Drug Interactions
Introduction:

Drug interactions have been
recognized for over 100 years.

Increasing
availability
of
complex therapeutic agents and
widespread polypharmacy has led to a
higher potential for drug interactions.

Drug interactions have become
an important cause of adverse drug
reactions (ADR).
Examples
of
Interactions:
Adverse
Drug
1. Mibefradil:

The worldwide withdrawal of the calcium channel blocker mibefradil shortly
after its launch.

Serious drug interactions were reported, highlighting the importance of
identifying potential interactions before marketing.
2. Medicines Withdrawn or Restricted:

Terfenadine, grepafloxacin, and cisapride were withdrawn from the market
due to adverse effects.

Thioridazine had its use restricted because of prolongation of the QT interval
on the electrocardiogram.

QT prolongation increases the risk of developing a life-threatening ventricular
arrhythmia called torsade de pointes.
3. Herbal and Complementary Medicines:

The increasing availability and nonprescription use of herbal and
complementary medicines have raised
awareness of their potential for adverse
interactions.

St. John's wort, a herbal extract for
depression,
can
cause
serious
interactions due to its enzyme-inducing
effects.
4. Food and Drink Interactions:

Monoamine
oxidase
inhibitor
antidepressants (MAOIs) have a wellknown interaction with tyraminecontaining foodstuffs.

Grapefruit juice inhibits cytochrome P450 3A4 and can interact with drugs
like simvastatin and atorvastatin, increasing the risk of adverse reactions.
Determining Clinically Significant Interactions:

The medical literature contains numerous drug interaction studies and case
reports.

However, only a relatively small number of interactions are likely to cause
clinically significant consequences.

Recognizing clinically significant interactions requires understanding
pharmacological mechanisms, high-risk drugs, and vulnerable patient groups.
Definition of Drug Interaction:

An interaction occurs when the effects of one drug are altered by the coadministration of another drug, herbal medicine, food, drink, or other
environmental chemical agents.

The combination can result in additive or enhanced effects, antagonism of
drug effects, or any other alteration in the effects of one or more drugs.
Clinically Significant Interactions:

Clinically significant interactions refer to combinations of therapeutic agents
that directly impact the patient's condition.

Certain drug interactions can provide therapeutic benefits. For example,
combining different antihypertensive drugs to improve blood pressure control
or using an opioid antagonist to reverse the effects of a morphine overdose.

However, this chapter focuses on clinically significant interactions that have
the potential for undesirable effects on patient care.
Importance of Clinically Significant Interactions:

Clinically significant interactions can lead to adverse drug reactions and
impact patient safety.

Understanding these interactions is crucial for healthcare professionals to
make informed decisions regarding medication management.

Identifying and managing clinically significant interactions helps prevent
potential harm, optimize treatment outcomes, and enhance patient care.
Examples of Clinically Significant Interactions:

Drug interactions that result in increased toxicity or reduced efficacy of a
medication.

Interactions that potentiate side effects or adverse reactions.

Interactions leading to altered drug metabolism or pharmacokinetics.

Interactions involving drugs with narrow therapeutic indices.

Interactions that affect drug levels or efficacy in specific patient populations
(e.g., elderly, pediatric, pregnant, or individuals with comorbidities).
Considerations for Managing Clinically Significant Interactions:

Regular review of medication regimens to identify potential interactions.

Consultation with pharmacists or
knowledgeable in drug interactions.

Adjusting drug doses, changing therapy, or selecting alternative medications
when necessary.
other
healthcare
professionals

Providing patient education regarding potential interactions and advising
them to inform healthcare providers about all medications, including overthe-counter drugs, herbal supplements, and dietary changes
Mechanisms of Drug Interactions:
1. Pharmacokinetic Interactions:

Pharmacokinetic interactions affect the processes of drug absorption,
distribution, metabolism, and excretion.

Interactions in these processes can result in changes in drug concentration at
the site of action, leading to toxicity or reduced efficacy.

