Usage, Dosage, and Medication Safety of Large Compound Formulas

The multi-target application of large compound formulas requires careful attention to medication safety. My personal approach to ensuring medication safety encompasses the following three key aspects:

First, Safety Must Be Considered in the Formulation Strategy

When adopting a multi-target approach with large compound formulas for treating diseases, the formulation strategy must be comprehensive. It is essential not only to treat the primary disease but also to protect the patient’s liver and kidney functions as well as their gastrointestinal tract. Therefore, the formulation should include herbs that provide hepatic, renal, and gastrointestinal protection.

Commonly used herbs for liver protection include Artemisiae Scopariae Herba (茵陈), Schisandrae Chinensis Fructus (五味子), Hedyotis Diffusae Herba (垂盆草), Moutan Cortex (牡丹皮), Forsythiae Fructus (连翘), Paeoniae Alba Radix (白芍), Bupleuri Radix (柴胡), Angelicae Sinensis Radix (当归), Astragali Radix (黄芪), Poria (茯苓), and Polyporus (猪苓). Common herbs for kidney protection include Leonuri Herba (益母草), Rehmanniae Radix Praeparata (熟地), Poria (茯苓), Astragali Radix (黄芪), Corni Fructus (山茱萸), Psoraleae Fructus (沙苑子), Cuscutae Semen (菟丝子), Ecliptae Herba (墨旱莲), and Ligustri Lucidi Fructus (女贞子). Herbs commonly used for gastrointestinal protection include Sepiae Endoconcha (乌贼骨), Bletillae Rhizoma (白及), Hordei Fructus Germinatus (焦麦芽), Crataegi Fructus Germinatus (焦山楂), Atractylodis Macrocephalae Rhizoma (白术), and Aurantii Fructus (枳壳). These can be added to the formulation at the physician’s discretion based on the patient’s specific condition.

For example, patients with a history of gastric or duodenal ulcers should be prescribed Sepiae Endoconcha (乌贼骨) and Bletillae Rhizoma (白及). This combination forms a classic traditional formula known as Wuji San (乌及散), which has excellent preventive and therapeutic effects on gastric and duodenal ulcers. For patients with elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, Artemisiae Scopariae Herba (茵陈), Schisandrae Chinensis Fructus (五味子), Hedyotis Diffusae Herba (垂盆草), and Moutan Cortex (牡丹皮) should be added to lower enzyme levels and protect the liver. For patients with compromised renal function, Leonuri Herba (益母草) should be utilized, potentially in combination with other renoprotective herbs. Both Dictionary of Chinese Materia Medica (中药大辞典) and Chinese Materia Medica (中华本草) specifically describe the renoprotective functions of Leonuri Herba (益母草). I have administered Leonuri Herba (益母草) to patients who suffered renal impairment due to Western medication treatments, and it has successfully restored renal function in some of these patients.

Of course, these are merely basic principles of herbal medication. In actual clinical practice, physicians must possess extensive knowledge of pharmacology and formula studies, flexibly combining hepatoprotective, renoprotective, and gastroprotective herbs based on the patient’s blood test indicators and clinical symptoms.

When using these herbs, care must be taken to avoid overshadowing the primary treatment goal. Treating the disease is the foremost objective. If the use of certain herbs significantly counteracts the effects of others, we must not excessively sacrifice therapeutic efficacy in the pursuit of a comprehensive prescription.

While large compound formulas offer distinct advantages in treating severe or complex diseases, patients often encounter various unexpected conditions during actual treatment. This requires physicians using large compound formulas to adapt flexibly and promptly implement corresponding auxiliary measures. Sometimes, it is necessary to suspend medication for several days or weeks to manage acute emergencies before resuming treatment with the large compound formula.

The treatment of chronic diseases is a long-term process. If a physician cannot consider all contingencies or lacks the ability to handle sudden emergencies, I strongly advise against employing the multi-target approach of large compound formulas. When a physician’s capabilities cannot adequately manage large compound formulas, the medical risks are high, and accidents are prone to occur.

