BACLOFEN- baclofen injection

United States - English - NLM (National Library of Medicine)

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Active ingredient:
BACLOFEN (UNII: H789N3FKE8) (BACLOFEN - UNII:H789N3FKE8)
Available from:
MAlA Pharmaceuticals, Inc.
Administration route:
INTRATHECAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Baclofen injection 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 baclofen injection 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.  Baclofen injection is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and, for chronic use, only with the Medtronic SynchroMed® II Programmable Pump or other pumps labeled for intrathecal administration of baclofen injection [see Clinical Studies (14)] . Prior to implan
Product summary:
Baclofen injection is a clear, colorless, sterile, pyrogen-free, isotonic solution consisting of the active ingredient, Baclofen USP, and the excipients Sodium Chloride USP and Water for Injection USP in single-dose clear glass vials. Baclofen injection is packaged in single-dose vials supplied as follows: One vial containing 20,000 mcg/20 mL (1,000 mcg/mL) (NDC 70511-123-20). Storage Does not require refrigeration. Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Do not freeze. Do not heat sterilize.
Authorization status:
Abbreviated New Drug Application
Authorization number:
70511-123-20

BACLOFEN- baclofen injection

MAlA Pharmaceuticals, Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use BACLOFEN INJECTION safely and

effectively. See full prescribing information for BACLOFEN INJECTION.Initial U.S. Approval: 1992

INDICATIONS AND USAGE

Baclofen injection is a gamma-aminobutyric acid (GABA) ergic agonist indicated for use in the management of severe

spasticity of cerebral or spinal origin in adult and pediatric patients age 4 years and above (1)

Baclofen injection should be reserved for patients unresponsive to oral baclofen therapy, or those who experience

intolerable central nervous system side effects at effective doses (1)

Patients should first respond to a screening dose of intrathecal baclofen prior to consideration for long term infusion via

an implantable pump. (1)

Spasticity due to traumatic brain injury: wait at least one year after injury before considering baclofen injection therapy

DOSAGE AND ADMINISTRATION

Baclofen injection is intended for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar

puncture) and, for chronic use in the Medtronic SynchroMed® II Programmable Pump or other pumps labeled for

intrathecal administration of baclofen injection; Refer to the pump manufacturer's manual and follow the specific

instructions and precautions for programming the pump and/or refilling the reservoir (2.1)

Screening: Patients who do not respond to a 100 mcg intrathecal bolus should not be considered for an implanted pump

for chronic infusion (2.2)

Dose Titration: Spasticity may be necessary to sustain upright posture and balance in locomotion or may be useful to

obtain optimal function and care (2.5)

Maintenance Therapy: Titrate patients individually; Lowest dose with an optimal response should be used, generally

300 mcg/day to 800 mcg/day for spasticity of spinal cord origin and 90 mcg/day to 700 mcg/day for spasticity of

cerebral origin; Titrate baclofen injection to maintain some degree of muscle tone and allow occasional spasms. (2.6)

CONTRAINDICATIONS

Hypersensitivity to baclofen (4)

Do not use baclofen injection for intravenous, intramuscular, subcutaneous or epidural administration. (4)

ADVERSE REACTIONS

The most common adverse reactions in patients with spasticity of spinal origin were somnolence, dizziness, nausea,

hypotension, headache, convulsions and hypotonia (6.1)

The most common adverse reactions in patients with spasticity of cerebral origin were agitation, constipation,

somnolence, leukocytosis, chills, urinary retention and hypotonia (6.2)

To report SUSPECTED ADVERSE REACTIONS, contact MAIA Pharmaceuticals, Inc. at 1-888-877-9064 or FDA

at 1-800-FDA-1088 or

www.fda.gov/medwatch

DRUG INTERACTIONS

Combined use with morphine: hypotension and dyspnea (7)

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm (8.1)

Pediatric use: Safety and effectiveness in pediatric patients below the age of 4 years have not been established (8.4)

Revised: 8/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: DO NOT DISCONTINUE ABRUPTLY See full prescribing information for complete

boxed warning

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Use Only with Medtronic SynchroMed® II Programmable Pump (or other pumps labeled for

intrathecal administration of baclofen injection)

2.2 Screening Phase

2.3 Preparation Information

2.4 Administration Information

2.5 Dose Titration

2.6 Maintenance Therapy

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Risk of Life-Threatening Overdose During Pump Refills

5.2 Potential for Contamination due to Non-sterile External Surface of Prefilled Syringe

5.3 Prescriber, Caregiver and Patient Training and Screening Procedure/Post- Implantation

Environment

5.4 Overdose

5.5 Withdrawal

5.6 Possible Exacerbation of Psychotic Disorders, Schizophrenia, or Confusional States

5.7 Fatalities

5.8 Use with Caution in Patients with a History of Autonomic Dysreflexia

5.9 Infections

5.10 Drowsiness

5.11 Intrathecal Mass Formation

5.12 Ovarian Cysts

6 ADVERSE REACTIONS

6.1 Spasticity of Spinal Cord Origin

6.2 Spasticity of Cerebral Origin

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Labor and Delivery

8.3 Nursing Mothers

8.4 Pediatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

FULL PRESCRIBING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

WARNING: DO NOT DISCONTINUE ABRUPTLY See full prescribing information for

complete boxed warning

Abrupt discontinuationof intrathecal baclofen, regardless of the cause, has resulted in

sequelae that include 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.

Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to

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 refill visits and should be educated on the early symptoms of baclofen

withdrawal. Special attention should be given to patients at apparent risk (e.g., spinal cord

injuries at T-6 or above, communication difficulties, history of withdrawal symptoms from

oral or intrathecal baclofen). Consult the technical manual of the implantable infusion

system for additional post-implant clinician and patient information [see Warnings and

Precautions (5.4)].

1 INDICATIONS AND USAGE

Baclofen injection 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 baclofen injection 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. Baclofen injection is intended

for use by the intrathecal route in single bolus test doses (via spinal catheter or lumbar puncture) and,

for chronic use, only with the Medtronic SynchroMed® II Programmable Pump or other pumps labeled

for intrathecal administration of baclofen injection [see Clinical Studies (14)].

Prior to implantation of a device for chronic intrathecal infusion of baclofen injection, patients must

show a response to baclofen injection in a screening trial [see Dosage and Administration (2.2)].

2 DOSAGE AND ADMINISTRATION

2.1 Use Only with Medtronic SynchroMed® II Programmable Pump (or other pumps labeled for

intrathecal administration of baclofen injection)

Baclofen injection is approved only for use with the Medtronic SynchroMed® II Programmable Pump

or other pumps labeled for intrathecal administration of baclofen injection. Refer to the manufacturer's

manual for specific instructions and precautions for programming the pump and/or refilling the

reservoir. It is important to select the appropriate refill kit for the pump used to administer baclofen

injection. Baclofen injection is not to be compounded with other medications.

2.2 Screening Phase

Prior to pump implantation and initiation of chronic infusion of baclofen injection, patients must

demonstrate a positive clinical response to a baclofen injection bolus dose administered intrathecally in

a screening trial. The screening trial employs baclofen injection at a concentration of 50 mcg/mL. A 1

mL syringe (50 mcg/mL) is available for use in the screening trial. The screening procedure is as

follows. An initial bolus containing 50 micrograms in a volume of 1 milliliter is administered into the

intrathecal space by barbotage over a period of not less than one minute. The patient is observed over

the ensuing 4 to 8 hours. A positive response consists of a significant decrease in muscle tone and/or

frequency and/or severity of spasms. If the initial response is less than desired, a second bolus injection

may be administered 24 hours after the first. The second screening bolus dose consists of 75

micrograms in 1.5 milliliters. Again, the patient should be observed for an interval of 4 to 8 hours. If the

response is still inadequate, a final bolus screening dose of 100 micrograms in 2 milliliters may be

administered 24 hours later.

Pediatric Patients

The starting screening dose for pediatric patients is the same as in adult patients, i.e., 50 mcg. However,

for very small patients, a screening dose of 25 mcg may be tried first.

Patients who do not respond to a 100 mcg intrathecal bolus should not be considered candidates for an

implanted pump for chronic infusion.

2.3 Preparation Information

Screening

Use the 1 mL screening syringe only (50 mcg/mL) for bolus injection into the subarachnoid space. For a

50 mcg bolus dose, use 1 mL of the screening syringe. 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 syringes).

Maintenance

The specific concentration that should be used depends upon the total daily dose required as well as the

delivery rate of the pump. For patients who require concentrations other than 500 mcg/mL, 1,000

mcg/mL or 2,000 mcg/mL, baclofen injection must be diluted with sterile preservative free Sodium

Chloride for Injection, USP.

2.4 Administration Information

Parenteral drug products should be inspected for particulate matter and discoloration prior to

administration, whenever solution and container permit.

The external surface of baclofen injection prefilled syringes (all strengths, including the 50 mcg/mL

strength) are non-sterile. The use of baclofen injection prefilled syringe in an aseptic setting (i.e.,

operating room) to fill sterile intrathecal pumps prior to implantation in patients is not recommended.

For outpatient use, modify aseptic procedures to avoid contamination of sterile surfaces through

contact with the non-sterile exterior of the baclofen injection prefilled syringe when filling the pump

reservoir [see Warnings and Precautions (5.2)].

Delivery Regimen

Baclofen injection is most often administered in a continuous infusion mode immediately following

implant. For those patients implanted with programmable pumps who have achieved relatively

satisfactory control on continuous infusion, further benefit may be attained using more complex

schedules of baclofen injection delivery. For example, 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 two hours before the time of desired clinical effect.

