Midazolam Injection, 10 Mg
FDA Drug Information
- Drug Class
- Benzodiazepine [EPC]
- Route
- INTRAMUSCULAR
- Dosage Form
- INJECTION, SOLUTION
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Monitor patients for respiratory depression and sedation [see Warnings and Precautions (5.1), Drug Interactions (7.1)]. The use of benzodiazepines, including midazolam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with a n increased frequency of serious adverse outcomes. Before prescribing Midazolam Injection and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction [see Warnings and Precautions (5.2)]. The continued use of benzodiazepines may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Although Midazolam Injection is indicated only for intermittent use [see Indications and Usage (1) and Dosage and Administration (2)], if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of Midazolam Injection may precipitate acute withdrawal reactions, which can be life-threatening. For patients using Midazolam Injection more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue Midazolam Injection [see Warnings and Precautions (5.3)]. WARNING: RISKS FROM CONCOMITANT USE WITH OPIOIDS; ABUSE, MISUSE, AND ADDICTION; and DEPENDENCE AND WITHDRAWAL REACTIONS See full prescribing information for complete boxed warning. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Monitor patients for respiratory depression and sedation. (5.1, 7.1) The use of benzodiazepines, including midazolam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing Midazolam Injection and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction. (5.2) Although Midazolam Injection is indicated only for intermitt ent use (1, 2), if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of Midazolam Injection may precipitate acute withdrawal reactions, which can be lifethreatening. For patients using Midazolam Injection more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue Midazolam Injection. (5.3)
Description
Midazolam is a white to light yellow crystalline compound, insoluble in water. The hydrochloride salt of midazolam, which is formed in situ, is soluble in aqueous solutions. Chemically, midazolam is 8-chloro-6- (2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4]benzodiazepine. Midazolam has the empirical formula C 18 H 13 ClFN 3 , a calculated molecular weight of 325.77 and the following structural formula: Midazolam Injection contains a sterile, nonpyrogenic solution for intramuscular injection in a single-dose prefilled autoinjector. Each 0.7 mL contains 10 mg midazolam (equivalent to 11.12 mg midazolam hydrochloride) compounded with 0.7% sodium chloride and 1.1% hydrochloric acid. The pH is adjusted to approximately 3 with hydrochloric acid. structure
What Is Midazolam Injection, 10 Mg Used For?
Midazolam Injection is indicated for the treatment of status epilepticus in adults. Midazolam Injection is a benzodiazepine indicated for the treatment of status epilepticus in adults. (1)
Dosage and Administration
Recommended Dose The recommended dose of Midazolam Injection is a single 10 mg dose, administered by intramuscular injection [see Dosage and Administration (2.2)]. Important Administration Instructions Midazolam Injection should be administered by trained personnel who have had adequate training in the recognition and treatment of status epilepticus and first aid/basic airway management. Midazolam Injection is for intramuscular use only as a single dose. Inject in the mid-outer thigh (vastus lateralis muscle) using the prefilled autoinjector. The Midazolam autoinjector can inject through clothing. Move all objects from in and around the patient’s clothing that may interfere with the injection. For people who do not have a lot of fat at the mid-outer thigh, bunch up the thigh at the injection site to provide a thicker area for administration. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit [see Dosage Forms and Strengths (3)]. Refer to the illustrated Midazolam Injection Instructions for Use for autoinjector administration instructions. Monitoring After administration of Midazolam Injection, continuous monitoring of respiratory and cardiac function is recommended until the patient is stabilized. Serious and life-threatening cardiorespiratory adverse reactions, such as hypoventilation, airway obstruction, apnea, and hypotension have been reported with the use of midazolam. Patients should be monitored in a setting that allows for immediate access to resuscitative drugs. Appropriate resuscitation equipment and personnel trained in their use and skilled in airway management should be available [see Warnings and Precautions (5.4), Adverse Reactions (6.1)]. Observation for signs of cardiorespiratory depression is particularly important in patients with chronic obstructive pulmonary disease (COPD), patients 60 or more years of age, and patients who have received concomitant narcotics or other central nervous system (CNS) depressants. The recommended dose is a single 10 mg dose, administered by intramuscular injection using the prefilled autoinjector. (2.1) Inject in the mid-outer thigh (vastus lateralis muscle). (2.2) Continuous monitoring of respiratory and cardiac function is recommended. (2.3)
Side Effects (Adverse Reactions)
