OXYL-IODIDE NOT ADMITTED TO N. N. R.

Report of the Council on Pharmacy and Chemistry

“Oxyl-Iodide” (Eli Lilly and Co.) is said to be the hydroiodid of cinchophen and the claim is made that it exerts the effects of cinchophen and of iodid. Because of inquiries which have been received the Council decided to determine the eligibility of “Oxyl-Iodide” for New and Non­official Remedies. Dr. P. J. Hanzlik—formerly Associate Professor of Pharmacology at Western Reserve University School of Medicine, now Professor of Pharmacology at Leland Stanford Junior University Medical School—who has made a study of the action of salicylates and cinchophen, was asked to report on the therapeutic value and the rationality of “Oxyl-Iodide.” This he consented to do and his report appears below.

After considering Doctor Hanzlik’s report, the Council declared “Oxyl-Iodide” inadmissible to New and Non­official Remedies because it is an irrational combination, marketed under claims that are unproved and consequently unwarranted.

W. A. Puckner, Secretary.

“Oxyl-Iodide,” marketed by Eli Lilly & Co., is claimed to be the hydroiodid of phenyl­cinchoninic acid, containing 33 per cent. of iodin and 67 per cent. of phenyl­cinchoninic acid (cinchophen). Its solubility resembles that of cinchophen, being low in water and acid mediums, and higher in the presence of alkalis. Whether “oxyl-iodide” is decomposed into its constituents in the presence of alkalis does not appear to have been determined. However, if this were the case, the intestine, after administration of “oxyl-iodide,” would contain cinchophen and sodium iodid in the same forms as if these agents were administered individually so that nothing would be gained by administering “oxyl-iodide.” Being, like cinchophen, practically insoluble in acid mediums, “oxyl-iodide” would have no advantage over the latter so far as gastric irritation is concerned.

DOSAGE

The dosage advised is from one to three tablets containing 3 grains (0.2 gm.) each of “oxyl-iodide.” The total dosage would depend on the condition to be treated. In rheumatic fever, which requires a full therapeutic or so-called, “toxic” dose of cinchophen, about 12 to 13 gm. would be administered intensively. Since each tablet of “oxyl-iodide” contains 0.13 gm. of cinchophen, the total number of tablets of “oxyl-iodide” required would be 100, or two and one-half bottles of forty tablets each. At the same time the patient would receive 6.6 gm. of iodin (as iodid). This might be distinctly objectionable because of the production of the disagreeable symptoms of iodism in some persons, and indicates that the fixed proportion of the iodin constituent would be objectionable.

Even a smaller dosage, such as 5 gm. of cinchophen, which gives partial relief in rheumatism and similar conditions, would still require a patient to take a full bottle, or forty tablets, of “oxyl-iodide,” and at the same time about 2.7 gm. of iodin would have to be ingested.

Furthermore, rheumatic fever, the arthritides, gout and related conditions in which cinchophen is indicated do not require iodid. Therefore, “oxyl-iodide” would not be the remedy of choice in these conditions, and its use would be irrational and illogical.

ACTIONS

No data on the pharmacologic actions of “oxyl-iodide” are presented in the manufacturer’s literature. Presumably, the compound would exhibit the actions of its individual components, i. e., cinchophen and iodin (as iodid), though probably less efficiently, owing to its low solubility. This is also indicated by the following statements of the manufacturer: “The analgesic action of ‘oxyl-iodide’ is gradual. A word of caution is necessary to those who may expect immediate relief from pain.” Therefore, why use “oxyl-iodide” in place of more dependable analgesics, such as salicylate or cinchophen. The following statements appear far-fetched: “There is a stimulation of the endocrines which is perhaps more marked in the thyroid gland, although it is probably shared by the pituitary and other glands which function in a chain-like control.... There is stimulation of cells with increased flow of secretion, visibly demonstrated by the nasal mucous membrane after ‘oxyl-iodide’ has been taken for some time. The general action on mucous membranes favors elimination of toxins and waste products.”