2.5 Dose Titration

Post-Implant Dose Titration Period

To determine the initial total daily dose of baclofen injection following implant, the screening dose that

gave a positive effect should be doubled and administered over a 24-hour period, 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 a 24-hour period. No dose increases should be given in the first 24

hours (i.e., until the steady state is achieved). In most patients, it will be necessary to increase the dose

gradually over time to maintain effectiveness; a sudden requirement for substantial dose escalation

gradually over time to maintain effectiveness; a sudden requirement for substantial dose escalation

typically indicates a catheter complication (i.e., catheter kink or dislodgement).

Adult Patients with Spasticity of Spinal Cord Origin

After the first 24 hours, for adult patients, the daily dosage should be increased slowly by 10% to 30%

increments and only once every 24 hours, until the desired clinical 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 clinical effect is achieved.

Pediatric Patients

After the first 24 hours, the daily dose should be increased slowly by 5% to 15% only once every 24

hours, until the desired clinical effect is achieved. 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.

Additional Considerations Pertaining to Dosage Adjustment

Careful dose titration of baclofen injection is needed when spasticity is necessary to sustain upright

posture and balance in locomotion or whenever spasticity is used to obtain optimal function and care. It

may be important to titrate the dose to maintain some degree of muscle tone and allow occasional spasms

to: 1) help support circulatory function, 2) possibly prevent the formation of deep vein thrombosis, 3)

optimize activities of daily living and ease of care.

Except in overdose related emergencies, the dose of baclofen injection should ordinarily 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 baclofen injection infusion. Reduction and discontinuation of oral antispasmotics should be

done slowly and with careful monitoring by the physician. Abrupt reduction or discontinuation of

concomitant antispastics should be avoided.

2.6 Maintenance Therapy

Spasticity of Spinal Cord Origin Patients

The clinical goal is to maintain muscle tone as close to normal as possible, and to minimize the

frequency and severity of spasms to the extent possible, without inducing intolerable side effects. Very

often, the maintenance dose needs to be adjusted during the first few months of therapy while patients

adjust to changes in lifestyle due to the alleviation of spasticity. 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. Most

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).

Maintenance dosage for long term continuous infusion of intrathecal baclofen has ranged from 12

mcg/day to 2,003 mcg/day, with most patients adequately maintained on 300 micrograms to 800

micrograms per day. There is limited experience with daily doses greater than

1,000 mcg/day. Determination of the optimal baclofen injection dose requires individual titration. The

lowest dose with an optimal response should be used.

Spasticity of Cerebral Origin Patients

The clinical goal is to maintain muscle tone as close to normal as possible and to minimize the

frequency and severity of spasms to the extent possible, without inducing intolerable side effects, or to

titrate the dose to the desired degree of muscle tone for optimal functions. Very often the maintenance

dose needs to be adjusted during the first few months of therapy while patients adjust to changes in

lifestyle due to the alleviation of spasticity.

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. 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).

Maintenance dosage for long term continuous infusion of intrathecal baclofen has ranged from 22

mcg/day to 1,400 mcg/day, with most patients adequately maintained on 90 micrograms to 703

micrograms per day. In clinical trials, only 3 of 150 patients required daily doses greater than 1,000

mcg/day.

Pediatric Patients

Use same dosing recommendations for patients with spasticity of cerebral origin. Pediatric patients

under 12 years seemed to require a lower daily dose in clinical trials. Average daily dose for patients

under 12 years was 274 mcg/day, with a range of 24 mcg/day to 1,199 mcg/day.

Dosage requirement for pediatric patients over 12 years does not seem to be different from that of adult

patients. Determination of the optimal baclofen injection dose requires individual titration. The lowest

dose with an optimal response should be used.

Potential Need for Dose Adjustments in Chronic Use

During long term treatment, approximately 5% (28/627) of patients become refractory to increasing

doses. There is not sufficient experience to make firm 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 baclofen over a 2 to 4 week period and switching to alternative

methods of spasticity management. After the “drug holiday,” intrathecal baclofen may be restarted at the

initial continuous infusion dose.

4 CONTRAINDICATIONS

Baclofen injection is contraindicated in patients with a hypersensitivity to baclofen. Do not use

baclofen injection for intravenous, intramuscular, subcutaneous or epidural administration.

5 WARNINGS AND PRECAUTIONS

Do not directly inject baclofen injection into the pump catheter access port, as this may cause a life-

threatening overdose (5.1)

Potential for contamination due to non-sterile external surface of prefilled syringe (5.2)

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 (5.3)

Overdose may cause drowsiness, lightheadedness, dizziness, somnolence, respiratory depression,

seizures, rostral progression of hypotonia and loss of consciousness progressing to coma (5.4)

Possible exacerbation of psychotic disorders, schizophrenia or confusional states (5.6)

5.1 Risk of Life-Threatening Overdose During Pump Refills

Use extreme caution when filling the Medtronic SynchroMed® II Programmable Pump which is

equipped with an injection port that allows direct access to the intrathecal catheter. Direct injection into

the catheter through the catheter access port may cause a life-threatening overdose.

the catheter through the catheter access port may cause a life-threatening overdose.

