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Drug overview for BACLOFEN (baclofen):
Generic name: BACLOFEN (BAK-loe-fen)
Drug class: Central Muscle Relaxants
Therapeutic class: Locomotor System
Baclofen, a gamma-aminobutyric acid (GABA) derivative, is a skeletal muscle relaxant and antispastic agent.
No enhanced Uses information available for this drug.
Generic name: BACLOFEN (BAK-loe-fen)
Drug class: Central Muscle Relaxants
Therapeutic class: Locomotor System
Baclofen, a gamma-aminobutyric acid (GABA) derivative, is a skeletal muscle relaxant and antispastic agent.
No enhanced Uses information available for this drug.
DRUG IMAGES
BACLOFEN 20 MG TABLET
BACLOFEN 10 MG TABLET
The following indications for BACLOFEN (baclofen) have been approved by the FDA:
Indications:
Muscle spasticity of spinal origin
Professional Synonyms:
None.
Indications:
Muscle spasticity of spinal origin
Professional Synonyms:
None.
The following dosing information is available for BACLOFEN (baclofen):
Oral dosage of baclofen should be individualized according to the patient's requirements and response using the lowest dosage that produces optimum response. Initially, low oral dosages of the drug should be administered.
For the management of spasticity, the initial oral dosage of baclofen is 5 mg 3 times daily. Oral daily dosage may be increased by 15 mg at 3-day intervals (i.e., 5 mg 3 times daily for 3 days, then 10 mg 3 times daily for 3 days, then 15 mg 3 times daily for 3 days, then 20 mg 3 times daily for 3 days) until optimum effect is achieved (usually at dosages of 40-80 mg daily). In patients with psychiatric or brain disorders and in geriatric patients, oral dosage should be increased more gradually.
In some patients, a smoother antispastic effect is obtained by administering the oral daily dosage in 4 divided doses. Some clinicians suggest that daily oral dosages of up to 150 mg are well tolerated and provide additional therapeutic benefit in some patients; however, the manufacturers state that total dosage should not exceed 80 mg daily (i.e., 20 mg 4 times daily ). Some patients require 1-2 months of treatment for full benefit; however, the length of baclofen trial should be determined by the clinical state of the patient.
If benefits are not evident after a reasonable trial, baclofen therapy should be discontinued by slowly reducing the daily dosage.
Prior to implantation of the controlled-infusion device (e.g., Medtronic SynchroMed(R) pump) and initiation of chronic intrathecal baclofen therapy, the patient must exhibit a positive response (defined as a clinically important decrease in muscle tone and/or frequency and/or severity of spasms over a 4- to 8-hour observation period) to initial intrathecal baclofen test dose(s). Initially, a dose containing 50 mcg (1 mL of a 50-mcg/mL solution) of baclofen is administered into the intrathecal space by barbotage over a period of at least 1 minute. If response observed at 4-8 hours after the initial test dose is less than desired, a second injection containing 75 mcg (1.5 mL of a 50-mcg/mL solution) of baclofen may be administered 24 hours after the first dose.
If response observed at 4-8 hours after the second test dose remains inadequate, a final injection containing 100 mcg (2 mL of a 50-mcg/mL solution) of baclofen may be administered 24 hours after the second dose. In pediatric patients, the initial test dose is the same as in adults (i.e., 50 mcg); however, in very small children, an initial dose of 25 mcg may be considered. Patients not responding to the 100-mcg intrathecal test dose of the drug are not considered candidates for chronic intrathecal baclofen therapy.
Following establishment of responsiveness to intrathecal baclofen and implantation of a compatible pump (e.g., SynchroMed(R) infusion system), the initial intrathecal dose of baclofen for the management of spasticity is twice the test dose that produced a positive response with a duration not exceeding 8 hours; this dose is infused intrathecally over 24 hours. For patients in whom a positive response to the test dose persisted for longer than 8 hours, the initial intrathecal dose is the same as the test dose that produced a positive response; this dose also is infused intrathecally over 24 hours. Dosage should not be increased within 24 hours after the initial intrathecal dose (i.e., until steady state is achieved).
