Diltiazem hydrochloride injection precautions: Difference between revisions
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==PRECAUTIONS== | |||
===General=== | |||
Diltiazem hydrochloride is extensively metabolized by the liver and excreted by the kidneys and in bile. The drug should be used with caution in patients with impaired renal or hepatic function (see [[Diltiazem hydrochloride injection warnings|WARNINGS]]). High intravenous dosages (4.5 mg/kg tid) administered to dogs resulted in significant bradycardia and alterations in AV conduction. In subacute and chronic dog and rat studies designed to produce toxicity, high oral doses of diltiazem were associated with hepatic damage. In special subacute hepatic studies, oral doses of 125 mg/kg and higher in rats were associated with histological changes in the liver, which were reversible when the drug was discontinued. In dogs, oral doses of 20 mg/kg were also associated with hepatic changes; however, these changes were reversible with continued dosing. | |||
Dermatologic events progressing to erythema multiforme and/or exfoliative dermatitis have been infrequently reported following oral diltiazem. Therefore, the potential for these dermatologic reactions exists following exposure to intravenous diltiazem. Should a dermatologic reaction persist, the drug should be discontinued. | |||
===Drug Interactions=== | |||
Due to potential for additive effects, caution is warranted in patients receiving diltiazem hydrochloride injection concomitantly with other agent(s) known to affect cardiac contractility and/or SA or AV node conduction (see [[Diltiazem hydrochloride injection warnings|WARNINGS]]). | |||
As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem hydrochloride undergoes extensive metabolism by the [[cytochrome P-450 ]]mixed function oxidase system. Although specific pharmacokinetic drug-drug interaction studies have not been conducted with single intravenous injection or constant rate intravenous infusion, coadministration of diltiazem hydrochloride injection with other agents which primarily undergo the same route of biotransformation may result in competitive inhibition of metabolism. | |||
====Digitalis. ====Intravenous diltiazem has been administered to patients receiving either intravenous or oral [[digitalis ]]therapy. The combination of the two drugs was well tolerated without serious adverse effects. However, since both drugs affect AV nodal conduction, patients should be monitored for excessive slowing of the heart rate and/or AV block. | |||
====Beta-blockers. ====Intravenous diltiazem has been administered to patients on chronic oral [[beta-blocker ]]therapy. The combination of the two drugs was generally well tolerated without serious adverse effects. If intravenous diltiazem is administered to patients receiving chronic oral [[beta-blocker]] therapy, the possibility for [[bradycardia]], [[AV block]], and/or depression of contractility should be considered (see[[Diltiazem hydrochloride injection contraindications| CONTRAINDICATIONS]]). Oral administration of diltiazem with [[propranolol ]]in five normal volunteers resulted in increased [[propranolol ]]levels in all subjects and bioavailability of [[propranolol ]]was increased approximately 50%. In vitro, propranolol appears to be displaced from its binding sites by diltiazem. | |||
====Anesthetics.==== The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with [[anesthetics ]]may be potentiated by [[calcium channel blockers]]. When used concomitantly, anesthetics and calcium blockers should be titrated carefully. | |||
====Cyclosporine.==== A pharmacokinetic interaction between diltiazem and [[cyclosporine ]]has been observed during studies involving renal and cardiac transplant patients. In renal and [[cardiac transplant]] recipients, a reduction of [[cyclosporine ]]dose ranging from 15% to 48% was necessary to maintain [[cyclosporine ]]trough concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted or discontinued. | |||
The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated. | |||
====Carbamazepine.==== Concomitant administration of oral diltiazem with [[carbamazepine ]]has been reported to result in elevated plasma levels of [[carbamazepine ]](by 40 to 72%), resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction.<ref name="dailymed.nlm.nih.gov">{{Cite web | last = | first = | title = DILTIAZEM HYDROCHLORIDE INJECTION [AKORN, INC.] | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=81c5cf23-a6f8-454a-9575-d01edf49ed34 | publisher = | date = | accessdate = 5 March 2014 }}</ref> | |||
