Byfavo

What Is Byfavo?

Byfavo (remimazolam) is a benzodiazepine used to induce and maintain procedural sedation in adults undergoing procedures lasting 30 minutes or less.

What Are Side Effects of Byfavo?

Side effects of Byfavo include:

• low blood pressure (hypotension),
• high blood pressure (hypertension),
• low blood oxygen (hypoxia),
• slow heart rate,
• fast heart rate,
• nausea,
• fever, and
• headache

Dosage for Byfavo

The dose of Byfavo is an initial dose administered intravenously as a 5 mg push injection over a 1-minute time period.

Byfavo In Children

Safety and effectiveness of Byfavo in pediatric patients have not been established. No studies are available in any pediatric population and extrapolation of adult effectiveness data to the pediatric population is not possible.

What Drugs, Substances, or Supplements Interact with Byfavo?

Byfavo may interact with other medicines such as:

• other central nervous system (CNS) depressant medications, including opioid analgesics, other benzodiazepines, and propofol

Tell your doctor all medications and supplements you use.

Byfavo During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Byfavo; benzodiazepines cross the placenta and may produce respiratory depression and sedation in neonates. There are reports of sedation in infants exposed to benzodiazepines through breast milk. Breastfeeding women may choose to pump and discard breast milk for 5 hours after treatment with Byfavo.

Additional Information

Our Byfavo (remimazolam) for Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

 

Byfavo Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Remimazolam can slow or stop your breathing, especially if you have recently used an opioid medication, alcohol, or other drugs that can slow your breathing. Your caregivers will watch you for symptoms such as weak or shallow breathing.

Tell your caregivers right away if you have:

• weak or shallow breathing;
• confusion;
• slow heartbeats; or
• a light-headed feeling, like you might pass out.

The sedative effects of remimazolam may last longer in older adults. Accidental falls are common in elderly patients who use benzodiazepines.

Common side effects may include:

• feeling light-headed;
• shallow breathing; or
• changes in blood pressure.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Byfavo (Remimazolam for Injection)

 

Byfavo Professional Information

SIDE EFFECTS

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 BYFAVO was evaluated in three prospective, randomized, double-blind, multicenter, parallel group clinical studies in 630 patients undergoing colonoscopy (two studies) or bronchoscopy (one study). Colonoscopy Study 1 and the bronchoscopy study evaluated American Society of Anesthesiologists (ASA) physical status I to III patients, and Colonoscopy Study 2 evaluated ASA III and IV patients.

All three studies evaluated the safety of BYFAVO compared to placebo with midazolam rescue and an open-label midazolam treatment arm. Patients were administered a total dose ranging from 5 to 30 mg of BYFAVO. In these studies, the most common adverse reactions (incidence greater than 10%) following BYFAVO administration were hypotension, hypertension, diastolic hypertension, systolic hypertension, hypoxia, and diastolic hypotension. There were two patients who experienced an adverse reaction that led to discontinuation of study drug. One patient in the BYFAVO arm in the bronchoscopy study discontinued treatment due to bradycardia, hypertension, hypotension, hypoxia, and respiratory rate increase. One patient in the open-label midazolam arm in Colonoscopy Study 2 discontinued due to respiratory acidosis. No deaths were reported during the studies.

Tables 1-3 provide a summary of the common adverse reactions observed in each of the three Phase 3 studies with BYFAVO.

Table 1: Common Adverse Reactions in Colonoscopy Study 1 (Incidence >2%), ASA I to III

Adverse Reaction	BYFAVO N = 296 n (%)	Placebo (with Midazolam Rescue*) N = 60 n (%)	Midazolam N = 102 n (%)
Hypotension§	115 (39%)	25 (42%)	63 (62%)
Hypertension†	59 (20%)	17 (28%)	18 (18%)
Bradycardia	33 (11%)	7 (12%)	16 (16%)
Diastolic hypertension†	29 (10%)	6 (10%)	9 (9%)
Tachycardia	23 (8%)	7 (12%)	13 (13%)
Diastolic hypotension§	23 (8%)	4 (7%)	9 (9%)
Systolic hypertension†	16 (5%)	5 (8%)	6 (6%)
‡ 57/60 (95%) patients received midazolam rescue. § Hypotension defined as a fall in systolic BP to ≤80 mmHg or in diastolic BP to ≤40 mmHg, or a fall in systolic or diastolic BP of 20% or more below baseline or necessitating medical intervention. †Hypertension defined as an increase in systolic BP to ≥180 mmHg or in diastolic BP to ≥100 mmHg, or an increase of systolic or diastolic BP of 20% or more over baseline or necessitating medical intervention.

