The effect of drugs on a person may be different than expected because that drug interacts with another drug the person is taking (drug - drug interaction), food, beverages, dietary supplements the person is consuming (drug - nutrient/food interaction) or another disease the person has (drug - disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own.
Medications & Interactions With Alcohol
Pain Medications / Muscle Relaxants
1. Used together will increase the side effects: impairment of speech, sedation, lethargy.
2. Alcohol with Acetaminophen (Tylenol) may result in liver damage. Use together sparingly.
3. Non-steroidal anti-inflammatory drugs (Aspirin, Ibuprofen, Naproxen - with alcohol may upset your stomach or cause irritation and bleeding. This combination can also cause kidney failure.
4. Alcohol can increase the drowsiness side effects of muscle relaxants.
Sedatives (Sleeping Aids)
1. Alcohol taken with sedatives will increase the drowsiness effects and cause breathing to decrease.
Anti-anxiety / Anti-depressants
1. Alcohol increases the effects of Diazepam (Valium).
2. Alcohol with Zanax (Alprazolam), Ativan (Lorazepam), and Valium will increase the drowsiness side effects.
3. Alcohol with tricyclic antidepressants (Amitriptyline, Amoxapine, Clomipramine, Despramine, Doxepin, Imipramine, Nortriptyline, Trimipramine) can likely cause blackouts.
4. Alcohol with Mirtazapine (Remeron) increases psychomotor (coordinated muscle movement) impairment.
5. Alcohol with Bupropin (Buspar) lowers the seizure threshold.
Drugs That Lower Blood Pressure
1. Alcohol with vasocilators (Nitroglycerin, Methyldopa, Hydralazine) can decrease blood pressure more.
2. Verapamil with alcohol can increase alcohol levels.
1. Alcohol and Aspirin can irritate the stomach and can cause GI bleeding. Together, the effect is increased.
2. Alcohol with Warfarin can either increase or decrease the anticoagulant effects of Warfarin.
1. Alcohol with oral agents (Sulfonylureas like Glyburide, Glipizide) can cause a decrease in blood sugar or can cause sweating, flusing, palpatations, headaches.
2. Alcohol and insulin can decrease blood sugar.
1. Many antifungals and antibiotics (Septra, Bactrim, Ketoconazole, Griseofulvin, Isoniazid, Metronidazole) taken with alcohol can cause severe nausea, flushing or headaches.
Medications & Interactions With Foods
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 associated with concomitant 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 invitro 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.
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).
Antidepressant activity of monoamine oxidase inhibitors (MAOIs) was initially noted in the 1950s. Although older monoamine oxidase inhibitors (MAOIs) are effective in the treatment of depressive disorders, they are under-utilized in clinical practice due to main concerns about interaction with tyramine-containing food (matured cheese, red vine, ripped bananas, yogurt, shrimp paste and salami) or so called cheese reaction, since they are capable of producing hypertensive crisis in patients taking MAOIs.
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).
Analgesics and Antipyretics
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.
Anti-tubercular drugs like isoniazid have been associated with tyramine and histamine interactions. Inhibition of monoamine oxidase and histaminase by isoniazid can cause significant drug-food interactions. Food greatly decreases isoniazid bioavailability. Oleanolic acid, a triterpenoid exists widely in food, medicinal herbs and other plants, has antimycobacterial activity against the Mycobacterium tuberculosis, when administered with isoniazid, it exerts synergistic effect.
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.
Recent evidence pointed out the role of gastric acid secretion on the subsequent intestinal absorption of thyroxine in relation with the timing of food ingestion as well as with pH impairment associated to frequent gastric disorders like Helicobacter pylori infection and gastric atrophy. Levothyroxine is a derivative of thyroxine. Grapefruit juice may slightly delay the absorption of levothyroxine, but it seems to have only a minor effect on its bioavailability. Accordingly, the clinical relevance of the grapefruit juice-levothyroxine interaction is likely to be small.
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.
A large number of drugs are introduced every year. Food-drug interactions can produce negative effects in safety and efficacy of drug therapy, as well in the nutritional status of the patient. Generally speaking, drug interactions are to be avoided, due to the possibility of poor or unexpected outcomes. Like food, drugs taken by mouth must be absorbed through the lining of the stomach or the small intestine. Consequently, the presence of food in the digestive tract may reduce absorption of a drug. Often, such interactions can be avoided by taking the drug 1 hour before or 2 hours after eating. Like drugs, foods are not tested as comprehensively so they may interact with prescription or over-the-counter drugs.
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