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Baclofen

Pronunciation

(BAK loe fen)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, External:

EnovaRX-Baclofen: 1% (60 g, 120 g) [contains cetyl alcohol]

Equipto-Baclofen: 2% (120 g)

Generic: 2% (60 g)

Solution, Intrathecal:

Gablofen: 40,000 mcg/20 mL (20 mL)

Solution, Intrathecal [preservative free]:

Gablofen: 10,000 mcg/20 mL (20 mL); 20,000 mcg/20 mL (20 mL) [antioxidant free]

Lioresal: 0.05 mg/mL (1 mL); 10 mg/20 mL (20 mL); 10 mg/5 mL (5 mL); 40 mg/20 mL (20 mL [DSC]) [antioxidant free]

Lioresal Intrathecal: 40 mg/20 mL (20 mL) [antioxidant free]

Solution Prefilled Syringe, Intrathecal [preservative free]:

Gablofen: 50 mcg/mL (1 mL) [antioxidant free, latex free]

Gablofen: 50 mcg/mL (1 mL); 10,000 mcg/20 mL (20 mL); 20,000 mcg/20 mL (20 mL); 40,000 mcg/20 mL (20 mL) [antioxidant free]

Suspension, Oral:

First-Baclofen 1: 1 mg/mL (120 mL) [contains saccharin sodium, sodium benzoate]

First-Baclofen 5: 5 mg/mL (60 mL, 120 mL) [contains saccharin sodium, sodium benzoate]

Tablet, Oral:

Generic: 10 mg, 20 mg

Brand Names: U.S.

  • EnovaRX-Baclofen
  • Equipto-Baclofen
  • First-Baclofen 1
  • First-Baclofen 5
  • Gablofen
  • Lioresal
  • Lioresal Intrathecal

Pharmacologic Category

  • Skeletal Muscle Relaxant

Pharmacology

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)

Onset of Action

Intrathecal bolus: 30 minutes to 1 hour; Continuous infusion: 6 to 8 hours after infusion initiation

Peak effect: Intrathecal bolus: 4 hours (effects may last 4 to 8 hours); Continuous infusion: 24 to 48 hours

Time to Peak

Serum: Oral: 1 hour (0.5 to 4 hours) (Brunton 2011)

Half-Life Elimination

Oral:

Pediatric patients with cerebral palsy (age range: 2 to 17 years): 4.5 hours (He 2014)

Adults: 3.75 ± 0.96 hours (Brunton 2011)

Intrathecal: CSF elimination half-life: 1.5 hours over the first 4 hours

Protein Binding

30%

Use: Labeled Indications

Spasticity:

Oral: Management of reversible spasticity associated with multiple sclerosis or spinal cord lesions

Intrathecal: Management of severe spasticity of spinal cord origin (eg, spinal cord injury, multiple sclerosis) or cerebral origin (eg, cerebral palsy, traumatic brain injury) in patients ≥4 years; may be considered as an alternative to destructive neurosurgical procedures.

Limitations of use: 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 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.

Off Label Uses

Alcoholic liver disease (alcohol abstinence)

In a randomized, placebo-controlled study in patients with alcoholic liver disease, treatment with baclofen significantly improved the proportion of patients who achieved and maintained alcohol abstinence [Addolorato 2007].

Based on the American Association for the Study of Liver Diseases (AASLD) guidelines for the management of adult patients with ascites due to cirrhosis, baclofen may be used to reduce alcohol craving and consumption in patients with ascites due to alcoholic liver disease.

Gastroesophageal reflux disease (adults)

Studies have demonstrated consistent findings of decreased transient lower esophageal sphincter relaxation episodes and increased pH after administration of baclofen to patients with gastroesophageal reflux disease (GERD). Clinical benefits, however, were not always measured or observed. In addition, most studies evaluated single bolus doses, whereas multiple daily doses would likely be needed for routine use. American College of Gastroenterology (ACG) guidelines for the management of GERD state that baclofen may be used in select patients as adjunctive therapy with other acid-suppressing agents.

Hiccups (singultus)

Baclofen may be a useful alternative in patients with intractable hiccups from various causes that have been unresponsive to other therapies.

Nystagmus

Inconsistent results have been reported with baclofen use for the treatment of nystagmus. It is unclear why some patients with nystagmus benefit from baclofen therapy and others do not. However, given the lack of a definitive symptomatic treatment for this disease, a therapeutic trial of baclofen may be warranted before more invasive or risky approaches such as botulinum toxin injections or surgery are attempted.

