Usual Adult Dose for Light Sedation

Patients younger than 60 years:
IM: 0.07 to 0.08 mg/kg IM once, up to 1 hour before surgery

IV: 1 to 2.5 mg slow IV every 2 minutes as necessary for sedation

• Maintenance dose: After thorough clinical evaluation, additional doses may be given in increments of 25% of the initial dose used to reach sedation.
• Maximum dose: 2.5 mg/dose

Comments:

• Some patients respond to IV doses of 1 mg.
• A total IV dose over 5 mg is usually not necessary.
• The need for continued sedation with maintenance doses should be carefully considered.

Uses:

• Preoperative sedation/anxiolysis/amnesia
• Agent for sedation/anxiolysis/amnesia prior to/during diagnostic, therapeutic/endoscopic procedures (e.g., bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures alone/in combination of with other central nervous system [CNS] depressants)

Usual Adult Dose for Light Anesthesia

Patients younger than 55 years:
Premedicated patients: 0.25 mg/kg IV once, administered over 20 to 30 seconds. Healthcare providers should allow 2 minutes for effect.

Unpremedicated patients:

• Initial dose: 0.3 to 0.35 mg/kg IV once, administered over 20 to 30 seconds. Healthcare providers should allow 2 minutes to for effect. If induction is not complete after 2 minutes, inhalation anesthetics and/or further doses of this drug in increments of 25% of the initial dose may be given.
• Maximum dose: 0.6 mg/kg

Comments:

• When used concomitantly with other drugs used to induce anesthesia, initial doses may be reduced by to up to 25%.
• Total doses of 0.6 mg/kg may be used in unpremedicated, resistant patients, but the dose could prolong recovery.
• Doses between 0.15 and 0.35 mg/kg have been used in premedicated patients.
• Fentanyl, used as premedication, should be administered 5 minutes before induction. Other narcotics used for premedication should be administered approximately 1 hour prior to induction.

Uses:

• Induction of general anesthesia before administration of other anesthetic agents
• Component of IV supplementation of nitrous oxide and oxygen (balanced anesthesia)

Usual Adult Dose for Sedation

Loading dose: 0.01 to 0.05 mg/kg IV via slow injection or infusion over several minutes; the dose may be repeated in 10 to 15-minute intervals until sedation is achieved.
Maintenance dose: 0.2 to 0.1 mg/kg via IV infusion per hour

Comments:

• Loading and/or maintenance doses may be increased in some circumstances.
• The initial infusion rate is usually 1 to 7 mg/hour.
• The lowest effective dose should be used, and patients should be regularly assessed for sedation.

Uses:

• As a component of anesthesia for sedation of intubated and mechanically ventilated patients
• During treatment of intubated and mechanically ventilated patients in critical care settings

Usual Adult Dose for Epilepsy

Nasal:

• Initial dose: 5 mg (1 spray) intranasally in 1 nostril ONCE
• Subsequent dose: 5 mg (1 spray) intranasally in the opposite nostril after 10 minutes if the patient has not responded to the initial dose
• Maximum dose: 10 mg/day

Comments:

• This drug should not be used to treat more than 1 episode every 3 days, and no more than 5 episodes/month.
• The subsequent dose should not be administered if the patient has difficulty breathing OR if the patient has sedation that is not typically observed during a seizure cluster episode.

Use: Acute treatment of intermittent, stereotypic episodes of frequent seizure activity (e.g., acute repetitive seizures, seizure clusters) that are distinct from a patient's usual seizure pattern

Usual Adult Dose for Seizures

Nasal:

• Initial dose: 5 mg (1 spray) intranasally in 1 nostril ONCE
• Subsequent dose: 5 mg (1 spray) intranasally in the opposite nostril after 10 minutes if the patient has not responded to the initial dose
• Maximum dose: 10 mg/day

Comments:

• This drug should not be used to treat more than 1 episode every 3 days, and no more than 5 episodes/month.
• The subsequent dose should not be administered if the patient has difficulty breathing OR if the patient has sedation that is not typically observed during a seizure cluster episode.

Use: Acute treatment of intermittent, stereotypic episodes of frequent seizure activity (e.g., acute repetitive seizures, seizure clusters) that are distinct from a patient's usual seizure pattern

Usual Geriatric Dose for Light Sedation

60 years and older:
IM: 0.02 to 0.05 mg/kg IM once up to 1 hour before surgery

IV: 1 mg slow IV every 2 minutes as needed for sedation

• Maintenance dose: 25% of the dose used to reach desired sedation level

Comments:

• Some patients may achieve sufficient sedation with an IM dose of 1 mg if the intensity and duration of sedation is less critical.
• IM dosing is intended for patients who are not receiving concomitant narcotic or central nervous system depressants; lower doses should be considered in patients older than 60 years who are receiving narcotic or CNS depressants.
• A total IV dose greater than 3.5 mg is usually not necessary.
• The need for continued sedation with maintenance dosing should be carefully considered.

