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INTERACTION PROBABILITY GUIDE

1. Certain

Interaction occurrence is definite. Available research and clinical experience both indicate that purposeful coadministration is likely to provide increased therapeutic effect in beneficial interactions. With adverse interaction, concomitant use is definitely to be avoided, even when under the active care of an appropriately trained and experienced health care professional. In most cases, however, it is inadvisable to make sudden changes in usage if the individual's medical condition has been stable.

2. Probable

There is relatively high probability of this interaction occurring, all other factors being equal . Conservative practice implies considering these interactions operationally as definite, unless there are compelling reasons to the contrary. Available evidence or clinical experience indicates that purposeful coadministration may enhance therapeutic intervention. With adverse interaction, concomitant use is generally to be avoided, except when under the active care of an appropriately trained and experienced health care professional. In most cases, however, it is inadvisable to make sudden changes in usage if the individual's medical condition has been stable.

3. Possible

There is variable probability of this interaction occurring, depending on specific circumstances . Operationally, the probability of the interaction may be relatively low for most individuals; however, interindividual and intraindividual variation in probable occurrence of the interaction is likely, depending on multifactorial circumstances, including atypical dosages, certain preexisting medical conditions altering pharmacokinetic or pharmacodynamic parameters, particular risk associated with life stage susceptibilities, and pharmacogenomic and biochemical variability.

4. Plausible

Interaction of plausible, but not proven, likelihood . Although the mechanism and rationale of this interaction appear reasonable based on current knowledge, the available evidence is inadequate to support a conclusive judgment as to the likelihood of its occurrence or the variables influencing the character of such an interaction. However, potential clinical significance of the interaction may warrant careful consideration within integrative therapeutic strategies. This may be based on currently accepted clinical practices among appropriately qualified professionals in botanical and nutritional therapeutics, despite lack of currently available published evidential support.

5. Improbable

This interaction is unlikely to occur in most individuals, all other factors being equal . When taken at commonly used dosages for appropriate medical conditions as prescribed by health care professional(s) trained and experienced in botanical and/or nutritional therapeutics, the probability of clinically significant interaction occurring appears to be minimal.

6. Unknown

Data are contradictory, inconclusive, or insufficient to assign probability status.

INTERACTION TYPE AND CLINICAL SIGNIFICANCE GUIDE

Type and Clinical Significance of Interaction

• If the individual's prior medical condition has been stable, any changes to the therapeutic regimen involving addition or withdrawal of nutrients, botanicals, or pharmaceuticals should not be made abruptly. Transitions in protocols are de facto potential foci for interaction instability that may, if ignored, significantly affect intended therapeutic outcomes.
• Individuals vary in response to any pharmacological agent because of individual biochemical or pharmacogenomic variability, as well as health status and medical conditions.
• Professional management implies supervision by collaborating health care professionals with appropriate training in nutritional and/or botanical therapeutics within an integrative medical framework.

Potential or Theoretical Adverse Interaction of Uncertain Severity

Interaction is theoretically possible based on known pharmacological characteristics of each substance. Inadequate information is currently available to determine clinical significance of potential risk. Pending conclusive research, close supervision and regular monitoring by a health care professional are warranted for any concomitant use.

Minimal to Mild Adverse Interaction—Vigilance Necessary

Interaction represents a low to moderate risk, but potential severity warrants supervision of patient during concomitant use. Concomitant use is therapeutically feasible within the context of multidisciplinary collaboration, along with supervision and monitoring by health care professional(s) trained in conventional pharmacology and experienced with clinical herbal medicine and/or therapeutic nutrition.

Potentially Harmful or Serious Adverse Interaction—Avoid

Interaction represents a significant to severe risk of adverse effect and should be avoided. Concomitant use should be deliberately avoided outside the context of close supervision and regular monitoring, including laboratory monitoring wherever feasible, by health care professional(s) trained in conventional pharmacology and experienced with clinical herbal medicine and/or therapeutic nutrition.

Impaired Drug Absorption and Bioavailability, Negligible Effect

Interaction is adverse but of minimal clinical significance. Nonetheless, modification of dosage, timing, or mode of administration may reduce potential for adverse effects of interaction.

