- Inamrinone uses
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Uses of Inamrinone
Inamrinone is a prescription medication used to treat congestive heart failure.
This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.
Inamrinone - Clinical Pharmacology
Inamrinone is a positive inotropic agent with vasodilator activity, different in structure and mode of action from either digitalis glycosides or catecholamines.
The mechanism of its inotropic and vasodilator effects has not been fully elucidated.
With respect to its inotropic effect, experimental evidence indicates that it is not a beta-adrenergic agonist. It inhibits myocardial cyclic adenosine monophosphate (c-AMP) phosphodiesterase activity and increases cellular levels of c-AMP. Unlike digitalis, it does not inhibit sodium-potassium adenosine triphosphatase activity.
With respect to its vasodilatory activity, Inamrinone reduces afterload and preload by its direct relaxant effect on vascular smooth muscle.
Following intravenous bolus (1 to 2 minutes) injection of 0.68 mg/kg to 1.2 mg/kg to normal volunteers, Inamrinone had a volume of distribution of 1.2 liters/kg, and following a distributive phase half-life of about 4.6 minutes in plasma, had a mean apparent first-order terminal elimination half-life of about 3.6 hours. In patients with congestive heart failure receiving infusions of Inamrinone the mean apparent first-order terminal elimination half-life was about 5.8 hours.
Inamrinone has been shown in one study to be 10% to 22% bound to human plasma protein by ultrafiltration in vitro, and in another study 35% to 49% bound by either ultrafiltration or equilibrium dialysis.
The primary route of excretion in man is via the urine as both Inamrinone and several metabolites (N-glycolyl, N-acetate, O-glucuronide and N-glucuronide). In normal volunteers, approximately 63% of an oral dose of 14C-Iabelled Inamrinone was excreted in the urine over a 96-hour period. In the first 8 hours, 51% of the radioactivity in the urine was Inamrinone with 5% as the N-acetate, 8% as the N-glycolate, and less than 5% for each glucuronide. Approximately 18% of the administered dose was excreted in the feces in 72 hours.
In a 24-hour nonradioactive intravenous study, 10% to 40% of the dose was excreted in urine as unchanged Inamrinone with the N-acetyl metabolite representing less than 2% of the dose.
In congestive heart failure patients, after a loading bolus dose, steady-state plasma levels of about 2.4 mcg/mL were able to be maintained by an infusion of 5 mcg/kg/min to 10 mcg/kg/min. In some congestive heart failure patients, with associated compromised renal and hepatic perfusion, it is possible that plasma levels of Inamrinone may rise during the infusion period; therefore, in these patients, it may be necessary to monitor the hemodynamic response and/or drug level. The principal measures of patient response include cardiac index, pulmonary capillary wedge pressure, central venous pressure, and their relationship to plasma concentrations. Additionally, measurements of blood pressure, urine output, and body weight may prove useful, as may such clinical symptoms as orthopnea, dyspnea, and fatigue.
In patients with depressed myocardial function, Inamrinone produces a prompt increase in cardiac output due to its inotropic and vasodilator actions.
Following a single intravenous bolus dose of Inamrinone of 0.75 mg/kg to 3 mg/kg in patients with congestive heart failure, dose-related maximum increases in cardiac output occur (of about 28% at 0.75 mg/kg to about 61% at 3 mg/kg). The peak effect occurs within 10 minutes at all doses. The duration of effect depends upon dose, lasting about 1/2 hour at 0.75 mg/kg and approximately 2 hours at 3 mg/kg.
Over the same range of doses, pulmonary capillary wedge pressure and total peripheral resistance show dose-related decreases (mean maximum decreases of 29% in pulmonary capillary wedge pressure and 29% in systemic vascular resistance). At doses up to 3 mg/kg dose-related decreases in diastolic pressure (up to 13%) have been observed. Mean arterial pressure decreases (9.7%) at a dose of 3 mg/kg. The heart rate is generally unchanged.
The changes in hemodynamic parameters are maintained during continuous intravenous infusion and for several hours thereafter.
Inamrinone is effective in fully digitalized patients without causing signs of cardiac glycoside toxicity. Its inotropic effects are additive to those of digitalis. In cases of atrial flutter/fibrillation, it is possible that Inamrinone may increase ventricular response rate because of its slight enhancement of A/V conduction. In these cases, prior treatment with digitalis is recommended.
Improvement in left ventricular function and relief of congestive heart failure in patients with ischemic heart disease have been observed. The improvement has occurred without inducing symptoms or electrocardiographic signs of myocardial ischemia.
At constant heart rate and blood pressure, increases in cardiac output occur without measurable increases in myocardial oxygen consumption or changes in arteriovenous oxygen difference.
Inotropic activity is maintained following repeated intravenous doses of Inamrinone. Inamrinone administration produces hemodynamic and symptomatic benefits to patients not satisfactorily controlled by conventional therapy with diuretics and cardiac glycosides.
Inamrinone is contraindicated in patients who are hypersensitive to it.
It is also contraindicated in those patients known to be hypersensitive to bisulfites.
Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Thrombocytopenia: Intravenous injection of Inamrinone resulted in platelet count reductions to below 100,000/mm3 or normal limits in 2.4 percent of the patients.