Uses:

• Preoperative sedation/anxiolysis/amnesia
• Agent for sedation/anxiolysis/amnesia prior to/during diagnostic, therapeutic/endoscopic procedures (e.g., bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures alone/in combination of with other central nervous system depressants)

Usual Geriatric Dose for Light Anesthesia

Over 55 years:
Premedicated patients: 0.2 mg/kg IV once, administered over 20 to 30 seconds

Unpremedicated patients: 0.2 to 0.3 mg/kg IV once, administered over 20 to 30 seconds

Comments:

• Initial doses of 0.15 mg/kg have been sufficient in inducing anesthesia in patients, especially in those with severe systemic disease or debilitation.
• Fentanyl, used as premedication, should be administered 5 minutes before induction. Other narcotics used for premedication should be administered approximately 1 hour prior to induction.

Uses:

• Induction of general anesthesia before administration of other anesthetic agents
• Component of IV supplementation of nitrous oxide and oxygen (balanced anesthesia)

Usual Pediatric Dose for Light Sedation

Oral:
6 months to 16 years: 0.25 to 1 mg/kg orally once before the procedure

• Maximum dose: 20 mg

Parenteral:
IM ADMINISTRATION: 0.1 to 0.15 mg/kg IM once, with some patients requiring doses of 0.5 mg/kg

• Maximum total dose: 10 mg

IV ADMINISTRATION:
6 months to 5 years:

• Initial dose: 0.05 to 0.1 mg/kg IV injection, with evaluation for sedation. If an optimal sedation levels is not reached after 2 to 3 minutes, doses may be readministered every 2 to 3 minutes, up to a maximum dose of 0.6 mg/kg.
• Maximum total dose: 6 mg

6 years to 12 years:

• Initial dose: 0.025 to 0.05 mg/kg IV injection, with evaluation for sedation. If an optimal sedation level is not reached, doses may be readministered every 2 to 3 minutes, up to a maximum dose of 0.4 mg/kg.
• Maximum total dose: 10 mg

12 years and older: 1 to 2.5 mg slow IV every 2 minutes as necessary for sedation

• Maintenance dose: After thorough clinical evaluation, additional doses may be given in increments of 25% of the initial dose used to reach sedation.
• Maximum total dose: 10 mg

Comments:

• Less cooperative and/or younger (e.g., less than 6 years) patients may require oral doses up to 1 mg/kg. -Oral doses of 0.25 mg/kg usually suffice for cooperative and/or patients 6 to 16 years, especially when sedation duration and intensity are less critical.
• IV injection doses should be administered over 2 to 3 minutes. Maximum IV doses typically do not exceed 6 mg (patients 6 months to 5 years) or 10 mg (patients 6 years and older), and maximum IM doses typically do not exceed 10 mg.
• Lower doses should be considered in patients with cardiac/respiratory compromise, high-risk surgical patients, and/or those who have received narcotics/CNS depressants.

Uses:

• Sedation, anxiolysis, and amnesia prior to diagnostic, therapeutic, or endoscopic procedures or before induction of anesthesia
• Preoperative sedation/anxiolysis/amnesia
• Agent for sedation/anxiolysis/amnesia prior to/during diagnostic, therapeutic/endoscopic procedures (e.g., bronchoscopy, gastroscopy, cystoscopy, coronary angiography, cardiac catheterization, oncology procedures, radiologic procedures, suture of lacerations and other procedures alone/in combination of with other central nervous system depressants)

Usual Pediatric Dose for ICU Agitation

Parenteral:
CONTINUOUS INFUSION:
Preterm and term neonates:
Less than 32 weeks with tracheal intubation:

• Initial dose: 0.03 mg/kg/hr (0.5 mcg/kg/min) IV

Over 32 weeks with tracheal intubation:

• Initial dose: 0.06 mg/kg/hr (1 mcg/kg/min) IV

Non-neonates and children:
Unpremedicated patients with tracheal intubation:

• Loading dose: 0.05 to 0.2 mg/kg IV once, administered over 2 to 3 minutes
• Initial dose: 0.06 to 0.12 mg/kg/hr (1 to 2 mcg/kg/min)

Premedicated patients with tracheal intubation:

• Initial dose: 0.06 to 0.12 mg/kg/hr (1 to 2 mcg/kg/min)

Hemodynamically compromised patients:

• Loading dose: The usual loading dosed should be increased in small increments.

