Digestive System

Adverse Reactions to Drugs & Supplements

Summary

Most of the time, medicines make our lives better. They reduce aches and pains, fight infections, and control problems such as high blood pressure or diabetes. But medicines can also cause unwanted reactions.

One problem is interactions, which may occur between

Two drugs, such as aspirin and blood thinners
Drugs and food, such as statins and grapefruit
Drugs and supplements, such as ginkgo and blood thinners
Drugs and diseases, such as aspirin and peptic ulcers

Interactions can change the actions of one or both drugs. The drugs might not work, or you could get side effects.

Side effects are unwanted effects caused by the drugs. Most are mild, such as a stomach aches or drowsiness, and go away after you stop taking the drug. Others can be more serious.

Drug allergies are another type of reaction. They can be mild or life-threatening. Skin reactions, such as hives and rashes, are the most common type. Anaphylaxis, a serious allergic reaction, is more rare.

When you start a new prescription or over-the-counter medication, make sure you understand how to take it correctly. Know which other medications and foods you need to avoid. Ask your health care provider or pharmacist if you have questions.

Fruit Juices

MedlinePlus-Dietary Supplements

MedlinePlus-Antioxidants

MedlinePlus-Vitamins

Among all fruit juices, grape fruit juice (GFJ) possesses high interaction with almost all types of drugs. The juice modifies the body’s way of metabolizing the medication, affecting the liver’s ability to work the drug through a person’s system. Taniguchi in 2007 reported a case of purpura (blood spots, pooling of blood underneath the skin) associated with the ingestion of cilostazol, aspirin and grapefruit juice in 79 years old man. His purpura disappeared upon cessation of grapefruit juice, although his medication was not altered. The most probable cause of his purpura is an increase in the blood level of cilostazol because of the inhibition of cilostazol metabolism by components of grapefruit juice; Taniguch.
Numerous reports have documented drug interactions with GFJ that occur via inhibition of CYP3A enzymes. Furanocoumarins present in GFJ inhibit the intestinal CYP 3A4 and have been shown to increase the oral bioavailability of medications that are CYP 3A4 substrates like Felodipine, midazolam, cyclosporine and raise their concentrations above toxic levels.
GFJ is generally contraindicated to patients taking psychotropics and it is advised to inform patients about described interaction. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol. The overall exposure of some drugs can be increased by more than fivefold when taken with GFJ and increase the risk of adverse effects.
With new anticonvulsants, serum iron and sodium need to be monitored. Additionally, users are advised to avoid drinking grape fruit juice within 1-2 hr(s) of taking these anticonvulsants. Furanocoumarines and active bioflavonoids present in GFJ are also inhibitors of OATP and when ingested concomitantly, can reduce the oral bioavailability of the OATP substrate, fexofenadine. Overall, a series of flavonoids present in GFJ are identified as esterase inhibitors, of which kaempferol and naringenin are shown to mediate pharmacokinetic drug interaction with most of the calcium channel antagonist and the statin groups of drugs such as enalapril and lovastatin due to their capability of esterase inhibition.
Cholesterol-lowering agent lovastatin should be taken with food to enhance gastrointestinal absorption and bioavailability. The absorption of rosuvastatin, another anti-hyper lipidemic agent, was significantly decreased in the fed state compared with the fasting state, which suggests that rosuvastatin should be administered on an empty stomach.
Simvastatin, Ezetimibe, pravastatin and fluvastatin may be taken without regards to food. However, high fiber diets may lower the efficacy of these drugs. Concomitant administration of statins with food may alter statin pharmacokinetics or pharmacodynamics, increasing the risk of adverse reactions such as myopathy or rhabdomyolysis or reducing their pharmacological action. Consumption of pectin or oat bran together with Lovastatin reduces absorption of the drug, while alcohol intake does not appear to affect the efficacy and safety of Fluvastatin treatment.

