Herbal-drug and herb-food interactions are common. Pharmacokinetic interactions occur when an herbal supplement shares the same absorption, distribution, metabolism, or excretion mechanisms as a drug, potentially changing the drug's concentration. Pharmacodynamic interactions involve direct effects of an herbal supplement on a drug's mechanism of action. Some potentially clinically significant interactions include St. John's Wort decreasing serum levels of drugs metabolized by CYP450 enzymes, kava potentiating central nervous system depressants, and ginkgo increasing bleeding risk when taken with anticoagulants or antiplatelets. Close monitoring is recommended when taking herbs and drugs together.

1. HERBAL-DRUG AND HERB-FOOD INTERACTIONS
K SUDHEER KUMAR
Assoc.Professor
MAK COLLEGE OF PHARMACY , HYDERABAD

2. Antacids – Take after meals to increase the duration of effect.
Antibacterials – Better absorption if taken on an empty stomach one hour before meals
or two hours after meals. However, they can be taken with food to reduce stomach upset.
Antihistamines – Alcohol increases the sedative effects of these drugs.
Grapefruit Juice – Avoid grapefruit juice while taking medications unless authorized by
your prescriber or pharmacist.
Herbal medications – Please check with your prescriber or pharmacist prior to initiating
any herbal supplement, as some may interact with the prescription medications you may be
taking.

3. Herbs are often administered in combination with
therapeutic drugs, raising the potential of herb-drug
interactions

4. Pharmacokinetic vs. Pharmacodynamic Interactions
Clinically important interactions between an herbal supplement and a drug typically
manifest as pharmacokinetic interactions, which affect a drug's concentration in the
blood and pharmacologic action. In many cases, pharmacokinetic interactions can be
safely countered by adjusting the drug's dosage.
Risk of a pharmacokinetic interaction occurs when an herbal supplement shares the same
mechanism of absorption, distribution, metabolism, or excretion (ADME) as a
coadministered drug. Competition between an herbal supplement and a drug for a shared
ADME mechanism may result in a change in the drug's concentration at the site of action

5. Less commonly, herb-drug interactions may manifest as pharmacodynamic interactions,
which involve direct pharmacologic actions of an herbal supplement that are unrelated to
changes in blood concentrations.
Risk of a pharmacodynamic interaction occurs when an herbal supplement has a direct
effect on the mechanism of action of a coadministered drug.
Direct pharmacologic effects of an herbal supplement may antagonize or exacerbate the
drug's clinical effects without changing the drug's concentration. In most cases, a change
in drug dosage will not counter a pharmacodynamic herb-drug interaction.

6. Clinicians who are able to distinguish between pharmacokinetic/ADME interactions and
pharmacodynamic interactions will be able to make better clinical decisions about
whether to adjust the drug's dosage or discontinue the supplement.
A change in drug dosage rarely results in a predictable change in clinical outcomes when a
pharmacodynamic interaction occurs (e.g., warfarin [Coumadin] dosage adjustment with
changes in daily leafy green vegetable intake).

7. Knowledge of the mechanisms underlying ADME processes for a drug and an herbal
supplement is needed to recognize pharmacokinetic herb-drug interactions. Most ADME
mechanisms fall under four large gene superfamilies comprising more than 1,000
proteins: the cytochrome P450 (CYP) drug metabolism enzymes; the uridine
diphosphate-glucuronosyltransferase (UGT) conjugating enzymes; the adenosine
triphosphate–binding cassette (ABC) drug uptake/efflux transporters; and the organic
anion-transporting polypeptide (OATP) drug transporters.
CYP and UGT enzymes make drugs more water-soluble, thus easier to eliminate from the
body, whereas the ABC transporters (e.g., efflux pump P-glycoprotein [P-gp]) and OATP
transporters are responsible for transporting drugs and their metabolites from various
body compartments.

8. Allium sativum (garlic) decreased the area under the plasma concentration-time curve
(AUC) and maximum plasma concentration of saquinavir, but not ritonavir and
paracetamol (acetaminophen),
A. sativum increased the clotting time and international normalised ratio of warfarin and
caused hypoglycaemia when taken with chlorpropamide
Ginkgo biloba (ginkgo) caused bleeding when combined with warfarin or aspirin
(acetylsalicylic acid), raised blood pressure when combined with a thiazide diuretic and even
caused coma when combined with trazodone in patients
Panax ginseng (ginseng) reduced the blood concentrations of alcohol (ethanol) and warfarin,
and induced mania when used concomitantly with phenelzine, but ginseng increased the
efficacy of influenza vaccination
Piper methysticum Kava enhanced the hypnotic effect of alcohol in mice, but this was not
observed in humans.