Comments:

• To establish therapeutic plasma levels in neonates, the infusion should be run more rapidly for the first several hours.
• Infusion rates should be reassessed to ensure that the lowest effective dose is used, especially after the first 24 hours.
• Extreme caution should be used in current/former preterm patients who do not have tracheal intubation.
• The rate of continuous infusion may be increased or decreased (e.g., usually by 25% of the initial/subsequent rate) as necessary in premedicated non-neonates. Supplemental IV doses may be given to increase/maintain the desired effect.
• Patients should be monitored closely for hemodynamic instability, respiratory rate, and oxygen saturation, especially when this drug is used in those with hemodynamic instability.

Use: Sedation of intubated and mechanically ventilated patients during treatment in a critical care setting

Usual Pediatric Dose for Epilepsy

Nasal:
12 years and older:

• Initial dose: 5 mg (1 spray) intranasally in 1 nostril ONCE
• Subsequent dose: 5 mg (1 spray) intranasally in the opposite nostril after 10 minutes if the patient has not responded to the initial dose
• Maximum dose: 10 mg/day

Comments:

• This drug should not be used to treat more than 1 episode every 3 days, and no more than 5 episodes/month.
• The subsequent dose should not be administered if the patient has difficulty breathing OR if the patient has sedation that is not typically observed during a seizure cluster episode.

Use: Acute treatment of intermittent, stereotypic episodes of frequent seizure activity (e.g., acute repetitive seizures, seizure clusters) that are distinct from a patient's usual seizure pattern

Usual Pediatric Dose for Seizures

Nasal:
12 years and older:

• Initial dose: 5 mg (1 spray) intranasally in 1 nostril ONCE
• Subsequent dose: 5 mg (1 spray) intranasally in the opposite nostril after 10 minutes if the patient has not responded to the initial dose
• Maximum dose: 10 mg/day

Comments:

• This drug should not be used to treat more than 1 episode every 3 days, and no more than 5 episodes/month.
• The subsequent dose should not be administered if the patient has difficulty breathing OR if the patient has sedation that is not typically observed during a seizure cluster episode.

Use: Acute treatment of intermittent, stereotypic episodes of frequent seizure activity (e.g., acute repetitive seizures, seizure clusters) that are distinct from a patient's usual seizure pattern

Renal Dose Adjustments

No adjustment recommended.

Liver Dose Adjustments

Chronic hepatic dysfunction: The dose should be titrated to the desired response.

Dose Adjustments

Obese patients:

• Dosing should be calculated based on the patient's ideal body weight.

Parenteral:
IM:
PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE, HIGHER-RISK SURGICAL PATIENTS, OR THOSE WHO RECEIVED CONCOMITANT NARCOTICS OR CENTRAL NERVOUS SYSTEM (CNS) DEPRESSANTS:

• Dosing should be reduced in patients receiving this drug for sedation.

DEBILITATED/CRITICALLY ILL PATIENTS AND/OR THOSE OVER 60 YEARS WHO RECEIVED CONCOMITANT NARCOTICS/CNS DEPRESSANTS:

• Patients should be given approximately 50% of the IM dose recommended for healthy adult patients.
• Maintenance dose: Approximately 25% of the IM dose first used to reach optimal sedation; however, the need for continued sedation with maintenance dosing should be carefully considered.

IV:
ADULT PATIENTS WHO RECEIVED CONCOMITANT NARCOTICS/CNS DEPRESSANTS:

• Patients should be given approximately 30% less of the dose than in patients who did not receive premedications.
• Maintenance dose: Approximately 25% of the dose first used to reach optimal sedation; however, the need for continued sedation with maintenance dosing should be carefully considered.

PREMEDICATED PATIENTS WITH SEVERE SYSTEMIC DISEASE/DEBILITATION:

• Usual dose: 0.15 mg/kg IV once may provide sufficient anesthesia

CONTINUOUS INFUSION:

• Doses should be adjusted up or down by 25% to 50% of the initial infusion rate to assure adequate sedation.
• Once maintenance dose levels are attained, the dose should be decreased by 10% to 25% every few hours to determine the lowest effective infusion rate.

Precautions

US BOXED WARNINGS:
INDIVIDUALIZATION OF DOSAGE:
Recommendations:

• This drug must never be used without individualization of dosage.
• The initial IV dose for sedation in adult patients may be as little as 1 mg but should not exceed 2.5 mg in a normal, healthy adult.
• Lower doses are necessary for older (over 60 ears) or debilitated patients, and in patients receiving concomitant narcotics or other central nervous system (CNS) depressants.
• The initial dose and all subsequent doses should always be titrated slowly; administer over at least 2 minutes and allow at least an additional 2 minutes to fully evaluate the sedative effect.
• The use of the 1 mg/mL formulation (or dilution of the 1 mg/mL or 5 mg/mL formulation) is recommended to facilitate slower injection.
• Doses of sedative medications in pediatric patients must be calculated on a mg/kg basis, and initial doses and all subsequent doses should always be titrated slowly.
• The initial pediatric dose of midazolam for sedation/anxiolysis/amnesia is age, procedure, and route-dependent.