It is more common in patients receiving prolonged therapy. To date, in closely-monitored clinical trials, in patients whose platelet counts were not allowed to remain depressed, no bleeding phenomena have been observed.
Platelet reduction is dose dependent and appears due to a decrease in platelet survival time. Several patients who developed thrombocytopenia while receiving Inamrinone had bone marrow examinations which were normal. There is no evidence relating platelet reduction to immune response or to a platelet activating factor.
Gastrointestinal Effects: Gastrointestinal adverse reactions reported with Inamrinone during clinical use included nausea (1.7%), vomiting (0.9%), abdominal pain (0.4%), and anorexia (0.4%).
Cardiovascular Effects: Cardiovascular adverse reactions reported with Inamrinone include arrhythmia (3%) and hypotension (1.3%).
Hepatic Toxicity: In dogs, at IV doses between 9 mg/kg/day and 32 mg/kg/day, Inamrinone showed dose-related hepatotoxicity manifested either as enzyme elevation or hepatic cell necrosis or both. Hepatotoxicity has been observed in man following long-term oral dosing and has been observed, in a limited experience (0.2%), following intravenous administration of Inamrinone. There have also been rare reports of enzyme and bilirubin elevation and jaundice.
Hypersensitivity: There have been reports of several apparent hypersensitivity reactions in patients treated with oral Inamrinone for about two weeks. Signs and symptoms were variable but included pericarditis, pleuritis and ascites (1 case), myositis with interstitial shadowing on chest x-ray and elevated sedimentation rate (1 case) and vasculitis with nodular pulmonary densities, hypoxemia, and jaundice (1 case). The first patient died, not necessarily of the possible reaction, while the last two resolved with discontinuation of therapy. None of the cases were rechallenged so that attribution to Inamrinone is not certain, but possible hypersensitivity reactions should be considered in any patient maintained for a prolonged period on Inamrinone.
General: Additional adverse reactions observed in intravenous Inamrinone clinical studies include fever (0.9%), chest pain (0.2%), and burning at the site of injection (0.2%).
Management of Adverse Reactions
Platelet Count Reductions: Asymptomatic platelet count reduction (to <150,000/mm3) may be reversed within one week of a decrease in drug dosage. Further, with no change in drug dosage, the count may stabilize at lower than pre-drug levels without any clinical sequelae. Pre-drug platelet counts and frequent platelet counts during therapy are recommended to assist in decisions regarding dosage modifications.
Should a platelet count less than 150,000/mm3 occur, the following actions may be considered:• Maintain total daily dose unchanged, since in some cases counts have either stabilized or returned to pretreatment levels. • Decrease total daily dose. • Discontinue Inamrinone if, in the clinical judgment of the physician, risk exceeds the potential benefit.
Gastrointestinal Side Effects: While gastrointestinal side effects were seen infrequently with intravenous therapy, should severe or debilitating ones occur, the physician may wish to reduce dosage or discontinue the drug based on the usual benefit-to-risk considerations.
Hepatic Toxicity: In clinical experience to date with intravenous administration, hepatotoxicity has been observed rarely. If acute marked alterations in liver enzymes occur together with clinical symptoms suggesting an idiosyncratic hypersensitivity reaction, Inamrinone therapy should be promptly discontinued.
If less than marked enzyme alterations occur without clinical symptoms, these nonspecific changes should be evaluated on an individual basis. The clinician may wish to continue Inamrinone, reduce dosage, or discontinue the drug based on the usual benefit/risk considerations.
How is Inamrinone Supplied
Inamrinone Injection USP is supplied in single-dose vials of 20 mL sterile, clear yellow solution individually boxed. NDC 55390-042-10.
Each 1 mL contains Inamrinone lactate equivalent to 5 mg of Inamrinone.
Protect from light. Packaging is light resistant for protection during storage. Retain in carton until time of use.
Store at controlled room temperature 15° to 30°C (59° to 86°F).
Manufactured by: Manufactured for:
Ben Venue Laboratories, Inc. Bedford Laboratories™
Bedford, OH 44146 Bedford, OH 44146
August 2002 AMR-P01
For the Consumer
Applies to inamrinone: parenteral injection for iv use
Side effects include:
Thrombocytopenia, arrhythmias, hypotension, nausea, vomiting, fever.
Inamrinone Pregnancy Warnings
Limited animal data revealed skeletal and gross external malformations in rabbits after administration of inamrinone dosages approximately one to three times the maximum recommended human dosage (on a per kg basis). Other animal (rabbit and rat) studies failed to corroborate these findings. A single case in which an inamrinone dosage regimen of 0.5 mg per kg, then 2 mcg per kg per minute was administered to a pregnant woman (18 weeks) with bacterial endocarditis and heart failure has been reported. No adverse fetal effects were observed. However, due to her serious underlying disease, the woman spontaneously aborted 11 weeks after discontinuation of inamrinone.
Inamrinone has been assigned to pregnancy category C by the FDA. Animal studies have revealed evidence of teratogenicity. There are no controlled data in human pregnancy. A case report of inamrinone use in a pregnant woman failed to reveal fetal toxicity, however, the pregnancy terminated in a spontaneous abortion several weeks following discontinuation of inamrinone. Inamrinone should be used during pregnancy only when benefit outweighs risk.