Variability among individuals in these processes makes it difficult to predict
the extent of these interactions.
Absorption:
- Drug absorption occurs when drugs are taken orally and are absorbed through the
mucous membranes of the gastrointestinal tract.
- Several factors can affect the rate and extent of drug absorption.
1. Changes in Gastrointestinal pH:
- The extent of drug absorption depends on the pH of the gastrointestinal tract.
- Weakly acidic drugs, such as salicylates, are better absorbed at low pH when they
exist in the non-ionized, lipid-soluble form.
- Alterations in gastric pH caused by antacids, histamine H2 antagonists, or proton
pump inhibitors can potentially affect the absorption of other drugs.
- Antacids and other medications that modify gastric pH can influence the rate of
absorption but have minimal impact on the extent of absorption, except for certain
drugs like ketoconazole and itraconazole, which require gastric acidity for optimal
absorption.
2. Adsorption, Chelation, and Complexing Mechanisms:
- Some drugs react within the gastrointestinal tract to form chelates or complexes,
rendering them unabsorbable.
- Tetracyclines and quinolone antibiotics can form insoluble complexes with
divalent or trivalent metal cations (e.g., iron) or with antacids containing calcium,
magnesium, or aluminum, leading to reduced plasma drug concentrations.
- Co-administration of bisphosphonates with calcium supplements can significantly
reduce the bioavailability of both drugs.
- Adsorbents like charcoal or anionic exchange resins (e.g., colestyramine) can
reduce the absorption of certain drugs, including propranolol, digoxin, warfarin,
tricyclic antidepressants, ciclosporin, and levothyroxine.
3. Effects on Gastrointestinal Motility:
- Drugs that alter gastric emptying or gut motility can impact drug absorption.
- Anticholinergic drugs (e.g., tricyclic antidepressants, phenothiazines, some
antihistamines) decrease gut motility and delay gastric emptying, potentially
affecting the absorption of concomitantly administered drugs.
- Opioids like diamorphine and pethidine inhibit gastric emptying and can reduce
the absorption rate of other drugs.
- Metoclopramide, on the other hand, increases gastric emptying and absorption rate,
which can be beneficial for drugs like paracetamol and propranolol.
4. Induction or Inhibition of Drug Transport Proteins:
- Drug transporter proteins, such as P-glycoprotein, limit the oral bioavailability of
certain drugs by actively pumping them back into the gut.
- Drugs that inhibit these transporters can increase the bioavailability of other drugs,
potentially leading to toxicity.
- For example, verapamil, an inhibitor of P-glycoprotein, can increase the
bioavailability of digoxin, potentially causing digoxin toxicity.
5. Malabsorption:
- Certain drugs or conditions can cause malabsorption, leading to reduced absorption
of other drugs.
- Drugs like neomycin can cause a malabsorption syndrome, affecting the absorption
of drugs such as digoxin.
- Orlistat, a lipase inhibitor used for weight loss, can reduce the absorption of fatsoluble drugs.
- It is important to note that most interactions in the gut result in reduced absorption,
primarily affecting the absorption rate rather than the extent of drug absorption.
- In cases where absorption rate is crucial, such as with short half-life drugs or those
requiring rapid achievement of high plasma concentrations, delayed absorption can
have clinical significance.
- Administering interacting drugs with an interval of 2-3 hours between doses can
often help avoid absorption interactions.
Drug Distribution:

After absorption, drugs undergo distribution to various tissues, including their
site of action.

Many drugs and their metabolites bind strongly to plasma proteins.

Acidic drugs, such as warfarin, are primarily bound to albumin, while basic
drugs like tricyclic antidepressants, lidocaine, disopyramide, and propranolol
are bound to α1-acid glycoprotein.

Drug interactions can occur during the distribution phase, mainly through
displacement from protein-binding sites.

A drug displacement interaction happens when the presence of another drug
reduces the extent of plasma protein binding of one drug, resulting in an
increased free or unbound fraction of the displaced drug.

In vitro studies have demonstrated that drugs can be displaced from plasma
proteins, but clinical pharmacokinetic studies suggest that once displacement
occurs, the concentration of the free drug rises temporarily and then rapidly
falls back to its previous steady-state concentration due to metabolism and
distribution.

