Fused (Fulsed)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceMidazolamMidazolam
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    • Dosage form: & nbspSolution for intravenous and intramuscular administration 1 mg / ml, 5 mg / ml.
    Composition:A solution of 5 mg / ml (ampoules):
    Each ml of the solution contains:
    Midazolam (as hydrochloride) 5 mg
    Excipients: disodium edetate 0.10 mg, sodium chloride for injection 8 mg, hydrochloric acid 1.683 μL, water for injection up to 1.00 ml.
    Solution 1 mg / ml (vials):
    Each ml of the solution contains:
    Midazolam (as hydrochloride) 1 mg
    Excipients: benzyl alcohol 0.01 ml, disodium edetate 0.10 mg, sodium chloride for injection 8
    Description:Transparent from colorless to light yellow liquid.
    Pharmacotherapeutic group:Sleeping pills.
    ATX: & nbsp

    N.05.C.D.08   Midazolam

    Pharmacodynamics:Fulsed (midazolam) belongs to the list of potent drugs BACCH. Midazolam is an imidazole derivative of a short-acting benzodiazepine. Due to the presence of the imidazole ring, at a low pH (<4) it is readily soluble in water (an open imidazole ring), and at physiological pH (> 4), it is readily soluble in fats (closed imidazole ring).
    Like other benzodiazepines, binding to the corresponding receptor enhances the action of γ-aminobutyric acid (GABA), which leads to the activation of the chlorine channel. It is also assumed that there are receptors for benzodiazepines not bound to GABA.
    Midazolam has a pronounced sleeping pills, central miorelaxing, anxiolytic and anticonvulsant action. Has some depressing effect on the cardiovascular system, causes antegrade amnesia. Pharmacological effects are characterized by rapid onset and short duration of action.
    When administered intravenously in small doses, it causes relaxation of skeletal muscles and pre- and postoperative amnesia, most pronounced 2-5 minutes after administration, with the preserved ability to communicate with the doctor (sedation with preservation of consciousness). After about 3 hours from the moment of drug administration, the patient completely restores his psychomotor activity.
    After intravenous administration to potentiate the effects of general anesthetics in combination with opioid premedication, the ciliary reflex depression occurs within about 1.5 minutes, and in patients without premedication, from 2 to 2.5 minutes.Opiates facilitate the induction of general anesthesia and can reduce the dose of the drug, speed up sleep and reduce the difference in the individual reaction to the drug.
    The use of a different kind of premedication (drugs from the group of benzodiazepines or other hypnotics and sedatives) does not enhance the effect of midazolam. Midazolam causes a small (to moderate) decrease in blood pressure, cardiac output and peripheral vascular resistance.
    When administered intravenously at a dose of 0.1 mg / kg body weight midazolam causes a decrease in the respiratory volume compensated by an increase in the respiratory rate, reduces the sensitivity of the respiratory center to carbon dioxide, especially in patients with concomitant respiratory failure. After the introduction of midazolam, apnea may occur; the threat of apnea increases with an increase in the dose of the drug and the rate of administration, and it is also higher in patients who have previously been injected with narcotic analgesics.
    Midazolam to a small extent reduces intracranial pressure, except for patients after trauma to the skull, which have a slight increase in intracranial pressure.
    Midazolam to a small extent reduces cerebral blood flow and oxygen consumption. Somewhat stronger than thiopental reduces renal blood flow.
    The drug appears after about 15 minutes, and reaches a maximum in the period of 30 to 60 minutes after intramuscular injection.
    Pharmacokinetics:After intramuscular injection, 80% to 100% of the administered dose of midazolam is absorbed, and the maximum plasma concentration is reached after about 45 minutes. The pharmacokinetics of the drug used in continuous infusion corresponds to the pharmacokinetics after the administration of a single dose.
    The volume of distribution in the equilibrium state is 0.95 to 6.61 l / kg. In elderly people, it is increased, for women and obese people more than for men and lean individuals.
    The connection with plasma proteins is 96%. In chronic renal failure, the degree of binding decreases.
    Small concentrations of midazolam are found in the cerebrospinal fluid.
    Midazolam biotransformed mainly to alpha-hydroxyimidazolam and in the form of this metabolite 50-70% of the dose is excreted through the kidneys within 24 hours after administration; whereas in the form of 4-hydroxymidazolam - 3% dose and alpha-hydroxymidazolam -1%.Small amounts are excreted in the urine unchanged. The half-life for midazolam and its metabolites is approximately 1.2 to 12.3 hours. The half-life of the drug is prolonged in obese and elderly people. The total plasma clearance in healthy people is 0.15-0.77 L / h / kg and decreases in elderly patients.
    In patients with chronic renal failure, the free fraction of midazolam in the plasma, the volume of distribution and plasma clearance are increased, the state of liver function does not affect the rate of its elimination.
