Seizalam Injection

Seizalam (midazolam) Injection is a benzodiazepine used to treat status epilepticus in adults.

• Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Monitor patients for respiratory depression and sedation.
• The use of benzodiazepines, including Seizalam, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Before prescribing Seizalam and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.
• Although Seizalam is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction of Seizalam may precipitate acute withdrawal reactions, which can be life-threatening. For patients using Seizalam more frequently than recommended, to reduce the risk of withdrawal reactions, use a gradual taper to discontinue Seizalam.

Side effects of Seizalam include:

• upper airway obstruction,
• agitation,
• fever, and
• decreased tidal volume and/or decreased respiratory rate.

Withdrawal symptoms, similar in character to those noted with barbiturates and alcohol (convulsions, hallucinations, tremor, abdominal and muscle cramps, vomiting and sweating), have occurred following abrupt discontinuation of benzodiazepines, including midazolam.

Recommended Dose

The recommended dose of Seizalam is 10 mg, administered by intramuscular injection.

Important Administration Instructions

• Seizalam should be administered by a healthcare professional who has had adequate training in the recognition and treatment of status epilepticus.
• Seizalam is for intramuscular use only. Inject in the mid-outer thigh (vastus lateralis muscle).
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Monitoring

• After administration of Seizalam, 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.
• 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.

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 Seizalam 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.

Cytochrome P450-3A4 Inhibitors

• Caution is advised when Seizalam 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.

• There are no adequate and well-controlled studies of Seizalam in pregnant women.
• Available data suggest that the class of benzodiazepines is not associated with marked increases in risk for congenital anomalies.
• Although some early epidemiological studies suggested a relationship between benzodiazepine use in pregnancy and congenital anomalies such as cleft lip and or palate, these studies had considerable limitations.
• More recently completed studies of benzodiazepine use in pregnancy have not consistently documented elevated risks for specific congenital anomalies.
• There is insufficient evidence to assess the effect of benzodiazepine pregnancy exposure on neurodevelopment.
• Midazolam is excreted in human milk. Studies assessing the effects of midazolam in breastfed children or on milk production/excretion have not been performed.
• Postmarketing experience suggests that breastfed infants of mothers taking benzodiazepines, such as Seizalam, may have effects of lethargy, somnolence and poor sucking.
• The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for midazolam and any potential adverse effects on the breastfed child from midazolam or from the underlying maternal condition.