DRUGS & SUPPLEMENTS

Digitek

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Digitek uses


INDICATIONS AND USAGE:

Heart Failure

Digitek Tablets are indicated for the treatment of mild to moderate heart failure. Digitek Tablets increase left ventricular ejection fraction and improve heart failure symptoms as evidenced by exercise capacity and heart failure-related hospitalizations and emergency care, while having no effect on mortality. Where possible, Digitek Tablets should be used with a diuretic and an angiotensin-converting enzyme inhibitor, but an optimal order for starting these three drugs cannot be specified.

Atrial Fibrillation

Digitek Tablets are indicated for the control of ventricular response rate in patients with chronic atrial fibrillation.

CONTRAINDICATIONS:

Digitalis glycosides are contraindicated in patients with ventricular fibrillation or in patients with a known hypersensitivity to Digitek. A hypersensitivity reaction to other digitalis preparations usually constitutes a contraindication to Digitek.

WARNINGS:

Sinus Node Disease and AV Block

Because Digitek slows sinoatrial and AV conduction, the drug commonly prolongs the PR interval. The drug may cause severe sinus bradycardia or sinoatrial block in patients with preexisting sinus node disease and may cause advanced or complete heart block in patients with preexisting incomplete AV block. In such patients consideration should be given to the insertion of a pacemaker before treatment with Digitek.

Accessory AV Pathway

After intravenous Digitek therapy, some patients with paroxysmal atrial fibrillation or flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, leading to a very rapid ventricular response or ventricular fibrillation. Unless conduction down the accessory pathway has been blocked (either pharmacologically or by surgery), Digitek should not be used in such patients. The treatment of paroxysmal supraventricular tachycardia in such patients is usually direct-current cardioversion.

Use in Patients with Preserved Left Ventricular Systolic Function

Patients with certain disorders involving heart failure associated with preserved left ventricular ejection fraction may be particularly susceptible to toxicity of the drug. Such disorders include restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Patients with idiopathic hypertrophic subaortic stenosis may have worsening of the outflow obstruction due to the inotropic effects of Digitek. Digitek should generally be avoided in these patients, although it has been used for ventricular rate control in the subgroup of patients with atrial fibrillation.

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PRECAUTIONS:

Use in Patients with Impaired Renal Function

Digitek is primarily excreted by the kidneys; therefore, patients with impaired renal function require smaller than usual maintenance doses of Digitek. Because of the prolonged elimination half-life, a longer period of time is required to achieve an initial or new steady-state serum concentration in patients with renal impairment than in patients with normal renal function. If appropriate care is not taken to reduce the dose of Digitek, such patients are at high risk for toxicity, and toxic effects will last longer in such patients than in patients with normal renal function.

Use in Patients with Electrolyte Disorders

In patients with hypokalemia or hypomagnesemia, toxicity may occur despite serum Digitek concentrations below 2 ng/mL, because potassium or magnesium depletion sensitizes the myocardium to Digitek. Therefore, it is desirable to maintain normal serum potassium and magnesium concentrations in patients being treated with Digitek. 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 nullity the effects of Digitek in humans; thus, Digitek may be ineffective until serum calcium is restored to normal. These interactions are related to the fact that Digitek affects contractility and excitability of the heart in a manner similar to that of calcium.

Use in Thyroid Disorders and Hypermetabolic States

Hypothyroidism may reduce the requirements for Digitek. Heart failure and/or atrial arrhythmias resulting from hypermetabolic or hyperdynamic states are best, treated by addressing the underlying condition. Atrial arrhythmias associated with hypermetabolic states are particularly resistant to Digitek treatment. Care must be taken to avoid toxicity if Digitek is used.

Use in Patients with Acute Myocardial Infarction

Digitek should be used with caution in patients with acute myocardial infarction. The use of inotropic drugs in some patients in this setting may result in undesirable increases in myocardial oxygen demand and ischemia.

