Lanoxin Information
Lanoxin (Digoxin) Description
Lanoxin (Digoxin) is one of the cardiac (or digitalis) glycosides, a closely related group of drugs having in common specific effects on the myocardium. These drugs are found in a number of plants. Digoxin is extracted from the leaves of . The term “digitalis” is used to designate the whole group of glycosides. The glycosides are composed of 2 portions: a sugar and a cardenolide (hence “glycosides”).
Digoxin is described chemically as (3β,5β,12β)-3-[(-2,6-dideoxy-β--hexopyranosyl-(1→4)--2,6-dideoxy-β-hexopyranosyl-(1→4)-2,6-dideoxy-β---hexopyranosyl)oxy]-12,14-dihydroxy-card-20(22)-enolide. Its molecular formula is CHO, its molecular weight is 780.95, and its structural formula is:
Digoxin exists as odorless white crystals that melt with decomposition above 230°C. The drug is practically insoluble in water and in ether; slightly soluble in diluted (50%) alcohol and in chloroform; and freely soluble in pyridine.
Lanoxin (Digoxin) Injection is a sterile solution of digoxin for intravenous or intramuscular injection. The vehicle contains 40% propylene glycol and 10% alcohol. The injection is buffered to a pH of 6.8 to 7.2 with 0.17% dibasic sodium phosphate and 0.08% anhydrous citric acid. Each 2-mL ampul contains 500 mcg (0.5 mg) digoxin (250 mcg [0.25 mg] per mL). Dilution is not required.
Lanoxin (Digoxin) Clinical Pharmacology
The times to onset of pharmacologic effect and to peak effect of preparations of Lanoxin (Digoxin) are shown in Table 2.
a
b
Lanoxin (Digoxin) Contraindications
Digitalis glycosides are contraindicated in patients with ventricular fibrillation or in patients with a known hypersensitivity to digoxin. A hypersensitivity reaction to other digitalis preparations usually constitutes a contraindication to digoxin.
Lanoxin (Digoxin) Precautions
In patients with hypokalemia or hypomagnesemia, toxicity may occur despite serum digoxin concentrations below 2.0 ng/mL, because potassium or magnesium depletion sensitizes the myocardium to digoxin. Therefore, it is desirable to maintain normal serum potassium and magnesium concentrations in patients being treated with digoxin. Deficiencies of these electrolytes may result from malnutrition, diarrhea, or prolonged vomiting, as well as the use of the following drugs or procedures: diuretics, amphotericin B, corticosteroids, antacids, dialysis, and mechanical suction of gastrointestinal secretions.
Hypercalcemia from any cause predisposes the patient to digitalis toxicity. Calcium, particularly when administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. On the other hand, hypocalcemia can nullify the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal. These interactions are related to the fact that digoxin affects contractility and excitability of the heart in a manner similar to that of calcium.
Potassium-depleting are a major contributing factor to digitalis toxicity.particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. , , and raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result. and(and possibly other ) and may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis intoxication may result. and by decreasing gut motility, may increase digoxin absorption. ,,, certain and may interfere with intestinal digoxin absorption, resulting in unexpectedly low serum concentrations. may decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin. There have been inconsistent reports regarding the effects of other drugs (e.g., ,) on serum digoxin concentration. administration to a digitalized, hypothyroid patient may increase the dose requirement of digoxin. Concomitant use of digoxin and increases the risk of cardiac arrhythmias. may cause a sudden extrusion of potassium from muscle cells, and may thereby cause arrhythmias in digitalized patients. Although calcium channel blockers and digoxin may be useful in combination to control atrial fibrillation, their additive effects on AV node conduction can result in advanced or complete heart block. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Digoxin concentrations are increased by about 15% when digoxin and carvedilol are administered concomitantly. Therefore, increased monitoring of digoxin is recommended when initiating, adjusting, or discontinuing carvedilol.
Due to the considerable variability of these interactions, the dosage of digoxin should be individualized when patients receive these medications concurrently. Furthermore, caution should be exercised when combining digoxin with any drug that may cause a significant deterioration in renal function, since a decline in glomerular filtration or tubular secretion may impair the excretion of digoxin.
Lanoxin (Digoxin) Adverse Reactions
In general, the adverse reactions of digoxin are dose-dependent and occur at doses higher than those needed to achieve a therapeutic effect. Hence, adverse reactions are less common when digoxin is used within the recommended dose range or therapeutic serum concentration range and when there is careful attention to concurrent medications and conditions.
Because some patients may be particularly susceptible to side effects with digoxin, the dosage of the drug should always be selected carefully and adjusted as the clinical condition of the patient warrants. In the past, when high doses of digoxin were used and little attention was paid to clinical status or concurrent medications, adverse reactions to digoxin were more frequent and severe. Cardiac adverse reactions accounted for about one-half, gastrointestinal disturbances for about one-fourth, and CNS and other toxicity for about one-fourth of these adverse reactions. However, available evidence suggests that the incidence and severity of digoxin toxicity has decreased substantially in recent years. In recent controlled clinical trials, in patients with predominantly mild to moderate heart failure, the incidence of adverse experiences was comparable in patients taking digoxin and in those taking placebo. In a large mortality trial, the incidence of hospitalization for suspected digoxin toxicity was 2% in patients taking Lanoxin (Digoxin) Tablets compared to 0.9% in patients taking placebo. In this trial, the most common manifestations of digoxin toxicity included gastrointestinal and cardiac disturbances; CNS manifestations were less common.
