Diabetes Mellitus

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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Warfarin - Blood Thinner

MedlinePlus-Blood Thinners

Warfarin is commonly used to treat or prevent thromboembolic events. Patients taking warfarin are at particular risk of interactions with dietary supplements, yet approximately 30% use herbal or natural product supplements on a regular basis. There is a possible interaction between warfarin and a high-protein diet. The potential for increased dietary protein intake to raise serum albumin levels and/or cytochrome P450 activity has been postulated as mechanisms for the resulting decrease in international normalized ratio (INRs).
Some vegetables (broccoli, Brussels sprouts, kale, parsley, spinach, and others) are high in vitamin K. Eating large quantities or making sudden changes in the amounts eaten of these vegetables, interferes with the effectiveness and safety of warfarin therapy.
Eating charbroiled food may decrease warfarin activity, while eating cooked onions may increase warfarin activity. Soy foods have been reported both to increase and to decrease warfarin activity. The significance of these last three interactions remains unclear. The combination of warfarin administration and cranberry juice ingestion appeared to be associated with an elevated INR without bleeding in elderly patient.
A number of studies have been documented on the interaction of warfarin and cranberry juice. Cranberry juice is a flavonoid, which has been shown to induce, inhibit, or act as a substrate for the biosynthesis of several cytochrome P-450 (CYP) isoenzymes. Specifically, cranberry juice may inhibit the activity of CYP2C9, the primary isoenzyme involved in the metabolism of S-warfarin. It was suggested that cranberry juice increased the International Normalized Ratio (INR) of patients taking warfarin, but neither clearly identified cranberry juice as the sole cause of INR elevation. If warfarin sodium is ingested with leafy green vegetables, the hypoprothrombinemic effect of warfarin may be decreased and thromboembolic complications may develop.

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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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Antidiabetics

MedlinePlus-Diabetes Medicines

Glimepiride is an antidiabetic and a new generation sulfonylurea derivative should be administered with breakfast or the first main meal of the day. It has absolute bioavailability and the absence of food interaction guarantee highly reproducible pharmacokinetics. Immediate release glipizide should be taken 30 minutes before meals. However, extended release tablets should be taken with breakfast. The maximum effectiveness of acarbose, an alpha-glucosidase inhibitor is attained when the drug is taken immediately at the start of each meal (not half an hour before or after), because it delays the carbohydrate absorption by inhibiting the enzyme alpha-glucosidase.

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Analgesics and Antipyretics

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.

Find out more - NIH

Cannabinoids

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Cannabinoid Related - FDA Recalls, Market Withdrawals and Safety Alerts

The list below provides information gathered from press releases and other public notices about certain recalls of FDA-regulated products. Not all recalls have press releases or are posted on this page. Certain product recalls sometimes merit expanded coverage due to the impact they have on public health. This section includes details of FDA's involvement in investigating recalls, a means to search recalled products, and information for consumers and industry representatives.

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National Center for Complementary and Integrative Health

The National Center for Complementary and Integrative Health (NCCIH) part of the National Institutes of Health, is the Federal Government’s lead agency for scientific research on the diverse medical and health care systems, practices, and products that are not generally considered part of conventional medicine. NCCIH was formerly known as the National Center for Complementary and Alternative Medicine.

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