Lanoxicaps Dosage

Generic name: digoxin
Dosage form: Solution in Capsules

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General

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. Due to the more complete absorption of digoxin from soft capsules, recommended oral doses are only 80 percent of those for Tablets and Elixir.

Because the significance of the higher peak serum concentrations associated with once daily capsules is not established, divided daily dosing is presently recommended for:

  1. Infants and children under 10 years of age;
  2. Patients requiring a daily dose of 300 mcg (0.3 mg) or greater;
  3. Patients with a previous history of digitalis toxicity;
  4. Patients considered likely to become toxic;
  5. Patients in whom compliance is not a problem.

Where compliance is considered a problem, single daily dosing may be appropriate.

In selecting a dose of digoxin, the following factors must be considered:

  1. The body weight of the patient. Doses should be calculated based upon lean (i.e., ideal) body weight.
  2. The patient’s renal function, preferably evaluated on the basis of estimated creatinine clearance.
  3. The patient’s age. Infants and children require different doses of digoxin 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).
  4. Concomitant disease states, concurrent medications, or other factors likely to alter the pharmacokinetic or pharmacodynamic profile of digoxin (see PRECAUTIONS).

Serum Digoxin Concentrations

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. 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:

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

  1. If rapid digitalization is considered medically appropriate, it may be achieved by administering a loading dose based upon projected peak digoxin body stores. Maintenance dose can be calculated as a percentage of the loading dose.
  2. More gradual digitalization may be obtained by beginning an appropriate maintenance dose, thus allowing digoxin body stores to accumulate slowly. Steady-state serum digoxin concentrations will be achieved in approximately 5 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 digoxin 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 digoxin distribution and elimination, projected peak body stores for patients with renal insufficiency should be conservative (i.e., 6 to 10 mcg/kg) [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 digoxin, then calculation of the maintenance dose should be based upon the amount actually given.

A single initial dose of 400 to 600 mcg (0.4 to 0.6 mg) of LANOXICAPS usually produces a detectable effect in 0.5 to 2 hours that becomes maximal in 2 to 6 hours. Additional doses of 100 to 300 mcg (0.1 to 0.3 mg) may be given cautiously at 6- to 8-hour intervals until clinical evidence of an adequate effect is noted. The usual amount of LANOXICAPS that a 70-kg patient requires to achieve 8 to 12 mcg/kg peak body stores is 600 to 1,000 mcg (0.6 to 1.0 mg).

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

Maintenance Dosing

The doses of digoxin tablets 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 digoxin 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 1,800 patients enrolled in the DIG trial (wherein dosing was based on an algorithm similar to that in Table 5) the mean (± SD) serum digoxin concentrations at 1 month and 12 months were 1.01 ± 0.47 ng/mL and 0.97 ± 0.43 ng/mL, respectively.

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 LANOXICAPS Capsules for patients with heart failure based upon lean body weight and renal function:

Table 5. Usual Daily Maintenance Dose Requirements (mcg) of LANOXICAPS Capsules for Estimated Peak Body Stores of 10 mcg/kg

Corrected Ccr

(mL/min per 70 kg)*

Lean Body Weight

Number of Days Before Steady State Achieved

kg

50

60

70

80

90

100

lb

110

132

154

176

198

220

0

50

100

100

100

150

150

22

10

100

100

100

150

150

150

19

20

100

100

150

150

150

200

16

30

100

150

150

150

200

200

14

40

100

150

150

200

200

250

13

50

150

150

200

200

250

250

12

60

150

150

200

200

250

300

11

70

150

200

200

250

250

300

10

80

150

200

200

250

300

300

9

90

150

200

250

250

300

350

8

100

200

200

250

300

300

350

7

*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.

If no loading dose administered.

50 mcg = 0.05 mg

Example

Based on the above table, 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 200 mcg (0.2 mg) daily of LANOXICAPS, usually taken as a divided dose of one 100-mcg (0.1-mg) capsule after the morning and evening meals. 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 these patients, where dosage adjustment is frequent and outside the fixed dosages available, LANOXICAPS may not be the formulation of choice. In the newborn period, renal clearance of digoxin 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:

Table 6. Usual Digitalizing and Maintenance Dosages for LANOXICAPS in Children With Normal Renal Function Based on Lean Body Weight

Age

Digitalizing* Dose

(mcg/kg)

Daily Maintenance Dose (mcg/kg)

2 to 5 Years

25 to 35

25% to 35% of

the oral or I.V.

digitalizing dose

5 to 10 Years

15 to 30

 

Over 10 Years

8 to 12

 

*IV digitalizing doses are the same as digitalizing doses of LANOXICAPS.

Divided daily dosing is recommended for children under 10 years of age.

Projected or actual digitalizing dose providing desired clinical response.

In children with renal disease, digoxin 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 digoxin 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 digoxin 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 absolute bioavailability of the capsule formulation is greater than that of the standard tablets and very near that of the intravenous dosage form. As a result, the doses recommended for LANOXICAPS Capsules are the same as those for LANOXIN Injection (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics). Adjustments in dosage will seldom be necessary when converting a patient from the intravenous formulation to LANOXICAPS. The difference in bioavailability between LANOXIN Injection or LANOXICAPS and LANOXIN Elixir Pediatric or LANOXIN 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 LANOXICAPS are approximately equivalent to 125-mcg (0.125-mg) and 250-mcg (0.25-mg) doses of LANOXIN Tablets and Elixir Pediatric, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics).

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