Use During Electrical Cardioversion

It may be desirable to reduce the dose of Digitek for 1 to 2 days prior to electrical cardioversion of atrial fibrillation to avoid the induction of ventricular arrhythmias, but physicians must consider the consequences of increasing the ventricular response if Digitek is withdrawn. If digitalis toxicity is suspected, elective cardioversion should be delayed. If it is not prudent to delay cardioversion, the lowest possible energy level should be selected to avoid provoking ventricular arrhythmias.

Use in Patients with Myocarditis

Digitek can rarely precipitate vasoconstriction and therefore should be avoided in patients with myocarditis.

Use in Patients with Beriberi Heart Disease

Patients with beriberi heart disease may fail to respond adequately to Digitek if the underlying thiamine deficiency is not treated concomitantly.

Laboratory Test Monitoring

Patients receiving Digitek should have their serum electrolytes and renal function assessed periodically; the frequency of assessments will depend on the clinical setting. For discussion of serum Digitek concentrations; see DOSAGE AND ADMINISTRATION section.

Drug Interactions

Potassium-depleting diuretics are a major contributing factor to digitalis toxicity. Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalized patients. Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum Digitek concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result. Erythromycin and clarithromycin (and possibly other macrolide antibiotics) and tetracycline may increase Digitek absorption in patients who inactivate Digitek by bacterial metabolism in the lower intestine, so that digitalis intoxication may result (see CLINICAL

Pharmacology: Absorption ). Propantheline and diphenoxylate, by decreasing gut motility, may increase Digitek absorption. Antacids, kaolin-pectin, sulfasalazine, neomycin, cholestyramine; certain anticancer drugs, and metoclopramide may interfere with intestinal Digitek absorption, resulting in unexpectedly low serum concentrations. Rifampin may decrease serum Digitek concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of Digitek. There have been inconsistent reports regarding the effects of other drugs [e.g., quinine, penicillamine] on serum Digitek concentration. Thyroid administration to a digitalized, hypothyroid patient may increase the dose requirement of Digitek. Concomitant use of Digitek and sympathomimetics increases the risk of cardiac arrhythmias. Succinylcholine may cause a sudden extrusion of potassium from muscle cells, and may thereby cause arrhythmias in digitalized patients. Although calcium channel blockers and Digitek 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. Digitek concentrations are increased by about 15% when Digitek and cervedilol are administered concomitantly. Therefore, increased monitoring of Digitek is recommended when initiating, adjusting, or discontinuing carvedilol.

Due to the considerable variability of these interactions; the dosage of Digitek should be individualized when patients receive these medications concurrently. Furthermore, caution should be exercised when combining Digitek 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 Digitek.

Drug/Laboratory Test Interactions

The use of therapeutic doses of Digitek may cause prolongation of the PR interval and depression of the ST segment on the electrocardiogram. Digitek may produce false positive ST-T changes on the electrocardiogram during exercise testing. These electrophysiologic effects reflect an expected effect of the drug and are not indicative of toxicity.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Digitek showed no genotoxic potential in vitro studies. No data are available on the carcinogenic potential of Digitek, nor have studies been conducted to assess its potential to affect fertility.

Pregnancy: Teratogenic Effects. Pregnancy Category C

Animal reproduction studies have not been conducted with Digitek. It is also not known whether Digitek can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Digitek should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Studies have shown that Digitek concentrations in the mother's serum and milk are similar. However, the estimated exposure of a nursing infant to Digitek via breastfeeding will be far below the usual infant maintenance dose. Therefore, this amount should have no pharmacologic effect upon the infant. Nevertheless, caution should be exercised when Digitek is administered to a nursing woman.

Pediatric Use

Newborn infants display considerable variability in their tolerance to Digitek. Premature and immature infants are particularly sensitive to the effects of Digitek, and the dosage of the drug must not only be reduced but must be individualized according to their degree of maturity. Digitalis glycosides can cause poisoning in children due to accidental ingestion.

