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Novaldin—Not Acceptable For A.D.R.
Council on Dental Therapeutics
133
in the treatment o f Vincent’s infection and other diseases o f the mouth associated with spirochetes. D osage: The maximum dosage by any route should prob ably not exceed 0.4 gm. or, at most, 0.S gm. It is applied locally either in aqueous or, preferably, in glycerin solutions. It is generally used in strengths o f 2 per cent, but strengths up to 6 per cent may be used. Sulpharsphenam ine-Squibb.— A brand o f sulfarsphenamineN.N.R. Manufactured by E. R. Squibb & Sons, New York City, under U. S. patent 1,024,993 (April 30, 1912, expired) by license of the Chemical Foundation, Inc. Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Sqmbb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb,
0.1 0.2 0.3 0.4 0.5 0.6 0.9 3.0
gm.. ampuls gm. ampuls gm. ampuls gm. ampuls gm. ampuls gm. ampuls gm. ampuls gm. ampuls
C H L O R A M IN E P R E P A R A T IO N S * C h loram in e-T Squibb.— A brand o f Chloramine-T, U.S.P. Manufactured by E. R. Squibb & Sons, New York, N. Y. No. U. S. patents or trademarks. Chloramine-T Tablets, 4.6 grains: One tablet dissolved in 1 fluid ounce of water will yield a 1 per cent solution for local application.
NOVALD1N—NOT ACCEPTABLE FOR A.D.R. The Council has authorized publication of the following report. S a m u e l M . G o r d o n , Secretary.
Consideration of Novaldin was undertaken because of inquiries concerning it coming to the Council and because the product has been exhibited at dental meetings and is being exploited before the dental profession. T h e manufacturer of the product is the W inthrop Chemical Company, Inc., N ew Y ork City, which was requested to supply information concerning the product. T h e secretary sent to the referee an advertising circular, a small specimen of the product and a copy o f the description of the product received from the manufacturer. This report is limited to the claims in the circular and separate state ment of description. Synonyms for Novaldin are stated to be Novalgin, which is a trademark for use in certain foreign countries, and Dipyrone, which is a descriptive name. T h e name Novaldin w ill be used in this report, this being the trademark used in the United States. T h e chemical composition of Novaldin is claimed to be phenyldimethylpyrazolon methylaminomethane sulphonate sodium. T h e phenyldimethylpyrazolon portion of the molecule corresponds to the composition of antipyrine, and the second portion of the molecule, namely, methylaminomethane, brings the compound into close relationship to aminopyrine. T h e compound is also close in composition to melubrine which, as an antipyretic or analgesic, has not found much popularity in this country. From this, N oval din might be expected to act pharmacologically and therapeutically like aminopyrine. T h e pharmacologic actions described in the advertising circular concern themselves with the follow in g: body temperature, circulation, respiration, and toxic and fatal doses in animals. It is claimed that Novaldin acts as antipyretic in the experimental fever of rabbits, which might be expected from the w ell-known actions o f amidopyrine or anti pyrine. T h e statement about intravenous toxic dosage in rabbits is not explicit. It is not clear whether the dose refers to 1 gram per kilogram of body weight or per animal, or whether the injection was slow or rapid. T h is large dose is stated to be without effect *Accepted Dental Remedies, 1935, page 123.
134
The Journal of the American Dental Association and The Dental Cosmos
on blood pressure and respiration; a statement which is not convincing to the referee. The fatal dose for white rats is claimed to be 4 grams per kilogram, which seems rather large, but if this is true, the toxicity of Novaldin for man might be comparatively small, although doses based on experiments on rats are not, as a rule, directly transferable to man. Fatal doses of drugs in the case of rats are generally larger than in other mam mals. M ore important than the acute fatal dose and toxicity o f such a product as Novaldin would be the effects o f continued administration over long periods, since such drugs are likely to be used repeatedly. N o results of such continued administration are mentioned in the circular. Since amidopyrine and antipyrine are regarded as possible factors in agranulocytosis, a careful determination of such possibilities as regards N oval din is in order. (Since this report was adopted and sent to the firm, such a casé has been reported. Benjamin and Biederman report the occurrence of a case of granulopenia from the ingestion of Novaldin. [Agranulocytic