Following the initial infusion dose in adults with spasticity of spinal cord origin, the daily dose can be increased slowly by 10-30% increments at 24-hour intervals until the desired clinical response is achieved; in pediatric patients with spasticity of spinal cord origin and adult and pediatric patients with spasticity of cerebral origin, the daily dose can be increased slowly by 5-15% increments at 24-hour intervals until the desired clinical response is achieved. If no substantive increase in response is observed with upward titration of intrathecal baclofen dosage, the function of the pump and patency of the catheter should be checked.
Adjustment of maintenance dosage often is needed during the initial months of intrathecal baclofen therapy as the patient adjusts to changes in life-style secondary to relief of spasticity. During periodic refills of the pump, the 24-hour dose may be increased by up to 10-40% or up to 5-20% in patients with spasticity of spinal cord origin or those with spasticity of cerebral origin, respectively, as necessary to maintain adequate control of symptoms. In patients who develop intolerable adverse effects, the 24-hour maintenance dose can be decreased by 10-20%.
During chronic therapy, gradual increases in dosage will be required in most patients to maintain optimal response. A sudden increase in dosage requirement should suggest the possibility of pump and/or catheter malfunction (i.e., catheter kink or dislodgement). In patients with spasticity of spinal cord origin, maintenance dosage during chronic intrathecal therapy has ranged from 12-2003 mcg daily, with most patients responding adequately to 300-800 mcg daily.
There is only limited experience with intrathecal baclofen dosages of 1000 mcg daily or greater in these patients. In patients with spasticity of cerebral origin, maintenance dosage during chronic intrathecal therapy has ranged from 22-1400 mcg daily, with most patients responding adequately to 90-703 mcg daily. In clinical studies in patients with spasticity of cerebral origin, only about 2% of patients required daily dosages exceeding 1000 mcg daily.
Maintenance dosage recommendations for pediatric patients are similar to those for patients with spasticity of cerebral origin. Pediatric patients younger than 12 years of age may require lower daily dosages; in clinical trials, the maintenance daily dosage averaged 274 mcg daily (range: 24-1199 mcg daily). Dosage requirements for pediatric patients older than 12 years of age does not appear to be different from that for adult patients.
Determination of optimum therapy requires individual titration. The lowest possible dosage that produces optimum response should be employed.
During prolonged intrathecal baclofen therapy for spasticity, approximately 5% of patients become refractory to increasing dosages of the drug. While experience currently is insufficient to make firm recommendations regarding amelioration of such tolerance, patients occasionally have been hospitalized and subjected to a ''drug holiday'' in which intrathecal dosage was decreased gradually over a 2- to 4-week period, during which baclofen therapy was alternated with other methods of spasticity management. After a few days, sensitivity to baclofen may return and continuous intrathecal baclofen therapy may be resumed at the previously effective initial dosage.
For patients achieving relatively satisfactory relief via continuous intrathecal infusion employing an implantable pump, further benefit may be possible with more complex dosing schedules. For example, patients who commonly experience an exacerbation of spasticity at night that disrupts sleep may require a 20% increase in the hourly infusion rate; such changes should be programmed to begin approximately 2 hours before the time of desired clinical benefit.
The manual provided by the manufacturer of the implantable infusion device (i.e., pump) must be consulted for additional information, including specific instructions and precautions for programming the pump and/or refilling the reservoir. Various pumps (with different reservoir volumes) and refill kits are available; clinicians must be familiar with these products in order to select the appropriate refill kit for the particular pump in use.
Because baclofen is excreted principally in urine as unchanged drug, it may be necessary to reduce either oral or intrathecal dosage in patients with impaired renal function. (See Cautions: Precautions and Contraindications.)
For the management of spasticity, the initial oral dosage of baclofen is 5 mg 3 times daily. Oral daily dosage may be increased by 15 mg at 3-day intervals (i.e., 5 mg 3 times daily for 3 days, then 10 mg 3 times daily for 3 days, then 15 mg 3 times daily for 3 days, then 20 mg 3 times daily for 3 days) until optimum effect is achieved (usually at dosages of 40-80 mg daily). In patients with psychiatric or brain disorders and in geriatric patients, oral dosage should be increased more gradually.
