Telotristat Ethyl: (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. Cobicistat is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of diazepam. Diazepam is a CYP2C19 substrate. 2002 Jul;2(4):121-124 Educate patients about the risks and symptoms of respiratory depression and sedation. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. If a mixed opiate agonist/antagonist is initiated for pain in a patient taking a benzodiazepine, use a lower initial dose of the opiate and titrate to clinical response. Sevoflurane: (Moderate) Concomitant administration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Belladonna; Opium: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. The generic name of Diazepam is diazepam. If direct IV access is not feasible, inject slowly via infusion tubing as close as possible to the vein insertion. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If the extended-release oxymorphone tablets are used concurrently with a CNS depressant, use an initial dosage of 5 mg PO every 12 hours. Suvorexant: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. Thalidomide: (Major) The use of benzodiazepine anxiolytics, sedatives, or hypnotics with thalidomide may cause an additive sedative effect and should be avoided. It may be prudent to separate dosing by 2 hours to limit any potential interaction. 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. Monitor for an increase in CNS or respiratory depression. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If bacitracin is administered parenterally during surgery, there may be increased skeletal muscle relaxation, and postoperative use may reinstate neuromuscular blockade. Colchicine; Probenecid: (Moderate) Probenecid may inhibit the metabolism of the benzodiazepines, including those which are metabolized by conjugation (e.g., lorazepam) or oxidation (e.g., midazolam). The CNS depressant effects of topiramate can be potentiated pharmacodynamically by concurrent use of CNS depressant agents such as the benzodiazepines. Besides ethanol, clinicians should use other anxiolytics, sedatives, and hypnotics cautiously with olanzapine. [58123] [61569] Alternately, 5 to 10 mg IV every 10 to 15 minutes as needed up to a maximum of 30 mg. May repeat in 2 to 4 hours, if needed.[43931]. Predictions regarding this interaction can be made based on the metabolic pathways of these drugs. Efavirenz should be used with caution with oxidized benzodiazepines including diazepam. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If parenteral diazepam is used with an opiate agonist, reduce the opiate agonist dosage by at least 1/3. Careers. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including benzodiazepines. Coadministration may increase the risk of CNS depressant-related side effects. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of diazepam. Limit the use of opiate pain medications with benzodiazepines to only patients for whom alternative treatment options are inadequate. If the extended-release tapentadol tablets are used concurrently with a benzodiazepine, use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for decreased pressor effect if these agents are administered concomitantly. If morphine is initiated in a patient taking a benzodiazepine, reduce initial dosages and titrate to clinical response. Diazepam is extensively metabolized to one major active metabolite desmethyldiazepam and two minor active metabolites temazepam (3-hydroxydiazepam) and oxazepam (3-hydroxy-N-diazepam), with half-lives of 30—100 hours, 9.5—12 hours, and 5—15 hours, respectively. The CNS depressant effects of benzodiazepines are additive to ethanol ingestion or other CNS depressants. Diphenhydramine; Naproxen: (Moderate) Coadministration can potentiate the CNS effects (e.g., increased sedation or respiratory depression) of either agent. Because diazepam can cause drowsiness and a decreased level of consciousness, there is a higher risk of falls, particularly in the elderly, with the potential for subsequent severe injuries. 2020 May;61(5):935-943. doi: 10.1111/epi.16506. The dose of any opiate agonist administered with parenteral diazepam should be reduced by at least one-third. Use caution with this combination. Dexmedetomidine: (Moderate) Co-administration of dexmedetomidine with benzodiazepines is likely to lead to an enhancement of CNS depression. Mean total dose: 0.38 mg/kg IV (range: 0.09 to 0.71 mg/kg). In one study of elderly volunteers, half of the patients received DHEA 200 mg/day PO for 2 weeks, followed by a single dose of triazolam 0.25 mg. Triazolam clearance was reduced by close to 30% in the DHEA-pretreated patients vs. the control group; however, the effect of DHEA on CYP3A4 metabolism appeared to vary widely among subjects. Homatropine; Hydrocodone: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. (Moderate) The coadministration of diazepam with antacids results in delayed diazepam absorption due to the fact that antacids delay gastric emptying. In Part I, dose proportionality was demonstrated for the diazepam autoinjector at 5, 10 and 15 mg doses by increases in mean maximum plasma concentration (C(max)), mean area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC(∞)), and mean AUC from time zero to time of last measurable concentration (AUC(last)). Bosentan: (Moderate) Bosentan is an inducer of cytochrome P450 enzymes, specifically the CYP2C9 and CYP3A4 isoenzymes, and may decrease concentrations of drugs metabolized by these enzymes, including diazepam. Because published benzodiazepine dose conversions are based on oral administration, parenteral formulations may not use the same conversion ratio. Mirtazapine: (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. If parental diazepam is used with an opiate agonist, reduce the opiate agonist dosage by at least 1/3. Patients receiving rifampin may require higher doses of diazepam to achieve the desired clinical effect. 