Skip to main content

Interactions between Ifex and Lorazepam

1 drug interaction and 28 additional warnings found for the following 2 drugs:

Add/remove drugs

Drug interactions

Moderate drug interactions

Moderate:

LORazepam ifosfamide

Applies to: lorazepam and Ifex (ifosfamide)
Monitor

Centrally-acting agents such as antiemetics, sedatives, narcotics, or antihistamines may add to the neurotoxic effects of ifosfamide. Administration of ifosfamide can cause CNS toxicity, which necessitates careful monitoring of the patient. Neurologic manifestations include somnolence, confusion, hallucinations, blurred vision, psychotic behavior, extrapyramidal symptoms, urinary incontinence, seizures, and in some instances, coma. There have also been reports of peripheral neuropathy. Ifosfamide neurotoxicity may occur within a few hours to a few days after initial administration and typically resolves within 48 to 72 hours of ifosfamide discontinuation. However, symptoms may persist for longer periods of time, and recovery has occasionally been incomplete. Fatal outcomes have been reported. There have also been reports of recurrence of CNS toxicity after several uneventful treatment courses.

Management

Due to the potential for additive effects, centrally-acting agents should be used with caution in combination with ifosfamide. Patients should be advised to avoid driving, operating machinery, or engaging in potentially hazardous activities requiring mental alertness and motor coordination until they know how the medications affect them. If ifosfamide-induced encephalopathy occurs, both ifosfamide and non-essential concomitant CNS agents should be discontinued. Supportive therapy should be initiated and maintained until complete resolution of neurotoxicity.

References (2)
  1. Simonian NA, Gilliam FG, Chiappa KH (1993) "Ifosfamide causes a diazepam-sensitive encephalopathy." Neurology, 43, p. 2700-2
  2. (2001) "Product Information. Ifex (ifosfamide)." Bristol-Myers Squibb

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

LORazepam Food/Lifestyle

Applies to: lorazepam
Generally avoid

Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Management

Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Moderate:

ifosfamide Food/Lifestyle

Applies to: Ifex (ifosfamide)
Generally avoid

Grapefruit and/or grapefruit juice may reduce the efficacy of ifosfamide, whose anticancer effect is dependent on its activation to the 4-hydroxyifosfamide metabolite via CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4 metabolism by certain compounds present in grapefruit. There are no data available about the effects of grapefruit on ifosfamide. However, in a small study, 8 patients with incurable malignancies received ifosfamide 3 g/m2 by infusion with the potent CYP450 3A4 inhibitor ketoconazole 200 mg orally twice daily for 4 days starting 1 day before the ifosfamide infusion. Ketoconazole decreased the clearance of ifosfamide by 11%, decreased systemic exposure (AUC) of the active metabolite 4-hydroxyifosfamide by 30%, and increased the AUC of the inactive but potentially neurotoxic metabolite 2-dechloroethylifosfamide by 23%, as compared to control. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

Generally avoid

Alcohol may potentiate the neurotoxic effects of ifosfamide. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, ifosfamide therapy may cause gastrointestinal disorders and alcohol consumption may increase nausea and vomiting.

Management

Given the potential for reduced efficacy of ifosfamide and increased risk of neurotoxicity and nephrotoxicity it may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with ifosfamide. In addition, patients receiving ifosfamide should be warned of the increased risk of neurotoxicity, nausea and vomiting when used in combination with alcohol. Patients should avoid or limit the consumption of alcohol during treatment with ifosfamide.

References (6)
  1. (2019) "Product Information. Ifosfamide (ifosfamide)." Hikma USA (formerly West-Ward Pharmaceutical Corporation)
  2. Kerbusch T, jansen rlh, mathot raa, huitema adr, Jansen RNM, Rijswijk REN, Beijen JH (2001) "Modulation of the cytochrome P450-mediated metabolism of ifosfamide by ketoconazole and rifampin" Clin Pharmacol and Therapeutic, 70, p. 132-141
  3. (2018) "Product Information. Ifex (ifosfamide)." Baxter Pharmaceutical Products, Inc
  4. (2018) "Product Information. Holoxan (iFOSFamide)." Baxter Healthcare Pty Ltd
  5. (2022) "Product Information. Ifosfamide (ifosfamide)." Baxter Healthcare Ltd
  6. (2018) "Product Information. Ifex (ifosfamide)." Baxter Corporation

Disease interactions

26 potential interactions Applies to: 21 conditions, including Depression, GERD, Weight Loss, Seizures, and Fever.

Acute Alcohol Intoxication

Major:

lorazepam

LORazepam 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.

Altered Consciousness

Major:

lorazepam

LORazepam 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.

Asphyxia

Major:

lorazepam

LORazepam 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.

Bleeding Disorder

Major:

Ifex

The ifosfamide in Ifex has a major potential interaction with Bleeding Disorder.

Treatment with ifosfamide may cause myelosuppression and significant suppression of immune responses, which can lead to severe or fatal infections. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Complete blood counts should be obtained prior to administration of each dose and unless clinically essential, ifosfamide should be withheld if white blood cell counts falls below 1,500 to 2,000/mm3 and/or platelet counts falls below 50,000/mm3. Ifosfamide should be given cautiously, if at all, to patients with presence of an infection, severe immunosuppression or compromised bone marrow reserve, as indicated by leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.