Leukopenia Induced by a D ru g Related to Aminopyrine, J .A .M .A ., 107:493 (A u g. 15) 1936.].) Important in this connection would be the effect of continued administration of Novaldin on the condition o f the blood and viscera; nutrition and appetite, general tolerance, habituation, etc. T h ere is no indica tion that attempts have been made to determine this. T h e clinical claims for Novaldin stress the absence of toxicity in therapeutic doses, the absence of harmful effects and the indications for use in fever and relief of pain. As for possible injurious effects and lack of toxicity, no consideration is given to possible injuries to the blood and to tissues and functions mentioned above. Special sensitivity and idiosyncrasy to Novaldin, as in the case of antipyrine, are not mentioned. A s for anti pyretic actions, these are the least important with drugs of the antipyrine group, since these drugs are no longer used as antipyretics; the antipyretic action being too rapid and erratic, and, therefore, uncontrollable. T his leaves only the analgesic action, which, of course, is well known fo r the antipyrine group, and is considerably emphasized in the therapeutic use of Novaldin. Therapeutic usefulness is claimed in headache, neuralgia, articular rheumatism, muscu lar rheumatism, colds and influenza, renal colic, biliary colic, otorhinitis, tuberculosis, the pain of childbirth, pain in surgical conditions, morphine addiction and malignant disease ; all of which conditions are outside the scope of dental therapeutics. Dental uses are not mentioned in the advertising circular, but such usage is indicated in the separate descrip tion sent by the manufacturer. As uses other than those of interest in dentistry have no place in advertising material for the dental profession, the inclusion of these in circulars for dentists and in advertising in dental journals is objectionable and unacceptable. M o re over, too much is suggested or advised in the way o f intravenous injections o f Novaldin, in the advertising circular, and this in the face of the safeness of the drug stressed in the same circular. T h e exploitation of intravenous injection of agents which can be used just as effectively by mouth is not countenanced by the Council. Th erefore, the advertising of ampuls for intravenous injection is objected to by the referee. Objection is also made to the inclusion of “ symptomatic relief of pain in general headache, neuralgia, rheumatism, and similar painful conditions” in the separate statement of descriptions and claims submitted by the manufacturer, for the reasons stated above. T h e referee be lieves that Novaldin is a superfluous and unnecessary product for the therapeutic armanentarium, in view of the fact that it resembles so closely antipyrine and amidopyrine, without obvious advantages over these official products. M oreover, its usefulness in dentistry is not established by clinical or experimental evidence. In view of the foregoing, Novaldin is declared not acceptable for A .D .R . ; i.e., because the claims for its usefulness are not established, the advertising claims are misleading and unacceptable, especially since the potential harmfulness of continued administration is not mentioned, and it has no advantage over antipyrine and amidopyrine, which are official in the United States Pharmacopeia, and are described in A .D .R .
133
in the treatment o f Vincent’s infection and other diseases o f the mouth associated with spirochetes. D osage: The maximum dosage by any route should prob ably not exceed 0.4 gm. or, at most, 0.S gm. It is applied locally either in aqueous or, preferably, in glycerin solutions. It is generally used in strengths o f 2 per cent, but strengths up to 6 per cent may be used. Sulpharsphenam ine-Squibb.— A brand o f sulfarsphenamineN.N.R. Manufactured by E. R. Squibb & Sons, New York City, under U. S. patent 1,024,993 (April 30, 1912, expired) by license of the Chemical Foundation, Inc. Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Sqmbb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb, Sulfarsphenamine-Squibb,
0.1 0.2 0.3 0.4 0.5 0.6 0.9 3.0
gm.. ampuls gm. ampuls gm. ampuls gm. ampuls gm. ampuls gm. ampuls gm. ampuls gm. ampuls
C H L O R A M IN E P R E P A R A T IO N S * C h loram in e-T Squibb.— A brand o f Chloramine-T, U.S.P. Manufactured by E. R. Squibb & Sons, New York, N. Y. No. U. S. patents or trademarks. Chloramine-T Tablets, 4.6 grains: One tablet dissolved in 1 fluid ounce of water will yield a 1 per cent solution for local application.
NOVALD1N—NOT ACCEPTABLE FOR A.D.R. The Council has authorized publication of the following report. S a m u e l M . G o r d o n , Secretary.