The time it takes for the free drug concentration to return to its previous steady
state depends on the half-life of the displaced drug.

The short-term rise in free drug concentration is generally of little clinical
significance but may need to be considered in therapeutic drug monitoring.

For example, if a drug displaces phenytoin from its protein-binding sites in a
patient taking phenytoin, the total plasma phenytoin concentration (free plus
bound) will decrease, while the free (active) concentration remains the same.

Clinically significant interactions solely due to protein-binding displacement
are rare.

In some cases, sustained changes in steady-state free plasma concentration
may occur with parenteral administration of drugs that are extensively bound
to plasma proteins and have non-restrictive clearance (efficient elimination by
organs).

Lidocaine is an example of a drug that fits these criteria
Drug Metabolism:
 Clinically important drug interactions often involve the effect of one drug on
the metabolism of another.
 Metabolism refers to the biochemical modification of drugs and other
compounds to facilitate their degradation and elimination from the body.
 The liver is the primary site of drug metabolism, although other organs such
as the gut, kidneys, lung, skin, and placenta also contribute.
 Drug metabolism involves phase I reactions
(oxidation, hydrolysis, reduction) and phase II
reactions (conjugation with substances like
glucuronic acid and sulphuric acid).
 Phase I metabolism is mainly mediated by the
cytochrome P450 (CYP450) mixed function
oxidase system, with the liver being the major site.
However, the enterocytes in the small intestinal
epithelium can also play a role.
 The CYP450 system consists of 57 isoenzymes,
each derived from an individual gene. They are
classified using a nomenclature system based on
family number, subfamily letter, and individual
enzyme number.
 Four main subfamilies (CYP1, CYP2, CYP3,
CYP4) of P450 isoenzymes are responsible for the
metabolism of about 90% of commonly used drugs
in humans.
 CYP2D6 (debrisoquine hydroxylase) is one of the
most extensively studied isoenzymes and exhibits
significant
interindividual
variability.
Polymorphisms in CYP2D6 can affect the
metabolism of substrate drugs.
 Certain CYP450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6,
CYP2E1, and CYP3A4) are responsible for the metabolism of most
commonly used drugs.
 Genetic variations (polymorphisms) in the genes encoding specific CYP450
isoenzymes can impact drug metabolism and vary between individuals and
ethnic groups.
 CYP3A4 and CYP3A5 are the two isoenzymes of the CYP3A family, which
plays a crucial role in drug metabolism. CYP3A4 is abundant in both the
intestinal epithelium and the liver, and it metabolizes a wide range of
chemically unrelated drugs from various drug classes.
 Drug interactions can occur through the inhibition or induction of CYP450
isoenzymes. Some drugs can be substrates for a particular isoenzyme and also
inhibit or induce that isoenzyme.
 The oxidation of a drug typically involves multiple CYP isoenzymes,
resulting in the production of several metabolites. Inhibition or induction of a
single isoenzyme may have little effect on drug plasma levels unless the drug
is primarily metabolized by that specific isoenzyme.
 If a drug is primarily metabolized by a single CYP450 isoenzyme and that
enzyme is inhibited or induced, it can significantly affect the plasma
concentrations of the drug.
 For example, taking erythromycin (CYP3A4 inhibitor) along with
carbamazepine (metabolized by CYP3A4) can lead to increased
carbamazepine concentrations and potential toxicity.