Geriatric Use

The majority of clinical experience gained with Digitek has been in the elderly population. This experience has not identified differences in response or adverse effects between the elderly and younger patients. However, this drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, which should be based on renal function, and it may be useful to monitor renal function (see DOSAGE AND ADMINISTRATION ).

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ADVERSE REACTIONS:

In general, the adverse reactions of Digitek are dose-dependent and occur at doses higher than those needed to achieve a therapeutic effect. Hence, adverse reactions are less common when Digitek 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 Digitek, 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 Digitek were used and little attention was paid to clinical status or concurrent medications, adverse reactions to Digitek 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 Digitek 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 Digitek and in those taking placebo. In a large mortality trial, the incidence of hospitalization for suspected Digitek toxicity was 2% in patients taking Digitek Tablets compared to 0.9% in patients taking placebo. In this trial, the most common manifestations of Digitek toxicity included gastrointestinal and cardiac disturbances; CNS manifestations were less common.

Adults: Cardiac

Therapeutic doses of Digitek may cause heart block in patients with pre-existing sinoatrial or AV conduction disorders; heart block can be avoided by adjusting the dose of Digitek. Prophylactic use of a cardiac pacemaker may be considered if the risk of heart block is considered unacceptable. High doses of Digitek may produce a variety of rhythm disturbances, such as first-degree, second-degree, or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation. Digitek produces PR prolongation and ST segment depression which should not by themselves be considered Digitek toxicity. Cardiac toxicity can also occur at therapeutic doses in patients who have conditions which may alter their sensitivity to Digitek (see WARNINGS and PRECAUTIONS ).

Gastrointestinal

Digitek may cause anorexia, nausea, vomiting, and diarrhea. Rarely, the use of Digitek has been associated with abdominal pain, intestinal ischemia, and hemorrhagic necrosis of the intestines.

CNS

Digitek can produce visual disturbances, headache, weakness, dizziness, apathy, confusion, and mental disturbances (such as anxiety, depression, delirium; and hallucination).

Other

Gynecomastia has been occasionally observed following the prolonged use of Digitek. Thrombocytopenia and maculopapular rash and other skin reactions have been rarely observed.

Table 4 summarizes the incidence of those adverse experiences listed above for patients treated with Digitek Tablets or placebo from two randomized, double-blind, placebo-controlled withdrawal trials. Patients in these trials were also receiving diuretics with or without angiotensin-converting enzyme inhibitors. These patients had been stable on Digitek, and were randomized to Digitek or placebo. The results shown in Table 4 reflect the experience in patients following dosage titration with the use of serum Digitek concentrations and careful follow-up. These adverse experiences are consistent with results from a large, placebo-controlled mortality trial (DIG trial) wherein over half the patients were not receiving Digitek prior to enrollment.

Adverse Experience Digitek Patients Placebo Patients
(n=123) (n=125)
Cardiac
Palpitation 1 4
Ventricular extrasystole 1 1
Tachycardia 2 1
Heart arrest 1 1
Gastrointestinal
Anorexia 1 4
Nausea 4 2
Vomiting 2 1
Diarrhea 4 1
Abdominal pain 0 6
CNS
Headache 4 4
Dizziness 6 5
Mental disturbances 5 1
Other
Rash 2 1
Death 4 3

Infants and Children

The side effects of Digitek in infants and children differ from those seen in adults in several respects. Although Digitek may produce anorexia, nausea, vomiting, diarrhea, and CNS disturbances in young patients, these are rarely the initial symptoms of overdosage. Rather, the earliest and most frequent manifestation of excessive dosing with Digitek in infants and children is the appearance of cardiac arrhythmias, including sinus bradycardia. In children, the use of Digitek may produce any arrhythmia. The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending Digitek intoxication, especially in infants, even in the absence of first-degree heart block. Any arrhythmia or alteration in cardiac conduction that develops in a child taking Digitek should be assumed to be caused by Digitek, until further evaluation proves otherwise.

