Knowing when to start anticonvulsant therapy is always a concern. In some cases, the dosages of the CNS depressants may need to be reduced. Diazepam 5 mg-MYL, orange, round,. Tricyclic antidepressants may also lower the seizure threshold leading to pharmacodynamic interactions with anticonvulsant benzodiazepines i. Diazepam is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Clarithromycin could theoretically inhibit the CYP3A4-mediated metabolism of oxidized benzodiazepines, such as diazepam. Cobicistat is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of diazepam.
If you are unsure of the pet's liver status, use phenobarbital and diazepam carefully. The most effective medication that can be used to stop an immediate seizure is diazepam. The most common reason for diazepam failing to stop a seizure is that enough was not given. In general, use 1 ml IV for small dogs 5 - 10 kg , 2 ml IV for medium dogs 10 - 20 kg and 3 ml or more IV for large dogs greater than 20 kg. For cats use 0. If you cannot get IV access give double the IV dose rectally.
Use a red rubber feeding tube inserted about 4 - 6 inches in the rectum and given as a bolus. If after giving a dose of diazepam the seizure does not stop within 2 - 3 minutes IV or 5 min rectal then give another dose. It is not that uncommon to have to give 2 - 4 doses of valium before the seizure stops. It sounds like a lot but it is very safe. If an animal has compromised liver function or you are suspicious of liver disease shunt or cirrhosis etc Once the seizure is stopped you can give a loading dose of phenobarbital or potassium bromide.
If you are going to refer the patient immediately, it might be better to wait on the loading dose so a more accurate exam can be performed. If the patient continues to have seizures after the initial doses of valium, they should be placed on a valium constant rate infusion. Use the amount of valium that it took to stop the seizure and give it over one hour as a CRI.
Patient counseling is important, as cisapride alone does not cause drowsiness or affect psychomotor function. Moderate Clinicians should use citalopram cautiously with diazepam since co-administration with citalopram could potentially result in additive pharmacodynamic effects within the CNS. 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.
Moderate Colesevelam may decrease the absorption of anticonvulsants. To minimize potential for interactions, consider administering oral anticonvulsants at least 1 hour before or at least 4 hours after colesevelam. Theoretically, similar pharmacokinetic effects could be seen with diazepam. Subsequent treatment with CYP3A substrates, such as diazepam, may be initiated no sooner than 1 week after completion of conivaptan therapy.
Moderate Monitor for increased diazepam-related adverse reactions including sedation and respiratory depression if coadministration with crizotinib is necessary. Data indicate that these compounds influence the pharmacokinetics of diazepam and may lead to increased and prolonged sedation. Moderate Dalfopristin; quinupristin is a major inhibitor of cytochrome P 3A4 and may decrease the elimination of drugs metabolized by this enzyme including diazepam.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Moderate Systemic exposure of diazepam and its metabolite, nordiazepam, were decreased when a single 2 mg dose was administered concurrently with ombitasvir; paritaprevir; ritonavir. If these drugs are given together, monitor for reduced diazepam efficacy; consider increasing the diazepam dose if clinically needed. Moderate Delavirdine is a potent inhibitor of the CYP3A4 and increased plasma concentrations of drugs extensively metabolized by this enzyme, such as diazepam, should be expected with concurrent use of delavirdine.
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 diazepam, 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 Coadministration of diazepam and digoxin has been reported to increase the half-life of digoxin due to reduced urinary excretion of digoxin. Consider measuring serum digoxin concentrations before initiating diazepam. Continue monitoring during concomitant treatment and decrease the digoxin dose as necessary. As a result, diazepam is susceptible to interactions with drugs that inhibit these hepatic enzymes, such as diltiazem.
Moderate Disulfiram may compete for the binding sites on hepatic cytochrome P CYP with benzodiazepines that undergo oxidative metabolism such as diazepam, thereby slowing the metabolism of diazepam and increasing its steady-state plasma concentrations. Moderate Use caution if the use of benzodiazepines are necessary with dronabinol, and monitor for additive dizziness, confusion, somnolence, and other CNS effects. Diazepam 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 Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines.