9. Piperine from black (Piper nigrum Linn) and long (P. longum Linn) peppers increased the
AUC of phenytoin, propranolol and theophylline in healthy volunteers and plasma
concentrations of rifamipicin (rifampin) in patients with pulmonary tuberculosis
Hypericum perforatum (hypericum; St John's wort) decreased the blood concentrations of
ciclosporin (cyclosporin), midazolam, tacrolimus, amitriptyline, digoxin, indinavir, warfarin,
phenprocoumon and theophylline, but did not alter the pharmacokinetics of
carbamazepine, pravastatin, mycophenolate mofetil and dextromethorphan
The clinical importance of herb-drug interactions depends on many factors associated
with the particular herb, drug and patient. Herbs should be appropriately labeled to alert
consumers to potential interactions when concomitantly used with drugs, and to
recommend a consultation with their general practitioners and other medical carers

10. Ginkgo (Ginkgo biloba) Potential increased bleeding risk with
warfarin (Coumadin)
Ginseng, American (Panax
quinquefolius)
may modestly reduce blood glucose
level
Milk thistle (Silybum marianum) May decrease concentrations of
medications metabolized by CYP2C9, such
as warfarin, phenytoin (Dilantin), and
diazepam

11. Antacids
· Aluminum/Magnesium
hydroxide/Simethicone
· Aluminum carbonate
basic
· Aluminum hydroxide
Avoid high protein meals High protein meals may lead to a decrease in the neutralizing
capacity of the antacid Avoid high protein meals while taking these agents. Maintain
normal diet

12. Calcium channel blockers
Felodipine
Nifedipine
Amlodipine
Avoid grapefruit juice
By drinking grapefruit juice with this medication you may have higher than desired blood
levels of the medications which you are taking.
Avoid grapefruit juice during therapy with a calcium channel blocker, unless otherwise
directed by your doctor. These higher levels may actually be harmful and cause
adverse effects.

13. Cephalosporins
· Cefotetan
· Cefoperazone
· Cefamandole
· Cefmetazole
Avoid alcoholic beverages When ingesting alcohol with these medications you can
develop a very severe reaction called a “disulfiram reaction” (see Disulfiram statement
below).
This adverse effect is characterized by flushing, vomiting, very fast breathing , and very
fast
heart rate) Avoid: all beverages and over the counter products containing
alcohol (i.e. cough and cold products containing alcohol)

14. Cyclosporine
Avoid grapefruit juice
By drinking grapefruit juice with this medication you may have higher than desired blood
levels of the medications which you are taking. These higher levels may actually be harmful
and cause adverse effects.
Avoid grapefruit juice during therapy with this agent, unless otherwise directed by your
doctor. For patients who regularly consume grapefruit juice (as per discussions with their
healthcare provider), cyclosporine blood levels should be closely monitored to make sure
your blood levels are in the normal range. Grapefruit juice should definitely be avoided in
patients with kidney problems.

15. Iron
Ferrous sulfate
Ferrous gluconate
1) Consume foods high in Vitamin C
2) Do not take dairy products together with your iron.
1) You may enhance the amount of iron your body absorbs by eating/drinking
foods/drinks high in vitamin C
2) When taken with food, the amount of iron your body absorbs may
be reduced.
1) Good sources of vitamin C include: oranges, orange juice, broccoli, green peppers,
strawberries, tomatoes, kiwi, potatoes
2) Iron and iron-containing products should not be administered together with dairy
products. Space appropriately.

16. Fluoroquinolones
· Ciprofloxacin
· Levofloxacin
· Gatifloxacin
· Sparfloxacin
Avoid calcium-richfoods, mineral supplements, and caffeine
You may decrease the amount of drug your body absorbs if taken together with calcium
and other minerals, which bind to form insoluble complexes.
Avoid coffee and colas
Take medication on an empty stomach or at least one to two hours before or after a
meal.