Table 2: Common Adverse Reactions in Bronchoscopy Study (Incidence >2%)

Adverse Reaction	BYFAVO N = 303 n (%)	Placebo (with Midazolam Rescue*) N = 59 n (%)	Midazolam N = 69 n (%)
Hypotension§	99 (33%)	28 (47%)	23 (33%)
Hypertension†	85 (28%)	9 (15%)	19 (28%)
Diastolic hypertension†	77 (25%)	15 (25%)	16 (23%)
Systolic hypertension†	67 (22%)	13 (22%)	17 (25%)
Hypoxia	66 (22%)	12 (20%)	13 (19%)
Respiratory rate increased	43 (14%)	6 (10%)	10 (14%)
Diastolic hypotension§	41 (14%)	17 (29%)	16 (23%)
Nausea	12 (4%)	2 (3%)	2 (3%)
Bradycardia	11 (4%)	4 (7%)	4 (6%)
Pyrexia	11 (4%)	1 (2%)	1 (1%)
Headache	8 (3%)	0 (0%)	3 (4%)
‡ 57/59 (97%) patients received midazolam rescue. § Hypotension defined as a fall in systolic BP to ≤80 mmHg or in diastolic BP to ≤40 mmHg, or a fall in systolic or diastolic BP of 20% or more below baseline or necessitating medical intervention. †Hypertension defined as an increase in systolic BP to ≥180 mmHg or in diastolic BP to ≥100 mmHg, or an increase of systolic or diastolic BP of 20% or more over baseline or necessitating medical intervention.

Table 3: Common Adverse Reactions in Colonoscopy Study 2 (Incidence >2%), ASA III and IV

Adverse Reaction	BYFAVO N = 31 n (%)	Placebo (with Midazolam Rescue*) N = 16 n (%)	Midazolam N = 30 n (%)
Hypotension§	18 (58%)	11 (69%)	17 (57%)
Hypertension†	13 (42%)	6 (38%)	13 (43%)
Respiratory acidosis	6 (19%)	2 (13%)	8 (27%)
Diastolic hypertension†	3 (10%)	0 (0%)	0 (0%)
Systolic hypertension†	2 (6%)	0 (0%)	0 (0%)
Bradycardia	1 (3%)	1 (6%)	4 (13%)
Respiratory rate decreased	1 (3%)	1 (6%)	2 (7%)
Diastolic hypotension§	1 (3%)	1 (6%)	0 (0%)
Blood pressure diastolic increased	1 (3%)	0 (0%)	0 (0%)
Blood pressure increased	1 (3%)	0 (0%)	0 (0%)
Blood pressure systolic increased	1 (3%)	0 (0%)	0 (0%)
Upper respiratory tract infection	1 (3%)	0 (0%)	0 (0%)
‡ 16/16 (100%) patients received midazolam rescue. § Hypotension defined as a fall in systolic BP to ≤80 mmHg or in diastolic BP to ≤40 mmHg, or a fall in systolic or diastolic BP of 20% or more below baseline or necessitating medical intervention. †Hypertension defined as an increase in systolic BP to ≥180 mmHg or in diastolic BP to ≥100 mmHg, or an increase of systolic or diastolic BP of 20% or more over baseline or necessitating medical intervention.

Adverse reaction data from Colonoscopy Study 1 and the bronchoscopy study analyzed according to the cumulative dose of concomitant fentanyl (<100 mcg, 100-150 mcg and >150 mcg) suggest an increase in some adverse reactions with increasing fentanyl dose, such as hypotension, hypertension, bradycardia, hypoxia, and increased respiratory rate (see Table 4 and Table 5). There were too few patients in each fentanyl stratum in Colonoscopy Study 2 to perform this analysis.

Table 4: Common Adverse Reactions* in Colonoscopy Study 1 by Cumulative Fentanyl Dose

Fentanyl dose (mcg)	BYFAVO			Placebo (with Midazolam Rescue*)			Midazolam
	<100	100-150	>150	<100	100-150	>150	<100	100-150	>150
	N = 148	N = 146	N = 2	N = 9	N = 43	N = 8	N = 31	N = 62	N = 9
Adverse Reaction	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Hypotension§	49 (33%)	64 (44%)	2 (100%)	5 (56%)	17 (40%)	3 (38%)	18 (58%)	36 (58%)	9 (100%)
Hypertension†	24 (16%)	35 (24%)	0 (0%)	1 (11%)	14 (33%)	2 (25%)	3 (10%)	12 (19%)	3 (33%)
Bradycardia	12 (8%)	20 (14%)	1 (50%)	0 (0%)	5 (12%)	2 (25%)	1 (3%)	13 (21%)	2 (22%)
Diastolic hypertension†	9 (6%)	20 (14%)	0 (0%)	0 (0%)	3 (7%)	3 (38%)	2 (6%)	7 (11%)	0 (0%)
Tachycardia	10 (7%)	12 (8%)	1 (50%)	0 (0%)	6 (14%)	1 (13%)	2 (6%)	8 (13%)	3 (33%)
Diastolic hypotension§	10 (7%)	13 (9%)	0 (0%)	0 (0%)	3 (7%)	1 (13%)	3 (10%)	4 (6%)	2 (22%)
Systolic hypertension†	5 (3%)	11 (8%)	0 (0%)	0 (0%)	3 (7%)	2 (25%)	4 (13%)	2 (3%)	0 (0%)
* Incidence >2% of patients. ‡ 57/60 (95%) patients received midazolam rescue. § Hypotension defined as a fall in systolic BP to ≤80 mmHg or in diastolic BP to ≤40 mmHg, or a fall in systolic or diastolic BP of 20% or more below baseline or necessitating medical intervention. †Hypertension defined as an increase in systolic BP to ≥180 mmHg or in diastolic BP to ≥100 mmHg, or an increase of systolic or diastolic BP of 20% or more over baseline or necessitating medical intervention.