In some patients, a smoother antispastic effect is obtained by administering the oral daily dosage in 4 divided doses. Some clinicians suggest that daily oral dosages of up to 150 mg are well tolerated and provide additional therapeutic benefit in some patients; however, the manufacturers state that total dosage should not exceed 80 mg daily (i.e., 20 mg 4 times daily ). Some patients require 1-2 months of treatment for full benefit; however, the length of baclofen trial should be determined by the clinical state of the patient.
If benefits are not evident after a reasonable trial, baclofen therapy should be discontinued by slowly reducing the daily dosage.
Prior to implantation of the controlled-infusion device (e.g., Medtronic SynchroMed(R) pump) and initiation of chronic intrathecal baclofen therapy, the patient must exhibit a positive response (defined as a clinically important decrease in muscle tone and/or frequency and/or severity of spasms over a 4- to 8-hour observation period) to initial intrathecal baclofen test dose(s). Initially, a dose containing 50 mcg (1 mL of a 50-mcg/mL solution) of baclofen is administered into the intrathecal space by barbotage over a period of at least 1 minute. If response observed at 4-8 hours after the initial test dose is less than desired, a second injection containing 75 mcg (1.5 mL of a 50-mcg/mL solution) of baclofen may be administered 24 hours after the first dose.
If response observed at 4-8 hours after the second test dose remains inadequate, a final injection containing 100 mcg (2 mL of a 50-mcg/mL solution) of baclofen may be administered 24 hours after the second dose. In pediatric patients, the initial test dose is the same as in adults (i.e., 50 mcg); however, in very small children, an initial dose of 25 mcg may be considered. Patients not responding to the 100-mcg intrathecal test dose of the drug are not considered candidates for chronic intrathecal baclofen therapy.
Following establishment of responsiveness to intrathecal baclofen and implantation of a compatible pump (e.g., SynchroMed(R) infusion system), the initial intrathecal dose of baclofen for the management of spasticity is twice the test dose that produced a positive response with a duration not exceeding 8 hours; this dose is infused intrathecally over 24 hours. For patients in whom a positive response to the test dose persisted for longer than 8 hours, the initial intrathecal dose is the same as the test dose that produced a positive response; this dose also is infused intrathecally over 24 hours. Dosage should not be increased within 24 hours after the initial intrathecal dose (i.e., until steady state is achieved).
Following the initial infusion dose in adults with spasticity of spinal cord origin, the daily dose can be increased slowly by 10-30% increments at 24-hour intervals until the desired clinical response is achieved; in pediatric patients with spasticity of spinal cord origin and adult and pediatric patients with spasticity of cerebral origin, the daily dose can be increased slowly by 5-15% increments at 24-hour intervals until the desired clinical response is achieved. If no substantive increase in response is observed with upward titration of intrathecal baclofen dosage, the function of the pump and patency of the catheter should be checked.
Adjustment of maintenance dosage often is needed during the initial months of intrathecal baclofen therapy as the patient adjusts to changes in life-style secondary to relief of spasticity. During periodic refills of the pump, the 24-hour dose may be increased by up to 10-40% or up to 5-20% in patients with spasticity of spinal cord origin or those with spasticity of cerebral origin, respectively, as necessary to maintain adequate control of symptoms. In patients who develop intolerable adverse effects, the 24-hour maintenance dose can be decreased by 10-20%.
During chronic therapy, gradual increases in dosage will be required in most patients to maintain optimal response. A sudden increase in dosage requirement should suggest the possibility of pump and/or catheter malfunction (i.e., catheter kink or dislodgement). In patients with spasticity of spinal cord origin, maintenance dosage during chronic intrathecal therapy has ranged from 12-2003 mcg daily, with most patients responding adequately to 300-800 mcg daily.
There is only limited experience with intrathecal baclofen dosages of 1000 mcg daily or greater in these patients. In patients with spasticity of cerebral origin, maintenance dosage during chronic intrathecal therapy has ranged from 22-1400 mcg daily, with most patients responding adequately to 90-703 mcg daily. In clinical studies in patients with spasticity of cerebral origin, only about 2% of patients required daily dosages exceeding 1000 mcg daily.
