Baclofen

Before taking baclofen,

• tell your doctor and pharmacist if you are allergic to baclofen or any other drugs.
• tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially muscle relaxants, sleeping pills, tranquilizers, and vitamins.
• tell your doctor if you have or have ever had kidney disease, epilepsy, ulcers, a stroke, a rheumatic disease, cerebral palsy, Parkinson's disease, or a psychiatric condition.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking baclofen, call your doctor immediately.
• you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how baclofen affects you.
• remember that alcohol can add to the drowsiness caused by this drug.

Baclofen is a prescription drug used to treat muscle spasms from multiple sclerosis and Huntington's disease as well as spinal cord injuries and spinal cord diseases.

Medical experts do not recommend baclofen for muscle spasms caused by rheumatoid arthritis, cerebral palsy, Parkinson's disease, or stroke, because research to date does not support such use.

Baclofen is an antispastic muscle relaxant. Researchers don't know exactly how baclofen works; however, in general, it blocks nerve signals from muscles at the level of the spinal cord and it may also depress the central nervous system.

The Food and Drug Administration (FDA) approved baclofen in 1977 under the brand name Lioresal, which was made by Novartis. The FDA approved generic baclofen in the 1980s.

Today, only generic versions of baclofen are available.

A case report published in Therapeutic Advances in Psychopharmacology in 2014 suggested that baclofen might be effective for treating marijuana dependence, particularly for those who have used the drug heavily for a long time. The research also showed that baclofen may help reduce withdrawal symptoms as well as the effects of marijuana.

A separate study, published in the Journal of Neuroscience in 2014, found that baclofen may also help people with drug addiction avoid possible triggers and prevent relapse. The drug works by interfering with the brain's early response to drug cues.

Baclofen Pump

You can take baclofen as a pill or via an intrathecal baclofen (ITB) pump.

In ITB therapy, your doctor will insert a small catheter under the skin of your abdomen, near your waist. The pump stores and releases the prescribed amount of baclofen through the catheter, using a small motor, directly into your spinal fluid.

ITB can be an option for people who experience side effects taking baclofen in pill form as it requires smaller doses of the drug and thus keeps side effects to a minimum.

Your doctor will need to refill your ITB pump system every one to three months. The system battery typically lasts five years, at which time your doctor will need to replace the device.

Baclofen Warnings

Once you start taking baclofen, don't stop taking it suddenly on your own. If you need to stop, your doctor will lower your dose gradually.

Stopping baclofen suddenly can lead to a dangerous withdrawal reaction that can include hallucinations (seeing or hearing things that are not there) and seizures.

Your kidneys eliminate baclofen from your system. Take baclofen with caution if you have kidney disease and reduced kidney function because the drug can build up in your system.

Baclofen is not recommended to treat muscle spasms caused by a stroke. Baclofen can cause more side effects in people with a history of stroke.

Baclofen can make you drowsy and affect your balance, so don't drive or operate heavy machinery until you know how baclofen affects you.

Other conditions you should tell your doctor about before taking baclofen include:

• Kidney disease
• Parkinson’s disease
• Stroke
• Seizures (epilepsy)
• Ulcers
• Cerebral palsy
• Mental health or mood disorders such as schizophrenia
• Rheumatoid arthritis

The FDA has not approved baclofen for children younger than 12.

Baclofen and Pregnancy

Studies have linked baclofen to birth defects in animals. Because of this, it is considered unsafe to use during pregnancy.

Before taking this drug, tell your doctor if you are pregnant or may become pregnant.

Baclofen may pass into breast milk, so also tell your doctor if you are breastfeeding or plan to breastfeed.

If you're a woman, ask your doctor about a possible risk for developing ovarian cysts while on baclofen. Make sure you doctor knows if you have a history of ovarian cysts.

Baclofen “High” and Recreational Use

Numerous online and anecdotal reports have suggested that some people abuse baclofen for a narcotic-like "high," because it can cause drowsiness.

There is a high risk of overdose associated with recreational use of baclofen, as high doses are needed for narcotic-like effect. Baclofen overdose can lead to:

• Coma
• Hypothhermia
• Dangerously slow heart rate/bradycardia
• High blood pressure/hypertension
• Hyporeflexia (slower than normal reflexes)

Take baclofen only as directed by your doctor, and keep this and all other drugs away from children, teenagers, and anyone for whom the drug has not been prescribed.

Some drugs may affect the way baclofen works, and baclofen may affect other drugs you're taking. It's very important to let your doctor know about all drugs you're taking, including any other prescription drugs, over-the-counter drugs, recreational or illegal drugs, herbs, vitamins, or supplements.

Other drugs that depress the central nervous system may make some side effects of baclofen worse. These drugs may include:

• Alcohol
• Sleeping pills
• Tranquilizers
• Muscle relaxants
• Vitamins

Don't drink alcohol while taking baclofen because that can worsen side effects such as drowsiness and dizziness.

Because baclofen relaxes muscles, it may cause weakness and imbalance, especially if you have muscle stiffness. Talk to your doctor about how baclofen may affect your balance.