Enzyme Induction:
Enzyme induction refers to the
process by which certain drugs or
substances increase the synthesis and
activity
of
drug-metabolizing
enzymes in the body, leading to
enhanced metabolism and clearance
of drugs.
Rifampicin, an antibiotic, and
antiepileptic
agents
such
as
barbiturates,
phenytoin,
and
carbamazepine are powerful enzyme
inducers commonly used in clinical
practice.
Some enzyme inducers, like barbiturates and carbamazepine, can induce their
own metabolism, a phenomenon known as autoinduction.
Other substances, including cigarette smoking, chronic alcohol use, and the
herbal preparation St. John's wort, can also induce drug-metabolizing
enzymes.
The process of enzyme induction requires new protein synthesis, so the effect
typically develops gradually over several days or weeks after initiating an
enzyme-inducing agent. Similarly, the effect persists for a similar duration
after discontinuing the drug.
 Enzyme-inducing drugs with short half-lives, like rifampicin, induce
metabolism more rapidly than those with longer half-lives, such as phenytoin,
due to reaching steady-state concentrations faster.
 The dose of an enzyme-inducing drug may influence the extent of enzyme
induction, although some drugs can induce enzymes at any dose.
 The pharmacological effect of the affected drug is generally decreased due to
enhanced metabolism and clearance resulting from enzyme induction.
 St. John's wort is a potent inducer of CYP3A, an important drug-metabolizing
enzyme. Taking St. John's wort along with drugs like ciclosporin, tacrolimus,
HIV-protease inhibitors, irinotecan, or imatinib can increase the risk of
therapeutic failure with these drugs.
 However, if the affected drug has active metabolites, enzyme induction may
lead to an increased pharmacological effect.
 The effects of enzyme induction can vary significantly among individuals and
are influenced by factors such as age, genetic variations, concurrent drug
treatments, and the presence of underlying diseases.
Enzyme Inhibition:
 Enzyme inhibition is a common mechanism
behind many clinically significant drug
interactions.
 Various drugs can act as inhibitors of
cytochrome P450 enzymes, which are
responsible for the metabolism of many drugs in
the body.
 The strength of an inhibitor is classified as
strong, moderate, or weak based on its ability to
cause changes in the plasma area-under-thecurve (AUC) value or clearance of sensitive
CYP3A substrates.
 Strong inhibitors can
cause a ≥5-fold increase
in the AUC value or
more
than
80%
decrease in clearance.
 Moderate inhibitors can
cause a ≥2- but <5-fold
increase in the AUC
value
or
50–80%
decrease in clearance.
 Weak inhibitors can
cause a ≥1.25- but <2fold increase in the
AUC value or 20–50% decrease in clearance.
 When an enzyme inhibitor is administered concurrently with a drug, it reduces
the metabolism of the drug, resulting in increased steady-state drug
concentrations.
 The degree of enzyme inhibition is often dose-dependent, with maximal
effects observed when the new steady-state plasma concentration is achieved.
 Effects may be seen within a few days for drugs with short half-lives, while
maximal effects may be delayed for drugs with long half-lives.
 The clinical significance of enzyme inhibition interactions depends on factors
such as dosage, alterations in pharmacokinetic properties of the affected drug,
and patient characteristics.
 Drugs with a narrow therapeutic range, such as theophylline, cyclosporine,
oral anticoagulants, and phenytoin, are particularly susceptible to interactions
resulting from enzyme inhibition.
 Examples of interactions due to enzyme inhibition include increased sildenafil
plasma concentrations when ritonavir (an enzyme inhibitor) is administered
concurrently and increased bioavailability of certain calcium channel blockers
(e.g., felodipine) when consumed with grapefruit juice, which inhibits CYP3A
enzymes.
 Enzyme inhibition in the intestinal epithelium can significantly impact drug
bioavailability and absorption.
 Enzyme inhibition typically leads to an increased pharmacological effect of
the affected drug. However, in cases where the affected drug is a pro-drug
requiring enzymatic metabolism to active metabolites, enzyme inhibition may
result in a reduced pharmacological effect.
 For example, proton pump inhibitors (such as lansoprazole), which inhibit
CYP2C19, can reduce the effectiveness of clopidogrel, a pro-drug that relies
on CYP2C19 metabolism to produce its active anti-platelet metabolite.
Predicting interactions involving drug metabolism can be challenging due to
several factors:
 Variability within drug classes: Different drugs within the same therapeutic
class can have varying effects on specific cytochrome P450 isoenzymes. For
example, ciprofloxacin and norfloxacin, both quinolone antibiotics, inhibit
CYP1A2 and increase plasma theophylline levels, while moxifloxacin,