Second, Non-Toxic or Low-Toxicity Herbs Should Be Selected, and Highly Toxic Herbs Must Be Avoided

I advocate avoiding highly toxic herbs as much as possible. Personally, I completely abstain from using highly toxic herbs (such as Arsenicum (砒霜), Strychni Semen Cruda (生马钱子), Aconiti Radix Cruda (生川乌), Pinelliae Rhizoma Cruda (生半夏), Aconiti Lateralis Radix Cruda (生附子), etc., and I rarely use even the processed products of these highly toxic herbs). Furthermore, I avoid herbs with severe hepatotoxicity and nephrotoxicity, as well as those with carcinogenic or teratogenic effects, such as Aristolochiae Manshuriensis Caulis (关木通) and Asari Radix et Rhizoma (细辛).

This approach is related to my personality; I am highly cautious and have always pursued “absolute safety.” Although I understand that this is nearly impossible to achieve perfectly, I remain exceptionally vigilant when prescribing medications.

Since we have consulted literature indicating that these herbs may harm patients, potentially causing carcinogenesis or nephrotoxicity, how can we use them without a shadow of doubt in our minds? I strongly suspect that some medical practitioners who abuse toxic herbs may not read medical literature and have failed to learn relevant pharmacotoxicology knowledge. The practice of using toxic herbs in large doses disregards the life and death of patients. When physicians treat diseases in this manner, it is only a matter of time before an adverse event occurs.

I once compiled a comprehensive ten-thousand-word article titled A Complete Guide to Toxicity Knowledge of Commonly Used Chinese Herbs and Detoxification Methods After Poisoning (常用中药毒性知识及服用中药中毒后解毒方法大全), detailing the toxicity and poisoning reactions of various commonly used Chinese herbs. Readers can access the full text via the link to that article, so I will not elaborate further here.

I emphasize one point: abandoning the use of highly toxic herbs is a wise choice. When we block a risky path for ourselves, we often find a better path in another direction. By giving up the use of highly toxic Chinese herbs, I have dedicated my energy to researching combinations of non-toxic or low-toxicity herbs, accumulating extensive experience in this area.

Currently, the therapeutic efficacy I achieve using high-safety Chinese herbs is significantly superior to that achieved with highly toxic herbs. This ensures both patient safety and physician safety, achieving a win-win outcome.

Some young practitioners enjoy boasting about their courage to use toxic herbs, even taking pride in administering high doses of toxic herbs. I do not understand what there is to boast about; does this demonstrate courage? Such vanity is unacceptable.

Medicine pursues safe, effective, and standardized medication use. In today’s complex social environment of doctor-patient relationships, physicians must strictly discipline themselves in this regard. A single medication safety accident can be enough to end a patient’s life and ruin a physician’s career.

Third, Safe Dosages Must Be Strictly Controlled

In clinical medication, the most critical aspect is controlling the safe dosage. Ensuring medication safety and efficacy requires keeping the dosage at a level that treats the disease without causing significant harm to the body.

For large compound formulas, I have always advocated using pills, powders, pastes, and boluses (丸散膏丹) rather than decoctions (汤剂). There are two reasons for this: first, the medication cost for pills, powders, pastes, and boluses is low, amounting to only a fraction of the cost of decoctions; second, pills, powders, pastes, and boluses allow for better dosage control than decoctions.

Furthermore, according to the dose-response curve of pharmacological quantity-response, when the dosage exceeds the maximum therapeutic dose, increasing the dosage further provides no significantly enhanced therapeutic effect. It merely wastes medicinal materials and unnecessarily increases the treatment costs for the patient’s family.

When using large compound formulas to treat diseases, strictly controlling the dosage is particularly important. Because the herbs in a large compound formula work synergistically, they can enhance sensitivity and efficacy, but they can equally enhance toxicity.

I have personal experience with this. When I increased the number of herbs in a compound formula, patients who previously tolerated 3 grams could no longer tolerate 2 grams, or even 1.5 grams, after the addition of more herbs.

After consulting with the patients, we reduced the dosage to a level where they felt comfortable and continued to observe the outcomes. We discovered that after increasing the herb variety, the therapeutic efficacy at lower dosages did not decrease; instead, it became more pronounced than before. It was precisely because of this patient feedback that I discovered the pattern that large compound formulas can enhance sensitivity, efficacy, and toxicity.

One point that must be emphasized here is that some people simplistically believe that using large compound formulas can reduce the toxicity of individual herbs. This understanding is one-sided and inconsistent with my observations. In reality, large compound formulas can enhance adverse toxic effects. These toxic side effects are reflected not only in the immediate reactions after medication but also in the cumulative toxic reactions from long-term medication use.

