Interactions between Ativan Injection and Eplerenone

The LORazepam in Ativan Injection has a major potential interaction with Acute Alcohol Intoxication.

The use of benzodiazepines with alcohol is not recommended. Patients with acute alcohol intoxication exhibit depressed vital signs. The central nervous system depressant effects of benzodiazepines may be additive with those of alcohol, and severe respiratory depression and death may occur. Therapy with benzodiazepines should be administered cautiously in patients who might be prone to acute alcohol intake.

The LORazepam in Ativan Injection has a major potential interaction with Altered Consciousness.

Benzodiazepines should not be administered by injection to patients in shock or coma. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.

The LORazepam in Ativan Injection has a major potential interaction with Asphyxia.

Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

The LORazepam in Ativan Injection has a moderate potential interaction with Depression.

Benzodiazepines depress the central nervous system and may cause or exacerbate mental depression and cause suicidal behavior and ideation. Episodes of mania and hypomania have also been reported in depressed patients treated with some of these agents. Therapy with benzodiazepines should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these patients.

The LORazepam in Ativan Injection has a major potential interaction with Drug Dependence.

Benzodiazepines have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use and/or excessive dosages. However, abrupt cessation following continual use of as few as 6 weeks at therapeutic levels has occasionally precipitated withdrawal symptoms. Addiction- prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance when treated with benzodiazepines. It may be prudent to refrain from dispensing large quantities of medication to these patients. After prolonged use or if dependency is suspected, withdrawal of benzodiazepine therapy should be undertaken gradually using a dosage- tapering schedule. If withdrawal symptoms occur, temporary reinstitution of benzodiazepines may be necessary.

The LORazepam in Ativan Injection has a moderate potential interaction with GERD.

The manufacturer recommends the use of caution when prescribing lorazepam for prolonged periods in patients with upper gastrointestinal disease, especially in the elderly. The appearance or worsening of upper gastrointestinal symptoms should be monitored.

The LORazepam in Ativan Injection has a major potential interaction with Glaucoma/Intraocular Hypertension.

The manufacturers consider the use of benzodiazepines to be contraindicated in patients with acute angle-closure glaucoma or untreated open-angle glaucoma. These agents do not possess anticholinergic activity but have very rarely been associated with increased intraocular pressure.

Eplerenone has a major potential interaction with Hyperkalemia.

The use of eplerenone is contraindicated in the presence of elevated serum potassium concentrations (> 5.5 mEq/L). Eplerenone is a blocker of aldosterone binding at the mineralocorticoid receptor and can cause hyperkalemia, which may result in life-threatening cardiac arrhythmias. Careful monitoring of serum potassium levels is necessary in patients who are at risk for the development of hyperkalemia (including those receiving concomitant ACE inhibitors or angiotensin II receptor antagonists), especially during initiation of therapy, after dosage adjustment, and during illness that could alter renal function. In clinical trials, monitoring occurred every 2 weeks for the first 1 to 2 months, then monthly thereafter. Eplerenone should be withdrawn immediately if hyperkalemia develops, and measures should be initiated to lower serum potassium if it exceeds 6.5 mEq/L.

The LORazepam in Ativan Injection has a moderate potential interaction with Hyperkinetic Syndrome of Childhood.

Paradoxical reactions, including excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams, have been reported with the use of benzodiazepines in psychiatric patients and pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with benzodiazepines. The manufacturers do not recommend the use of benzodiazepines for the treatment of psychosis.

The LORazepam in Ativan Injection has a major potential interaction with Liver Disease.

The use of some benzodiazepines such as clonazepam and diazepam (oral tablets), is considered by the manufacturer to be contraindicated in patients with clinical or biochemical evidence of significant liver disease. These drugs are primarily metabolized by the liver and there is a risk of excess accumulation. Although all benzodiazepines may worsen hepatic encephalopathy, the manufacturer specifically recommends that lorazepam should be avoided in these patients.

Eplerenone has a moderate potential interaction with Liver Disease.

Eplerenone is primarily metabolized by the liver. In patients with moderate (Child-Pugh Class B) hepatic impairment given eplerenone 400 mg, the steady-state peak plasma concentration (Cmax) and systemic exposure (AUC) of eplerenone were increased by 3.6% and 42%, respectively, compared to those in normal subjects. In 16 patients with mild to moderate hepatic impairment who received 400 mg of eplerenone, no elevations in serum potassium above 5.5 mmol/L were observed. Their mean increase in serum potassium was 0.12 mEq/L compared to 0.13 mEq/L in normal controls. No adjustment of the starting dosage is recommended for patients with mild to moderate hepatic impairment. The use of eplerenone in patients with severe hepatic impairment has not been evaluated, thus caution is advised.

The LORazepam in Ativan Injection has a major potential interaction with Prematurity/Underweight in Infancy.

Parenteral medications formulated in multidose vials often contain benzyl alcohol as a preservative. Their use is considered by drug manufacturers to be contraindicated in neonates, particularly premature infants and infants of low birth weight. When used in bacteriostatic saline intravascular flush and endotracheal tube lavage solutions, benzyl alcohol has been associated with fatalities and severe respiratory and metabolic complications in low-birth-weight premature infants. Thus, single-dose formulations should always be used in infants whenever possible. However, many experts feel that, in the absence of benzyl alcohol-free equivalents, the amount of the preservative present in these formulations should not necessarily preclude their use if they are clearly indicated. The American Academy of Pediatrics considers benzyl alcohol in low doses (such as when used as a preservative in some medications) to be safe for newborns. However, the administration of high dosages of these medications must take into account the total amount of benzyl alcohol administered. The level at which toxicity may occur is unknown.