KEMSTRO™ (baclofen orally disintegrating tablets) is a muscle relaxant and antispastic. Baclofen USP is a white to off-white, odorless or practically odorless crystalline powder. It is slightly soluble in water, very slightly soluble in methanol, and insoluble in chloroform. Its chemical name is 4-amino-3- (4-chlorophenyl)-butanoic acid. The molecular weight of baclofen is 213.66 and the empirical formula is C10H12C1NO2. The structural formula is represented below:

KEMSTRO™ (baclofen) is available as 10 mg and 20 mg orally disintegrating tablets. Each orally disintegrating tablet also contains as inactive ingredients: aspartame, colloidal silicon dioxide, crospovidone, magnesium stearate, mannitol, microcrystalline cellulose, natural and artificial orange flavor and povidone.

The precise mechanism of action of baclofen is not fully known. Baclofen is capable of inhibiting both monosynaptic and polysynaptic reflexes at the spinal level, possibly by hyperpolarization of afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Although baclofen is an analog of the putative inhibitory neurotransmitter gamma-amino-butyric acid (GABA), there is no conclusive evidence that actions on GABA systems are involved in the production of its clinical effects. In studies with animals, baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.

Pharmacokinetics

Baclofen is rapidly and extensively absorbed. Absorption may be dose-dependent, being reduced with increasing doses. KEMSTRO™ (baclofen) given with or without water is bioequivalent to the baclofen conventional tablet. Thus KEMSTRO™ (baclofen) can be placed on the tongue until it disintegrates and then be swallowed with or without water. Following a single 20 mg oral dose of KEMSTRO™ (baclofen) , the peak plasma concentration was reached about 1½ hours after administration.

The apparent volume of distribution is 59 liters. Baclofen does not readily cross the blood-brain barrier. Plasma protein binding is approximately 30%.

In a study using radiolabeled baclofen, approximately 85% of the dose was excreted unchanged in the urine and feces. About 15% of the dose was metabolized, primarily by deamination. The y-hydroxy metabolite, 3-(p-chlorophenyl)-4-hydroxybutyric acid, is formed after deamination of baclofen.

Baclofen is rapidly and extensively eliminated. There is a relatively large intersubject variation in elimination. Baclofen is excreted primarily by the kidney as unchanged drug; 70 - 80% of a dose appears in the urine as unchanged drug. The remainder is excreted as unchanged drug in the feces or as metabolites in the urine and feces. Excretion is complete within 72 hours after administration. The elimination half-life of KEMSTRO™ (baclofen) is approximately 5½ hours. Total systemic clearance is 180 mL/min and renal clearance is 103 mL/min.

Special Populations

The pharmacokinetics of baclofen tablets were evaluated in elderly patients (69-81 years) and in healthy younger subjects (23-53 years) after a single 10 mg dose. The Cmax was lower (119 ng/mL vs. 178 ng/mL) and the Tmax was longer (3 hours vs. 1 hour) in the elderly patients compared to the younger subjects. The AUCs were similar in the two groups. In this study, the elimination half-life was slightly prolonged in the elderly patients compared to the younger subjects, 4.43 hours vs. 3.75 hours, respectively.

Before taking baclofen, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to any ingredient in baclofen
• have kidney disease
• have epilepsy or seizures
• have cerebral palsy
• have Parkinson's disease
• have a psychiatric condition
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

If you take too much this medication, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Contraindications

• Known hypersensitivity to baclofen or any ingredient in the formulation.113 128

Warnings/Precautions

Warnings

Abrupt discontinuance of oral baclofen may result in hallucinations and seizures.127 128

Abrupt discontinuance of intrathecal baclofen has resulted in high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity; in rare cases, progression to rhabdomyolysis, multisystem organ failure, and death have occurred.113

Symptoms usually appear within hours to days following interruption of therapy.113 Early symptoms may include return of baseline spasticity, pruritus, hypotension, and paresthesias.113 Advanced withdrawal syndrome may resemble autonomic dysreflexia, sepsis, malignant hyperthermia, neuroleptic malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis.113

Rapid, accurate diagnosis and treatment in emergency room or intensive care setting are needed to prevent potentially life-threatening CNS and systemic effects.113

Restore intrathecal baclofen therapy at or near the dosage used prior to interruption.113

If reinstitution of intrathecal delivery is delayed, drugs that enhance GABA effects (e.g., oral or enteral baclofen; oral, enteral, or IV benzodiazepines) may prevent potentially fatal sequelae.113 However, do not rely on oral or enteral baclofen alone to halt progression of intrathecal baclofen withdrawal.113

Should be administered intrathecally only by qualified individuals familiar with the administration techniques and patient management problems.113 115

Initial test for responsiveness to intrathecal baclofen, implantation of pump, and subsequent periods of dosage titration must be performed in a medically supervised setting that is adequately equipped for the management of potential complications; resuscitative equipment should be readily available.113 115

