Chemicals / Complex Chemical Agents/ Chemical:

Midazolam (with special reference to Bears, Lagomorphs, Ferrets, Great Apes and Cranes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 

Benzodiazepine sedative, shorter-acting than diazepam, used mainly for pre-medication before anaesthesia. (B201.6.w6, B263)

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Names and Formulae

Type Imidazobenzodiazepine. (B263)
Alternative Names Midazolam hydrochloride. (B263)
Chemical Formula --
Chemical Structure --
Molecular Weight --
Related Chemicals Diazepam

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Physical Properties / Chemistry

Appearance

Crystalline powder, white to light yellow. (B263)

Melting point --
Boiling point --
Density --
Water solubility Depends on the pH: 10.3 mg in 1 mL water at 25 C and pH 3.4. (B263)
Other solubility Highly lipid soluble at body pH. (B263)
Acid/Base pKa 6.15. Commercially prepared injection about pH 3. (B263)

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Pharmacology & General Information

Pharmacology --
Storage / Stability Store at 15-30 C, protect from light. Stable at pH 3.0 - 3.6. Shown to be physically stable having been frozen for three days then allowed to thaw at room temperature. (B263)
Legal Category (In UK) --

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References

Associated Techniques

ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5)
Referees Suzanne I. Boardman (V.w6)

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Therapeutic Information

Uses/Indications

Activity --
Appropriate Use
  • For premedication prior to anaesthesia, particularly in debilitated or elderly animals, high-risk cardiac patients, epileptics, and before procedures such as myelography which may induce epileptiform seizures. (B201.6.w6)
  • For sedation in intensive care. (B201.6.w6)
  • Foals under one month old: premedication prior to anaesthesia. (B201.6.w6)
Limitations --
Notes --

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Pharmacokinetics and Drug Interactions

Absorption /Bioavailability
  • After intravenous administration, very rapid onset of action, due to high lipophilicity. (B263)
  • After intramuscular administration, rapid absorption; 91% absorbed. (B263)
  • Oral administration gives good absorption but only 31-72% bioavailability due to a rapid first-pass effect. (B263)
Distribution
Plasma Protein binding / Storage
  • Highly plasma protein bound. (B263)
Elimination Route
  • Metabolised in the liver, mainly by microsomal oxidation. (B263)
    • The active metabolite alpha-hydroxymidazolam probably has minimal clinical effect due to a lower activity and very short half-life. (B263)
Elimination half-life / Clearance Rate
  • Shorter half-life than diazepam. (B263)
    • In humans, elimination half-life average about two hours (versus 30 hours for diazepam). (B263)
Drug Interactions Physically compatible with: "D5W, normal saline, lactated Ringer's, atropine sulfate, fentamil citrate, glycopyrrolate, hydroxine HCl, ketamine HCl, meperidine HCl, morphine sulfate, nalbuphine HCl, promethazine HCl, sufentanil citrate and scopolamine HBr." Note that compatibility may be affected by pH, concentration, temperature and diluents used. (B263)

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Administration

Formulations available
  • UK: Hypnovel (Roche) POM. 5 mL containing midazolam as hydrochloride, 2 mg/mL; 2 mL, containing midazolam as hydrochloride 5 mg/mL. (B201.6.w6)
Doses / Administration Routes / Frequencies Dogs:
  • 100-200 micrograms/kg by intravenous injection. For sedation. (B201.6.w6)
  • 0.066-0.22 mg/kg intramuscularly or intravenously. For premedication. (B263)
Cats:
  • 0.066-0.22 mg/kg intramuscularly or intravenously. For premedication. (B263)

Bears:

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 1.0 mg/kg intravenously or 1.0 - 3.0 mg/kg intramuscularly. (B546)
  • Up to 2 mg/kg intramuscularly or intravenously. (B602.41.w41)
  • 0.5 - 2.- mg/kg intramuscularly or intravenously. (B603.5.w5)
  • 0.5 - 2.0 mg/kg intramuscularly. "Provides excellent sedation for minor procedures." (J213.2.w3)
    • Note: can be reversed with flumazenil given intravenously at 1 part flumazenil per 13 parts midazolam. (J213.2.w3)

Ferrets - Mustela putorius furo - Ferret:

