ADVERSE REACTIONS:
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 premedication 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 of adverse events occurring during the premedication period, before induction of 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 midazolam administration 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 the premedication period.
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 HCl 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
No. Patients with Adverse Events | Treatment Regimen | Overall |
|---|
0.25 mg/kg
(n=132)
No. (%) | 0.5 mg/kg
(n=132)
No. (%) | 1 mg/kg
(n=133)
No. (%) | (n=397)
No. (%) |
|---|
| Gastrointestinal Sytem Disorders | | | | |
| Emesis | 1 (0.76%) | 1 (0.76%) | 1 (0.75%) | 3 (0.76%) |
| Nausea | | | 2 (1.5%) | 2 (0.50%) |
| Respiratory System Disorders | | | | |
| Laryngospasm | | | 1This adverse event occurred precisely at the time of induction.(0.75%) | 1 (0.25%) |
| Sneezing/Rhinorrhea | | | 1 (0.75%) | 1 (0.25%) |
| ALL BODY SYSTEMS | 1 (0.76%) | 1 (0.76%) | 5 (3.8%) | 7 (1.8%) |
Table 6. Adverse Events (≥1%) From the Randomized, Double-Blind, Parallel-Group Trial on Entire Monitoring Period (premedication, anesthesia, recovery) | Body System | Treatment Regimen | Overall |
|---|
| No. Patients with Adverse Events | 0.25 mg/kg
(n=132) | 0.5 mg/kg
(n=132) | 1 mg/kg
(n=133) | (n=397) |
|---|
| No. | (%) | No. | (%) | No. | (%) | No. | (%) |
|---|
| Gastrointestinal System Disorders | | | | |
| Emesis | 11 | (8%) | 5 | (4%) | 15 | (11%) | 31 | (8%) |
| Nausea | 6 | (5%) | 2 | (2%) | 6 | (5%) | 14 | (4%) |
| Overall | 16 | (12%) | 8 | (6%) | 16 | (12%) | 40 | (10%) |
| Respiratory System Disorders | | | | | | | | |
| Hypoxia | 0 | | 5 | (4%) | 4 | (3%) | 9 | (2%) |
| Laryngospasm | 0 | | 1 | (<1%) | 5 | (4%) | 6 | (2%) |
| Respiratory Depression | 2 | (2%) | 1 | (<1%) | 2 | (2%) | 5 | (1%) |
| Rhonchi | 2 | (2%) | 1 | (<1%) | 2 | (2%) | 5 | (1%) |
| Airway Obstruction | 2 | (2%) | 2 | (2%) | 0 | | 4 | (1%) |
| Upper Airway Congestion | 2 | (2%) | 0 | | 2 | (2%) | 4 | (1%) |
| Overall | 7 | (5%) | 9 | (7%) | 15 | (11%) | 31 | (8%) |
| Psychiatric Disorders | | | | | | | | |
| Agitated | 1 | (<1%) | 2 | (2%) | 3 | (2%) | 6 | (2%) |
| Overall | 1 | (<1%) | 3 | (2%) | 4 | (3%) | 8 | (2%) |
| Heart Rate, Rhythm Disorders | | | | | | | | |
| Bradycardia | 1 | (<1%) | 3 | (2%) | 0 | | 4 | (1%) |
| Bigeminy | 2 | (2%) | 0 | | 0 | | 2 | (<1%) |
| Overall | 3 | (2%) | 3 | (2%) | 1 | (<1%) | 7 | (2%) |
| Central & Peripheral Nervous System Disorders | | | | | | | | |
| Prolonged Sedation | 0 | | 0 | | 2 | (2%) | 2 | (<1%) |
| Overall | 2 | (2%) | 0 | | 3 | (2%) | 5 | (1%) |
| Skin and Appendages Disorders | | | | | | | | |
| Rash | 2 | (2%) | 0 | | 0 | | 2 | (<1%) |
| Overall | 2 | (2%) | 2 | (2%) | 0 | | 4 | (1%) |
| 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 HCl 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%.
Respiratory: apnea, hypercarbia, desaturation, stridor.
Cardiovascular: decreased systolic and diastolic blood pressure, increased heart rate.
Gastrointestinal: nausea, vomiting, hiccoughs, gagging, salivation, drooling.
Central Nervous System: dysphoria, disinhibition, excitation, aggression, mood swings, hallucinations, adverse behavior, agitation, dizziness, confusion, ataxia, vertigo, dysarthria.
Special Senses: diplopia, strabismus, loss of balance, blurred vision.
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REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO MIDAZOLAM
Below is a sample of reports where side effects / adverse reactions may be related to Midazolam. The information is not vetted and should not be cosidered as verified clinical evidence.
Possible Midazolam side effects / adverse reactions in 73 year old female
Reported by a pharmacist from United States on 2007-07-26
Patient: 73 year old female
Reactions: Cyanosis, Loss of Consciousness
Adverse event resulted in: hospitalization
Suspect drug(s):
Fentanyl
Dosage: 200mcg once iv
Indication: Sedation
Midazolam
Dosage: 7mg once iv
Indication: Sedation
Possible Midazolam side effects / adverse reactions in 41 year old female
Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2007-07-27
Patient: 41 year old female
Reactions: Anaphylactic Reaction, Circulatory Collapse, Erythema
Adverse event resulted in: life threatening event, hospitalization
Suspect drug(s):
Decadron
Start date: 2007-06-08
End date: 2007-06-08
Fentanyl
Start date: 2007-06-08
Midazolam
Start date: 2007-06-08
Propofol
Start date: 2007-06-08
Succinylcholine Bromide
Start date: 2007-06-08
Possible Midazolam side effects / adverse reactions in 35 year old male
Reported by a health professional (non-physician/pharmacist) from Australia on 2007-10-09
Patient: 35 year old male
Reactions: Laryngospasm, Oxygen Saturation Decreased
Suspect drug(s):
Rocuronium Bromide
Indication: Induction of Anaesthesia
Propofol
Indication: Induction of Anaesthesia
Fentanyl
Indication: Induction of Anaesthesia
Midazolam
Indication: Induction of Anaesthesia
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