Trigeminal neuralgia

Small controlled trials and uncontrolled trials indicate that baclofen provides pain relief in two-thirds to three-fourths of patients with trigeminal neuralgia. Baclofen has also been used in combination with carbamazepine and phenytoin, resulting in better pain relief than single-drug therapy. Baclofen has been well tolerated for this indication, with 10% or fewer subjects discontinuing therapy because of adverse effects. A larger controlled study is needed to firmly establish efficacy, optimal dose, dose titration, and possible combinations with other drugs for trigeminal neuralgia.

Additional Off-Label Uses

Spasticity in cerebral palsy (children/adolescents) (short-term treatment)

Contraindications

Hypersensitivity to baclofen or any component of the formulation

Intrathecal: IV, IM, SubQ, or epidural administration

Dosing: Adult

Spasticity:

Oral: Initial: 5 mg 3 times daily; may increase by 5 mg per dose every 3 days (ie, 5 mg 3 times daily for 3 days, then 10 mg 3 times daily for 3 days, etc.) until optimal response is reached. Usual dosage range: 40 to 80 mg daily. Do not exceed 80 mg daily (20 mg 4 times daily).

Intrathecal:

Screening dose: Initial: 50 mcg for 1 dose; following initial administration, observe patient for 4 to 8 hours. A positive response consists of a significant decrease in muscle tone and/or frequency and/or severity of spasms. If response is inadequate, may give 75 mcg as a second screening dose 24 hours after the first screening dose; observe patient for 4 to 8 hours. If response is still inadequate, may repeat a final screening dose of 100 mcg given 24 hours after the second screening dose. Patients not responding to screening dose of 100 mcg should not be considered for chronic infusion/implanted pump.

Dose titration following pump implant: After positive response to screening dose, a maintenance intrathecal infusion can be administered via an implanted intrathecal pump.

Initial total daily dose via pump: Double the screening dose that gave a positive response and administer over 24 hours, unless efficacy of the bolus dose was maintained for >8 hours, then infuse a dose equivalent to the screening dose over 24 hours. Do not increase dose in first 24 hours (to allow steady state to be achieved); thereafter, dosage adjustments may be made by increasing daily dose slowly by 10% to 30% (spasticity of spinal cord origin) or 5% to 15% (spasticity of cerebral origin) once every 24 hours until satisfactory response.

Maintenance: Daily dose may be increased 5% to 20% (maximum increase: 20%) (spasticity of cerebral origin) or by 10% to 40% (maximum increase: 40%) (spasticity of spinal cord origin). Dose may also be decreased 10% to 20% for adverse effects. Most patients have been adequately maintained on 90 mcg to 703 mcg daily (spasticity of cerebral origin) or 300 mcg to 800 mcg daily (spasticity of spinal cord origin). Experience with doses >1,000 mcg daily is limited.

Note: Dosage adjustments may be required often during the first few months of therapy to adjust for life style changes due to alleviation of spasticity. Maintain lowest dose that produces adequate response. Most patients require gradual increases over time to maintain optimal response. Sudden large requirements for a dose increase may indicate a catheter complication (eg, kink, dislodgement).Titrate dose to allow sufficient muscle tone and occasional spasms to optimize activities of daily living, support circulation, and possibly prevent DVT formation. Use extreme caution when filling the pump; follow manufacturer instructions carefully. 5% to 10% of patients receiving chronic therapy become refractory to dose adjustments; may consider a drug holiday (hospitalized patients only) with a gradual withdrawal over 2 to 4 weeks and use of alternative spasticity management methods. Following the drug holiday intrathecal baclofen may be resumed at the initial continuous infusion dose.

Alcoholic liver disease, alcohol abstinence (off-label use): Oral: Initial: 5 mg 3 times daily for 3 days; Maintenance: 10 mg 3 times daily (AASLD [Runyon 2012]; Addolorato 2007)

Gastroesophageal reflux disease (off-label use): Oral: 10 mg 4 times daily (Ciccaglione 2003)

Hiccups (off-label use): Oral: 5 to 10 mg 3 times daily (maximum: 75 mg daily in divided doses) (Guelaud 1995; Zhang 2014)

Nystagmus (off-label use): Oral: 5 mg 3 times daily; may increase at weekly intervals until optimal response is reached or intolerable adverse effects occur. Dosage range studied: 15 to 120 mg daily in divided doses (Cormer 2006; Dieterich 1991). Additional data may be necessary to further define the role of baclofen in the treatment of this condition.