Potentially life-threatening CNS depression, cardiovascular collapse, and respiratory failure reported following intrathecal administration.113 Fatalities (including one case of unexpected death after administration of 3 test doses and 2 cases of sudden and unexpected death occurring within 2 weeks of pump implantation) reported rarely during intrathecal therapy; however, manufacturer states that causal relationship not established.113

Patients, caregivers, and health-care providers should receive adequate information regarding the risks of intrathecal baclofen therapy, including information on recognition and management of potential overdosage and proper care of the pump and catheter insertion site.113

Delay implantation of controlled-infusion device until response to test dose(s) is adequately evaluated.113

Familiarization with the implantable infusion device (e.g., instructions and precautions for pump programming and refilling) is essential.113

Fill drug reservoir under aseptic conditions (to avoid bacterial contamination and serious infection), following the directions provided by the device’s manufacturer; only fully trained and qualified personnel should fill reservoir.113 Follow proper refill frequency to avoid depletion of drug reservoir during use.113 114 115

Monitor patient carefully, particularly during the initial phase of pump use, dosage titration, and reservoir refilling to ensure an acceptable, reasonably stable response.113

Any sudden increase in dosage requirement should suggest the possibility of pump and/or catheter malfunction (i.e., catheter kink or dislodgement).113 If no increase in response is observed with upward titration of dosage, check pump function and catheter patency.113 115

Signs of intrathecal baclofen overdose may appear suddenly or over a period of time.113

Acute, massive overdose may present as coma.113

Less sudden and/or less severe forms of overdose may present with drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, seizures, rostral progression of hypotonia, and loss of consciousness progressing to coma.113

Overdose generally related to pump malfunction or dosing error.113

If overdose appears likely, immediately take patient to hospital for assessment and emptying of pump reservoir.113

Fill pump with extreme caution; refill only through the pump reservoir refill septum.113 If reservoir refill septum is not properly accessed, inadvertent injection into sub-Q tissue can occur, possibly resulting in life-threatening overdosage or early depletion of reservoir.113 Some pumps are equipped with a catheter access port that allows direct access to the intrathecal catheter; direct injection into this catheter may cause life-threatening overdosage.113

General Precautions

Use intrathecal baclofen with caution in patients with a history of autonomic dysreflexia; the presence of nociceptive stimuli or abrupt withdrawal of therapy may precipitate episode of dysreflexia.113

Risk of sedation and/or drowsiness.113 128 Performance of activities requiring mental alertness may be impaired.113 128

Concurrent use of other CNS depressants may potentiate CNS depression.113 128 (See Specific Drugs under Interactions.)

Use with caution and titrate dosage carefully when spasticity is necessary to sustain upright posture and balance in locomotion or whenever spasticity is used to obtain increased or optimal body function.113 128

Possible exacerbation of psychotic disorders, schizophrenia, or confusional states; use with caution and monitor such patients carefully.113

Possible deterioration in seizure control and EEG in epileptic patients; monitor patient’s clinical state and EEG at regular intervals.128

If intrathecal therapy is to be employed, attempt to discontinue concomitant oral antispasmodic drugs to avoid possible overdose and drug interactions, either prior to screening phase or following implantation of infusion device.113 Monitor patient carefully; avoid abrupt dosage reduction or discontinuance of concomitant antispasmodics.113

Presence of infection may interfere with assessment of the patient’s response to baclofen test dose(s),113 increase surgical complications after pump implantation, and complicate attempts to adjust dosage.113 115

Patients being considered for intrathecal baclofen therapy should be without concurrent infection.113

Development of intrathecal mass at the tip of implanted catheter reported following long-term intrathecal baclofen therapy.113 Most common sequelae or manifestations include decreased therapeutic response (i.e., worsening spasticity, return of spasticity despite previous response, withdrawal symptoms, poor response to escalating doses, frequent or large dosage increases), pain, and neurologic deficit or dysfunction.113

Monitor patients carefully for any new neurologic manifestations.113 If new neurologic manifestations suggestive of an intrathecal mass occur, consider neurosurgical consultation, since many symptoms of inflammatory mass are similar to those associated with severe spasticity.113 In some cases, an imaging procedure may be appropriate to confirm or rule out diagnosis of an intrathecal mass.113

Ovarian cysts found in about 4% of multiple sclerosis patients receiving oral baclofen for up to 1 year; cysts disappeared spontaneously despite continued baclofen use in most patients.113 128 Estimated rate of occurrence in healthy females is approximately 1–5%.113 128

Specific Populations

Category C.113

Distributed into milk following oral administration; not known whether baclofen distributes into milk following intrathecal administration.113

Nursing not recommended in women receiving oral baclofen.128 Women receiving intrathecal baclofen should nurse infant only if potential benefit justifies potential risks to infant.113

Safety and efficacy of oral baclofen not established in children <12 years of age.128

Safety and efficacy of intrathecal baclofen not established in children <4 years of age.113

Children being considered for intrathecal therapy should have sufficient body mass to accommodate the pump.113 Consult directions provided by the device’s manufacturer.113

Excreted principally in urine as unchanged drug; use with caution in patients with impaired renal function.113 128 (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

For oral baclofen, drowsiness, dizziness, weakness, fatigue.128

For intrathecal baclofen in patients with spasticity of spinal cord origin, somnolence, dizziness, nausea, hypotension, headache, seizures, hypotonia.113

For intrathecal baclofen in patients with spasticity of cerebral origin, agitation, constipation, somnolence, leukocytosis, chills, urinary retention, hypotonia.113

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For baclofen, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to baclofen or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Studies on baclofen have been done only in adult patients, and there is no specific information comparing use of baclofen in children with use in other age groups.

