BOXED WARNING
Adult and Pediatrics
Intravenous midazolam HCl has been associated with respiratory depression and respiratory arrest, especially when used for sedation in noncritical care settings. In some cases, where this was not recognized promptly and treated effectively, death or hypoxic encephalopathy has resulted. Intravenous midazolam HCl should be used only in hospital or ambulatory care settings, including physicians’ and dental offices, that provide for continuous monitoring of respiratory and cardiac function, ie, pulse oximetry. Immediate availability of resuscitative drugs and age- and size-appropriate equipment for bag/valve/mask ventilation and intubation, and personnel trained in their use and skilled in airway management should be assured (see WARNINGS). For deeply sedated pediatric patients, a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure.
The initial intravenous dose for sedation in adult patients may be as little as 1 mg, but should not exceed 2.5 mg in a normal healthy adult. Lower doses are necessary for older (over 60 years) or debilitated patients and in patients receiving concomitant narcotics or other central nervous system (CNS) depressants. The initial dose and all subsequent doses should always be titrated slowly; administer over at least 2 minutes and allow an additional 2 or more minutes to fully evaluate the sedative effect. The use of the 1 mg/mL formulation or dilution of the 1 mg/mL or 5 mg/mL formulation is recommended to facilitate slower injection. Doses of sedative medications in pediatric patients must be calculated on a mg/kg basis, and initial doses and all subsequent doses should always be titrated slowly. The initial pediatric dose of midazolam HCl for sedation/anxiolysis/amnesia is age, procedure and route dependent (see DOSAGE AND ADMINISTRATION for complete dosing information).
Neonates
Midazolam HCl should not be administered by rapid injection in the neonatal population. Severe hypotension and seizures have been reported following rapid IV administration, particularly with concomitant use of fentanyl (see DOSAGE AND ADMINISTRATION for complete information).
|
| |
SUMMARY
Midazolam Hydrochloride Injection
CIV
Rx only
Midazolam HCl is a water-soluble benzodiazepine available as a sterile, nonpyrogenic parenteral dosage form for intravenous or intramuscular injection. Each mL contains midazolam hydrochloride equivalent to 1 mg or 5 mg midazolam compounded with 0.8% sodium chloride and 0.01% edetate disodium, with 1% benzyl alcohol as preservative; the pH is adjusted to 2.9-3.7 with hydrochloric acid and, if necessary, sodium hydroxide. Midazolam is a white to light yellow crystalline compound, insoluble in water. The hydrochloride salt of midazolam, which is formed in situ, is soluble in aqueous solutions.
Midazolam hydrochloride injection is indicated:
· intramuscularly or intravenously for preoperative sedation/anxiolysis/amnesia;
· intravenously as an agent for sedation/anxiolysis/amnesia prior to or during diagnostic, therapeutic or endoscopic procedures, such as bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures either alone or in combination with other CNS depressants;
· intravenously for induction of general anesthesia, before administration of other anesthetic agents. With the use of narcotic premedication, induction of anesthesia can be attained within a relatively narrow dose range and in a short period of time. Intravenous midazolam can also be used as a component of intravenous supplementation of nitrous oxide and oxygen (balanced anesthesia);
· continuous intravenous infusion for sedation of intubated and mechanically ventilated patients as a component of anesthesia or during treatment in a critical care setting.
Midazolam HCl is associated with a high incidence of partial or complete impairment of recall for the next several hours (see CLINICAL PHARMACOLOGY).
|
NEWS HIGHLIGHTS
Published Studies Related to Midazolam Injection (Midazolam)
Midazolam as an antiemetic in patients receiving epidural morphine for postoperative pain relief. [2009.07]
PURPOSE: Epidural morphine has been associated with a significant incidence of postoperative nausea and vomiting (PONV). The authors have evaluated the prophylactic effects of midazolam in preventing nausea and vomiting following epidural morphine for postoperative pain control... CONCLUSION: The authors conclude that low-dose midazolam infusion is effective in the prevention of nausea, vomiting, and pruritus following epidural morphine for postoperative pain control.
Effects of intravenous small dose ketamine and midazolam on postoperative pain following knee arthroscopy. [2009.07]
BACKGROUND: The aim of this randomized, double blind, controlled study was to assess the effect of intravenous coadministration of small dose midazolam with ketamine on postoperative pain and spinal block level... CONCLUSION: Ketamine improved the postoperative pain patient satisfaction, increased the maximal sensory level, and was associated with lower sedation scores in the first 15 minutes after administration. Group I was also associated with decreased total meperidine consumption and delayed the time to first recue analgesic administration. Coadministration of ketamine and midazolam did not provide any further benefit over ketamine alone.
