Drug Interaction Report
1 drug interaction and 37 additional warnings found for the following 2 drugs:
- ezogabine
- perphenazine
Drug interactions
Moderate drug interactions
Moderate:perphenazine ezogabine
Applies to: perphenazine, ezogabine
Using perphenazine together with ezogabine can increase the risk of an irregular heart rhythm that may be serious and potentially life-threatening, although it is a relatively rare side effect.
You may be more susceptible if you have:
- a heart condition called congenital long QT syndrome
- other cardiac diseases
- conduction abnormalities
- electrolyte disturbances (for example, magnesium or potassium loss due to severe or prolonged diarrhea or vomiting)
Talk to your doctor if you have any questions or concerns.
You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with these medications, whether together or alone.
It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:Alcohol (Ethanol) perphenazine
Applies to: perphenazine
Ask your doctor before using perphenazine together with ethanol (alcohol).
This can cause:
- uncontrollable movements
- agitation
- seizures
- severe dizziness or fainting
- coma
- very deep sleep
- irregular heartbeats
- high or low body temperature
Use caution when driving, operating machinery, or performing other hazardous activities, these medicaions may cause dizziness or drowsiness. If you experience dizziness or drowsiness, avoid these activities.
It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
Moderate:Food/Lifestyle ezogabine
Applies to: ezogabine
Alcohol can increase the blood levels of ezogabine and worsen side effects such as:
- drowsiness
- dizziness
- nausea
- constipation
- difficulty urinating
- blurred vision
- memory impairment
- tremor
You should avoid or limit the use of alcohol while being treated with ezogabine. Also avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you.
Ezogabine may be taken with or without food.
It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.
Disease interactions
35 potential interactionsApplies to: 30 conditions, including High Blood Pressure, Depression, Seizures, Arrhythmia, and Breast Cancer.
Acute Alcohol Intoxication
Major:perphenazine
Perphenazine has a major potential interaction with Acute Alcohol Intoxication.
Phenothiazines are contraindicated in the presence of large amounts of central nervous system depressants such as alcohol. The risk of suicide and the danger of overdose may be increased in patients who use alcohol excessively. Phenothiazines should be used with caution in patients experiencing alcohol withdrawal.
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Acute Alcohol Intoxication.
The use ezogabine with alcohol increases the systemic exposure to ezogabine. Patients should be advised of possible worsening of dose-related adverse reactions if they take ezogabine with alcohol.
Alcoholism
Major:perphenazine
Perphenazine has a major potential interaction with Alcoholism.
Phenothiazines are contraindicated in the presence of large amounts of central nervous system depressants such as alcohol. The risk of suicide and the danger of overdose may be increased in patients who use alcohol excessively. Phenothiazines should be used with caution in patients experiencing alcohol withdrawal.
Altered Consciousness
Major:perphenazine
Perphenazine has a major potential interaction with Altered Consciousness.
The use of phenothiazines is contraindicated in comatose patients and patients with severe central nervous system depression. Phenothiazines may potentiate the CNS and respiratory depression in these patients.
Arrhythmia
Major:perphenazine
Perphenazine has a major potential interaction with Arrhythmia.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
Bone Marrow Depression/Low Blood Counts
Major:perphenazine
Perphenazine has a major potential interaction with Bone Marrow Depression/Low Blood Counts.
Phenothiazines may cause hematologic toxicity. In patients with preexisting blood dyscrasias, bone marrow suppression, or a history of drug-induced leukopenia or neutropenia, phenothiazines should not be used or are contraindicated. Complete blood counts should be regularly monitored in patients with risk factors for blood dyscrasias. If white blood cell counts indicate cellular depression, discontinue treatment and institute appropriate therapy.
Breast Cancer
Moderate:perphenazine
Perphenazine has a moderate potential interaction with Breast Cancer.
The chronic use of phenothiazines is associated with persistent elevations in prolactin levels. The clinical significance in patients with a history of breast cancer is unknown and should be considered prior to therapy; approximately one-third of human breast cancers are thought to be prolactin-dependent. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in animal studies; however, evidence is inconclusive in humans.