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Antihypertensive Drugs

MedlinePlus-Blood Pressure Medicines

Patients placed on anti hypertensive drugs will benefit from concomitant moderate sodium restricted diets. Propranolol serum levels may be increased if taken with rich protein food. A change in diet from high carbohydrates/low protein to low carbohydrate/high protein may result in increased oral clearance. Smoking may decrease its plasma levels of by increasing its metabolism. The intestinal absorption of celiprolol (beta-blocker) is inhibited when it is taken with orange juice. Hesperidin, present in orange juice, is responsible for the decreased absorption of celiprolol. The absorption of ACEs inhibitors is increased when taken on an empty stomach. While GFJ increases the bioavailability of felodipine (Ca2 channel blocker).
Licorice extract, a common ingredient of dietary supplement contains glycyrrhizin and glycyrrhetinic acid. It is a potent inhibitor of 11- bet- hydroxyl steroid dehydrogenase, it increases excess of cortisol to mineralocorticoid receptors causing sodium retention and potassium depletion, so it may interfere with various medicines including antihypertensive and antiarrhythmic agents. A high intake of liquorice can cause hypermineralocorticoidism with sodium retention and potassium loss, oedema, increased blood pressure and depression of the renin-angiotensin-aldosterone system. Studies showed that a daily consumption of glycyrrhizic acid of 95 mg or more caused an increase in blood pressure. A practical guideline for an acceptable daily intake of glycyrrhizic acid seems to be 9.5 mg a day. This means no more than 10-30g liquorice and no more than half a cup of liquorice tea a day.

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Antibiotics

MedlinePlus-Antibiotics

Antibiotics are widely prescribed in medical practice. Many of them induce or are subject to interactions that may diminish their anti-infectious efficiency or elicit toxic effects. Food intake can influence the effectiveness of an antibiotic. Avoid co-administration of antibiotics with milk products which are rich sources of divalent ions, such as calcium and magnesium that complex with some antibiotics and prevent their absorption. The intake of dairy products, however, needs to be monitored and encouraged with appropriate consideration of specific antibiotics involved.
A number of studies give evidence that fluoroquinolones forming slightly soluble complex with metal ions of food show reduced bioavailability. Casein and calcium present in milk decrease the absorption of ciprofloxacin. The effect of interaction of five fruit juices on the dissolution and absorption profiles of ciprofloxacin tablets were determined. It was found that the absorption of ciprofloxacin (500 mg) tablets can be reduced by concomitant ingestion of the GFJ. Therefore, to avoid drug therapeutic failures and subsequent bacterial resistance as a result of sub-therapeutic level of the drug in the systemic circulation, ingestion of the juice with ciprofloxacin should be discouraged. Azithromycin absorption is decreased when taken with food, resulting in a 43% reduction in bioavailability. Tetracycline should be taken one hour before or two hours after meals, and not taken with milk because it binds calcium and iron, forming insoluble chelates, and influencing its bioavailability. The effect of milk added to coffee or black tea on the bioavailability of tetracycline was evaluated in healthy individuals. Results showed that even a little quantity of milk containing extremely small amounts of calcium severely impair the absorption of the drug, so that the presence of this metal ion should be carefully controlled in order to avoid decreasing the available tetracycline.
Food-drug interactions may reduce the bioavailability of drugs taken after meals (negative food effects). However, enteric-coated tablets that start to disintegrate when they reach the middle-to-lower region of the small intestine could reduce negative food effects. Results indicated that food-drug interactions were avoided by separating the main absorption site of drugs from that of food components.

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Analgesics and Antipyretics (Pain Reliever)

MedlinePlus-Pain Relievers

Analgesics and antipyretics are used to treat mild to moderate pain and fever. For rapid relief, acetaminophen should be taken in an empty stomach because food may slow the body absorption of acetaminophen. Co-administration of acetaminophen with pectin delays its absorption and onset. NSAIDs like ibuprofen, naproxen, ketoprofen and others can cause stomach irritation and thus they should be taken with food or milk. Avoid or limit the use of alcohol because chronic alcohol use can increase the risk of liver damage or stomach bleeding. The absorption of ibuprofen and oxycodone when given in the combination tablet was affected by the concomitant ingestion of food.
The Cmax and AUC0-alpha of ibuprofen were significantly increased after single and multiple doses of Coca-Cola, thereby indicating increased extent of absorption of ibuprofen. The daily dosage and frequency of ibuprofen must be reduced when administered with Coca-Cola. Food intake did not appear to affect the extent of absorption (ie, total exposure) of oral Diclofenac potassium soft gelatin capsule at doses.