Table 5: Common Adverse Reactions* in Bronchoscopy Study by Cumulative Fentanyl Dose

Fentanyl dose (mcg)	BYFAVO			Placebo (with Midazolam Rescue*)			Midazolam
	<100	100-150	>150	<100	100-150	>150	<100	100-150	>150
	N = 215	N = 63	N = 25	N = 26	N = 18	N = 15	N = 29	N = 27	N = 13
Adverse Reaction	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)	n (%)
Hypotension§	52 (24%)	32 (51%)	16 (64%)	7 (27%)	9 (50%)	12 (80%)	7 (24%)	7 (26%)	9 (69%)
Hypertension†	43 (20%)	25 (40%)	18 (72%)	2 (8%)	2 (11%)	5 (33%)	3 (10%)	8 (30%)	8 (62%)
Diastolic hypertension†	65 (30%)	12 (19%)	0 (0%)	11 (42%)	3 (17%)	1 (7%)	10 (34%)	6 (22%)	0 (0%)
Systolic hypertension†	55 (26%)	11 (17%)	1 (4%)	10 (38%)	3 (17%)	0 (0%)	9 (31%)	6 (22%)	2 (15%)
Hypoxia	35 (16%)	22 (35%)	9 (36%)	6 (23%)	2 (11%)	4 (27%)	2 (7%)	5 (19%)	6 (46%)
Respiratory rate increased	22 (10%)	12 (19%)	9 (36%)	1 (4%)	2 (11%)	3 (20%)	2 (7%)	5 (19%)	3 (23%)
Diastolic hypotension§	28 (13%)	13 (21%)	0 (0%)	8 (31%)	7 (39%)	2 (13%)	7 (24%)	6 (22%)	3 (23%)
Nausea	9 (4%)	1 (2%)	2 (8%)	0 (0%)	0 (0%)	2 (13%)	1 (3%)	1 (4%)	0 (0%)
Bradycardia	3 (1%)	4 (6%)	4 (16%)	2 (8%)	1 (6%)	1 (7%)	0 (0%)	2 (7%)	2 (15%)
Pyrexia	7 (3%)	2 (3%)	2 (8%)	0 (0%)	0 (0%)	1 (7%)	1 (3%)	0 (0%)	0 (0%)
Headache	5 (2%)	2 (3%)	1 (4%)	0 (0%)	0 (0%)	0 (0%)	0 (0%)	3 (11%)	0 (0)%
* Incidence >2% of patients. ‡ 57/59 (97%) patients received midazolam rescue. § Hypotension defined as a fall in systolic BP to ≤ 80 mmHg or in diastolic BP to ≤40 mmHg, or a fall in systolic or diastolic BP of 20% or more below baseline or necessitating medical intervention. †Hypertension defined as an increase in systolic BP to ≥180 mmHg or in diastolic BP to ≥100 mmHg, or an increase of systolic or diastolic BP of 20% or more over baseline or necessitating medical intervention.

DRUG INTERACTIONS

Opioid Analgesics And Other Sedative-Hypnotics

The sedative effect of intravenous BYFAVO can be accentuated by concomitantly administered CNS depressant medications, including opioid analgesics, other benzodiazepines, and propofol. Continuously monitor vital signs during sedation and through the recovery period. Titrate the dose of BYFAVO when administered with opioid analgesics and sedative-hypnotics to the desired clinical response [see WARNINGS AND PRECAUTIONS].

Drug Abuse And Dependence

Controlled Substance

BYFAVO contains remimazolam, a Schedule IV controlled substance (CIV).

Abuse

BYFAVO contains the benzodiazepine, remimazolam. Benzodiazepines are a class of sedative drugs with a known potential for abuse. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. In a human abuse potential study conducted in recreational sedative abusers (n = 39), remimazolam (5 and 10 mg, IV) produced responses on positive subjective measures such as “Drug Liking,” “Overall Drug Liking,” “Take Drug Again,” and “Good Drug Effects” that were statistically similar to those produced by the sedative midazolam (2.5 and 5 mg), and statistically greater than the responses on these measures that were produced by placebo.

Dependence

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. In a monkey physical dependence study, chronic administration of remimazolam produced withdrawal signs such as tremors, muscle rigidity, restlessness, impaired motor activity, and a reduction in food consumption upon drug discontinuation. One monkey of six in this study exhibited systemic convulsions and dissociation from the environment. These behaviors are consistent with benzodiazepine withdrawal, which suggests that remimazolam produces physical dependence.

Read the entire FDA prescribing information for Byfavo (Remimazolam for Injection)