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 diazepam. In addition, efavirenz inhibits CYP2C9 in vitro; diazepam is also metabolized via this isoenzyme. Monitor patients closely for excessive side effects. Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: Moderate Administering diazepam with elbasvir; grazoprevir may result in elevated diazepam 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 Monitor for withdrawal symptoms or lack of efficacy if coadministration of diazepam with enzalutamide is necessary. Moderate Erythromycin may inhibit the CYP3A4-mediated metabolism of oxidized benzodiazepines, such as diazepam. Monitor patient clinically for enhanced response from diazepam. Moderate The effect of escitalopram on benzodiazepine metabolism is not known.
The combined administration of citalopram with triazolam has not been reported to significantly affect the pharmacokinetics of either drug. However, clinicians should use citalopram or escitalopram cautiously with alprazolam or diazepam since coadministration could potentially result in additive pharmacodynamic effects within the CNS.
Since esomeprazole is an inhibitor of the CYP2C19 isozyme, plasma levels of diazepam may increase. According to the manufacturer, this interaction is not likely to be clinically relevant. However, it would be prudent to monitor patients more closely, particularly if other CNS depressants are prescribed. The manufacturer reports that use of diazepam does not appear to alter the pharmacokinetic profile of esomeprazole. 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: Moderate Ethotoin is a hepatic enzyme inducer and thus may accelerate the metabolism of several other anticonvulsants, and can theoretically add to the CNS-depressant effects of other CNS depressants, including the anxiolytics, sedatives, and hypnotics which may be used concomitantly for seizure control or as psychotropics.
Ethotoin should be used cautiously with diazepam, as decreased diazepam serum concentrations may be seen when coadministered with phenytoin. In addition, diazepam has been reported to have an unpredictable effect on phenytoin serum concentrations e. Since definitive controlled trial data are lacking, phenytoin concentrations should be monitored more closely when diazepam is added or discontinued. Coadministration of etravirine and diazepam, a CYP2C19 substrate, may result in increased diazepam plasma concentrations.
Coadminister these drugs with caution, closely monitoring the patient for adverse effects related to diazepam; a decrease in diazepam dose may be needed. Concomitant use of fenofibric acid with CYP2C19 substrates, such as diazepam, has not been formally studied. Fenofibric acid may theoretically increase plasma concentrations of CYP2C19 substrates and could lead to toxicity for drugs that have a narrow therapeutic range. Monitor the therapeutic effect of diazepam during coadministration with fenofibric acid.
Moderate Fluconazole could theoretically inhibit CYP3A4 metabolism of oxidized benzodiazepines, such as diazepam. Coadminister these drugs with caution. 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. Fluoxetine impairs both of these pathways at therapeutic doses.
This can result in substantial increases in the half-life of diazepam, and the psychomotor and physiological response may be altered. 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.
Major Fluvoxamine decreases the oxidative hepatic metabolism of diazepam. Monitor the patient closely for sedation, CNS depression, and prolonged benzodiazepine effects. Dose reduction may be necessary. N-Desmethyldiazepam AUC values were also significantly increased. These data suggest the interaction is likely to have clinical significance.
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 Phenytoin is a hepatic enzyme inducer and thus may accelerate the metabolism of several other anticonvulsants, and can theoretically add to the CNS-depressant effects of other CNS depressants, including the anxiolytics, sedatives, and hypnotics which may be used concomitantly for seizure control or as psychotropics.
Fosphenytoin should be used cautiously with clonazepam and diazepam, as decreased clonazepam or diazepam serum concentrations may be seen. Major Orally-administered diazepam may interact with grapefruit juice. Grapefruit juice has been shown to increase diazepam peak serum concentrations Cmax and exposure AUC by 1. Grapefruit juice contains furano-coumarins and certain flavonoids which may inhibit the CYP3A4 isozyme.
Increased sedation or other CNS effects may be possible. To prevent this interaction, it would be prudent to avoid taking oral diazepam with grapefruit juice. 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 diazepam.
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 Imatinib is a potent inhibitor of cytochrome P 3A4 and may increase concentrations of other drugs metabolized by this enzyme including diazepam. Moderate Concomitant use of isavuconazonium with diazepam may result in increased serum concentrations of diazepam. Diazepam is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme.