Trigeminal neuralgia (off-label use): Oral: Initial: 5 to 10 mg 3 times daily (dose may be as low as 10 mg daily); may increase dose by 10 mg every other day over 1 to 2 weeks. Dosage range studied: 30 to 80 mg daily in 3 to 4 divided doses (Fromm 1984). Additional data may be necessary to further define the role of baclofen in the treatment of this condition.

Dosing: Geriatric

Oral: Refer to adult dosing; use with caution. If benefits are not observed, withdraw the drug slowly.

Dosing: Pediatric

Oral: Note: Use the lowest effective dose; patients who fail to respond within a reasonable amount of time should be slowly withdrawn from therapy (avoid abrupt withdrawal of drug).

Spasticity:

Oral:

Children ≥12 years and Adolescents: Refer to adult dosing.

Infants, Children, and Adolescents (off-label): Note: Dose-related side effects (eg, sedation) may be minimized by slow titration; lower initial doses than described below (2.5 to 10 mg daily) may be used with subsequent titration to 8 hourly doses. There is limited published data in infants and children; the following is a compilation of small prospective studies (Milla 1977; Scheinberg 2006) and one large retrospective analysis of baclofen use in children (Lubsch 2006). Efficacy results variable (AAN [Delgado] 2010)

Infants ≥4 months and Children <2 years: Limited data available: 10 to 20 mg daily divided every 8 hours; begin at low end of range and titrate dose to patient response, titration intervals of every 3 days to weekly have been used in pediatric patients ≥2 years (Millia 1997; Scheinberg 2006). Maximum daily dose: 40 mg/day (Lubsch 2006). Note: To minimize dose-related side effects (eg, sedation), lower initial doses (eg, 2.5 mg once daily) and slower titration may be considered (eg, weekly) and has been reported in pediatric patients >2 years (Scheinberg 2006).

2 to 7 years: Limited data available: 20 to 40 mg daily divided every 8 hours; begin at low end of range (or even lower [2.5 to 10 mg daily] and titrate dose to patient response; titration intervals of every 3 days to weekly have been used in pediatric patients. Maximum daily dose: 60 mg/day (Lubsch 2006; Millia 1997; Scheinberg 2006).

≥8 years and Adolescents: Limited data available in children <12 years: 30 to 40 mg daily divided every 8 hours; begin at low end of range (or even lower [10 mg to 15 mg daily in 3 divided doses]) and titrate dose to patient response, titration intervals of every 3 days to weekly have been used (Millia 1997; Scheinberg 2006); some patients ≥12 years may require every 6 hour dosing; usual maximum daily dose range: 60 to 80 mg/day (Lubsch 2006; Millia 1977). Note: Higher maximum daily doses (up to 200 mg/day) have been described in some patients in a retrospective review, usually the higher doses were needed over time (Lubsch 2006).

Intrathecal: Children ≥4 years and Adolescents:

Screening dose: Refer to adult dosing. Note: A 25 mcg initial screening dose may be considered in very small pediatric patients.

Dose titration following pump implant: After positive response to screening dose, a maintenance intrathecal infusion can be administered via an implanted intrathecal pump.

Initial total daily dose via pump: Double the screening dose that gave a positive response and administer over 24 hours, unless efficacy of the bolus dose was maintained for >8 hours, then infuse a dose equivalent to the screening dose over 24 hours. Do not increase dose in first 24 hours (to allow steady state to be achieved); thereafter, increase daily dose slowly by 5% to 15% once every 24 hours until satisfactory response.

Maintenance: Daily dose may be increased 5% to 20% (maximum increase: 20%). Dose may also be decreased 10% to 20% for adverse effects. Patients <12 years required lower daily doses in clinical trials (average dose: 274 mcg daily; dosage range: 24 mcg to 1,199 mcg/day).

Note: Dosage adjustments may be required often during the first few months of therapy to adjust for life style changes due to alleviation of spasticity. Maintain lowest dose that produces adequate response. Most patients require gradual increases over time to maintain optimal response. Sudden large requirements for a dose increase may indicate a catheter complication (eg, kink, dislodgement).Titrate dose to allow sufficient muscle tone and occasional spasms to optimize activities of daily living, support circulation, and possibly prevent DVT formation. Use extreme caution when filling the pump; follow manufacturer instructions carefully. 5% to 10% of patients receiving chronic therapy become refractory to dose adjustments; may consider a drug holiday (hospitalized patients only) with a gradual withdrawal over 2 to 4 weeks and use of alternative spasticity management methods. Following the drug holiday intrathecal baclofen may be resumed at the initial continuous infusion dose.

