In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Moderate Concurrent use of many CNS-active drugs with milnacipran or levomilnacipran has not been evaluated by the manufacturer. Tier Description 1 This drug is available at the lowest co-pay. Do not change your doses or medication schedule without your doctor's advice. Clonazepam belongs to a class of drugs called benzodiazepines that affects chemicals in the brain.
Tears: Clonazepam doses available
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|CLONAZEPAM DOSAGE ANXIETY 7MG GOOD DOSE OF ATIVAN FOR MRI||The difference available Klonopin doses placebo in clonazepam from baseline in the number of full panic attacks was approximately 1 panic attack per week. Call your doctor right away if you have serious side effects. If possible, use one pharmacy for all your prescription medications and clonazepam products. Drospirenone; Ethinyl Estradiol; Levomefolate: Drug available clonazepam dosages available herein may doses time sensitive.|
|Clonazepam vs xanax dosages alprazolam||Clonazepam 1 mg side effects|
However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. Data were analyzed from drugs with adequately designed clinical trials including carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide. However, this is considered to be a class effect. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior.
Anticonvulsants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. Clonazepam should be used cautiously in patients with bipolar disorder because mania and hypomania have been reported in conjunction with the use of benzodiazepines in mood disorders. Due to CNS depression, patients should be cautioned against driving or operating machinery until they know how clonazepam may affect them.
Some patients may experience excessive sedation and impaired ability to perform tasks. Increased CNS effects may be seen with use of clonazepam in patients with acute ethanol intoxication or psychosis. Patients with ethanol intoxication who have also consumed clonazepam have an increased risk of respiratory suppression and coma. Clonazepam should be used with caution in patients with a neuromuscular disease, such as muscular dystrophy, myotonia, or myasthenia gravis as these conditions can be exacerbated.
Patients with late stage Parkinson's disease may experience worsening of their psychosis or impaired cognition with administration of benzodiazepines. Benzodiazepines may also cause incoordination or paradoxical reactions that may worsen symptoms of Parkinson's disease. Clonazepam may infrequently increase the risk for hypersalivation and should be used cautiously in patients with Parkinson's disease. When used in patients in whom several different types of seizure disorders coexist, clonazepam may increase the incidence or precipitate the onset of generalized tonic-clonic seizures.
The addition of appropriate anticonvulsants or an increase in their dosages may be indicated. The concomitant use of valproic acid and clonazepam may produce absence status. Patients with a history of a seizure disorder should not be withdrawn abruptly from benzodiazepines due to the risk of precipitating a seizure. Flumazenil should not be used to reverse the actions of clonazepam in epileptic patients due to the risk of precipitating a seizure. Clonazepam can cause physical and psychological dependence, and should be used with extreme caution in patients with known, suspected, or history of substance abuse.
Tolerance or tachyphylaxis may develop to the sedative effects of benzodiazepines. Dosage adjustment may reestablish efficacy, in some cases. Abrupt discontinuation of clonazepam after prolonged use should be avoided. Abrupt discontinuation of benzodiazepine therapy has been reported to cause withdrawal symptoms and status epilepticus, especially following high dose or prolonged therapy. However, benzodiazepine dependence can occur following administration of therapeutic doses for as few as 1 to 2 weeks, and withdrawal symptoms may be seen following the discontinuation of therapy.
Patients with a seizure history or who are taking other drugs that lower the seizure threshold i. Clonazepam should be withdrawn slowly, using a gradual dosage-tapering schedule. During benzodiazepine withdrawal in general, the greatest risk of seizure appears to be during the first 24 to 72 hours. When clonazepam is being gradually withdrawn, the simultaneous substitution of another anticonvulsant may be indicated.
Clonazepam is contraindicated in patients with clinical or biochemical evidence of significant hepatic disease, as the drug undergoes hepatic metabolism. Metabolites of clonazepam are excreted by the kidneys; to avoid their excess accumulation, caution should be exercised in the administration of the drug to patients with renal impairment or renal failure. In general, initial dose selection should be in the lower range and dosage titration should proceed cautiously.
