大家好，我是新手，依诺昔酮的英文说明书，找了好几天了，都没找到，真是急死了，所以来园子里请高手帮忙！能否帮我一把！万分感谢啊！ Enoximone
Drug Nomenclature
Date of monograph revision: 04-Jul-1997; 12-Aug-1998; 21-Sep-2000; 30-Oct-2001; 17-Jul-2002; 13-Jul-2006
Synonyms: Enoksimoni; Enoximon; Enoximona; Enoximonum; Fenoximone; MDL-17043; MDL-19438; RMI-17043; YMDL-17043
BAN: Enoximone
USAN: Enoximone
INN: Enoximone
INN: Enoximona
INN: Énoximone
INN: Enoximonum
INN: Еноксимон
Chemical name: 4-Methyl-5--4-imidazolin-2-one
Molecular formula: C12H12N2O2S =248.3
CAS: 77671-31-9
ATC code: C01CE03
Read code: y01oJ; y07j5
Chemical Structure of Enoximone
Physicochemical Characteristics
Incompatibility.
Crystal formation has occurred when enoximone injection was mixed in glass containers or syringes; the manufacturer recommends that only plastic containers or syringes are used for dilutions. The manufacturer also recommends that only sodium chloride 0.9% or water be used as diluents. Glucose solutions should not be used for dilution as crystal formation may occur.
Adverse Effects
Long-term oral treatment with enoximone has been reported to increase the mortality rate and enoximone is now only given intravenously for short-term use.
Enoximone may cause ventricular and supraventricular tachyarrhythmias, ectopic beats, and hypotension.
Adverse effects of enoximone affecting the gastrointestinal tract include diarrhoea, nausea, and vomiting. Other adverse effects include headache, insomnia, chills, oliguria, fever, urinary retention, and limb pain. There have been reports of thrombocytopenia and abnormal liver enzyme values.
Effects on the nervous system.
Tonic-clonic convulsions have been reported1 in a patient given enoximone 6 micrograms/kg per minute by intravenous infusion. The convulsions subsided when enoximone was discontinued.
1. Appadurai I, et al. Convulsions induced by enoximone administered as a continuous intravenous infusion. BMJ 1990; 300: 613–14. PubMed
Hyperosmolality.
Hyperosmolality occurred in an infant during intravenous infusion of enoximone 20 micrograms/kg per minute. The probable cause was propylene glycol in the enoximone injection providing a dose of 2.4 mg/kg per minute.1
1. Huggon I, et al. Hyperosmolality related to propylene glycol in an infant treated with enoximone infusion. BMJ 1990; 301: 19–20. PubMed
Precautions
Enoximone should be used with caution in patients with hypertrophic cardiomyopathy or severe obstructive aortic or pulmonary valvular disease.
Blood pressure, heart rate, ECG, fluid and electrolyte status, and renal function should be monitored during therapy. Platelet count and liver enzyme values should also be monitored.
The injection has a high pH (about 12) and must be diluted before use (but see Incompatibility, ). Extravasation should be avoided during administration.
Doses may need to be reduced in hepatic or renal impairment (see under Uses and Administration, ).
Pharmacokinetics
Although enoximone is absorbed from the gastrointestinal tract it is no longer given orally. The plasma elimination half-life varies widely; it may be about 1 to 4 hours in healthy subjects and about 3 to 8 hours in patients with heart failure, but longer times have been reported. Enoximone is about 85% bound to plasma proteins. It is metabolised in the liver and is excreted in the urine, mainly as metabolites. After intravenous administration about 70% of a dose is excreted in the urine as metabolites and less than 1% as unchanged drug.
General references.
1. Rocci ML, Wilson H. The pharmacokinetics and pharmacodynamics of newer inotropic agents. Clin Pharmacokinet 1987; 13: 91–109. PubMed Correction. ibid. 1988; 14: (contents page).
2. Booker PD, et al. Enoximone pharmacokinetics in infants. Br J Anaesth 2000; 85: 205–10. PubMed
Uses and Administration
Enoximone is a phosphodiesterase inhibitor similar to amrinone () with positive inotropic and vasodilator activity. It is given intravenously in the short-term management of heart failure. In some long-term studies it was given by mouth, but an increased mortality rate was reported.
The usual initial dose of enoximone by intravenous injection is 0.5 to 1.0 mg/kg given at a rate not greater than 12.5 mg/minute. This may be followed by doses of 0.5 mg/kg every 30 minutes until a satisfactory response is obtained or a total dose of 3 mg/kg has been given. Alternatively, the initial dose may be given as a continuous intravenous infusion in a dose of 90 micrograms/kg per minute over 10 to 30 minutes until the desired response is achieved.