Geriatric

Side effects such as hallucinations, confusion or mental depression, other mood or mental changes, and severe drowsiness may be especially likely to occur in elderly patients, who are usually more sensitive than younger adults to the effects of baclofen.

Pregnancy

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking baclofen, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using baclofen with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Bromazepam
• Buprenorphine
• Butorphanol
• Codeine
• Dihydrocodeine
• Donepezil
• Doxylamine
• Fentanyl
• Flibanserin
• Hydrocodone
• Hydromorphone
• Levorphanol
• Meperidine
• Methadone
• Morphine
• Morphine Sulfate Liposome
• Nalbuphine
• Oxycodone
• Oxymorphone
• Pentazocine
• Periciazine
• Remifentanil
• Sodium Oxybate
• Sufentanil
• Tapentadol
• Tramadol
• Zolpidem

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of baclofen. Make sure you tell your doctor if you have any other medical problems, especially:

• Type 2 diabetes mellitus—Baclofen may raise blood sugar levels

• Epilepsy or
• Kidney disease or
• Mental or emotional problems or
• Stroke or other brain disease—The chance of side effects may be increased

Baclofen Tablets USP, 10 mg are available as a white, round, flat-faced, beveled-edge tablet debossed with “4096” on one side and “TV” with a partial score on the other side, containing 10 mg Baclofen, USP packaged in bottles of 100 (NDC 0172-4096-60) and 1000 (NDC 0172-4096-80) tablets.

Baclofen Tablets USP, 20 mg are available as a white, round, flat-faced, beveled-edge tablet debossed with “4097” on one side and “TV” with a partial score on the other side, containing 20 mg Baclofen, USP packaged in bottles of 100 (NDC 0172-4097-60) and 1000 (NDC 0172-4097-80) tablets.

PHARMACIST: Dispense in a well-closed container as defined in the USP, with a child-resistant closure (as required).

Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Manufactured In Croatia By:

PLIVA HRVATSKA d.o.o.

Zagreb, Croatia

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. B 10/2015

Baclofen Tablets USP 10 mg 100s Label Text

NDC 0172-4096-60

Baclofen
Tablets USP
10 mg

Rx only

100 TABLETS

TEVA

Inhibits the transmission of both monosynaptic and polysynaptic reflexes at the spinal cord level, possibly by hyperpolarization of primary afferent fiber terminals, with resultant relief of muscle spasticity

Absorption

Oral: Rapid; absorption from the GI tract is thought to be dose dependent; in pediatric patients (age range: 2 to 17 years) with cerebral palsy, absorption from GI tract highly variable and delayed (reported time lag: 0.59 ± 0.28 hours) (He 2014)

Metabolism

Hepatic (15% of dose) (He 2014)

Excretion

Urine (>70% as unchanged drug) and feces (Brunton 2011)

Oral and intrathecal: There are no dosage adjustments provided in the manufacturer’s labeling.

Do not use baclofen at a time when you need muscle tone for safe balance and movement during certain activities. In some situations, it may be dangerous for you to have reduced muscle tone.

Drinking alcohol with this medicine can cause side effects.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Applies to baclofen: compounding powder, intrathecal solution, oral suspension, oral tablet

Cardiovascular

Common (1% to 10%): Cardiac output decreased, hypotension, hypertension, diminished cardiovascular functions, peripheral edema
Rare (less than 0.1%): Arrhythmias, palpitations, chest pain
Frequency not reported: Bradycardia, orthostatic hypotension[Ref]

Dermatologic

Common (1% to 10%): Rash, hyperhidrosis, urticaria/pruritus, facial edema
Uncommon (0.1% to 1%): Alopecia, diaphoresis
Frequency not reported: Rash, sweating, contact dermatitis, skin ulcer[Ref]

Endocrine

Common (1% to 10%): Ovarian cysts are palpable in 4% of women treated with for up to one year[Ref]

Gastrointestinal

Very common (10% or more): Nausea (especially at start of therapy) (up to 11%)
Common (1% to 10%): Dry mouth, GI disorder/disturbance, constipation, diarrhea, retching, vomiting, increased salivation
Uncommon (0.1% to 1%): Dysphagia, dehydration, ileus, decreased taste sensation
Rare (less than 0.1%): Colicky abdominal pain, anorexia
Frequency not reported: GI hemorrhage[Ref]