Assess renal function during prolonged therapy and adjust dosage as clinically indicated. Clonazepam is contraindicated in patients with acute closed-angle glaucoma. Clonazepam may be used in patients with open angle glaucoma who are receiving appropriate therapy. Clonazepam may have a porphyrogenic effect and should be used cautiously in patients with porphyria. Clinical studies of clonazepam did not include sufficient numbers of geriatric patients to determine whether they respond differently from younger subjects.
Reported clinical experience has not identified differences in responses between geriatric and younger adults. Sedatives may be associated with falls, confusion and over-sedation in the older adult. Due to its long half-life and the availability of safer alternatives, clonazepam is not a preferred benzodiazepine for the treatment of insomnia in the elderly, and its use for this purpose should generally be avoided.
If treatment with clonazepam is necessary in a geriatric patient, initiate treatment with a low dose followed by slow titration and close observation. According to the Beers Criteria, benzodiazepines are considered potentially inappropriate medications PIMs for use in geriatric patients and avoidance is generally recommended, although some agents from this class may be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, severe generalized anxiety disorder, peri-procedural anesthesia, and end of life care.
Older adults have an increased sensitivity to benzodiazepines and slower metabolism of long-acting agents, which increases their risk of cognitive impairment, delirium, falls, fractures, and motor vehicle accidents. The Panel recommends avoiding benzodiazepines in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: If a benzodiazepine must be used in a patient with a history of falls or fractures, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk.
Specific criteria for anxiolytics must be met, including 1 limiting use to indications specified in the OBRA guidelines e. Anxiolytics should be used for delirium, dementia, or other cognitive disorders only when there are associated behaviors that are 1 quantitatively and objectively documented, and 2 are persistent, and 3 are not due to preventable or correctable reasons, and 4 constitute clinically significant distress or dysfunction to the LTCF resident or represent a danger to the resident or others.
There are exceptions that may warrant the use of an anxiolytic such as a long-acting benzodiazepine for withdrawal from a short-acting benzodiazepine, use for neuromuscular syndromes e. The need for indefinite continuation of clonazepam e. Benzodiazepines may increase the risk of confusion, sedation, and falls. OBRA provides dosing guidance for clonazepam as an anxiolytic. When a medication is used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.
There are no adequate and well-controlled studies of clonazepam in pregnant women. Available human data on the risk of teratogenicity are inconclusive. There is insufficient evidence in humans to assess the effect of benzodiazepine exposure during pregnancy on neurodevelopment. Perinatal complications have been reported in neonates born to mothers who have been receiving benzodiazepines late in pregnancy, including findings suggestive of either excess benzodiazepine exposure or of withdrawal phenomena.
Symptoms of perinatal problems in the exposed neonate may include hypothermia, hypotonia, respiratory depression, and difficulty feeding. Animal data indicate teratogenic effects of clonazepam. Pregnant rabbits were given clonazepam doses lower or similar to maximum human doses during the period of organogenesis. Cleft palate, open eyelid, fused sternebrae, and limb defects were observed in a low, non-dose related incidence in exposed litters from all dosage groups.
No maternal or embryo-fetal anomalies were noted in mice and rats receiving 4 and 20 times the maximum recommended human dose. Clonazepam has not been studied for use during labor or obstetric delivery. Physicians are advised to recommend that pregnant patients receiving clonazepam enroll in the North American Antiepileptic Drug NAAED Pregnancy Registry to provide information about the effects of in utero exposure to the drug.
This can be done by calling the registry at , and must be done by patients themselves. Information on this registry can also be found at the website www. Avoid prolonged use of clonazepam during breast-feeding, and consider alternative shorter-acting drugs, such as lorazepam. Clonazepam is excreted in breast milk in low concentrations with a milk to plasma ratio of approximately 0. However, drug accumulation may occur in the infant due to a long half-life.
Sedative effects in the infant, with resultant poor feeding, have been occasionally reported with maternal use of clonazepam. Observational studies suggest that benzodiazepine use, including the use of clonazepam, does not prohibit the initiation of breast-feeding, and that continued maternal use may ensue with close monitoring of the breast-fed infant for sedation, poor feeding, problems with weight gain, and apnea; however, more study is needed.