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. Intravenous diazepam should be injected slowly to reduce the possibility of local reactions; avoid intraarterial administration or extravasation. Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Rifampin is a potent inducer of the hepatic isoenzyme CYP3A4, one of the pathways responsible for the hepatic metabolism of diazepam. (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. Ethinyl Estradiol; Norgestimate: (Minor) Ethinyl estradiol may inhibit the clearance of benzodiazepines that undergo oxidation, thereby increasing serum concentrations of concomitantly administered benzodiazepines. Mitotane is a strong CYP3A4 inducer; diazepam is predominantly metabolized by CYP2C19, but at high concentrations, CYP3A4 is also involved. 0.2 mg/kg/dose PR once; round dose upward to the next available dosage strength. According to the manufacturer, this interaction is not likely to be clinically relevant. Benzodiazepines may be used in patients with open-angle glaucoma who are receiving appropriate therapy. Administration of esomeprazole with diazepam resulted in a 45% reduced clearance of diazepam. Antacids: (Moderate) The coadministration of diazepam with antacids results in delayed diazepam absorption due to the fact that antacids delay gastric emptying. 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. Educate patients about the risks and symptoms of respiratory depression and sedation. Itraconazole: (Moderate) Monitor for increased and prolonged sedation if coadministration of itraconazole and diazepam is necessary. Omeprazole can increase the plasma concentrations and the elimination half-life of diazepam. Additionally, barbiturates may increase the metabolism of diazepam. Do NOT give emulsion form (Dizac) as IM or SC. The dose proportionality study compared the pharmacokinetics of a single diazepam 10‐mg autoinjector with that of 2 diazepam 10‐mg autoinjectors given simultaneously (20 mg). Co-administration with nicardipine may lead to an increase in serum levels of drugs that are CYP3A4 substrates including diazepam. Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and benzodiazepines. Abrupt discontinuation of diazepam after prolonged use should be avoided. If hydrocodone is initiated in a patient taking a benzodiazepine, reduce initial dosage and titrate to clinical response; for hydrocodone extended-release products, initiate hydrocodone at 20% to 30% of the usual dosage. Diazepam/Dizac/Valium Intramuscular Inj Sol: 1mL, 5mg Diazepam/Dizac/Valium Intramuscular Sol: 1mL, 5mg Diazepam/Dizac/Valium Intravenous Inj Sol: 1mL, 5mg Diazepam/Dizac/Valium Intravenous Sol: 1mL, 5mg Diazepam/Valium Oral Tab: 2mg, 5mg, 10mg The product's dosage form is injection, solution and is administered via intramuscular; intravenous form. Sodium Oxybate: (Severe) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Monitor patients closely for excessive side effects. Henney HR 3rd, Sperling MR, Rabinowicz AL, Bream G, Carrazana EJ. Lower doses of one or both agents may be required. Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Concomitant use of opiate agonists with benzodiazepines may cause respiratory depression, hypotension, profound sedation, and death. 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. Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Moderate) Additive CNS and/or respiratory depression may occur. Prolonged sedation and respiratory depression can occur. 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. 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. Educate patients about the risks and symptoms of respiratory depression and sedation. Monitor closely for signs of reduced diazepam effects. Monitor patients closely. Patients receiving rifampin may require higher doses of diazepam to achieve the desired clinical effect. The dose is 0.2 mg/kg IM. Pharmacists should contact Rx Hope at 1—800—511—2120 for replacement product.Diastat AcuDial is available in the following delivery system units: 2.5 mg, 10 mg, and 20 mg. In addition, diazepam has been reported to have an unpredictable effect on phenytoin serum concentrations (e.g., to increase, decrease, or cause no change in phenytoin serum concentrations). Intravenous doses of 270 mg over 45 minutes and 2,335 mg over a period of 4 days have been reported. Bioavailability and dose proportionality of intramuscular diazepam administered by autoinjector. If parental diazepam is used with an opiate agonist, reduce the mixed opiate agonist/antagonist dosage by at least 1/3. Ivacaftor is a CYP3A inhibitor, and diazepam is a CYP3A substrate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Additive sedation and somnolence may occur. Drugs metabolized by CYP3A4 and CYP2C8/9, such as diazepam, may require dosage adjustments when administered concurrently with rifabutin. Hydroxychloroquine: (Moderate) Caution is warranted with the coadministration of hydroxychloroquine and antiepileptic drugs, such as diazepam. 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.

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