Caution and close monitoring are advised if these drugs are used together. Moderate Concurrent use of isoniazid, INH and diazepam can increase serum concentrations of diazepam due to alterations in the half-life and clearance of diazepam. Although patient response to diazepam has not been reported, patients should be observed for signs of altered diazepam effects if isoniazid therapy is initiated or discontinued. Major Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4, one of the pathways responsible for the hepatic metabolism of diazepam.
Patients receiving rifampin may require higher doses of diazepam to achieve the desired clinical effect. Moderate Monitor for increased and prolonged sedation if coadministration of itraconazole and diazepam is necessary. A dose reduction of diazepam may be necessary. Moderate Use caution when administering ivacaftor and diazepam concurrently because patients may be at increased risk for adverse effects from diazepam. Diazepam is also metabolized by CYP2C19, which is not affected by ivacaftor.
Co-administration of ivacaftor with midazolam, another CYP3A substrate, increased midazolam exposure by 1. Kava Kava, Piper methysticum: Major The German Commission E warns that any substances that act on the CNS, including psychotropic agents, may interact with kava kava. While the interactions can be pharmacodynamic in nature, kava kava has been reported to inhibit many CYP isozymes i. Patients on benzodiazepine therapy should avoid concomitant administration of kava kava.
Patients should discuss the use of herbal supplements with their health care professional prior to consuming kava kava and should not abruptly stop taking their prescribed medications. Moderate Ketoconazole could theoretically inhibit CYP3A4 metabolism of oxidized benzodiazepines such as diazepam. Moderate Plasma concentrations of diazepam could be increased when administered concurrently with letermovir.
The magnitude of this interaction may be elevated in patients who are also receiving cyclosporine. If these drugs are given together, closely monitor for reduced diazepam efficacy and diazepam-related adverse events. Diazepam is a substrate of CYP3A4. Letermovir is a moderate inhibitor of CYP3A4. Moderate Concomitant administration of benzodiazepines with CNS-depressant drugs, including opiate agonists, can potentiate the CNS effects of either agent.
Moderate Concurrent use of many CNS active drugs, including benzodiazepines, with levomilnacipran has not been evaluated by the manufacturer. Therefore, caution is advisable when combining anxiolytics, sedatives, and hypnotics or other psychoactive medications with levomilnacipran. If seizures occur, amphetamine discontinuation may be necessary. Moderate Because lithium has the potential to impair cognitive and motor skills, caution is advisable during concurrent use of other medications with centrally-acting effects including anxiolytics, sedatives, and hypnotics.
Minor Although loratadine is considered a 'non-sedating' antihistamine, dose-related sedation has been noted. For this reason, it would be prudent to monitor for drowsiness when used concurrently with other CNS depressants like benzodiazepines. Monitor patients for adverse effects of diazepam, such as CNS effects and respiratory depression.
In vitro, therapeutic doses of luliconazole inhibit the activity of CYP2C19 and CYP3A4 and small systemic concentrations may be noted with topical application, particularly when applied to patients with moderate to severe tinea cruris. No in vivo drug interaction trials were conducted prior to the approval of luliconazole. Moderate Lumacaftor; ivacaftor may reduce the efficacy of diazepam by decreasing its systemic exposure.
If used together, monitor patients closely for loss of diazepam efficacy; a diazepam dosage adjustment may be required to obtain the desired therapeutic effect. Moderate Due to the CNS effects of lurasidone, caution should be used when lurasidone is given in combination with other centrally acting medications such as anxiolytics, sedatives, and hypnotics, including benzodiazepines. Minor Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as benzodiazepines.
Caution should be exercised when using these agents concurrently. Moderate Benzodiazepines or other CNS depressants should be combined cautiously with maprotiline because they could cause additive depressant effects and possible respiratory depression or hypotension. The combination of benzodiazepines and maprotiline is commonly used clinically and is considered to be safe as long as patients are monitored for excessive adverse effects from either agent.
