engines like google [10:<30 C (86 F). IV is stable for 24 hours at room temperature in D5W, NS, D5NS, or D5LR. Drug Interactions Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Aliskiren: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Aliskiren may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Management: Aliskiren use with ACEIs or ARBs in patients with diabetes is contraindicated. Combined use in other patients should be avoided, particularly when CrCl is less than 60 mL/min. If combined, monitor potassium, creatinine, and blood pressure closely. Consider therapy modification Allopurinol: Angiotensin-Converting Enzyme Inhibitors may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Consider therapy modification Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Angiotensin II Receptor Blockers: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Angiotensin II Receptor Blockers may increase the serum concentration of Angiotensin-Converting Enzyme Inhibitors. Management: In US labeling, use of telmisartan and ramipril is not recommended. It is not clear if any other combination of an ACE inhibitor and an ARB would be any safer. Consider alternatives to the combination when possible. Consider therapy modification Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy Aprotinin: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy AzaTHIOprine: Angiotensin-Converting Enzyme Inhibitors may enhance the myelosuppressive effect of AzaTHIOprine. Monitor therapy Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Monitor therapy Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Canagliflozin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Canagliflozin may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Ciprofloxacin (Systemic): Angiotensin-Converting Enzyme Inhibitors may enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy Dapoxetine: May enhance the orthostatic hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Dipeptidyl Peptidase-IV Inhibitors: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy Drospirenone: Angiotensin-Converting Enzyme Inhibitors may enhance the hyperkalemic effect of Drospirenone. Monitor therapy DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy Eplerenone: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Everolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Specifically, the risk of angioedema may be increased. Monitor therapy Ferric Gluconate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Gluconate. Monitor therapy Ferric Hydroxide Polymaltose Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Ferric Hydroxide Polymaltose Complex. Specifically, the risk for angioedema or allergic reactions may be increased. Monitor therapy Gold Sodium Thiomalate: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Gold Sodium Thiomalate. An increased risk of nitritoid reactions has been appreciated. Monitor therapy Grass Pollen Allergen Extract (5 Grass Extract): Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Grass Pollen Allergen Extract (5 Grass Extract). Specifically, ACE inhibitors may increase the risk of severe allergic reaction to Grass Pollen Allergen Extract (5 Grass Extract). Consider therapy modification Heparin: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Heparins (Low Molecular Weight): May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy Icatibant: May diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Iron Dextran Complex: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Iron Dextran Complex. Specifically, patients receiving an ACE inhibitor may be at an increased risk for anaphylactic-type reactions. Management: Follow iron dextran recommendations closely regarding both having resuscitation equipment and trained personnel on-hand prior to iron dextran administration and the use of a test dose prior to the first therapeutic dose. Consider therapy modification Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy Lithium: Angiotensin-Converting Enzyme Inhibitors may increase the serum concentration of Lithium. Management: Lithium dosage reductions will likely be needed following the addition of an ACE inhibitor. Monitor patient response to lithium closely following addition or discontinuation of concurrent ACE inhibitor treatment. Consider therapy modification Loop Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Loop Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Nicorandil: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Monitor therapy Nonsteroidal Anti-Inflammatory Agents: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the combination may result in a significant decrease in renal function. Nonsteroidal Anti-Inflammatory Agents may diminish the antihypertensive effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Consider therapy modification Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Monitor therapy Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Potassium Salts: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Potassium-Sparing Diuretics: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Pregabalin: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Pregabalin. Specifically, the risk of angioedema may be increased. Monitor therapy Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy Sacubitril: Angiotensin-Converting Enzyme Inhibitors may enhance the adverse/toxic effect of Sacubitril. Specifically, the risk of angioedema may be increased with this combination. Avoid combination Salicylates: May enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Sirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Sodium Phosphates: Angiotensin-Converting Enzyme Inhibitors may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Management: Consider avoiding this combination by temporarily suspending treatment with ACEIs, or seeking alternatives to oral sodium phosphate bowel preparation. If the combination cannot be avoided, maintain adequate hydration and monitor renal function closely. Consider therapy modification Temsirolimus: May enhance the adverse/toxic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Thiazide and Thiazide-Like Diuretics: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy TiZANidine: May enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Tolvaptan: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Trimethoprim: May enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy Test Interactions May lead to false-negative aldosterone/renin ratio (ARR) (Funder 2016). Adverse Reactions Since enalapril is converted to enalaprilat, adverse reactions associated with enalapril may also occur with enalaprilat (also refer to Enalapril monograph). Frequency ranges include data from hypertension and cardiac failure trials. Higher rates of adverse reactions have generally been noted in patients with cardiac failure. However, the frequency of adverse effects associated with placebo is also increased in this population. 