Genitourinary

Very common (10% or more): Urinary retention (up to 12%)
Common (1% to 10%): Urinary incontinence, urination impaired, sexual dysfunction, urinary frequency, enuresis, dysuria
Rare (less than 0.1%): Erectile dysfunction
Frequency not reported: Dysuria, abnormal ejaculation, oliguria, vaginitis[Ref]

Hematologic

Frequency not reported: Leukocytosis, petechial rash[Ref]

Hepatic

Rare (less than 0.1%): Disorders of hepatic function (e.g., increased AST)[Ref]

Immunologic

Common (1% to 10%): Pneumonia
Uncommon (0.1% to 1%): Septicemia[Ref]

Metabolic

Common (1% to 10%): Decreased appetite
Frequency not reported: Blood glucose increased[Ref]

Musculoskeletal

Very common (10% or more): Hypotonia (up to 52%), lower extremity weakness (up to 15%), disturbances of gait and balance
Common (1% to 10%): Muscular weakness, myalgia, upper extremity weakness, back pain, muscular hypertonia[Ref]

Nervous system

Very common (10% or more): Somnolence (up to 28%), drowsiness (up to 18%), headache (up to 16%), seizures (especially on discontinuation of therapy) (up to 15%), sedation, dizziness (up to 12%)
Common (1% to 10%): Fatigue, ataxia, tremor, lightheadedness, lassitude, exhaustion, numbness/itching/tingling, slurred speech, lethargy, hypertonia, paresthesia
Rare (less than 0.1%): Dysarthria, dysgeusia, syncope, dyskinesia, coma, potentially life-threatening withdrawal symptoms (as a result of sudden interruption of drug delivery)[Ref]

Other

Common (1% to 10%): Tinnitus, pain, asthenia
Uncommon (0.1% to 1%): Accidental injury, weight loss
Very rare (less than 0.01%): Hypothermia
Frequency not reported: Drug withdrawal syndrome
Uncommon (0.1% to 1%): Subdural hemorrhage, accidental injury, weight loss[Ref]

Ocular

Common (1% to 10%): Nystagmus, visual impairment, accommodation disorder, blurred vision, double vision, amblyopia[Ref]

Psychiatric

Common (1% to 10%): Confusional state, hallucination, depression, insomnia, euphoric mood, nightmare, personality changes
Uncommon (0.1% to 1%): Memory loss/impairment, suicidal ideation, attempted suicide
Rare (less than 0.1%): Excitement[Ref]

Renal

Very rare (less than 0.01%): Kidney calculus[Ref]

Respiratory

Common (1% to 10%): Respiratory depression, hypoventilation, dyspnea, bradypnea, feeling of pressure in the chest[Ref]

Some side effects of baclofen may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

INTRATHECAL:
SCREENING PHASE: Prior to administering this drug as a continuous intrathecal infusion, patients must show a positive response to administration of an intrathecal test dose in an initial test phase:
-FIRST TEST DOSE: 50 mcg (in a volume of 1 mL) injected into the intrathecal space by barbotage over at least 1 minute. Observe patient for 4 to 8 hours for a positive response.
-SECOND TEST DOSE (if no positive response to first test dose): 75 mcg (in a volume of 1.5 mL) may be administered 24 hours after the first test dose. Observe patient for 4 to 8 hours for a positive response.
-THIRD TEST DOSE (if no positive response to second test dose): 100 mcg (in a volume of 2 mL) may be administered 24 hours after the second test dose. Observe patient for 4 to 8 hours for a positive response. If no positive response to third test dose, the patient should not be considered for chronic intrathecal therapy.

POST-IMPLANT DOSE TITRATION PERIOD:
-The test dose that received a positive response should be doubled and given over 24 hours, unless the efficacy of the bolus dose was maintained for more than 8 hours, in which case the starting daily dose should be the screening dose delivered over 24 hours.
-No dose increases should be given in the first 24 hours.

-ADULT PATIENTS WITH SPASTICITY OF SPINAL CORD ORIGIN: After the first 24 hours, the daily dosage should be increased slowly by 10% to 30% increments and only once every 24 hours, until the desired effect is achieved.
-ADULT PATIENTS WITH SPASTICITY OF CEREBRAL ORIGIN: After the first 24 hours, the daily dose should be increased slowly by 5% to 15% only once every 24 hours, until the desired effect is achieved.

MAINTENANCE DOSING FOR SPASTICITY OF SPINAL CORD ORIGIN PATIENTS:
-During periodic refills of the pump, the daily dose may be increased by 10% to 40%, but no more than 40%, to maintain adequate symptom control.
-The daily dose may be reduced by 10% to 20% if patients experience side effects.
-Maintenance dosage for long term continuous infusion: 12 to 2003 mcg/day, with most patients adequately maintained on 300 to 800 mcg/day; there is limited experience with daily doses greater than 1000 mcg/day.