Revision as of 21:10, 5 March 2014
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Abdurahman Khalil, M.D. [2]
PRECAUTIONS
General
Diltiazem hydrochloride is extensively metabolized by the liver and excreted by the kidneys and in bile. The drug should be used with caution in patients with impaired renal or hepatic function (see WARNINGS). High intravenous dosages (4.5 mg/kg tid) administered to dogs resulted in significant bradycardia and alterations in AV conduction. In subacute and chronic dog and rat studies designed to produce toxicity, high oral doses of diltiazem were associated with hepatic damage. In special subacute hepatic studies, oral doses of 125 mg/kg and higher in rats were associated with histological changes in the liver, which were reversible when the drug was discontinued. In dogs, oral doses of 20 mg/kg were also associated with hepatic changes; however, these changes were reversible with continued dosing. Dermatologic events progressing to erythema multiforme and/or exfoliative dermatitis have been infrequently reported following oral diltiazem. Therefore, the potential for these dermatologic reactions exists following exposure to intravenous diltiazem. Should a dermatologic reaction persist, the drug should be discontinued.
Drug Interactions
Due to potential for additive effects, caution is warranted in patients receiving diltiazem hydrochloride injection concomitantly with other agent(s) known to affect cardiac contractility and/or SA or AV node conduction (see WARNINGS). As with all drugs, care should be exercised when treating patients with multiple medications. Diltiazem hydrochloride undergoes extensive metabolism by the cytochrome P-450 mixed function oxidase system. Although specific pharmacokinetic drug-drug interaction studies have not been conducted with single intravenous injection or constant rate intravenous infusion, coadministration of diltiazem hydrochloride injection with other agents which primarily undergo the same route of biotransformation may result in competitive inhibition of metabolism.
====Digitalis. ====Intravenous diltiazem has been administered to patients receiving either intravenous or oral digitalis therapy. The combination of the two drugs was well tolerated without serious adverse effects. However, since both drugs affect AV nodal conduction, patients should be monitored for excessive slowing of the heart rate and/or AV block.
====Beta-blockers. ====Intravenous diltiazem has been administered to patients on chronic oral beta-blocker therapy. The combination of the two drugs was generally well tolerated without serious adverse effects. If intravenous diltiazem is administered to patients receiving chronic oral beta-blocker therapy, the possibility for bradycardia, AV block, and/or depression of contractility should be considered (see CONTRAINDICATIONS). Oral administration of diltiazem with propranolol in five normal volunteers resulted in increased propranolol levels in all subjects and bioavailability of propranolol was increased approximately 50%. In vitro, propranolol appears to be displaced from its binding sites by diltiazem. ====Anesthetics.==== The depression of cardiac contractility, conductivity, and automaticity as well as the vascular dilation associated with anesthetics may be potentiated by calcium channel blockers. When used concomitantly, anesthetics and calcium blockers should be titrated carefully.
====Cyclosporine.==== A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. In renal and cardiac transplant recipients, a reduction of cyclosporine dose ranging from 15% to 48% was necessary to maintain cyclosporine trough concentrations similar to those seen prior to the addition of diltiazem. If these agents are to be administered concurrently, cyclosporine concentrations should be monitored, especially when diltiazem therapy is initiated, adjusted or discontinued.
The effect of cyclosporine on diltiazem plasma concentrations has not been evaluated.
====Carbamazepine.==== Concomitant administration of oral diltiazem with carbamazepine has been reported to result in elevated plasma levels of carbamazepine (by 40 to 72%), resulting in toxicity in some cases. Patients receiving these drugs concurrently should be monitored for a potential drug interaction.[1]
References
- ↑ "DILTIAZEM HYDROCHLORIDE INJECTION [AKORN, INC.]". Retrieved 5 March 2014.