Gablofen

GABLOFEN is indicated for use in the management of severe spasticity in adult and pediatric patients age 4 years and above. Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via an implantable pump. For spasticity of spinal cord origin, chronic infusion of GABLOFEN via an implantable pump should be reserved for patients unresponsive to oral baclofen 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 baclofen therapy. GABLOFEN is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only in pumps labeled for intrathecal administration of GABLOFEN[see Clinical Studies].

Prior to implantation of a device for chronic intrathecal infusion of GABLOFEN, patients must show a response to GABLOFEN in a screening trial [see DOSAGE AND ADMINISTRATION].

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.

In a recent clinical study, 153 adult and pediatric patients with spasticity of spinal cord or cerebral origin were treated with Gablofen 3,000 mcg/mL. The adverse reactions seen in this study were similar to that found with lower concentrations of Gablofen.

Spasticity Of Spinal Cord Origin

In pre- and post-marketing clinical trials, the most common adverse reactions associated with use of intrathecal baclofen which were not seen at an equivalent incidence among placebo-treated patients were: somnolence, dizziness, nausea, hypotension, headache, convulsions and hypotonia.

8/474 patients with spasticity of spinal cord origin receiving long term infusion of intrathecal baclofen in pre- and post-marketing clinical studies in the U.S. discontinued treatment due to adverse reactions. These include: pump pocket infections (3), meningitis (2), wound dehiscence (1), gynecological fibroids (1) and pump overpressurization (1) with unknown, if any, sequela. Eleven patients who developed coma secondary to overdose had their treatment temporarily suspended, but all were subsequently re-started and were not, therefore, considered to be true discontinuations.

Fatalities - [see WARNINGS AND PRECAUTIONS].

Experience with intrathecal baclofen obtained in parallel, placebo-controlled, randomized studies provides only a limited basis for estimating the incidence of adverse reactions because the studies were of very brief duration (up to three days of infusion) and involved only a total of 63 patients. The following events occurred among the 31 patients receiving intrathecal baclofen in two randomized, placebo-controlled trials: hypotension (2), dizziness (2), headache (2), dyspnea (1). No adverse reactions were reported among the 32 patients receiving placebo in these studies.

Adverse events associated with the use of intrathecal baclofen reflect experience gained with 576 patients followed prospectively in the United States. They received intrathecal baclofen for periods of one day (screening) (N=576) to over eight years (maintenance) (N=10). The usual screening bolus dose administered prior to pump implantation in these studies was typically 50 mcg. The maintenance dose ranged from 12 mcg to 2,003 mcg per day. Because of the open, uncontrolled nature of the experience, a causal linkage between events observed and the administration of intrathecal baclofen cannot be reliably assessed in many cases and many of the adverse reactions reported are known to occur in association with the underlying conditions being treated. Nonetheless, many of the more commonly reported reactions . hypotonia, somnolence, dizziness, paresthesia, nausea/vomiting and headache . appear clearly drug-related.

Adverse experiences reported during all U.S. studies (both controlled and uncontrolled) are shown in Table 1. Eight of 474 patients who received chronic infusion via implanted pumps had adverse experiences which led to a discontinuation of long term treatment in the pre- and post-marketing studies.

Table 1: Most Common (≥1%) Adverse Reactions in Patients with Spasticity of Spinal Origin in Prospectively Monitored Clinical Trials

In addition to the more common (1% or more) adverse reactions reported in the prospectively followed 576 domestic patients in pre- and post-marketing studies, experience from an additional 194 patients exposed to intrathecal baclofen from foreign studies has been reported. The following adverse reactions, not described in the table, and arranged in decreasing order of frequency, and classified by body system, were reported:

Nervous System: Abnormal gait, thinking abnormal, tremor, amnesia, twitching, vasodilatation, cerebrovascular accident, nystagmus, personality disorder, psychotic depression, cerebral ischemia, emotional lability, euphoria, hypertonia, ileus, drug dependence, incoordination, paranoid reaction and ptosis.

Digestive System: Flatulence, dysphagia, dyspepsia and gastroenteritis.