17. COA reductase inhibitors
· Atorvastatin
· Lovastatin
· Simvastatin
Avoid grapefruit juice
By drinking grapefruit juice with this medication you may have higher than desired blood
levels of the medications which you are taking. These higher
levels may actually be harmful and cause serious adverse effects.
Avoid grapefruit juice during therapy with this agent, unless otherwise directed by your
doctor. Orange juice may be substituted.

18. Isoniazid
Do not take with food If you take this drug with food you will significantly decrease the
amount of drug that your body will absorb and therefore the drug may not work as well
as it can.
Take this drug at least one hour before or two hours after a meal with water or liquids
such as tea, coffee, juice, or skim milk.
Avoid: all beverages and over the counter products containing alcohol. aged cheeses,
aged meats, smoked or pickled fish, yeast, red wine, beer (alcoholic and non-alcoholic),
figs, avocados, bananas, caffeine, chocolate and the herbal product ginseng

19. Ketoconazole
Avoid alcoholic beverages When ingesting alcohol with this medication you can develop a
very severe reaction called a “disulfiram reaction” (see Disulfiram statement above).
This adverse effect is characterized by flushing, vomiting, increased breathing rate, and
very fast heart rate. Avoid: all beverages and over the counter products containing alcohol
Metronidazole
Avoid alcoholic Beverages When ingesting alcohol with this medication you can develop a
very severe reaction called a “disulfiram reaction”
This adverse effect is characterized by flushing, vomiting, rapid breathing rate, and very fast
heart rate.
Avoid: all beverages and over the counter products containing alcohol

20. Oral diabetic agents
Chlorpropramide
Glimepiride
Glipizide
Glyburide
(Avoid alcoholic Beverages When ingesting alcohol with this medication you can
develop a very severe reaction called a “disulfiram reaction” (see Disulfiram above).
This adverse effect is characterized by flushing, vomiting, increased breathing rate, and
very fast heart rate.
Avoid: all beverages and over the counter products containing
alcohol.

21. Potassium depleting diuretics
Furosemide
Hydrochlorthiazide
Consume foods high in potassium Due to the fact that these medications may allow your
body to lose more potassium than normal it may be wise to add some potassium-rich
foods to your diet.
Remember; maintain consistent consumption & have potassium levels checked regularly
by your healthcare provider. Good sources of potassium: oranges, orange juice, tomatoes,
cantaloupe, bananas, dried fruits, potatoes, spinach

22. Tetracycline
Avoid dairy products and food and drugs high in calcium, magnesium, or iron
Taking this medication with dairy products and food and drugs high in calcium,
magnesium, or iron may result in lower than desired doxycycline blood levels and
therefore the drug may not work as well as it can.
Take doxycycline at least 2 hours before or after eating/drinking dairy products, antacids,
or iron containing preparations

23. Theophylline
Avoid large intake of caffeine-containing Beverages If you take this drug and consume
large amounts of caffeine-containing beverages you may experience some adverse effects
which include nervousness and insomnia.
Avoid: Coffee, teas, colas, chocolate, and other caffeinecontaining products.
Warfarin
Vitamin K rich foods: If you eat thee foods while taking this medication you may alter the
blood thinning response you will have to the drug warfarin.
Maintain consistent diet (Do not significantly vary the amount of these vegetables in your
normal daily diet!).
Limit foods high in vitamin K (i.e. Dark green leafy vegetables, spinach, kale, broccoli,
lettuce, turnips cabbage, green tea, brussels sprouts, soybean & vegetable oil, beef liver,
raw cauliflower). Please speak to your healthcare provider for more information.

24. Potentially Clinically Significant Herb-Drug/Food Interactions
HYPERCIUM , St. John’s Wort.
St. John’s Wort is a commonly found herbal medication which is useful for the treatment
of depression and as an antiviral agent.
The major chemical constituent of St. John’s Wort is hypericin which is a phenolic
glycoside. St. John’s wort is also included in the British Pharmacopoeia (B.P) and in the
United States Pharmacopoeias (USP) as treatment for depression.
Biological Source Dried aerial parts of Hypericum perforatumFamilyHypericaceae
(Clusiaceae)
Chemistry St. John’s Wart consists of a variety of constituents including
napthodianthrones (less than 0.1%-0.15%), flavonoids, phloroglucinols and essential oils.
Uses St.John’s wort has potential antidepressant and antiviral effects. It is also useful as
an antibacterial, anti-inflammatory and is known to have wound-healing and skin-healing
properties

