Claris Lifesciences


Macropharma Corp
Full Prescribing Info
Sedoz also contains midazolam 1 mg, benzyl alcohol 1% v/v as preservative and water for injection.
Midazolam is a short-acting, water soluble benzodiazepine used as a sedative and anesthetic agent. Because of its water solubility, it is well tolerated locally at the sites of IV or IM injection. Another notable feature of midazolam is the good cardiovascular stability associated with its use. Midazolam is an imidazobendiazepine. It is 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo(1,5-a)(1,4) benzodiazepine. The empirical formula of midazolam is C18H13CIFN3 and its molecular weight is 325.8.
Pharmacology: Mechanism of Action: Midazolam has anxiolytic hypnotic, anticonvulsant, muscle relaxant and anterograde amnestic effects. The mechanism of action of midazolam is not clearly understood, however, it is probably similar to that of other benzodiazepines ie, through interference with the re-uptake of the inhibitory neurotransmitter γ-amino butyric acid (GABA), thereby causing accumulation of GABA. Midazolam has a relatively high affinity (about twice that of diazepam) for the benzodiazepine receptor. The site and mechanism of the amnestic action of midazolam are not known.
Pharmacokinetics: Midazolam is rapidly absorbed following IM administration with a bioavailability >90%. The peak plasma effect of Midazolam is reached within 15-60 min following IM injection. Midazolam is widely distributed in the body including cerebrospinal fluid and brain. It is extensively bound to plasma proteins (97%). Midazolam is rapidly metabolized to 1-hydroxymethyl midazolam and 4-hydroxy midazolam. The pharmacological activity of these metabolites is negligible as compared to that of the parent compound. Midazolam is excreted mainly through the renal route as glucuronide conjugates. Less than 0.03% of an IV dose is excreted unchanged. The elimination t½ of midazolam is about 2.5 hrs.
For preoperative sedation, conscious sedation prior to short diagnostic or endoscopic procedures, induction of general anesthesia prior to administration of other anesthetic agents.
Dosage/Direction for Use
Sedoz is a potent sedative agent and requires slow administration and individualization of dosage. Sedoz injection is compatible with 5% dextrose in water, 0.9% sodium chloride and lactated Ringer's solution.
Adults: Usual Dose: Preoperative Sedation: IM: The recommended premedication dose of Sedoz for adult patients <60 years is 0.07-0.08 mg/kg administered about 1 hr before surgery. The dose must be individualized and reduced when Sedoz is administered to patients with chronic obstructive pulmonary disease (COPD), patients >60 years and patients who have received concomitant narcotics or other CNS depressants and other high-risk surgical patients. For IM use, Sedoz should be injected deep in a large muscle mass.
Conscious Sedation: IV: When used for conscious sedation, dosage must be individualized and titrated. Sedoz should not be administered by rapid or single IV bolus administration. Sedoz 1 mg/mL is recommended for conscious sedation to facilitate slower injection. Both 1 and 5 mg/mL formulations may be diluted with 0.9% sodium chloride or 5% dextrose in water. Maintenance Dose: Additional doses to maintain the desired level of sedation may be given in increments of 25% of the dose used to first reach the sedative endpoint, but again only by slow titration, especially in the elderly and chronically-ill or debilitated patient. These additional doses should be given only when a thorough clinical evaluation clearly indicates the need for additional sedation.
Healthy Adults <60 years: Titrate slowly to the desired effect eg, the initiation of slurred speech, no more than 2.5 mg should be given at first over a period of at least 2 min. Wait for an additional ≥2 min to fully evaluate the sedative effect. If further titration is necessary, continue to titrate using small increments to the appropriate level of sedation. A total dose >5 mg is not usually necessary to reach the desired endpoint.
Patients ≥60 years and Debilitated or Chronically-Ill Patients: As the danger of under ventilation or apnea is greater in elderly patients and those with chronic disease states or decreased pulmonary reserve and because the peak effect may take longer in these patients, increments should be smaller and the rate of injection slower. Some patients may respond to as little as 1 mg. No more than 1.5 mg should be given over a period of no less than 2 min, waiting an additional ≥2 min to fully evaluate the sedative effect. If additional titration is necessary, it should be given at a rate of no more than 1 mg over a period of 2 min, waiting for an additional ≥2 min each time to fully evaluate the sedative effect. Total doses >3.5 mg are not usually necessary.
Induction of Anesthesia: Unpremedicated Patients: In the absence of premedication, an average adult <55 years will require an initial dose of 0.3-0.35 mg/kg for induction, administered over 20-30 sec and allowing 2 min for effect. If needed, increments of approximately 25% of the patient's initial dose may be used to complete induction. In resistant cases, up to 0.6 mg/kg may used for induction but such large doses may prolong recovery.
Unpremedicated patients >55 years usually require less Sedoz for induction; an initial dose of 0.3 mg/kg is recommended. Unpremedicated patients with severe systemic disease or other debilitation usually require less Sedoz for induction. An initial dose of 0.25 mg/kg will usually suffice; in some cases, as little as 0.15 mg/kg may suffice.
Premedicated Patients: When the patient has received sedative or narcotic premedication, the range of recommended doses is 0.15-0.36 mg/kg.
In adults <55 years, a dose of 0.25 mg/kg, administered over 20-30 sec and allowing 2 min for effects, will usually suffice.