To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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OVERDOSAGE:

Signs and Symptoms

The signs and symptoms of toxicity are generally similar to those described in the ADVERSE REACTIONS section but may be more frequent and can be more severe. Signs and symptoms of Digitek toxicity become more frequent with levels above 2 ng/mL. However, in deciding whether a patient's symptoms are due to Digitek, the clinical state together with serum electrolyte levels and thyroid function are important factors.

Adults

In adults without heart disease, clinical observation suggests that an overdose of Digitek of 10 to 15 mg was the dose resulting in death of half of the patients. If more than 25 mg of Digitek was ingested by an adult without heart disease, death or progressive toxicity responsive only to digoxin-binding Fab antibody fragments resulted. Cardiac manifestations are the most frequent and serious sign of both acute and chronic toxicity. Peak cardiac effects generally occur 3 to 6 hours following overdosage and may persist for the ensuing 24 hours or longer. Digitek toxicity may result in almost any type of arrhythmia (see ADVERSE REACTIONS ). Multiple rhythm disturbances in the same patient are common. Cardiac arrest from asystole or ventricular fibrillation due to Digitek toxicity is usually fatal.

Among the extra-cardiac manifestations, gastrointestinal symptoms (e.g., nausea, vomiting, anorexia) are very common (up to 80% incidence) and precede cardiac manifestations in approximately half of the patients in most literature reports. Neurologic manifestations (e.g., dizziness, various CNS disturbances), fatigue, and malaise are very common. Visual manifestations may also occur with aberration in color vision (predominance of yellow green) the most frequent. Neurological and visual symptoms may persist after other signs of toxicity have resolved. In chronic toxicity, non-specific extra-cardiac symptoms, such as malaise and weakness, may predominate.

Children

In children aged 1 to 3 years without heart disease, clinical observation suggests that an overdose of Digitek of 6 to 10 mg was the dose resulting in death in half of the patients. If more than 10 mg of Digitek was ingested by a child aged 1 to 3 years without heart disease, the outcome was uniformly fatal when Fab fragment treatment was not given. Most manifestations of toxicity in children occur during or shortly after the loading phase with Digitek. The same arrhythmias or combination of arrhythmias that occur in adults can occur in pediatrics. Sinus tachycardia, supraventricular tachycardia, and rapid atrial fibrillation are seen less frequently in the pediatric population. Pediatric patients are more likely to present with an AV conduction disturbance or a sinus bradycardia. Any arrhythmia or alteration in cardiac conduction that develops in a child taking Digitek should be assumed to be caused by Digitek, until further evaluation proves otherwise.

The frequent extracardiac manifestations similar to those seen in adults are gastrointestinal, CNS, and visual. However, nausea and vomiting are not frequent in infants and small children.

In addition to the undesirable effects seen with recommended doses, weight loss in older age groups and failure to thrive in infants, abdominal pain due to mesenteric artery ischemia, drowsiness, and behavioral disturbances including psychotic manifestations have been reported in overdose.

Treatment

In addition to cardiac monitoring, Digitek 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 (see WARNINGS and PRECAUTIONS: Drug Interactions ). Once the adverse reaction has resolved, therapy with Digitek may be reinstituted, following a careful reassessment of dose.

When the primary manifestation of Digitek 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 Digitek Immune Fab (Ovine) [DIGIBIND® or DigiFab®] (see Massive Digitalis Overdosage subsection), the use of atropine, or the insertion of a temporary cardiac pacemaker. Digitek Immune Fab (Ovine) is a specific antidote for Digitek and may be used to reverse potentially life-threatening ventricular arrhythmias due to Digitek 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.

Administration of Potassium

Before administering potassium in Digitek overdose for hypokalemia, the serum potassium must be known and every effort should be made to maintain the serum potassium concentration between 5 and 5.5 mmol/L. Potassium salts should be avoided as they may be dangerous in patients who manifest bradycardia or heart block due to Digitek (unless primarily related to supraventricular tachycardia) and in the setting of massive digitalis overdosage. Potassium is usually administered orally, but when correction of the arrhythmia is urgent and the serum potassium concentration is low, potassium may be administered cautiously by the intravenous route. The electrocardiogram should be monitored for any evidence of potassium toxicity (e.g., peaking of T waves) and to observe the effect on the arrhythmia.

