Midazolam in Sodium Chloride

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 The most common adverse reactions (≥15%) were decreased tidal volume, decreased respiratory rate, and apnea. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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Midazolam in Sodium Chloride Midazolam in Sodium Chloride MIDAZOLAM HYDROCHLORIDE MIDAZOLAM SODIUM CHLORIDE SODIUM HYDROXIDE HYDROCHLORIC ACID Midazolam in Sodium Chloride Midazolam in Sodium Chloride MIDAZOLAM HYDROCHLORIDE MIDAZOLAM SODIUM CHLORIDE SODIUM HYDROXIDE HYDROCHLORIC ACID

ANDA216159

Midazolam in Sodium Chloride

Midazolam in Sodium Chloride

62778-348

HUMAN PRESCRIPTION DRUG

INTRAVENOUS

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 Inner label