Paregoric

Paregoric, or camphorated tincture of opium, also known as tinctura opii camphorata, is a traditional patent medicine known for its antidiarrheal, antitussive, and analgesic properties.

Old bottle of Paregoric, circa 1940s. The large red X on the label indicates that it was classified as an "exempt narcotic", sold without prescription even though it contains morphine.

According to Goodman and Gilman's 1965 edition, "Paregoric is a 4% opium tincture in which there is also benzoic acid, camphor, and anise oil. ... Paregoric by tradition is used especially for children."[1]

The term "paregoric" has also been used for boiled sweets which contained the substance, in particular the Army & Navy brand.[2]

Properties

In 1944, two clinicians who evaluated the expectorant action of paregoric, concluded:

The survival of paregoric through the centuries, and particularly through recent critical decades, is probably due to keen clinical observation and stubborn adherence to the clinical deduction that paregoric is useful in certain types of cough.[3]

History

In the very early 18th century, Jakob Le Mort (1650–1718),[4] a professor of chemistry at Leiden University, prepared an elixir for asthma and called it "paregoric".[5] The word "paregoric" comes from the Greek word "paregoricon" which was originally applied to oratory – to speak, but, more accurately, talk over, soothe,[6] and finally came to have the same meaning as "anodyne".[3]

Le Mort's elixir, consisting of "honey, licorice, flowers of Benjamin, and opium, camphor, oil of aniseed, salt of tartar and spirit of wine," was listed as "Elixir Asthmaticum" in the London Pharmacopoeia of 1721. Its ingredients were assembled according to the humoral theory of the time. Paregoric was used in various formulations for hundreds of years.

Paregoric was a household remedy in the 18th and 19th centuries when it was widely used to control diarrhea in adults and children, as an expectorant and cough medicine, to calm fretful children, and to rub on the gums to counteract the pain from teething.

A formula for paregoric from Dr. Chase's Recipes (1865):[7]

Best opium 1/2 dr., dissolve it in about 2 tablespoons of boiling water; then add benzoic acid 1/2 dr.; oil of anise 1/2 a fluid dr.; clarified honey 1 oz.; camphor gum 1 scruple; alcohol, 76 percent, 11 fluid ozs.; distilled water 4-1/2 fluid ozs.; macerate, (keep warm,) for two weeks. Dose – For children, 5 to 20 drops, adults, 1 to 2 tea-spoons.

The Medical Companion, Or Family Physician, a book from 1827, gave the following recipe:

Paregoric Elixir – Take of purified opium, flowers of Benzoin, camphor, and essential oil of annis-seed, each, two drachms; brandy, two pints. Digest for eight or ten days, frequently shaking the bottle, and then strain the elixir.[8]

Use during the twentieth century

During the twentieth century its use declined as governments regulated its ingredients (opium is a controlled substance in many countries.)

Beginning in late 2011, there was a period in which paregoric was not being manufactured in the United States. As of August 2012, however, the manufacture of paregoric had resumed.[9]

Regulation

The early twentieth century brought increased regulation of all manner of narcotics, including paregoric, as the addictive properties of opium became more widely understood, and "patent medicines came under fire largely because of their mysterious compositions".[10] In the United States, the Pure Food and Drug Act of 1906 required that certain specified drugs, including alcohol, cocaine, heroin, morphine, and cannabis, be accurately labeled with contents and dosage. Previously many drugs had been sold as patent medicines with secret ingredients or misleading labels. Cocaine, heroin, cannabis, and other such drugs continued to be legally available without prescription as long as they were labeled. It is estimated that sale of patent medicines containing opiates decreased by 33% after labeling was mandated.[11] In 1906 in Britain and in 1908 in Canada "laws requiring disclosure of ingredients and limitation of narcotic content were instituted".[10]

The Harrison Narcotics Act of 1914 restricted the manufacture and distribution of opiates, including laudanum, and coca derivatives in the United States; this was followed by France's Loi des stupefiants in 1916, and Britain's Dangerous Drugs Act in 1920.[10]

In the United States, the Harrison Narcotics Act of 1914[12] regulated "opium or coca leaves, or any compound, manufacture, salt, derivative or preparation thereof", but not some medical products containing relatively low concentrations of these substances.[13] Paregoric was classified as an "Exempt Narcotic", as were other medical products containing small amounts of opium or their derivatives.[14]

Regulation and use since 1970

Until 1970, paregoric could be purchased in the United States at a pharmacy without a medical prescription, in accordance with federal law. Federal law dictated that no more than two ounces of paregoric be dispensed by any pharmacy to the same purchaser within a 48-hour period. Purchasers were also required to sign a register or logbook, and pharmacies were technically required to request identification from any purchaser not personally known to the pharmacist. Some states further limited the sale of paregoric, or banned over-the-counter sales entirely. For example, Michigan law allowed over-the-counter (non-prescription) sale of paregoric until April 1964, but still allowed OTC sales of certain exempt cough medication preparations that contain 60 mg of codeine per fluid ounce."[5] Even where legally permissible by law, OTC sale of paregoric was subject to the discretion of individual pharmacists.