another quinolone antibiotic, is a weaker inhibitor and does not interact in the
same way.
 Metabolic pathways: Different drugs are metabolized by different cytochrome
P450 isoenzymes or may not be metabolized by the CYP450 system at all.
For example, atorvastatin and simvastatin are predominantly metabolized by
CYP3A4, while fluvastatin is metabolized by CYP2C9, and pravastatin is not
significantly metabolized by the CYP450 system.
 In vitro vs in vivo studies: In vitro techniques are used to identify cytochrome
P450 isoenzymes involved in drug metabolism during the drug development
process. However, the findings from in vitro studies may not always
accurately reflect what happens in vivo. Further drug interaction studies may
be required to identify potential interactions more comprehensively.
 Limited detection: Some drug interactions may only affect a small proportion
of individuals, making it necessary to study large numbers of volunteers or
patients to identify these interactions.
 Case reports and formal studies: Suspected drug interactions are often initially
reported in case reports and then evaluated in formal studies. For example,
case reports suggest that certain antibiotics reduce the effectiveness of oral
contraceptives, but this interaction has not been consistently demonstrated in
formal studies.
 Overlapping mechanisms: The drug transporter protein P-glycoprotein (P-gp)
and CYP3A4 share overlapping substrates and inhibitors/inducers. This
means that drug interactions previously attributed solely to effects on
CYP3A4 may also involve P-gp. Understanding the contribution of both
mechanisms is important in comprehending certain drug interactions.
Elimination interactions involving drug excretion can occur through various
mechanisms, including changes in urinary pH, active renal tubule excretion,
renal blood flow, biliary excretion, and drug transporter proteins. Here are the
detailed notes:
1. Changes in urinary pH: The passive reabsorption of drugs in the kidney
tubules depends on their ionization state. Weakly acidic drugs (pKa 3.0–7.5)
exist as ionized lipid-insoluble molecules at alkaline pH, resulting in their
excretion in urine. On the other hand, weak bases (pKa 7.5–10) have higher
clearance in acidic urine. Strong acids and bases are virtually completely
ionized over the physiological range of urinary pH and are not affected by pH
changes. However, this mechanism has limited clinical significance because
most weak acids and bases are primarily eliminated by hepatic metabolism
rather than renal excretion.
2. Changes in active renal tubule excretion: Drugs that utilize the same active
transport system in the kidney tubules can compete with each other for
excretion. This competition can be therapeutically advantageous. For
example, probenecid is administered to increase the plasma concentration of
penicillins by delaying their renal excretion. Probenecid inhibits the renal
secretion of many other anionic drugs via organic anion transporters (OATs).
3. Changes in renal blood flow: Renal vasodilatory prostaglandins help regulate
blood flow through the kidneys. Inhibition of prostaglandin synthesis by drugs
like indomethacin can reduce the renal excretion of lithium, leading to
increased plasma levels of lithium. However, the exact mechanism of this
interaction is not fully understood, as plasma lithium levels are not affected
by other potent prostaglandin synthetase inhibitors such as aspirin. When
prescribing an NSAID to a patient taking lithium, close monitoring of plasma
lithium levels is recommended.
4. Biliary excretion and the enterohepatic shunt: Some drugs are excreted in the
bile, either unchanged or as conjugates, and can undergo enterohepatic
recycling. The gut flora metabolize some of these conjugates back into the
parent compound, which is then reabsorbed. If the gut flora is diminished by
the presence of antibiotics, the drug is not recycled and is eliminated more
rapidly. This mechanism has been suggested as a basis for an interaction
between broad-spectrum antibiotics and oral contraceptives. Antibiotics may
reduce the enterohepatic circulation of ethinylestradiol conjugates, leading to
reduced circulating estrogen levels and a potential for contraceptive failure.
However, the evidence from pharmacokinetic studies supporting this
interaction is not conclusive.
5. Drug transporter proteins: Drug transporters are carrier proteins that facilitate
the movement of drugs across biological membranes. One notable transporter
is P-glycoprotein (P-gp), encoded by the ABCB1 gene. P-gp is found in
various tissues, including the kidneys, liver, intestine, and blood-brain barrier.
It acts as an efflux pump, exporting substances, including drugs, into urine,
bile, and the intestinal lumen. Some drugs can induce or inhibit the pumping