    Midazolam penetrates the placental barrier and is excreted in breast milk.
    Indications:Intramuscularly:
    Premedication before general anesthesia.
    Intravenously:
    - Induction of general anesthesia before using another drug for general anesthesia or supporting anesthesia with inhalational anesthetics during short-term surgical manipulations.
    - Before diagnostic and small surgical procedures performed under local or conduction anesthesia.
    - Insomnia (short-term treatment) - to achieve rapid sedation.
    Contraindications:Hypersensitivity to benzodiazepines or other components of the drug. Acute respiratory failure, shock, coma, acute alcohol poisoning, myasthenia gravis, angle-closure glaucoma, sleep disorders in psychoses and severe depression, muscular dystrophy, chronic obstructive pulmonary disease (COPD) (severe course), pregnancy (I trimester), birth , the period of breastfeeding.
    Carefully:Organic diseases of the brain, liver failure, chronic renal failure, chronic heart failure, respiratory failure, obesity, apnea syndrome (during sleep), children's age.
    Pregnancy and lactation:Benzodiazepines, used in the first trimester of pregnancy, increase the risk of congenital malformations. The use of midazolam during pregnancy is allowed only if there is no possibility of introducing an alternative drug, and the use of midazolam is absolutely necessary in connection with the patient's condition. It is necessary to inform the patient about the risk associated with the use of midazolam in pregnancy.
    Midazolam penetrates the placental barrier.Benzodiazepines, used in the last weeks of pregnancy, can cause CNS depression in a newborn.
    It is not recommended to use midazolam in the period of childbirth.
    Midazolam is excreted in breast milk. Woman receiving midazolam, should not breast-feed.
    Dosing and Administration:The dose must be selected individually.
    Dosing in adults:
    1. Premedication before general anesthesia (intramuscularly):
    Patients in good general condition: 0.07 to 0.08 mg / kg body weight (about 5 mg), deep into the muscle, approximately 60 minutes before the onset of anesthesia.
    In patients with COPD, over 60 years of age, depleted, with renal failure, which was followed by additional premedication with opiates or other drugs that depress the central nervous system, it is necessary to reduce the dose.
    2. Induction of general anesthesia (intravenously):
    Fulsed can significantly reduce the initial dose of other drugs for general anesthesia.
    without premedication:
    - Patients younger than 55 years of age: usually administered intravenously 0.3 to 0.35 mg / kg body weight for 5-30 seconds; it is necessary to wait for about 2 minutes until the effect is achieved; if additional injection is necessary for complete induction, it is administered at a dose of about 25% of the initial dose,or begin inhalation anesthesia; sometimes even doses of up to 0.6 mg / kg of body weight are required, however, they can slow the patient's awakening process.
    - Patients older than 55 years: the initial dose of 0.15-0.3 mg / kg body weight.
    - Depleted patients, with renal insufficiency: 0.15-0.25 mg / kg body weight.
    after premedication, especially narcotic analgesics:
    - Patients younger than 55 years of age: an initial dose of 0.15-0.25 mg / kg body weight.
    - Patients older than 55 years in good general condition (ASA I and II): 0.2 mg / kg body weight.
    - Patients older than 55 years old, malnourished, with renal insufficiency: 0.15 mg / kg body weight.
    3. Achieving a lasting sedative effect in intensive care units:
    Fulsed should be administered intravenously in the form of single injections or continuous infusion. Doses in each case are determined individually depending on the clinical condition and age of the patient, as well as the drugs currently taken.
    with a single injection:
    - Without additional drugs: reintroduce small doses of Fulceda 1 mg - 2 mg until a sedative effect is achieved.
    - With the use of opiates: firstly, you need to inject an analgesic, and then Fulsed in a dose of 1 mg - 2 mg, repeating the introduction before achieving a sedative effect.
    with continuous intravenous administration:
    - Dose 1-2.5 mg administered for 20-30 seconds every 5 minutes, the total loading dose - 0.03-0.3 mg / kg, but not more than 15 mg. Maintenance dose: 0.03 - 0.2 mg / kg / hour. Introduction should start with low doses. The dose should be reduced or from a maintenance dose altogether discarded in patients with hypovolemia, spasm of blood vessels or hypothermia.
    - In combination with opioids, it is recommended first to administer Fulzed in a low dose of 0.01-0.1 mg / kg / h. The rate of infusion with the combined use of Fulceda and opiates should be reduced.
    4. Sedative effect with preservation of consciousness in diagnostic and surgical manipulations under local and conductive anesthesia:
    Fuldseed should be administered intravenously slowly, in small doses, adapting the dose to the patient's individual response. Individual reaction depends on age, health status and simultaneous administration of other drugs. Premedication with other drugs that depress the central nervous system can reduce the need for Fulceda by 50%. To maintain a sedative effect, additional doses may be required,while taking into account the patient's condition and paying special attention to that additional doses should not exceed 25% of the dose that caused the effect of "confused" speech.
