INDICES> methyldigoxin (2)

["Clinica Tossicologia" <clintox@ospedaliriuniti.bergamo.it>]

INDICES> methyldigoxin (2)
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Dear Tuning Nina,

1.     Beta-methyldigoxin is registred in Italy as proprietary preparation
since 1972

2.     Efficacy and safety (compared to digoxin): see attachment

3.     All information about purities or impurities are available in the
Japan Pharmacopoeia; for the specific proprietary preparations see "Drug
Master File" available only from the Manufacturing Industry and the
Ministry
of Health

(See attached file)

Best regards

Dr. Maria Luisa Farina
Clinical Toxicology Unit
Ospedali Riuniti - Bergamo (Italy)

Email: clintox@ospedaliriuniti.bergamo.it  [manually added by moderator;
WB]

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[Methyldigoxin = Medigoxin]

§ 1. ATRIAL FIBRILLATION 
§ a. SUMMARY: Oral medigoxin has been similar in efficacy to oral digoxin
in patients with atrial fibrillation; there appears to be no reason to use
medigoxin over digoxin in this setting. Two open cross-over studies have
reported the similar efficacy of medigoxin 0.2 to 0.3 milligram daily and
digoxin 0.25 to 0.5 milligram daily in controlling the ventricular response
in patients with atrial fibrillation (Coburn et al, 1979; Halley &
Counihan, 1980). Similarly, another study (Andersson et al, 1977) reported
the comparable efficacy of medigoxin 0.1 milligram twice daily and digoxin
0.13 milligram twice daily in slowing the ventricular rate at rest in
decompensated patients with atrial fibrillation. During exercise, heart
rate was slightly but significantly higher in patients receiving digoxin.
The reasons for this difference were unclear, although it is of doubtful
clinical significance. 
§ 2. CONGESTIVE HEART FAILURE 
§ a. SUMMARY: Despite evidence of its more rapid and complete absorption,
available data do not suggest that medigoxin will offer any clinical
advantage over digoxin in treating patients with congestive heart failure;
however, adequate comparisons of onset and magnitude of inotropic responses
following intravenous and oral administration of these agents in heart
failure patients are lacking. In 1 double-blind study involving 86 patients
with congestive heart failure, medigoxin 0.15 milligram daily was similarly
as effective as digoxin 0.3 milligram daily as maintenance therapy (Kimura
& Sakuma, 1980). 
§ b. In a study involving healthy volunteers, time to maximal response and
magnitude of cardiac (inotropic) effects were similar with equivalent doses
of oral medigoxin and oral digoxin, despite the better absorption of the
former. Positive inotropic responses to intravenous digoxin and intravenous
medigoxin were similar and of greater magnitude than with oral
administration of these agents. Time to maximal response was similar (4
hours) regardless of the agent administered or route of administration.
Thus, the higher serum levels observed with oral medigoxin, which persisted
for about 4 hours, were of no benefit in providing more rapid or superior
cardiac effects in comparison to oral digoxin in this population. These
data do not support the contention that oral medigoxin could obviate the
need for intravenous digoxin in acute situations (Das et al, 1977; Das,
1989). 
§ c. For medigoxin to be considered further as a potential alternative to
digoxin, similar types of investigations are needed in congestive heart
failure patients. Any future studies should also compare the stable
solution/capsule formulation of digoxin (Lanoxicaps(R)) with medigoxin. The
bioavailability of digoxin as Lanoxicaps(R) is 90% to 100% (AMA, 1986). 
§ 3. PHARMACOKINETICS 
§ a. Based on pharmacokinetic data, it would appear that the dose of
digoxin would have to be increased by at least 1.5-fold compared to
medigoxin in order to achieve comparable serum glycoside concentrations.
Clinically, a maintenance dose ratio of 1:2 for medigoxin:digoxin has
produced similar improvement in patients with heart failure (0.15 milligram
medigoxin/day versus 0.3 milligram digoxin/day) (Ito et al, 1975; Kimura &
Sakuma, 1980). 
§ b. One study (Halley & Counihan, 1980) reported higher steady-state serum
glycoside levels with lower doses of medigoxin as compared to digoxin in
patients with atrial fibrillation. Serum levels of 1.3 and 0.8
nanograms/milliliter were observed with medigoxin 0.2 milligram daily and
digoxin 0.25 milligram daily, respectively. With oral doses of 0.3
milligram medigoxin and 0.5 milligram digoxin, corresponding levels were
1.3 and 1 nanogram/milliliter, respectively. An even greater difference in
glycoside levels was reported with higher doses of each drug (1.6
nanograms/milliliter with medigoxin 0.4 mg daily and 1 nanogram/milliliter
with digoxin 0.625 milligram daily). However, in other studies, similar
mean steady-state plasma glycoside concentrations (1.4 to 1.5
nanogram/milliliter) have been reported with both medigoxin 0.3 milligram
daily and digoxin 0.5 milligram daily (Coburn et al, 1979; Kongola et al,
1976).
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