MAINTENANCE DOSING FOR SPASTICITY OF CEREBRAL ORIGIN PATIENTS:
-During periodic refills of the pump, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control.
-The daily dose may be reduced by 10% to 20% if patients experience side effects.
-Maintenance dosage for long term continuous infusion: 22 to 1400 mcg/day, with most patients adequately maintained on 90 to 703 mcg/day; there is limited experience with daily doses greater than 1000 mcg/day.

POTENTIAL NEED FOR DOSE ADJUSTMENTS IN CHRONIC USE:
-During long term treatment, approximately 5% of patients become refractory to increasing doses. There is not sufficient experience to make recommendations for tolerance treatment; however, this tolerance has been treated on occasion, in hospital, by a "drug holiday" consisting of the gradual reduction of intrathecal dosing over a 2 to 4 week period and switching to alternative methods of spasticity management.
-After the "drug holiday," intrathecal dosing may be restarted at the initial continuous infusion dose.

Comments:
-Determination of the optimal dose requires individual titration. The lowest dose with an optimal response should be used.
-For patients with spasticity due to head injury, it is recommended not to proceed to long-term until the symptoms of spasticity are stable (i.e., at least one year after the injury).
-A positive response consists of a significant decrease in muscle tone and/or frequency and/or severity of spasms.
-Many patients require gradual increases in dose over time to maintain optimal response during chronic therapy.
-A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).
-Careful dose titration is needed when spasticity is necessary to sustain upright posture and balance in locomotion or whenever spasticity is used to obtain optimal function. Allowing occasional spasms may help support circulatory function, possibly prevent the formation of deep vein thrombosis, and optimize activities of daily living.
-Except in overdose related emergencies, dosing should be reduced slowly if the drug is discontinued for any reason.
-An attempt should be made to discontinue concomitant oral antispasticity medication to avoid possible overdose or adverse drug interactions, either prior to screening or following implant and initiation of chronic infusion.
If there is not a substantive clinical response to increases in the daily dose, check for proper pump function and catheter patency. Patients must be monitored closely in a fully equipped and staffed environment during the screening phase and dose-titration period immediately following implant. Resuscitative equipment should be immediately available for use in case of life-threatening or intolerable side effects.

Use: For the management of severe spasticity. Patients should first respond to a screening dose prior to consideration for long term infusion via an implantable pump. For spasticity of spinal cord origin, chronic infusion via an implantable pump should be reserved for patients unresponsive to oral therapy, or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal therapy.

PEDIATRIC PATIENTS:
-The starting screening dose for pediatric patients is the same as in adult patients, (50 mcg); however, for very small patients, a screening dose of 25 mcg may be tried first:
INTRATHECAL:
SCREENING PHASE: Prior to administering this drug as a continuous intrathecal infusion, patients must show a positive response to administration of an intrathecal test dose in an initial test phase:
-FIRST TEST DOSE: 25 to 50 mcg (in a volume of 1 mL) injected into the intrathecal space by barbotage over at least 1 minute. Observe patient for 4 to 8 hours for a positive response.
-SECOND TEST DOSE (if no positive response to first test dose): 75 mcg (in a volume of 1.5 mL) may be administered 24 hours after the first test dose. Observe patient for 4 to 8 hours for a positive response.
-THIRD TEST DOSE (if no positive response to second test dose): 100 mcg (in a volume of 2 mL) may be administered 24 hours after the second test dose. Observe patient for 4 to 8 hours for a positive response. If no positive response to third test dose, the patient should not be considered for chronic intrathecal therapy.

POST-IMPLANT DOSE TITRATION PERIOD:
-The test dose that received a positive response should be doubled and given over 24 hours, unless the efficacy of the bolus dose was maintained for more than 8 hours, in which case the starting daily dose should be the screening dose delivered over 24 hours.
-No dose increases should be given in the first 24 hours for programmable pumps and in the first 48 hours for nonprogrammable pumps.

AFTER THE FIRST 24 HOURS: The daily dosage should be increased slowly by 5% to 15% increments and only once every 24 hours, until the desired effect is achieved.

MAINTENANCE DOSING:
The same dosing recommendations for adults with spasticity of cerebral origin are used in pediatric patients:
-During periodic refills of the pump, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control.
-The daily dose may be reduced by 10% to 20% if patients experience side effects.

MAINTENANCE DOSAGE FOR LONG TERM CONTINUOUS INFUSION:
-Age 12 YEARS AND OLDER: 22 to 1400 mcg/day, with most patients adequately maintained on 90 to 703 mcg/day; there is limited experience with daily doses greater than 1000 mcg/day.
-LESS THAN 12 YEARS OF AGE:
-Pediatric patients under 12 years seem to require a lower daily dose in clinical trials: 274 mcg/day, with a range of 24 to 1199 mcg/day

POTENTIAL NEED FOR DOSE ADJUSTMENTS IN CHRONIC USE:
-During long term treatment, approximately 5% of patients become refractory to increasing doses. There is not sufficient experience to make recommendations for tolerance treatment; however, this tolerance has been treated on occasion, in hospital, by a "drug holiday" consisting of the gradual reduction of intrathecal dosing over a 2 to 4 week period and switching to alternative methods of spasticity management.
-After the "drug holiday," intrathecal dosing may be restarted at the initial continuous infusion dose.