    Adults under the age of 60 years in good general condition: the initial dose of about 1 mg to 2.5 mg maximum (0.035 mg / kg body weight) is administered intravenously slowly for 2-3 minutes.
    Injections of the drug should be repeated until the development of "confused" speech. To fully assess sedation, wait 2 or more minutes. If subsequent administration of the drug is necessary, it should be used at low doses (about 1 mg or less), making a 2-minute break after each regular dose, usually enough to obtain a dose effect of up to 5 mg.
    Elderly patients are depleted with renal failure: an initial dose of about 1-1.5 mg, after a 2-minute wait, the next dose can be administered. Usually, a dose of up to 3.5 mg is sufficient to obtain the effect.
    Dosing in children:
    The dose of the drug should be set individually.
    Premedication: intravenously, usually from 0.08 mg / kg body weight to 0.2 mg / kg body weight.
    General anesthesia: intravenously, usually 0.05 mg / kg body weight to 0.2 mg / kg body weight.
    Side effects:Falsed can cause a decrease in the respiratory volume and respiratory rate (in 23.3% of cases after intravenous administration and in 10.8% of cases after intramuscular injection), fluctuations in blood pressure and pulse rate. In some patients, oxygen saturation of hemoglobin below 80% may decrease. The purpose of oxygen quickly compensates for this decline.
    After intramuscular administration of Fulceda, a headache (about 1.3%) is observed. In elderly people or at high risk, respiratory and cardiovascular activity can be suppressed, in most cases, when other drugs depressing the central nervous system, especially the respiratory center (narcotic analgesics) are introduced.
    Also occur: hiccough (about 4%), nausea and vomiting (2-3%), cough (1.3%), excessive sedation (1.5%), drowsiness after waking up (1.2%).
    Less frequently observed (<1%)
    From the respiratory system: spasm of the larynx, narrow breathing, bronchospasm, dyspnea, hyperventilation (tachypnea), shallow breathing.
    From the cardiovascular system:     extrasystole, up to bigemini, bradycardia, sometimes tachycardia, lowering blood pressure, stopping the heart.
    From the gastrointestinal tract: "sour" taste in the mouth, hypersalivation, belching.
    From the nervous system: retrograde amnesia, antegrade amnesia, euphoria, hallucinations, confusion, dysphoric reactions, anxiety, vestibular disorders, unsteadiness of gait, delusions, agitation in the derivation of general anesthesia, prolonged awakening after general anesthesia, athetoid movements, ataxia, dizziness, dysphoria, paresthesia , sleep disturbances, nightmares after discontinuation of the drug.
    From the sense organs: blurred vision or diplopia, nystagmus, constriction of the pupils, twitching eyelids, blurred vision, difficulty focusing vision, a feeling of fullness ears.
    From the skin: swelling or burning sensation, heat or cold at the injection site.
    Hypersensitivity reactions: allergic reactions, including anaphylactic reactions, urticaria, rash, itching.
    Others: too deep, long sleep, chills, feeling of weakness, tooth pain, fainting, prolonged use - drug dependence, withdrawal syndrome (abstinence).
    Pain at the site of intravenous administration is rare, and phlebitis develops in approximately 0.4% of cases.
    Overdose:There is no information on acute overdose of midazolam.
    Symptoms of overdose correspond to a deeper therapeutic effect: too strong sedative effect, weakening of reflexes, slowing of the pulse and respiration, coma.
    Therapeutic tactics
    As with an overdose of other drugs from the benzodiazepine group, monitoring of patient breathing, pulse and blood pressure is necessary, and symptomatic treatment with intensive care is indicated. Particular attention should be paid to maintaining the patency of the airways and conducting auxiliary ventilation. With a decrease in blood pressure, intravenous administration of solutions, the position of the patient's body with raised lower limbs, the use of vasoconstrictive drugs is recommended. There is insufficient data on the effectiveness of forced diuresis, peritoneal dialysis and hemodialysis.
    A specific antidote is flumazenil, a benzodiazepine receptor antagonist, which is prescribed in the case of confirmed or suspected benzodiazepine poisoning and removes the inhibitory effect of benzodiazepines on the centralnervous system. Before flumazenil administration, it is necessary to ensure airway patency and access to the vein. The duration of action of flumazenil is shorter than midazolam, therefore in the case of recurrence of CNS depression it is necessary to repeat the administration of flumazenil. Flumazenil is a complement to the treatment and does not replace the corresponding symptomatic therapy. The administration of flumazenil is associated with the risk of seizures, especially in people taking benzodiazepines for a long time, and with an overdose of cyclic antidepressants.