Massive Digitalis Overdosage

Manifestations of life-threatening toxicity include ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias, or heart block. Digitek Immune Fab (Ovine) should be used to reverse the toxic effects of ingestion of a massive overdose. The decision to administer Digitek Immune Fab (Ovine) to a patient who has ingested a massive dose of Digitek but who has not yet manifested life-threatening toxicity should depend on the likelihood that life-threatening toxicity will occur.

Digitek is not effectively removed from the body by dialysis due to its large extravascular volume of distribution. Patients with massive digitalis ingestion should receive large doses of activated charcoal to prevent absorption and bind Digitek in the gut during enteroenteric recirculation. Emesis may be indicated especially if ingestion has occurred within 30 minutes of the patient's presentation at the hospital. Emesis should not be induced in patients who are obtunded. If a patient presents more than 2 hours after ingestion or already has toxic manifestations, it may be unsafe to induce vomiting because such maneuvers may induce an acute vagal episode that can worsen digitalis-related arrhythmias.

In cases where a large amount of Digitek has been ingested, hyperkalemia may be present due to release of potassium from skeletal muscle. Hyperkalemia caused by massive digitalis toxicity is best treated with Digitek Immune Fab (Ovine); initial treatment with glucose and insulin may also be required if hyperkalemia itself is acutely life-threatening.

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DOSAGE AND ADMINISTRATION:

General

Recommended dosages of Digitek 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. In selecting a dose of Digitek, the following factors must be considered:

  • The body weight of the patient. Doses should be calculated based upon lean body weight.
  • The patient's renal function, preferably evaluated on the basis of estimated creatinine clearance.
  • The patient's age. Infants and children require different doses of Digitek than adults. Also, advanced age may be indicative of diminished renal function even in patients with normal serum creatinine concentration (i.e., below 1.5 mg/dL).
  • Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of Digitek (see PRECAUTIONS ).

Serum Digitek Concentrations

In general, the dose of Digitek used should be determined on clinical grounds. However, measurement of serum Digitek concentrations can be helpful to the clinician in determining the adequacy of Digitek therapy and in assigning certain probabilities to the likelihood of Digitek intoxication. About two-thirds of adults considered adequately digitalized (without evidence of toxicity) have serum Digitek concentrations ranging from 0.8 to 2 ng/mL (lower serum trough concentrations of 0.5 to 1 ng/mL may be appropriate in some adult patients, see Maintenance Dosing .) However, Digitek may produce clinical benefits even at serum concentrations below this range. About two-thirds of adult patients with clinical toxicity have serum Digitek concentrations greater than 2 ng/mL. However, since one-third of patients with clinical toxicity have concentrations less than 2 ng/mL, values below 2 ng/mL do not rule out the possibility that a certain sign or symptom is related to Digitek therapy. Rarely, there are patients who are unable to tolerate Digitek at serum concentrations below 0.8 ng/mL. Consequently, the serum concentration of Digitek 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 Digitek 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 Digitek 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 Digitek 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:

  • Analytical problems in the assay procedure.
  • Inappropriate serum sampling time.
  • Administration of a digitalis glycoside other than Digitek.
  • Conditions (described in WARNINGS and PRECAUTIONS ) causing an alteration in the sensitivity of the patient to Digitek.
  • Serum Digitek concentration may decrease acutely during periods of exercise without any associated change in clinical efficacy due to increased binding of Digitek to skeletal muscle.

Heart Failure: Adults

Digitalization may be accomplished by either of two general approaches that vary in dosage and frequency of administration, but reach the same endpoint in terms of total amount of Digitek accumulated in the body.