Effects of oral posaconazole on the pharmacokinetic properties of oral and intravenous midazolam: a phase I, randomized, open-label, crossover study in healthy volunteers. [2009.02]
BACKGROUND: Like itraconazole and ketoconazole, posaconazole, a broad-spectrum oral triazole antifungal, inhibits the activity of the cytochrome P450 (CYP) isozyme 3A4. Midazolam, a short-acting benzodiazepine, is metabolized by CYP3A4. Potential drug interactions can be expected in patients who are concurrently receiving inhibitors and substrates of CYP3A4 (eg, ketoconazole, posaconazole) and benzodiazepines (eg, midazolam). Because of the potential for drug interactions, it is important to determine the effects of posaconazole on the pharmacokinetic properties of midazolam. OBJECTIVE: The aim of this study was to compare the effects of oral administration of posaconazole versus ketoconazole on the pharmacokinetic properties of orally and intravenously administered midazolam... CONCLUSIONS: The results from this study in a small, all-white population of healthy volunteers suggest that posaconazole was a potent inhibitor of CYP3A4, but to a lesser extent than was ketoconazole. Monitoring patients for adverse events, the need for dose adjustments, or both during coadministration with posaconazole may be warranted in patients being treated with benzodiazepines that are predominantly metabolized through CYP3A4 (eg, midazolam).
Effect of intravenous flumazenil on oral midazolam pharmacokinetics and pharmacodynamics for use as a cytochrome P450 3A probe. [2009.02]
Phenotyping intestinal and hepatic cytochrome P450 (CYP) 3A activity with oral midazolam can be limited by midazolam-induced central nervous system (CNS) side effects. Determining methods to minimize CNS side effects optimizes use of midazolam as a CYP3A probe. OBJECTIVE: The objective of this study was to determine the effect of intravenous (i.v.) flumazenil on midazolam apparent oral clearance (a surrogate marker of CYP3A activity). Midazolam pharmacodynamics were also evaluated... CONCLUSION: i.v. flumazenil can be used in conjunction with oral midazolam for CYP3A phenotyping.
Comparative study of postoperative analgesia and sedation after upper abdominal surgery with thoracic epidural administration of bupivacaine with/without midazolam. [2009.01]
Currently continuous epidural administration of local anaesthetics with opioids is widely used for postoperative analgesia. To avoid the side-effects of opioids a drug that can replace opioids is most welcome...
Clinical Trials Related to Midazolam Injection (Midazolam)
Clinical Trial of Oral Midazolam in Pediatric Endoscopy [Completed]
The objective of our study was to compare the safety and efficacy of oral midazolam during
pediatric endoscopy.
Safety and Efficacy of Oral Midazolam for Perioperative Anxiety Relief of Patients Undergoing Mohs Micrographic Surgery [Active, not recruiting]
Midazolam is an approved sedative medication used for medical procedures. This study is
being done to document the safety and efficacy of midazolam in improving anxiety, heart rate,
and blood pressure in the setting of Mohs micrographic surgery performed for the treatment of
skin cancer (basal cell carcinoma or squamous cell carcinoma). Midazolam may make a patient
relaxed and sleepy. It also has beneficial effects on blood pressure, which may improve
surgical results. These effects last for about 2 hours.
If you agree to be in the study and there exist no contraindications to your participation in
this study, you will be asked to complete three brief questionnaires as well as have blood
pressure and other vital signs checked during surgery. Participation in the study does not
require a follow up visit, blood work, or other invasive procedures.
The Efficacy of Midazolam & Ketamine Versus Midazolam & Fentanyl for Sedation in Ambulatory Colonoscopies [Completed]
Providing adequate sedation and analgesia is an integral part of the practice of colonoscopy
procedure.
There are various protocols and methods used to prevent discomfort and alleviate pain.
Conscious sedation is one of the options recommended by the American Society for
Gastrointestinal Endoscopy, although the choice of the exact protocol is left to the
physician's discretion.
This study will attempt to recommend a preferred protocol based on a double blind randomized
prospective method.
The efficacy of midazolam and ketamine will be compared to the efficacy of midazolam and
fentanyl for sedation in ambulatory colonoscopies.
The results will be compiled from objective data and patient and physician interviews.
Remifentanil and Propofol Versus Fentanyl and Midazolam for Sedation During Therapeutic Hypothermia. A Randomised, Controlled Trial [Enrolling by invitation]
The aim of this study is to increase knowledge about drug properties and effects during
therapeutic hypothermia. The primary end point of this study is the time from termination of
sedation to extubation in patients treated with therapeutic hypothermia, after treatment with
the combination remifentanil and propofol versus that of fentanyl and midazolam.
Clonidine Versus Midazolam for Premedication [Completed]
alpha2-agonists like clonidine offer several useful effects that make these drugs an
interesting alternative to benzodiazepines for pharmacological premedication. We therefore
sought to determine the effect of pre-anesthetic medication with clonidine vs. midazolam in a
randomized, double-blind, placebo controlled study. Effects of pre-anesthetic medication were
assessed on (1) bispectral index (BIS),(2) sedation score and visual analog scales for
anxiety and pain, (3) neuropsychologic tests to assess cognitive function and (4) circulating
stress hormones.
|
|
|
|
Page last updated: 2009-10-20
|