Reservoir refilling must be performed by fully trained and qualified personnel following the directions

provided by the pump manufacturer. Carefully calculate refill intervals to prevent depletion of the

reservoir, as this would result in the return of severe spasticity and possibly symptoms of withdrawal.

Strict aseptic technique in filling is required to avoid bacterial contamination and serious infection. A

period of observation appropriate to the clinical situation should follow each refill or manipulation of

the drug reservoir.

5.2 Potential for Contamination due to Non-sterile External Surface of Prefilled Syringe

Although the drug solution and pathway in the baclofen injection prefilled syringes are sterile, the

external surface of the prefilled syringes (all strengths, including the 50 mcg/mL strength) are non-

sterile. This has the potential to lead to contamination and consequent adverse reactions.

The use of baclofen injection prefilled syringe in an aseptic setting (e.g., operating room) to fill sterile

intrathecal pumps prior to implantation in patients is not recommended, unless the external surface of the

prefilled syringe is treated to ensure sterility. Baclofen injection supplied in vials may be used with

conventional aseptic technique to fill intrathecal pumps prior to implantation. Procedures should also be

put in place while refilling implantable intrathecal pumps in an outpatient setting to avoid contamination

of sterile surfaces through contact with the non-sterile exterior of the baclofen injection prefilled

syringe.

5.3 Prescriber, Caregiver and Patient Training and Screening Procedure/Post- Implantation

Environment

Baclofen injection is for use in single bolus intrathecal injections (via a catheter placed in the lumbar

intrathecal space or injection by lumbar puncture) and in the implantable Medtronic SynchroMed® II

Programmable Pump or other pumps labeled for intrathecal administration of baclofen injection.

Because of the possibility of potentially life-threatening CNS depression, cardiovascular collapse,

and/or respiratory failure, physicians must be adequately trained and educated in chronic intrathecal

infusion therapy.

The pump system should not be implanted until the patient's response to bolus baclofen injection is

adequately evaluated. Evaluation (consisting of a screening procedure) requires that baclofen injection

be administered into the intrathecal space via a catheter or lumbar puncture [see Dosage and

Administration (2.2)]. Because of the risks associated with the screening procedure and the adjustment

of dosage following pump implantation, these phases must be conducted in a medically supervised and

adequately equipped environment following the instructions outlined in the Dosage and Administration

section [see Dosage and Administration (2.2 and 2.5)].

Resuscitative equipment should be available.

Following surgical implantation of the pump, particularly during the initial phases of pump use, the

patient should be monitored closely until it is certain that the patient's response to the infusion is

acceptable and reasonably stable.

On each occasion that the dosing rate of the pump and/or the concentration of baclofen injection in the

reservoir is adjusted, close medical monitoring is required until it is certain that the patient's response to

the infusion is acceptable and reasonably stable.

It is mandatory that the patient, all patient caregivers, and the physicians responsible for the patient

receive adequate information regarding the risks of this mode of treatment. All medical personnel and

caregivers should be instructed in 1) the signs and symptoms of overdose, 2) procedures to be followed

in the event of overdose and 3) proper home care of the pump and insertion site.

5.4 Overdose

Signs of overdose may appear suddenly or insidiously. Acute massive overdose may present as coma.

Less sudden and/or less severe forms of overdose may present with signs of drowsiness,

lightheadedness, dizziness, somnolence, respiratory depression, seizures, rostral progression of

hypotonia and loss of consciousness progressing to coma. Should overdose appear likely, the patient

should be taken immediately to a hospital for assessment and emptying of the pump reservoir. In cases

reported to date, overdose has generally been related to pump malfunction or dosing error [see

Overdosage (10)].

Extreme caution must be used when filling the implantable pump.

The Medtronic SynchroMed® II Programmable Pump should only be refilled through the reservoir

refill septum. The Medtronic SynchroMed® II Programmable Pump is also equipped with a catheter

access port that allows direct access to the intrathecal catheter. Direct injection into this catheter access

port may cause a life-threatening overdose.

5.5 Withdrawal

Abrupt withdrawal of intrathecal baclofen, regardless of the cause, has resulted in sequelae that

included high fever, altered mental status, exaggerated rebound spasticity and muscle rigidity that in

rare cases progressed to rhabdomyolysis, multiple organ-system failure, and death. In the first 9 years

of post-marketing experience, 27 cases of withdrawal temporally related to the cessation of baclofen

therapy were reported; six patients died. In most cases, symptoms of withdrawal appeared within hours

to a few days following interruption of baclofen therapy.

Common reasons for abrupt interruption of intrathecal baclofen therapy included malfunction of the

catheter (especially disconnection), low volume in the pump reservoir, and end of pump battery life;

human error may have played a causal or contributing role in some cases. Cases of intrathecal mass at

the tip of the implanted catheter leading to withdrawal symptoms have also been reported, most of them

involving pharmacy compounded analgesic admixtures [see Warnings and Precautions (5.10)].

Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to 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 refill visits and should be

educated on the early symptoms of baclofen withdrawal.

All patients receiving intrathecal baclofen therapy are potentially at risk for withdrawal. Early symptoms

of baclofen withdrawal may include return of baseline spasticity, pruritus, hypotension, and

paresthesias. Some clinical characteristics of the advanced intrathecal baclofen withdrawal syndrome

may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, neuroleptic-malignant

syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis.

Rapid, accurate diagnosis and treatment in an emergency-room or intensive-care setting are important in

order to prevent the potentially life-threatening central nervous system and systemic effects of

intrathecal baclofen withdrawal. The suggested treatment for intrathecal baclofen withdrawal is the

restoration of intrathecal baclofen at or near the same dosage as before therapy was interrupted.

However, if restoration of intrathecal delivery is delayed, treatment with

GABA-ergic agonist drugs such as oral or enteral baclofen, or oral, enteral, or intravenous

benzodiazepines may prevent potentially fatal sequelae. Oral or enteral baclofen alone should not be

relied upon to halt the progression of intrathecal baclofen withdrawal.

Seizures have been reported during overdose and with withdrawal from intrathecal baclofen as well as

in patients maintained on therapeutic doses of intrathecal baclofen.

5.6 Possible Exacerbation of Psychotic Disorders, Schizophrenia, or Confusional States

Patients suffering from psychotic disorders, schizophrenia, or confusional states should be treated

cautiously with baclofen injection and kept under careful surveillance, because exacerbations of these

conditions have been observed with oral administration.

5.7 Fatalities

Spasticity of Spinal Cord Origin

There were 16 deaths reported among the 576 U.S. patients treated with intrathecal baclofen in pre- and

post-marketing studies evaluated as of December 1992. Because these patients were treated under

uncontrolled clinical settings, it is impossible to determine definitively what role, if any, intrathecal

baclofen played in their deaths. As a group, the patients who died were relatively young (mean age was

47 with a range from 25 to 63), but the majority suffered from severe spasticity of many years duration,

were nonambulatory, had various medical complications such as pneumonia, urinary tract infections, and

decubiti, and/or had received multiple concomitant medications. A case-by-case review of the clinical

course of the 16 patients who died failed to reveal any unique signs, symptoms, or laboratory results

that would suggest that treatment with intrathecal baclofen caused their deaths. Two patients, however,

did suffer sudden and unexpected death within 2 weeks of pump implantation and one patient died

unexpectedly after screening.

One patient, a 44 year-old male with Multiple Sclerosis, died in hospital on the second day following

pump implantation. An autopsy demonstrated severe fibrosis of the coronary conduction system. A

second patient, a 52 year-old woman with MS and a history of an inferior wall myocardial infarction,

was found dead in bed 12 days after pump implantation, 2 hours after having had documented normal vital

signs. An autopsy revealed pulmonary congestion and bilateral pleural effusions. It is impossible to

determine whether intrathecal baclofen contributed to these deaths. The third patient underwent three

baclofen screening trials. His medical history included spinal cord injury, aspiration pneumonia, septic

shock, disseminated intravascular coagulopathy, severe metabolic acidosis, hepatic toxicity, and status

epilepticus. Twelve days after screening (he was not implanted), he again experienced status epilepticus

with subsequent significant neurological deterioration. Based upon prior instruction, extraordinary

resuscitative measures were not pursued and the patient died.

Spasticity of Cerebral Origin

There were three deaths occurring among the 211 patients treated with intrathecal baclofen in pre-

marketing studies as of March 1996. These deaths were not attributed to the therapy.

5.8 Use with Caution in Patients with a History of Autonomic Dysreflexia

Baclofen injection should be used with caution in patients with a history of autonomic dysreflexia. The

presence of nociceptive stimuli or abrupt withdrawal of baclofen injection may cause an autonomic

dysreflexic episode.

5.9 Infections

Patients should be infection-free prior to the screening trial with baclofen injection because the

presence of a systemic infection may interfere with an assessment of the patient's response to bolus

baclofen injection Patients should be infection-free prior to implantation of the pump because the

presence of infection may increase the risk of surgical complications. Moreover, a systemic infection

may complicate dosing.

5.10 Drowsiness

Drowsiness has been reported in patients on intrathecal baclofen. Patients should be cautioned

regarding the operation of automobiles or other dangerous machinery, and activities made hazardous by

decreased alertness. Patients should also be cautioned that the central nervous system depressant effects

of intrathecal baclofen may be additive to those of alcohol and other CNS depressants.

5.11 Intrathecal Mass Formation

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 are: 1) 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), 2) pain, 3) neurological deficit/dysfunction.

Clinicians should monitor patients on intraspinal therapy carefully for any new neurological signs or

symptoms. In patients with new neurological signs or symptoms suggestive of an intrathecal mass,

consider a neurosurgical consultation, since many of the symptoms of inflammatory mass are not unlike

the symptoms experienced by patients with severe spasticity from their disease. In some cases,

performance of an imaging procedure may be appropriate to confirm or rule-out the diagnosis of an

intrathecal mass.

