The Use, Dosage, and Medication Safety of Large Compound Formulas

The multi-target use of large compound formulas requires attention to medication safety. The medication-safety principles I advocate are the following three points:

First, be safe in the rationale of formula composition.

When using the large-compound, multi-target approach to treat disease, the rationale must be comprehensive. One must consider not only treating the disease but also protecting the patient's liver, kidneys, and gastrointestinal tract; the formula should include herbs that protect the liver, kidneys, and stomach.

Common liver-protecting herbs include Yinchen (Herba Artemisiae Scopariae), Wuweizi (Schisandrae Fructus), Chuipencao (Sedi Herba), Mudanpi (Moutan Cortex), Lianqiao (Forsythiae Fructus), Baishao (Paeoniae Alba Radix), Chaihu (Bupleuri Radix), Danggui (Angelicae Sinensis Radix), Huangqi (Astragali Radix), Fuling (Poria), and Zhuling (Polyporus). Common kidney-protecting herbs include Yimucao (Leonuri Herba), Shudi (Rehmanniae Praeparata Radix), Fuling, Huangqi, Shanzhuyu (Corni Fructus), Shayuanzi (Astragali Complenati Semen), Tusizi (Cuscutae Semen), Mohanlian (Ecliptae Herba), and Nüzhenzi (Ligustri Lucidi Fructus). Common gastrointestinal-protecting herbs include Wuzeigu (Sepiae Endoconcha), Baiji (Bletillae Rhizoma), Jiao Maiya (charred Hordei Fructus Germinatus), Jiao Shanzha (charred Crataegi Fructus), Baizhu (Atractylodis Macrocephalae Rhizoma), and Zhiqiao (Aurantii Fructus). Add an appropriate portion according to the patient's specific condition.

For example, those with a history of gastric or duodenal ulcer should add Wuzeigu and Baiji; these two form the famous classical formula "Wu Ji San," which has an excellent preventive and therapeutic effect on gastric and duodenal ulcers. For those with elevated ALT and AST, add Yinchen, Wuweizi, Chuipencao, and Mudanpi to lower enzymes and protect the liver. For those with poor kidney function, use some Yimucao and even combine other kidney-protecting herbs. The Chinese Materia Medica (Zhongyao Da Cidian) and the Zhonghua Bencao both specifically describe Yimucao's kidney-protecting function. I have used Yimucao for some patients with kidney damage caused by Western drugs, and it restored kidney function in some of them.

Of course, these are only rudimentary points. In actual prescribing, the doctor needs sufficient knowledge of pharmacology and formulaology to flexibly combine liver-, kidney-, and stomach-protecting herbs based on the patient's blood indices and clinical symptoms.

When using these herbs, one must also be careful not to let the guest overshadow the host. Treatment is the primary goal; the use of some herbs may clearly counteract the effect of others, and at such times we must not sacrifice efficacy in pursuit of a comprehensive prescription.

Large compound formulas have certain advantages for treating major or severe diseases, but in actual treatment patients often develop all kinds of unexpected conditions. This also requires the doctor, when using a large formula, to adapt to changes and take appropriate supportive measures at any time. Sometimes one may pause medication for several days or weeks, handle the sudden situation, and then resume the large-formula treatment.

Treating chronic disease is a long process. If one does not think things through thoroughly and lacks the ability to handle the patient's sudden situations at any time, I suggest not using the large-compound, multi-target approach; when a doctor cannot master a large formula, the medical risk is high and accidents are easy to cause.

• In selecting herbs, choose non-toxic or low-toxicity herbs and avoid highly toxic ones.

I advocate avoiding highly toxic herbs as much as possible. I personally do not use highly toxic drugs at all (such as arsenic trioxide, raw Maqianzi, raw Chuanwu, raw Banxia, raw Fuzi, etc.; even their processed forms are rarely used), nor do I use drugs with high hepatotoxicity or nephrotoxicity, or drugs with carcinogenic or teratogenic effects—for example, Guanmutong (Aristolochiae Manshurensis Caulis) and Xixin (Asari Radix et Rhizoma).

This is related to my personality: I am very cautious and have always pursued "absolute safety." Although I know this is hardly achievable, I still pay special attention when prescribing.

Since we consult the literature and know these drugs may harm patients, causing cancer or renal failure, how can we use them without a shadow on our conscience? I strongly suspect that some medical practitioners who abuse toxic drugs may not like reading medical literature and have not learned the relevant pharmacotoxicology. The practice of using toxic drugs in large doses is even more reckless with patients' lives; when a doctor treats patients this way, an accident is only a matter of time.

I have separately compiled a 10,000-word article, "A Complete Guide to the Toxicity of Commonly Used Chinese Herbs and Detoxification Methods After Herbal Poisoning," listing the toxicity and poisoning reactions of various commonly used herbs. Readers can click the link to see the full text; I will not repeat it here.

I make one point: giving up highly toxic herbs is a wise choice. When we block off one risky road, we often find a better road in another direction. After I myself gave up the more toxic Chinese herbs and devoted my energy to studying combinations of non-toxic or less-toxic herbs, I accumulated rich experience in this regard.

Now the efficacy I achieve with highly safe Chinese herbs is markedly stronger than what I could achieve with highly toxic ones. This secures both the patient's safety and my own—a win-win.

Some young people like to compete over who dares to use toxic drugs, and even pride themselves on using toxic drugs in large doses on themselves. I do not see what there is to compete about—to show how bold they are? This kind of vanity is not acceptable.