In 1970, paregoric was classified as a Schedule III drug under the Controlled Substances Act (DEA #9809);[15] however, drugs that contained a mixture of kaolin, pectin, and paregoric (e.g., Donnagel-PG, Parepectolin, and their generic equivalents) were classified as Schedule V drugs. They were available over-the-counter without a prescription in many states until the early 1990s, at which time the FDA banned the sale of anti-diarrheal drugs containing kaolin and pectin; also, Donnagel-PG contained tincture of belladonna, which became prescription-only on January 1. 1993. Paregoric is currently listed in the United States Pharmacopeia. Manufacture of the drug was discontinued for several months beginning in late 2011; however, production and distribution resumed in 2012, so the drug is still available in the United States by prescription. Thus, it is unclear as to whether the lapse in manufacture actually resulted in a shortage of the drug at any time, since prescription drugs are often still available for many months after manufacture has been discontinued. In France, paregoric was available without prescription until 1986; nowadays, it is used to wean infants born to opiate-addicted women.

Paregoric, U.S.P. formula

The principal active ingredient in paregoric is powdered opium. In the United States the formula for Paregoric, U.S.P. is tincture of opium 40 ml, anise oil 4 ml, benzoic acid 4 g, camphor 4 g, glycerin 40 ml, alcohol 450 ml, purified water 450 ml, diluted alcohol[16] to 1000 ml, and contains the equivalent of 0.4 mg/ml of anhydrous morphine; one ounce of paregoric contains 129.6 mg (2 grains) of powdered opium, or the equivalent of 13 mg of anhydrous morphine.[17][18] The average adult dose is 4 ml by mouth which corresponds to 16 mg of opium, or 1.6 mg of anhydrous morphine."[5]

It is unclear when the current formula for Paregoric, U.S.P. was developed in the United States, and more research is needed. For example, one formula for "Camphorated Tincture of Opium (Paregoric Elixir)" attributed to the United States Pharmacoepia of 1863 is: "Macerate 1 drachm each powdered opium and benzoic acid, 1 fluid drachm of anise, 2 ounces clarified honey, and 2 scruples camphor, in 2 pints diluted alcohol for 7 days, and filter through paper."[19] A slightly different formula is given in the 1926 pharmacoepia.[20]

The current formula for Paregoric, U.S.P. should not be assumed to be universal. For example, in the United Kingdom the formula for Paregoric, B.P. is tincture of opium 5 ml, benzoic acid 500 mg, camphor 300 mg, anise oil 0.3 ml, alcohol (60%) to 100 ml, and contains about 1/30th grain of anhydrous morphine in 60 minims,[17] which is 25% stronger than Paregoric, U.S.P.

Dosage

Paregoric is sometimes confused with Laudanum, because their chemical names are similar: Camphorated Tincture of Opium (Paregoric) vs. Tincture of Opium (Laudanum). However, Laudanum contains 10 milligrams of morphine per milliliter, 25 times more than Paregoric. Confusion between the two drugs has led to overdose and death in patients.[21] Thus the term "Paregoric" should be used instead of "Camphorated Opium Tincture", since the latter may be confused with Laudanum.[22]

Bottle of Paregoric

The differences between Tincture of Opium (Laudanum) and Camphorated Tincture of Opium (Paregoric) are important and should be kept in mind when administering either of these drugs. Care and caution should always be taken in administering doses of Tincture of Opium, such as the use of a dosage syringe or other suitable measurement device, and by pharmacists in preparing Paregoric from Laudanum, and to note that the dosages noted here refer to Apothecaries weight and fluid measure. In particular, "the difference between a minim and a drop should be borne in mind when figuring doses. A minim is always a sixtieth part of a fluid drachm regardless of the character of the substance, while a drop varies from a forty-fifth to a two-hundred-and-fiftieth part, according to the surface tension of the fluid."[23] Tincture of Opium (Laudanum) and Camphorated Tincture of Opium (Paregoric) each have 50.9 drops per gram; 50.0 drops per cc; 185.0 drops per fluid drachm; and 3.10 drops per minim."[24] The importance of these distinctions is evident in view of the dangers of erroneously relying upon more general descriptions of Apothecaries' fluid measures, which typically list 60 minims per fluid dram, and 8 fluid drams per fluid ounce (480 minims).[25]

