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Trade names | Byfavo |
Other names | CNS-7056 [1] |
AHFS/Drugs.com | Monograph |
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Routes of administration | Intravenous |
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Formula | C21H19BrN4O2 |
Molar mass | 439.313 g·mol−1 |
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Remimazolam, sold under the brand name Byfavo, is a medication for the induction and maintenance of procedural sedation in adults for invasive diagnostic or surgical procedures lasting 30 minutes or less. [2] [5] [6] It is a benzodiazepine drug, developed by PAION AG in collaboration with several regional licensees as an alternative to the short-acting imidazobenzodiazepine midazolam, for use in the induction of anesthesia and conscious sedation for minor invasive procedures. Remimazolam was found to have both a more rapid onset and a shorter duration than midazolam, and human clinical trials showed a faster recovery time and predictable, consistent pharmacokinetics, suggesting some advantages over existing drugs for these applications. [7] [8]
The most common side effects for procedural sedation include low blood pressure, high blood pressure, diastolic hypertension, systolic hypertension, low blood oxygen level, and diastolic hypotension. [5] [6]
Remimazolam was approved for medical use in the United States in July 2020, [5] [6] and in the European Union in March 2021. [3]
Remimazolam is indicated for the induction and maintenance of procedural sedation in adults (lasting 30 minutes or less in the USA). [5] [6] [9]
Remimazolam was approved for medical use in the United States in July 2020. [5] [6]
The U.S. Food and Drug Administration (FDA) approved remimazolam based on evidence from three clinical trials (Trial 1/NCT02290873, Trial 2/NCT02296892 and Trial 3/NCT02532647) in adults undergoing short procedures. [5] Trials were conducted at 32 sites in the United States. [5]
Trials 1 and 3 were conducted in participants undergoing colonoscopy and Trial 2 was conducted in participants undergoing bronchoscopy procedures. [5]
In the trials, participants were randomly divided in three groups: one group received remimazolam, one group received placebo and one group received midazolam (similar, but approved drug). [5] In the first two groups, neither participants nor investigators knew which medications were given and participants could also receive midazolam as a rescue drug when needed for sedation. [5] In the third group, all participants received midazolam only [5] Additionally, in all three trials participants received a medication for pain control [5]
Trials 1 and 2 compared participants who received remimazolam to participants in the other two groups, measuring the success of sedation with the set of pre-determined criteria. [5] Data from Trial 3 were used primarily to assess the side effects of remimazolam when multiple dosing is used. [5]
On 28 January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Byfavo, intended for procedural sedation. [10] The applicant for this medicinal product is PAION Netherlands B.V. [10] Remimazolam (Byfavo) was approved for medical use in the European Union in March 2021. [3]
Phase I [11] and Ib [12] dose-finding studies for procedural sedation with patients recovering faster from remimazolam than midazolam. Phase II trials comparing remimazolam to the standard anesthesia protocols for cardiac surgery and colonoscopy were presented at major conferences in October 2014. [13]
A Phase IIa trial comparing remimazolam to midazolam for upper endoscopy was published in December 2014, finding a similar safety profile. [14] Remimazolam was originally synthesized in the late 1990s at Glaxo Wellcome in their labs in Research Triangle Park, North Carolina. [15] [16] [17]
Anesthesia or anaesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia, paralysis, amnesia, and unconsciousness. An individual under the effects of anesthetic drugs is referred to as being anesthetized.
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, propofol, etomidate, ketamine, pentobarbital, lorazepam and midazolam.
General anaesthesia (UK) or general anesthesia (US) is a method of medically inducing loss of consciousness that renders a patient unarousable even with painful stimuli. This effect is achieved by administering either intravenous or inhalational general anaesthetic medications, which often act in combination with an analgesic and neuromuscular blocking agent. Spontaneous ventilation is often inadequate during the procedure and intervention is often necessary to protect the airway. General anaesthesia is generally performed in an operating theater to allow surgical procedures that would otherwise be intolerably painful for a patient, or in an intensive care unit or emergency department to facilitate endotracheal intubation and mechanical ventilation in critically ill patients. Depending on the procedure, general anaesthesia may be optional or required. Regardless of whether a patient may prefer to be unconscious or not, certain pain stimuli could result in involuntary responses from the patient that may make an operation extremely difficult. Thus, for many procedures, general anaesthesia is required from a practical perspective.
Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was approved under the brand name Diprivan. Numerous generic versions have since been released. Intravenous administration is used to induce unconsciousness after which anesthesia may be maintained using a combination of medications. It is manufactured as part of a sterile injectable emulsion formulation using soybean oil and lecithin, giving it a white milky coloration.
Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.
Midazolam, sold under the brand name Dormicum and Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It induces sleepiness, decreases anxiety, and causes anterograde amnesia.
An anesthetic or anaesthetic is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.
Premedication is using medication before some other therapy to prepare for that forthcoming therapy. Typical examples include premedicating with a sedative or analgesic before surgery; using prophylactic (preventive) antibiotics before surgery; and using antiemetics or antihistamines before chemotherapy.
Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.
Butorphanol is a morphinan-type synthetic agonist–antagonist opioid analgesic developed by Bristol-Myers. Butorphanol is most closely structurally related to levorphanol. Butorphanol is available as the tartrate salt in injectable, tablet, and intranasal spray formulations. The tablet form is only used in dogs, cats and horses due to low bioavailability in humans.
Etomidate is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardioversion and electroconvulsive therapy. It was developed at Janssen Pharmaceutica in 1964 and was introduced as an intravenous agent in 1972 in Europe and in 1983 in the United States.
Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation associated with schizophrenia or bipolar I or II disorder.
Ro48-6791 is a drug, an imidazobenzodiazepine derivative developed by Hoffman-LaRoche in the 1990s.
Procedural sedation and analgesia (PSA) is a technique in which a sedating/dissociative medication is given, usually along with an analgesic medication, in order to perform non-surgical procedures on a patient. The overall goal is to induce a decreased level of consciousness while maintaining the patient's ability to breathe on their own. Airway protective reflexes are not compromised by this process and therefore endotracheal intubation is not required. PSA is commonly used in the emergency department, in addition to the operating room.
Twilight anesthesia is an anesthetic technique where a mild dose of sedation is applied to induce anxiolysis, hypnosis, and anterograde amnesia. The patient is not unconscious, but sedated. During surgery or other medical procedures, the patient is under what is known as a "twilight state", where the patient is relaxed and "sleepy", able to follow simple directions by the doctor, and is responsive. Generally, twilight anesthesia causes the patient to forget the surgery and the time right after. It is used for a variety of surgical procedures and for various reasons. Just like regular anesthesia, twilight anesthesia is designed to help a patient feel more comfortable and to minimize pain associated with the procedure being performed and to allow the medical practitioner to practice without interruptions.
JM-1232 is a sedative and hypnotic drug being researched as a potential anesthetic. It has similar effects to sedative-hypnotic benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine hypnotic. It was developed by a team at Maruishi Pharmaceutica.
Difelikefalin, sold under the brand name Korsuva, is an opioid peptide used for the treatment of moderate to severe itch. It acts as a peripherally-restricted, highly selective agonist of the κ-opioid receptor (KOR).
Coinduction in anesthesia is a pharmacological tool whereby a combination of sedative drugs may be used to greater effect than a single agent, achieving a smoother onset of general anesthesia. The use of coinduction allows lower doses of the same anesthetic agents to be used which provides enhanced safety, faster recovery, fewer side-effects, and more predictable pharmacodynamics. Coinduction is used in human medicine and veterinary medicine as standard practice to provide optimum anesthetic induction. The onset or induction phase of anesthesia is a critical period involving the loss of consciousness and reactivity in the patient, and is arguably the most dangerous period of a general anesthetic. A great variety of coinduction combinations are in use and selection is dependent on the patient's age and health, the specific situation, and the indication for anesthesia. As with all forms of anesthesia the resources available in the environment are a key factor.
Total intravenous anesthesia (TIVA) refers to the intravenous administration of anesthetic agents to induce a temporary loss of sensation or awareness. The first study of TIVA was done in 1872 using chloral hydrate, and the common anesthetic agent propofol was licensed in 1986. TIVA is currently employed in various procedures as an alternative technique of general anesthesia in order to improve post-operative recovery.
Ciprofol is a novel 2,6-disubstituted phenol derivative that is used for the intravenous induction of general anesthesia. A short-acting and highly selective γ-aminobutyric acid agonist, ciprofol is 4–6 times more potent than other phenol derivatives such as propofol or fospropofol.