• Speech disorder (0.2-3.5%)
• Dry mouth (0.2-3.3%)
• Peripheral edema (2.3-3.3%)
• Death (0.2-3%)
• Increased salivation (2.6-2.7%)
• Ambylopia (0.2-2.3%)
• Diarrhea (0.5-2.3%)
• Confusion (0.5-2.3%)
• Hypoventilation (0.2-2.1%)
• Back pain (0.9-2%)
• Urinary incontinence (0.8-2%)
• Pneumonia (0.2-2%)
• Urinary retention (0.7-1.9%)
• Impotence (0.2-1.6%)
• Insomnia (0.4-1.6%)
• Depression (1.6%)
• Thinking abnormal (0.5-1.3%)
• Agitation (0.5-1.3%)
• Asthenia (0.7-1.4%)
• Tremor (1.3%)
• Coma (0.9-1.2%)
• Urticaria (0.2-1.2%)
• Dyspnea (0.3-1.2%)

<1%

Intrathecal

• Anorexia (0.4-0.9%)
• Diplopia (0.4-0.9%)
• Dysautonomia (0.2-0.9%)
• Anxiety (0.2-0.9%)
• Urinary frequency (0.6-0.9%)
• Fever (0.2-0.7%)
• Hypertension (0.2-0.6%)
• Hallucinations (0.3-0.5%)

Frequency Not Defined

Oral solution/tablets

• Neuropsychiatric: Euphoria, excitement, depression, hallucinations, paresthesia, muscle pain, tinnitus, slurred speech, coordination disorder, tremor, rigidity, dystonia, ataxia, blurred vision, nystagmus, strabismus, miosis, mydriasis, diplopia, dysarthria, epileptic seizure
• Cardiovascular: dyspnea, palpitation, chest pain, syncope Gastrointestinal: dry mouth, anorexia, taste disorder, abdominal pain, vomiting, diarrhea, and positive test for occult blood in stool
• Genitourinary: Enuresis, urinary retention, dysuria, impotence, inability to ejaculate, nocturia, hematuria
• Other: Rash, pruritus, ankle edema, excessive perspiration, weight gain, nasal congestion

Postmarketing Reports

Onset of scoliosis or worsening of a pre-existing scoliosis

Sexual dysfunction in men and women, including decreased libido and orgasm dysfunction

Erectile dysfunction in men following baclofen withdrawal

Contraindications

Hypersensitivity

Intrathecal use: IV, IM, SC or epidural administration

Cautions

Use with caution in patients who have had a stroke; baclofen has not significantly benefited patients with stroke; patients have also shown poor tolerability to the drug

Not indicated for spasm with rheumatic disease, stroke, Parkinson

May take with food to avoid stomach upset

Not significantly beneficial for patient with stroke

Use with caution in seizure disorders and renal impairment

Abrupt drug discontinuation has resulted in adverse reactions that include hallucinations, seizures, high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multiple organ-system failure, and death

May cause acute urinary retention that may be related to underlying disease; use caution in patients with urinary obstruction

Animal studies have shown increased incidence in ovarian cysts; effect in humans inconclusive

Use with caution in patients with decreased GI motility, peptic ulcer disease, and/or gastrointestinal obstructive disorders

Use with caution in patients with a history of autonomic dysreflexia; presence of nociceptive stimuli or abrupt withdrawal may cause autonomic dysreflexia episode

Possible exacerbation of psychotic disorders, schizophrenia or confusional state

Neonatal withdrawal symptoms can occur; gradually reduce the dosage and discontinue oral baclofen before delivery

Patients should avoid the operation of automobiles or other dangerous machinery until they know how the drug affects them; advise patients that the central nervous system effects may be additive to those of alcohol and other CNS depressants

Use with caution in patients where spasticity is utilized to sustain upright posture and balance in locomotion or whenever spasticity is utilized to obtain increased function