Previous American Academy of Pediatrics AAP recommendations considered benzodiazepines to be drugs whose effect on the nursing infant is not known but may be of concern, particularly with prolonged exposure. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for clonazepam and any potential adverse effects on the breast-fed infant from clonazepam or the underlying maternal condition.
Long-term administration of clonazepam to adolescents, children, and infants with seizure activity should be carefully considered via a benefit-risk evaluation, given the possibility that adverse effects on physical or mental development could become apparent only after many years. Safety and effectiveness of clonazepam have not been established for treating panic disorder in patients pediatric patients under the age of 18 years.
Minor Patients taking benzodiazepines for insomnia should not use caffeine-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine. Moderate Monitoring of clonazepam concentrations or dosage adjustment may be necessary if used concurrently with barbiturates due to decreased clonazepam concentrations. Clonazepam is a CYP3A4 substrate. Barbiturates are strong CYP3A4 inducers. Acetaminophen; Butalbital; Caffeine; Codeine: Major Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death.
Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If an opiate agonist is initiated in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response.
If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial dose of the benzodiazepine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation. Avoid prescribing opiate cough medications in patients taking benzodiazepines.
Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: Moderate Coadministration can potentiate the CNS effects e. Use caution with this combination. Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Moderate The therapeutic effect of phenylephrine may be decreased in patients receiving benzodiazepines.
Monitor patients for decreased pressor effect if these agents are administered concomitantly. Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: Moderate The CNS depressant effects of dichloralphenazone can be potentiated by benzodiazepines.
Avoid opiate cough medications in patients taking benzodiazepines. If oxycodone is initiated in a patient taking a benzodiazepine, reduce dosages and titrate to clinical response. The dose of any opiate agonist administered with parenteral diazepam should be reduced by at least one-third. Therefore, psychotropic pharmacodynamic interactions could occur following concomitant administration of drugs with significant CNS activity.
Moderate Amiodarone is a CYP3A4 inhibitor and may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity. Moderate Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery. Clarithromycin is a CYP3A4 inhibitor.
There have been some case reports describing an interaction between omeprazole and benzodiazepines metabolized via the cytochrome P system, such as clonazepam. Patients should be monitored to determine if it is necessary to adjust the dosage of the benzodiazepine when taken concomitantly with omeprazole. Amphetamines may decrease the seizure threshold and may increase the risk of seizures. Protease inhibitors are CYP3A4 inhibitors.
Moderate Administration of nitrates such as amyl nitrite to patients receiving other hypotension-producing agents, such as benzodiazepines, can cause additive hypotensive or orthostatic effects. Moderate Monitor patients for decreased efficacy and a change in clonazepam dosage requirements when giving concurrently with apalutamide. Moderate Apomorphine causes significant somnolence.
Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects. Minor No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. Theoretically, apraclonidine might potentiate the effects of CNS depressant drugs such as the anxiolytics, sedatives, and hypnotics, including barbiturates or benzodiazepines. Major Use caution if clonazepam and aprepitant, fosaprepitant are used concurrently and monitor for an increase in clonazepam-related adverse effects for several days after administration of a multi-day aprepitant regimen.
If a benzodiazepine is necessary, a dosage adjustment of the multi-day regimen may be necessary depending on the clinical situation e. Consider selection of an agent that is not metabolized via CYP3A4 isoenzymes e. As a single mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.
After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant mg IV as a single dose increased the AUC of midazolam given on days 1 and 4 by approximately 1.
Less than a 2-fold increase in the midazolam AUC is not considered clinically important. Moderate Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. The intensity of sedation and orthostatic hypotension is greater during concurrent use of lorazepam and oral aripiprazole and during use of a parenteral benzodiazepine and intramuscular IM aripiprazole compared to aripiprazole alone; therefore, patients receiving a benzodiazepine with oral or parenteral aripiprazole should be monitored for sedation and blood pressure and the dose should be adjusted accordingly.
Data from the manufacturer indicate there are no clinically significant pharmacokinetic changes when aripiprazole is given with lorazepam. Moderate Drugs that can cause CNS depression, if used concomitantly with asenapine, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when asenapine is given in combination with other centrally-acting medications including anxiolytics, sedatives, and hypnotics including barbiturates , buprenorphine, buprenorphine; naloxone, butorphanol, dronabinol, THC, nabilone, nalbuphine, opiate agonists, pentazocine, acetaminophen; pentazocine, aspirin, ASA; pentazocine, and pentazocine; naloxone.