Dosing: Renal Impairment

Oral: There are no dosage adjustments provided in the manufacturer’s labeling. However, baclofen is primarily eliminated renally; use with caution; dosage reduction may be necessary.

The following dosage adjustments have been recommended (Vlavonou 2014; renal function estimated using the Cockcroft-Gault formula):

CrCl >80 mL/minute: No initial dosage adjustment necessary.

CrCl 50 to 80 mL/minute: Initial: 5 mg every 12 hours

CrCl 30 to <50 mL/minute: Initial: 2.5 mg every 8 hours

CrCl <30 mL/minute (not on dialysis): Initial: 2.5 mg every 12 hours.

ESRD on hemodialysis: Avoid use (based on case reports; Chen 1997; El-Husseini 2011; Lee 2013; Su 2009); if baclofen must be used, initiate at a low dose with careful monitoring for toxicity (Lee 2013). Baclofen is readily removed by hemodialysis, with a report of 79% removal in a 4 hour session (Roberts 2015).

Intrathecal: There are no dosage adjustments provided in the manufacturer’s labeling. However, baclofen is primarily renally eliminated; use with caution; dosage reduction may be necessary.

Dosing: Hepatic Impairment

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

Reconstitution

Intrathecal: Screening doses are a 50 mcg/mL concentration and only the 1 mL screening ampul or screening syringe (50 mcg/mL) is used; do not further dilute. Maintenance infusions for patients who require concentrations other than 500 mcg/mL, 1,000 mcg/mL, or 2,000 mcg/mL must be diluted with preservative-free sodium chloride.

Extemporaneously Prepared

A 5 mg/mL oral suspension may be made with tablets. Crush thirty 20 mg tablets in a mortar and reduce to a fine powder. Add a small amount of glycerin and mix to a uniform paste. Mix while adding Simple Syrup, NF in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add a sufficient quantity of vehicle to make 120 mL. Label “shake well” and “refrigerate”. Stable for 35 days (Johnson, 1993).

A 10 mg/mL oral suspension may be made with tablets. Crush one-hundred-twenty 10 mg tablets in a mortar and reduce to a fine powder. Add small portions (60 mL) of a 1:1 mixture of Ora-Sweet® and Ora-Plus® and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 120 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 120 mL. Label “shake well” and “refrigerate”. Stable for 60 days (Allen, 1996).

Allen LV Jr and Erickson MA 3rd, "Stability of Baclofen, Captopril, Diltiazem Hydrochloride, Dipyridamole, and Flecainide Acetate in Extemporaneously Compounded Oral Liquids," Am J Health Syst Pharm, 1996, 53(18):2179-84.8879325Johnson CE and Hart SM, “Stability of an Extemporaneously Compounded Baclofen Oral Liquid,” Am J Hosp Pharm, 1993, 50(11):2353-5.8266961

Administration

Intrathecal: For screening dosages, administer as a bolus injection (50 mcg/mL concentration) by barbotage into the subarachnoid space over at least 1 minute, followed by maintenance continuous infusion.

Oral: Administer without regards to meals.

Storage

Injection: Do not store above 30°C (86°F). Does not require refrigeration. Do not freeze or heat sterilize. Discard any unused solution.

Tablets: Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Lacidipine: Baclofen may enhance the hypotensive effect of Lacidipine. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Opioid Analgesics: CNS Depressants may enhance the CNS depressant effect of Opioid Analgesics. Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Tolperisone: May enhance the adverse/toxic effect of Muscle Relaxants (Centrally Acting). Management: Monitor for increased sedation or CNS effects if tolperisone is combined with other centrally acting muscle relaxants. Consider decreasing the tolperisone dose if these agents are combined. Consider therapy modification

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Adverse Reactions

>10%:

Central nervous system: Hypotonia (2% to 35%), drowsiness (6% to 21%), confusion (1% to 11%), headache (2% to 11%)

Gastrointestinal: Nausea (1% to 12%), vomiting (2% to 11%)

1% to 10%:

