Mifepristone

“ Finally, in January 2023, FDA approved a modified REMS for mifepristone lifting the in-person dispensing requirement. See REMS Single Shared System for Mifepristone 200 mg (Jan. 2023) , https://perma.cc/MJT5-35LF (the “2023 Mail-Order Decision”) . [2]
C.
In November 2022, plaintiffs (physicians and physician organizations) filed this suit against FDA, HHS, and a several agency heads in the official capacities. Plaintiffs first challenged FDA’s 2000 Approval of the drug. But they also requested multiple grounds of alternative relief for FDA’s subsequent actions. ”

“ The FDA has previously invoked enforcement discretion to permit the distribution of mifepristone in a way that the regulations then in force prohibited, and here, the Government has not dispelled legitimate doubts that it would even obey an unfavorable order in these cases, much less that it would choose to take enforcement actions to which it has strong objections. ”

“ Plaintiffs’ Motion for Preliminary Injunction (ECF No. 3) is GRANTED in part. Pursuant to Federal Rule of Civil Procedure 65 (a) , Defendants and their officers, agents, servants, employees, attorneys, and any person in active concert or participation, are PRELIMINARILY ENJOINED from: “altering the status quo and rights as it relates to the availability of Mifepristone under the current operative January 2023 Risk Evaluation and Mitigation Strategy under 21 U.S.C. § 355-1 in Plaintiff States.” No bond shall be required. ”

“ Plaintiffs are doctors and national medical associations that provide healthcare for pregnant and post-abortive women and girls. Plaintiffs sued Defendants to challenge multiple administrative actions culminating in the 2000 Approval of the chemical abortion regimen for mifepristone. ”

“ The Supreme Court has explicitly instructed this court to review a new agency action finalized after litigation commenced and while the appeal was pending because this decision was a “final agency action” for purposes of 5 U.S.C. § 704. Biden v. Texas, 142 S. Ct. 2528, 2544-45 (2022) (quotation omitted) . ↑ As both parties recognize, this order would have the practical effect of an injunction because it would remove mifepristone from the market. ”

“ The Court finds Plaintiffs have satisfied the “alternative” Cottrell test. At this point, the Court will issue a status quo preliminary injunction but not a mandatory preliminary injunction.
D. Relief The Court turns to Plaintiffs’ remedy. Defendants contend that Plaintiffs’ requested relief exceeds any permissible scope where Plaintiffs seek an order enjoining “any action to remove mifepristone from the market or otherwise cause the drug to become less available.” ”

“ It is clear that RU-486 not only is unsafe in women, but it is also not completely effective. And when it is not effective, the results are devastating.”) . ↑ Sheryl Gay Stolberg, FDA Adds Hurdles in Approval of Abortion Pill, The New York Times (June 8, 2000) , https://www.nytimes.com/2000/06/08/us/fda-adds-hurdles-in-approval-of-abortion-pill.html. ↑ Id. ↑ Stolberg, supra note 59. ↑ See also Lars Noah, A Miscarriage in the Drug Approval Process?: Mifepristone Embroils the FDA in Abortion Politics, 36 Wake Forest L. Rev. ”

“ A physician prescribes opium as an anodyne, and the patient finds from its use the relief which was anticipated. Very frequently he finds not merely that his pain has been relieved, but that with this relief has been associated a feeling of positive, perhaps of extreme enjoyment. A recurrence of the same pain infallibly suggests a recurrence to the same remedy. The advice of the medical man is not invoked, because the patient knows that morphine or laudanum was the simple remedy that proved so efficacious before, and this he can procure as well without as with the direction of his physician. ”

“ All drugs previously approved under Subpart H, including Mifeprex, were deemed to have a REMS in place. Pub. L. No. 110-85, tit. IX, § 909 (b) . Under the Federal Food, Drug and Cosmetic Act (“FDCA”) , a new drug cannot be marketed and prescribed until it undergoes a rigorous approval process to determine that it is safe and effective. 21 U.S.C. § 355.
In 2011, FDA issued a new REMS for Mifeprex incorporating the same restrictions under which the drug was approved eleven years earlier. Id., ¶ 90; ECF No. 51-2. In 2013, FDA reviewed the existing REMS and reaffirmed the restrictions in place. ”