Adverse Drug Effect on Herbal Therapeutics, Strategic Concern

Interaction in which drug may interfere with therapeutic effect of herbal prescription because of the drug's pharmacological properties. Alterations in drug dosage, timing, or other factors may prevent, ameliorate, or compensate for adverse effects of or interference with herbal therapeutics and optimize therapeutic effect, with appropriate clinical management within an integrative therapeutic strategy, without compromising therapeutic efficacy of either intervention.

Adverse Drug Effect on Nutritional Therapeutics, Strategic Concern

Interaction in which drug may interfere with therapeutic effect of nutrient prescription because of the drug's pharmacological properties. Alterations in drug dosage, timing, or other factors may prevent, ameliorate, or compensate for adverse effects of or interference with nutritional therapeutics and optimize therapeutic effect, with appropriate clinical management within an integrative therapeutic strategy, without compromising therapeutic efficacy of either intervention.

Impaired Drug Absorption and Bioavailability, Precautions Appropriate

Interaction is of mild to moderate severity. Modification of dosage, timing, or mode of administration will reduce adverse effects of interaction.

Drug-Induced Effect on Nutrient Function, Supplementation Contraindicated, Professional Management Appropriate

Interaction in which prescription pharmaceutical agent intentionally interferes with normal physiological nutrient function through predicted drug action. Nutrient dietary intake is typically restricted and supplementation or administration contraindicated to optimize therapeutic effect and avoid compromising therapeutic efficacy of pharmaceutical intervention.

Impaired Drug Absorption and Bioavailability, Avoidance Appropriate

Interaction has clinically significant adverse effects. Concomitant use should be avoided, especially outside the context of close supervision and regular monitoring by health care professional(s) trained in conventional pharmacology and experienced with clinical herbal medicine and/or therapeutic nutrition. Modification of dosage, timing, or mode of administration may contribute to minimizing severity in cases in which benefit of concurrent administration outweighs risks.

Drug-Induced Adverse Effect on Nutrient Function, Coadministration Therapeutic, with Professional Management

Interaction in which standard-practice use of pharmaceutical agent will usually interfere with normal physiological nutrient function because of predicted drug action. Appropriate coadministration of nutrient, with appropriate clinical management within an integrative therapeutic strategy, will counter adverse metabolic effects of drug on nutrient and may optimize therapeutic effect without compromising therapeutic efficacy of pharmaceutical intervention.

Drug-Induced Adverse Effect on Nutrient Function, Supplementation Therapeutic, Not Requiring Professional Management

Interaction in which standard-practice use of pharmaceutical agent will usually interfere with normal physiological nutrient function because of drug action. Appropriate concomitant supplementation with (or coadministration of) nutrient will counter adverse metabolic effects of drug on nutrient and may optimize therapeutic effect without compromising therapeutic efficacy of pharmaceutical intervention. Clinical management is usually not required.

Bimodal or Variable Interaction, with Professional Management

Interaction is inherently neither beneficial nor adverse, unless ignored. Based on known pharmacological characteristics of each substance (or reasonable extrapolations therefrom), interaction is theoretically possible. Depending on the specific clinical contextualization (patient, population, diagnosis, setting) and practitioner training and experience, the interaction may be deliberately utilized by an appropriately trained and experienced health care professional for increasing clinical efficacy with appropriate clinical management within an integrative therapeutic strategy. Although clinically significant in certain circumstances, this interaction may be of only minor significance in other contexts.

Note: In situations in which “Bimodal” is assigned to an interaction dyad in the text, the possible variations are also listed.

Potential or Theoretical Beneficial or Supportive Interaction, with Professional Management

Beneficial interaction is theoretically possible based on known pharmacological data. However, inadequate substantive data exist currently to determine clinical significance of potential benefit. Coordinated use with appropriate clinical management within an integrative therapeutic strategy may theoretically increase therapeutic efficacy. Pending conclusive research, concomitant use may warrant close supervision and regular monitoring by a health care professional.