Maintenance dosage recommendations for pediatric patients are similar to those for patients with spasticity of cerebral origin. Pediatric patients younger than 12 years of age may require lower daily dosages; in clinical trials, the maintenance daily dosage averaged 274 mcg daily (range: 24-1199 mcg daily). Dosage requirements for pediatric patients older than 12 years of age does not appear to be different from that for adult patients.
Determination of optimum therapy requires individual titration. The lowest possible dosage that produces optimum response should be employed.
During prolonged intrathecal baclofen therapy for spasticity, approximately 5% of patients become refractory to increasing dosages of the drug. While experience currently is insufficient to make firm recommendations regarding amelioration of such tolerance, patients occasionally have been hospitalized and subjected to a ''drug holiday'' in which intrathecal dosage was decreased gradually over a 2- to 4-week period, during which baclofen therapy was alternated with other methods of spasticity management. After a few days, sensitivity to baclofen may return and continuous intrathecal baclofen therapy may be resumed at the previously effective initial dosage.
For patients achieving relatively satisfactory relief via continuous intrathecal infusion employing an implantable pump, further benefit may be possible with more complex dosing schedules. For example, patients who commonly experience an exacerbation of spasticity at night that disrupts sleep may require a 20% increase in the hourly infusion rate; such changes should be programmed to begin approximately 2 hours before the time of desired clinical benefit.
The manual provided by the manufacturer of the implantable infusion device (i.e., pump) must be consulted for additional information, including specific instructions and precautions for programming the pump and/or refilling the reservoir. Various pumps (with different reservoir volumes) and refill kits are available; clinicians must be familiar with these products in order to select the appropriate refill kit for the particular pump in use.
Because baclofen is excreted principally in urine as unchanged drug, it may be necessary to reduce either oral or intrathecal dosage in patients with impaired renal function. (See Cautions: Precautions and Contraindications.)
Baclofen is administered orally or intrathecally. Abrupt discontinuance of the drug, including inadvertent discontinuance of the intrathecal infusion, should be avoided because of the risk of precipitating withdrawal.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| BACLOFEN 10 MG TABLET | Maintenance | Adults take 1 tablet (10 mg) by oral route 3 times per day |
| BACLOFEN 20 MG TABLET | Maintenance | Adults take 1 tablet (20 mg) by oral route 3 times per day |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| BACLOFEN 10 MG TABLET | Maintenance | Adults take 1 tablet (10 mg) by oral route 3 times per day |
| BACLOFEN 20 MG TABLET | Maintenance | Adults take 1 tablet (20 mg) by oral route 3 times per day |
The following drug interaction information is available for BACLOFEN (baclofen):
There are 0 contraindications.
There are 1 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Opioids (Cough and Cold)/Muscle Relaxants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of opioids and muscle relaxants may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids and other CNS depressants, such as muscle relaxants, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Avoid prescribing opioid-including cough medications for patients taking CNS depressants such as muscle relaxants.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) If concurrent use is necessary, monitor patients for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(4) A retrospective cohort study compared the risk of opioid overdose associated with concomitant use of opioids and skeletal muscle relaxants versus opioid use alone. The study examined two types of opioid users (naive opioid use and prevalent opioid use) with and without exposure to skeletal muscle relaxants. The adjusted hazard ratios (HR) were 1.09 and 1.26 in the naive and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21. The risk increased with treatment duration (less than or equal to 14 days: 0.91; 15-60 days: 1.37; and greater than 60 days: 1.80) and for the use of baclofen and carisoprodol (HR 1.83 and 1.84, respectively). Elevated risk was associated with concomitant users with daily opioid dose greater than 50 mg and benzodiazepine use (HR 1.50 and 1.39, respectively).(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
