ATOPHAN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

The Council has authorized publication of the following report explaining why Atophan has been omitted from New and Non­official Remedies. Schering and Glatz, Inc., the firm which markets this brand of cinchophen in the United States, has refused to place either the U. S. Pharmacopeial name, “Phenyl­cinchoninic Acid (Acidum Phenyl­cinchon­inicum)” or the N. N. R. name, “Cinchophen,” on the label and in the advertising matter so as to make the identity of the product clear to physicians. Furthermore, the product is sold under therapeutic claims which the Council holds to be exaggerated and unwarranted.

W. A. Puckner, Secretary.

COMMERCIAL HISTORY OF CINCHOPHEN

The substance, 2-phenyl-quinolin-4-carboxylic acid, was described by Doebner and Gieseke in 1887 (Ann. d. Chem. [Liebig’s] 242:291). The therapeutic properties of this compound were described by Nicolaier and Dohrn in 1908 (Deutsch. Arch. f. klin. Med. 93:331). Subsequently the product was placed on the market and extensively advertised by the Chemische Fabrik auf Actien (vorm. E. Schering), Berlin, Germany. This firm also took out a patent in the United States on its production and in 1911 secured a U. S. trademark on the name “Atophan.” In 1912 Atophan was passed on by the Council and admitted to New and Non­official Remedies.

When the government of the United States took charge of German-owned patents during the World War, the Federal Trade Commission, and later the Chemical Foundation, Inc., issued licenses to American firms whereby these were authorized to manufacture the compound. In the meantime, Schering and Glatz, Inc., who had been the U. S. representatives for the Chemische Fabrik auf Actien, also undertook to supply the drug, but did not obtain a license from the boards in charge of German patents. Also, this firm secured, in 1919, a trademark of the word “Atophan,” apparently after the German-owned trademark had been canceled.

The drug “Atophan” was admitted to the U. S. Pharmacopeia as “Phenyl­cinchoninic Acid (Acidum Phenyl­cinchon­inicum).” As this name proved too cumbersome, the Council on Pharmacy and Chemistry coined the abbreviated name “Cinchophen” for it, and this name is now used by all the firms which are marketing the product in the United States, with the exception of Schering and Glatz, Inc., who use the term “Atophan,” first owned by the Chemische Fabrik auf Actien.

ATOPHAN, A BRAND OF CINCHOPHEN

Because of the confusion which is bound to arise from giving various names to one drug, the Council selects a common name and provides standards of identity, purity and strength for any drug which, by reason of the absence or lapse of patent rights or for other reason, is open to manufacture by more than one firm. The Council, then, will accept such article only if it is marketed under the title adopted for New and Non­official Remedies. The rules provide, however, that when the Council adopts a common name for an article that has been admitted under another name, such article will be retained in New and Non­official Remedies under the older name if the Council name is given prominence on the label and in the circulars and advertisements, in order to avoid confusion. Accordingly, when the period of acceptance for Atophan in New and Non­official Remedies was about to expire, Schering and Glatz were notified that Atophan could be retained in that publication only on condition that the name, “Cinchophen,” or else the pharmacopeial name, “Phenyl­cinchoninic Acid (Acidum Phenyl­cinchon­inicum)” be placed on the label and used in the circulars and advertising.

UNWARRANTED THERAPEUTIC CLAIMS FOR ATOPHAN

At the time that the Council asked Schering and Glatz to adopt cinchophen or phenyl­cinchoninic acid as a synonym for Atophan, the firm was also requested to omit from future advertising a number of therapeutic claims to which the Council was obliged to take exception. Schering and Glatz refused the first request and made no definite promise with regard to the second. The Council, therefore, directed the omission of Atophan from New and Non­official Remedies, 1921.

The advertising to which the Council took exception does not appear to be distributed at present. A pamphlet has been sent out, however, which is equally objectionable. It contains unwarranted therapeutic claims and suggests that Atophan be used in conditions in which it is not indicated. For instance:

“No longer the vague, hypothetical, ‘test-tube demonstrated’ principle of uric acid elimination by solution, but a definite, scientifically and clinically established, physiologic stimulation of the uric acid excretion. Performed innocuously and controllable to a nicety by dosage and by urine and blood tests.”