Beneficial or Supportive Interaction, with Professional Management

Interaction in which intentional therapeutic use of nutrient or botanical preparation concomitantly with drug therapy can provide additive or synergistic effect and increase therapeutic efficacy for most individuals when taken at appropriate dosages with professional supervision and monitoring as needed. Some individuals may derive greater benefit because of medical conditions or individual pharmacogenomic and biochemical variability. Coadministration can be therapeutically efficacious within the context of multidisciplinary collaboration and supervision by health care professional(s) trained in conventional pharmacology and experienced with clinical herbal medicine and/or therapeutic nutrition.

Beneficial or Supportive Interaction, Not Requiring Professional Management

Interaction in which concurrent administration can generally be considered safe for patient self-care. Based on available evidence, it is improbable that the therapeutic benefit of additive or synergistic interaction or nutritive support has the potential to induce an undesired and possibly adverse additive or interference effect, although discussion and communication with prescribing physician are advised.

Drug-Induced Nutrient Depletion, Supplementation Therapeutic, with Professional Management

Interaction in which appropriate use of nutrient, given clinical management within an integrative therapeutic strategy, can prevent or counter nutrient depletion caused by drug without compromising therapeutic efficacy for most individuals when taken at commonly used dosages. Concomitant use therapeutically efficacious within the context of multidisciplinary collaboration and supervision by health care professional(s) trained in conventional pharmacology and experienced with clinical therapeutic nutrition.

Drug-Induced Nutrient Depletion, Supplementation Therapeutic, Not Requiring Professional Management

Interaction in which simultaneous use can generally be considered safe for patient self-care. Based on examined evidence, appropriate therapeutic use of nutrient adjunctively with drug therapy likely to provide correct drug-induced nutrient depletion pattern and improve therapeutic outcomes for most individuals, without interfering with drug efficacy, when taken at appropriate dosages. Based on available evidence, it is improbable that the therapeutic benefit of additive or synergistic interaction or nutritive support has the potential to induce an undesired and possibly adverse additive or interference effect, although discussion and communication with prescribing physician are advised.

Drug-Induced Nutrient Depletion, Supplementation Contraindicated, Professional Management Appropriate

Interaction in which prescription medication intentionally interferes with normal physiological nutrient metabolism and may produce nutrient depletion pattern through predicted drug action. Nutrient dietary intake is typically restricted and supplementation (or coadministration) contraindicated to optimize therapeutic effect and avoid compromising therapeutic efficacy of pharmaceutical intervention. Concomitant use is generally contraindicated for most individuals. In some unusual circumstances, nutrient might be prescribed under appropriate parameters of dosage, timing, and duration, with clinical management and monitoring within the context of multidisciplinary collaboration and supervision by health care professional(s) trained in conventional pharmacology and experienced with therapeutic nutrition.

Prevention or Reduction of Drug Adverse Effect

Interaction in which intentional coadministration of nutrient or herb concurrently with drug therapy within an integrative therapeutic strategy can prevent, reduce, or counter adverse drug effects without compromising therapeutic efficacy for most individuals when taken at appropriate dosages, under professional guidance.

Prevention or Reduction of Herb or Nutrient Adverse Effect

Interaction in which appropriate use of medication is intended to prevent, reduce, or counter adverse nutrient or herb effects in conditions characterized by nutrient overload, exogenous toxicity, and metabolic derangement, without inducing clinically significant nutrient deficiency pattern or obstructing the role of herbal prescription for appropriate individuals when taken at therapeutic dosages. Concomitant use is contraindicated unless specifically determined as therapeutically efficacious within the context of multidisciplinary collaboration and supervision by health care professional(s) trained in conventional pharmacology and experienced with therapeutic nutrition.

Interaction Possible but Uncertain Occurrence and Unclear Implications

Interaction is of uncertain character, significance, and predictability of occurrence, reflective of inconsistent and/or inadequate evidence. Prudence dictates avoiding concomitant use while assuming neither risk nor benefit until more data become available. Pending further clinical research findings, it is prudent to avoid concomitant use outside the context of close supervision and regular monitoring by health care professional(s) trained in conventional pharmacology and experienced with clinical herbal medicine and/or therapeutic nutrition.