actions of P-gp. For example, verapamil, a P-gp inhibitor, can increase the
plasma levels of digoxin, a P-gp substrate, potentially leading to digoxin
toxicity. There is an overlap between inhibitors/inducers and substrates of
both P-gp and CYP3A4, and both mechanisms may contribute to many drug
interactions previously attributed solely to changes in CYP3A4
Pharmacodynamics
1. Antagonistic
Interactions:
- Drugs with agonist actions at a
particular receptor can be
antagonized by drugs acting as
antagonists at the same receptor.
For example, the bronchodilator
effect of a selective β2adrenoreceptor
agonist
like
salbutamol can be antagonized by
β-adrenoreceptor antagonists.
- Therapeutically, specific antagonists may be used to reverse the effects of
another drug at receptor sites. Examples include naloxone (opioid antagonist) and
flumazenil (benzodiazepine antagonist).
- Certain drug classes have opposing pharmacological actions, such as
anticoagulants and vitamin K or levodopa and dopamine antagonist
antipsychotics.
2. Additive or Synergistic Interactions:
- When two drugs with similar
pharmacological
effects
are
administered together, their effects
can be additive.
- Combinations of drugs with
CNS-depressant effects, such as
antidepressants,
hypnotics,
antiepileptics, and antihistamines,
can lead to excessive drowsiness.
- Combinations of drugs with
arrhythmogenic potential, such as
antiarrhythmics,
neuroleptics,
tricyclic antidepressants, and those causing electrolyte imbalance (e.g., diuretics),
may lead to ventricular arrhythmias and should be avoided.
- Concurrent use of multiple drugs that can prolong the QT interval on the
electrocardiogram may increase the risk of ventricular tachycardia and torsade de
pointes.
3. Serotonin Syndrome:
- Serotonin syndrome is characterized by an excess of serotonin resulting from
therapeutic drug use, overdose, or interactions between drugs.
- It occurs when two or more drugs affecting serotonin are given concurrently
or when one serotonergic drug is stopped, and another is started.
- Symptoms include confusion, disorientation, abnormal movements,
exaggerated reflexes, fever, sweating, diarrhea, and changes in blood pressure.
- It is best prevented by avoiding combinations of serotonergic drugs, and
special care is needed when switching between selective serotonin reuptake
inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs).
4. Drug or Neurotransmitter Uptake Interactions:
- Monoamine oxidase inhibitors (MAOIs) can interact with other drugs and
foods. MAOIs inhibit the breakdown of noradrenaline in the adrenergic nerve
endings.
- Concurrent use of MAOIs and indirectly acting sympathomimetic amines
(e.g., amphetamines, tyramine) can lead to a hypertensive crisis, potentially
causing severe symptoms like hypertension, headache, hyperpyrexia, and cardiac
arrhythmias.
- Tyramine, present in certain foods like cheese and red wine, can cause a
sympathetic overactivity syndrome in patients taking MAOIs.
- Patients taking irreversible MAOIs should avoid indirectly acting
sympathomimetic amines, and they need to be cautious about cough and cold
remedies, illicit drug use, and dietary restrictions.
Drug Food interactions
Certainly! Here are the detailed notes on drug-food interactions:
1. Effects on Drug Absorption:
- Food can significantly affect drug absorption by influencing gastrointestinal
absorption and motility.
- Some drugs should not be taken with food to optimize their absorption. Examples
include iron tablets and certain antibiotics.
- Tyramine in certain foods can interact with monoamine oxidase inhibitors
(MAOIs), leading to a hypertensive crisis.
- Grapefruit juice can interact with the calcium channel blocker felodipine by
inhibiting intestinal CYP3A4, which metabolizes the drug.
- Grapefruit juice mainly affects orally administered drugs metabolized by
CYP3A4, while intravenous preparations are less affected.
- The active constituents in grapefruit juice, such as naringin, naringenin,
bergamottin, and dihydroxybergamottin, are thought to inhibit CYP3A4 and drug
transporters.
2. Cranberry Juice and Warfarin:
- Initial reports suggested an interaction between cranberry juice and warfarin,
leading to regulatory advice to closely monitor the international normalized ratio
(INR) in patients taking this combination.
- However, subsequent controlled studies have not confirmed these interactions.
3. Cruciferous Vegetables and CYP1A2:
- Cruciferous vegetables like Brussels sprouts, cabbage, and broccoli contain
substances that induce the CYP450 isoenzyme CYP1A2.
- Chemicals formed by burning meats (e.g., barbecuing) also possess these
inducing properties.
- While these foods do not typically cause clinically significant drug interactions
on their own, their consumption can complicate drug interaction studies by
introducing another variable.
Drug Herb interactions
1. Herbal Products and Active Ingredients:

