How Does The Grapefruit-Drug Interaction Occur?Grapefruit contains large amounts of the flavanoid naringin. Furanocoumarins like bergamottin and dihydroxybergamottin are also present in the fruit. These active ingredients of fresh grapefruit and grapefruit juice interact with and inhibit the CYP3A4 enzyme, which inactivates or metabolizes several drugs in the intestinal lining and the liver. As a consequence, the blood levels of the drugs metabolized by the enzyme increase. This increased serum drug level is the cause for severe adverse effects.
What Are The Possible Drug Interactions With Grapefruit?Food-drug interaction is an interaction of a drug with some food when taken together. The possible drug interactions with grapefruit which could be harmful are as follows:
- Statins - HMG CoA Reductase Inhibitors
- Calcium Channel Blockers
- Antiallergic Drugs
- Hypnotics and Anti-anxiety Drugs
- Cardiovascular Drugs/Anti-arrhythmic Drugs
- Drugs used in Organ Transplantation
- Other Drugs
Statins like simvastatin, atorvastatin, pravastatin and lovastatin inhibit the enzyme HMG CoA reductase and help in the treatment of high cholesterol levels. Grapefruit juice when taken with atorvastatin, simvastatin, and lovastatin increases the serum drug levels by reducing the breakdown of the drugs. The levels of fluvastatin, rosuvastatin, or pravastatin are however not affected since they are metabolized differently. High blood levels of statins achieved with grapefruit juice may produce a better effect in reducing cholesterol levels but also have a potential to cause a serious adverse effect called rhabdomyolysis (breakdown of skeletal muscle).
Calcium Channel Blockers:
Dihydropyridine derivatives like felodipine, nifedipine, and nitradepine are calcium channel blockers which are used for the treatment of high blood pressure. Felodipine is normally converted into an inactive metabolite dehydrofelodipine by the CYP3A4 enzyme. Grapefruit juice inhibits the enzyme thereby increasing the plasma level of the drug. Elevated drug levels in the blood will produce increased heart rate and severe lowering of blood pressure as adverse effects.
These drugs are used for the treatment of allergies and allergic reactions that are produced in the body. The antihistaminic drug fexofenadine is commonly used to provide relief from symptoms of seasonal allergies. Grapefruit juice reduces the absorption of fexofenadine by blocking certain proteins called transporters that mediate the absorption. Grapefruit juice also increases the level of an antihistamine called terfenadine due to inhibition of the CYP3A4 enzyme. This may result in a cardiac complication called torsades de pointes.
Hypnotics and Anti-anxiety Drugs:
Midazolam and triazolam are drugs that belong to a class of benzodiazepines and are used as hypnotic agents to induce sleep. Buspirone is used as an anti-anxiety drug. Grapefruit juice is found to increase the side effects of these drugs like drowsiness and dizziness since it increases their blood levels.
Cardiovascular Drugs/Anti-arrhthymic Drugs:
Drugs which are used in the treatment of arrhythmias (abnormal heart rhythms) are known as antiarrthymic drugs. Amiodarone, disopyramide and quinidine are some of the anti-arrhythmic drugs whose toxic effects increase when combined with grapefruit intake. Carvedilol, which is used in the treatment of congestive heart failure, should not be taken with grapefruit as the fruit may decrease the metabolism of the drug and increase its levels.
Drugs Used in Organ TransplantationImmunosuppressants are drugs which inhibit immune response in the body and are used in the treatment of autoimmune disorders and during transplantation of organs. Cyclosporin when given with grapefruit juice may increase the damage caused to the kidneys and bone marrow due to higher blood levels.
Other Important Drug Interactions with Grapefruit:
- Antibiotics like erythromycin which help fight against certain bacterial infections are made more potent and can cause side effects when taken with grapefruit.
- The antiplatelet drug clopidogrel has to be activated by enzymes to bring about its effect. Grapefruit juice may inhibit the enzymes and reduce the effect of clopidogrel.
- Grapefruit juice when taken with drugs that are used in the treatment of malaria like primaquine may enhance the side effects of primaquine.
- Drugs that are used in the treatment of cancer such as dasatinib, everolimus, eroltinib, lapatinib when administered with grapefruit may cause bone marrow and kidney damage and may increase the heart rate that could lead to sudden death of the individual.
- Grapefruit juice may enhance drowsiness produced by medicines used in the treatment of cough and cold that contain dextromethorphan, and problems with breathing due to opioid painkillers.
- The blood sugar lowering effect of the anti-diabetes drug repaglinide may be enhanced by grapefruit juice.
How To Prevent Grapefruit - Drug InteractionGrapefruit-Drug interaction can be prevented by following measures:
- Consult a doctor or a pharmacist about whether you can have fruit juice while using the prescribed medicines.
- Read the information leaflet that is given with the drug to know whether the drug shows any possible interactions with grapefruit.
- It is important that people are educated and are made aware about the serious effects that the drugs cause when taken with fruit juices.
- If any adverse effect is reported, the patient must be taken to the hospital immediately and recovery measures should be provided as soon as possible.