The LORazepam in Ativan Injection has a moderate potential interaction with Psychosis.

Benzodiazepines depress the central nervous system and may cause or exacerbate mental depression and cause suicidal behavior and ideation. Episodes of mania and hypomania have also been reported in depressed patients treated with some of these agents. Therapy with benzodiazepines should be administered cautiously in patients with a history of depression or other psychiatric disorders. Patients should be monitored for any changes in mood or behavior. It may be prudent to refrain from dispensing large quantities of medication to these patients.

The LORazepam in Ativan Injection has a moderate potential interaction with Psychosis.

Paradoxical reactions, including excitability, irritability, aggressive behavior, agitation, nervousness, hostility, anxiety, sleep disturbances, nightmares and vivid dreams, have been reported with the use of benzodiazepines in psychiatric patients and pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with benzodiazepines. The manufacturers do not recommend the use of benzodiazepines for the treatment of psychosis.

The LORazepam in Ativan Injection has a major potential interaction with Pulmonary Impairment.

Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

Eplerenone has a major potential interaction with Renal Dysfunction.

The use of eplerenone is contraindicated in patients with renal impairment as defined by serum creatinine above 2.0 mg/dL for males or 1.8 mg/dL for females, or a creatinine clearance (CrCl) below 50 mL/min. These patients are at increased risk of developing persistent hyperkalemia, which is the principal adverse effect of eplerenone and can lead to potentially life-threatening cardiac arrhythmias. The incidence of hyperkalemia increases with decreasing renal function. In clinical studies of eplerenone, serum potassium levels exceeding 5.5 mEq/L were observed in 10.4% of treated patients with baseline calculated CrCl less than 70 mL/min, 5.6% of patients with baseline CrCl 70 to 100 mL/min, and 2.6% of patients with baseline CrCl greater than 100 mL/min. Careful monitoring of serum potassium levels is necessary in patients treated with eplerenone who are at risk for the development of hyperkalemia, especially during initiation of therapy, after dosage adjustment, and during illness that could alter renal function. In clinical trials, monitoring occurred every 2 weeks for the first 1 to 2 months, then monthly thereafter. Eplerenone should be withdrawn immediately if hyperkalemia develops, and measures should be initiated to lower serum potassium if it exceeds 6.5 mEq/L.

The LORazepam in Ativan Injection has a moderate potential interaction with Renal Dysfunction.

Benzodiazepines are excreted by the kidneys and should be used with caution in patients with impaired renal function and end-stage kidney disease.

The LORazepam in Ativan Injection has a major potential interaction with Respiratory Arrest.

Benzodiazepines may cause respiratory depression and apnea, usually when given in high dosages and/or by intravenous administration. However, some patients may be susceptible at commonly used dosages, including the elderly, debilitated or severely ill patients, those receiving other CNS depressants, and those with limited ventilatory reserve, chronic pulmonary insufficiency or other respiratory disorders. Therapy with benzodiazepines should be administered cautiously in these patients. Appropriate monitoring and individualization of dosage are particularly important, and equipment for resuscitation should be immediately available if the parenteral route is used. Benzodiazepines, especially injectable formulations, should generally be avoided in patients with sleep apnea, severe respiratory insufficiency, or hypoxia.

The LORazepam in Ativan Injection has a major potential interaction with Seizures.

The use of benzodiazepines in patients with seizure disorders may increase the incidence or precipitate the onset of generalized tonic-clonic seizures (grand mal). Appropriate anticonvulsant medication might need to be initiated or the dosage increased. Abrupt cessation of benzodiazepine therapy may precipitate seizures and other withdrawal symptoms, particularly after prolonged use and/or excessive dosages. Status epilepticus may occur in patients with a history of seizures withdrawn rapidly from benzodiazepine therapy. Following chronic administration, cessation of benzodiazepine therapy should occur gradually with incrementally reduced dosages. Patients should be advised not to discontinue medication without first consulting with the physician.

The LORazepam in Ativan Injection has a major potential interaction with Shock.

Benzodiazepines should not be administered by injection to patients in shock or coma. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.

Eplerenone has a major potential interaction with Type 2 Diabetes.

The use of eplerenone is contraindicated in patients with type II diabetes mellitus and microalbuminuria. These patients are at increased risk of developing persistent hyperkalemia, which is the principal adverse effect of eplerenone and can lead to potentially life-threatening cardiac arrhythmias. In a study of such patients treated with a 200 mg/day dose, the frequency of maximum serum potassium levels exceeding 5.5 mEq/L was 33% with eplerenone alone and 38% in combination with enalapril. In other patient populations, the frequency has been reported at 1% for the 200 mg/day dose and 8.7% for the 400 mg/day dose. Careful monitoring of serum potassium levels is necessary in patients treated with eplerenone who are at risk for the development of hyperkalemia, especially during initiation of therapy, after dosage adjustment, and during illness that could alter renal function. In clinical trials, monitoring occurred every 2 weeks for the first 1 to 2 months, then monthly thereafter. Eplerenone should be withdrawn immediately if hyperkalemia develops, and measures should be initiated to lower serum potassium if it exceeds 6.5 mEq/L.

The LORazepam in Ativan Injection has a moderate potential interaction with Weight Loss.

The plasma half-lives of benzodiazepines may be prolonged in obese patients, presumably due to increased distribution into fat. Marked increases in distribution (> 100%) have been reported for diazepam and midazolam, and moderate increases (25% to 100%) for alprazolam, lorazepam, and oxazepam. Therapy with benzodiazepines should be administered cautiously in obese patients, with careful monitoring of CNS status. Longer dosing intervals may be appropriate. When dosing by weight, loading doses should be based on actual body weight, while maintenance dose should be based on ideal body weight to avoid toxicity.