It is probable that “oxyl-iodide” acts as a uric acid eliminant, though there is no reason to suppose that it is more effective than cinchophen alone. No data are given for this in the manufacturer’s literature.

USES

Successful use of “oxyl-iodide” is claimed in brachial and sciatic neuritis, lumbago, muscular rheumatism, arthritis deformans, chronic arthritis (“... in some instances were apparently cured”), subacute bronchitis, circumflex neuritis, traumatic orchitis, eczema and rheumatism. However, a careful reading of the protocols of seven cases, representing these conditions, gives an unfavorable impression as to the real contribution to the recovery by, or value received from, “oxyl-iodide.” Summarized, the opinions as quoted by the manufacturers in support of their claims for “oxyl-iodide” are briefly as follows:

Case 1. “Of course, the case is not complete yet, but I am looking for continued betterment.”

Case 2. “For two weeks past her improvement has been marvelous.”

Case 3. “The joints are still enlarged and we do not hope to clear them entirely....”

Case 4. “Undoubtedly, removal of the kidney had much to do with improvement.”

Case 5. “I think I have gotten very good results.”

Case 6. “Some apparent benefit.”

Case 7. “She is practically free from pain, and the muscle and joint stiffness is now slight.”

These inconclusive opinions certainly do not agree with the favorable impression which other portions of the manufacturer’s literature create. If the factor of natural recovery in the conditions represented by these seven cases is given due weight, little, if anything, is left to the credit of “oxyl-iodide.” Such clinical evidence as is supplied by the manufacturer indicates that the therapeutic efficiency of “oxyl-iodide” is doubtful, and not an improvement over either cinchophen or iodid.

IODISM

Iodism cannot be avoided by the use of “oxyl-iodide,” for the manufacturer’s literature states that “the dosage of ‘oxyl-iodide’ may be pushed to iodism as manifested by skin symptoms.... To avoid iodism there should be an occasional interruption of treatment.” “Oxyl-iodide,” therefore, has no advantage over ordinary sodium iodid to avoid iodism. Usually, the conditions which require cinchophen do not require the simultaneous administration of iodids, and vice versa. If administration of iodid and cinchophen together should be indicated or desirable, these can be given separately with the added advantage that the iodid can be easily reduced or withdrawn in case iodism supervenes, and the cinchophen could be continued if necessary. Since conditions do not arise frequently enough to warrant the use of iodid and cinchophen together, the existence of such a product as “oxyl-iodide” is unwarranted.

Finally, the manufacturer himself recognizes that phenyl­cinchoninic acid (cinchophen) can take the place of “oxyl-iodide.” Under “dosage,” the circular states: “A few patients may be idiosyncratic to the iodides and find they cannot take ‘oxyl-iodide.’ For the latter chloroxyl, the hydrochloride of phenyl­cinchoninic acid, is recommended.” The action of the hydrochlorid of phenyl­cinchoninic acid does not differ, of course, from that of cinchophen. The difficulties of assigning a clear-cut, definite, therapeutic rôle to “oxyl-iodide” in order to justify its existence, alongside well-known and tried remedies are self-evident.

CONCLUSION

“Oxyl-iodide” is pharmacologically and thera­peutically an illogical, irrational and unjustified substitute for cinchophen and iodids. The conditions which require the administration of cinchophen do not as a rule require the administration of iodid and vice versa. If it is desirable to secure the effects of iodid and cinchophen together, these can be more conveniently and advantageously administered as separate agents, permitting in that way a better control of their actions. This cannot be accomplished with “oxyl-iodide,” in which the proportion of iodid and cinchophen are fixed. Symptoms of iodism cannot be avoided by the administration of “oxyl-iodide.” The objective evidences for its actions and uses are totally lacking; and the clinical opinions concerning its therapeutic benefits in different disease conditions are inconclusive and hedging, and, if anything, contradictory to the favorable impressions which the language of the advertising matter is likely to create.—(From The Journal A. M. A., July 2, 1921.)