The vast majority of monographs pertain to single herbs, that is, herb sold as drug products generally referred to as monopreparations, as distinguished from more complex formulas containing multiple herbs in combination. As noted in table 15, there are 296 monographs dealing with single herbs: 186 approved and 110 unapproved.

Fixed combinations refer to formulas containing multiple herbal ingredients. In phytotherapy the use of fixed combinations is quite typical (Schilcher, 1997b). Until 1990 the majority of herbs used in German phytotherapy were combinations. The Commission reviewed a total of only 72 combinations of herbs. Of these, 66 were approved and 6 were not approved. Unlike some of the classic herbal formulas described in systems of traditional medicine in Asia (e.g., Traditional Chinese Medicine and Ayurvedic medicine of India) where formulas routinely contain up to a dozen or more botanicals, the herbal formulas reviewed by Commission E generally contain two to three herbs, sometimes four, or occasionally five. According to German drug regulations in the AMG for the registration of combinations, a manufacturer must prove that "every medicinally active component contributes to the positive evaluation of the medicine." (Steinhoff, 1997b.)

A review of the approved combinations indicates that the largest single category of use is for digestive complaints (35 combinations). These contain most possible combinations of the following herbs (or their essential oils): Anise seed, Angelica root, Bitter Orange peel, Caraway seed, German Chamomile flower, Fennel seed, Gentian root, Peppermint leaf, and Wormwood. Some formulas also include Artichoke leaf or Dandelion root to help increase bile production.

The next largest category of fixed combinations consists of herb formulas approved for colds, flus and catarrhal conditions of the upper respiratory tract with or without viscous phlegm, dry or spastic cough, and related conditions (21 combinations). In general, these formulas include Camphor, Eucalyptus essential oil, or Purified Turpentine oil, combined with other herbs, such as Ivy leaf and Primrose root.

The third largest category of indications for which fixed combinations are approved is unrest and insomnia due to nervousness. The herbs in these combinations are Hops, Lemon Balm, Passionflower, and Valerian root.

In at least one instance, an Unapproved herb is included in an Approved Fixed Combination based on the effective action of the herb with the other Approved herbs. Oleander leaf powdered extract (unapproved by itself), with its positively inotropic and negatively chronotropic actions, is combined with Pheasant's Eye fluidextract, Lily-of-the-valley powdered extract, and Squill powdered extract for "Mild, limited heart action and circulatory instability." The Oleander leaf monograph (Unapproved) reads, "Since the effectiveness of oleander leaf preparations is not yet adequately documented, and in considering that there is no correlation between the content of individual glycosides and the efficacy of the herb, a therapeutic administration of oleander leaf is not justifiable." This was the case in 1990, when the Oleander monograph was written. By 1993, when the Fixed Combination containing Oleander powdered leaf extract was approved, however, the pharmacokinetics of oleandrin were better known. "For oleandrin, an absorption rate of 86 percent is given." This rate is similar to that of digoxin (Schilcher, 1997b). This is in keeping with the general trend of the Commission after 1993 to approve plant extracts rather than whole plants.

The medicinally active components each must make a positive contribution to the evaluation of the total preparation; they must contribute to its effectiveness and safety. Proof of effectiveness may be established through clinical or pharmacological documentation for each component, or through documentation for the whole preparation. The components must be at a dosage appropriate for effectiveness.

A positive evaluation is given when the medicinally active component contributes to therapeutic effectiveness. Medicinally active components may also be present, whose contribution to the effectiveness of the whole combination can be explained on the basis of its effects. The combination must specifically indicate therapy or prophylaxis. An indication is a condition of illness, a functional disturbance, a syndrome, or a pathological unit of a known type. It is conceivable that the single components of a fixed combination can, at the same time, bring relief for various symptoms of such a condition or illness. Yet, it would not be correct to consider each symptom as an indication for a fixed combination, since this symptom may also occur with other diseases, and the other components may be irrelevant for this symptom. A combination with components acting in the same way is possible.

1. Considerable pharmacokinetic and/or pharmacodynamic interactions exist that do not improve the benefit/risk ratio, or even worsen it.

2. The half-life and/or the duration of the actions of the medicinally active components differ widely. However, this is not necessarily correct, if it can be demonstrated that the combination is clinically of benefit, despite this time-related difference.

3. The combination contains a component which is intended to effect an unpleasant reaction, in order to prevent abuse.

The safety of all fixed combinations is to be tested with suitable methods. However, this is not necessary for fixed combinations with components known to be medicinally active, if the safety is determined from the formulation, dosage, form of administration, and range of indications based on scientific data. (Federal Health Agency, 1989)

Component characteristics refer to herbal materials added to various combinations of herbs and other substances for which the efficacy of the formula may depend on the safety and efficacy of a particular ingredient. For example, in the case of Cajeput oil, the Commission decided that there was adequate evidence to approve the combination of this essential oil with other botanical ingredients in 43 formulas corresponding to 43 claimed uses found in the German market. Similarly, the Commission approved Nasturtium herb and leaf as an ingredient in 12 botanical formulas and their 12 corresponding uses found in the market.

The Commission found 10 herbs for which it did not approve combinations with the herb as a component, including Aspen bark, Basil oil, California Poppy, Purple Coneflower root ( Echinacea purpurea ), and Mistletoe berry and stem. Interestingly, in the same year that the Commission published the monograph on Echinacea purpurea root as an Unapproved Component Characteristic (1992), a clinical study was published in which an extract of E. purpurea root was found to be effective in shortening the severity and duration of colds and flus (Bräunig et al., 1992).

Many of the Unapproved Component Characteristics are combined with homeopathic drugs, vitamins and other nutritional components (e.g., alpha-tocopherol acetate), phytochemicals (e.g., cineole, globulin from pumpkin seed flower, beta-sitosterol, esculin), and Unapproved Herbs (e.g., Night-blooming Cereus flowers, Sassafras root bark). Many herbs that are combined with the primary component herb are listed by common name only in the Approved and Unapproved Component Characteristics sections. Because of the number of botanicals listed and their minor importance, we have not included the Latin binomial for each herb listed.

Therapeutic baths containing herbs are a popular method of treatment in Europe, where this practice is known as balneology . By putting crude herbs or herbal extracts and essential oils into hot bath water, the body is able to gradually absorb some of the active phytochemicals from the herbs, as the pores open in the hot water. Although some herbs are approved for use in baths (e.g.,Chamomile, Valerian), the Commission did not review herbs to be used in this manner. In 1988 Commission B8 was established to assess the safety and efficacy of all bath additives, thereby removing such review from the scope of Commission E (Busse, 1997b).