Indications

The main effects of paregoric are to increase the muscular tone of the intestine, to inhibit normal peristalsis, and as an expectorant; a peer-reviewed clinical study in 1944 reported "that all of [its] ingredients have been found to contribute toward the expectorant action of paregoric, and, further, that an advantage is contained in the combination over the sum of the effects of the individual constituents," that Paregoric "is expectorant by virtue of a reflex from the stomach," and "preparations of paregoric which have aged for two or three years are superior as an expectorant to preparations aged for less time.".[26] Its main medical use is to control fulminant diarrhea, and as an antitussive (cough suppressant). Problems with its use include opiate dependency and analgesia which can mask symptoms of diseases that need treatment.

However, Paregoric was characterized as "a needlessly complex pharmacopeial mixture... of a former day" by a 1966 study.[5] In the 21st century its two main uses have been largely supplanted by minimally psychoactive cough-suppressant drugs (such as dextromethorphan) and non-psychoactive antidiarrheal drugs (such as loperamide).

References
  1. Goodman and Gilman, Pharmacological basis of therapeutics, Macmillan 1965, p. 261.
  2. Hughes, Emma (3 February 2017). "Nine stories behind the great British sweets of your childhood". Country Life. Future plc. Retrieved 7 June 2021.
  3. Boyd, EM; Maclachlan, ML (1944). "The Expectorant Action of Paregoric". Can Med Assoc J. 50 (4): 338–44. PMC 1581631. PMID 20323061.
  4. Bibliotheca Chemica. Royal College of Science and Technology (Glasgow, Scotland), n.d. Vol. 2. 2009. pp. 24–25. ISBN 9781113188182. Retrieved July 11, 2010.
  5. A. Martin Lerner. "The abuse of paregoric in Detroit, Michigan (1956–1965)". UNDOC Bulletin on Narcotics, 1966, Issue 3. pp. 13–19. Archived from the original on October 2, 2012. Retrieved July 11, 2010.
  6. "paregoric" – via The Free Dictionary.
  7. Chase, Alvin Wood (1865). Dr. Chase's Recipes (25th ed.). Ann Arbor, Michigan. p. 133.
  8. Ewell, James (1827). The Medical Companion, Or Family Physician; Treating of the Diseases of the United States, with Their Symptoms, Causes, Cure and Means of Prevention: Common Cases in Surgery, as Fractures, Dislocations, &c. The Management and Diseases of Women and Children. A Dispensatory, for Preparing Family Medicines, and a Glossary Explaining Technical Terms. To which are Added, A Brief Anatomy and Physiology of the Human Body, Shewing, on Rational Principles, the Cause and Cure of Diseases: An Essay on Hygiene, Or the Art of Preserving Health, Without the Aid of Medicine: An American Materia Medica, Pointing Out the Virtues and Doses of Our Medicinal Plants. Also, the Nurse's Guide, The Seventh Edition, Revised, Enlarged, and Very Considerably Improved (7 ed.). proprietors. Paregoric.
  9. "Current Drug Shortages - Paregoric". Archived from the original on 2012-03-20.
  10. In the Arms of Morpheus: The Tragic History of Laudanum, Morphine, and Patent Medicines," by Barbara Hodgson. Buffalo, New York: Firefly Books, 2001, page 126.
  11. Musto, David F. (1999). The American Disease: Origins of Narcotic Control. Oxford University Press (3 ed.). ISBN 0-19-512509-6.
  12. The Harrison Narcotics Act (Public Law 63-223, December 17, 1914) was named for its sponsor, Sen. Francis Burton Harrison (1873–1957)
  13. According to one source, the 1914 Act "profoundly changed the nature of the narcotics problem in the United States. This law was intended as a revenue and control measure and was not designed to penalize the user of the drug, to whom no direct reference was made. The enforcement of the law was entrusted to the Bureau of Internal Revenue of the U.S. Treasury Department. It was evidently assumed or hoped that by requiring all persons who handled drugs to register with the government and maintain records the flow of drugs would be subject to public control. The act applied equally to cocaine and to opiates and made no distinctions between them. It required all persons who imported, manufactured, produced, compounded, sold, dealt in, dispensed, or gave away any derivative of opium or of coca leaves (cocaine) to register with the Collector of Internal Revenue, to pay special taxes, and to keep records of their transactions. Preparations containing minute quantities of cocaine or of opiates were exempted from the regulations." (See drugtext.org, visited February 6, 2008 Archived October 22, 2010, at the Wayback Machine).