For maintenance therapy the initial dose (up to a total of 3 mg/kg) may be repeated as required every 3 to 6 hours or a continuous or intermittent infusion may be given in a dose of 5 to 20 micrograms/kg per minute.
The total dose over 24 hours should not exceed 24 mg/kg.
Dosage may need to be reduced in patients with hepatic or renal impairment (see ).
General references.
1. Vernon MW, et al. Enoximone: a review of its pharmacological properties and therapeutic potential. Drugs 1991; 42: 997–1017. PubMed
Administration in hepatic and renal impairment.
The elimination half-life of enoximone after intravenous administration was 2.16 hours in a patient with hepatic impairment and 1.33 hours in a patient with renal impairment. The mean elimination half-life in patients with normal hepatic and renal function was 1.26 hours. It was suggested that patients with renal impairment should be monitored and have plasma concentrations measured during continuous infusions and that in hepatic disease the dosage may need to be modified.1 Similarly, in a study2 in paediatric patients receiving intravenous enoximone clearance was reduced in those with renal or hepatic impairment and it was suggested that the infusion rate should be decreased in such patients.
1. Desager JP, et al. Plasma enoximone concentrations in cardiac patients. Curr Ther Res 1990; 47: 743–52.
2. Booker PD, et al. Enoximone pharmacokinetics in infants. Br J Anaesth 2000; 85: 205–10. PubMed
Beta blocker overdosage.
Enoximone, given intravenously as a bolus dose of 0.5 mg/kg followed by an infusion of 15 micrograms/kg per minute, successfully increased the cardiac output and stroke volume in a woman who had ingested 10 g of metoprolol.1 It was suggested that enoximone may be useful in such patients since its action does not involve the beta-adrenergic system.
1. Hoeper MM, Boeker KHW. Overdose of metoprolol treated with enoximone. N Engl J Med 1996; 335: 1538. PubMed
Heart failure.
Enoximone is one of several drugs that may be used in heart failure (), but because of an increased mortality rate reported following long-term oral use it is only given intravenously for short-term management of heart failure unresponsive to other treatments. In a comparison of oral enoximone and placebo in patients with moderate to moderately severe heart failure,1 enoximone was no better than placebo in improving exercise duration over the 16-week study period. Although the overall incidence of adverse effects was similar in the two groups, 5 patients receiving enoximone died compared with none in the placebo group.
1. Uretsky BF, et al. Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure: lack of benefit compared with placebo. Circulation 1990; 82: 774–80. PubMed
Preparations
Single-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
Drug Nomenclature
Date of monograph revision: 04-Jul-1997; 12-Aug-1998; 21-Sep-2000; 30-Oct-2001; 17-Jul-2002; 13-Jul-2006
Synonyms: Enoksimoni; Enoximon; Enoximona; Enoximonum; Fenoximone; MDL-17043; MDL-19438; RMI-17043; YMDL-17043
BAN: Enoximone
USAN: Enoximone
INN: Enoximone
INN: Enoximona
INN: Énoximone
INN: Enoximonum
INN: Еноксимон
Chemical name: 4-Methyl-5--4-imidazolin-2-one
Molecular formula: C12H12N2O2S =248.3
CAS: 77671-31-9
ATC code: C01CE03
Read code: y01oJ; y07j5
Chemical Structure of Enoximone
Physicochemical Characteristics
Incompatibility.
Crystal formation has occurred when enoximone injection was mixed in glass containers or syringes; the manufacturer recommends that only plastic containers or syringes are used for dilutions. The manufacturer also recommends that only sodium chloride 0.9% or water be used as diluents. Glucose solutions should not be used for dilution as crystal formation may occur.
Adverse Effects
Long-term oral treatment with enoximone has been reported to increase the mortality rate and enoximone is now only given intravenously for short-term use.
Enoximone may cause ventricular and supraventricular tachyarrhythmias, ectopic beats, and hypotension.
Adverse effects of enoximone affecting the gastrointestinal tract include diarrhoea, nausea, and vomiting. Other adverse effects include headache, insomnia, chills, oliguria, fever, urinary retention, and limb pain. There have been reports of thrombocytopenia and abnormal liver enzyme values.
Effects on the nervous system.
Tonic-clonic convulsions have been reported1 in a patient given enoximone 6 micrograms/kg per minute by intravenous infusion. The convulsions subsided when enoximone was discontinued.
1. Appadurai I, et al. Convulsions induced by enoximone administered as a continuous intravenous infusion. BMJ 1990; 300: 613–14. PubMed
Hyperosmolality.
Hyperosmolality occurred in an infant during intravenous infusion of enoximone 20 micrograms/kg per minute. The probable cause was propylene glycol in the enoximone injection providing a dose of 2.4 mg/kg per minute.1
1. Huggon I, et al. Hyperosmolality related to propylene glycol in an infant treated with enoximone infusion. BMJ 1990; 301: 19–20. PubMed
Precautions
Enoximone should be used with caution in patients with hypertrophic cardiomyopathy or severe obstructive aortic or pulmonary valvular disease.
