Attempted answers to questions related to Feprazone
https://mp.weixin.qq.com/s/JqouOhN5D1BTM9qWsTvPlw
The following content, unless otherwise specially noted, is cited from Meyler’s Side Effects of Drugs. The International Encyclopedia of Adverse Drug Reactions and Interactions[1]
Overview of Feprazone
Feprazone is a type of nonsteroidal anti-inflammatory drug (NSAIDs), a derivative of butazone
The chemical structure is quite different from the well-known aspirin, but I have no concept of pharmacy and do not know how these structural differences affect it
Overview of NSAIDs Adverse Reactions
Here is a quoted passage (translated; the English original is shown below), the general meaning is that NSAID adverse reactions are complex and mechanisms are unclear, sometimes research is not clear but clinical observation shows serious adverse reactions sufficient to stop use.
Many NSAIDs have been shown to have an unacceptable adverse reaction profile. Many NSAIDs have been withdrawn from the market or had their clinical trials terminated due to unexpected toxicity. Choosing an NSAID can be difficult because reliable information about their relative efficacy and adverse effects is often limited.
Although NSAIDs differ in physicochemical properties, pharmacokinetics, and pharmacodynamics, it is unclear how these differences affect the risk-benefit balance for individual patients. Of course, they influence adverse reaction and general effect patterns for specific NSAID subclasses or particular compounds, but this still does not reliably predict what an individual patient will experience.
The acidity and lipophilicity of these compounds are important. NSAID lipid solubility determines penetration into the central nervous system and thus influences the incidence of neurologic adverse effects, which may also relate to skin adverse reactions. Weak acidity affects tissue distribution. This explains why NSAIDs act at some sites (e.g., synovial tissue in inflamed joints) and contribute to certain adverse reactions at other sites (e.g., stomach and renal medulla).
Pharmacokinetics play a key role in some adverse reactions in certain patients. NSAIDs are almost completely absorbed from the gastrointestinal tract. The rate and site of GI absorption may be important; formulations aimed at avoiding gastric toxicity may harm the intestinal wall, with Osmosin seeming to be such a case. Some research on NSAID chronopharmacology also exists. NSAID absorption in the morning may be better but is associated with more adverse reactions compared to evening dosing.
NSAIDs extensively bind plasma proteins. Theoretically, high protein binding makes patients prone to drug interactions; among patients taking hypoglycemics or oral anticoagulants, some NSAIDs (e.g., phenylbutazone) are more commonly implicated. The unbound fraction responsible for NSAID pharmacologic effects varies with plasma albumin concentration, which can be affected by active rheumatoid arthritis, genetics, sex, age, pregnancy, other drugs, and disease, especially involving kidney and liver. Few NSAIDs show correlation between dose or plasma concentration and anti-inflammatory effect and no direct evidence links increased unbound drug concentration with greater toxicity. However, there is convincing evidence that the dose relates to some adverse reactions (e.g., gastrointestinal and renal). A record linkage study has shown an association between NSAID dose and upper gastrointestinal bleeding.
NSAIDs are roughly divided into short and long half-life. Although clinical differences between these two classes are little known, half-life provides a rough guide for dosing; long half-life compounds are administered once daily. These NSAIDs are also more likely to cause adverse reactions, at least in some patients. Because the half-life of these NSAIDs varies widely among patients, drug accumulation may occur in some individuals. When using long half-life NSAIDs, a loading dose may be given to quickly reach high drug concentrations but may be associated with increased adverse reactions, especially gastrointestinal intolerance.
NSAIDs are primarily cleared by the liver; clearance is expected to decrease with age. Their metabolites are usually inactive and excreted in urine, with minimal unchanged drug. In contrast, several inactive NSAIDs act as prodrugs because they have active metabolites; some compounds, such as suxibuzone, undergo enterohepatic circulation. There is no conclusive evidence that these prodrugs are less toxic than other compounds. Some NSAIDs, including ketoprofen, fenoprofen, indomethacin, ketorolac, and naproxen, are metabolized to acyl glucuronides; metabolites are retained and hydrolyzed to regenerate the parent compound. This may be a mechanism of toxicity in patients with renal impairment.
Response to Questions
From the above overview, you should get a sense that feprazone is an NSAID quite different from aspirin. There are many NSAID products; many drugs produce numerous or severe adverse reactions due to unclear mechanisms. If feprazone behaves similarly, it is not surprising that it is not recommended, even if it is very effective.
In fact, such cases have occurred, but there are also reports indicating it is not problematic (due to limited energy, I have not read the original literature).
In an 8-week trial in 2693 patients with rheumatoid arthritis and osteoarthritis, 30% reported adverse effects and 11% failed to complete the study. [2]
However, two large short-term multicenter studies in general practices in 11000 patients in Italy reported a very low percentage (1.2-9.8%) of adverse reactions [3]
Can Feprazone be used for tenosynovitis?
As a member of NSAIDs, feprazone certainly can treat tenosynovitis, just like ibuprofen or celecoxib.
Can Feprazone be used when other NSAIDs are ineffective?
This does not mean admitting feprazone is effective but emphasizes its relatively large adverse reactions. Clinical doctors can use it according to specific situations. In fact, such cases I recently encountered in pediatrics: when treating mycoplasma pneumonia, the first choice is azithromycin; tetracyclines, quinolones, and aminoglycosides are used only if that fails. Because these latter have reported adverse reactions (tetracycline teeth, aminoglycoside ototoxicity and nephrotoxicity, etc.), they are used cautiously, but when azithromycin resistance is severe and azithromycin is nearly ineffective, these drugs will be used.
Similarly, if clinical experience indicates poor response to conventional NSAIDs like ibuprofen, trying feprazone is a reasonable empirical choice, of course the physician should be aware of its adverse effect severity and probability.
Why can Feprazone relieve wind and spasm?
Reviewing the medical case mentioned in the public account:
This article mentions muscle strain
- From a Western medicine perspective, sterile inflammation caused by muscle strain is reasonably treated with NSAIDs, no further explanation is needed.
- From a traditional Chinese medicine perspective, after strain local tension and contraction cause blockage of qi flow; blockage causes pain. Techniques like massage and acupuncture relax local tissue to improve symptoms effectively. NSAIDs relieve pain and inflammation so patients no longer focus their attention on the affected area; without conscious tension, muscles naturally relax. Think of your own painful area — you often worry about it and are cautious, fearing pain will reoccur (which indeed often happens). Over time, the area becomes even more tense and your attention more focused, creating a worsening spiral. But if symptoms are treated to relieve pain and reduce your worry, breaking this bad cycle, muscles can recover by themselves.
As for the article mentioning replacement of centipede with feprazone, I cannot figure it out at the moment.
References
Desai C. Meyler’s side effects of drugs: The international encyclopedia of adverse drug reactions and interactions. Indian J Pharmacol. 2016 Mar-Apr;48(2):224. PMCID: PMC4825447. ↩︎
Montanari C. Large cooperative multicentric trial with feprazone in the inflammatory process of dental tissues. Curr Ther Res Clin Exp 1975; 17 (2): 166-74. ↩︎
Chierichetti S. Esempio di monitoraggio attivo su un farmaco: il feprazone. [Example of active monitoring of a drug: feprazone.] Emerg Med 1976;500:. ↩︎