This requires close monitoring of the patient’s physical condition during medication. I require patients undergoing this treatment to undergo regular liver and kidney function tests and to provide feedback on their medication experiences. Typically, during the initial 1 to 3 months, liver and kidney functions must be rechecked every 2 to 4 weeks; after 3 months, the frequency is reduced to once every 1 to 2 months; and after 6 months, it is reduced to once every 3 months.

Moreover, I do not easily use large compound formulas to treat diseases. I only apply this treatment method to patients with refractory diseases. For common, easily treatable diseases, I invariably use small formulas, sometimes using only one or two herbs steeped in boiling water as a tea substitute. My purpose in writing a monograph to introduce the multi-target therapy of large compound formulas is solely to conquer the world’s most challenging medical problems to the greatest extent possible, not to encourage learners to abuse this method for treating all diseases.

This semester, I studied Western Pharmacology at school. According to the modern pharmacological dose-response curve (the figure below is a dose-response curve graph), a drug must reach a certain dosage to be effective; pharmacology refers to this as the minimum effective dose. In addition to the minimum effective dose, there are the maximum therapeutic dose, minimum toxic dose, and minimum lethal dose. These are all data points we must master when prescribing medications.

For each herb in a compound formula constructed according to the multi-target treatment approach of large compound formulas, the minimum effective dose, maximum therapeutic dose, and minimum toxic dose will be significantly reduced.

Because large compound formulas are not prescribed arbitrarily—as I mentioned in previous articles—they must follow the principle of combining similar formulas and similar herbs. Similar formulas and herbs have highly similar effects, and their chemical compositions may also be close. Pharmacologically speaking, the active ingredients in these herbs may bind to the same receptors on human cells to exert their effects. Therefore, it is logical that their minimum dosage and minimum toxic dose are significantly reduced.

If my current medication dosages are examined individually, the dosage of each herb may be far below the minimum effective dose. If one mechanically deconstructs and studies such a formula in this manner, one might doubt whether it could possibly be effective. However, based on the principles I described above, it is easy to understand the rationale behind how such formulas produce clinical efficacy.

Modern pharmacology focuses on the action patterns of individual drugs. Large compound formulas are extremely complex in composition and follow a different set of pharmacological rules. Some contemporary scholars refer to this as the “network action” of drugs, while I personally prefer to describe it as “synergistic action.” When we understand its internal logic, we can better master such large formulas.

In summary, the safety of large compound formulas requires us to control every detail. In actual clinical practice, physicians must instruct patients to start with a low dosage (as low as 0.5 grams). If there is no adverse reaction, the dosage should be increased by 0.5 grams each time, gradually escalating until mild adverse reactions occur. The dosage should then be moderately reduced to a level where the patient feels comfortable. Simultaneously, changes in liver and kidney functions and other adverse reactions from long-term medication must be closely monitored to avoid iatrogenic harm.

To utilize its benefits, one must first understand its drawbacks. Yesterday, I published two articles summarizing the top ten adverse drug reactions in modern pharmacology and the toxicity knowledge of common Chinese herbs. I hope those studying the multi-target therapy of large compound formulas will read this article alongside the previous two. Mastering the knowledge and skills of safe medication will better safeguard our patients in clinical practice.

When we attempt to use the multi-target therapy of large compound formulas to treat refractory diseases, we are essentially swimming into the deepest waters of medicine. Entering this zone requires full concentration and extreme caution. Here, there are no ready-made literature or guidelines for reference, and no teachers to instruct us on how to operate; we are the pioneers in this field.

For the patients who entrust their entire trust to us, we are likely the last stop in their lives. Most have already undergone treatments by other doctors using conventional methods without success before making this attempt. Whether we are dedicated and professional at this final stop directly determines their survival period and quality of life.

Note: This article is part of My Medical Philosophy (我的医学理念). To shorten the titles for easier reading, future articles in the My Medical Philosophy (我的医学理念) series will no longer include the My Medical Philosophy (我的医学理念) tag in the title. Related articles will be categorized under the My Medical Philosophy (我的医学理念) directory; readers can click the directory tag to access all content of this book.