Consideration of Novaldin was undertaken because of inquiries concerning it coming to the Council and because the product has been exhibited at dental meetings and is being exploited before the dental profession. T h e manufacturer of the product is the W inthrop Chemical Company, Inc., N ew Y ork City, which was requested to supply information concerning the product. T h e secretary sent to the referee an advertising circular, a small specimen of the product and a copy o f the description of the product received from the manufacturer. This report is limited to the claims in the circular and separate state ment of description. Synonyms for Novaldin are stated to be Novalgin, which is a trademark for use in certain foreign countries, and Dipyrone, which is a descriptive name. T h e name Novaldin w ill be used in this report, this being the trademark used in the United States. T h e chemical composition of Novaldin is claimed to be phenyldimethylpyrazolon methylaminomethane sulphonate sodium. T h e phenyldimethylpyrazolon portion of the molecule corresponds to the composition of antipyrine, and the second portion of the molecule, namely, methylaminomethane, brings the compound into close relationship to aminopyrine. T h e compound is also close in composition to melubrine which, as an antipyretic or analgesic, has not found much popularity in this country. From this, N oval din might be expected to act pharmacologically and therapeutically like aminopyrine. T h e pharmacologic actions described in the advertising circular concern themselves with the follow in g: body temperature, circulation, respiration, and toxic and fatal doses in animals. It is claimed that Novaldin acts as antipyretic in the experimental fever of rabbits, which might be expected from the w ell-known actions o f amidopyrine or anti pyrine. T h e statement about intravenous toxic dosage in rabbits is not explicit. It is not clear whether the dose refers to 1 gram per kilogram of body weight or per animal, or whether the injection was slow or rapid. T h is large dose is stated to be without effect *Accepted Dental Remedies, 1935, page 123.
134
The Journal of the American Dental Association and The Dental Cosmos
on blood pressure and respiration; a statement which is not convincing to the referee. The fatal dose for white rats is claimed to be 4 grams per kilogram, which seems rather large, but if this is true, the toxicity of Novaldin for man might be comparatively small, although doses based on experiments on rats are not, as a rule, directly transferable to man. Fatal doses of drugs in the case of rats are generally larger than in other mam mals. M ore important than the acute fatal dose and toxicity o f such a product as Novaldin would be the effects o f continued administration over long periods, since such drugs are likely to be used repeatedly. N o results of such continued administration are mentioned in the circular. Since amidopyrine and antipyrine are regarded as possible factors in agranulocytosis, a careful determination of such possibilities as regards N oval din is in order. (Since this report was adopted and sent to the firm, such a casé has been reported. Benjamin and Biederman report the occurrence of a case of granulopenia from the ingestion of Novaldin. [Agranulocytic Leukopenia Induced by a D ru g Related to Aminopyrine, J .A .M .A ., 107:493 (A u g. 15) 1936.].) Important in this connection would be the effect of continued administration of Novaldin on the condition o f the blood and viscera; nutrition and appetite, general tolerance, habituation, etc. T h ere is no indica tion that attempts have been made to determine this. T h e clinical claims for Novaldin stress the absence of toxicity in therapeutic doses, the absence of harmful effects and the indications for use in fever and relief of pain. As for possible injurious effects and lack of toxicity, no consideration is given to possible injuries to the blood and to tissues and functions mentioned above. Special sensitivity and idiosyncrasy to Novaldin, as in the case of antipyrine, are not mentioned. A s for anti pyretic actions, these are the least important with drugs of the antipyrine group, since these drugs are no longer used as antipyretics; the antipyretic action being too rapid and erratic, and, therefore, uncontrollable. T his leaves only the analgesic action, which, of course, is well known fo r the antipyrine group, and is considerably emphasized in the therapeutic use of Novaldin. Therapeutic usefulness is claimed in headache, neuralgia, articular rheumatism, muscu lar rheumatism, colds and influenza, renal colic, biliary colic, otorhinitis, tuberculosis, the pain of childbirth, pain in surgical conditions, morphine addiction and malignant disease ; all of which conditions are outside the scope of dental therapeutics. Dental uses are not mentioned in the advertising circular, but such usage is indicated in the separate descrip tion sent by the manufacturer. As uses other than those of interest in dentistry have no place in advertising material for the dental profession, the inclusion of these in circulars for dentists and in advertising in dental journals is objectionable and unacceptable. M o re over, too much is suggested or advised in the way o f intravenous injections o f Novaldin, in the advertising circular, and this in the face of the safeness of the drug stressed in the same circular. T h e exploitation of intravenous injection of agents which can be used just as effectively by mouth is not countenanced by the Council. Th erefore, the advertising of ampuls for intravenous injection is objected to by the referee. Objection is also made to the inclusion of “ symptomatic relief of pain in general headache, neuralgia, rheumatism, and similar painful conditions” in the separate statement of descriptions and claims submitted by the manufacturer, for the reasons stated above. T h e referee be lieves that Novaldin is a superfluous and unnecessary product for the therapeutic armanentarium, in view of the fact that it resembles so closely antipyrine and amidopyrine, without obvious advantages over these official products. M oreover, its usefulness in dentistry is not established by clinical or experimental evidence. In view of the foregoing, Novaldin is declared not acceptable for A .D .R . ; i.e., because the claims for its usefulness are not established, the advertising claims are misleading and unacceptable, especially since the potential harmfulness of continued administration is not mentioned, and it has no advantage over antipyrine and amidopyrine, which are official in the United States Pharmacopeia, and are described in A .D .R .