The “innocuousness” of Atophan has not been proved; on the other hand there is evidence that it is not innocuous, as the recent investigations of Hanzlik and Scott and their collaborators (Cinchophen, Neocinchophen and Novaspirin in Rheumatic Fever, J. A. M. A. 76:1728 [June 18] 1921) show that it may injure the kidney.

The circular also contains the following:

“No longer, hit and miss relief of pain at the expense of the heart, the intestines, the kidneys and the nervous system, but the promptest and most reliable analgesic, anti-inflammatory and decongestive action so far known, with notable freedom from heart depressant, renal irritant, constipating and cumulative toxic by-effects. No contraindications, except chronic nephritis and the presence of kidney concretions.”

This is misleading. The drug depresses the circulation, injures the kidney and produces symptoms of salicylism or “toxicity.” It is not the promptest and most reliable analgesic; morphin is superior and salicylate is just as efficient. The phrase “decongestive action” is vague. Treatment of pulmonary congestion from phosgene, and congestion of the conjunctiva in mustard oil chemosis of cats, with large doses of Atophan was ineffective; in fact, it proved distinctly harmful. This was shown by such workers as Laqueur and Magnus, and Heubner and Gildemeister (Ztschr. f. d. ges. exper. Med. 13:200, 1921). It is incorrect to ascribe “decongestive” or “anticongestive” action in the true sense to Atophan (cinchophen). The principal assets of the salicylate-cinchophen class of drugs in the treatment of rheumatism and gout are their analgesic and antipyretic qualities.

The claim is made:

“In Rheumatic and Gouty Disorders, whether of the well-known muscular and arthritic type, or their Eye, Ear, Nose and Throat manifestations.”

The suggestion that Atophan is indicated in “their Eye, Ear, Nose and Throat manifestations” is a vague generalization without definite meaning, but nevertheless calculated to impress physicians and promote the sale of Atophan for common and minor ailments. Rhinitis and sore throat are, of course, self-limited conditions which require chiefly good habits, personal and general hygiene as prophylactic measures, and simple hot baths with rest, instead of medication, for symptomatic relief. When it comes to ear and eye conditions, Atophan certainly would do no good in otitis media, panophthalmitis, choroiditis, retinitis, etc.

The administration of Atophan is proposed “in Migrains, Hemicrania, Eyestrain, etc., often vaguely grouped as ‘Headaches.’ ” Eyestrain and headaches are vague symptoms often arising from numerous causes that require no medication, but rather good habits, hygiene and similar corrective measures. There is always the possibility of habituation from the use of drugs for such common and vague symptoms, resulting eventually in more harm than good to the patient.

The use of Atophan is proposed “In Influenza (Grippe) for the ready alleviation of the respiratory congestion, pain and stiffness of limbs and back.” Probably the entire claim is without warrant, since influenza is a self-limited disease. Atophan might relieve pain in the joints, reduce the fever, etc., but at the same time it would tend to impair the functional efficiency of the heart, which may be impaired already by the disease. Cardiac failure is one of the causes of death in influenza. The recommendation for “alleviating respiratory congestion” is certainly without warrant, since in actual trial in pulmonary congestion by Magnus et al., Atophan was found to be deleterious and not beneficial. Phosgenized cats are probably as good a test object for the alleged decongestive action of Atophan as anything could be, since, according to Underhill and Ringer (J. A. M. A. 75:1531, 1920) the pathological physiology of the circulation and respiration in phosgene poisoning and influenza are nearly identical.

Further, Atophan is recommended “In Pyorrhea Alveolaris as a systemic support to local and specific measures.” Atophan is not indicated here. Pyorrhea requires local medication, if anything at all. It could exert no local beneficial effects in this condition; indeed, the employment of Atophan might lead to irritation. Good dental treatment is more essential than medication.

Finally, Schering and Glatz advise Atophan “In Eczema, Pruritus and similar irritant and itching Skin Diseases with lowered blood alkalinity.” The assumption that blood alkalinity is lowered in irritant and itching disease is unsupported by evidence in medical literature and the recommendation is incorrect and misleading. Neither does Atophan alter the reaction of the blood. Amelioration in these capricious conditions occurs without medication so that any relief that might be obtained could not be attributed to Atophan. The entire paragraph is misleading and will undoubtedly tend to extend the use of Atophan in conditions for which it is not suited.—(From Reports of Council on Pharmacy and Chemistry, 1921, p. 8.)