Methylprednisoloneinteractions

Local Anesthetics: The toxic effects of local anesthetics are additive. Monitor for neurologic and cardiovascular effects when additional local anesthetics are administered. Monoamine Oxidase Inhibitors and Tricyclic Antidepressants: Administration of Bupivacaine Hydrochloride and Epinephrine Injection to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided.

Ergot-Type Oxytocic Drugs: Concurrent administration of Bupivacaine Hydrochloride and Epinephrine Injection and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.

Nonselective Beta-Adrenergic Antagonists: Administration of Bupivacaine Hydrochloride and Epinephrine Injection (containing a vasoconstrictor) in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided.

Drugs Associated with Methemoglobinemia: Patients are at increased risk of developing methemoglobinemia when concurrently exposed to nitrates, nitrites, local anesthetics, antineoplastic agents, antibiotics, antimalarials, anticonvulsants, and other drugs.

Potent Inhalation Anesthetics: Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine are used in patients during or following the administration of potent inhalation anesthetics.

7.1 Local Anesthetics

The toxic effects of local anesthetics are additive. If coadministration of other local anesthetics with Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection cannot be avoided, monitor patients for neurologic and cardiovascular effects related to local anesthetic systemic toxicity.

7.2 Monoamine

Oxidase Inhibitors and Tricyclic Antidepressants The administration Bupivacaine Hydrochloride and Epinephrine Injection to patients receiving monoamine oxidase inhibitors, or tricyclic antidepressants may produce severe, prolonged hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient's hemodynamic status is essential.

7.3 Ergot-Type

Oxytocic Drugs Concurrent administration of Bupivacaine Hydrochloride and Epinephrine Injection and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents. Avoid use of Bupivacaine Hydrochloride and Epinephrine concomitantly with ergot-type oxytocic drugs.

7.4 Nonselective

Beta-Adrenergic Antagonists Administration of Bupivacaine Hydrochloride and Epinephrine Injection (containing a vasoconstrictor) in patients receiving nonselective beta-adrenergic antagonists may cause severe hypertension and bradycardia. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful monitoring of the patient's blood pressure and heart rate is essential.

7.5 Drugs Associated with

Methemoglobinemia Patients who are administered Bupivacaine Hydrochloride Injection/Bupivacaine Hydrochloride and Epinephrine Injection are at increased risk of developing methemoglobinemia when concurrently exposed to following drugs, which could include other local anesthetics. Examples of Drugs Associated with Methemoglobinemia: Class Examples Nitrates/Nitrites nitric oxide, nitroglycerin, nitroprusside, nitrous oxide Local anesthetics articaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, procaine, ropivacaine, tetracaine Antineoplastic agents cyclophosphamide, flutamide, hydroxyurea, isofamide, rasburicase Antibiotics dapsone, nitrofurantoin, para-aminosalicylic acid, sulfonamides Antimalarials chloroquine, primaquine Anticonvulsants phenobarbital, phenytoin, sodium valproate Other drugs acetaminophen, metoclopramide, quinine, sulfasalazine

7.6 Potent Inhalation

Anesthetics Serious dose-related cardiac arrhythmias may occur if preparations containing a vasoconstrictor such as epinephrine (e.g., Bupivacaine Hydrochloride and Epinephrine Injection) are used in patients during or following the administration of potent inhalation anesthetics.

7.7 Phenothiazines and

Butyrophenones Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of Bupivacaine Hydrochloride and Epinephrine Injection and these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.

Drug Interactions Aminoglutethimide: Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression. Amphotericin B injection and potassium-depleting agents: When corticosteroids are administered concomitantly with potassium depleting agents (e.g., amphotericin B, diuretics), patients should be observed closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.

Antibiotics: Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance (see PRECAUTIONS: Drug Interactions, Hepatic Enzyme Inhibitors ).

Anticholinesterases: Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy. Anticoagulants, oral: Co-administration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.

Antidiabetics: Because corticosteroids may increase blood glucose concentration, dosage adjustments of antidiabetic agents may be required.

Antitubercular drugs: Serum concentrations of isoniazid may be decreased.

Cholestyramine: Cholestyramine may increase the clearance of oral corticosteroids.

Cyclosporine: Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.

Digitalis glycosides: Patients on digitalis glycosides may be at risk of arrhythmias due to hypokalemia. Estrogens, including oral contraceptives: Estrogens may decrease the hepatic metabolism of certain corticosteroids, thereby increasing their effect. Hepatic Enzyme Inducers (e.g., barbiturates, phenytoin, carbamazepine, rifampin): Drugs which induce cytochrome P450 3A4 enzyme activity may enhance the metabolism of corticosteroids and require that the dosage of the corticosteroid be increased. Hepatic Enzyme Inhibitors (e.g., ketoconazole, macrolide antibiotics such as erythromycin and troleandomycin): Drugs which inhibit cytochrome P450 3A4 have the potential to result in increased plasma concentrations of corticosteroids.

Ketoconazole: Ketoconazole has been reported to significantly decrease the metabolism of certain corticosteroids by up to 60%, leading to an increased risk of corticosteroid side effects. Nonsteroidal anti-inflammatory drugs (NSAIDs): Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.

Skin tests: Corticosteroids may suppress reactions to skin tests.

Vaccines: Patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible (see WARNINGS: Infections, Vaccinations ).

Clinically Significant Drug Interactions The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged hypertension. Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential. Concurrent administration of vasopressor drugs (for the treatment of hypotension related to obstetric blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.