25. Interaction causes symptoms associated with a histamine release reaction resulting in
flushing, chills, hypertension, tachycardia, palpitations, restlessness, and insomnia.
There is some concern that prescription antidepressants taken together with St. John’s
wort could interact with each other and lead to adverse side effects including serotonin
syndrome.
Concomitant administration may lead to decreased serum concentrations of these
agents. Monitor serum drug concentrations for efficacy/toxicity.
Avoid combination of Indinavir and St. John’s Wort.
Concomitant administration may lead to lowering of the INR
Reports of breakthrough bleeding have been identified with concomitant administration

26. KAVA-KAVA
is a beverage or extract that is made from Piper methysticum, Family Piperaceae (black
pepper)
The dried rhizome and roots of P. methysticum, a large shrub widely cultivated on many
Pacific islands, including Hawaii, Tahiti, and New Guinea, are consumed in various forms
as kava.
people take kava by mouth to calm anxiety, stress, and restlessness, and to treat
sleeping problems (insomnia).
It is also used for attention deficit-hyperactivity disorder
(ADHD), epilepsy, psychosis, depression, migraines and other headaches, chronic fatigue
syndrome (CFS), common cold and other respiratory tract infections, tuberculosis, muscle
pain, and cancer prevention.
 urinary tract infections (UTIs), pain and swelling of the uterus, venereal disease,
menstrual discomfort, and to increase sexual desire.

27. Kava Kava can potentiate the effects of agents that depress the central nervous system,
causing over-sedation and coma. It may also induce tremors, abnormal movements, or
muscle spasms that may decrease the effectiveness of anti-Parkinson’s medications or
may potentiate the extrapyramidal movements seen with antipsychotic medications.

28. Ginkgo biloba is a popular supplement and one of the top-selling herbal medicines.
Ginkgo biloba extract is collected from the dried green leaves of the plant and is available
as liquid extracts, capsules, and tablets. People use it for a variety of reasons.
Gingko contains high levels of flavonoids and terpenoids, antioxidants that provide
protection against oxidative cell damage from harmful free radicals. In this way,
antioxidants are believed to help reduce the risk of cancer.
Also known as the maidenhair tree, ginkgo is one of the oldest species of tree in the
world.
The tree is considered to be a "living fossil," meaning that it has continued to survive
even after major extinction events.
The extract can be taken as a supplement, and the dried leaves of the plant can be used
to make tea.

29. Even ibuprofen combined with Gingko can increase the risk of internal bleeding.
Patients with blood circulation disorders or individuals on anticoagulants, such
as aspirin, are at risk of experiencing undesirable effects after taking ginkgo.
Those taking selective serotonin reuptake inhibitors (SSRI) as antidepressants should
not take ginkgo as it inhibits monoamine oxidase, reducing the effectiveness of the
medications.
Combining the two may also increase the risk of a potentially fatal condition known as
serotonin syndrome.
Gingko can also exaggerate both the good and bad effects of another type of
antidepressant, known as monoamine oxidase inhibitors (MAOIs).
Ginkgo leaves contain long-chain alkylphenols, which are highly allergenic.
The National Center for Complementary and Integrative Health state that eating raw or
roasted ginkgo seeds can be poisonous and may lead to serious side effects.
Gingko acts as blood thinner and therefore the use of this agent with other blood
thinning agents could increase the risk for stroke or excessive bleeding.

30. GINSENG , PANAX GINSENG
is an herbal supplement that has been used for centuries in Chinese medicine.
Ginseng is believed to restore and enhance wellbeing. It is one of the most popular herbal
remedies.
Panax ginseng is also used for depression, anxiety, general fatigue and chronic fatigue
syndrome (CFS), multiple sclerosis, for boosting the immune system, and for fighting
particular infections in a lung disease called cystic fibrosis.
Ginseng may interact with Warfarin by decreasing the efficacy of Warfarin
or reversing the drug’s effects.
Panax ginseng might decrease blood sugar. Insulin is also used to decrease blood sugar.
Taking Panax ginseng along with insulin might cause your blood sugar to be too low.
Monitor your blood sugar closely. The dose of your insulin might need to be changed.