  14. Section 6 of the 1914 Act did not apply "to the sale, distribution, giving away, dispensing or possession of preparations and remedies which do not contain more than two grains of opium, or more than one-fourth of a grain of morphine, or more than one-eighth of grain of heroin, or more than one grain of codeine, or any salt or derivative of them, in one fluid ounce, or, if a solid or semisolid preparation, in one avoirdupois ounce; or to liniments, ointments, or other preparations which are prepared for external use only, except liniments, ointments, or other preparations which contain cocaine or any of its salts."
  15. "DEA #9809 is for an "opium combination product 25 mg/du" (that is, 25 mg per dosage unit) under the Controlled Substances Act of 1970, which includes Paregoric; see www.deadiversion.usdoj.gov, visited July 12, 2010" (PDF). Archived (PDF) from the original on April 17, 2016.
  16. Diluted alcohol is a mixture of equal portions of purified water and 190 proof alcohol (95% alcohol by volume).
  17. The Extra Pharmacoepia Martindale, Vol. 1, 24th Edition. London: The Pharmaceutical Press, 1958, p. 924.
  18. American Druggist and Pharmaceutical Record. Vol. XXXII, January to June 1898. New York: American Druggist Publishing Co. 1898. p. 252 (. Retrieved July 11, 2010. Describes its preparation as follows: "Dissolve the benzoic acid, camphor and oil of anise in the alcohol, add the glycerin and then the water, very slowly and in divided portions, agitating after each addition. Lastly add the tinct. opii deod. and filter through paper, returning the first portions if necessary until clear. When the liquid ceases to drop from the funnel pass enough diluted alcohol through the filter to make the finished product measure one thousand cubic centimeters."
  19. Encyclopedia of Practical Receipts and Processes, by William B. Dick. 5th edition. New York: Dick & Fitzgerald, Publishers, 1890, p. 416. The Dictionary lists a number of formulas for other opium-based tinctures and compounds, such as: Ammoniated Tincture of Opium, Squibb's Compound Tincture of Opium, Dover's Tincture, McMunn's Elixir of Opium, Murphy's Carminative, Oil of Opium, Battley's Sedative Solution of Opium, and Eisenmann's Opiated Wine of Colchicum.
  20. The 1926 formula is 4 g each of powdered opium, benzoic acid, and camphor; and 5  of oil of anise, prepared as a tincture by "macerating the ingredients in a mixture of 40 cc of glycerin and 950 cc of diluted alcohol, completing the preparation with diluted alcohol." Source: The Pharmacoepia of the United States of America, 10th Decennial revision (U.S.P. X), official from January 1, 1926. Philadelphia: J. B. Lippincott Company, 1925, p. 401.
  21. Wharton, Francis (1855). A Treatise on the Law of Homicide: To Which is Appended A Series of Leading Cases on Homicide, Now Out of Print, or Existing Only as Manuscript. Philadelphia: Kay & Brother, 17 & 19 South Fifth Street, East Side. p. 144. Upon an indictment for the manslaughter of a child, it appeared that the child being ill, the mother sent to a chemist for a pennyworth of paregoric; the chemist's apprentice delivered a phial, with a paregoric label on it, but with laudanum in it; and the mother, supposing it to be a paregoric, gave the child six or seven drops, which killed it. The laudanum bottle and the paregoric bottle stood side by side.
  22. "FDA Patient Safety News: Show #27, May 2004". Archived from the original on 2011-01-04. Retrieved 2010-11-30.
  23. The Art of Compounding, by Wilbur S. Scoville and Justin L. Powers. 6th edition. Philadelphia: P. Blakiston's Son & Co., Inc., 1937, page 16. The normal drop counter "shall have an exit with an external diameter of 3 millimeters, and shall discharge drops of distilled water at 15°C, of such a size that 20 drops shall weigh 1 gram."
  24. The Art of Compounding, by Wilbur S. Scoville and Justin L. Powers. 6th edition. Philadelphia: P. Blakiston's Son & Co., Inc., 1937, page 18.
  25. Arithmetic of Pharmacy, by A. B. Stevens. 6th edition, revised and enlarged by Charles H. Stocking and Justin L. Powers. New York: D. Van Nostrand Company, Inc., 1926, page 2.
  26. Boyd, Elden M.; MacLachan, Marian L. (1944). "The Expectorant Action of Paregoric". Can. Med. Assoc. J. 50 (4): 344. PMC 1581631. PMID 20323061. The authors note: "Because of its marked expectorant action paregoric is superior to morphine, which has probably no expectorant action, and to tincture of opium which has very little expectorant action.
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