Cardiovascular Conditions and Disorders
Major:perphenazine
Perphenazine has a major potential interaction with Cardiovascular Conditions and Disorders.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
Central Nervous System Disorders
Moderate:perphenazine
Perphenazine has a moderate potential interaction with Central Nervous System Disorders.
Phenothiazines can lower the seizure threshold. Caution is recommended during administration in patients with a history of convulsive disorders or EEG abnormalities. Anticonvulsant therapy should be maintained or adequately adjusted during phenothiazine treatment.
Cerebrovascular Insufficiency
Major:perphenazine
Perphenazine has a major potential interaction with Cerebrovascular Insufficiency.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
Dementia
Major:perphenazine
Perphenazine has a major potential interaction with Dementia.
Antipsychotic drugs are not approved for the treatment of patients with dementia-related psychosis. Older patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death; although the causes were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. A causal relationship with antipsychotic use has not been established. In controlled trials in older patients with dementia-related psychosis, patients randomized to risperidone, aripiprazole, and olanzapine had higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, compared to patients treated with placebo.
Depression
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Depression.
Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
Electrolyte Abnormalities
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Electrolyte Abnormalities.
QT prolongation was observed in patients treated with ezogabine. It is recommended to monitor the QT interval when ezogabine is used with medicines known to increase QT interval and in patients with known prolonged QT interval, congestive heart failure, ventricular hypertrophy, hypokalemia, or hypomagnesemia.
Head Injury
Major:perphenazine
Perphenazine has a major potential interaction with Head Injury.
Perphenazine is contraindicated in patients with suspected or established subcortical brain damage, with or without hypothalamic involvement. Perphenazine can interfere with thermoregulatory mechanisms, and a hyperthermic reaction with temperatures in excess of 40C (104F) may occur in such patients, sometimes not until 14 to 16 hours after drug administration.
Heart Disease
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Heart Disease.
QT prolongation was observed in patients treated with ezogabine. It is recommended to monitor the QT interval when ezogabine is used with medicines known to increase QT interval and in patients with known prolonged QT interval, congestive heart failure, ventricular hypertrophy, hypokalemia, or hypomagnesemia.
High Blood Pressure
Major:perphenazine
Perphenazine has a major potential interaction with High Blood Pressure.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
History - Cerebrovascular Disease
Major:perphenazine
Perphenazine has a major potential interaction with History - Cerebrovascular Disease.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
Major:perphenazine
Perphenazine has a major potential interaction with History - Cerebrovascular Disease.
Perphenazine is contraindicated in patients with suspected or established subcortical brain damage, with or without hypothalamic involvement. Perphenazine can interfere with thermoregulatory mechanisms, and a hyperthermic reaction with temperatures in excess of 40C (104F) may occur in such patients, sometimes not until 14 to 16 hours after drug administration.
History - Myocardial Infarction
Major:perphenazine
Perphenazine has a major potential interaction with History - Myocardial Infarction.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
Hyperbilirubinemia
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Hyperbilirubinemia.
Ezogabine has been shown to interfere with clinical laboratory assays of both serum and urine bilirubin, which can result in falsely elevated readings.
Hypokalemia
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Hypokalemia.
QT prolongation was observed in patients treated with ezogabine. It is recommended to monitor the QT interval when ezogabine is used with medicines known to increase QT interval and in patients with known prolonged QT interval, congestive heart failure, ventricular hypertrophy, hypokalemia, or hypomagnesemia.
Hypotension
Major:perphenazine
Perphenazine has a major potential interaction with Hypotension.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
Liver Disease
Major:perphenazine
Perphenazine has a major potential interaction with Liver Disease.
The manufacturer considers the use of perphenazine to be contraindicated in patients with preexisting liver damage. Phenothiazines are extensively metabolized by the liver and may accumulate in patients with hepatic impairment.