“ A morphine manufacturer has no particular interest in ascertaining the amount of water in the opium he purchases. All he requires to know is the percentage of morphine which the drug contains. It is otherwise with the pharmaceutist, whose preparations have to be made with dried opium. ”

“ PREVENTION If the patient is weak, the circulation depressed, the blood pressure low, and the heart rapid, the drug advisable to produce rest and sleep is almost always morphin or some other form of opium. Morphin, with few exceptions, is a cardiac tonic and a cardiac stimulant, unless the dose is much too large. As long as the bowels are daily moved and the food is not given at the time of the full action of the morphin, when digestion might be delayed or interfered with, in most patients the action of this drug during serious illness is entirely for good. ”

“ Your opium-eater does not reduce himself to a state of coma. He usually keeps well within the limits of the tolerance that has been established. The conclusion that emerges is, I think, that the drug was administered by some other person; and the most likely person seems to be Mr. Weiss."
"Isn't morphine a very unusual poison?"
"Very; and most inconvenient except in a single, fatal dose, by reason of the rapidity with which tolerance of the drug is established. But we must not forget that slow morphine poisoning might be eminently suitable in certain cases. ”

“ Although pilocarpine quickens the pulse of man, it slows, according to Langley, [542] the heart of the warm-blooded animals, and that of the frog. With regard to the frog, Dr. S. Ringer’s researches are confirmatory. With large doses the heart stops in diastole. If to the heart thus slowed, or even when recently stopped, a minute quantity of atropine be applied, it begins to beat again. There is also a most complete antagonism between atropine and pilocarpine in other respects, atropine stopping the excessive perspiration, and relieving the headache and pain about the pubes, &c. ”

“ Morphine is the greatest anodyne we possess, and no drug yet discovered equals it in pain-relieving power. The most frequent mode of administration is the hypodermic method, on account of the extreme rapidity with which it is absorbed. In pain due to violent sciatica relief and even permanent cure has been obtained by the injection of morphine directly into the muscle of the affected part, and in the treatment of renal and hepatic colic morphine given subcutaneously will relieve the acute pain consequent on the passage of biliary and urinary calculi. ”

“ So, too, with belladonna, and atropine, its active principle, they are a deadly poison for man, but almost without effect on rabbits: the dose of atropine that would suffice to kill ten men would hardly be enough to kill one rabbit. The difference is not so great with respect to morphine, yet morphine specially affects man; hence in this article we will consider only this one opium alkaloid. ”

“ In the third stage the patient can no longer be aroused (coma) , the respiration becomes shallow and irregular, the pulse becomes rapid and weak, the pupils finally dilate, and the patient dies from failure of the respiration. [Pg 37]
Even after small doses of opium many patients suffer from headache and nausea. Children are much more sensitive to its action than adults. Morphin resembles opium in action, but is more powerful, less nauseating, and less constipating. Codein is less powerful as a hypnotic and less depressing than morphin. ”

“ Medication.—The most important of all the remedies is opium; in preventive treatment it may be called a specific. It is far preferable to the hypodermic injection of morphine, serving to relax and quiet the uterine muscle and to lessen hemorrhage; for the latter purpose it is often combined with acetate of lead—from 1⁄4 to 1 grain of opium mixed with 1⁄2 to 1 grain of acetate of lead, to be given at a dose and repeated when necessary. Ipecacuanha combined with opium acts well in relaxing the tension. ”

“ If the patient does not sleep, he must be made to sleep. The whole body and the nervous system must have periods of rest. If the heart is very weak, small closes of morphin may be used. If the heart is not weak, bromids or chloral may be given. If the blood pressure is high, such hypnotics will lower it, or if the heart is strong and the condition does not contraindicate it, aconite may be used in small doses, for a day or two, unless the fever is high and it seems advisable to use one of the coal-tar antipyretics, which reduce the blood tension and the heart activity. ”