Cobicistat is a CYP3A4 inhibitor. Moderate Concurrent use of benzodiazepines and other CNS active medications including neuromuscular blockers, can potentiate the CNS effects of either agent. Lower doses of one or both agents may be required. The severity of this interaction may be increased when additional CNS depressants are given. Atropine; Hyoscyamine; Phenobarbital; Scopolamine: Moderate Scopolamine may cause dizziness and drowsiness. Belladonna Alkaloids; Ergotamine; Phenobarbital: Moderate CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of benztropine.
Moderate Close clinical monitoring is advised when administering clonazepam with boceprevir due to an increased potential for clonazepam-related adverse events. If clonazepam dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of clonazepam.
Clonazepam is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated clonazepam plasma concentrations. Moderate Bosentan is a hepatic inducer and can theoretically increase the clearance of benzodiazepines metabolized by oxidative metabolism leading to lower benzodiazepine concentrations. Moderate Monitor for decreased efficacy of clonazepam if coadministration with brigatinib is necessary.
Moderate Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines. Moderate Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including benzodiazepines.
In patients treated with buprenorphine for opioid use disorder, cessation of benzodiazepines or other CNS depressants is preferred in most cases. Consider alternatives to benzodiazepines for conditions such as anxiety or insomnia in patients receiving buprenorphine maintenance treatment. Moderate It is common for patients to overlap anxiety treatment when switching from benzodiazepines to buspirone. Buspirone has a slow onset of action and the drug will not block the withdrawal syndrome often seen with cessation of benzodiazepine therapy in those with benzodiazepine dependence.
Therefore, before starting therapy with buspirone, withdraw patients gradually from the benzodiazepine. Alternatively, conversion to buspirone therapy may require treatment overlap to allow for the downward titration of the benzodiazepine while buspirone takes effect. It should be noted that the combination of buspirone and benzodiazepines can potentiate the CNS effects e. Moderate Monitoring of clonazepam concentrations or dosage adjustment may be necessary if used concurrently with carbamazepine due to decreased clonazepam concentrations.
Carbamazepine is a strong CYP3A4 inducer. Additive CNS depression may also occur. Moderate Due to the CNS effects of cariprazine, caution should be used when cariprazine is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics. Moderate Monitor for clonazepam-related adverse reactions, including sedation and respiratory depression, if coadministration of clonazepam with ceritinib is necessary.
Although clinical studies have not been performed, inhibitors of this enzyme system may increase clonazepam exposure. Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Moderate Cimetidine can decrease the hepatic oxidative metabolism of clonazepam if administered concomitantly. Moderate Ciprofloxacin is a CYP3A4 inhibitor and may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity.
Moderate Cisapride may enhance the sedative effects of benzodiazepines. Patients should not drive or operate heavy machinery until they know how the combination affects them. Patient counseling is important, as cisapride alone does not cause drowsiness or affect psychomotor function. Major Concomitant administration of clobazam with other CNS depressant drugs including anxiolytics, sedatives, and hypnotics, can potentiate the CNS effects i.
In addition, concurrent use of clobazam and other benzodiazepines should generally be avoided since this may represent duplicative therapy, and centrally-mediated adverse effects may be potentiated. Midazolam is a substrate of CYP3A4 and clobazam is a mild inducer of this isoenzyme. According to the manufacturer, dosage adjustments of CYP3A4 substrates are not considered necessary.
Moderate If concurrent therapy with clozapine and a benzodiazepine is necessary, it is advisable to begin with the lowest possible benzodiazepine dose and closely monitor the patient, particularly at initiation of treatment and following dose increases. Although the combination has been used safely, adverse reactions such as confusion, ataxia, somnolence, delirium, collapse, cardiac arrest, respiratory arrest, and death have occurred rarely in patients receiving clozapine concurrently or following benzodiazepine therapy.
