Midazolam Hydrochloride Syrup
"FDA is recommending health care professionals discontinue prescribing and dispensing prescription combination drug products that contain more than 325 milligrams (mg) of acetaminophen per tablet, capsule or other dosage unit. There are no"...
Midazolam Hydrochloride Syrup
The distribution of adverse events occurring in patients evaluated in a randomized, double-blind, parallel-group trial are presented in Tables 5 and 6 by body system in order of decreasing frequency: for the pre-medication period (eg, sedation period prior to induction of anesthesia) alone, see Table 5; for over the entire monitoring period including premedication, anesthesia and recovery, see Table 6.
The distribution ofadverse events occurring during the premedication period, before inductionof anesthesia, is presented in Table 5. Emesis which occurred in 31/397 (8%) patients over the entire monitoring period, occurred in 3/397 (0.8%) of patients during the premedication period (from midazolamadministration to mask induction). Nausea, which occurred in 14/397 (4%) patients over the entire monitoring period (premedication, anesthesia and recovery), occurred in 2/397 (0.5%) patients during thepremedicationperiod.
This distribution of all adverse events occurring in ≥ 1% of patients over the entire monitoring period are presented in Table 6. For the entire monitoring period (premedication, anesthesia and recovery), adverse events were reported by 82/397 (21%) patients who received midazolam overall. The most frequently reported adverse events were emesis occurring in 31/397 (8%) patients and nausea occurring in 14/397 (4%) patients. Most of these gastrointestinal events occurred after the administration of other anesthetic agents.
For the respiratory system overall, adverse events (hypoxia, laryngospasm, rhonchi, coughing, respiratory depression, airway obstruction, upper-airway congestion, shallow respirations), occurred during the entire monitoring period in 31/397 (8%) patients and increased in frequency as dosage was increased: 7/132 (5%) patients in the 0.25 mg/kg dose group, 9/132 (7%) patients in the 0.5 mg/kg dose group, and 15/133 (11%) patients in the 1 mg/kg dose group.
Most of the respiratory adverse events occurred during induction, general anesthesia or recovery. One patient (0.25%) experienced a respiratory system adverse event (laryngospasm) during the premedication period. This adverse event occurred precisely at the time of induction. Although many of the respiratory complications occurred in settings of upper airway procedures or concurrently administered opioids, a number of these events occurred outside of these settings as well. In this study, administration of midazolam HCI syrup was generally accompanied by a slight decrease in both systolic and diastolic blood pressures, as well as a slight increase in heart rate.
Table 5. Adverse Events Occurring During the Premedication Period Before Mask Induction in the Randomized, Double-Blind, Parallel-Group Trial
|Body System||Treatment Regimen||Overall|
|No.Patients with Adverse Events||0.25 mg/kg
|Gastrointestinal Sytem Disorders|
|Emesis||1 (0.76%)||1 (0.76%)||1 (0.75%)||3 (0.76%)|
|Nausea||2 (1.5%)||2 (0.50%)|
|Sneezing/Rhinorrhea||1 (0.75%)||1 (0.25%)|
|ALL BODY SYSTEMS||1 (0.76%)||1 (0.76%)||5 (3.8%)||7 (1.8%)|
|*This adverse event occurred precisely at the time of induction.|
Table 6. Adverse Events (≥1%) From the Randomized, Double-Blind,
Parallel-Group Trial on Entire Monitoring Period (premedication, anesthesia,
|Body System||Treatment Regimen||Overall|
|No.Patients with Adverse Events||0.25mg/kg
|Gastrointestinal System Disorders|
|Respiratory System Disorders|
|Heart Rate, Rhythm Disorders|
|Central & Peripheral Nervous System Disorders|
|Skin and Appendages Disorders|
|ALL BODY SYSTEMS||26(20%)||23(17%)||33(25%)||82(21%)|
There were no deaths during the study and no patient withdrew from the study due to adverse events. Serious adverse events (both respiratory disorders) were experienced postoperatively by two patients: one case of airway obstruction and desaturation (SpO2 of 33%) in a patient given midazolam HCI syrup 0.25 mg/kg, and one case of upper airway obstruction and respiratory depression following 0.5 mg/kg. Both patients had received intravenous morphine sulfate (1.5 mg total for both patients).
