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Midazolam In Sodium Chloride

FDA Drug Information • Also known as: Midazolam In Sodium Chloride

Brand Names
Midazolam In Sodium Chloride
Route
INTRAVENOUS
Dosage Form
INJECTION, SOLUTION
Product Type
HUMAN PRESCRIPTION DRUG

⚠ Boxed Warning (Black Box)

WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS Personnel and Equipment for Monitoring and Resuscitation

  • Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Midazolam in 0.9% Sodium Chloride Injection [ see Dosage and Administration ( 2.1 ) , Warnings and Precautions ( 5.1 )].
  • Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation [ see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.1 )].
  • Resuscitative drugs, and age- and size-appropriate equipment for bag/valve/mask assisted ventilation must be immediately available during administration of Midazolam in 0.9% Sodium Chloride Injection [ see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.1 ) ].
  • Continuously monitor vital signs during sedation and during the recovery period [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.1 )]. Risks from Concomitant Use with Opioid Analgesics and Other Sedative Hypnotics Concomitant use of benzodiazepines, including Midazolam in 0.9% Sodium Chloride Injection, and opioids may result in profound sedation, respiratory depression, coma, and death. Continuously monitor patients for respiratory depression and depth of sedation [see Warnings and Precautions ( 5.2 ) and Drug Interaction ( 7.1 )]. WARNING: PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION, AND RISKS FROM CONCOMITANT USE WITH OPIOID ANALGESICS AND OTHER SEDATIVE-HYPNOTICS See full prescribing information for complete boxed warning Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Midazolam Injection. ( 2.1 , 5.1 ) Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation. (2.1 , 5.1 ) Resuscitative drugs, and age- and size-appropriate equipment for bag/valve/mask assisted ventilation must be immediately available during administration of Midazolam Injection. ( 2.1 , 5.1 ) Continuously monitor vital signs during sedation and through the recovery period. ( 2.1 , 5.1 ) Concomitant use of benzodiazepines with opioid analgesics may result in profound sedation, respiratory depression, coma, and death. Continuously monitor patients for respiratory depression and depth of sedation. ( 5.2 , 7.1 )

    • Description

    11 DESCRIPTION Midazolam in 0.9% Sodium Chloride Injection is a benzodiazepine available as a sterile, preservative-free, nonpyrogenic solution of midazolam and sodium chloride in water for injection for intravenous use. Each single-dose bag of Midazolam in 0.9% Sodium Chloride Injection contains either 50 mg/50 mL (1mg/mL) or 100 mg/100 mL (1 mg/mL) of midazolam and 9 mg/mL of sodium chloride in water for injection. Midazolam in 0.9% Sodium Chloride Injection may contain hydrochloric acid and/or sodium hydroxide for pH adjustment. The pH is approximately 2.5-3.5. Midazolam is a white or yellowish powder, practically insoluble in water, Chemically, midazolam is 8-chloro-6-(2-fluorophenyl)-1-methyl-4 H -imidazo[1,5-a][1,4]-benzodiazepine. Midazolam has the empirical formula C 18 H 13 ClFN 3 , a calculated molecular weight of 325.8 and the following structural formula: Midazolam-Structure

    What Is Midazolam In Sodium Chloride Used For?

    1 INDICATIONS AND USAGE Midazolam in 0.9% Sodium Chloride Injection is indicated:

  • Continuous intravenous infusion for sedation of intubated and mechanically ventilated adult, pediatric, and neonatal patients as a component of anesthesia or during treatment in a critical care setting. Midazolam in 0.9% Sodium Chloride Injection is a benzodiazepine indicated for: continuous intravenous infusion for sedation of intubated and mechanically ventilated adult, pediatric, and neonatal patients as a component of anesthesia or during treatment in a critical care setting. (1)

    • Dosage and Administration

    2 DOSAGE AND ADMINISTRATION

  • For intravenous injection only. Avoid intra-arterial injection or extravasation. ( 2.1 )
  • Individualize dosing and titrate to desired clinical response, taking into account patient age, clinical status, and concomitant use of other CNS depressants. (2.1 )
  • See Full Prescribing Information for complete dosage and administration information. ( 2 ) 2.1 Important Dosage and Administration Instructions Midazolam in 0.9% Sodium Chloride Injection should only be administered intravenously. Avoid intra-arterial injection or extravasation [see Warnings and Precautions ( 5.7 )].
  • Only personnel trained in the administration of procedural sedation, and not involved in the conduct of the diagnostic or therapeutic procedure, should administer Midazolam in 0.9% Sodium Chloride Injection.
  • Administering personnel must be trained in the detection and management of airway obstruction, hypoventilation, and apnea, including the maintenance of a patent airway, supportive ventilation, and cardiovascular resuscitation.
  • Supplemental oxygen, resuscitative drugs, and age‑ and size-appropriate equipment for bag/valve/mask assisted ventilation must be immediately available during administration of Midazolam in 0.9% Sodium Chloride Injection. A benzodiazepine reversal agent should be immediately available.
  • Continuously monitor vital signs during sedation and through the recovery period [see Warnings and Precautions ( 5.1 )]. Midazolam must never be used without individualization of dosage particularly when used with other medications capable of producing central nervous system depression [Warnings and Precautions ( 5.2 )]. Midazolam in 0.9% Sodium Chloride Injection can cause respiratory depression. It is a potent sedative agent that requires slow administration and individualization of dosage. Excessive single doses or rapid intravenous administration may result in respiratory depression, airway obstruction and/or arrest. Continuously monitor patients for early signs of hypoventilation, airway obstruction, and apnea using capnography, pulse oximetry, and clinical assessment [see Warnings and Precautions ( 5.3 )]. Reactions such as agitation, involuntary movements, hyperactivity and combativeness have been reported in adult and pediatric patients. Should such reactions occur, the response to each dose of midazolam and all other drugs, including local anesthetics, should be evaluated before proceeding. Reversal of such responses with flumazenil has been reported in pediatric patients [see Warnings and Precautions ( 5.4 )]. Visually inspect parenteral drug products for particulate matter and discoloration prior to administration, whenever solution and container permit. If solution is discolored or particulate matter is present, do not use. 2.2 General Dosing Information Individualize dosing and titrate to desired clinical response, taking into account patient age, clinical status, and concomitant use of other CNS depressants. Titrate to...