Maprotiline may lower the seizure threshold, so when benzodiazepines are used for anticonvulsant effects the patient should be monitored for desired clinical outcomes. Moderate Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control.
Monitoring of the anticonvulsant serum concentration is recommended. Dosage adjustments may be required during and after therapy with mefloquine. Major Use caution when combining melatonin with the benzodiazepines; when the benzodiazepine is used for sleep, co-use of melatonin should be avoided. In animal studies, melatonin has been shown to increase benzodiazepine binding to receptor sites.
In one case report, a benzodiazepine-dependent woman with an 11 year history of insomnia weaned and discontinued her benzodiazepine prescription within a few days without rebound insomnia or apparent benzodiazepine withdrawal when melatonin was given. In another case report, the ingestion of excessive melatonin along with normal doses of chlordiazepoxide and an antidepressant resulted in lethargy and short-term amnestic responses.
Both cases suggest additive pharmacodynamic effects. In a clinical trial, there was clear evidence for a transitory pharmacodynamic interaction between melatonin and another hypnotic agent one hour following co-dosing. Concomitant administration resulted in increased impairment of attention, memory and coordination compared to the hypnotic agent alone. Use of more than one agent for hypnotic purposes may increase the risk for over-sedation, CNS effects, or sleep-related behaviors.
Be alert for unusual changes in moods or behaviors. Patients reporting unusual sleep-related behaviors likely should discontinue melatonin use. Moderate CNS depression can be increased when mepenzolate is combined with other CNS depressants such as skeletal muscle relaxants. Moderate Concomitant administration of benzodiazepines with meprobamate can potentiate the CNS effects e. Minor Oral contraceptives can increase the effects of diazepam because they 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 diazepam. Major Concurrent use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. If concurrent use is necessary, use the lowest effective dose and minimum duration possible.
If methadone is initiated for pain in an opioid-naive patient taking a benzodiazepine, use an initial methadone dose of 2. If a benzodiazepine is prescribed for an indication other than epilepsy in a patient taking an opiate agonist, use a lower initial benzodiazepine dose and titrate to response. In patients treated with methadone 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 during methadone maintenance treatment. Moderate Concurrent use of benzodiazepines and other CNS active medications including skeletal muscle relaxants, can potentiate the CNS effects of either agent. Moderate CNS depression can be increased when methscopolamine is combined with other CNS depressants such as any anxiolytics, sedatives, and hypnotics. Minor Combined use of metoclopramide and other CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase possible sedation.
Other drugs that may also cause drowsiness, such as benzodiazepines, should be used with caution. Moderate The concomitant administration of metyrosine with benzodiazepines can result in additive sedative effects. Moderate Concurrent use of many CNS-active drugs with milnacipran or levomilnacipran has not been evaluated by the manufacturer. Therefore, caution is advisable when combining anxiolytics, sedatives, and hypnotics or other psychoactive medications with these medications.
Minor Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as benzodiazepines. Moderate Consistent with the pharmacology of mirtazapine and the drug's side effect profile, additive effects may occur with other CNS-active agents, including benzodiazepines. Major Use caution if mitotane and diazepam are used concomitantly, and monitor for decreased efficacy of diazepam and a possible change in dosage requirements.
Coadministration may result in decreased plasma concentrations of diazepam. Additionally, mitotane can cause sedation, lethargy, vertigo, and other CNS adverse reactions; additive CNS effects may occur initially when mitotane is given concurrently with diazepam. Moderate Modafinil has demonstrated an inhibition of the CYP2C19 hepatic microsomal isoenzyme at pharmacologically relevant concentrations. Drugs that are largely eliminated via CYP2C19 metabolism, such as diazepam, may have prolonged elimination upon co-administration of modafinil.
Moderate Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required when benzodiazepines are used in the treatment of epilepsy. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. For extended-release tablets, start with morphine 15 mg PO every 12 hours, and for extended-release capsules, start with 30 mg PO every 24 hours or less.
Moderate Concomitant use of nabilone with other CNS depressants can potentiate the effects of nabilone on respiratory depression. In vitro, the metabolism of paclitaxel is inhibited by diazepam but concentrations used exceeded those found in vivo following normal therapeutic doses. As a result, diazepam is susceptible to interactions with drugs that inhibit these hepatic enzymes including nefazodone. Moderate Nevirapine may induce the metabolism of certain benzodiazepines that are metabolized through the cytochrome P system, including diazepam.