“ Even opium, in large doses, sometimes produces by its powerful stimulus the same symptoms which are produced by the stimulus of marsh miasmata. These symptoms are a slow pulse, coma, a vomiting, cold sweats, a sallow colour of the face, and a suppression of the discharges by the urinary passages and bowels.
Error is often perpetuated by words. A belief in the putrefaction of the blood has done great mischief in medicine. The evil is kept up, under the influence of new theories, by the epithet putrid, [46] which is still applied to fever in all our medical books. ”

“ Our treatment is intended to effect permanent cures. We do not use those narcotics and compounds of antipyrine and other similar agents which are very depressing in their effects, and, like morphine and other preparations of opium, give only temporary relief, and interfere with the action of the heart, but we use treatment that builds up the system, removes the cause of the difficulty and restores the nervous system and all the organs of the body to a normal and healthful condition. ”

“ They act, in some way, more powerfully upon the spirits while exerting the same anæsthetic influence, and the injurious effects of each dose are more marked and less easily counteracted. Laudanum, containing proof spirit as well as morphine, and through the proof spirit diffusing the narcotic influence more rapidly and affecting the brain more quickly and decidedly, is perhaps the worst vehicle through which the essential drug can be taken. Again, morphine, in its liquid forms can be injected under the skin; as solid opium it can be smoked or eaten, as morphia it can be swallowed or injected. ”

“ Finally, ephemeral fever, ushered in by chills or rigors and accompanied by headache, vertigo, thirst, malaise, restlessness, and even mild delirium, and terminating with profuse perspiration, occasionally occurs immediately after the injection of large doses of morphine.
The course of the opium habit, when once established, is, notwithstanding its occasional transient interruptions, gradual and progressive. Certain individuals endure enormous doses of opium or morphine for years without serious symptoms. ”

“ So great is the danger of such injurious results, few careful practitioners have cared to adopt the heroic "antipyretic" medication recommended by experimenters, preferring to allow their patients to burn with fever, mitigated only by such simple means as are commonly employed by nurses, than to require them to combat the poisonous influences of a drug in addition to the morbid element of the disease. ”

“ If there is much fever, this result is best accomplished by means of alternate doses of Aconite and Apis, a few drops of the third potency, shaken together with twelve tablespoonfuls of water, each drug by itself, the dose to be repeated every hour; and if the temperature is rather depressed, by giving Apis without the Aconite, a tablespoonful every hour or two hours. In favorable cases the fever becomes more remittent within one to three days; a moderate and pleasant perspiration breaks out all over the skin; the sleep becomes calm and natural, and the typhoid symptoms abate. ”

“ Give 10 grains of permanganate of potassium in a pint of water acidulated with sulphuric acid, and repeat the dose every half hour. Belladonna by mouth, or atropine hypodermically. Patient must be kept roused by dashing cold water over him, flagellating with a wet towel, walking about, etc. In conditions of collapse, however, this treatment must not be continued, but everything should be done to preserve the strength. Treatment must be continued as long as life remains.
Method of Extraction from the Stomach.—Opium itself cannot be directly detected, but we test for morphine and meconic acid. ”

“ Pyramidon is a proprietary preparation derived from, and having the antipyretic and anodyne properties of, antipyrin. While some observers have asserted that it is more likely to cause collapse than are either antipyrin or acetphenetidin there is no positive evidence of this assertion. That the use of pyramidon has been until recently practically restricted to physicians may account for the fact that its toxic effects are not as well known as are those of antipyrin, acetphenetidin, acetanilid, etc., which for some years have been in­dis­crim­in­ate­ly used by the public. ”

“ Morphine is intrinsically far worse than opium itself, for opium has certain properties which partly counteract the effect of the morphine [Pg 216] that it contains. But morphine is not only the active principle, but the actively evil principle, of the drug.
The user of morphine always retains his faculties. He is usually capable of intelligent conversation. Unlike the alcoholic’s brain, his is not inflamed. It is impossible for the physician intelligently to discuss his symptoms with an alcoholic; with a victim of drugs, on the other hand, he can thresh out every detail of the case. ”