HYCODAN, HYDROCODONE-CHLORPHENIRAMNE ER, HYDROCODONE-HOMATROPINE MBR, HYDROMET, PROMETHAZINE-CODEINE, TUXARIN ER |
There are 5 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Opioids (Extended Release)/Muscle Relaxants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids and muscle relaxants may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids and other CNS depressants, such as muscle relaxants, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing opioid analgesics with CNS depressants such as muscle relaxants to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(4) A retrospective cohort study compared the risk of opioid overdose associated with concomitant use of opioids and skeletal muscle relaxants versus opioid use alone. The study examined two types of opioid users (naive opioid use and prevalent opioid use) with and without exposure to skeletal muscle relaxants. The adjusted hazard ratios (HR) were 1.09 and 1.26 in the naive and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21. The risk increased with treatment duration (less than or equal to 14 days: 0.91; 15-60 days: 1.37; and greater than 60 days: 1.80) and for the use of baclofen and carisoprodol (HR 1.83 and 1.84, respectively). Elevated risk was associated with concomitant users with daily opioid dose greater than 50 mg and benzodiazepine use (HR 1.50 and 1.39, respectively).(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
BUPRENORPHINE, BUTRANS, CONZIP, FENTANYL, HYDROCODONE BITARTRATE ER, HYDROMORPHONE ER, HYSINGLA ER, MORPHINE SULFATE ER, MS CONTIN, NUCYNTA ER, OXYCODONE HCL ER, OXYCONTIN, OXYMORPHONE HCL ER, TRAMADOL HCL ER, XTAMPZA ER |
| Opioids (Immediate Release)/Muscle Relaxants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of opioids and muscle relaxants may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of opioids and other CNS depressants, such as muscle relaxants, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing opioid analgesics with CNS depressants such as muscle relaxants to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(4) A retrospective cohort study compared the risk of opioid overdose associated with concomitant use of opioids and skeletal muscle relaxants versus opioid use alone. The study examined two types of opioid users (naive opioid use and prevalent opioid use) with and without exposure to skeletal muscle relaxants. The adjusted hazard ratios (HR) were 1.09 and 1.26 in the naive and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21. The risk increased with treatment duration (less than or equal to 14 days: 0.91; 15-60 days: 1.37; and greater than 60 days: 1.80) and for the use of baclofen and carisoprodol (HR 1.83 and 1.84, respectively). Elevated risk was associated with concomitant users with daily opioid dose greater than 50 mg and benzodiazepine use (HR 1.50 and 1.39, respectively).(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
ACETAMIN-CAFF-DIHYDROCODEINE, ACETAMINOPHEN-CODEINE, APADAZ, ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BELBUCA, BELLADONNA-OPIUM, BENZHYDROCODONE-ACETAMINOPHEN, BUPRENORPHINE HCL, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTORPHANOL TARTRATE, CARISOPRODOL-ASPIRIN-CODEINE, CODEINE PHOSPHATE, CODEINE SULFATE, DEMEROL, DIHYDROCODEINE BITARTRATE, DILAUDID, DSUVIA, DURAMORPH, ENDOCET, FENTANYL CITRATE, FENTANYL CITRATE-0.9% NACL, FENTANYL CITRATE-D5W, FENTANYL CITRATE-STERILE WATER, FENTANYL CITRATE-WATER, FENTANYL-BUPIVACAINE-0.9% NACL, FENTANYL-BUPIVACAINE-NACL, FENTANYL-ROPIVACAINE-0.9% NACL, FENTANYL-ROPIVACAINE-NACL, FIORICET WITH CODEINE, HYDROCODONE BITARTRATE, HYDROCODONE-ACETAMINOPHEN, HYDROCODONE-IBUPROFEN, HYDROMORPHONE HCL, HYDROMORPHONE HCL-0.9% NACL, HYDROMORPHONE HCL-D5W, HYDROMORPHONE HCL-NACL, HYDROMORPHONE HCL-WATER, INFUMORPH, LEVORPHANOL TARTRATE, MEPERIDINE HCL, MEPERIDINE HCL-0.9% NACL, MITIGO, MORPHINE SULFATE, MORPHINE SULFATE-0.9% NACL, MORPHINE SULFATE-NACL, NALBUPHINE HCL, NALOCET, NUCYNTA, OLINVYK, OPIUM TINCTURE, OXYCODONE HCL, OXYCODONE HYDROCHLORIDE, OXYCODONE-ACETAMINOPHEN, OXYMORPHONE HCL, PENTAZOCINE-NALOXONE HCL, PERCOCET, PRIMLEV, PROLATE, QDOLO, REMIFENTANIL HCL, ROXICODONE, ROXYBOND, SUFENTANIL CITRATE, TRAMADOL HCL, TRAMADOL HCL-ACETAMINOPHEN, TREZIX, ULTIVA |