Co-administration with nicardipine may lead to an increase in serum levels of drugs that are CYP3A4 substrates including diazepam. Minor Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as benzodiazepines. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with benzodiazepines.
Moderate Coadministration of oritavancin and diazepam may result in increases or decreases in diazepam exposure and may increase side effects or decrease efficacy of diazepam. If these drugs are administered concurrently, monitor the patient for signs of toxicity or lack of efficacy. Moderate Additive CNS depression may occur when oxybutynin is used concomitantly with other CNS-depressant drugs, including anxiolytics, sedatives, and hypnotics. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, use an initial dosage of 5 mg PO every 12 hours.
Moderate Drugs that can cause CNS depression, if used concomitantly with paliperidone, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when paliperidone is given in combination with other centrally-acting medications including anxiolytics, sedatives, and hypnotics, buprenorphine, butorphanol, dronabinol, THC, ethanol, nabilone, nalbuphine, opiate agonists, and pentazocine.
Moderate Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation. Coadministration of pazopanib and diazepam, a CYP3A4 substrate, may cause an increase in systemic concentrations of diazepam. Use caution when administering these drugs concomitantly. Major A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents.
Dosage adjustments of anticonvulsants may be necessary during simultaneous use of these drugs. Moderate Patients taking benzodiazepines with perampanel may experience increased CNS depression. Monitor patients for adverse effects; dose adjustment of either drug may be necessary. Moderate Phenothiazines are CNS depressant drugs that may have cumulative effects when administered concurrently and they should be used cautiously with anxiolytic, sedative, and hypnotic type drugs, such as the benzodiazepines.
Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension. Additionally, sleep-related behaviors, such as sleep-driving, are more likely to occur during concurrent use of other CNS depressants than with sedatives alone. Monitor for additive effects, unusual moods or behaviors, and warn about the potential effects to driving and other activities.
The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Concurrent use of topiramate and benzodiazepines associated with thrombocytopenia e. Phenytoin should be used cautiously with diazepam, as decreased diazepam serum concentrations may be seen. Moderate Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including benzodiazepines.
While more study is needed, benzodiazepine-induced CNS sedation and other adverse effects might be increased in some individuals if DHEA is co-administered. Moderate Pregabalin can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Moderate Probenecid may inhibit the metabolism of the benzodiazepines, including those which are metabolized by conjugation e. In addition, pretreatment with probenecid shortened the induction time 85 vs.
Patients receiving alprazolam therapy should be monitored for signs of altered benzodiazepine response when probenecid is initiated or discontinued. Minor CNS depressants benzodiazepines can potentiate the CNS depression caused by procarbazine therapy, so these drugs should be used together cautiously. Major CYP3A4 inhibitors, such as protease inhibitors, may reduce the metabolism of diazepam and increase the potential for benzodiazepine toxicity.
Prolonged sedation and respiratory depression can occur. A decrease in the diazepam dose may be needed Quetiapine: Moderate Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects. Moderate Ramelteon is a sleep-promoting agent; therefore, additive pharmacodynamic effects are possible when combining ramelteon with benzodiazepines or other miscellaneous anxiolytics, sedatives, and hypnotics.
Pharmacokinetic interactions have been observed with the use of zolpidem. Ramelteon use with hypnotics of any kind is considered duplicative therapy and these drugs are generally not co-administered. Moderate CYP3A4 inhibitors, like ranolazine, may reduce the metabolism of diazepam and increase the potential for benzodiazepine toxicity.
Moderate The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including buprenorphine, butorphanol, dronabinol, THC, nabilone, nalbuphine, and anxiolytics, sedatives, and hypnotics. Use these drugs cautiously with MAOIs; warn patients to not drive or perform other hazardous activities until they know how a particular drug combination affects them.