The use of herbal products, including Chinese herbal medicines and
Ayurvedic medicines, has increased in the UK.

Herbal remedies often contain pharmacologically active ingredients
that can interact with conventional drugs.

Liquorice (Glycyrrhizin glabra) extracts used for digestive disorders
can interact with digoxin and diuretics. It may exacerbate hypokalemia
induced by diuretic drugs and precipitate digoxin toxicity.

Some herbal products, such as Chinese ginseng (Panax ginseng), Chan
Su (containing bufalin), and Danshen, may contain digoxin-like
compounds that can interfere with digoxin assays, leading to falsely
elevated levels.
2. Herbal Products with Anti-Platelet and Anticoagulant Properties:

Certain herbal products have anti-platelet and anticoagulant properties,
increasing the risk of bleeding when used with aspirin or warfarin.

Herbal extracts containing coumarin-like constituents, such as Alfalfa
(Medicago sativa), Angelica (Angelica archangelica), Dong Quai
(Angelica polymorpha, A. dahurica, A. atropurpurea), chamomile,
horse chestnut, and red clover (Trifolium pratense), can potentially
interact with warfarin.

Herbal products with anti-platelet properties include Borage (Borago
officinalis), Bromelain (Ananas comosus), capsicum, feverfew, garlic,
Ginkgo (Ginkgo biloba), turmeric, and others.
3. Other Examples of Drug-Herb Interactions:

Some herbal products can enhance hypoglycemic effects (e.g., Asian
ginseng) or hypotensive effects (e.g., hawthorn).

Certain herbal products, such as evening primrose oil and
Shankapushpi, may lower the seizure threshold.

St. John's wort (Hypericum extract), commonly used for depression, is
known for its potential drug-herb interactions, but there are many other
potential interactions to consider
Awareness and Information:
Healthcare workers need to be alert to the possibility of drug interactions and take
appropriate steps to minimize their occurrence.
Drug formularies and the Summary of Product Characteristics provide useful
information about interactions.
Resources such as drug safety updates from regulatory agencies like the Medicines
and Healthcare products Regulatory Agency (MHRA), interaction alerts in
prescribing software, and specific websites for drug classes (e.g., HIV drugs) can be
helpful.
Interventions to Minimize Risk:
Possible interventions to avoid or minimize the risk of drug interactions include
switching one of the potential interacting drugs.
Allowing an interval of 2-3 hours between the administration of interacting drugs
can help.
Altering the dose of one of the drugs involved in the interaction may be necessary.
The dose can be reduced if the interaction enhances the drug's effect or increased if
the interaction reduces the drug's effects. Monitoring for toxic effects or therapeutic
failure is crucial.
Patients should be advised to seek guidance if they plan to stop smoking or start a
herbal remedy, as close monitoring may be necessary during the transition.
Anticipating Clinically Significant Consequences:
It is important to anticipate when a potential drug interaction might have clinically
significant consequences for the patient.
Advice should be given on how to minimize the risk of harm, such as recommending
an alternative treatment to avoid the combination of risk, making dose adjustments,
or closely monitoring the patient.