Cardiovascular: Hypotension (≤9%), peripheral edema (≤3%)

Central nervous system: Seizure (≤10%), dizziness (2% to 8%), insomnia (≤7%), paresthesia (≤7%), hypertonia (≤6%), pain (≤4%), speech disturbance (≤4%), depression (2%), coma (≤2%), abnormality in thinking (≤1%), agitation (≤1%), chills (≤1%)

Dermatologic: Pruritus (4%), urticaria (≤1%)

Gastrointestinal: Constipation (≤6%), sialorrhea (≤3%), xerostomia (≤3%), diarrhea (≤2%)

Genitourinary: Urinary retention (≤8%), urinary frequency (≤6%), difficulty in micturition (2%), impotence (≤2%), urinary incontinence (≤2%)

Neuromuscular & skeletal: Back pain (≤2%), weakness (≤2%), tremor (≤1%)

Ophthalmic: Ambylopia (≤2%)

Respiratory: Hypoventilation (≤4%), pneumonia (≤2%), dyspnea (≤1%)

Miscellaneous: Accidental injury (≤4%)

<1% (Limited to important or life-threatening): Abdominal pain, accommodation disturbance, akathisia, albuminuria, alopecia, amnesia, ankle edema, anorexia, anxiety, apnea, ataxia, blurred vision, bradycardia, carcinoma, chest pain, contact dermatitis, decreased libido, deep vein thrombophlebitis, dehydration, dermal ulcer, diaphoresis, diplopia, dysarthria, dysautonomia, dysgeusia, dysphagia, dystonia, dysuria, epilepsy, erectile dysfunction, euphoria, excitement, facial edema, fecal incontinence, fever, gastrointestinal hemorrhage, hallucination, hematuria, hyperglycemia, hyperhidrosis, hypertension, hyperventilation, hypothermia, hysteria, inhibited ejaculation, intestinal obstruction, leukocytosis, loss of postural reflex, malaise, miosis, muscle rigidity, myalgia, mydriasis, nasal congestion, nephrolithiasis, nocturia, nystagmus, occult blood in stools, oliguria, opisthotonus, orgasm disturbance, pallor, palpitations, paranoia, personality disorder, petechial rash, priapism, pulmonary embolism, scoliosis, scoliosis progression, sedation, sexual disorder, skin rash, slurred speech, strabismus, suicidal ideation, syncope, taste disorder, tinnitus, tongue irritation, vaginitis, vasodilatation, weight gain, weight loss

ALERT: U.S. Boxed Warning

Abrupt withdrawal (injection):

Abrupt discontinuation of intrathecal baclofen, regardless of the cause, has resulted in sequelae that include high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, which 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. Advise patients and caregivers of the importance of keeping scheduled refill visits and educate them on the early symptoms of baclofen withdrawal. Give special attention to patients at apparent risk (eg, 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 postimplant clinician and patient information.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Intrathecal mass: Cases (most from pharmacy compounded preparations) of intrathecal mass formation at the implanted catheter tip have been reported; patients may experience worsening or return of spasticity, pain, inadequate response to dose adjustments, and/or neurological deficit/dysfunction. Neurosurgical evaluation and/or an appropriate imaging study should be considered if a mass is suspected.

• Urinary retention: May cause acute urinary retention (may be related to underlying disease); use with caution in patients with urinary obstruction.

Disease-related concerns:

• Autonomic dysreflexia: Use intrathecal baclofen with caution in patients with a history of autonomic dysreflexia; presence of nociceptive stimuli or abrupt baclofen withdrawal may cause an autonomic dysreflexic episode.

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

• Psychiatric disease: Use with caution in patients with psychotic disorders, schizophrenia, or confusional states; may cause exacerbation of condition.

• Renal impairment: Use with caution in patients with renal impairment; baclofen is eliminated primarily unchanged via the kidneys. Multiple cases describing neurotoxicity due to oral baclofen accumulation in adult patients with varying levels of renal impairment have been reported in the literature. In patients with renal impairment, initiation of oral baclofen at lower doses and/or extended intervals has been suggested (Aisen 1994; Chen 1997; Chou 2006; El-Husseini 2011; Peces 1998; Su 2009; Vlavonu 2014).

• Respiratory disease: Use with caution in patients with respiratory disease.

• Seizure disorder: Use with caution in patients with a history of seizure disorder; monitor regularly for loss of seizure control. Seizures have been reported with withdrawal from intrathecal baclofen as well as in patients maintained on therapeutic doses of intrathecal baclofen.