| Buprenorphine for MAT/Muscle Relaxants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of buprenorphine and muscle relaxants may result in additive CNS depression.(1,2) CLINICAL EFFECTS: Concurrent use of buprenorphine and other CNS depressants, such as muscle relaxants, may result in profound sedation, respiratory depression, coma, and/or death.(1,2) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Medication assisted treatment (MAT) with buprenorphine is not contraindicated in patients taking CNS depressants; however, discontinuation of CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering may be appropriate. In others, gradual tapering or decreasing to the lowest effective dose of the CNS depressant is appropriate. Ensure that other health care providers prescribing other CNS depressants are aware of the patient's buprenorphine treatment.(2) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(3) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(4) DISCUSSION: Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(5) A retrospective cohort study compared the risk of opioid overdose associated with concomitant use of opioids and skeletal muscle relaxants versus opioid use alone. The study examined two types of opioid users (naive opioid use and prevalent opioid use) with and without exposure to skeletal muscle relaxants. The adjusted hazard ratios (HR) were 1.09 and 1.26 in the naive and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21. The risk increased with treatment duration (less than or equal to 14 days: 0.91; 15-60 days: 1.37; and greater than 60 days: 1.80) and for the use of baclofen and carisoprodol (HR 1.83 and 1.84, respectively). Elevated risk was associated with concomitant users with daily opioid dose greater than 50 mg and benzodiazepine use (HR 1.50 and 1.39, respectively).(6) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(7) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(8) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(9) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(10) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(11) While concomitant use of MAT with CNS depressants increases the risk of adverse reactions, barriers to MAT can pose a greater risk of morbidity and mortality due to opioid use disorder.(2) |
BRIXADI, BUPRENORPHINE HCL, BUPRENORPHINE-NALOXONE, SUBLOCADE, SUBOXONE, ZUBSOLV |
| Methadone (Immediate Release)/Selected Muscle Relaxants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of methadone and muscle relaxants may result in additive CNS depression.(1) CLINICAL EFFECTS: Concurrent use of methadone and other CNS depressants, such as muscle relaxants, may result in profound sedation, respiratory depression, coma, and/or death.(1) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Limit prescribing methadone with CNS depressants such as muscle relaxants to patients for whom alternatives are inadequate.(1) If concurrent use is necessary, limit the dosages and duration of each drug to the minimum possible while achieving the desired clinical effect. If starting a CNS depressant (for an indication other than epilepsy) with an opioid analgesic, prescribe a lower initial dose of the CNS depressant than indicated in the absence of an opioid and titrate based upon clinical response. If an opioid analgesic is indicated in a patient already taking a CNS depressant, prescribe a lower dose of the opioid and titrate based upon clinical response.(1) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(2) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(3) DISCUSSION: Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(4) A retrospective cohort study compared the risk of opioid overdose associated with concomitant use of opioids and skeletal muscle relaxants versus opioid use alone. The study examined two types of opioid users (naive opioid use and prevalent opioid use) with and without exposure to skeletal muscle relaxants. The adjusted hazard ratios (HR) were 1.09 and 1.26 in the naive and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21. The risk increased with treatment duration (less than or equal to 14 days: 0.91; 15-60 days: 1.37; and greater than 60 days: 1.80) and for the use of baclofen and carisoprodol (HR 1.83 and 1.84, respectively). Elevated risk was associated with concomitant users with daily opioid dose greater than 50 mg and benzodiazepine use (HR 1.50 and 1.39, respectively).(5) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(6) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(7) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(8) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(9) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(10) |
METHADONE HCL, METHADONE HCL-0.9% NACL, METHADONE HCL-NACL |
