6 ADVERSE REACTIONS

The following serious adverse reactions are discussed in greater detail in other sections:

• Cardiorespiratory Adverse Reactions [see Warnings and Precautions (5.3)]
• Paradoxical Behavior [see Warnings and Precautions (5.4)]
• Dependence and Withdrawal [see Warnings and Precautions (5.5)]
• Impaired Cognitive Function [see Warnings and Precautions (5.8)]
• Hypotension and Seizure in Preterm Infants and Neonates [see Warnings and Precautions (5.9)]
• Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.10), Use in Specific Populations (8.1)]
• Pediatric Neurotoxicity [see Warnings and Precautions (5.11)]

The following adverse reactions have been identified from literature or postmarketing reports of midazolam. Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Fluctuations in vital signs were the most frequently seen findings following parenteral administration of midazolam in adults and included decreased tidal volume and/or respiratory rate decrease (23.3% of patients following intravenous administration) and apnea (15.4% of patients following intravenous administration), as well as variations in blood pressure and pulse rate. The majority of serious adverse reactions, particularly those associated with oxygenation and ventilation, have been reported when midazolam is administered with other medications capable of depressing the central nervous system. The incidence of such events is higher in patients undergoing procedures involving the airway without the protective effect of an endotracheal tube, (e.g., upper endoscopy and dental procedures).

Adults

Table 2: Additional Adverse Reactions Reported Subsequent to Intravenous Administration as a Single Sedative/anxiolytic/amnestic Agent in Adult Patients:

hiccoughs (3.9%)                                                 Local effects at the intravenous site

nausea (2.8%)                                                      tenderness (5.6%)

vomiting (2.6%)                                                   pain during injection (5%)

coughing (1.3%)                                                  redness (2.6%)

"oversedation" (1.6%)                                          induration (1.7%)

headache (1.5%)                                                  phlebitis (0.4%)

 drowsiness (1.2%)      

Pediatric Patients

The following adverse events related to the use of intravenous midazolam in pediatric patients were reported in the medical literature: desaturation 4.6%, apnea 2.8%, hypotension 2.7%, paradoxical reactions 2%, hiccough 1.2%, seizure-like activity 1.1% and nystagmus 1.1%. The majority of airway-related events occurred in patients receiving other CNS depressing medications and in patients where midazolam was not used as a single sedating agent.

Neonates

There have been reports of hypotensive episodes and seizures following the administration of midazolam to neonates, [see Warnings and Precautions (5.9)].

Other Adverse Reactions Occurring at an Incidence of <1% Following Intravenous Injection as a Single Sedative/Anxiolytic/Amnesia Agent

Respiratory: Laryngospasm, bronchospasm, dyspnea, hyperventilation, wheezing, shallow respirations, airway obstruction, tachypnea

Cardiovascular: Bigeminy, premature ventricular contractions, vasovagal episode, bradycardia, tachycardia, nodal rhythm

Gastrointestinal: Acid taste, excessive salivation, retching

CNS/Neuromuscular: Retrograde amnesia, euphoria, hallucination, confusion, argumentativeness, nervousness, anxiety, grogginess, restlessness, emergence delirium or agitation, prolonged emergence from anesthesia, dreaming during emergence, sleep disturbance, insomnia, nightmares, athetoid movements, seizure-like activity, ataxia, dizziness, dysphoria, slurred speech, dysphonia, paresthesia

Special Senses: Blurred vision, diplopia, nystagmus, pinpoint pupils, cyclic movements of eyelids, visual disturbance, difficulty focusing eyes, ears blocked, loss of balance, light-headedness

Integumentary: Hive-like elevation at injection site, swelling or feeling of burning, warmth or coldness at injection site

Hypersensitivity: Allergic reactions including anaphylactic reactions, hives, rash, pruritus

Miscellaneous: Yawning, lethargy, chills, weakness, toothache, faint feeling, hematoma

PRINCIPAL DISPLAY PANEL 50 mL

High Alert Medication

NDC 0143-9379-01 Rx only

Midazolam in 0.9% Sodium Chloride Injection CIV

50 mg per 50 mL (1 mg/mL)

For Intravenous Use ONLY  - Do Not Dilute

PRINCIPAL DISPLAY PANEL 100 mL

High Alert Medication

NDC 0143-9380-01 Rx only

Midazolam in 0.9% Sodium Chloride Injection CIV

100 mg per 100 mL (1 mg/mL)

For Intravenous Use ONLY - Do Not Dilute