    Interaction:Midazolam strengthens the influence of alcohol on the central nervous system, while taking with alcohol - amnesia pre- and postoperative period. Midazolam intensifies the oppressive effect on the central nervous system of narcotic analgesics, antidepressants, neuroleptics, barbiturates, antiepileptic, antihistamines and other sedative and analgesic drugs, which can lead to deep and prolonged respiratory depression. Administration of midazolam simultaneously with a high dose of fentanyl can cause a significant reduction in blood pressure.Premedication with the use of narcotic analgesics (for example, morphine, fentanyl), barbiturates or fentanyl with droperidol, reduces the need for midazolam. There is a moderate decrease in the need for sodium thiopente (approximately 15%) after intramuscular administration of midazolam in the composition of the premedication. Intravenous administration of midazolam reduces the proportionately minimum alveolar concentration (MAC) of halothane necessary to maintain general anesthesia in proportion to the dose.
    Tachycardia and hypertension caused by ketamine in doses for general anesthesia decrease with midazolam. With the use of midazolam, there is a decrease in the incidence of psychotic reactions after ketamine anesthesia. Erythromycin, cimetidine, amiodarone and antipsychotic drugs can cause a decrease in plasma clearance of midazolam.
    Special instructions:Fulsed injection is not intended for epidural and subdural spinal anesthesia.
    Taking into account the significant individual differences in the reaction to the drug, the Fulcea dose should be set strictly individually.There have been cases of serious complications after intravenous administration of midazolam, namely: depression of the cardiovascular and respiratory system (up to apnea and asystole). Only experienced anesthetists can inject Fuldsed intravenously, in conditions that allow rapid resuscitation (artificial lung ventilation, monitoring of vital functions). During anesthesia and during recovery from anesthesia, close monitoring of the patient is necessary. at untimely carrying out of corresponding actions probably hypoventilation development or an apnea with the subsequent occurrence of a hypoxia or a blood circulation stop.
    In isolated cases, during the surgical and diagnostic manipulations after administration of midazolam, a drop in blood pressure was observed, requiring urgent medical measures. With the use of the sedation method with preservation of consciousness, these complications developed mainly in patients after opiate premedication. In this procedure, you can not use midazolam method of rapid intravenous administration.
    Attention: Fulsed does not prevent the increase in intracranial and arterial pressure, as well as tachycardia, which often occur with intubation of the trachea under conditions of general surface anesthesia. Special care should be taken when administering the drug to patients with COPD, given the risk of respiratory depression.
    In patients with a high risk of developing respiratory depression, elderly, malnourished, renal insufficiency and congestive heart failure, Fulsed should be used with caution in small doses.
    Do not take alcohol before and within 8 hours after Fulcea's administration.
    It is not known what consequences the intra-arterial administration of midazolam can cause, therefore, one should be especially careful not to introduce Fulsed intraarterially. Less than 1% of patients, there may come a paradoxical reaction to the drug (agitation, anxiety, fright, sometimes aggressive behavior, possible involuntary movements: muscle tremors, tonic-clonic convulsions). The cause may be an inappropriate dose or method of administration.
    It is necessary to consider the possibility of developing brain hypoxia or reactions to other drugs taken in combination with Fulced (including local anesthetics).There is evidence of the effectiveness of flumazenil in the event of paradoxical reactions to midazolam.
    Particular care must be given to patients with electrolyte imbalance, who receive Fulsed intravenously.
    Effect on the ability to drive transp. cf. and fur:The time that must elapse from the introduction of Fulzed until the restoration of functions requiring full mental performance, such as vehicle management and maintenance mechanisms, must be established individually, especially in cases of outpatient drug use. It should take into account the effect of other, prescribed drugs at the same time. It is difficult to predict that the rate of response of a patient under stress will not be slow. It is generally accepted that vehicle management and servicing of mechanisms are not allowed for 8 hours or more after the administration of the drug, unless the effects of its effects have disappeared (manifested, for example, by drowsiness).
    Form release / dosage:Solution for injection 1 mg / ml.
    Solution for injection 5 mg / ml.
    Packaging:Solution for injection 1 mg / ml: for 5 or 10 ml in bottles of glass I of amber type, sealed with a gray cork made of halobutyl rubber with a tear-off lid; 5 bottles on a cardboard stand with instructions for use in a cardboard box.
    Solution for injection 5 mg / ml: 1 ml in ampoules of transparent glass type I with green rings on the neck; 10 ampoules on a cardboard stand, along with instructions for use in a cardboard bundle.
    Storage conditions:Store in a dark place at a temperature of no higher than 25 ° C. Do not freeze. Keep out of the reach of children.
    Shelf life:2 years.
    Do not use after the date shown on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:П N011911 / 01
    Date of registration:26.05.2006 / 19.07.2011
    Expiration Date:Unlimited
    The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India
    Manufacturer: & nbsp
    Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED
    Information update date: & nbsp2016-10-03
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