Lanoxin (Digoxin) Overdosage
In addition to cardiac monitoring, digoxin should be temporarily discontinued until the adverse reaction resolves and may be all that is required to treat the adverse reaction such as in asymptomatic bradycardia or digoxin-related heart block. Every effort should also be made to correct factors that may contribute to the adverse reaction (such as electrolyte disturbances, thyroid function, or concurrent medications) (see WARNINGS and PRECAUTIONS: Drug Interactions). Once the adverse reaction has resolved, therapy with digoxin may be reinstituted, following a careful reassessment of dose.
When the primary manifestation of digoxin overdosage is a cardiac arrhythmia, additional therapy may be needed.
If the rhythm disturbance is a symptomatic bradyarrhythmia or heart block, consideration should be given to the reversal of toxicity with Digoxin Immune Fab (Ovine) [DIGIBIND or DIGIFAB] (see Massive Digitalis Overdosage subsection), the use of atropine, or the insertion of a temporary cardiac pacemaker. Digoxin Immune Fab (Ovine) is a specific antidote for digoxin and may be used to reverse potentially life-threatening ventricular arrhythmias due to digoxin overdosage.
If the rhythm disturbance is a ventricular arrhythmia, consideration should be given to the correction of electrolyte disorders, particularly if hypokalemia (see Administration of Potassium subsection) or hypomagnesemia is present. Ventricular arrhythmias may respond to lidocaine or phenytoin.
Lanoxin (Digoxin) Dosage And Administration
Recommended dosages of digoxin may require considerable modification because of individual sensitivity of the patient to the drug, the presence of associated conditions, or the use of concurrent medications.
Parenteral administration of digoxin should be used only when the need for rapid digitalization is urgent or when the drug cannot be taken orally. Intramuscular injection can lead to severe pain at the injection site, thus intravenous administration is preferred. If the drug must be administered by the intramuscular route, it should be injected deep into the muscle followed by massage. No more than 500 mcg (2 mL) should be injected into a single site.
Lanoxin (Digoxin) Injection can be administered undiluted or diluted with a 4-fold or greater volume of Sterile Water for Injection, 0.9% Sodium Chloride Injection, or 5% Dextrose Injection. The use of less than a 4-fold volume of diluent could lead to precipitation of the digoxin. Immediate use of the diluted product is recommended.
If tuberculin syringes are used to measure very small doses, one must be aware of the problem of inadvertent overadministration of digoxin. The syringe should be flushed with the parenteral solution after its contents are expelled into an indwelling vascular catheter.
Slow infusion of Lanoxin (Digoxin) Injection is preferable to bolus administration. Rapid infusion of digitalis glycosides has been shown to cause systemic and coronary arteriolar constriction, which may be clinically undesirable. Caution is thus advised and Lanoxin (Digoxin) Injection should probably be administered over a period of 5 minutes or longer. Mixing of Lanoxin (Digoxin) Injection with other drugs in the same container or simultaneous administration in the same intravenous line is not recommended.
In selecting a dose of digoxin, the following factors must be considered:
In general, the dose of digoxin used should be determined on clinical grounds. However, measurement of serum digoxin concentrations can be helpful to the clinician in determining the adequacy of digoxin therapy and in assigning certain probabilities to the likelihood of digoxin intoxication. About two-thirds of adults considered adequately digitalized (without evidence of toxicity) have serum digoxin concentrations ranging from 0.8 to 2.0 ng/mL (lower serum trough concentrations of 0.5 to 1 ng/mL may be appropriate in some adult patients, see Maintenance Dosing). However, digoxin may produce clinical benefits even at serum concentrations below this range. About two-thirds of adult patients with clinical toxicity have serum digoxin concentrations greater than 2.0 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2.0 ng/mL, values below 2.0 ng/mL do not rule out the possibility that a certain sign or symptom is related to digoxin therapy. Rarely, there are patients who are unable to tolerate digoxin at serum concentrations below 0.8 ng/mL. Consequently, the serum concentration of digoxin should always be interpreted in the overall clinical context, and an isolated measurement should not be used alone as the basis for increasing or decreasing the dose of the drug.
To allow adequate time for equilibration of digoxin between serum and tissue, sampling of serum concentrations should be done just before the next scheduled dose of the drug. If this is not possible, sampling should be done at least 6 to 8 hours after the last dose, regardless of the route of administration or the formulation used. On a once-daily dosing schedule, the concentration of digoxin will be 10% to 25% lower when sampled at 24 versus 8 hours, depending upon the patient’s renal function. On a twice-daily dosing schedule, there will be only minor differences in serum digoxin concentrations whether sampling is done at 8 or 12 hours after a dose.
If a discrepancy exists between the reported serum concentration and the observed clinical response, the clinician should consider the following possibilities:
Lanoxin (Digoxin) How Supplied
Lanoxin (Digoxin) Injection, 500 mcg (0.5 mg) in 2 mL (250 mcg [0.25 mg] per mL); Boxes of 10 (NDC 0173-0260-10) and 50 ampuls (NDC 0173-0260-35).
Lanoxin (Digoxin) and DIGIBIND are registered trademarks of GlaxoSmithKline
DIGIFAB is a registered trademark of Prostherics Inc.
Manufactured by
Draxis Pharma Inc.
Kirkland, Canada H9H 4J4 for
GlaxoSmithKline
Research Triangle Park, NC 27709
©2009, GlaxoSmithKline. All rights reserved.
August 2009
LNJ:1PI
Lanoxin (Digoxin) Principal Display Panel
Lanoxin (Digoxin) Injection 500 MCG
(0.5 MG) in 2 ML
Digoxin (250 mcg [0.25mg] per mL)
5 x 2 ml Ampuls