1% to 10%: Cardiovascular: Hypotension (2% to 5%) Central nervous system: Headache (3%) Gastrointestinal: Nausea (1%)> <1% (Limited to important or life-threatening): Angioedema, constipation, cough, dizziness, fatigue, fever, myocardial infarction, skin rash ALERT: U.S. Boxed Warning Fetal toxicity: When pregnancy is detected, discontinue enalaprilat as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Warnings/Precautions Concerns related to adverse effects: Angioedema: At any time during treatment (especially following first dose) angioedema may occur rarely with ACE inhibitors; it may involve the head and neck (potentially compromising airway) or the intestine (presenting with abdominal pain). African-Americans may be at an increased risk. Risk may also be increased with concomitant use of mTOR inhibitor (eg, everolimus) therapy. Prolonged frequent monitoring may be required especially if tongue, glottis, or larynx are involved as they are associated with airway obstruction. Patients with a history of airway surgery may have a higher risk of airway obstruction. Aggressive early and appropriate management is critical. Use in patients with idiopathic or hereditary angioedema or previous angioedema associated with ACE inhibitor therapy is contraindicated. Cholestatic jaundice: A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, which may progress to fulminant hepatic necrosis; discontinue if marked elevation of hepatic transaminases or jaundice occurs. Cough: An ACE inhibitor cough is a dry, hacking, nonproductive one that usually occurs within the first few months of treatment and should generally resolve within 1-4 weeks after discontinuation of the ACE inhibitor. Other causes of cough should be considered (eg, pulmonary congestion in patients with heart failure) and excluded prior to discontinuation. Hyperkalemia: May occur with ACE inhibitors; risk factors include renal dysfunction, diabetes mellitus, concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salts. Use cautiously, if at all, with these agents and monitor potassium closely. Hypersensitivity reactions: Anaphylactic/anaphylactoid reactions can occur with ACE inhibitors. Severe anaphylactoid reactions may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of anaphylactoid reactions have been reported in patients undergoing sensitization treatment with hymenoptera (bee, wasp) venom while receiving ACE inhibitors. Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses); effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation; close monitoring of patient is required especially with initial dosing and dosing increases; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation. Neutropenia/agranulocytosis: Another ACE inhibitor, captopril, has been associated with rare cases of agranulocytosis, neutropenia, or leukopenia with myeloid hypoplasia. Patients with renal impairment are at high risk of developing neutropenia. Patients with both renal impairment and collagen vascular disease (eg, systemic lupus erythematosus) are at an even higher risk of developing neutropenia. Periodically monitor CBC with differential in these patients. Renal function deterioration: May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotemia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients with progressive and/or significant deterioration in renal function. Disease-related concerns: Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia. Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs. Collagen vascular disease: Use with caution in patients with collagen vascular disease especially with concomitant renal impairment; may be at increased risk for hematologic toxicity. Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition. Renal artery stenosis: Use with caution in patients with unstented unilateral/bilateral renal artery stenosis. When unstented bilateral renal artery stenosis is present, use is generally avoided due to the elevated risk of deterioration in renal function unless possible benefits outweigh risks. Renal impairment: Use with caution in preexisting renal insufficiency; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment. Concurrent drug therapy issues: Angiotensin receptor blockers (ARBs) and renin inhibitors: Concomitant use of an ARB or renin inhibitor (eg, aliskiren) is associated with an increased risk of hypotension, hyperkalemia, and renal dysfunction. Concomitant use with aliskiren should be avoided in patients with GFR> <60 mL/minute and is contraindicated in patients with diabetes mellitus (regardless of GFR). Special populations: Pregnancy: [U.S. Boxed Warning]: Based on human data, ACEIs can cause injury and death to the developing fetus when used in the second and third trimesters. ACEIs should be discontinued as soon as possible once pregnancy is detected. Dosage form specific issues: Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol ( 99 mg/kg/day) have been associated with a potentially fatal toxicity ( gasping syndrome ) in neonates; the gasping syndrome consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer s labeling. Other warnings/precautions: Surgery: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension. However, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis, 2011). Monitoring Parameters Blood pressure; serum creatinine and potassium; if patient has collagen vascular disease and/or renal impairment, periodically monitor CBC with differential Pregnancy Risk Factor C (1st trimester); D (2nd and 3rd trimesters) Pregnancy Considerations [U.S. Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected. Enalapril crosses the placenta; the active metabolite enalaprilat can be detected in the newborn (Schubiger 1988). Drugs that act on the renin-angiotensin system are associated with oligohydramnios. Oligohydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. The use of these drugs in pregnancy is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate. Teratogenic effects may occur following maternal use of an ACE inhibitor during the first trimester, although this finding may be confounded by maternal disease. Because adverse fetal events are well documented with exposure later in pregnancy, ACE inhibitor use in pregnant women is not recommended (Seely 2014; Weber 2014). Infants exposed to an ACE inhibitor in utero should be monitored for hyperkalemia, hypotension, and oliguria. Oligohydramnios may not appear until after irreversible fetal injury has occurred. Exchange transfusions or dialysis may be required to reverse hypotension or improve renal function, although data related to the effectiveness in neonates is limited Chronic maternal hypertension itself is also associated with adverse events in the fetus/infant and mother. ACE inhibitors are not recommended for the treatment of uncomplicated hypertension in pregnancy (ACOG 2013) and they are specifically contraindicated for the treatment of hypertension and chronic heart failure during pregnancy by some guidelines (Regitz-Zagrosek 2011). In addition, ACE inhibitors should generally be avoided in women of reproductive age (ACOG 2013). If treatment for hypertension in pregnancy is needed, other agents should be used (ACOG 2013; Regitz-Zagrosek 2011). Patient Education Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?) Have patient report immediately to prescriber signs of infection, signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, or numbness or tingling feeling), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), severe dizziness, passing out, persistent cough, angina, severe abdominal pain, severe nausea, or vomiting (HCAHPS). Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions. Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients. Print this page> ]} Recently Approved Lonhala Magnair Lonhala Magnair (glycopyrrolate) is a long-acting muscarinic antagonist (LAMA) bronchodilator for... Ozempic Ozempic (semaglutide) is a glucagon-like peptide-1 (GLP-1) analog administered once-weekly for the... Ogivri Ogivri (trastuzumab-dkst) is a HER2 / neu receptor antagonist biosimilar to Herceptin indicated for... Sublocade Sublocade (buprenorphine) is a once-monthly injectable partial opioid agonist formulation for the... More} } modern
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