  • If rapid digitalization is considered medically appropriate, it may be achieved by administering a loading dose based upon projected peak Digitek body stores. Maintenance dose can be calculated as a percentage of the loading dose.
  • More gradual digitalization may be obtained by beginning an appropriate maintenance dose, thus allowing Digitek body stores to accumulate slowly. Steady-state serum Digitek concentrations will be achieved in approximately five half-lives of the drug for the individual patient. Depending upon the patient's renal function, this will take between 1 and 3 weeks.

Rapid Digitalization with a Loading Dose

Peak Digitek body stores of 8 to 12 mcg/kg should provide therapeutic effect with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm. Because of altered Digitek distribution and elimination, projected peak body stores for patients with renal insufficiency should be conservative (see PRECAUTIONS ).

The loading dose should be administered in several portions, with roughly half the total given as the first dose. Additional fractions of this planned total dose may be given at 6- to 8-hour intervals, with careful assessment of clinical response before each additional dose.

If the patient's clinical response necessitates a change from the calculated loading dose of Digitek, then calculation of the maintenance dose should be based upon the amount actually given.

A single initial dose of 500 to 750 mcg (0.5 to 0.75 mg) of Digitek Tablets usually produces a detectable effect in 0.5 to 2 hours that becomes maximal in 2 to 6 hours. Additional doses of 125 to 375 mcg (0.125 to 0.375 mg) may be given cautiously at 6- to 8-hour intervals until clinical evidence of an adequate effect is noted. The usual amount of Digitek Tablets that a 70 kg patient requires to achieve 8 to 12 mcg/kg peak body stores is 750 to 1250 mcg (0.75 to 1.25 mg).

Digitek Injection is frequently used to achieve rapid digitalization, with conversion to Digitek Tablets for maintenance therapy. If patients are switched from intravenous to oral Digitek formulations, allowances must be made for differences in bioavailability when calculating maintenance dosages (see Table 1, CLINICAL PHARMACOLOGY ).

Maintenance Dosing

The doses of Digitek used in controlled trials in patients with heart failure have ranged from 125 to 500 mcg (0.125 to 0.5 mg) once daily. In these studies, the Digitek dose has been generally titrated according to the patient's age, lean body weight, and renal function. Therapy is generally initiated at a dose of 250 mcg (0.25 mg) once daily in patients under age 70 with good renal function, at a dose of 125 mcg (0.125 mg) once daily in patients over age 70 or with impaired renal function, and at a dose of 62.5 mcg (0.0625 mg) in patients with marked renal impairment. Doses may be increased every 2 weeks according to clinical response.

In a subset of approximately 1800 patients enrolled in the DIG trial (wherein dosing was based on an algorithm similar to that in Table 5) the mean (± SD) serum Digitek concentrations at 1 month and 12 months were 1.01 ± 0.47 ng/mL and 0.97 ± 0.43 ng/mL, respectively. There are no rigid guidelines as to the range of serum concentrations that are most efficacious. Several post hoc analyses of heart failure patients in the DIG trial suggest that the optimal trough Digitek serum level may be 0.5 ng/mL to 1 ng/mL.

The maintenance dose should be based upon the percentage of the peak body stores lost each day through elimination. The following formula has had wide clinical use:

Maintenance Dose = Peak Body Stores (i.e., Loading Dose) x % Daily Loss
100
Where: % Daily Loss = 14 + Ccr/5
(Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area.)

Table 5 provides average daily maintenance dose requirements of Digitek Tablets for patients with heart failure based upon lean body weight and renal function:


* Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area. For adults, if only serum creatinine concentrations (Scr) are available, a Ccr (corrected to 70 kg body weight) may be estimated in men as (140 - Age)/Scr. For women, this result should be multiplied by 0.85. Note: This equation cannot be used for estimating creatinine clearance in infants or children.


lf no loading dose administered.