Several benzodiazepines, including clonazepam, oxazepam, flurazepam, diazepam, clobazam, flunitrazepam, and lorazepam have been implicated in these reactions. At least one case of sudden death was reported following intravenous administration of lorazepam to a patient receiving clozapine. Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Moderate Because promethazine causes pronounced sedation, an enhanced CNS depressant effect or additive drowsiness may occur when it is combined with other CNS depressants including benzodiazepines.
To minimize potential for interactions, consider administering oral anticonvulsants such as clonazepam at least 4 hours before colesevelam. Theoretically, similar pharmacokinetic effects could be seen with clonazepam. Subsequent treatment with CYP3A substrates, such as clonazepam, may be initiated no sooner than 1 week after completion of conivaptan therapy. Moderate Monitor for an increase in clonazepam-related adverse reactions including sedation and respiratory depression if coadministration with crizotinib is necessary.
Although clinical studies have not been performed, based on the involvement of CYP3A in clonazepam metabolism, inhibitors of this enzyme system may increase clonazepam exposure and should be used cautiously. Moderate CYP3A4 inhibitors, such as streptogramins, may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity. Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Delavirdine is a CYP3A4 inhibitor.
Moderate Concurrent use with benzodiazepines can decrease the minimum alveolar concentration MAC of desflurane needed to produce anesthesia. Moderate Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as clonazepam, may have additive effects and worsen drowsiness or sedation. Moderate Co-administration of dexmedetomidine with benzodiazepines is likely to lead to an enhancement of CNS depression. Moderate Dicyclomine can cause drowsiness, so it should be used cautiously in patients receiving CNS depressants like benzodiazepines.
Moderate CYP3A4 inhibitors, such as diltiazem, may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity. Moderate Disulfiram can decrease the hepatic oxidative metabolism of clonazepam if administered concomitantly. Patients receiving clonazepam should be monitored for signs of an exaggerated response if disulfiram is used concomitantly. Moderate Use caution if the use of benzodiazepines are necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects.
Clonazepam is a substrate for CYP3A4. The concomitant administration of dronedarone and CYP3A substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution. Major Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes. In December , the FDA issued a black box warning regarding the use of droperidol and its association with QT prolongation and potential for cardiac arrhythmias based on post-marketing surveillance data.
Risk factors for the development of prolonged QT syndrome may include the use of benzodiazepines. Also, droperidol and benzodiazepines can both cause CNS depression. If used with a benzodiazepine, droperidol should be initiated at a low dose and adjusted upward, with caution, as needed to achieve the desired effect. Minor Oral contraceptives can increase the effects of clonazepam because oral contraceptives inhibit oxidative metabolism, thereby increasing serum concentrations of concomitantly administered benzodiazepines that undergo oxidation.
Patients receiving oral contraceptive therapy should be observed for evidence of increased response to clonazepam. Drospirenone; Ethinyl Estradiol; Levomefolate: Patients receiving benzodiazepines that are metabolized by these isoenzymes may experience decreased benzodiazepine serum concentrations, if administered concurrently with efavirenz.
Efavirenz should be used with caution with oxidized benzodiazepines including e. Monitor patients closely for excessive side effects. Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: Moderate Administering clonazepam with elbasvir; grazoprevir may result in elevated clonazepam plasma concentrations. If these drugs are used together, closely monitor for signs of adverse events. Moderate Concomitant administration can potentiate the CNS effects e. Moderate Erythromycin may inhibit the CYP3A4-mediated metabolism of oxidized benzodiazepines, such as clonazepam.
Monitor patient clinically for enhanced clonazepam response. Moderate Concomitant administration of benzodiazepines with eszopiclone can potentiate the CNS effects e. The concurrent use of eszopiclone with other anxiolytics, sedatives, and hypnotics at bedtime or in the middle of the night is not recommended. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
If used together, a reduction in the dose of one or both drugs may be needed. Major Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications.
In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol. Ethinyl Estradiol; Ethynodiol Diacetate: Ethinyl Estradiol; Norethindrone Acetate: Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: Ethinyl Estradiol; Norethindrone; Ferrous fumarate: Also, hepatic enzyme inducers such as hydantoins can theoretically increase the clearance of clonazepam.