5.12 Ovarian Cysts

A dose-related increase in incidence of ovarian cysts was observed in female rats treated chronically

with oral baclofen. Ovarian cysts have been found by palpation in about 4% of the multiple sclerosis

patients who were treated with oral baclofen for up to one year. In most cases these cysts disappeared

spontaneously while patients continued to receive the drug. Ovarian cysts are estimated to occur

spontaneously in approximately 1% to 5% of the normal female population.

6 ADVERSE REACTIONS

6.1 Spasticity of Spinal Cord Origin

Most Common Adverse Reactions in Patients with Spasticity of Spinal 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.

Adverse Reactions Associated with Discontinuation of Treatment

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 (5.6)].

Incidence in Controlled Trials

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.

Events Observed during the Pre- and Post-marketing Evaluation of Intrathecal Baclofen

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

Adverse Reaction

Percent

N=576

Screening

Percent

N=474

T itration

Percent

N=430

Maintenance

Hypotonia

13.5

25.3

Somnolence

20.9

Dizziness

Paresthesia

Nausea and Vomiting

Headache

Constipation

Convulsion

Urinary Retention

Dry Mouth

Accidental Injury

Asthenia

Confusion

Death

Pain

Speech Disorder

Hypotension

Ambylopia

Diarrhea

Hypoventilation

Coma

Impotence

Peripheral Edema

Urinary Incontinence

Insomnia

Anxiety

Depression

Dyspnea

Fever

Pneumonia

Urinary Frequency

Urticaria

Anorexia

Diplopia

Dysautonomia

Hallucinations

Hypertension

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.

6.2 Spasticity of Cerebral Origin

Most Common Adverse Reactions

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).

Fatalities

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.

Incidence in Controlled Trials

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

Following administration of test bolus

Two month period following implant

Beyond two months following implant N=Total number of patients entering

each period %=% of patients evaluated

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, placebo-

controlled trials involving cerebral palsy and head injury patients, respectively: agitation, constipation,

somnolence, leukocytosis, nausea, vomiting, nystagmus, chills, urinary retention, and hypotonia.

Events Observed during the Pre-marketing Evaluation of Intrathecal Baclofen

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

Adverse Reaction

Percent

N=211

Screening

Percent

N=153

T itration

Percent

N=150

Maintenance

Hypotonia

14.4

34.7

Somnolence

10.5

18.7

Headache

10.7

Nausea and Vomiting

10.5

Vomiting

Urinary Retention

Convulsion

10.0

Dizziness

Nausea

Hypoventilation

Hypertonia

Paresthesia

Hypotension

Increased Salivation

Back Pain

Constipation

Pain

Pruritus

Diarrhea

Peripheral Edema

Thinking Abnormal

Agitation

Asthenia

Chills

Coma

Dry Mouth

Pneumonia

Speech Disorder

Tremor

Urinary Incontinence

Urination Impaired

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.

7 DRUG INTERACTIONS

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 baclofen injection and epidural morphine include hypotension and dyspnea.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies in pregnant women. Baclofen injection should be

used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Baclofen 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.

8.2 Labor and Delivery

Following administration of test bolus

Two month period following implant

Beyond two months following implant N=Total number of patients

entering each period. 211 patients received drug; (1 of 212) received

placebo only

The effect of baclofen on labor and delivery is unknown.

8.3 Nursing Mothers

At therapeutic oral doses, baclofen is excreted in human milk. It is not known whether detectable levels

of drug are present in milk of nursing mothers receiving baclofen injection. Because of the potential

for serious adverse reactions in nursing infants from baclofen injection, a decision should be made

whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to

the mother.

8.4 Pediatric Use

Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion.

Please consult pump manufacturer's manual for specific recommendations. Safety and effectiveness in

pediatric patients below the age of 4 have not been established.

10 OVERDOSAGE

Special attention must be given to recognizing the signs and symptoms of overdosage, especially during

the initial screening and dose-titration phase of treatment, but also during re-introduction of baclofen

injection after a period of interruption in therapy.

Symptoms of Intrathecal Baclofen Overdose

Drowsiness, lightheadedness, dizziness, somnolence, respiratory depression, seizures, rostral

progression of hypotonia and loss of consciousness progressing to coma of up to 72 hours duration. In

most cases reported, coma was reversible without sequelae after drug was discontinued. Symptoms of

intrathecal baclofen overdose were reported in a sensitive adult patient after receiving a 25 mcg

intrathecal bolus.

Treatment Suggestions for Overdose

There is no specific antidote for treating overdoses of baclofen injection; however, the following steps

should ordinarily be undertaken:

1) Residual intrathecal baclofen solution should be removed from the pump as soon as possible.

2) Patients with respiratory depression should be intubated if necessary, until the drug is eliminated.