Blood pressure, heart rate, ECG, fluid and electrolyte status, and renal function should be monitored during therapy. Platelet count and liver enzyme values should also be monitored.
The injection has a high pH (about 12) and must be diluted before use (but see Incompatibility, ). Extravasation should be avoided during administration.
Doses may need to be reduced in hepatic or renal impairment (see under Uses and Administration, ).
Pharmacokinetics
Although enoximone is absorbed from the gastrointestinal tract it is no longer given orally. The plasma elimination half-life varies widely; it may be about 1 to 4 hours in healthy subjects and about 3 to 8 hours in patients with heart failure, but longer times have been reported. Enoximone is about 85% bound to plasma proteins. It is metabolised in the liver and is excreted in the urine, mainly as metabolites. After intravenous administration about 70% of a dose is excreted in the urine as metabolites and less than 1% as unchanged drug.
General references.
1. Rocci ML, Wilson H. The pharmacokinetics and pharmacodynamics of newer inotropic agents. Clin Pharmacokinet 1987; 13: 91–109. PubMed Correction. ibid. 1988; 14: (contents page).
2. Booker PD, et al. Enoximone pharmacokinetics in infants. Br J Anaesth 2000; 85: 205–10. PubMed
Uses and Administration
Enoximone is a phosphodiesterase inhibitor similar to amrinone () with positive inotropic and vasodilator activity. It is given intravenously in the short-term management of heart failure. In some long-term studies it was given by mouth, but an increased mortality rate was reported.
The usual initial dose of enoximone by intravenous injection is 0.5 to 1.0 mg/kg given at a rate not greater than 12.5 mg/minute. This may be followed by doses of 0.5 mg/kg every 30 minutes until a satisfactory response is obtained or a total dose of 3 mg/kg has been given. Alternatively, the initial dose may be given as a continuous intravenous infusion in a dose of 90 micrograms/kg per minute over 10 to 30 minutes until the desired response is achieved.
For maintenance therapy the initial dose (up to a total of 3 mg/kg) may be repeated as required every 3 to 6 hours or a continuous or intermittent infusion may be given in a dose of 5 to 20 micrograms/kg per minute.
The total dose over 24 hours should not exceed 24 mg/kg.
Dosage may need to be reduced in patients with hepatic or renal impairment (see ).
General references.
1. Vernon MW, et al. Enoximone: a review of its pharmacological properties and therapeutic potential. Drugs 1991; 42: 997–1017. PubMed
Administration in hepatic and renal impairment.
The elimination half-life of enoximone after intravenous administration was 2.16 hours in a patient with hepatic impairment and 1.33 hours in a patient with renal impairment. The mean elimination half-life in patients with normal hepatic and renal function was 1.26 hours. It was suggested that patients with renal impairment should be monitored and have plasma concentrations measured during continuous infusions and that in hepatic disease the dosage may need to be modified.1 Similarly, in a study2 in paediatric patients receiving intravenous enoximone clearance was reduced in those with renal or hepatic impairment and it was suggested that the infusion rate should be decreased in such patients.
1. Desager JP, et al. Plasma enoximone concentrations in cardiac patients. Curr Ther Res 1990; 47: 743–52.
2. Booker PD, et al. Enoximone pharmacokinetics in infants. Br J Anaesth 2000; 85: 205–10. PubMed
Beta blocker overdosage.
Enoximone, given intravenously as a bolus dose of 0.5 mg/kg followed by an infusion of 15 micrograms/kg per minute, successfully increased the cardiac output and stroke volume in a woman who had ingested 10 g of metoprolol.1 It was suggested that enoximone may be useful in such patients since its action does not involve the beta-adrenergic system.
1. Hoeper MM, Boeker KHW. Overdose of metoprolol treated with enoximone. N Engl J Med 1996; 335: 1538. PubMed
Heart failure.
Enoximone is one of several drugs that may be used in heart failure (), but because of an increased mortality rate reported following long-term oral use it is only given intravenously for short-term management of heart failure unresponsive to other treatments. In a comparison of oral enoximone and placebo in patients with moderate to moderately severe heart failure,1 enoximone was no better than placebo in improving exercise duration over the 16-week study period. Although the overall incidence of adverse effects was similar in the two groups, 5 patients receiving enoximone died compared with none in the placebo group.
1. Uretsky BF, et al. Multicenter trial of oral enoximone in patients with moderate to moderately severe congestive heart failure: lack of benefit compared with placebo. Circulation 1990; 82: 774–80. PubMed
Preparations
Single-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.