In some cases, the dosages of the CNS depressants may need to be reduced. Moderate Use caution if coadministration of ribociclib with diazepam is necessary, as the systemic exposure of diazepam may be increased resulting in increase in treatment-related adverse reactions; adjust the dose of diazepam if necessary. Ribociclib is a CYP3A4 inhibitor in vitro at clinically relevant concentrations. Patients receiving these drugs together may require higher doses of diazepam to achieve the desired clinical effect.
In addition, patients should be monitored closely for signs of reduced diazepam effects if a rifapentine is added. Moderate Due to the primary CNS effects of risperidone, caution should be used when risperidone is given in combination with other centrally acting medications including anxiolytics, sedatives, and hypnotics. Moderate Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Major Concomitant use of rotigotine with other CNS depressants, such as benzodiazepines, can potentiate the sedative effects of rotigotine. Moderate Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event.
Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as benzodiazepines. Moderate Sincalide-induced gallbladder ejection fraction may be affected by benzodiazepines. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
Moderate Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. Severe Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate GHB has the potential to impair cognitive and motor skills. For example, the concomitant use of barbiturates and benzodiazepines increases sleep duration and may contribute to rapid onset, pronounced CNS depression, respiratory depression, or coma when combined with sodium oxybate.
John's Wort, Hypericum perforatum: It would be prudent to avoid co-administration of St. John's Wort with diazepam. Benzodiazepines that are not metabolized by CYP3A4 such as oxazepam or lorazepam may be alternatives if a benzodiazepine is required in combination with St. Moderate CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant.
A reduction in dose of the CNS depressant may be needed in some cases. These agents include the benzodiazepines. Major Tacrine is an inhibitor of CYP1A2 and could potentially increase plasma concentrations of diazepam. However, clinical documentation of interactions is lacking. If tapentadol is initiated in a patient taking a benzodiazepine, a reduced initial dosage of tapentadol is recommended.
If the extended-release tapentadol tablets are used concurrently with a benzodiazepine, use an initial tapentadol dose of 50 mg PO every 12 hours. Moderate Teduglutide may increase absorption of benzodiazepines or other psychotropic agents because of it's pharmacodynamic effect of improving intestinal absorption. In studies with teduglutide, one of the subjects was receiving concomitant treatment with prazepam and experienced dramatic deterioration in mental status progressing to coma during her first week of teduglutide therapy.
Both drugs were discontinued, and the coma resolved 5 days later. Careful monitoring and possible dose adjustment of the psychotropic agent is recommended. Moderate Close clinical monitoring is advised when administering diazepam with telaprevir due to an increased potential for diazepam-related adverse events. If diazepam dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Diazepam is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme.
Moderate Diazepam is metabolized by oxidative metabolism which may be decreased by telithromycin and caution is recommended. Patients should be monitored for needed dosage adjustments in accordance with response. Moderate Use caution if coadministration of telotristat ethyl and diazepam is necessary, as the systemic exposure of diazepam may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of diazepam; consider increasing the dose of diazepam if necessary.
Moderate Concurrent use of tetrabenazine and drugs that can cause CNS depression, such as benzodiazepines, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, dizziness, and orthostatic hypotension. Major The use of benzodiazepine anxiolytics, sedatives, or hypnotics with thalidomide may cause an additive sedative effect and should be avoided. Thalidomide frequently causes drowsiness and somnolence. Dose reductions may be required.
Patients should be instructed to avoid situations where drowsiness may be a problem and not to take other medications that may cause drowsiness without adequate medical advice. Moderate Aminophylline has been reported to counteract the pharmacodynamic effects of diazepam. A proposed mechanism is competitive binding of aminophylline to adenosine receptors in the brain. Whether a similar interaction occurs with other benzodiazepines is not known.
If aminophylline therapy is initiated or discontinued, monitor the clinical response to benzodiazepines. Moderate Theophylline has been reported to counteract the pharmacodynamic effects of diazepam. A proposed mechanism is competitive binding of theophylline to adenosine receptors in the brain. If theophylline therapy is initiated or discontinued, monitor the clinical response to benzodiazepines.