Neonates:
Recommendations:

• This drug should not be administered by rapid injection in the neonatal population.
• Severe hypotension and seizures have been reported following rapid IV administration, especially with the concomitant use of fentanyl.

PERSONNEL AND EQUIPMENT FOR MONITORING AND RESUSCITATION:
Adults and Pediatrics:

• IV and oral syrup formulations have been associated with respiratory depression and respiratory arrest, especially when used for sedation in noncritical care settings.
• Oral syrup formulations have been associated with reports of airway obstruction, apnea, desaturation, hypoxia, and respiratory depression, most often when used concomitantly with other CNS depressants.
• In some cases, where this was not recognized promptly and treated effectively, death or hypoxic encephalopathy has resulted.

Recommendations:

• IV and oral syrup formulations should be used only in hospital or ambulatory care settings, including health care providers' and dental offices, that provide for continuous monitoring of respiratory and cardiac function (e.g., pulse oximetry).
• Immediate availability of resuscitative drugs and age- and size-appropriate equipment for bag/valve/mask ventilation and intubation, and personnel trained in their use and skilled in airway management should be assured.
• IV formulations: For deeply sedated pediatric patients, a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure.
• Oral syrup formulations: For deeply sedated patients, a dedicated individual, other than the practitioner performing the procedure, should monitor the patient throughout the procedure.

RISKS FROM CONCOMITANT USE WITH OPIOIDS:

• Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and/or death.

Recommendations:

• Concomitant prescribing of these drugs should be reserved for use in patients for whom alternative treatment options are inadequate.
• Patients should be monitored for respiratory depression and sedation.
• Doses and the duration of therapy should be limited to the minimum required.

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• Patients with acute narrow-angle glaucoma
• Intrathecal or epidural administration (parenteral formulations containing benzyl alcohol)
• Use in premature infants (parenteral formulations containing benzyl alcohol)

Safety and efficacy of oral syrup formulations have not been established in patients younger than 6 months.

Safety and efficacy of nasal spray formulations have not been established in patients younger than 12 years.

Consult WARNINGS section for additional precautions.

US Controlled Substance: Schedule IV

Dialysis

Data not available

Other Comments

Administration advice:

• IV formulations should be administered slowly (e.g., over 2 minutes), and the patient's sedation level should be evaluated for at least 2 minutes before administering another dose.
• Oral syrup: Once the correct dose is measured, the oral syrup should be administered directly into the mouth. Dilution with other liquids should be avoided.
• Oromucosal solution: The solution should be inserted slowly into the space between the gum and cheek. Smaller patients and/or larger volumes may receive half of the dose in one side of the mouth, and the rest of the dose in the other side of the mouth.
• Parenteral solution: Prior to administration, this drug should be inspected for particulate matter and discoloration. This formulation should be given IV or IM, and extravasation should be avoided.
• Rectal formulations: Rectal solutions should be administered with a plastic applicator fixed on the end of a syringe. If the volume of the solution is too small, water may be added to a total volume of 10 mL.

Storage requirements:

• Oral syrup: Once the correct dose is measured, the oral dispenser/syringe may be covered with a cap tip.
• Parenteral solution: At 0.5% concentrations, this drug is compatible with 5% dextrose in water and 0.9% sodium chloride for up to 24 hours and with lactated Ringer's solution for up to 4 hours.

Reconstitution/preparation techniques:

• Parenteral solution: A 1 mg/mL solution may be diluted with 0.9% sodium chloride or 5% dextrose in water.

IV compatibility:

• The parenteral solution may be mixed in the same syringe with morphine sulfate, meperidine, atropine sulfate, or scopolamine.

General:

• This drug does not protect against increases in intracranial pressure or heart rate/blood pressure rise associated with endotracheal intubation under light general anesthesia.
• Limitations of use: This drug should be limited to healthcare providers who are capable of monitoring and treating respiratory/cardiovascular adverse events, including respiratory and cardiac resuscitation. Chronic and/or home use should be avoided.
• The dose of this drug should be determined by patient response, the type/duration of the procedure, and the type/dose of concomitant medications.

Monitoring:

• Sedation
• Heart rate and blood pressure
• Respiratory rate and oxygen saturation

Patient advice:

• Advise patients to speak to their healthcare provider if they become pregnant, intend to become pregnant, or are breastfeeding.
• Inform patients that this drug may cause drowsiness, and they should avoid driving or operating machinery until the full effects of the drug are seen.
• Patients and their caregivers should be told to report any signs/symptoms of respiratory depression or profound sedation.
• Patients should be advised to report alcohol consumption and all concurrent prescription and nonprescription medications or herbal products they are taking.

Frequently asked questions

• What is the correct way to use Nayzilam Nasal Spray?