Clonazepam in a CYP3A4 substrate. Fluconazole is a CYP3A4 inhibitor. Because binding at the receptor is competitive and flumazenil has a much shorter duration of action than do most benzodiazepines, it is possible for the effects of flumazenil to dissipate sooner than the effects of the benzodiazepine. Flumazenil does not affect the pharmacokinetics of the benzodiazepines. Abrupt awakening can cause dysphoria, agitation, and possibly increased adverse effects.
If administered to patients who have received a benzodiazepine chronically, abrupt interruption of benzodiazepine agonism by flumazenil can induce benzodiazepine withdrawal including seizures. Flumazenil has minimal effects on benzodiazepine-induced respiratory depression; suitable ventilatory support should be available, especially in treating acute benzodiazepine overdose. Flumazenil does not reverse the actions of barbiturates, opiate agonists, or tricyclic antidepressants.
Patients should be monitored for clinical response, and adjust benzodiazepine dosage if needed. Drugs that can cause CNS depression, if used concomitantly with olanzapine, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension. Besides ethanol, clinicians should use other anxiolytics, sedatives, and hypnotics cautiously with olanzapine.
In theory, co-administration of clonazepam and a potent CYP3A4 inhibitor, such as fluvoxamine, may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity. Fluoxetine, another CYP3A4 inhibitor, does not affect the pharmacokinetics of clonazepam. Monitor patients closely for excessive clonazepam side effects, including changes in psychomotor performance and sedation.
Major Coadministration of marijuana with benzodiazepines may result in an exaggerated sedative effect. Instruct patients receiving these medications concurrently not to drive or operate machinery. Moderate Closely monitor for loss of seizure control, increased anxiety, or panic attacks if clonazepam and fosphenytoin, a prodrug of phenytoin, are used concurrently.
Monitoring of phenytoin serum concentrations is recommended. Monitor for increased adverse effects from phenytoin, such as nystagmus, ataxia, slurred speech, nausea, vomiting, confusion, or lethargy. The metabolism of clonazepam by CYP3A4 may be induced by phenytoin resulting in decreased clonazepam concentrations. The effect of the interaction on phenytoin concentrations is unpredictable, and the mechanism of interaction is unclear.
In a study that assessed the effect of clonazepam on phenytoin plasma concentrations, 9 patients experienced increased phenytoin concentrations when clonazepam was introduced. The magnitude of concentration increase is not reported. Phenytoin concentrations decreased in 1 patient and remained unchanged in 3 patients when clonazepam was introduced. It is unclear if the concentration increases were due to a drug interaction or increased compliance with phenytoin therapy.
Minor Patients taking benzodiazepines for insomnia should not use caffeine-containing products, such as green tea, prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine. Moderate Guanabenz is associated with sedative effects. Guanabenz can potentiate the effects of CNS depressants such as benzodiazepines, when administered concomitantly. Moderate Guanfacine has been associated with sedative effects and can potentiate the actions of other CNS depressants including benzodiazepines.
Minor Caffeine, an active constituent of guarana, is a CNS stimulant associated with heightened attentiveness and insomnia, and is used to treat or prevent drowsiness or fatigue; patients taking benzodiazepines for insomnia should not use guarana-containing products prior to going to bed as these products may antagonize the sedative effects of the benzodiazepine or zolpidem. Moderate Haloperidol can potentiate the actions of other CNS depressants, such as benzodiazepines, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
Moderate Methyldopa is associated with sedative effects. Methyldopa can potentiate the effects of CNS depressants such as barbiturates, benzodiazepines, opiate agonists, or phenothiazines when administered concomitantly. Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Moderate Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as clonazepam.
Hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use. Moderate Drugs that can cause CNS depression, if used concomitantly with iloperidone, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Caution should be used when iloperidone is given in combination with other centrally-acting medications including anxiolytics, sedatives, and hypnotics. Moderate CYP3A4 inhibitors, such as imatinib, may reduce the metabolism of clonazepam and increase the potential for benzodiazepine toxicity. Moderate The use of intrathecal radiopaque contrast agents is associated with a risk of seizures. Patients should be instructed to continue using benzodiazepines during procedures or exams that require the use of intrathecal radiopaque contrast agents as abrupt discontinuation of benzodiazepines may also increase seizure risk.