Intrathecal administration

• Intrathecal used with implanted pump
• Not for injection into pump catheter access port, as this may cause a life-threatening overdose
• Delivery of more drug volume than the programmed rate (over infusion) can result in unexpected overdose, or withdrawal caused by early emptying of pump reservoir; refer to manufacturer's pump manual and instructions for refilling the reservoir
• Potential for contamination due to non-sterile external surface of prefilled syringe; use of baclofen prefilled syringe in an aseptic setting (eg, operating room) to fill sterile intrathecal pumps prior to implantation in patients not recommended, unless external surface of prefilled syringe is treated to ensure sterility
• Potentially life-threatening CNS depression, cardiovascular collapse, and/or respiratory failure
• Resuscitative equipment and trained staff must be available during screening, dose titration, and refills
• Intrathecal mass: Cases of intrathecal mass at the tip of the implanted catheter have been reported, most of them involving pharmacy-compounded analgesic admixtures; the most frequent symptoms associated with intrathecal mass include decreased therapeutic response (worsening spasticity, return of spasticity when previously well controlled, withdrawal symptoms, poor response to escalating doses, or frequent or large dosage increases), pain, and neurologic deficit/dysfunction
• Inadvertent injection into the SC tissue can occur if the intrathecal reservoir refill septum is not properly accessed; SC injection may result in symptoms of a systemic overdose or early depletion of the reservoir

Drug interaction overview

• Baclofen may cause CNS depression, including drowsiness and sedation, which may be additive when used concomitantly with other CNS depressants or alcohol

Pregnancy

There are no adequate data on the developmental risk associated with the use in pregnant women

Oral administration of baclofen to pregnant rats resulted in an increased incidence of fetal structural abnormalities at a dose which was also associated with maternal toxicity

Clinical considerations

• May increase the risk of late-onset neonatal withdrawal symptoms

Animal data

• Baclofen given orally has been shown to increase the incidence of omphaloceles (ventral hernias) in fetuses of rats given ~13 times on a mg/kg basis, or 3 times on a mg/m2 basis, the maximum oral dose recommended for human use; this dose also caused reductions in food intake and weight gain in the dams
• This abnormality was not seen in mice or rabbits

Lactation

At recommended oral doses, baclofen is present in human milk

There are no human data on the effects of baclofen on milk production

There are no adequate data on the effects of baclofen on the breastfed infant

Withdrawal symptoms can occur in breastfed infants when maternal administration is stopped, or when breastfeeding is stopped

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need and any potential adverse effects on the breastfed infant or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Precise mechanism of action of baclofen is not fully understood

Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by decreasing excitatory neurotransmitter release from afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect

It is a structural analog of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), and may exert its effects by stimulation of the GABAB receptor subtype

Absorption

Onset: 6-8 hr (IT)

Duration: 4-8 hr

Peak plasma time: 28-48 hr (IT); 0.75 hr (PO)

Elimination

Half-life: 1.51 hr (IT); 5.7 hr (PO)

Clearance: 30 mL/hr (IT)

Excretion: Urine and feces (85%; unchanged)

Oral Administration

Take with or without food

Discontinuing: slowly reduce dose and avoid abrupt withdrawal to minimize risk of serious adverse events (eg, hallucinations, seizures, high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, rhabdomyolysis, multiple-organ failure, death)

Intrathecal Preparation

Inspect ampules for particulate matter and discoloration before administration, whenever solution and container permit

Screening use

• The 1 mL screening ampule only (50 mcg/mL) for bolus injection into the subarachnoid space
• For a 50 mcg bolus dose, use 1 mL of the screening ampule
• Use 1.5 mL of 50 mcg/mL baclofen injection for a 75 mcg bolus dose
• For the maximum screening dose of 100 mcg, use 2 mL of 50 mcg/mL baclofen injection (2 screening ampules)

Maintenance

• Concentrations other than 500 mcg/mL or 2000 mcg/mL, drug must be diluted
• Dilute with sterile preservative free NaCl

Intrathecal Administration

Often administered in a continuous infusion mode immediately following implant

Patients implanted with programmable pumps who have achieved relatively satisfactory control on continuous infusion, further benefit may be attained using more complex schedules of drug delivery (eg, patients who have increased spasms at night may require a 20% increase in their hourly infusion rate; changes in flow rate should be programmed to start 2 hr before the time of desired clinical effect)

Storage

Oral solution: Refrigerate at 2-8ºC (36-46ºF); dispense in a tight, light-resistant container with a child-resistant closure

Tablet: Store at 2-25ºC (68-77ºF)

Injection: Does not require refrigeration; do not store above 86ºF (30ºC); do not freeze; do not heat sterilize