62.5 mcg = 0.0625 mg

Corrected Ccr Lean Body Weight Number of
(mL/min kg 50 60 70 80 90 100 Days Before
per 70 kg)* lb 110 132 154 176 198 220 Steady State Achieved
0 62.5 125 125 125 187.5 187.5 22
10 125 125 125 187.5 187.5 187.5 19
20 125 125 187.5 187.5 187.5 250 16
30 125 187.5 187.5 187.5 250 250 14
40 125 187.5 187.5 250 250 250 13
50 187.5 187.5 250 250 250 250 12
60 187.5 187.5 250 250 250 375 11
70 187.5 250 250 250 250 375 10
80 187.5 250 250 250 375 375 9
90 187.5 250 250 250 375 500 8
100 250 250 250 375 375 500 7

Example

Based on Table 5, a patient in heart failure with an estimated lean body weight of 70 kg and a Ccr of 60 mL/min should be given a dose of 250 mcg daily of Digitek Tablets, usually taken after the morning meal. If no loading dose is administered, steady-state serum concentrations in this patient should be anticipated at approximately 11 days.

Infants and Children

In general, divided daily dosing is recommended for infants and young children (under age 10). In the newborn period, renal clearance of Digitek is diminished and suitable dosage adjustments must be observed. This is especially pronounced in the premature infant. Beyond the immediate newborn period, children generally require proportionally larger doses than adults on the basis of body weight or body surface area. Children over 10 years of age require adult dosages in proportion to their body weight. Some researchers have suggested that infants and young children tolerate slightly higher serum concentrations than do adults.

Daily maintenance doses for each age group are given in Table 6 and should provide therapeutic effects with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm. These recommendations assume the presence of normal renal function:

Age Daily Maintenance Dose
(mcg/kg)
2 to 5 Years 10 to 15
5 to 10 Years 7 to 10
Over 10 Years 3 to 5

In children with renal disease, Digitek must be carefully titrated, based upon clinical response.

It cannot be overemphasized that both the adult and pediatric dosage guidelines provided are based upon average patient response and substantial individual variation can be expected. Accordingly, ultimate dosage selection must be based upon clinical assessment of the patient.

Atrial Fibrillation

Peak Digitek body stores larger than the 8 to 12 mcg/kg required for most patients with heart failure and normal sinus rhythm have been used for control of ventricular rate in patients with atrial fibrillation. Doses of Digitek used for the treatment of chronic atrial fibrillation should be titrated to the minimum dose that achieves the desired ventricular rate control without causing undesirable side effects. Data are not available to establish the appropriate resting or exercise target rates that should be achieved.

Dosage Adjustment When Changing Preparations

The difference in bioavailability between Digitek Injection or Digoxin Tablets must be considered when changing patients from one dosage form to another.

Doses of 100 mcg (0.1. mg) and 200 mcg (0.2 mg) of Digitek solution in capsules are approximately equivalent to 125 mcg (0.125 mg) and 250 mcg (0.25 mg) doses of Digitek tablets and Digitek pediatric elixir, respectively (see Table 1 in CLINICAL

Pharmacology: Pharmacokinetics ).

HOW SUPPLIED:

Digitek Tablets, USP 0.125 mg are Yellow, Round, Scored Tablets, Debossed "W 40" on Scored Side and are available in:

  • Bottles of 100 tablets.
  • Bottles of 1000 tablets.
  • Bottles of 5000 tablets.

Digitek Tablets, USP 0.25 mg are White, Round, Scored Tablets, Debossed "WW 41" on Scored Side and are available in:

  • Bottles of 100 tablets.
  • Bottles of 1000 tablets.
  • Bottles of 5000 tablets.

Store at 20-25ºC (68-77ºF) in a dry place.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Digibind® is a registered trademark of GlaxoSmithKline.

DigiFab is a registered trademark of Prostherics Inc.

Manufactured By:

West-ward Pharmaceutical Corp.

Eatontown, NJ 07724

Revised December 2011

Digitek 0.25 MG Tablet

Structural Formula

Digitek pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Digitek available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Digitek destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Digitek Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Digitek pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."DIGOXIN TABLET [BRYANT RANCH PREPACK]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."DIGOXIN: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "digoxin". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Digitek?

Depending on the reaction of the Digitek after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Digitek not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Digitek addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Digitek, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Digitek consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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