Meperidineinteractions

Table 1 includes clinically significant drug interactions with Meperidine Hydrochloride Tablets and Oral Solution. Table 1: Clinically Significant Drug Interactions with Meperidine Hydrochloride Tablets and Oral Solution Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: Meperidine is contraindicated in patients who are receiving monoamine oxidase inhibitors (MAOIs) or those who have recently received such agents. Therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received such agents within 14 days. The mechanism of these reactions is unclear, but may be related to a preexisting hyperphenylalaninemia. Some have been characterized by coma, severe respiratory depression, cyanosis, and hypotension, and have resembled the syndrome of acute opioid overdose. Serotonin syndrome with agitation, hyperthermia, diarrhea, tachycardia, sweating, tremors and impaired consciousness may also occur. In other reactions the predominant manifestations have been hyperexcitability, convulsions, tachycardia, hyperpyrexia, and hypertension. Intervention: Do not use Meperidine Hydrochloride Tablets or Oral Solution in patients taking MAOIs or within 14 days of stopping such treatment. Intravenous hydrocortisone or prednisolone have been used to treat severe reactions, with the addition of intravenous chlorpromazine in those cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of opioid overdose reversal agents in the treatment of these reactions is unknown. Examples: phenelzine, tranylcypromine, linezolid Inhibitors of CYP3A4 and CYP2B6 Clinical Impact: The concomitant use of Meperidine Hydrochloride Tablets or Oral Solution and CYP3A4 or CYP2B6 inhibitors can increase the plasma concentration of meperidine, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of Meperidine Hydrochloride Tablets or Oral Solution and CYP2B6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of Meperidine Hydrochloride Tablets or Oral Solution is achieved. After stopping a CYP3A4 or CYP2B6 inhibitor, as the effects of the inhibitor decline, the meperidine plasma concentration will decrease, resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to meperidine. Intervention: If concomitant use is necessary, consider dosage reduction of Meperidine Hydrochloride Tablets or Oral Solution until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4 or CYP2B6 inhibitor is discontinued, consider increasing the meperidine dosage until stable drug effects are achieved. Assess for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 and CYP2B6 Inducers Clinical Impact: The concomitant use of meperidine and CYP3A4 or CYP2B6 inducers can decrease the plasma concentration of meperidine, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to meperidine. After stopping a CYP3A4 or CYP2B6 inducer, as the effects of the inducer decline, the meperidine plasma concentration will increase, which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the Meperidine Hydrochloride Tablets or Oral Solution dosage until stable drug effects are achieved. Assess for signs of opioid withdrawal. If a CYP3A4 or CYP2B6 inducer is discontinued, consider meperidine dosage reduction and evaluate patients at frequent intervals for signs of respiratory depression and sedation. Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider recommending or prescribing an opioid overdose reversal agent. Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids (gabapentin or pregabalin), other opioids, alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue Meperidine Hydrochloride Tablets or Oral Solution if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase inhibitors (MAOIs) (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue) Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of meperidine and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Meperidine may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Because respiratory depression may be greater than otherwise expected, decrease the dosage of Meperidine Hydrochloride Tablets and Oral Solution and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider recommending or prescribing an opioid overdose reversal agent. Examples: cyclobenzaprine, metaxalone Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Evaluate patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Evaluate patients for signs of urinary retention or reduced gastric motility when Meperidine Hydrochloride Tablets or Oral Solution is used concomitantly with anticholinergic drugs. Acyclovir Clinical Impact: The concomitant use of acyclovir may increase the plasma concentrations of meperidine and its metabolite, normeperidine. Intervention: If concomitant use of acyclovir and Meperidine Hydrochloride Tablets or Oral Solution is necessary, evaluate patients for respiratory depression and sedation at frequent intervals. Cimetidine Clinical Impact: The concomitant use of cimetidine may reduce the clearance and volume of distribution of meperidine also the formation of the metabolite, normeperidine, in healthy subjects. Intervention: If concomitant use of cimetidine and Meperidine Hydrochloride Tablets or Oral Solution is necessary, evaluate patients for respiratory depression and sedation at frequent intervals.

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with Meperidine Hydrochloride Tablets or Oral Solution because they may reduce analgesic effect of Meperidine Hydrochloride Tablets or Oral Solution or precipitate withdrawal symptoms.