An initial dose of 0.2 mg/kg is recommended for surgical patients >55 years.
Symptoms: While there is insufficient human data on overdosage with Sedoz, the manifestations of Sedoz overdosage are expected to be similar to those observed with other benzodiazepines and including sedation, somnolence, confusion, impaired coordination, diminished reflexes, coma and untoward effects on vital signs.
Treatment: Respiration, pulse rate and blood pressure should be monitored and general supportive measures should be employed. Attention should be given to the maintenance of a patient airway and support of ventilation. An IV infusion should be started. Should hypotension develop, treatment may include IV fluid therapy, repositioning, judicious uses of vasopressors appropriate to the clinical situation.
Flumazenil, a specific benzodiazepine-receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when overdose with a benzodiazepine is known or suspected.
Known hypersensitivity to benzodiazepines. Patients with acute narrow glaucoma. Benzodiazepines may be used in patients with open-angle glaucoma only if they receive appropriate therapy.
High-risk surgical patients and elderly patients require lower doses, whether premedicated or not. Patients with COPD are unusually sensitive to the respiratory depressant effect of Sedoz. The initial dose should be reduced in patients with impaired renal function and in the elderly.
Sedoz must never be used without individualization of dosage. Prior to IV administration of Sedoz in any dose, the immediate availability of oxygen, resuscitative equipment and skilled personnel for the maintenance of a patient airway and support of ventilation should be ensured. Patients should be continuously monitored for early signs of underventilation or apnea, which can lead to hypoxia/cardiac arrest unless effective countermeasures are taken immediately. Vital signs should continue to be monitored during recovery period. When used for conscious sedation, Sedoz should not be administered by rapid or single IV bolus administration.
Concomitant use of barbiturates, alcohol or other CNS depressants increases the risk of underventilation or apnea and may contribute to prolonged drug effect.
Special Precautions
General: Impairment of psychomotor skills may occur following Sedoz sedation or anesthesia and may persist for varying lengths of time depending upon the combination of medications and total dosages administered.
Effects on the Ability to Drive or Operate Machinery: Possible adverse effects on the patient's ability to drive or perform other tasks requiring alertness and coordination should be kept in mind when Sedoz is administered for an outpatient procedure. It is recommended that the patient should not operate hazardous machinery or a motor vehicle until the effects of Sedoz eg, drowsiness and amnesia have subsided or until the day after anesthesia and surgery, whichever is longer.
Drug Abuse and Dependence: Sedoz produced physical dependence of a mild to moderate intensity in cynomolgus monkeys after 5-10 weeks of administration. Available data concerning the drug abuse and dependence potential of Sedoz suggest that its abuse potential is equivalent to that of diazepam.
Carcinogenicity, Mutagenicity & Impairment of Fertility: A marked increase in the incidence of hepatic tumors in female mice and an increase in benign thyroid follicular cell tumors in male mice were noted after chronic administration of Sedoz at the dose of 80 mg/kg/day. Dosages of 9 mg/kg (25 times of the usual dose in humans) do not increase the incidence of these tumors. Sedoz did not have mutagenic activity in the Ames' test, Chinese hamster lung cell test, human lymphocytes or in the micronucleus test in mice.
Use in pregnancy: Sedoz did not cause any impairment of fertility when given at doses up to 10 times the human dose of 0.35 mg/kg.
Use in lactation: Sedoz is secreted in human milk. It is not recommended for use in nursing mothers.
Use in children: Appropriate studies on the relationship of age to the effects of Sedoz have not been performed in children ≤18 years. However, no pediatric specific problems have been documented to date.
Use in the elderly: Due to age-related decrease in renal function, elderly patients may require a reduction in dosage.
Use In Pregnancy & Lactation
Use in pregnancy: Sedoz did not cause any impairment of fertility when given at doses up to 10 times the human dose of 0.35 mg/kg.
Use in lactation: Sedoz is secreted in human milk. It is not recommended for use in nursing mothers.
Adverse Reactions
Fluctuations in vital signs are the most frequently seen effects following parenteral administration of Sedoz. Apnea may occur in some patients following IV administration. Local effects at the IV site include pain and tenderness during injection, redness and phlebitis. Other adverse effects that have been infrequently reported are hiccups, nausea, vomiting, headache, drowsiness, bronchospasm, retrograde amnesia, emergence delirium and prolonged emergence from anesthesia.
Drug Interactions
Sedation with Sedoz IV is accentuated by premedication particularly with morphine, meperidine and fentanyl. Consequently, the dosage of Sedoz should be adjusted according to the amount of premedication administered.
Following IV administration of Sedoz, moderate reduction in the required dose of thiopentone for induction has been noted.
Hypotensive effects may be potentiated when medication eg, β-blockers, calcium channel blockers, diuretics, ACE inhibitors, levodopa, magnesium sulfate, nitrates and other hypotensive agents are used concurrently.
Sedoz IV decreases the minimum alveolar concentration of halothane required for general anesthesia. Inhibition of cytochrome P-450 enzyme system by cimetidine and ranitidine may cause a decrease in the hepatic metabolism of Sedoz which may result in delayed elimination and increased blood concentration.
Store at temperatures not exceeding 25°C. Protect from light. Do not freeze.
ATC Classification
N05CD08 - midazolam ; Belongs to the class of benzodiazepine derivatives. Used as hypnotics and sedatives.
Inj 1 mg/mL (vial) x 5 mL.
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