Special populations:

• Elderly: Use with caution in elderly patients; may be more sensitive to adverse CNS effects, especially at higher doses.

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

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Abrupt withdrawal: [US Boxed Warning]: Abrupt withdrawal of intrathecal baclofen, regardless of the cause, has resulted in sequelae (hyperpyrexia, altered mental status, exaggerated rebound spasticity, and muscle rigidity, which, in rare cases, has advanced to rhabdomyolysis), multiple organ-system failure, and death. Prevention of abrupt discontinuation requires careful attention to programming and monitoring of infusion system, refill scheduling and procedures, and pump alarms. Advise patients and caregivers of the importance of keeping scheduled refill visits and educate them on the early symptoms of baclofen withdrawal. Give special attention to patients at apparent risk (eg, 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 postimplant clinician and patient information. In most cases, symptoms of withdrawal (eg, return of baseline spasticity, hypotension, paresthesia, pruritus) appear within hours to a few days following interruption of therapy. Priapism may develop or recur if treatment with intrathecal baclofen is interrupted. Clinically, 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. Suggested treatment for intrathecal baclofen withdrawal is restoration of intrathecal baclofen at or near the same dosage as before therapy was interrupted. Abrupt withdrawal of oral therapy has been associated with hallucinations and seizures; gradual dose reductions (over ~1 to 2 weeks) are recommended in the absence of severe adverse reactions.

• Appropriate use: Intrathecal: For use only in an FDA-approved implantable pump for intrathecal baclofen administration; health care providers should be experienced with chronic intrathecal infusion therapy and resuscitative equipment should be readily available. Ensure patient is infection-free and then evaluate patient’s response to bolus intrathecal injection (screening phase) prior to implanting pump. Monitor closely during the initial phase of pump use and when adjusting the dosing rate and/or the concentration in the reservoir. Educate patients and caregivers on proper home care of the pump and insertion site. Use extreme caution when filling an implantable pump; pumps should only be refilled through the reservoir refill septum. Inadvertent injection into the subcutaneous tissue can occur if the reservoir refill septum is not properly accessed. Some pumps are equipped with a catheter access port that allows direct access to the intrathecal catheter; direct injection into this catheter access port or inadvertent injection into the subcutaneous tissue may cause a life-threatening overdose. Except in overdose related emergencies, intrathecal baclofen should be reduced slowly if discontinuation is necessary.

• Appropriate use: Oral: Efficacy of oral baclofen has not been established in patients with stroke, Parkinson disease, or cerebral palsy; therefore, use is not recommended. Not indicated for spasticity associated with rheumatic disorders. Use with caution when spasticity is utilized to sustain upright posture and balance in locomotion, or when spasticity is necessary to obtain increased function.

• Overdose: Intrathecal use: Monitor closely for signs and symptoms of overdose which may appear suddenly or insidiously, especially during the initial screening and dose-titration phase of treatment, and during reintroduction of therapy after a period of interruption. Signs/symptoms of overdose may include drowsiness, dizziness, somnolence, hypothermia, respiratory depression, seizures, rostral progression of hypotonia and loss of consciousness progressing to coma. If overdose is suspected, patient should be evaluated immediately in a hospital setting and the pump reservoir emptied.

Monitoring Parameters

Regular electroencephalogram (EEG) in patients with epilepsy (loss of seizure control has been reported).

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Withdrawal symptoms in the neonate were noted in a case report following the maternal use of oral baclofen 20 mg 4 times/day throughout pregnancy (Ratnayaka 2001). Plasma concentrations following administration of intrathecal baclofen are significantly less than those with oral doses; exposure to the fetus is expected to be limited (Morton 2009).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience insomnia, nausea, headache, or constipation. Have patient report immediately to prescriber signs of withdrawal (high fever, mental changes, increased spasm, or muscle rigidity), loss of strength and energy, severe dizziness, passing out, confusion, fatigue, polyuria, behavioral changes, seizures, vision changes, angina, muscle pain, burning or numbness feeling, signs of breathing problems (shortness of breath, wheezing, coughing, or breathing gets worse), urinary retention, change in amount of urine passed, hematuria, mood changes, hallucinations, abnormal movements, twitching, change in balance, difficulty swallowing, difficulty speaking, involuntary eye movements, or abnormal heartbeat (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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