Igalmi

IGALMI is indicated for the acute treatment of agitation associated with schizophrenia or bipolar I or II disorder in adults.

• IGALMI should be administered under the supervision of a healthcare provider. A healthcare provider should monitor vital signs and alertness after IGALMI administration to prevent falls and syncope. (
  2.1 Important Recommendations Prior to Initiating IGALMI and During Therapy

  IGALMI should be administered under the supervision of a healthcare provider. A healthcare provider should monitor vital signs and alertness after IGALMI administration to prevent falls and syncope

  [see Warnings and Precautions (5.5)]

  .

  IGALMI is for sublingual or buccal administration. Do not chew or swallow IGALMI. Do not eat or drink for at least 15 minutes after sublingual administration, or at least one hour after buccal administration.
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• Administer sublingually or buccally. Do not chew or swallow. (
  2.1 Important Recommendations Prior to Initiating IGALMI and During Therapy

  IGALMI should be administered under the supervision of a healthcare provider. A healthcare provider should monitor vital signs and alertness after IGALMI administration to prevent falls and syncope

  [see Warnings and Precautions (5.5)]

  .

  IGALMI is for sublingual or buccal administration. Do not chew or swallow IGALMI. Do not eat or drink for at least 15 minutes after sublingual administration, or at least one hour after buccal administration.
  )
• Recommended dosage (
  2.2 Recommended Dosage

  Table 1 includes dosage recommendations for IGALMI based on agitation severity for adults, patients with hepatic impairment, and geriatric patients. Lower dosages are recommended for patients with hepatic impairment and geriatric patients

  [see Warnings and Precautions (5.1)and Use in Specific Populations (8.5, 8.6)].

  If agitation persists after the initial dose, up to two additional doses may be administered at least two hours apart. The dosage recommendations for additional doses vary depending upon the patient population and agitation severity (see Table 1). Assess vital signs including orthostatic measurements prior to the administration of any subsequent doses.

  Due to risk of hypotension, additional half-doses are not recommended in patients with systolic blood pressure (SBP) less than 90 mmHg, diastolic blood pressure (DBP) less than 60 mmHg, heart rate (HR) less than 60 beats per minute, or postural decrease in SBP ≥ 20 mmHg or in DBP ≥ 10 mmHg.

  Table 1: Dosage Recommendations for IGALMI in Adults, Adult Patients with Hepatic Impairment, and Geriatric Patients with Agitation Associated with Schizophrenia or Bipolar I or II Disorder

  Patient Population	Agitation Severity	Initial DoseIGALMI 120 mcg and 180 mcg dosage strengths may be cut in half to obtain the 60 mcg and 90 mcg doses, respectively [see Dosage and Administration (2.3)] .	Optional 2nd/3rdDoses	Maximum Recommended Total Daily Dosage
  Adults	Mild or Moderate	120 mcg	60 mcg	240 mcg
  	Severe	180 mcg	90 mcg	360 mcg
  Patients with Mild or Moderate Hepatic ImpairmentHepatic impairment: Mild (Child-Pugh Class A); Moderate (Child-Pugh Class B); Severe (Child-Pugh Class C)	Mild or Moderate	90 mcg	60 mcg	210 mcg
  	Severe	120 mcg	60 mcg	240 mcg
  Patients with Severe Hepatic Impairment	Mild or Moderate	60 mcg	60 mcg	180 mcg
  	Severe	90 mcg	60 mcg	210 mcg
  Geriatric Patients (≥ 65 years old)	Mild, Moderate, or Severe	120 mcg	60 mcg	240 mcg
  ):

  Patient Population	Agitation Severity	Initial DoseSee Full Prescribing Information for recommendations on administering up to two additional doses and maximum recommended dosages.
  Adults	Mild or Moderate	120 mcg
  	Severe	180 mcg
  Mild or Moderate Hepatic Impairment	Mild or Moderate	90 mcg
  	Severe	120 mcg
  Severe Hepatic Impairment	Mild or Moderate	60 mcg
  	Severe	90 mcg
  Geriatric Patients (≥ 65 years old)	Mild, Moderate, or Severe	120 mcg

• IGALMI 120 mcg and 180 mcg dosage strengths may be cut in half to obtain the 60 mcg and 90 mcg doses, respectively. See Full Prescribing Information for preparation and administration instructions. (
  2.3 Preparation and Administration Instructions

  Keep IGALMI in the foil pouch until ready to administer. IGALMI should be immediately administered once the pouch is opened and the dose prepared.

  Prepare and administer IGALMI under the supervision of a healthcare provider as follows:

  Healthcare Professional: Prepare IGALMI Dose for Patient
  1	Open the sealed foil pouch by tearing straight across at the notch.
  Perform Steps 2a, 2b, 2c and 2d only if a 60 mcg or 90 mcg dose (half of a film) is needed, then proceed to Step 3. If administering a full dose (1 film), proceed directly to Step 3.
  2a	Remove the film from the pouch with clean dry hands.
  2b	Cut the film in half between the dots with clean, dry scissors.
  2c	Discard unused half in waste container.
  2d	Place the half film for administration to the patient back into the pouch.
  3	Immediately give the pouch to the patient.
  4	Instruct patient to remove the film from the pouch with clean dry hands.
  5	For sublingual administration: Instruct patient to place film under the tongue. The film will stick in place. Note: Patient may not eat or drink for 15 minutes after sublingual administration.
  	For buccal administration: Instruct patient to place film behind lower lip. The film will stick in place. Note: Patient may not eat or drink for one hour after buccal administration.
  6	Instruct patient to: Close their mouth. Allow the film to dissolve. Do not chew or swallow the film.

