MON-ARSONE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report.

W. A. Puckner, Secretary.

Mon-Arsone is offered by the Harmer Laboratories Company as “a new and non-toxic arsenical for the treatment of syphilis.” In the advertisements for Mon-Arsone it has been claimed that with this drug “the toxic, corrosive and uncertain reactions attending the use of arsphenamine have been entirely eliminated” and that “it has a therapeutic value equal to arsphenamine, but extensive case reports fail to record the slightest toxic reaction following its use.”

According to the manufacturers, Mons-Arsone is disodiumethylarsonate, the sodium salt of ethylarsonic acid, derived from arsenic acid by replacement of one hydroxyl group by the ethyl group—AsO(CH₂CH₃)(OH)₂. Mons-Arsone is related to sodium cacodylate, which is the sodium salt of dimethyl-arsenic acid—AsO(CH₃)₂OH—derived from arsenic acid by replacement of two hydroxyl groups by two methyl groups. Ethylarsonic acid and its potassium salt were described by La Coste [139] more than thirty-five years ago, and the use of the sodium salt of methylarsonic acid was proposed in France some years ago. The Harmer Laboratories Company claims originality for Mons-Arsone in that it was the first to prepare the sodium salt of ethylarsonic acid and to propose its therapeutic use.

It was reported several years ago by Castelli [140] that sodium cacodylate and the sodium salt of methyl arsenic acid were devoid of effect on experimental trypanosomiasis and spirochete infections. Careful clinical observations in this country by H. J. Nichols [141] and H. N. Cole [142] have demonstrated the inefficacy of sodium cacodylate in the treatment of human syphilis.

Animal experiments carried out in the U. S. Hygienic Laboratory by Voegtlin and Smith [143] show that Mon-Arsone is devoid of any practical trypanocidal action. Thus the “therapeutic ratio” (the ratio of the minimal effective dose to the lethal dose) was about 1, that is, it was effective therapeutically only in approximately fatal doses; the therapeutic ratio for arsphenamine in similar conditions was 17, and that of neoarsphenamine, 28.

The findings that sodium dimethylarsenate (sodium cacodylate), sodium methylarsenate, and sodium ethylarsenate are devoid of any practical trypanocidal action and the conclusion that sodium cacodylate is inefficient in the treatment of human syphilis does not prove that Mon-Arsone is without effect on the disease. These findings, however, certainly demand convincing therapeutic evidence to warrant the recommendation for the use of the drug in the treatment of syphilis—particularly because the drug is proposed as a substitute for arsphenamine, the value of which is established.

When the Council first took up the consideration of Mon-Arsone, the only evidence for the claim that it “has a therapeutic value at least equal to that of arsphenamine” consisted, with one exception, of reports from those who had experimented with the drug for the Harmer Laboratories Company, including a report by B. L. Wright, L. A. Kennell, and L. M. Hussey,[144] the latter of the Harmer Laboratories Company. These reports appeared to show that the administration of Mon-Arsone caused less reaction than arsphenamine, and that the immediate effects, judged by clinical symptoms and the response to the Wassermann test, appeared to be good. These trials extended over too short a period of time to permit judgment as to the permanence of the results. A report by an independent observer seemed to indicate that Mon-Arsone does not have the sterilizing action on syphilitic lesions which it is usually believed arsphenamine exercises.

After examining the available evidence, the Council advised the Harmer Laboratories Company that the claim that Mon-Arsone has a therapeutic value equal to arsphenamine appeared unwarranted; that, in the opinion of the Council, Mon-Arsone should not be used except under conditions that justify the experimental trial of an unproved drug, and should not be used in a routine way until the permanence of its effects has been established; and consequently any advertising propaganda for the drug by the Harmer Laboratories Company was to be deprecated.

In its reply the Harmer Laboratories Company admitted that its advertising claim, that Mon-Arsone was at least equal to arsphenamine therapeutically, had been based on reports on fifty cases and on additional reports that were beginning to come in at that time. The Harmer Laboratories Company submitted a list of hospitals and physicians using Mon-Arsone. A letter of inquiry sent by the Council to those who, according to the names in the list supplied by the Harmer Laboratories Company, had used Mon-Arsone, brought seven replies.

The clinical evidence contained in these replies was to the effect that Mon-Arsone had been used in the various types of syphilis and that there was a certain beneficial effect, both clinically and as shown by the Wassermann reaction. In certain instances the Wassermann reaction changed from a four plus to a negative reaction. The reports showed that the efficiency of Mon-Arsone as compared with that of arsphenamine preparations has not been adequately studied. One physician who has used Mon-Arsone extensively reports that in many of the cases treated there seemed to be nearly as good results from the use of Mon-Arsone as is frequently obtained in the use of arsphenamine. He reports, however, that it was necessary in eleven out of one hundred cases to change from Mon-Arsone to neoarsphenamine.

In view of the fact that there is definite lack of evidence to show that Mon-Arsone is the equal of arsphenamine therapeutically, and because of the reports that in some cases it is inferior, Mon-Arsone should not be used in the treatment of syphilis generally until its therapeutic status has been more rigidly investigated and conclusive evidence of its superiority to arsphenamine preparations obtained.

The Council voted not to admit Mon-Arsone to New and Nonofficial Remedies and reaffirmed its conclusion that the claim that Mon-Arsone has a therapeutic value equal to that of arsphenamine is premature and unwarranted; that Mon-Arsone should not be used except under conditions that justify the experimental trial of an unproved drug; and that the advertising propaganda for the drug by the Harmer Laboratories Company is to be deprecated.

When the preceding report was sent to the Harmer Laboratories Company, the firm submitted a reply in which it was stated:

1. That in certain instances patients improved under Mon-Arsone who, previously, had not improved under arsphenamine, and that this should be taken to offset the report of the one hundred cases in which the use of Mon-Arsone had to be abandoned in 11 per cent. of the cases.

2. That the Harmer Laboratories Company has abandoned the claim that Mon-Arsone is therapeutically equal to arsphenamine and that it now furnishes the drug to such men as care to use it simply on the basis of its special and useful characteristics.

The Council heartily endorses the recent warning against the use of untried medicaments which was issued by the U. S. Public Health Service.[145]

Since the Council’s report was prepared a report on the effects of Mon-Arsone on experimental syphilis has been published by Nichols,[146] from the Division of Laboratories, Army Medical School, which concludes:

1. Disodium-ethylarsinate, or mon-arsone, tested on rabbits infected with syphilis shows no spirocheticidal power. The tissues are fatally poisoned as soon as or before the spirochetes are affected.

“2. For its practical use in syphilis there is no such germicidal basis as exists in case of the arsphenamine group.”—(From The Journal A. M. A., June 18, 1921.)