| Selected Opioids for MAT/Selected Muscle Relaxants SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of diacetylmorphine or methadone and muscle relaxants may result in additive CNS depression.(1-3) Levomethadone is an enantiomer of methadone.(4) CLINICAL EFFECTS: Concurrent use of diacetylmorphine or methadone and other CNS depressants, such as muscle relaxants, may result in profound sedation, respiratory depression, coma, and/or death.(1-3) PREDISPOSING FACTORS: Concurrent use of alcohol or other CNS depressants may increase the risk of adverse effects. PATIENT MANAGEMENT: Medication assisted treatment (MAT) with diacetylmorphine or methadone is not contraindicated in patients taking CNS depressants; however, discontinuation of CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering may be appropriate. In others, gradual tapering or decreasing to the lowest effective dose of the CNS depressant is appropriate. Ensure that other health care providers prescribing other CNS depressants are aware of the patient's diacetylmorphine or methadone treatment.(2) Respiratory depression can occur at any time during opioid therapy, especially during therapy initiation and following dosage increases. Consider this risk when using concurrently with other agents that may cause CNS depression.(5) Monitor patients receiving concurrent therapy for unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.(1) Discuss naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat opioid use disorder (OUD). Consider prescribing naloxone to patients prescribed medicines to treat OUD or opioid analgesics (such as those taking CNS depressants) who are at increased risk of opioid overdose and when a patient has household members/close contacts at risk for accidental overdose.(6) DISCUSSION: Between 2002 and 2014, the number of patients receiving an opioid analgesic increased 8%, from 75 million to 81 million patients, and the number of patients receiving a benzodiazepine increased 31%, from 23 million to 30 million patients. During this time, the proportion of patients receiving concurrent therapy increased 31%, from 23 million to 30 million patients.(7) A retrospective cohort study compared the risk of opioid overdose associated with concomitant use of opioids and skeletal muscle relaxants versus opioid use alone. The study examined two types of opioid users (naive opioid use and prevalent opioid use) with and without exposure to skeletal muscle relaxants. The adjusted hazard ratios (HR) were 1.09 and 1.26 in the naive and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21. The risk increased with treatment duration (less than or equal to 14 days: 0.91; 15-60 days: 1.37; and greater than 60 days: 1.80) and for the use of baclofen and carisoprodol (HR 1.83 and 1.84, respectively). Elevated risk was associated with concomitant users with daily opioid dose greater than 50 mg and benzodiazepine use (HR 1.50 and 1.39, respectively).(8) From 2004 to 2011, the rate of nonmedical use-related emergency room visits involving both opioids and benzodiazepines increased from 11 to 34.2 per 100,000 and drug overdose deaths involving both opioids and benzodiazepines increased from 0.6 to 1.7 per 100,000. The proportion of prescription opioid analgesic deaths which also involved benzodiazepines increased from 18% to 31% during this time.(9) A prospective observational cohort study in North Carolina found that the rates of overdose death among patients co-dispensed opioid analgesics and benzodiazepines were 10 times higher than patients receiving opioid analgesics alone.(10) A case-cohort study of VA data from 2004-2009 found that the risk of death from overdose increased with concomitant opioid analgesics and benzodiazepines. Compared to patients with no history of benzodiazepines, patients with a history of benzodiazepine use (hazard ratio [HR] = 2.33) and patients with a current benzodiazepine prescription (HR=3.86) had an increased risk of fatal overdose.(11) A study found that opioid analgesics contributed to 77% of deaths in which benzodiazepines were determined to be a cause of death and that benzodiazepines contributed to 30% of deaths in which opioid analgesics were determined to be a cause of death. This study also found that other CNS depressants (including barbiturates, antipsychotic and neuroleptic drugs, antiepileptic and antiparkinsonian drugs, anesthetics, autonomic nervous system drugs, and muscle relaxants) were contributory to death in many cases where opioid analgesics were also implicated.(12) A study found that alcohol was involved in 18.5% of opioid analgesic abuse-related ED visits and 22.1 percent of opioid analgesic-related deaths.(13) While concomitant use of MAT with CNS depressants increases the risk of adverse reactions, barriers to MAT can pose a greater risk of morbidity and mortality due to opioid use disorder.(2) |