31. Caffeine can speed up the nervous system. By speeding up the nervous system, caffeine
can make you feel jittery and speed up your heartbeat. Panax ginseng might also speed
up the nervous system. Taking Panax ginseng along with caffeine might cause serious
problems including increased heart rate and high blood pressure. Avoid taking caffeine
along with Panax ginseng

32. Garlic (Allium sativum belonging to family Liliaceae.), widely as a flavoring in cooking,
but it has also been used as a medicine throughout ancient and modern history; it has
been taken to prevent and treat a wide range of conditions and diseases.
Allicin, a yellow liquid responsible for the odour of garlic, is the active principle of the
drug. The other constituents reported in Garlic are alliin, volatile and fatty oils, mucilage
and albumin. Alliin.
Garlic is carminative, aphrodisiac, expectorant, stimulant, and used in fevers, coughs,
febrifuge in intermittent fevers, respiratory diseases such as chronic bronchitis, bronchial
asthma, whooping cough, and tuberculosis. It is also used in atherosclerosis and
hypertension.
Garlic (therapeutic doses) reduces platelet aggregation and increases fibrinolytic
activity, therefore monitor bleeding times. patients on antiplatelet agents and warfarin
Garlic decreases blood pressure and therefore may potentiate blood pressure
medications

33. PEPPER Pipper nigrum Family: Piperaceae, Piperine, Piperidine.
Carminative. Stomachic. Stimulant, Flatulent, Antiarthritis, Antimalerial, Useful in sore
throat, piles and dyspepsia, Useful in treatment of gonorrhea and chronic bronchitis.
People take black pepper by mouth for arthritis, asthma, upset stomach, bronchitis,
a bacterial infection that causes diarrhea (cholera), colic, depression, diarrhea, tiredness,
gas, headache, sex drive, menstrual pain, stuffy nose, sinus infection, dizziness,
discolored skin (vitiligo), exercise performance, weight loss, and cancer.
It is LIKELY UNSAFE when taken by mouth in large amounts during pregnancy. It might
cause an abortion
It is POSSIBLY UNSAFE when taken by mouth in large amounts. Deaths have been
reported from large amounts of black pepper accidentally entering the lungs.
iperine, a chemical in black pepper, might slow blood clotting. In theory, taking black
pepper in amounts greater than those in food might increase the risk of bleeding in people
with bleeding disorders.

34. Black and white pepper might increase how much phenytoin the body absorbs. Taking
black and white pepper along with phenytoin might increase the effects and side effects of
phenytoin.
Taking black and white pepper along with propranolol might increase the effects and side
effects of propranolol .
Taking black and white pepper along with rifampin might increase the effects and side
effects of rifampin.
Bleeding conditions: Piperine, a chemical in black pepper, might slow blood clotting.

35. EPHEDRA
Ephedra gerardiana , belonging to family Ephadreaceae.
Ephedra contains alkaloids Ephedrine, Norpseudoephedrine The leaves and stems of
ephedra also contain many potentially active compounds, such as tannins, saponin,
flavone and volatile oils.
Ephedrine is antiallergenic, antiasthmatic, antispasmodic, decongestant, cough
suppressant, stimulant and vasoconstrictor. Pseudoephedrine is decongestant, cough
suppressant and norpseudoephedrine is peripheral vasodilator used to treat angina. As a
whole it is decongestant; it opens sinuses, increases sweating, dilates bronchioles
(antiasthmatic use), diuretic, CNS stimulant, raises blood pressure, alleviates aches and
rheumatism, alleviates hay fever/colds,

36. Taking Ephedra with other stimulants can increase the risk of hypertension,
arrhythmias, nervousness, heart attack, or stroke.
Ephedra can increase the speed of your heartbeat. Taking ephedra along with
medications that can cause an irregular heartbeat might cause serious side effects
including heart attack.
Taking ephedra along with methylxanthines might cause side effects such as jitteriness,
nervousness, a fast heartbeat, high blood pressure, and anxiety.
Ephedra can increase blood pressure. Ergot derivatives can also increase blood
pressure. Taking ephedra with ergot derivatives might increase blood pressure too much.
Ephedra contains chemicals that stimulate the body. Some medications used for
depression can increase these chemicals. Taking ephedra with these medications used
for depression might cause serious side effects including fast heartbeat, high blood
pressure, seizures, nervousness, and others