Anecdotal reports suggest that intravenous physostigmine may reverse central side effects, notably

drowsiness and respiratory depression. Caution in administering physostigmine is advised, however,

because its use has been associated with the induction of seizures and bradycardia.

Physostigmine Doses for Adult Patients

Administer 2 mg of physostigmine intramuscularly or intravenously at a slow controlled rate of no more

than 1 mg per minute. Dosage may be repeated if life-threatening signs, such as arrhythmia, convulsions

or coma occur.

Physostigmine Doses for Pediatric Patients

Administer 0.02 mg/kg physostigmine intramuscularly or intravenously, do not give more than

0.5 mg per minute. The dosage may be repeated at 5 to 10 minute intervals until a therapeutic effect is

obtained or a maximum dose of 2 mg is attained.

Physostigmine may not be effective in reversing large overdoses and patients may need to be maintained

with respiratory support.

If lumbar puncture is not contraindicated, consideration should be given to withdrawing 30 to 40 mL of

CSF to reduce CSF baclofen concentration.

11 DESCRIPTION

Baclofen injection is a muscle relaxant and antispastic. Baclofen's pharmacological class is a gamma-

aminobutyric acid (GABA) ergic agonist. Baclofen's chemical name is 4-amino- 3-(4-chlorophenyl)

butanoic acid, and its structural formula is:

Baclofen is a white to off-white, odorless or practically odorless crystalline powder, with a molecular

weight of 213.66. It is slightly soluble in water, very slightly soluble in methanol, and insoluble in

chloroform.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The precise mechanism of action of baclofen as a muscle relaxant and antispasticity agent is not fully

understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly

by decreasing excitatory neurotransmitter release from primary afferent terminals, although actions at

supraspinal sites may also occur and contribute to its clinical effect. Baclofen is a structural analog of

the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and may exert its effects by

stimulation of the GABAB receptor subtype.

Baclofen when introduced directly into the intrathecal space permits effective CSF concentrations to be

achieved with resultant plasma concentrations 100 times less than those occurring with oral

administration. In people, as well as in 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.

12.2 Pharmacodynamics

Intrathecal Bolus

Adult Patients

The onset of action is generally one-half hour to one hour after an intrathecal bolus. Peak spasmolytic

effect is seen at approximately four hours after dosing and effects may last four to eight hours. Onset,

peak response, and duration of action may vary with individual patients depending on the dose and

severity of symptoms.

Pediatric Patients

The onset, peak response and duration of action is similar to those seen in adult patients.

Continuous Infusion

AdultPatients

Intrathecal baclofen's antispastic action is first seen at 6 to 8 hours after initiation of continuous

infusion. Maximum activity is observed in 24 to 48 hours.

Pediatric Patients

Pediatric Patients

No additional information on continuous infusions is available for pediatric patients.

12.3 Pharmacokinetics

The pharmacokinetics of cerebrospinal fluid (CSF) clearance of intrathecal baclofen calculated from

intrathecal bolus or continuous infusion studies approximates CSF turnover, suggesting elimination is

by bulk-flow removal of CSF.

Intrathecal Bolus

After a bolus lumbar injection of 50 mcg or 100 mcg intrathecal baclofen in seven patients, the average

CSF elimination half-life was 1.51 hours over the first four hours and the average CSF clearance was

approximately 30 mL/hour.

Continuous Infusion

The mean CSF clearance for intrathecal baclofen was approximately 30 mL/hour in a study involving ten

patients on continuous intrathecal infusion. Concurrent plasma concentrations of baclofen during

intrathecal administration are expected to be low (0 to 5 ng/mL). Limited pharmacokinetic data suggest

that a lumbar-cisternal concentration gradient of about 4:1 is established along the neuroaxis during

baclofen infusion. This is based upon simultaneous CSF sampling via cisternal and lumbar tap in 5

patients receiving continuous baclofen infusion at the lumbar level at doses associated with therapeutic

efficacy; the interpatient variability was great. The gradient was not altered by position. Six pediatric

patients (age 8 to 18 years) receiving continuous intrathecal baclofen infusion at doses of 77 to 400

mcg/day had plasma baclofen levels near or below 10 ng/mL.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No increase in tumors was seen in rats receiving baclofen orally for two years at approximately 30 to

60 times on a mg/kg basis, or 10 to 20 times on a mg/m2 basis, the maximum oral dose recommended for

human use. Mutagenicity assays with baclofen have not been performed.

14 CLINICAL STUDIES

Spasticity of Spinal Cord Origin

Evidence supporting the efficacy of intrathecal baclofen was obtained in randomized, controlled

investigations that compared the effects of either a single intrathecal dose or a three day intrathecal

infusion of intrathecal baclofen to placebo in patients with severe spasticity and spasms due to either

spinal cord trauma or multiple sclerosis. Intrathecal baclofen was superior to placebo on both principal

outcome measures employed: change from baseline in the Ashworth rating of spasticity and the

frequency of spasms.