Cardiovascular: Postural hypotension, bradycardia, palpitations, syncope, arrhythmia ventricular, deep thrombophlebitis, pallor and tachycardia.

Respiratory: Respiratory disorder, aspiration pneumonia, hyperventilation, pulmonary embolus and rhinitis.

Urogenital: Hematuria and kidney failure.

Skin and Appendages: Alopecia and sweating.

Metabolic and Nutritional Disorders: Weight loss, albuminuria, dehydration and hyperglycemia.

Special Senses: Abnormal vision, abnormality of accommodation, photophobia, taste loss and tinnitus.

Body as a Whole: Suicide, lack of drug effect, abdominal pain, hypothermia, neck rigidity, chest pain, chills, face edema, flu syndrome and overdose.

Hemic and Lymphatic System: Anemia.

Spasticity Of Cerebral Origin

In pre-marketing clinical trials, the most common adverse reactions associated with use of intrathecal baclofen which were not seen at an equivalent incidence among placebo-treated patients included: agitation, constipation, somnolence, leukocytosis, chills, urinary retention and hypotonia.

Adverse Reactions Associated with Discontinuation of Treatment

Nine of 211 patients receiving intrathecal baclofen in pre-marketing clinical studies in the U.S. discontinued long-term infusion due to adverse reactions associated with intrathecal therapy.

The nine adverse reactions leading to discontinuation were: infection (3), CSF leaks (2), meningitis (2), drainage (1), and unmanageable trunk control (1).

Three deaths, none of which were attributed to intrathecal baclofen, were reported in patients in clinical trials involving patients with spasticity of cerebral origin. See Warnings on other deaths reported in spinal spasticity patients.

Experience with intrathecal baclofen obtained in parallel, placebo-controlled, randomized studies provides only a limited basis for estimating the incidence of adverse reactions because the studies involved a total of 62 patients exposed to a single 50 mcg intrathecal bolus. The following adverse reactions occurred among the 62 patients receiving intrathecal baclofen in two randomized, placebocontrolled trials involving cerebral palsy and head injury patients, respectively: agitation, constipation, somnolence, leukocytosis, nausea, vomiting, nystagmus, chills, urinary retention, and hypotonia.

Adverse events associated with the use of intrathecal baclofen reflect experience gained with a total of 211 U.S. patients with spasticity of cerebral origin, of whom 112 were pediatric patients (under age 16 at enrollment). They received intrathecal baclofen for periods of one day (screening) (N=211) to 84 months (maintenance) (N=1). The usual screening bolus dose administered prior to pump implantation in these studies was 50 mcg to 75 mcg. The maintenance dose ranged from 22 mcg to 1,400 mcg per day. Doses used in this patient population for long-term infusion are generally lower than those required for patients with spasticity of spinal cord origin.

Because of the open, uncontrolled nature of the experience, a causal linkage between events observed and the administration of intrathecal baclofen cannot be reliably assessed in many cases. Nonetheless, many of the more commonly reported reactions . somnolence, dizziness, headache, nausea, hypotension, hypotonia and coma . appear clearly drug-related.

The most frequent (≥1%) adverse reactions reported during all clinical trials are shown in Table 2. Nine patients discontinued long term treatment due to adverse reactions.

Table 2: Most Common (≥1%) Adverse Reactions in Patients with Spasticity of Cerebral Origin

The more common (1% or more) adverse reactions reported in the prospectively followed 211 patients exposed to intrathecal baclofen have been reported. In the total cohort, the following adverse reactions, not described in Table 2, and arranged in decreasing order of frequency, and classified by body system, were reported:

Nervous System: Akathisia, ataxia, confusion, depression, opisthotonos, amnesia, anxiety, hallucinations, hysteria, insomnia, nystagmus, personality disorder, reflexes decreased, and vasodilitation.

Digestive System: Dysphagia, fecal incontinence, gastrointestinal hemorrhage and tongue disorder.

Cardiovascular: Bradycardia.

Respiratory: Apnea, dyspnea and hyperventilation.