Bone Marrow Depression/Low Blood Counts

Major:

Ifex

The ifosfamide in Ifex has a major potential interaction with Bone Marrow Depression/Low Blood Counts.

Treatment with ifosfamide may cause myelosuppression and significant suppression of immune responses, which can lead to severe or fatal infections. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Complete blood counts should be obtained prior to administration of each dose and unless clinically essential, ifosfamide should be withheld if white blood cell counts falls below 1,500 to 2,000/mm3 and/or platelet counts falls below 50,000/mm3. Ifosfamide should be given cautiously, if at all, to patients with presence of an infection, severe immunosuppression or compromised bone marrow reserve, as indicated by leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.

Depression

Moderate:

lorazepam

LORazepam 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.

Drug Dependence

Major:

lorazepam

LORazepam 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.

Fever

Major:

Ifex

The ifosfamide in Ifex has a major potential interaction with Fever.

Treatment with ifosfamide may cause myelosuppression and significant suppression of immune responses, which can lead to severe or fatal infections. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Complete blood counts should be obtained prior to administration of each dose and unless clinically essential, ifosfamide should be withheld if white blood cell counts falls below 1,500 to 2,000/mm3 and/or platelet counts falls below 50,000/mm3. Ifosfamide should be given cautiously, if at all, to patients with presence of an infection, severe immunosuppression or compromised bone marrow reserve, as indicated by leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.

GERD

Moderate:

lorazepam

LORazepam 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.

Glaucoma/Intraocular Hypertension

Major:

lorazepam

LORazepam 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.

Hyperkinetic Syndrome of Childhood

Moderate:

lorazepam

LORazepam 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.

Infection

Major:

Ifex

The ifosfamide in Ifex has a major potential interaction with Infection.

Treatment with ifosfamide may cause myelosuppression and significant suppression of immune responses, which can lead to severe or fatal infections. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Complete blood counts should be obtained prior to administration of each dose and unless clinically essential, ifosfamide should be withheld if white blood cell counts falls below 1,500 to 2,000/mm3 and/or platelet counts falls below 50,000/mm3. Ifosfamide should be given cautiously, if at all, to patients with presence of an infection, severe immunosuppression or compromised bone marrow reserve, as indicated by leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.

Major:

Ifex

The ifosfamide in Ifex has a major potential interaction with Infection.

Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.

Liver Disease

Major:

lorazepam

LORazepam 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.

Moderate:

Ifex

The ifosfamide in Ifex has a moderate potential interaction with Liver Disease.

Ifosfamide is metabolized by the liver to a biologically active form. Metabolic activation and therapeutic activity may be altered in patients with hepatic impairment. Therapy with ifosfamide should be administered cautiously in patients with compromised hepatic function. Clinical monitoring of hepatic function is recommended.

Prematurity/Underweight in Infancy

Major:

lorazepam

LORazepam 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.

Psychosis

Moderate:

Ifex

The ifosfamide in Ifex has a moderate potential interaction with Psychosis.

Administration of ifosfamide can cause CNS toxicity and other neurotoxic effects. The risk of CNS toxicity and other neurotoxic effects necessitates careful monitoring of the patient. Neurologic manifestations consisting of somnolence, confusion, hallucinations, blurred vision, psychotic behavior, and extrapyramidal symptoms, have been reported following ifosfamide therapy. There have also been reports of peripheral neuropathy associated with ifosfamide Episodes of depressive psychoses and hallucinations have been reported during ifosfamide therapy. These neurological symptoms are usually reversible, but ifosfamide should be discontinued and supportive care maintained until symptoms completely resolve. Therapy with ifosfamide should be administered cautiously in patients with a history of or predisposition to psychotic episodes.

Moderate:

lorazepam

LORazepam 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.

Moderate:

lorazepam

LORazepam 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.

Pulmonary Impairment

Major:

lorazepam

LORazepam 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.

Renal Dysfunction

Moderate:

Ifex

The ifosfamide in Ifex has a moderate potential interaction with Renal Dysfunction.

Ifosfamide is primarily eliminated by the kidney. Approximately 12% to 18% of ifosfamide is excreted unchanged in the urine. Additionally, iIfosfamide is both nephrotoxic and urotoxic. Hemorrhagic cystitis due to metabolites excreted in the urine can develop during therapy with ifosfamide. Adequate hydration and use of a prophylactic agent such as mesna prior to each course of ifosfamide therapy can reduce bladder irritation and hematuria. Clinical signs of renal toxicity such as elevation in BUN or serum creatinine or decrease in creatinine clearance have been reported. Therapy with ifosfamide should be administered cautiously in patients with a history of or predisposition to cystitis or impaired renal function. Close clinical monitoring of serum and urinary chemistries is recommended.

Moderate:

lorazepam

LORazepam 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.

Respiratory Arrest

Major:

lorazepam

LORazepam 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.

Seizures

Major:

lorazepam

LORazepam 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.

Shock

Major:

lorazepam

LORazepam 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.

Weight Loss

Moderate:

lorazepam

LORazepam 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.

More resources

Ifex

A total of 604 drugs are known to interact with Ifex.

lorazepam

A total of 415 drugs are known to interact with lorazepam.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.