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Interactions with Insulin regular

If you are currently being treated with any of the following medications, you should not use Insulin regular without reading these interactions.

Rosiglitazone (oral)

ADJUST DOSE: Coadministration of a thiazolidinedione in combination with insulin may increase the risk of edema compared to insulin alone. The mechanism is unknown but may involve enhancement of the antinatriuretic and/or peripheral vasodilatory effects of insulin. In a retrospective study of 79 patients who were initially on a thiazolidinedione or insulin separately but were subsequently given both in combination, 20 patients (25.3%) developed edema during the combination, compared to 7 of 71 patients (9.9%) during insulin alone and 1 of 8 patients (12.5%) during thiazolidinedione alone. In a study of 319 type 2 diabetic patients inadequately controlled on twice-daily insulin monotherapy, edema occurred in 13.1% and 16.2% of the patients coadministered rosiglitazone 4 mg/day and 8 mg/day, respectively, compared to 4.7% of those coadministered a matching placebo. The specific combination of rosiglitazone and insulin has also been associated with an increased incidence of heart failure and other cardiovascular adverse events compared to insulin and placebo. Data are derived from three 26-week trials involving 876 patients with type 2 diabetes, including those with longstanding diabetes and a high prevalence of preexisting medical conditions (peripheral neuropathy, retinopathy, ischemic heart disease, vascular disease, and congestive heart failure). An increased incidence of edema, heart failure, and other adverse effects occurred in the patients receiving the combination compared to patients receiving insulin alone. In the studies, patients who experienced heart failure with the combination were on average older, had a longer duration of diabetes, and were mostly on the higher 8 mg daily dosage of rosiglitazone. However, 3 of 10 had no known prior evidence of any underlying cardiac condition. A subsequent study involving 220 type 2 diabetes patients with chronic renal failure found no difference in cardiovascular adverse events among patients receiving the combination and controls receiving insulin with placebo.

MANAGEMENT: When used with insulin, the manufacturer recommends that rosiglitazone dosage not exceed 4 mg/day and that patients be monitored for cardiovascular adverse effects. The combination should be discontinued if there is a lack of response (defined as a reduction in HbA1c or insulin dose after 4 to 5 months) or significant adverse effects occur. Patients should be advised to notify their physician immediately if they experience signs and symptoms of heart failure such as fluid retention, edema, rapid weight gain, or shortness of breath. Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms of hypoglycemia such as headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations.

Gatifloxacin

CONTRAINDICATED: Gatifloxacin may interfere with the therapeutic effects of oral antidiabetic agents and insulin. The use of various quinolones has been associated with disturbances in blood glucose homeostasis possibly stemming from effects on pancreatic beta cell ATP-sensitive potassium channels that regulate insulin secretion. However, hypoglycemia and hyperglycemia have been reported more frequently with gatifloxacin than with other quinolones. Gatifloxacin-induced hypoglycemic episodes have generally occurred within the first 3 days of therapy and sometimes even after the first dose, while hyperglycemia usually occurred 4 to 10 days after initiation of therapy. Death has been reported in severe cases. Coadministration of gatifloxacin with sulfonylureas (most often glyburide) and/or other oral hypoglycemic agents has resulted in severe, refractory hypoglycemia and hypoglycemic coma. Elderly patients and patients with reduced renal function are particularly susceptible.

MANAGEMENT: The use of gatifloxacin is contraindicated in patients with diabetes mellitus. Other quinolones may be safer alternatives in such patients, although all quinolones should be used with caution. Blood glucose should be monitored closely whenever quinolones are prescribed to patients receiving oral antidiabetic agents and/or insulin, especially if they are elderly or have renal impairment. Patients should be counseled to recognize symptoms of hypoglycemia such as headache, dizziness, drowsiness, nausea, tremor, weakness, hunger, excessive perspiration, and palpitations. If hypo- or hyperglycemia occur during quinolone therapy, patients should initiate appropriate remedial therapy immediately, discontinue the antibiotic, and contact their physician.