Major:perphenazine
Perphenazine has a major potential interaction with Liver Disease.
Therapy with phenothiazines should be administered cautiously or are contraindicated in patients with preexisting liver disease or with a history of jaundice due to phenothiazine hypersensitivity. Patients with a history of hepatic encephalopathy due to cirrhosis may have increased sensitivity to the central nervous system effects of some phenothiazines (e.g., chlorpromazine). Treatment should be discontinued if jaundice occurs.
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Liver Disease.
No dosage adjustment is recommended in patients with mild hepatic impairment. Dosage adjustment is recommended in patients with moderate or severe hepatic impairment. Close monitoring is recommended.
Neuroleptic Malignant Syndrome
Moderate:perphenazine
Perphenazine has a moderate potential interaction with Neuroleptic Malignant Syndrome.
Therapy with phenothiazines may precipitate or aggravate a potentially fatal symptom complex known as neuroleptic malignant syndrome (NMS). Treatment should not be initiated in patients with active NMS, and should be immediately discontinued if currently administered in such patients. In patients with a history of NMS, introduction or reintroduction of phenothiazines should be carefully considered, since NMS may recur.
Pheochromocytoma
Major:perphenazine
Perphenazine has a major potential interaction with Pheochromocytoma.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
Psychosis
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Psychosis.
Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.
Renal Dysfunction
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Renal Dysfunction.
Dosage adjustment is recommended in patients with creatinine clearance <50 mL/min or patients with end-stage renal disease receiving hemodialysis. A supplemental dose is recommended immediately following hemodialysis. Close monitoring is recommended.
Moderate:perphenazine
Perphenazine has a moderate potential interaction with Renal Dysfunction.
Phenothiazines should be used with caution in patients with renal dysfunction. Patients with renal insufficiency may be more prone to hypotension. Periodic renal function tests are recommended for all patients during prolonged therapy.
Respiratory Arrest
Major:perphenazine
Perphenazine has a major potential interaction with Respiratory Arrest.
The use of phenothiazines is contraindicated in comatose patients and patients with severe central nervous system depression. Phenothiazines may potentiate the CNS and respiratory depression in these patients.
Retinal Disorders
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Retinal Disorders.
The use of ezogabine can cause abnormalities of the retina. Patients should have baseline ophthalmologic testing by an ophthalmic professional and follow-up testing as clinically indicated. Patients who cannot be monitored should not be treated with ezogabine. The ophthalmologic monitoring program should include visual acuity testing, dilated fundus photography, and optical coherence tomography. Additional testing may include fluorescein angiograms, perimetry, and electroretinograms. If retinal pigmentary abnormalities or vision changes are detected, ezogabine should be discontinued unless no other suitable treatment options are available and the benefits of treatment outweigh the potential risk of vision loss.
Seizures
Moderate:perphenazine
Perphenazine has a moderate potential interaction with Seizures.
Phenothiazines can lower the seizure threshold. Caution is recommended during administration in patients with a history of convulsive disorders or EEG abnormalities. Anticonvulsant therapy should be maintained or adequately adjusted during phenothiazine treatment.
Urinary Retention
Moderate:ezogabine
Ezogabine has a moderate potential interaction with Urinary Retention.
The use of ezogabine may cause urinary retention. A comprehensive evaluation of urologic symptoms should be conducted prior to and during treatment with ezogabine as clinically indicated. It is recommended to monitor closely for urologic symptoms in patients at risk.
Valvular Heart Disease
Major:perphenazine
Perphenazine has a major potential interaction with Valvular Heart Disease.
Phenothiazines may cause hypotension. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, cardiovascular disease, or a severe cardiac reserve deficiency (e.g., mitral insufficiency) may be more prone to hypotensive reactions. Close monitoring is recommended during treatment if used in at-risk patients; some products may be contraindicated (e.g., thioridazine). Large doses and parenteral administration should be used cautiously, or avoided, in patients with impaired cardiovascular systems.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
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