Spasticity of Cerebral Origin

The efficacy of intrathecal baclofen was investigated in three controlled clinical trials; two enrolled

patients with cerebral palsy and one enrolled patients with spasticity due to previous brain injury. The

first study, a randomized controlled cross-over trial of 51 patients with cerebral palsy, provided strong,

statistically significant results; intrathecal baclofen was superior to placebo in reducing spasticity as

measured by the Ashworth Scale. A second cross-over study was conducted in 11 patients with

spasticity arising from brain injury. Despite the small sample size, the study yielded a nearly significant

test statistic (p=0.066) and provided directionally favorable results. The last study, however, did not

provide data that could be reliably analyzed.

16 HOW SUPPLIED/STORAGE AND HANDLING

16 HOW SUPPLIED/STORAGE AND HANDLING

Baclofen injection is a clear, colorless, sterile, pyrogen-free, isotonic solution consisting of the active

ingredient, Baclofen USP, and the excipients Sodium Chloride USP and Water for Injection USP in

single-dose clear glass vials.

Baclofen injection is packaged in single-dose vials supplied as follows:

One vial containing 20,000 mcg/20 mL (1,000 mcg/mL) (NDC 70511-123-20).

Storage

Does not require refrigeration.

Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP

Controlled Room Temperature].

Do not freeze.

Do not heat sterilize.

17 PATIENT COUNSELING INFORMATION

Risks Related to Sudden Withdrawal of Baclofen Injection

Advise patients and caregivers that sudden withdrawal of baclofen injection, regardless of the cause,

can result in serious complications that include high fever, confusion, muscle stiffness, multiple organ-

system failure, and death. Inform patients that early symptoms of baclofen injection withdrawal may

include increased spasticity, itching, and tingling of extremities. If baclofen injection withdrawal or a

pump malfunction is suspected, patients should be brought immediately to a hospital for assessment and

treatment.

Inform patients and caregivers that sudden withdrawal occurs most frequently due to a delivery problem

with the catheter or the pump, or failure to refill the pump on schedule. Advise patients and their

caregivers to pay careful attention to infusion system alarms. Instruct patients and caregivers that if they

miss their scheduled pump refill, they should immediately contact their physician to reschedule the

refill before the pump runs out of drug.

Baclofen Injection Overdose

Inform patients and their caregivers that baclofen injection overdose may occur suddenly or insidiously,

and that symptoms may include confusion, drowsiness, lightheadedness, dizziness, slow or shallow

breathing, seizures, loss of muscle tone, loss of consciousness, and coma. If an overdose appears

likely, patients should be brought immediately to a hospital for assessment and possible emptying of the

pump.

Operation of Automobiles and Other Dangerous Machinery

Advise patients that baclofen injection may cause drowsiness, and that they should exercise caution

regarding the operation of automobiles or other dangerous machinery, or activities made hazardous by

decreased alertness.

Increased Risk of Drowsiness with Alcohol and Other CNS Depressants

Inform patients and their caregivers that the drowsiness associated with baclofen injection use can be

worsened by alcohol and other CNS depressants. Advise patients to read all medicine labels carefully,

and to tell their physician about all prescription and nonprescription drugs they may use.

Trademarks are the property of their respective owners.

Manufactured for:

MAIA Pharmaceuticals, Inc.

707 State Road

Suite 104, Princeton, NJ 08540

Made in India

Principal Display Panel

Vial Label

NDC 70511-123-120

Baclofen Injection

20,000 mcg/20 mL

(1,000 mcg/mL)

For Intrathecal Use Only

20 mL Single Dose Vial

Carton Label

NDC 70511-123-20

Baclofen Injection

20,000 mcg/20 mL

(1,000 mcg/mL)

For Intrathecal Use Only

20 mL Single Dose Vial

Discard unused portion

Rx Only

BACLOFEN

baclofen injection

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:70 511-123

Route of Administration

INTRATHECAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

BACLO FEN (UNII: H78 9 N3FKE8 ) (BACLOFEN - UNII:H78 9 N3FKE8 )

BACLOFEN

10 0 0 ug in 1 mL

MAlA Pharmaceuticals, Inc.

Inactive Ingredients

Ingredient Name

Stre ng th

SO DIUM CHLO RIDE (UNII: 451W47IQ8 X)

9 mg in 1 mL

WATER (UNII: 0 59 QF0 KO0 R)

Packag ing

#

Item Code

Package Description

Marketing Start

Date

Marketing End Date

1

NDC:70 511-123-

1 in 1 CARTON

0 8 /13/20 19

1

20 mL in 1 VIAL, GLASS; Type 0 : No t a Co mbinatio n

Pro duc t

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA210 315

0 8 /13/20 19

Labeler -

MAlA Pharmaceuticals, Inc. (079211845)

Registrant -

MAlA Pharmaceuticals, Inc. (079211845)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

PCAS Finland Oy

36 9 58 7311

api manufacture(70 511-123)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Gland Pharma Limited

9 18 6 0 1238

ma nufa c ture (70 511-123)

Revised: 8/2019

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