Levobetaxolol ophthalmic

MONITOR: Beta blockers may inhibit some of the normal physiological response to hypoglycemia. Symptoms of hypoglycemia such as tremors and tachycardia may be absent, making it more difficult for patients to recognize an oncoming episode. In addition, multiple effects on glucose metabolism have been reported, usually with the non-cardioselective beta blockers (e.g., propranolol, pindolol, timolol) but occasionally also with relatively beta-1 selective agents (e.g., metoprolol). Specifically, inhibition of catecholamine-mediated glycogenolysis and glucose mobilization in association with beta blockade can potentiate insulin-induced hypoglycemia in diabetics and delay the recovery of normal blood glucose levels. Prolonged and severe hypoglycemia may occur, although these events have rarely been reported. Significant increases in blood pressure and bradycardia can also occur during hypoglycemia in diabetics treated with insulin and beta blockers due to antagonism of epinephrine's effect on beta-2 adrenergic receptors, which leads to unopposed alpha adrenergic effects including vasoconstriction. Other effects reported with various beta blockers include decreased glucose tolerance and decreased glucose-induced insulin secretion.

MANAGEMENT: In general, cardioselective beta blockers are considered safer than non-cardioselective agents in the treatment of diabetic patients. Nevertheless, caution is advised if they are prescribed to patients treated with insulin or oral antidiabetic agents that can cause hypoglycemia (e.g., insulin secretagogues), as cardioselectivity is not absolute and larger doses of beta-1 selective agents may pose some of the same risks as nonselective agents. Patients should be instructed about the need for regular monitoring of blood glucose levels and be aware that certain symptoms of hypoglycemia such as tremors and tachycardia may be masked. However, other symptoms such as headache, dizziness, drowsiness, nausea, hunger, and sweating may be unaffected. The same precautions are applicable in diabetic patients treated with ophthalmic beta blockers.

Pioglitazone (oral)

MONITOR: Coadministration of a thiazolidinedione in combination with insulin may increase the risk of edema compared to insulin alone. The mechanism is unknown but may involve enhancement of the antinatriuretic and/or peripheral vasodilatory effects of insulin. In a study of 319 type 2 diabetic patients inadequately controlled on twice-daily insulin monotherapy, edema occurred in 13.1% and 16.2% of the patients coadministered rosiglitazone 4 mg/day and 8 mg/day, respectively, compared to 4.7% of those coadministered a matching placebo. Small but statistically significant decreases in hemoglobin and hematocrit were also observed with rosiglitazone compared to placebo. These events were classified as mild to moderate and not considered serious. In a similar study involving 566 patients on stable insulin monotherapy, mild or moderate edema occurred in 12.6% and 17.6% of patients who received pioglitazone 15 mg/day and 30 mg/day, respectively, compared to 7.0% of those who received placebo. Additionally, mild or moderate hypoglycemia occurred in 8% and 15% of patients who received pioglitazone 15 mg/day and 30 mg/day, respectively, compared to 5.0% of those who received placebo. Also, mean change from baseline body weight was 2.3 kg for the 15 mg pioglitazone group and 3.7 kg for the 30 mg pioglitazone group, whereas no change occurred in the placebo group. In a retrospective study of 79 patients who were initially on a thiazolidinedione or insulin separately but were subsequently given both in combination, 20 patients (25.3%) developed edema during the combination, compared to 7 of 71 patients (9.9%) during insulin alone and 1 of 8 patients (12.5%) during thiazolidinedione alone. The mean time to onset of edema was 135 days once combination therapy was initiated. There was no documentation of new-onset or exacerbation of congestive heart failure during combination therapy. However, one patient developed flash pulmonary edema after 2 months of combination therapy and died.

MANAGEMENT: Caution is advised during coadministration of thiazolidinedione and insulin therapy. Patients at risk for heart failure should be closely monitored. Patients should be advised to notify their physician immediately if they experience signs and symptoms of heart failure such as fluid retention, edema, rapid weight gain, or shortness of breath. Patients should also be apprised of the increased risk of hypoglycemia and be alert to potential signs and symptoms of hypoglycemia such as headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations.

Moxifloxacin, Gemifloxacin

MONITOR: Quinolone antibiotics may interfere with the therapeutic effects of oral antidiabetic agents and insulin. The use of certain quinolones such as clinafloxacin, gatifloxacin, temafloxacin, levofloxacin, and moxifloxacin has been associated with disturbances in blood glucose homeostasis possibly stemming from effects on pancreatic beta cell ATP-sensitive potassium channels that regulate insulin secretion. Hypoglycemia and, less frequently, hyperglycemia have been reported during use of quinolones, although the latter may also occur due to underlying infection alone. Coadministration of sulfonylureas (most often glyburide) and/or other oral hypoglycemic agents with ciprofloxacin, norfloxacin, and especially gatifloxacin has occasionally resulted in severe, refractory hypoglycemia and hypoglycemic coma. Elderly patients and patients with reduced renal function are particularly susceptible. Ciprofloxacin may also inhibit the hepatic metabolism of glyburide. Hypoglycemia in association with elevated serum glyburide level occurred in a patient after one week of ciprofloxacin therapy.