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Antihistamines

MedlinePlus-Cold and Cough Medicines

Fexofenadine, loratadine, rupatadine, cimetidine cetirizine, are all antihistamines. It is best to take prescription antihistamines on an empty stomach to increase their effectiveness. Rupatadine is commonly used for the management of diseases with allergic inflammatory conditions. A study indicates that concomitant intake of food with a single 20 mg oral dose of rupatadine exhibits a significant increase in rupatadine bioavailability. Cimetidine is given with food to assist the maintenance of a therapeutic blood concentration. A fraction of cimetidine is absorbed in the presence of food, allowing the remaining drug to be dissolved once the gut is cleared. Thus, therapeutic levels are maintained throughout the dosing interval. A study was conducted on a latest molecule esomeprazole (acid-reducer), and it was observe that its bioavailability was reduced when taken within 15 min before eating a high-fat meal vs. that while fasting.

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Antitumor and Anticancer

MedlinePlus-Cancer Chemotherapy

Mercaptopurine is a purine analog used for acute lymphoblastic leukemia and chronic myelogenous leukemias. Since it is inactivated by xanthine oxidase (XO), concurrent intake of substances containing XO may potentially reduce bioavailability of mercaptopurine. Cow’s milk is known to contain a high level of XO. This interaction may be clinically significant. Therefore most patients should try to separate the timing of taking mercaptopurine and drinking milk.
Tamoxifen is a successful anti-tumor agent. If taken with sesame seeds, it negatively interferes with tamoxifen in inducing regression of established MCF-7 tumor size but beneficially interacts with tamoxifen on bone in ovariectomized athymic mice. Xue et al. had compared the influence of dietary elements on cancer progression, chemotherapy efficacy, and toxicity, particularly severe, late onset diarrhea related to irinotecan (CPT-11) treatment. They suggest that glutamine and n-3 fatty acids might be potentially useful adjuncts with CPT-11 treatment.

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Cannabinoids

U.S. National Library of Medicine - PubMed Center

PubMed Central® (PMC) is a free full-text archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health's National Library of Medicine (NIH/NLM). In keeping with NLM’s legislative mandate to collect and preserve the biomedical literature, PMC serves as a digital counterpart to NLM’s extensive print journal collection. PMC was developed and is managed by NLM’s National Center for Biotechnology Information (NCBI). PMC makes all content free to read (in some cases, following an embargo period), as NLM believes that the best way to ensure the accessibility and viability of digital material over time is through consistent and active use of the archive.

Contraindications and Adverse Reactions

Digestive System

Table of Contents

Body Location

Food & Drug Reaction

Cannabinoids

Astragalus

Fullerene Carbon 60

Hydrogen Rich Water (HRW)

Adverse Reactions to Drugs & Supplements

Summary

Fruit Juices

Antihypertensive Drugs

Antibiotics

Analgesics and Antipyretics (Pain Reliever)

Antihistamines

Antitumor and Anticancer

Cannabinoids

U.S. National Library of Medicine - PubMed Center

Cannabinoid Related - FDA Recalls, Market Withdrawals and Safety Alerts

U.S. National Institutes of Health - MedlinePlus

National Center for Complementary and Integrative Health

Astragalus

U.S. National Library of Medicine - PubMed Center

Astragalus Related - FDA Recalls, Market Withdrawals and Safety Alerts

U.S. National Institutes of Health - MedlinePlus

National Center for Complementary and Integrative Health

Fullerene Carbon 60

U.S. National Library of Medicine - PubMed Center

Carbon 60 Related - FDA Recalls, Market Withdrawals and Safety Alerts

U.S. National Institutes of Health - MedlinePlus

National Center for Complementary and Integrative Health

Hydrogen Rich Water (HRW)

U.S. National Library of Medicine - PubMed Center

HRW Related - FDA Recalls, Market Withdrawals and Safety Alerts

U.S. National Institutes of Health - MedlinePlus

National Center for Complementary and Integrative Health

Digestive System

The Anus and Rectum

The Appendix and Large Intestine

The Esophagus

The Gallbladder

The Appendix and Large Intestine

The Liver

The Pancreas

The Anus and Rectum

The Small Intestine

The Stomach