Closely (1)rucaparib will increase the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.sageMinor (2)clonazepam and sage both increase sedation. Minor/Significance Unknown. sage decreases effects of clonazepam by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical interaction; some species of sage may cause convulsions.salmeterolMonitor Closely (1)clonazepam increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.saquinavirMonitor Closely (1)saquinavir increases levels of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available. Consider lowering benzodiazepine dose.scullcapMonitor Closely (1)clonazepam and scullcap both increase sedation. Use Caution/Monitor.secobarbitalMonitor Closely (2)secobarbital will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May also enhance CNS depressant effect of clonazepam secobarbital and clonazepam both increase sedation. Use Caution/Monitor.selinexorSerious - Use Alternative (1)selinexor, clonazepam. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.serdexmethylphenidate/dexmethylphenidateMinor (1)serdexmethylphenidate/dexmethylphenidate increases effects of clonazepam by decreasing metabolism. Minor/Significance Unknown.sevelamerMonitor Closely (1)sevelamer decreases levels of clonazepam by increasing elimination. Use Caution/Monitor.sevofluraneMonitor Closely (1)sevoflurane and clonazepam both increase sedation. Use Caution/Monitor.shepherd's purseMonitor Closely (1)clonazepam and shepherd's purse both increase sedation. Use Caution/Monitor.sodium oxybateSerious - Use Alternative (1)clonazepam, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.stiripentolMonitor Closely (2)stiripentol, clonazepam. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence. stiripentol, clonazepam. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.succinylcholineMinor (1)clonazepam decreases effects of succinylcholine by pharmacodynamic antagonism. Minor/Significance Unknown.sufentanilMonitor Closely (1)clonazepam and sufentanil both increase sedation. Use Caution/Monitor.sufentanil SLSerious - Use Alternative (1)sufentanil SL, clonazepam. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.suvorexantMonitor Closely (1)suvorexant and clonazepam both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarytapentadolMonitor Closely (1)clonazepam and tapentadol both increase sedation. Use Caution/Monitor.tazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.teduglutideMonitor Closely (1)teduglutide increases levels of clonazepam by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.temazepamMonitor Closely (1)clonazepam and temazepam both increase sedation. Use Caution/Monitor.terbutalineMonitor Closely (1)clonazepam increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.thioridazineMonitor Closely (1)clonazepam and thioridazine both increase sedation. Use Caution/Monitor.thiothixeneMonitor Closely (1)clonazepam and thiothixene both increase sedation. Use Caution/Monitor.tipranavirMonitor Closely (1)tipranavir increases levels of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available. Consider lowering benzodiazepine dose.topiramateMonitor Closely (1)clonazepam and topiramate both increase sedation. Modify Therapy/Monitor Closely.tramadolMonitor Closely (1)clonazepam and tramadol both increase sedation. Use Caution/Monitor.trazodoneMonitor Closely (1)clonazepam and trazodone both increase sedation. Use Caution/Monitor.triazolamMonitor Closely (1)clonazepam and triazolam both increase sedation. Use Caution/Monitor.triclofosMonitor Closely (1)clonazepam and triclofos both increase sedation. Use Caution/Monitor.trifluoperazineMonitor Closely (1)clonazepam and trifluoperazine both increase sedation. Use Caution/Monitor.trimipramineMonitor Closely (1)clonazepam and trimipramine both increase sedation. Use Caution/Monitor.triprolidineMonitor Closely (1)triprolidine and clonazepam both increase sedation. Use Caution/Monitor.tucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valerianSerious - Use Alternative (1)valerian and clonazepam both increase sedation. Avoid or Use Alternate Drug.valproic acidMinor (1)clonazepam, valproic acid. Mechanism: unknown. Minor/Significance Unknown. Possible risk of absence seizure.vecuroniumMinor (1)clonazepam decreases effects of vecuronium by pharmacodynamic antagonism. Minor/Significance Unknown.vinpocetineMinor (1)clonazepam increases effects of vinpocetine by unspecified interaction mechanism. Minor/Significance Unknown. Desirable interaction enhanced memory improvement (based on preliminary trial).voriconazoleMonitor Closely (1)voriconazole will increase the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of clonazepam by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.xylometazolineMonitor Closely (1)clonazepam increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.yohimbineMonitor Closely (1)clonazepam increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.ziconotideMonitor Closely (1)clonazepam and ziconotide both increase sedation. Use Caution/Monitor.ziprasidoneMonitor Closely (1)clonazepam and ziprasidone both increase sedation. Use Caution/Monitor.zolpidemMinor (1)zolpidem, clonazepam. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.zotepineMonitor Closely (1)clonazepam and zotepine both increase sedation. Use Caution/Monitor. >10% Somnolence (37%) 1-10% Abnormal coordination (5-10%) Ataxia (5-10%) Depression (5-10%) Dizziness (5-10%) Fatigue (5-10%) Memory impairment (5-10%) Upper respiratory infection (5-10%) Confusion (1-5%) Dysarthria (1-5%) Rhinitis (1-5%) Coughing (1-5%) Urinary frequency (1-5%) Impotence (1-5%) Decreased libido (1-5%) Frequency Not Defined Increased salivation Worsening tonic-clonic seizures Black Box Warnings Concomitant use of benzodiazepines and opioids may result in profound respiratory depression, coma, and death; administer concomitantly when there are no alternative options; limit dosages and durations to minimum required; monitor for signs and symptoms of respiratory depression and sedation Addiction, abuse, and misuse On September 2020, FDA addressed serious risks of benzodiazepine addiction, abuse, and misuse, which can lead to overdose and death Physical dependence can occur when taken steadily for several days to weeks, even as prescribed Stopping abruptly or reducing dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes; before prescribing and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction Assess each patient’s risk prior to prescribing and monitor regularly for the development of these conditions Risks of dependence and withdrawal increase with longer treatment duration and higher daily dose; although injection is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, including seizures, which can be life-threatening; use gradual taper when discontinuing therapy to reduce withdrawal reactions risk Contraindications Significant hepatic impairment Documented hypersensitivity Acute narrow angle glaucoma Cautions Withdraw gradually when used for panic disorder Use caution in COPD, sleep apnea, renal/hepatic disease, open-angle glaucoma (questionable), depression, suicidal ideation Not recommended in patients with depressed neuroses, psychotic reactions, severe respiratory depression, myasthenia gravis (allowable in limited circumstances), acute alcohol intoxication Anterograde amnesia reported benzodiazepine use May cause CNS depression and impairs ability to perform hazardous tasks Hyperactive or aggressive behavior reported with benzodiazepines in pediatric/adolescent patients and in psychiatric patients Increased risk of suicidal thoughts/behavior reported with antiepileptic agents; monitor patient for suicidal behavior and notify health-care provider immediately Use with caution in patients with a history of drug abuse or acute alcoholism; drug dependency possible; prolonged use may result in psychological and physical dependence Use with caution in patients with compromised respiratory function May have porphyrogenic effect; use with caution in patients with porphyria Not for concomitant administration with alcohol or other CNS-depressant drugs When used in patients in whom several different types of seizure disorders coexist, clonazepam may increase incidence or precipitate onset of generalized tonic-clonic seizures (grand mal); may require addition of appropriate anticonvulsants or increase in dosages; concomitant use of valproic acid and clonazepam may produce absence status Abrupt withdrawal, particularly in patients on long-term, high-dose therapy, may precipitate status epilepticus; when discontinuing clonazepam, gradual withdrawal essential; while being gradually withdrawn, simultaneous substitution of another anticonvulsant may be indicated Use of drug, particularly in patients at elevated risk, necessitates counseling about risks and proper use of drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate For patients using treated more frequently than recommended, to reduce risk of withdrawal reactions, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose) Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months May produce increase in salivation; consider before giving drug to patients who have difficulty handling secretions In some studies, up to 30% of patients who initially responded have shown a loss of anticonvulsant activity, often within 3 months of administration; in some cases, dosage adjustment may reestablish efficacy Paradoxical reactions, such as agitation, irritability, aggression, anxiety, anger, nightmares, hallucinations, and psychoses may occur when using benzodiazepines; discontinue therapy, should this occur; paradoxical reactions are more likely to occur in children and in the elderly Pregnancy There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, such as Klonopin, during pregnancy; healthcare providers are encouraged to recommend that pregnant women taking this medication enroll in the NAAED Pregnancy Registry by calling 1-888-233-2334 or online at http://www.aedpregnancyregistry.org/ There are no adequate and well-controlled studies of Klonopin in pregnant women; available human data on risk of teratogenicity are inconclusive; there is insufficient evidence in humans to assess effect of benzodiazepine exposure during pregnancy on neurodevelopment; administration of benzodiazepines immediately prior to or during childbirth can result in a syndrome of hypothermia, hypotonia, respiratory depression, and difficulty feeding; in addition, infants born to mothers who have taken benzodiazepines during later stages of pregnancy can develop dependence, and subsequently withdrawal, during the postnatal period Monitor neonates exposed to this drug during pregnancy for signs of withdrawal; manage these neonates accordingly Data for other benzodiazepines suggest possibility of adverse developmental effects (long-term effects on neurobehavioral and immunological function) in animals following prenatal exposure to benzodiazepines Lactation This drug is excreted in human milk; there are reports of sedation, poor feeding and poor weight gain in infants exposed to benzodiazepines through breast milk Infants exposed to this drug through breast milk should be monitored for sedation, poor feeding, and poor weight gain Effects on breastfed infant and on milk production are unknown; developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action