Midazolam dosing

Kales A, Soldatos CR, Bixler EO, et al. Midazolam dose-response studies of effectiveness and rebound insomnia. Pharmacology 1983 26 138-149. 

If CNS depressants are used concomitantly, midazolam dose should be reduced by half or more... 

In a study in 50 women undergoing surgery midazolam markedly potentiated the anaesthetic action of halothane a mean midazolam dose of 278 micrograms/kg reduced the halothane MAC by 51.3%. ... 

Based on the way midazolam interaets with similarly potent inhibitors of CYP3A4, aprepitant may be expeeted to increased the drowsiness and length of sedation and amnesia in patients given midazolam. Consider re-dueing the midazolam dose in patients given aprepitant and monitor the outeome of eoneurrent use earefully. The manufaeturer notes that the potential effeets of inereased levels of other benzodiazepines metabolised via CYP3A4, sueh as alprazolam and triazolam, should be eonsidered if... 

This interaction is of clinical importance be alert for the need to reduce the midazolam dosage in the presence of saquinavir. The authors of the study suggest that continuous intravenous midazolam doses should be reduced by 50%, but do not consider dose adjustments to single intravenous doses necessary. The same precautions would seem appropriate with triazolam. However, the manufacturer of saquinavir contraindicates the concurrent use of oral midazolam and triazolam. They note that no studies have been conducted with ritonavir-boosted saquinavir but that a 3 to 4-fold increase in intravenous midazolam levels would be expected. Use of intravenous midazolam with saquinavir is not contraindicated but they... 

FIGURE 6.7 The PK profiles of midazolam, I -hydroxymid-azolam and 4-hydroxymidazolam from a cynomolgus monkey following a single oral midazolam dose of 0.5 mg/kg [18]. 

The calculated concentrations of the analytes were used to construct a concentration-time profile. Figure 6.7 shows concentration-time profiles of midazolam, I -hydroxymidazolam, and 4-hydroxymidazolam from a cynomolgus monkey following a single oral midazolam dose of 0.5 mg/kg. llie metabolites demonstrated a parallel concentration profile to the parent drug. The profiles were used to determine the pharmacokinetic parameters such as maximum concentration (Cmax), half-life (ti/2), area under the curve (AUC), and so on [18]. 

Midazolam Midazolam is water-soluble and can be administered intravenously, intramuscularly,13 buccally,14,15 and nasally.16,17 At physiologic pH, it becomes more lipophilic and can diffuse into the CNS. Compared to diazepam and lorazepam, it has fewer effects on the respiratory and cardiovascular systems. Its short half-life requires that it be re-dosed... 

A loading dose of 0.2 mg/kg (repeated up to a maximum of 2 mg/kg) followed by a continuous infusion of 0.05 to 2 mg/kg per hour is recommended in RSE.29-31 The dose must be adjusted during prolonged infusions, especially in patients with renal impairment, as the active metabolite can accumulate.32 Breakthrough seizures are common with midazolam infusions and usually respond to a bolus and a 20% increase in the rate. Despite this, tachyphylaxis can occur and the patient should be switched to another agent if seizure activity continues. 

Pentobarbital is commonly loaded at a dose of 10 to 15 mg/kg over 1 to 2 hours, followed by a continuous infusion of 0.5 to 4 mg/kg per hour. Therapy can be tapered off after 12 to 24 hours of seizure control as evident on the EEG.35 One metaanalysis reported a lower incidence of treatment failure with pentobarbital (3%) when compared to midazolam (21%) or propofol (20%), although the risk of hypotension requiring vasopressor therapy was higher when pentobarbital was used.36 This relative efficacy for pentobarbital must be considered... 

Midazolam (Versed) 0.2 mg/kg IV bolus followed by 0.05-0.6 mg/kg per hour continuous infusion Bolus dose may also be given intranasally, buccally, or intramuscularly... 

In vitro kinetic constants obtained from homogenate or whole-cell experiments under controlled conditions were used, and the constants were scaled to the in vivo scenario using appropriate physiological scale factors. Figure 18.6 shows our simulated results for absorption and metabolism of midazolam when dosed with and without grapefruit juice. Midazolam is metabolized by the gut and liver by cytochrome 3A4. Saquinavir is also metabolized in the gut and liver by 3A4, and it is also a substrate for efflux by P-gp. Figure 18.7 shows our simulated results for absorption and metabolism of saquinavir when dosed with and without grapefruit juice. In both cases, it can be seen that the simulation correctly predicts the... 

A benzodiazepine (BZ) should be administered as soon as possible if the patient is actively seizing. Generally one or two IV doses will stop seizures within 2 to 3 minutes. Diazepam, lorazepam, and midazolam are equally effective. If seizures have stopped, a longer-acting anticonvulsant should be given. 

Midazolam has been suggested by some practitioners as the first-line treatment for refractory GCSE. Most patients respond within 1 hour, but the infusion rate should be increased every 15 minutes in those who do not. Tachyphylaxis can develop, and dosing should be guided by EEG response. 

MIDAZOLAM HYDROCHLORIDE INJECTION 5ML MULTI DOSE VIAL 10VIALS/PG 6505012721975 PG 66,54 ... 

General anesthesia - Remifentanil is not recommended as the sole agent in general anesthesia because loss of consciousness cannot be assured and because of a high incidence of apnea, muscle rigidity, and tachycardia. Remifentanil is synergistic with other anesthetics and doses of thiopental, propofol, isoflurane, and midazolam have been... 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Efavirenz (Sustiva) [Antiretroviral/NNRTI] Uses Hiv infxns Action Antiretroviral nonnucleoside RTI Dose Adults. 600 mg/d PO qhs Feds. See package insert avoid high-fat meals Caution [D, ] CDC recommends HIV-infected mothers not breast-feed Contra Component sensitivity Disp Caps SE Somnolence, vivid dreams, dizziness, rash, N/V/D Interactions T Effects W/ ritonavir T effects OF CNS depressants, ergot derivatives, midazolam, ritonavir, simvastatin, triazolam, warfarin X effects W/ carbamazepine, phenobarbital, rifabutin, rifampin, saquinavir, St. John s wort i effects OF amprenavir, carbamazepine, clarithromycin, indinavir, phenobarbital, saquinavir, warfarin may alter effectiveness OF OCPs EMS Concurrent EtOH usage can t CNS d ression OD May cause muscle contractions and adverse CNS effects activated charcoal may be effective... 

---