Isavuconazole, the active moiety of isavuconazonium, is a CYP3A4 inhibitor. Moderate Isoniazid, INH can decrease the hepatic oxidative metabolism of clonazepam if administered concomitantly. Patients receiving clonazepam should be monitored for signs of an exaggerated response if isoniazid is used concomitantly. Treatment should be discontinued gradually, with a decrease of 0. There is no body of evidence available to answer the question of how long the patient treated with clonazepam should remain on it.
Therefore, the physician who elects to use Klonopin for extended periods should periodically reevaluate the long-term usefulness of the drug for the individual patient. There is no clinical trial experience with Klonopin in panic disorder patients under 18 years of age. There is no clinical trial experience with Klonopin in panic disorder patients 65 years of age and older. Klonopin tablets are available as scored tablets with a K-shaped perforation - 0.
The adverse experiences for Klonopin are provided separately for patients with seizure disorders and with panic disorder. The most frequently occurring side effects of Klonopin are referable to CNS depression. Others, listed by system, including those identified during postapproval use of Klonopin are:. Hair loss, hirsutism , skin rash, ankle and facial edema.
Anorexia , coated tongue, constipation, diarrhea, dry mouth , encopresis , gastritis , increased appetite, nausea, sore gums. Dysuria , enuresis , nocturia , urinary retention. Anemia , leukopenia , thrombocytopenia , eosinophilia. Hepatomegaly , transient elevations of serum transaminases and alkaline phosphatase. Dehydration, general deterioration, fever, lymphadenopathy , weight loss or gain. Confusion, depression, amnesia , hysteria, increased libido , insomnia, psychosis the behavior effects are more likely to occur in patients with a history of psychiatric disturbances.
The following paradoxical reactions have been observed: Chest congestion , rhinorrhea , shortness of breath, hypersecretion in upper respiratory passages. Adverse events during exposure to Klonopin were obtained by spontaneous report and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories.
In the tables and tabulations that follow, CIGY dictionary terminology has been used to classify reported adverse events, except in certain cases in which redundant terms were collapsed into more meaningful terms, as noted below. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed.
An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Table 3 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during acute therapy of panic disorder from a pool of two 6- to 9-week trials. The prescriber should be aware that the figures in Table 3 cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials.
Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence in the population studied.
While these findings are noteworthy, Hamilton Depression Rating Scale HAM-D data collected in these trials revealed a larger decline in HAM-D scores in the clonazepam group than the placebo group suggesting that clonazepamtreated patients were not experiencing a worsening or emergence of clinical depression. Following is a list of modified CIGY terms that reflect treatment-emergent adverse events reported by patients treated with Klonopin at multiple doses during clinical trials. All reported events are included except those already listed in Table 3 or elsewhere in labeling, those events for which a drug cause was remote, those event terms which were so general as to be uninformative, and events reported only once and which did not have a substantial probability of being acutely life-threatening.
It is important to emphasize that, although the events occurred during treatment with Klonopin, they were not necessarily caused by it. Events are further categorized by body system and listed in order of decreasing frequency. Body as a Whole: Central and Peripheral Nervous System Disorders: Hearing and Vestibular Disorders: Metabolic and Nutritional Disorders: Skin and Appendages Disorders: The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration.
When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid -related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and follow patients closely for respiratory depression and sedation. Clonazepam does not appear to alter the pharmacokinetics of carbamazepine or phenobarbital.
Clonazepam has the potential to influence concentrations of phenytoin. Monitoring of phenytoin concentration is recommended when clonazepam is co-administrated with phenytoin. The effect of clonazepam on the metabolism of other drugs has not been investigated. Literature reports suggest that ranitidine , an agent that decreases stomach acidity, does not greatly alter clonazepam pharmacokinetics. Although clinical studies have not been performed, based on the involvement of the cytochrome P 3A family in clonazepam metabolism, inhibitors of this enzyme system, notably oral antifungal agents e.