DISKETS, METHADONE HCL, METHADONE INTENSOL, METHADOSE |
The following contraindication information is available for BACLOFEN (baclofen):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 2 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min |
| Chronic kidney disease stage 5 (failure) GFr<15 ml/min |
There are 3 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min |
| Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min |
| Kidney disease with likely reduction in glomerular filtration rate (GFr) |
There are 16 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Acute cognitive impairment |
| Alcohol use disorder |
| Autonomic dysreflexia |
| Cerebrovascular accident |
| Diabetes mellitus |
| Drug abuse |
| Functional disorder of bladder neck and sphincter mechanism |
| History of drug abuse |
| Hypertension |
| Lower seizure threshold |
| Parkinsonism |
| Porphyria |
| Psychotic disorder |
| Schizophrenia |
| Seizure disorder |
| Suicidal ideation |
The following adverse reaction information is available for BACLOFEN (baclofen):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 9 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. | None. |
| Rare/Very Rare |
|---|
|
Abnormal hepatic function tests Chest pain Drug-induced hepatitis Hematuria Hypersensitivity drug reaction Pruritus of skin Skin rash Syncope Urine discoloration |
There are 26 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute cognitive impairment Constipation Dizziness Drowsy General weakness Headache disorder Hypotension Increased urinary frequency Insomnia Muscle weakness Nausea |
Fatigue |
| Rare/Very Rare |
|---|
|
Abnormal sexual function Alopecia Anorexia Body fluid retention Dysuria Erectile dysfunction Facial edema False sense of well-being Gastrointestinal irritation Nasal congestion Oliguria Palpitations Peripheral edema Tremor |
The following precautions are available for BACLOFEN (baclofen):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Reproduction studies in rats receiving oral baclofen at a dosage approximately 13 or 3 times the maximum recommended human oral dosage on a mg/kg or mg/m2 basis, respectively, demonstrated an increased incidence of omphaloceles (ventral hernias) in the fetuses; substantial reductions in food intake and weight gain occurred in pregnant rats receiving this dosage. An increased incidence of omphaloceles did not occur in mice or rabbit fetuses. An increased incidence of incomplete sternebral ossification occurred in the fetuses of rats receiving approximately 13 times the maximum recommended human dosage, and an increased incidence of unossified phalangeal nuclei of the forelimbs and hindlimbs occurred in the fetuses of rabbits receiving approximately 7 times the maximum recommended dosage.
No teratogenic effects occurred in mice, although reduction in mean fetal weight with consequent delay in skeletal ossification occurred in offspring of mice receiving 17 or 34 times the human daily dosage of baclofen. There are no adequate and controlled studies using baclofen in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
No teratogenic effects occurred in mice, although reduction in mean fetal weight with consequent delay in skeletal ossification occurred in offspring of mice receiving 17 or 34 times the human daily dosage of baclofen. There are no adequate and controlled studies using baclofen in pregnant women, and the drug should be used during pregnancy only when the potential benefits justify the possible risks to the fetus.
Baclofen is distributed into milk following oral administration; it not known whether the drug distributes into milk following intrathecal administration. At least one manufacturer states that nursing should not be undertaken by women receiving oral baclofen. Nursing should be undertaken by women receiving intrathecal baclofen only if the potential benefit justifies the potential risks to the infant.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for BACLOFEN (baclofen):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for BACLOFEN (baclofen)'s list of indications:
| Muscle spasticity of spinal origin | |
| G81.1 | Spastic hemiplegia |
| G81.10 | Spastic hemiplegia affecting unspecified side |
| G81.11 | Spastic hemiplegia affecting right dominant side |
| G81.12 | Spastic hemiplegia affecting left dominant side |
| G81.13 | Spastic hemiplegia affecting right nondominant side |
| G81.14 | Spastic hemiplegia affecting left nondominant side |
| M62.83 | Muscle spasm |
| M62.830 | Muscle spasm of back |
| M62.831 | Muscle spasm of calf |
| M62.838 | Other muscle spasm |
| R25.2 | Cramp and spasm |
Formulary Reference Tool