MANAGEMENT: Coadministration of amiodarone with medications that can cause potassium and/or magnesium disturbances should generally be avoided. Serum electrolytes should be evaluated and any abnormalities corrected prior to initiating therapy with amiodarone. Patients should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsades de pointes such as dizziness, palpitations, or syncope.
bumetanide ↔ metformin
Applies to: bumetanide, metformin
MONITOR: Diuretic-induced renal impairment and dehydration may increase the risk of lactic acidosis in patients who are concomitantly taking metformin. In addition, thiazides and other diuretics may interfere with glucose control by causing hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.
MANAGEMENT: Close clinical monitoring is recommended if diuretics are coadministered with antidiabetic agents. Patients should be advised to monitor their blood glucose and to promptly notify their doctor if they experience possible signs of lactic acidosis (such as malaise, myalgia, respiratory distress, hyperventilation, slow or irregular heartbeat, somnolence, abdominal upset) or loss of glycemic control. Dose adjustments of metformin may be required. Likewise, patients should be observed for hypoglycemia if diuretics are withdrawn from their therapeutic regimen.
amiodarone ↔ atorvastatin
Applies to: amiodarone, atorvastatin
MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of HMG-CoA reductase inhibitors (i.e., statins) that are metabolized by the isoenzyme. Lovastatin and simvastatin are particularly susceptible because of their low oral bioavailability, but others such as atorvastatin and cerivastatin may also be affected. High levels of HMG-CoA reductase inhibitory activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis has also occurred rarely, which may be accompanied by acute renal failure secondary to myoglobinuria and may result in death. Clinically significant interactions have been reported with potent CYP450 3A4 inhibitors such as macrolide antibiotics, azole antifungals, protease inhibitors and nefazodone, and moderate inhibitors such as amiodarone, cyclosporine, danazol, diltiazem and verapamil.
MANAGEMENT: Caution is advised if atorvastatin, cerivastatin, lovastatin, simvastatin, or red yeast rice (which contains lovastatin) is prescribed in combination with a CYP450 3A4 inhibitor. A lower statin dosage may be required in some cases. All patients receiving statin therapy should be advised to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. Fluvastatin, pravastatin, and rosuvastatin are not expected to interact with CYP450 3A4 inhibitors.
aspirin ↔ bumetanide
Applies to: aspirin, bumetanide
Salicylates in anti-inflammatory dosages may blunt the diuretic and natriuretic response to loop diuretics. The interaction has been demonstrated in patients with ascites secondary to liver cirrhosis and in normal volunteers. Investigators theorize that salicylates may inhibit the renal effects of loop diuretics that are mediated by prostaglandins, including increases in sodium excretion, renal blood flow, and plasma renin activity. Since renal prostaglandins are believed to play a major role in the maintenance of renal blood flow and glomerular filtration rate in cirrhotics with ascites, the interaction may be particularly important in this population. No clinical interventions are generally required, but the possibility of a potential interaction should be considered in patients with ascites treated with a loop diuretic and salicylate or salicylate-related product.
No other interactions were found between your selected drugs.
Note: this does not necessarily mean no interactions exist. ALWAYS consult with your doctor or pharmacist.
Other drugs that your selected drugs interact with
* amiodarone interacts with more than 300 other drugs.
* aspirin interacts with more than 200 other drugs.
* atorvastatin interacts with more than 100 other drugs.
* bumetanide interacts with more than 300 other drugs.
* ferrous sulfate interacts with more than 70 other drugs.
* metformin interacts with more than 200 other drugs.
Interactions between your selected drugs and food
amiodarone ↔ food
Applies to: amiodarone
GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered amiodarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 11 nonsmoking, healthy volunteers, grapefruit juice (300 mL with drug administration, then 3 hours and 9 hours later) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amiodarone (17 mg/kg single dose) by 84% and 50%, respectively, compared to water. Formation of the pharmacologically active metabolite, N-desethylamiodarone (N-DEA), was completely inhibited. Clinically, this interaction can lead to altered efficacy of amiodarone, since antiarrhythmic properties of amiodarone and N-DEA appear to differ. In the study, mean increases in PR and QTc intervals of 17.9% and 11.3%, respectively, were observed 6 hours postdose with water, while increases of 10.2% and 3.3%, respectively, were observed after administration with grapefruit juice.
ADJUST DOSING INTERVAL: Food increases the rate and extent of absorption of amiodarone. The mechanism appears to involve the effect of food-induced physiologic changes on drug release from its formulation. In 30 healthy volunteers, administration of a single 600 mg dose of amiodarone following a high-fat meal resulted in a Cmax and AUC that were 3.8 and 2.4 times the respective values under fasting conditions. The time to reach peak plasma concentration (Tmax) was decreased by 37%, indicating an increased rate of absorption. Mean Cmax and AUC for the active metabolite, N-DEA, also increased by 32% and 55%, respectively, but there was no change in the Tmax.
MANAGEMENT: Patients treated with oral amiodarone should avoid consumption of grapefruits and grapefruit juice. In addition, oral amiodarone should be administered consistently with regard to meals.
atorvastatin ↔ food
Applies to: atorvastatin
GENERALLY AVOID: In small studies, the consumption of large amounts of grapefruit juice was associated with significantly increased plasma concentrations of lovastatin and simvastatin and their active acid metabolites. Similar results but to a lesser degree were reported for atorvastatin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. Increased risk of musculoskeletal toxicity (myopathy with grossly elevated creatine kinase and rhabdomyolysis with or without acute renal failure secondary to myoglobinuria) has been associated with high levels of HMG-CoA reductase inhibitory activity in plasma.
ADJUST DOSING INTERVAL: Fibers such as oat bran and pectin may diminish the pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption from the gastrointestinal tract.
MANAGEMENT: Patients receiving therapy with atorvastatin, lovastatin, simvastatin, or red yeast rice (which contains lovastatin) should be advised to avoid the regular consumption of large amounts of grapefruits and grapefruit juice (the manufacturers of simvastatin and lovastatin advise against ingestion of greater than 1 quart per day). Pravastatin and fluvastatin are metabolized by other enzymes and may be preferable alternatives in some individuals. Patients should be advised to immediately notify their physician if they experience unexplained muscle pain, tenderness, or weakness. In addition, they should either refrain from the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the administration times by at least 2 to 4 hours.
ferrous sulfate ↔ food
Applies to: ferrous sulfate
Food taken in conjunction with oral iron supplements may reduce the bioavailability of the iron. However, in many patients intolerable gastrointestinal side effects occur necessitating administration with food. Some studies suggest administration of iron with ascorbic acid may enhance bioavailability. Ideally, iron products should be taken on an empty stomach, but if this is not possible, administer with meals and monitor the patient more closely for a subtherapeutic effect.
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