Medicine pursues safe, effective, and standardized medication. In today's social environment of complex doctor–patient relationships, one should restrain oneself even more strictly in this regard. A single medication-safety accident may be enough to end a patient's life and enough to end a doctor's career.

• Control the safe dose well.

In clinical prescribing, the most critical step is controlling the safe dose. Only by keeping the dose at a level that treats the disease without causing obvious harm to the body can we ensure safe and effective medication.

For large compound formulas, I have consistently advocated using pills, powders, pastes, and pellets (wan san gao dan) rather than decoctions. There are two reasons: first, the cost of pills/powders/pastes is low, only a few fractions of a decoction; second, the dosage of pills/powders/pastes is easier to control than that of decoctions.

Moreover, according to the dose–response curve of drug effects, once the dose exceeds the maximum therapeutic dose, further increasing it produces no more obvious therapeutic effect; it merely wastes herbs and adds to the family's treatment cost.

When using large compound formulas to treat disease, controlling the dose is especially important, because the herbs in a large formula act synergistically—enhancing sensitivity and potency—and can likewise enhance toxicity.

I have direct experience of this: when I increased the number of herbs in a compound, a patient who previously tolerated 3 g could no longer tolerate 2 g, or even 1.5 g, after the addition.

I negotiated with the patient, lowering the dose to a comfortable level and continued observing. We found that after increasing the number of herbs, the efficacy at a lower dose not only did not decline but became more pronounced than before. It was precisely through this feedback that I discovered the rule that large compound formulas can enhance sensitivity, potency, and toxicity.

One point to emphasize: some people simplistically believe that using a large compound reduces the toxicity of each herb. This view is one-sided and inconsistent with my observations. In practice, large-compound use actually enhances toxic and side effects—manifested not only in the patient's immediate reactions after dosing but also in cumulative poisoning reactions during long-term use.

This requires close monitoring of the patient's condition while medicating. I require patients receiving this treatment to have their liver and kidney function rechecked regularly and to report their medication experience. Usually, in the first 1–3 months, liver and kidney function should be rechecked every 2–4 weeks; after 3 months, reduce to every 1–2 months; after half a year, reduce to every 3 months.

Moreover, I do not use large compound formulas lightly; I only use this treatment on patients with refractory diseases. For common, easily treated diseases, I always use small formulas—sometimes only one or two herbs steeped in boiling water as a tea. I wrote a monograph on the large-compound, multi-target therapy only to overcome world-class medical problems to the greatest extent, not to encourage learners to abuse this method for every disease.

This semester I am studying Western Pharmacology at school. According to the modern pharmacology dose–response curve (shown below), a drug must reach a certain dose to be effective; pharmacology calls this the minimum effective dose. Besides the minimum effective dose, there is also a maximum therapeutic dose, a minimum toxic dose, and a minimum lethal dose—all data we must master when prescribing.

For each herb in a compound composed according to the large-compound, multi-target approach, the minimum effective dose, maximum therapeutic dose, and minimum toxic dose all decrease markedly.

Because a large formula is not prescribed randomly—as I mentioned in an earlier article, it is composed by following the principle of combining similar formulas and similar herbs. Similar formulas and similar herbs have highly similar actions and possibly related components. Pharmacologically, the active ingredients in these herbs may bind to the same receptors on human cells to exert their effects, so it makes sense that their minimum effective dose and minimum toxic dose are markedly lower.

If you look at my current doses individually, the amount of each single herb is far below its minimum effective dose. If one were to mechanically disassemble and study such a formula, one would doubt it could possibly work. But if you follow the reasoning I described above, it is not hard to understand why such a formula produces clinical efficacy.

Modern pharmacology studies the action of a single drug; a large compound has an extremely complex composition and follows another set of pharmacological rules. Some contemporary scholars call this the network action of drugs; I personally prefer the term synergistic action. Once we understand its internal logic, we can better master such large formulas.

In short, the safety of large-compound medication requires us to control every detail. In practice, the doctor should instruct the patient to start from a small dose (as little as 0.5 g); if there is no discomfort, increase by 0.5 g each time, gradually raising the dose until a mild adverse reaction appears, then moderately lower the dose to a level the patient finds comfortable. At the same time, closely observe changes in liver and kidney function and other adverse reactions during long-term use, to avoid iatrogenic harm.

To enjoy its benefits, one must first know its drawbacks. Yesterday I published two articles: the ten major adverse drug reactions summarized by modern pharmacology, and the toxicity of common Chinese herbs. I hope those studying the large-compound, multi-target therapy will read this article together with the previous two, master the knowledge and skills of safe medication, and better protect patients in clinical practice.

When we attempt to treat refractory diseases with the large-compound, multi-target therapy, we have actually swum to the deepest part of medicine's deep waters. Entering this region requires total focus and extraordinary caution, because there is no ready literature or guideline to consult, and no teacher to show us how; we ourselves are the pioneers in this field.

For the patients who place their full trust in us, we are most likely the last stop of their lives; most have already failed treatment by other doctors and conventional methods before trying this. Whether we are dedicated and professional at this stop directly determines their survival time and quality of life.

Note: This article is part of my book My Medical Philosophy. To shorten titles for easier reading, future articles in the "My Medical Philosophy" series will no longer carry the "My Medical Philosophy" label in their titles; related articles are all categorized under the "My Medical Philosophy" directory, and readers can click the directory tag to read the entire book.