METAXALONE Drug Interactions: What You Need to Know

INTERACTIONS

7.1 Serotonergic Drugs If concomitant use of metaxalone tablets and another serotonergic drug is warranted, carefully observe the patient, particularly during treatment initiation and dosage modification. Discontinue metaxalone tablets if serotonin syndrome is suspected or if it occurs. Serotonin syndrome has resulted from concomitant use of metaxalone tablets (within the recommended dosage range) with other serotonergic drugs <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6 )]</span>. Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, opioids (particularly fentanyl, meperidine, and methadone), drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including monoamine oxidase (MAO) inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).

7.2 CNS Depressants If concomitant use of metaxalone tablets and another CNS depressant is warranted, closely monitor for signs of respiratory depression and sedation, particularly during treatment initiation and dosage increases. Due to the additive pharmacologic effect, concomitant use of metaxalone tablets with other CNS depressants may increase the risk of sedation and respiratory depression <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 )]</span>.

7.3 Interaction of Metaxalone Tablets with Benedict’s Tests False-positive Benedict&apos;s tests, due to an unknown reducing substance, have been noted in metaxalone tablets-treated patients. A glucose-specific test will differentiate findings.

The use of Metaxalone Tablets, 640 mg is contraindicated in patients with: Known hypersensitivity to any components of this product. Known tendency for drug-induced, hemolytic, or other anemias. Severe renal or hepatic impairment.

• Known hypersensitivity to any components of this product. ( 4 )
• Known tendency to drug induced, hemolytic, or other anemias. ( 4 )
• Severe renal or hepatic impairment. ( 4 )

Warnings and Precautions Serotonin Syndrome Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of serotonergic drugs with metaxalone used within the recommended dosage range (see PRECAUTIONS: DRUG INTERACTIONS) and with metaxalone as a single agent taken at doses higher than the recommended dose (see OVERDOSAGE). Serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, opioids (particularly fentanyl, meperidine, and methadone), drugs that affect the serotonergic neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and drugs that impair metabolism of serotonin (including monoamine oxidase (MAO) inhibitors, both those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) (see PRECAUTIONS: DRUG INTERACTIONS). Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination, rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms generally occurs within several hours to a few days, but may occur later than that. Discontinue metaxalone if serotonin syndrome is suspected. Risks from Concomitant Use with Alcohol or other CNS Depressants The sedative effects of metaxalone and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants (TCAs)) may be additive. Exercise caution with patients who take more than one of these CNS depressants simultaneously. Follow patients closely for signs and symptoms of respiratory depression and sedation (see PRECAUTIONS: DRUG INTERACTIONS). Metaxalone should be administered with great care to patients with pre-existing liver damage. Serial liver function studies should be performed in these patients. False-positive Benedict’s tests, due to an unknown reducing substance, have been noted. A glucose-specific test will differentiate findings. Taking metaxalone with food may enhance general CNS depression; elderly patients may be especially susceptible to this CNS effect (see CLINICAL PHARMACOLOGY: PHARMACOKINETICS and PRECAUTIONS: INFORMATION FOR PATIENTS). Information for Patients Driving or Operating Heavy Machinery Metaxalone may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle, especially when used with alcohol or other CNS depressants.

Serotonin Syndrome

Inform patients that metaxalone tablets could cause a rare but potentially life-threatening condition resulting from administration of doses higher than the recommended dose or from concomitant administration of serotonergic drugs with metaxalone tablets used within the recommended dosage range. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare providers if they are taking, or plan to take, serotonergic medications (see WARNINGS, PRECAUTIONS: DRUG INTERACTIONS, and OVERDOSAGE).

Drug

Interactions CNS Depressants The sedative effects of metaxalone and other CNS depressants (e.g., alcohol, benzodiazepines, opioids, tricyclic antidepressants (TCAs)) may be additive. Exercise caution with patients who take more than one of these CNS depressants simultaneously. Follow patients closely for signs and symptoms of respiratory depression and sedation (see WARNINGS).

Serotonergic Drugs

Serotonin syndrome has resulted from concomitant use of serotonergic drugs with metaxalone used within the recommended dosage range (see WARNINGS). If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue metaxalone if serotonin syndrome is suspected. Examples of serotonergic drugs include: selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, opioids (particularly fentanyl, meperidine, and methadone), drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Carcinogenesis, Mutagenesis, Impairment of Fertility The carcinogenic potential of metaxalone has not been determined.

Pregnancy

Reproduction studies in rats have not revealed evidence of impaired fertility or harm to the fetus due to metaxalone. Post marketing experience has not revealed evidence of fetal injury, but such experience cannot exclude the possibility of infrequent or subtle damage to the human fetus. Safe use of metaxalone has not been established with regard to possible adverse effects upon fetal development. Therefore, metaxalone tablets should not be used in women who are or may become pregnant and particularly during early pregnancy unless, in the judgement of the physician, the potential benefits outweigh the possible hazards.

Nursing

Mothers It is not known whether this drug is secreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug since many drugs are excreted in human milk.

Pediatric Use

Safety and effectiveness in children 12 years of age and below have not been established.