Comments:
-Determination of the optimal dose requires individual titration. The lowest dose with an optimal response should be used.
-For patients with spasticity due to head injury, it is recommended not to proceed to long-term until the symptoms of spasticity are stable (i.e., at least one year after the injury).
-A positive response consists of a significant decrease in muscle tone and/or frequency and/or severity of spasms.
-Many patients require gradual increases in dose over time to maintain optimal response during chronic therapy.
-A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).
-Careful dose titration is needed when spasticity is necessary to sustain upright posture and balance in locomotion or whenever spasticity is used to obtain optimal function. Allowing occasional spasms may help support circulatory function, possibly prevent the formation of deep vein thrombosis, and optimize activities of daily living.
-Except in overdose related emergencies, dosing should be reduced slowly if the drug is discontinued for any reason.
-An attempt should be made to discontinue concomitant oral antispasticity medication to avoid possible overdose or adverse drug interactions, either prior to screening or following implant and initiation of chronic infusion.
If there is not a substantive clinical response to increases in the daily dose, check for proper pump function and catheter patency. Patients must be monitored closely in a fully equipped and staffed environment during the screening phase and dose-titration period immediately following implant. Resuscitative equipment should be immediately available for use in case of life-threatening or intolerable side effects.

Use: For the management of severe spasticity. Patients should first respond to a screening dose prior to consideration for long term infusion via an implantable pump. For spasticity of spinal cord origin, chronic infusion via an implantable pump should be reserved for patients unresponsive to oral therapy, or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal therapy.

PEDIATRIC PATIENTS:
-The starting screening dose for pediatric patients is the same as in adult patients, (50 mcg); however, for very small patients, a screening dose of 25 mcg may be tried first:
INTRATHECAL:
SCREENING PHASE: Prior to administering this drug as a continuous intrathecal infusion, patients must show a positive response to administration of an intrathecal test dose in an initial test phase:
-FIRST TEST DOSE: 25 to 50 mcg (in a volume of 1 mL) injected into the intrathecal space by barbotage over at least 1 minute. Observe patient for 4 to 8 hours for a positive response.
-SECOND TEST DOSE (if no positive response to first test dose): 75 mcg (in a volume of 1.5 mL) may be administered 24 hours after the first test dose. Observe patient for 4 to 8 hours for a positive response.
-THIRD TEST DOSE (if no positive response to second test dose): 100 mcg (in a volume of 2 mL) may be administered 24 hours after the second test dose. Observe patient for 4 to 8 hours for a positive response. If no positive response to third test dose, the patient should not be considered for chronic intrathecal therapy.

POST-IMPLANT DOSE TITRATION PERIOD:
-The test dose that received a positive response should be doubled and given over 24 hours, unless the efficacy of the bolus dose was maintained for more than 8 hours, in which case the starting daily dose should be the screening dose delivered over 24 hours.
-No dose increases should be given in the first 24 hours for programmable pumps and in the first 48 hours for nonprogrammable pumps.

AFTER THE FIRST 24 HOURS: The daily dosage should be increased slowly by 5% to 15% increments and only once every 24 hours, until the desired effect is achieved.

MAINTENANCE DOSING:
The same dosing recommendations for adults with spasticity of cerebral origin are used in pediatric patients:
-During periodic refills of the pump, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control.
-The daily dose may be reduced by 10% to 20% if patients experience side effects.

MAINTENANCE DOSAGE FOR LONG TERM CONTINUOUS INFUSION:
-Age 12 YEARS AND OLDER: 22 to 1400 mcg/day, with most patients adequately maintained on 90 to 703 mcg/day; there is limited experience with daily doses greater than 1000 mcg/day.
-LESS THAN 12 YEARS OF AGE:
-Pediatric patients under 12 years seem to require a lower daily dose in clinical trials: 274 mcg/day, with a range of 24 to 1199 mcg/day

POTENTIAL NEED FOR DOSE ADJUSTMENTS IN CHRONIC USE:
-During long term treatment, approximately 5% of patients become refractory to increasing doses. There is not sufficient experience to make recommendations for tolerance treatment; however, this tolerance has been treated on occasion, in hospital, by a "drug holiday" consisting of the gradual reduction of intrathecal dosing over a 2 to 4 week period and switching to alternative methods of spasticity management.
-After the "drug holiday," intrathecal dosing may be restarted at the initial continuous infusion dose.