Moderate Thiothixene can potentiate the CNS-depressant action of other drugs such as benzodiazepines. Moderate Because of the possible additive effects of drugs that depress the central nervous system, benzodiazepines should be used with caution in patients receiving tiagabine. Moderate Tobacco smoke contains polycyclic aromatic hydrocarbons that induce hepatic CYP microsomal enzymes; tobacco smoking may thus increase the clearance of selected drugs.
Tobacco smoke does not affect the metabolism of the parent drug diazepam, but does accelerate the metabolism of its major active metabolite, N-desmethyldiazepam, by up to 3-fold. Moderate Verapamil inhibits CYP3A4 metabolism, and therefore may inhibit the metabolism of oxidized benzodiazepines, including diazepam. Moderate Trazodone can lower the seizure threshold of anticonvulsants, although the overall risk is low at therapeutic doses.
Patients may require increased concentrations of anticonvulsants to achieve equivalent effects if trazodone is added. Moderate Concomitant administration of benzodiazepines with CNS-depressant drugs, such as tricyclic antidepressants, can potentiate the CNS effects of either agent. Tricyclic antidepressants may also lower the seizure threshold leading to pharmacodynamic interactions with anticonvulsant benzodiazepines i. The significance of this interaction has not been described; therefore, patients should be monitored closely for symptoms of tricyclic toxicity during coadministration of these agents with alprazolam.
Moderate CNS depressants, such as anxiolytics, sedatives, and hypnotics, can increase the sedative effects of trihexyphenidyl. Moderate The concurrent use of trimethobenzamide with other medications that cause CNS depression, like the benzodiazepines, may potentiate the effects of either trimethobenzamide or the benzodiazepine.
Moderate Coadministration of diazepam and valdecoxib may result in increased exposure to diazepam. Although the magnitude of the change in diazepam exposure does not necessitate a dosage change, patients may experience increased sedative effects due to the increase in diazepam exposure. Major Any substances that act on the CNS, including psychoactive drugs and drugs used as anesthetic adjuvants e.
The valerian derivative, dihydrovaltrate, binds at barbiturate binding sites; valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain; the non-volatile monoterpenes valepotriates have sedative activity. These interactions are probably pharmacodynamic in nature. There is a possibility of interaction with valerian at normal prescription dosages of anxiolytics, sedatives, and hypnotics including barbiturates and benzodiazepines.
Patients taking medications such as tricyclic antidepressants, lithium, MAOIs, skeletal muscle relaxants, SSRIs and serotonin norepinephrine reuptake inhibitors e. Patients should not abruptly stop taking their prescribed psychoactive medications. Valproic Acid, Divalproex Sodium: Minor The administration of valproic acid to patients receiving diazepam can cause an increase in diazepam serum concentrations. If therapeutic effect is altered in patients receiving these medications, an alternative anticonvulsant should be instituted.
Moderate Vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as diazepam, could be expected with concurrent use. Use caution, and monitor therapeutic effects of diazepam when coadministered with vemurafenib. Moderate Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Caution should be used when vigabatrin is given in combination with benzodiazepines. Moderate Due to the CNS effects of vilazodone, caution should be used when vilazodone is given in combination with other centrally acting medications such as the benzodiazepines. Moderate In vitro data indicate that zafirlukast inhibits the CYP2C9 and CYP3A4 isoenzymes at concentrations close to the clinically achieved total plasma concentrations. Until more clinical data are available, zafirlukast should be used cautiously in patients stabilized on drugs metabolized by CYP3A4, such as diazepam.
Moderate In premarketing studies, zaleplon potentiated the CNS effects of ethanol, imipramine, and thioridazine for at least 2 to 4 hours. Other drugs that may have additive CNS effects with zaleplon but have not been studied include benzodiazepines. As a result, diazepam is susceptible to interactions with drugs that inhibit these hepatic enzymes.
Zileuton may inhibit the metabolism of diazepam. While diazepam clearance may be inhibited, diazepam pharmacodynamics are not always affected. Consider dose reduction of diazepam if clinically indicated. Monitor for an increase in CNS or respiratory depression. Moderate Ziprasidone has the potential to impair cognitive and motor skills. Moderate Concomitant administration of benzodiazepines with zolpidem can potentiate the CNS effects e.