VENARSEN
Report of the Council on Pharmacy and Chemistry
The report which appears below was sent to the Intravenous Products Company for consideration. Having considered the firm’s reply, the Council has authorized publication of its report along with the explanation sent by the Intravenous Products Company in reference to the variable composition reported for Venarsen, namely, that “only the first few experimental ampules, sent to the doctors for clinical tests, were made without the Mercuric Iodide.”
W. A. Puckner, Secretary.
This product is prepared by the Intravenous Products Company, Denver. The advertising circulars contain inconsistent statements as to its composition. According to one circular Venarsen is
“... a comparatively non-toxic organic arsenic compound, 0.6 Gm. representing 247 Mg. (33⁄4 grains) of metallic arsenic in chemical combination....”
According to another circular Venarsen is
“... a comparatively non-toxic organic arsenic compound, 0.6 Gm., representing 247 Mg. (33⁄4 grains) of metallic arsenic and .78 Mg. (3⁄250 grain) metallic mercury in chemical combination.”
Neither one of these statements gives any information as to the actual composition of the product. Inquiry addressed to the manufacturers elicited the reply that:
“Venarsen contains in each 5 c.c. 0.6 Gm. Sodium Dimethyl Arsenate, .0016 grams of Mercuric Iodide, .0048 grams of Sodium Iodide in solution in a suitable vehicle for intravenous administration.”
The following report of the examination of Venarsen is submitted by the Association’s Chemical Laboratory:
LABORATORY REPORT
Three ampules of Venarsen were examined. The first ampule was labeled
“A comparatively non-toxic organic arsenic compound, representing 247 Mg. (33⁄4 grs.) of metallic arsenic in chemical combination. 5 c.c.—0.6 Gm.”
Practically the same statement appeared in an advertising circular wrapped around the ampule. The second and third ampules bore labels identical with the first. The circulars differed from that accompanying the first ampule in that the presence of mercury is also announced, thus:
“Venarsen is a comparatively non-toxic organic arsenic compound, 0.6 Gm., representing 247 Mg. (33⁄4 grains) of metallic arsenic and .78 Mg. (3⁄250 grain) metallic mercury in chemical combination and is so prepared and enhanced as to present the ingredients to the blood in their most acceptable form.”
Thus, although the potent elements said to be contained in Venarsen are named, its chemical character (the combination in which the elements occur) is not disclosed.
The ampules contained a transparent, odorless solution, possessing the yellow color of salvarsan solution (an aqueous solution of sodium cacodylate, mercuric iodid and sodium iodid in the amounts said to be present in Venarsen is colorless). Qualitative tests demonstrated the presence in each of the three ampules of sodium cacodylate (sodium dimethyl arsenate), and the absence of arsenites, arsenates, phosphates, arsanilates (atoxyl, soamin) and arsenphenolamins (salvarsan, neosalvarsan). Titrated with normal hydrochloric acid, using methyl orange as indicator (as outlined in New and Nonofficial Remedies, 1915, p. 40), the three ampules were found to contain the equivalent of respectively, 0.219, 0.253 and 0.216 Gm., or an average of 0.244 Gm. arsenic. (According to statements of the firm each 5 c.c. of Venarsen contains 0.6 Gm. sodium dimethyl arsenate [sodium cacodylate], equivalent to 0.247 Gm. arsenic or 41.66 per cent. Sodium dimethyl arsenate, as described in New and Nonofficial Remedies, contains 3 molecules of water and 35 per cent. arsenic. This indicates that the sodium dimethyl arsenate used in Venarsen contains less water of crystallization than the N. N. R. product).
Neither mercury nor iodid could be found in the first ampule. (The company has since explained that mercury was absent only from the first experimental samples.) The second and third ampules contained iodid and mercury in small amount. The exact quantity was not determined because, on the basis of the mercury content declared, a single accurate mercury estimation would have required the purchase of something like 25 to 100 ampules. As each ampule sells for two dollars, the cost of the material was considered prohibitive.
From the foregoing we conclude that the first ampule examined consisted essentially of a solution containing 0.625 Gm. of sodium cacodylate, N. N. R., while the second and third ampules contained 0.722 Gm. and 0.617 Gm. sodium cacodylate, respectively, and in addition, a mercury compound, probably mercuric iodid, dissolved by sodium iodid.
In other terms, Venarsen as now marketed is a simple solution containing approximately 9 grains of sodium cacodylate, 1⁄40 grain of mercury “biniodide” and 3⁄4 grain of sodium iodid to each full dose.
In the past the preparation has been in conflict—especially serious because of the potent character of the drug—with Rule 1 (secrecy of composition). The manufacturers have removed this conflict by furnishing a statement of composition; and it is to be expected that they will likewise take steps to remove the manifestly erroneous impression now likely to be gathered from the circulars, namely, that the preparation is rather analogous to salvarsan. These conflicts, however, call for comment, since physicians have doubtless used the material under misapprehensions.
As to therapeutic claims, the preparation is said to be effective and safe in syphilis; “lower toxicity and greater spirochaetacidal power than other known arsenic compounds” are among the claims. No real evidence for either of these claims is presented. Sodium cacodylate has been tried as an antisyphilitic, but with indifferent success; certainly the results have not been comparable to those of salvarsan. The mercury could conceivably enhance its effect, but the dosage appears too small and the course too short for this influence to be pronounced. Moreover, a careful physician would not give arsenic and mercury in fixed proportions.
The claim of comparative non-toxicity is probable enough from what is known about the cacodylate. No physician should feel “safe,” however, when injecting intravenously 0.6 gm. of sodium cacodylate every four to six days. Aside from the grave dangers of intravenous injection in general, the possibility of idiosyncrasies to arsenicals should always be borne in mind.
Finally, Venarsen is claimed to be “indicated” in pellagra, tuberculosis, anemia, etc. No evidence is presented on which to base an opinion as to its efficiency in pellagra. Those who have studied that disease would not be likely to resort to this treatment. In tuberculosis and anemia, there is no sufficient advantage in giving the cacodylate intravenously.
To summarize, Venarsen treatment consists essentially in the intravenous injection of large doses of sodium cacodylate. The other ingredients, as well as the name, merely constitute so much mystification. While the cacodylate probably has some effect on the conditions for which it is advised, there is no evidence that its value even approaches that of salvarsan in syphilis, or that the intravenous use is preferable to the ordinary methods. The dangers are manifest, although they may not be so great as with salvarsan. No justification has been established for its use in tuberculosis and pellagra.
Physicians who wish to try intravenous cacodylate administration should have a full realization of the dangers of such treatment, and in order to avoid further risks, will do well to refrain from combining other drugs with the cacodylate in fixed proportions.
It is recommended that Venarsen be held in conflict with Rule 6 (unwarranted therapeutic claims), Rule 7 (poisonous ingredients not stated on label), Rule 8 (name does not express the chemical composition) and Rule 10 (unscientific combination) and that this report be published.—(From The Journal A. M. A., May 22, 1915.)