MANAGEMENT: Blood glucose should be monitored closely whenever quinolones are prescribed to patients receiving oral antidiabetic agents and/or insulin, especially if they are elderly or have renal impairment. Patients should be counseled to recognize symptoms of hypoglycemia such as headache, dizziness, drowsiness, nausea, tremor, weakness, hunger, excessive perspiration, and palpitations. If hypo- or hyperglycemia occur during quinolone therapy, patients should initiate appropriate remedial therapy immediately, discontinue the antibiotic, and contact their physician.

Conjugated estrogens (vaginal), Amprenavir, Ma huang (ephedra), Ziprasidone, Etonogestrel (implant), Aripiprazole, Atazanavir (oral), Fosamprenavir, Tipranavir, Darunavir, Vorinostat, Arformoterol inhalation, Paliperidone, Temsirolimus

MONITOR: The efficacy of oral hypoglycemic agents and insulin may be diminished by certain drugs, including thiazides and other diuretics, corticosteroids, estrogens, progestins, thyroid hormones, human growth hormone, phenothiazines, atypical antipsychotics, sympathomimetic amines, protease inhibitors, phenytoin, clozapine, megestrol, danazol, isoniazid, asparaginase, pegaspargase, diazoxide, temsirolimus, as well as pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.

MANAGEMENT: Close clinical monitoring of glycemic control is recommended if these drugs are coadministered with antidiabetic agents. Likewise, patients should be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen. Dose adjustments of the hypoglycemic agent may be required.

Perindopril, Escitalopram, Rasagiline, Mecasermin, Mecasermin rinfabate

MONITOR: The hypoglycemic effect of insulin may be potentiated by certain drugs, including ACE inhibitors, anabolic steroids, fibrates, monoamine oxidase inhibitors (MAOIs), salicylates, selective serotonin reuptake inhibitors (SSRIs), sulfonamides, disopyramide, propoxyphene, quinine, and quinidine. These drugs may increase the risk of hypoglycemia by enhancing insulin sensitivity (ACE inhibitors, fibrates); stimulating insulin secretion (salicylates, disopyramide, quinine, quinidine, MAOIs); increasing peripheral glucose utilization (SSRIs, insulin-like growth factor); and/or inhibiting gluconeogenesis (SSRIs, MAOIs, insulin-like growth factor). Clinical hypoglycemia has been reported during use of these agents alone or with insulin and/or insulin secretagogues.

MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if these drugs are coadministered with insulin, particularly in patients with advanced age and/or renal impairment. The insulin dosage may require adjustment if an interaction is suspected. Patients should be apprised of the signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations), how to treat it, and to contact their physician if it occurs. Patients should be observed for loss of glycemic control when these drugs are withdrawn.

Pegvisomant

MONITOR: Treatment with pegvisomant may increase glucose tolerance in some diabetic patients, potentially reducing their dosage requirement of insulin and/or oral antidiabetic agents. The mechanism is pegvisomant antagonism of endogenous growth hormone, the latter of which normally decreases insulin sensitivity and opposes the effects of insulin on carbohydrate metabolism. However, clinically relevant hypoglycemia was not observed in patients with diabetes mellitus who were treated with pegvisomant in premarketing trials.

MANAGEMENT: Close clinical monitoring of glycemic control is recommended if pegvisomant is used in patients treated with insulin and/or oral antidiabetic agents, and the dosages of these agents adjusted as necessary. Likewise, patients may be at risk for hyperglycemia when pegvisomant is withdrawn from their therapeutic regimen.

Garlic

Some authors suggest that garlic may potentiate the hypoglycemic effect of insulin and oral antidiabetic agents, although supportive evidence is scarce. While garlic has been used in the treatment of diabetes, data from small, randomized trials in individuals with and without diabetes have not demonstrated clinically significant effects on blood glucose or insulin sensitivity. There has been a case report describing a potential interaction between chlorpropamide and a curry containing garlic and karela to which the author attributed primarily to the latter ingredient.

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