Other adverse events that have been reported in the literature with the oral administration of midazolam (not necessarily midazolam syrup), are listed below. The incidence rate for these events was generally <1%.
Cardiovascular: decreased systolic and diastolic blood pressure, increased heart rate. Gastrointestinal: nausea, vomiting, hiccoughs, gagging, salivation, drooling.
Drug Abuse And Dependence
Midazolam HCI syrup is a benzodiazepine and is a Schedule IV controlled substance that can produce drug dependence of the diazepam-type. Therefore, midazolam HCI syrup may be subject to misuse, abuse and addiction. Benzodiazepines can cause physical dependence. Physical dependence results in withdrawal symptoms in patients who abruptly discontinue the drug. Withdrawal symptoms (ie, convulsions, hallucinations, tremors, abdominal and muscle cramps, vomiting and sweating), similar in characteristics to those noted with barbiturates and alcohol have occurred following abrupt discontinuation of midazolam following chronic administration. Abdominal distention, nausea, vomiting, and tachycardia are prominent symptoms of withdrawal in infants.
The handling of midazolam HCI syrup should be managed to minimize the risk of diversion, including restriction of access and accounting procedures as appropriate to the clinical setting and as required by law.
Read the Midazolam Hydrochloride Syrup (midazolam hcl syrup) Side Effects Center for a complete guide to possible side effects
Inhibitors of CYP3A4 Isozymes: Caution is advised when midazolam is administered concomitantly with drugs that are known to inhibit the cytochrome P450 3A4 enzyme system (ie, some drugs in the drug classes of azole antimycotics, protease inhibitors, calcium channel antagonists, and macrolide antibiotics). Drugs such as diltiazem, erythromycin, fluconazole, itraconazole, ketoconazole, saquinavir, and verapamil were shown to significantly increase the Cmax and AUC of orally administered midazolam. These drug interactions may result in increased and prolonged sedation due to a decrease in plasma clearance of midazolam. Although not studied, the potent cytochrome P450 3A4 inhibitors ritonavir and nelfinavir may cause intense and prolonged sedation and respiratory depression due to a decrease in plasma clearance of midazolam. Caution is advised when midazolam HCI syrup is used concomitantly with these drugs. Dose adjustments should be considered and possible prolongation and intensity of effect should be anticipated (see PHARMACOKINETICS: Drug-Drug Interactions).
Inducers of CYP3A4 Isozymes: Cytochrome P450 inducers, such as rifampin, carbamazepine, and phenytoin, induce metabolism and caused a markedly decreased Cmax and AUC of oral midazolam in adult studies. Although clinical studies have not been performed, phenobarbital is expected to have the same effect. Caution is advised when administering midazolam HCI syrup to patients receiving these medications and if necessary dose adjustments should be considered.
CNS Depressants: One case was reported of inadequate sedation with chloral hydrate and later with oral midazolam due to a possible interaction with methylphenidate administered chronically in a 2-year-old boy with a history of Williams syndrome. The difficulty in achieving adequate sedation may have been the result of decreased absorption of the sedatives due to both the gastrointestinal effects and stimulant effects of methylphenidate.
The sedative effect of midazolam HCI syrup is accentuated by any concomitantly administered medication which depresses the central nervous system, particularly narcotics (eg, morphine, meperidine and fentanyl), propofol, keta-mine, nitrous oxide, secobarbital and droperidol. Consequently, the dose of midazolam HCI syrup should be adjusted according to the type and amount of concomitant medications administered and the desired clinical response (see DOSAGE AND ADMINISTRATION).
No significant adverse interactions with common premedications (such as atropine, scopolamine, glycopyrrolate, diazepam, hydroxyzine, and other muscle relaxants) or local anesthetics have been observed.
Drug/Laboratory Test Interactions: Midazolam has not been shown to interfere with results obtained in clinical laboratory tests.
Last reviewed on RxList: 6/25/2008
This monograph has been modified to include the generic and brand name in many instances.
Additional Midazolam Hydrochloride Syrup Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.