  

  

  

  

  

  

  

  

  

  

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IGALMI is a blue rectangular sublingual film containing on its surface two darker blue spots in dose strengths of 120 mcg and 180 mcg.

There are no available data on IGALMI use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal effects. Available data from published randomized controlled trials and case reports over several decades of use with intravenously administered dexmedetomidine during pregnancy have not identified a drug-associated risk of major birth defects or miscarriage; however, the reported exposures occurred after the first trimester. Most of the available data are based on studies with exposures that occurred at the time of cesarean-section delivery, and these studies have not identified an adverse effect on maternal outcomes or infant Apgar scores. Available data indicate that dexmedetomidine crosses the placenta.

In animal reproductive studies fetal toxicity occurred in the presence of maternal toxicity with subcutaneous administration of dexmedetomidine to pregnant rats during organogenesis at doses 5 times the maximum recommended human dose [MRHD] of 360 mcg/day based on mg/m² body surface area. Adverse developmental effects, including early implantation loss and decreased viability of second generation offspring, occurred when pregnant rats were subcutaneously administered doses less than or equal to the MRHD based on mg/m² from late pregnancy through lactation and weaning

The estimated 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 clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

• Hypotension, Orthostatic Hypotension, and Bradycardia:
  Avoid use of IGALMI in patients with hypotension, orthostatic hypotension, advanced heart block, severe ventricular dysfunction, or history of syncope. Ensure that patients are alert and not experiencing orthostatic or symptomatic hypotension prior to resuming ambulation. (
  5.1 Hypotension, Orthostatic Hypotension, and Bradycardia

  IGALMI causes dose-dependent hypotension, orthostatic hypotension, and bradycardia

  .

  In clinical studies, 18%, 16%, and 9% of patients treated with 180 mcg of IGALMI, 120 mcg of IGALMI, and placebo, respectively, experienced orthostatic hypotension (defined as SBP decrease ≥ 20 mmHg or DBP decrease ≥ 10 mmHg after 1, 3, or 5 minutes of standing) at 2 hours post-dose. In those studies, 7%, 6%, and 1% of patients treated with 180 mcg of IGALMI, 120 mcg of IGALMI, and placebo, respectively, experienced HR ≤ 50 beats per minute within 2 hours of dosing

  [see Adverse Reactions (6.1)].

  In clinical studies with IGALMI, patients were excluded if they had treatment with alpha-1 noradrenergic blockers, benzodiazepines, other hypnotics or antipsychotic drugs four hours prior to study drug administration; had a history of syncope or syncopal attacks; SBP < 110 mmHg; DBP < 70 mmHg; HR < 55 beats per minute; or had evidence of hypovolemia or orthostatic hypotension.

  Reports of hypotension and bradycardia, including some resulting in fatalities, have been associated with the use of another dexmedetomidine product given intravenously (IGALMI is for sublingual or buccal use and is not approved for intravenous use). Clinically significant episodes of bradycardia and sinus arrest have been reported after administration of this other dexmedetomidine product to young, healthy adult volunteers with high vagal tone and when this product was given by rapid intravenous or bolus administration.

  Because IGALMI decreases sympathetic nervous system activity, hypotension and/or bradycardia may be more pronounced in patients with hypovolemia, diabetes mellitus, or chronic hypertension, and in geriatric patients

  [see Dosage and Administration (2.2)and Use in Specific Populations (8.5)].

  Avoid use of IGALMI in patients with hypotension, orthostatic hypotension, advanced heart block, severe ventricular dysfunction, or history of syncope. After IGALMI administration, patients should be adequately hydrated and should sit or lie down until vital signs are within normal range. If a patient is unable to remain seated or lying down, precautions should be taken to reduce the risk of falls. Ensure that a patient is alert and not experiencing orthostatic hypotension or symptomatic hypotension prior to allowing them to resume ambulation

  [see Dosage and Administration (2.1)].
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• QT Interval Prolongation:
  IGALMI prolongs the QT interval; avoid use in patients with risk factors for prolonged QT interval. (
  5.2 QT Interval Prolongation

  IGALMI prolongs the QT interval. Avoid use of IGALMI in patients at risk of torsades de pointes or sudden death including those with known QT prolongation, a history of other arrhythmias, symptomatic bradycardia, hypokalemia or hypomagnesemia, and in patients receiving other drugs known to prolong the QT interval

  [see Drug Interactions (7.1)and Clinical Pharmacology (12.2)].
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• Somnolence:
  Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or operating hazardous machinery for at least eight hours after taking IGALMI. (
  5.3 Somnolence

  IGALMI can cause somnolence. In placebo-controlled clinical studies in adults with agitation associated with schizophrenia or bipolar I or II disorder, somnolence (including fatigue and sluggishness) was reported in 23% and 22% of patients treated with IGALMI 180 mcg and 120 mcg, respectively, compared to 6% of placebo-treated patients. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or operating hazardous machinery, for at least eight hours after taking IGALMI

  [see Adverse Reactions (6.1)]

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