  • 0.3 - 1.0 mg/kg subcutaneously or intramuscularly. (B602.41.w41)
    • Ketamine 5 - 10 mg/kg plus midazolam 0.25 - 0.5 mg/kg intravenously. (B602.41.w41)
  • 0.25 - 5.0 mg/kg subcutaneously or intramuscularly. Usually used in combination with ketamine. (B626.App.w22)
    • Ketamine 5 - 10 mg/kg plus midazolam 5 mg/kg intramuscularly. As pre-medication before gaseous anaesthesia. (B626.App.w22)
  • 0.25 - 0.3 mg/kg intramuscularly or intravenously. Used in combination anaesthetics. Effects may last two to four hours. (B631.22.w22)
    • Ketamine 5 - 10 mg/kg ten minutes after 0.25 mg/kg midazolam. Provides heavy sedationinduction; inhalant anaesthetic then required. (B631.22.w22)
  • 1 m/kg intramuscularly or subcutaneously (premedication for anaesthesia). (J213.3.w1)

Great Apes

  • 0.05 - 0.15 mg/kg intramuscularly or intravenously.
    • This is used in combination with other drugs, in chemical restraint. (B336.39.w39)
    • Can be reversed with flumazenil, 0.02 - 0.1 mg/kg intravenously. (B336.39.w39)
  • Induction of anaesthesia
    • Ketamine 3.0 mg/kg plus Butorphanol 0.4 mg/kg plus Midazolam 0.3 mg/kg can be used for induction of anaesthesia in great apes. Oxygen should be supplied, plus additional inhalant anaesthetic agent as required. The anaesthetised individual should be monitored closely. (B336.39.w39)
      • Naloxone can be used for reversal of the butorphanol, and flumazenil for reversal of the midazolam. (B336.39.w39)
  • Adult Pan troglodytes - Chimpanzee: 1.0 - 2.5 mg/kg intravenously or 5.0 mg/kg intramuscularly. (W768.Jun2012.w1)

Cranes

  • 15 mg/kg intramuscularly, once. Tranquilizer. (B115.8.w4)
Monitoring parameters
  • Sedation level. (B263)
  • Cardiovascular and respiratory parameters. (B263)

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Withdrawal period / Withholding time

Notes --

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Toxic Information

Toxic effects of Pharmaceutical Products

Contraindications / Precautions
  • Minimal cardiovascular effects. (B201.6.w6)
  • Respiratory effects are minimal in healthy individuals, but in debilitated individuals clinically significant respiratory depression may occur. (B201.6.w6)
  • Avoid intra-arterial injection. (B263)
  • Use with caution in individuals with hepatic or renal impairment, debilitated and geriatric patients. (B263)
  • Drug elimination may be slower in individuals with congestive hear failure. (B263)
  • Administer very cautiously in individuals with significant respiratory depression, in shock or in coma. (B263)
  • Contraindicated in individuals with hypersensitivity to diazepines, and those with acute narrow-angle glaucoma.
Adverse Effects / Side Effects / Warnings
  • The main concern in veterinary medicine is the possibility of respiratory depression. (B263)
  • In humans, effects of respiratory rate, blood pressure and heart rate. In less than 5% nut more than 1% of patients, "pain on injection, local irritation, headache, nausea, vomiting, and hiccups." In individuals with COPD or who have received narcotics, respiratory depression may be seen. (B263)
Operator Warnings --
Overdose / Acute Toxicity --

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Detailed Toxicological Information

Classification --
Acute Toxicity
  • In mice: reported LD50 for intravenous injection 86 mg/kg. (B263)
Chronic Toxicity --
Reproductive effects
  • In humans, where mothers have received large benzodiazepine doses shortly before parturition, infants have been reported to suffer from "apnea, impaired metabolic response to cold stress, difficulty in feeding, hyperbilirubinemia, hypotonia etc." (B263)
Teratogenic effects
  • Human: Congenital abnormalities have been reported in infants following maternal use of benzodiazepines in the first trimester of pregnancy. (B263)
  • A meta-analysis of cohort and case-control studies found that, based on cohort studies, there was no association between use of benzodiazepines in the first trimester of pregnancy and development of fetal abnormalities. However, data from case-control studies indicated an increased risk of major malformations or of oral cleft. (J258.317.w1)
  • Some, but not all, animal studies have indicated an association between benzodiazepines and teratogenic effects such as skeletal abnormalities and cleft palate. (J258.317.w1)
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data

Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses

Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Sources in the Environment

Natural sources --
Human-associated sources

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Effects on the Environment

Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment

Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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