    • Side Effects (Adverse Reactions)

    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 (5.0%) 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 2.0%, 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 <1.0% 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...

    • Drug Interactions

    7 DRUG INTERACTIONS Opioid Analgesics and Other Sedative Hypnotics: Risk of respiratory depression is increased. (7.1) Cytochrome P450-3A4 Inhibitors: May result in prolonged sedation due to decreased plasma clearance of midazolam. ( 7.2 ) 7.1 Opioid Analgesics and Other Sedative Hypnotics The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABA A sites and opioids interact primarily at mu receptors. When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Monitor patients closely for respiratory depression and sedation. The sedative effect of intravenous midazolam is accentuated by any concomitantly administered medication which depresses the central nervous system, particularly opioids (e.g., morphine, meperidine and fentanyl) and also secobarbital and droperidol. Consequently, the dosage of midazolam should be adjusted according to the type and amount of concomitant medications administered and the desired clinical response [ see Dosage and Administration ( 2 )]. 7.2 Cytochrome P450-3A4 Inhibitors Concomitant administration with drugs that are known to inhibit the P450-3A4 enzyme system, such as cimetidine (not ranitidine), erythromycin, diltiazem, verapamil, ketoconazole and itraconazole, may result in prolonged sedation due to a decrease in plasma clearance of midazolam. The effect of single oral doses of 800 mg cimetidine and 300 mg ranitidine on steady-state concentrations of midazolam was examined in a randomized crossover study (n=8). Cimetidine increased the mean midazolam steady-state concentration from 57 to 71 ng/mL. Ranitidine increased the mean steady-state concentration to 62 ng/mL. No change in choice reaction time or sedation index was detected after dosing with the H2 receptor antagonists. In a placebo-controlled study, erythromycin administered as a 500 mg dose, three times a day, for 1 week (n=6), reduced the clearance of midazolam following a single 0.5 mg/kg intravenous dose. The half-life was approximately doubled. The effects of diltiazem (60 mg three times a day) and verapamil (80 mg three times a day) on the pharmacokinetics and pharmacodynamics of oral midazolam were investigated in a three-way crossover study (n=9). The half-life of midazolam increased from 5 to 7 hours when midazolam was taken in conjunction with verapamil or diltiazem. No interaction was observed in healthy subjects between midazolam and nifedipine. 7.3 Saquinavir In a placebo-controlled study, saquinavir administered as a 1200 mg dose, tid, for 5 days (n=12), a 56% reduction in the clearance of midazolam following a single 0.05 mg/kg intravenous dose was observed. The half-life was approximately doubled. 7.4 Thiopental A moderate reduction in induction dosage requirements of thiopental (about 15%) has...

    Contraindications

    4 CONTRAINDICATIONS Midazolam in 0.9% Sodium Chloride Injection is contraindicated in patients with:

  • Known hypersensitivity to midazolam
  • Acute narrow-angle glaucoma Midazolam in 0.9% Sodium Chloride Injection is contraindicated in patients with:
  • known hypersensitivity to midazolam. ( 4 )
  • acute narrow-angle glaucoma. ( 4 )

    • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Neonates born to mothers using benzodiazepines, including midazolam, late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions (5.10), and Clinical Considerations]. Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects (see Data). Available data from randomized controlled trials, cohort studies and case reports over several decades with midazolam use in pregnant women for anesthesia have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Most of the reported exposures to midazolam occurred at the time of cesarean delivery. Rare case reports of the prolonged use of midazolam in pregnant women for sedation in a critical care setting are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes ( see Data ). In pregnant rats and rabbits, midazolam did not cause adverse effects to the fetus at doses of up to 1.85 times the human induction dose of 0.35 mg/kg based on body surface area comparisons. Published studies in pregnant primates demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of peak brain development increases neuronal apoptosis in the developing brain of the offspring when used for longer than 3 hours. There are no data on pregnancy exposures in primates corresponding to periods prior to the third trimester in humans ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in...

    Overdosage

    10 OVERDOSAGE Clinical Presentation Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal [ see Warnings and Precautions ( 5.2 )]. Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage. No evidence of specific organ toxicity from midazolam overdosage has been reported. Management of Overdosage In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil use may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of...

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Midazolam in 0.9% Sodium Chloride Injection is a clear, colorless solution supplied in single-dose bags with an aluminum overwrap available as: Product Code Total Strength per Total Volume Strength per mL 10 single-dose bags NDC Bag and Overwrap NDC 651050 *50 mg per 50 mL 1 mg/mL 65219-650-50 65219-650-05 651010 100 mg per 100 mL 1 mg/mL 65219-650-10 65219-650-02 *Partial fill container 50 mL volume in 100 mL container Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from Freezing. Individual containers may be used up to 48 hours after initial penetration. Discard unused portion.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.