The CNS-depressant action of the benzodiazepine class of drugs may be potentiated by alcohol, narcotics, barbiturates, nonbarbiturate hypnotics, antianxiety agents, the phenothiazines, thioxanthene and butyrophenone classes of antipsychotic agents, monoamine oxidase inhibitors and the tricyclic antidepressants , and by other anticonvulsant drugs.
Withdrawal symptoms , similar in character to those noted with barbiturates and alcohol e. The more severe withdrawal symptoms have usually been limited to those patients who received excessive doses over an extended period of time. Generally milder withdrawal symptoms e. Addiction- prone individuals such as drug addicts or alcoholics should be under careful surveillance when receiving clonazepam or other psychotropic agents because of the predisposition of such patients to habituation and dependence.
Following the short-term treatment of patients with panic disorder in Studies 1 and 2 see Clinical Trials , patients were gradually withdrawn during a 7-week downward-titration discontinuance period. Overall, the discontinuance period was associated with good tolerability and a very modest clinical deterioration, without evidence of a significant rebound phenomenon. However, there are not sufficient data from adequate and well-controlled long-term clonazepam studies in patients with panic disorder to accurately estimate the risks of withdrawal symptoms and dependence that may be associated with such use.
Concomitant use of benzodiazepines , including Klonopin, and opioids may result in profound sedation, respiratory depression , coma, and death. Because of these risks, reserve concomitant prescribing of benzodiazepines and opioids for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone.
If a decision is made to prescribe Klonopin concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. Since Klonopin produces CNS depression, patients receiving this drug should be cautioned against engaging in hazardous occupations requiring mental alertness, such as operating machinery or driving a motor vehicle.
Antiepileptic drugs AEDs , including Klonopin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of placebo-controlled clinical trials mono- and adjunctive therapy of 11 different AEDs showed that patients randomized to one of the AEDs had approximately twice the risk adjusted Relative Risk 1.
In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27, AED-treated patients was 0. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed. The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed.
The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age 5— years in the clinical trials analyzed. The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing Klonopin or any other AED must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and with an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
Behaviors of concern should be reported immediately to healthcare providers. Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines see Drug Abuse And Dependence. When used in patients in whom several different types of seizure disorders coexist, Klonopin may increase the incidence or precipitate the onset of generalized tonic-clonic seizures grand mal. This may require the addition of appropriate anticonvulsants or an increase in their dosages.
The concomitant use of valproic acid and Klonopin may produce absence status. In some cases, dosage adjustment may reestablish efficacy. Periodic blood counts and liver function tests are advisable during long-term therapy with Klonopin. Physical And Psychological Dependence. Paradoxical reactions are more likely to occur in children and in the elderly. The abrupt withdrawal of Klonopin, particularly in those patients on long-term, high-dose therapy, may precipitate status epilepticus.
Therefore, when discontinuing Klonopin, gradual withdrawal is essential. While Klonopin is being gradually withdrawn, the simultaneous substitution of another anticonvulsant may be indicated. Metabolites of Klonopin are excreted by the kidneys; to avoid their excess accumulation, caution should be exercised in the administration of the drug to patients with impaired renal function. Klonopin may produce an increase in salivation.
This should be considered before giving the drug to patients who have difficulty handling secretions. Klonopin may cause respiratory depression and should be used with caution in patients with compromised respiratory function e. Klonopin may have a porphyrogenic effect and should be used with care in patients with porphyria. A Klonopin Medication Guide must be given to the patient each time Klonopin is dispensed, as required by law.
Patients should be instructed to take Klonopin only as prescribed. Physicians are advised to discuss the following issues with patients for whom they prescribe Klonopin:. Inform patients and caregivers that potentially fatal additive effects may occur if Klonopin is used with opioids and not to use such drugs concomitantly unless supervised by a health care provider see WARNINGS: To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing this drug.
Because benzodiazepines have the potential to impair judgment, thinking or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Klonopin therapy does not affect them adversely. Patients, their caregivers, and families should be counseled that AEDs, including Klonopin, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.
This registry is collecting information about the safety of antiepileptic drugs during pregnancy. Patients should be advised to notify their physician if they are breastfeeding or intend to breastfeed during therapy. Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions.
Carcinogenicity studies have not been conducted with clonazepam.