Urogenital: Abnormal ejaculation, kidney calculus, oliguria and vaginitis.

Skin and Appendages: Rash, sweating, alopecia, contact dermatitis and skin ulcer.

Special Senses: Abnormality of accommodation.

Body as a Whole: Death, fever, abdominal pain, carcinoma, malaise and hypothermia.

Hemic and Lymphatic System: Leukocytosis and petechial rash.

Read the entire FDA prescribing information for Gablofen (Baclofen Injection)

Gablofen is a prescription medication used to relieve spasms and increased muscle tone caused by multiple sclerosis or spinal injury. This medication belongs to a group of drugs called muscle relaxants. Although the way it works is not fully understood, Gablofen may decrease the number and severity of muscle spasms by inhibiting nerve signals.

This medication comes as an injectable liquid to be given directly into the spinal fluid by a healthcare professional.

Common side effects include weakness, drowsiness, and dizziness. Do not drive or operate machinery until you know how this medication affects you.

​Serious side effects have been reported. See "Gablofen Precautions" section.

Common side effects include:

• drowsiness
• dizziness
• weakness
• fatigue
• headache
• insomnia
• nausea

Less common side effects include:

• confusion
• low blood pressure (hypotension)
• constipation
• frequent urination

This is not a complete list of Gablofen side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Serious side effects have been reported including:

• hallucinations and seizures after stopping medication too quickly. Withdrawal symptoms can occur if Gablofen is stopped too quickly. Talk to your doctor before stopping this medication, especially if you have been taking it for a long time. For intrathecal Gablofen, see "Gablofen FDA Warning" section.
• increased risk of seizures. Gablofen can increase risk of seizures, especially in those with seizure disorders (epilepsy).
• worsening mental illness. Talk to your doctor about mental illness.

Dose reduction may be necessary in patients with kidney disease. This medication is excreted by the kidneys. If you have kidney disease, your doctor may recommend a lower dose.

People who have suffered a stroke may be less able to tolerate Gablofen and may not benefit from taking it.

Do not take Gablofen if you are allergic to any of its ingredients.

Gablofen can cause drowsiness. Do not drive or operate machinery until you know how it affects you.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling sleepy.
• Dizziness.
• Feeling tired or weak.
• Not able to sleep.
• Upset stomach.
• Headache.
• Hard stools (constipation).

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

There is inadequate systematic experience with the use of intrathecal baclofen in combination with other medications to predict specific drug-drug interactions. Interactions attributed to the combined use of Gablofen and epidural morphine include hypotension and dyspnea.

Gablofen is a muscle relaxer and an antispastic agent.

Gablofen is used to treat severe spasticity, a movement disorder often brought on by multiple sclerosis, cerebral palsy, spinal cord injury, brain trauma and stroke.

Gablofen may also be used for other purposes not listed in this medication guide.

Do not use this medication if you are allergic to Gablofen.

Before taking Gablofen, tell your doctor if you are allergic to any drugs, or if you have:

• kidney disease;
• epilepsy or other seizure disorder; or
• a history of stroke or blood clots.

If you have any of these conditions, you may need a dose adjustment or special tests to safely take this medication.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether Gablofen passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Older adults may be more sensitive to the effects of this medicine.

Do not give this medication to a child younger than 4 years old.

Gablofen is given as an injection into the space around your spinal cord (intrathecal injection) using a computerized, portable infusion pump to control the rate of medication you receive. You may need to use this medication for a long period of time.

Gablofen must be given only as an intrathecal injection through an infusion pump and should not be injected directly into a vein or other part of the body. Your doctor, nurse, or other healthcare provider will give you this injection.

Your doctor may occasionally change your dose or infusion pump flow rate to make sure you get the best results from this medication.

You may have withdrawal symptoms such as seizures or hallucinations, when you stop using Gablofen after using it over a long period of time. Do not stop using this medication suddenly. Always talk to your doctor. You may need to use less and less before you stop the medication completely.

Store Gablofen at room temperature away from moisture and heat.

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