Comments:
-Determination of the optimal dose requires individual titration. The lowest dose with an optimal response should be used.
-For patients with spasticity due to head injury, it is recommended not to proceed to long-term until the symptoms of spasticity are stable (i.e., at least one year after the injury).
-A positive response consists of a significant decrease in muscle tone and/or frequency and/or severity of spasms.
-Many patients require gradual increases in dose over time to maintain optimal response during chronic therapy.
-A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).
-Careful dose titration is needed when spasticity is necessary to sustain upright posture and balance in locomotion or whenever spasticity is used to obtain optimal function. Allowing occasional spasms may help support circulatory function, possibly prevent the formation of deep vein thrombosis, and optimize activities of daily living.
-Except in overdose related emergencies, dosing should be reduced slowly if the drug is discontinued for any reason.
-An attempt should be made to discontinue concomitant oral antispasticity medication to avoid possible overdose or adverse drug interactions, either prior to screening or following implant and initiation of chronic infusion.
If there is not a substantive clinical response to increases in the daily dose, check for proper pump function and catheter patency. Patients must be monitored closely in a fully equipped and staffed environment during the screening phase and dose-titration period immediately following implant. Resuscitative equipment should be immediately available for use in case of life-threatening or intolerable side effects.

Use: For the management of severe spasticity. Patients should first respond to a screening dose prior to consideration for long term infusion via an implantable pump. For spasticity of spinal cord origin, chronic infusion via an implantable pump should be reserved for patients unresponsive to oral therapy, or those who experience intolerable CNS side effects at effective doses. Patients with spasticity due to traumatic brain injury should wait at least one year after the injury before consideration of long term intrathecal therapy.

Administration advice:
-The oral formulation of this drug should be taken with food.
-The specific concentration of this drug that should be used for intrathecal infusion depends on the total daily dose required as well as the delivery rate of the pump.
-Patients who do not respond (i.e., demonstrate a significant decrease in muscle tone and/or frequency and/or severity of spasms) following a 100 mcg intrathecal test dose should not be administered additional increases in dose or be considered for continuous intrathecal infusion.
-Over time during maintenance intrathecal therapy, many patients will require gradual dose increases to maintain the desired clinical effect. However, a sudden requirement for a significant increase in dose may signify a catheter complication or pump malfunction. Some patients may require a more complicated dose delivery which coincides with increased or decreased spasticity at different times of the day (e.g., increased infusion rate at night). Some patients may become refractory and develop tolerance to increasing doses. Cessation of intrathecal therapy for a few days may restore sensitivity. Treatment may be restarted at the initial continuous infusion rate and titrated accordingly.

General:
-The oral tablets and liquid are considered bioequivalent.
-In patients who do not exhibit an improvement in symptoms within 6 to 8 weeks of achieving the maximum dosage of the oral formulation, continuation of therapy should be reconsidered.
-The intrathecal formulation of this drug should be reserved for patients unresponsive to oral therapy, or those who experience intolerable central nervous system side effects at effective doses.
-The intrathecal injection is intended for administration in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, in implantable pumps suitable for continuous administration into the intrathecal space.
-Children should be of sufficient body mass to accommodate the intrathecal implantable pump for chronic infusion.
-The pump system should not be implanted until the patient response to bolus intrathecal injection and/or dose titration is adequately evaluated and found to be clinically safe and effective.
-The use of the intrathecal route of administration should only be undertaken by physicians adequately trained in chronic intrathecal infusion therapy, in a medically supervised and adequately equipped environment.
-Specific instructions for implanting, programming, and/or refilling of the implantable pump for intrathecal administration recommended by its manufacturer should be strictly adhered to.
-Do not administer the intrathecal formulation of this drug by any route apart from the intrathecal route.
-During the intrathecal dose titration phase, dose increases should occur once every 24 hours in patients with programmable pumps and every 48 hours in patients with nonprogrammable pumps.
-All patients on intrathecal therapy are at risk for withdrawal. Common reasons for abrupt interruption include malfunction of the catheter, low volume in the pump reservoir, and end of pump battery life; human error may play a causal or contributing role. Prevention of abrupt discontinuation requires careful attention to proper programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled visits for pump refilling and be educated on early symptoms of withdrawal.
-For patients with spasticity due to traumatic brain injury, intrathecal therapy should be delayed until the symptoms of spasticity are stable (i.e., at least one year after the injury).
-No specific dose adjustment guidelines have been suggested for elderly patients; however, caution is recommended in dose selection.
-A suggested treatment of intrathecal baclofen withdrawal is restoration of treatment at or near the same dosage as before therapy was interrupted. If restoration of intrathecal therapy is delayed, treatment with GABA-ergic agonist drugs should be considered. Oral or enteral baclofen alone should not be relied upon to stop intrathecal baclofen withdrawal.

Storage requirements:
-Refer to the manufacturer product information.

Reconstitution/preparation techniques:
-Refer to the manufacturer product information.

Patient advice:
-This drug should be taken during meals with a glass of water.

This drug should be used during pregnancy only if the benefit outweighs the risk. AU TGA pregnancy category: B3 US FDA pregnancy category: -Intrathecal: C -Oral tablet: Not Assigned

This drug given orally has been shown to increase the incidence of omphaloceles (ventral hernias) in fetuses of rats given approximately 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. There are no controlled data in human pregnancy. It is not known whether this drug can cause fetal harm or adversely affect reproductive capacity in humans. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D and X are being phased out.

LactMed Record Number

337

Last Revision Date

20160401

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