The following serious adverse reactions are discussed in greater detail in other sections: Risks from Concomitant Use with Opioids [see Warnings and Precautions (5.1)] Abuse, Misuse, and Addiction [see Warnings and Precautions (5.2)] Dependence and Withdrawal Reactions After Use of Midazolam Injection More Frequently Than Recommended [see Warnings and Precautions (5.3)] Risks of Cardiorespiratory Adverse Reactions [see Warnings and Precautions (5.4)] Other Adverse Reactions [see Warnings and Precautions (5.5)] Risks from Concomitant Use of Central Nervous System Depressants [see Warnings and Precautions (5.6)] Impaired Cognitive Function [see Warnings and Precautions (5.7)] Glaucoma [see Warnings and Precautions (5.8)] Neonatal Sedation and Withdrawal Syndrome [see Warnings and Precautions (5.9)] Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of Midazolam Injection has been established by data from an adequate and well-controlled study of a different midazolam injection in adult patients with status epilepticus [see Clinical Studies (14)]. Below is a display of the adverse reactions of midazolam injection in this adequate and well-controlled study. Adverse Reactions in the Controlled Study of Intramuscular Midazolam in Patients with Status Epilepticus In a double-blind, randomized, active-controlled clinical study, 448 patients were assigned to receive intramuscular (IM) midazolam via an autoinjector, and 445 were assigned to receive intravenous (IV) lorazepam. Approximately 45% of patients were female, and the mean age was 43 years. Patients were administered treatment by a healthcare professional (e.g., paramedic) prior to arrival at a hospital. Table 1 lists the adverse reactions occurring in 2% or more of the IM midazolam-treated patients and at a rate greater than the IV lorazepam-treated patients. Table 1 Adverse Reactions in 2% or More of IM Midazolam-Treated Patients and More Frequent than in IV Lorazepam-Treated Patients in Out of Hospital Treatment of Status Epilepticus Adverse Reactions in Other Midazolam Studies Midazolam Injection is only indicated for status epilepticus, but for uses other than that for which Midazolam Injection is indicated, 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 [11% of patients following intramuscular administration], as well as variations in blood pressure and pulse rate. The majority of serious adverse effects, particularly those associated with oxygenation and ventilation, have been reported when midazolam was administered with other medications capable of depressing the CNS. The incidence of such events was higher in patients undergoing procedures involving the airway without the protective effect of an endotracheal tube (e.g., upper endoscopy and dental procedures). The following additional adverse reactions were reported after intramuscular administration in adults: Headache (1.3%), and local effects at the IM injection site including pain (3.7%), induration (0.5%), redness (0.5%), and muscle stiffness (0.3%). The most common adverse reactions (incidence >3%) in clinical trials in patients with status epilepticus were upper airway obstruction, agitation, and pyrexia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Rafa Laboratories, Ltd. at 1-386-418-7911 or FDA at 1-800-FDA-1088 or www.fda.gov.medwatch. AEs clinical trials
Drug Interactions
Effect of Concomitant Use of Benzodiazepines and Opioids 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 GABAA 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. Limit dosage and duration of concomitant use of benzodiazepines and opioids. Monitor patients closely for respiratory depression and sedation. Other CNS Depressants and Alcohol The sedative effect of Midazolam Injection is accentuated by concomitantly administered medication that depresses the central nervous system, particularly opioids (e.g., morphine, meperidine, and fentanyl), secobarbital, and droperidol, and also by alcohol [see Warnings and Precautions (5.1, 5.4, 5.6)]. Cytochrome P450-3A4 Inhibitors Caution is advised when Midazolam Injection is administered concomitantly with drugs that are known to inhibit the P450-3A4 enzyme system (e.g., cimetidine, erythromycin, diltiazem, verapamil, ketoconazole, and itraconazole). These drug interactions may result in prolonged sedation caused by a decrease in plasma clearance of midazolam [see Clinical Pharmacology (12.3)]. Benzodiazepines and Opioids: Risk of respiratory depression is increased. (7.1) Other CNS Depressants and Alcohol: Sedative effect of midazolam is increased. (7.2) Cytochrome P450-3A4 Inhibitors: May result in prolonged sedation due to decreased plasma clearance of midazolam. (7.3)
Contraindications
Midazolam Injection is contraindicated in patients with a known hypersensitivity to midazolam. Hypersensitivity to midazolam. (4)
Overdosage
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. In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway maintenance. 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 benzodiazepine overdosage. See the flumazenil injection Prescribing Information. Consider contacting a poison center (1-800-221-2222) or a medical...
How Supplied
How Supplied Midazolam Injection is a clear, colorless to slightly yellow sterile solution available in single-dose prefilled autoinjectors containing 10 mg/0.7 mL. Midazolam Injection is supplied in the following packaging configurations: Carton of 480 prefilled autoinjectors: NDC 71053-595-01 Storage and Handling Store at 20 ºC to 25 ºC (68 ºF to 77 ºF); excursions permitted between 15 ºC and 30 ºC (59 ºF and 86 ºF) [See USP Controlled Room Temperature]. DO NOT FREEZE.
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.