Interactions between Antrocol and Clozapine
2 drug interactions and 87 additional warnings found for the following 2 drugs:
- Antrocol (atropine/phenobarbital)
- clozapine
Drug interactions
Major drug interactions
Major:
atropine cloZAPine
Applies to: Antrocol (atropine / phenobarbital) and clozapine
Monitor closely
Concomitant use of clozapine with drugs that have anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may increase the risk for anticholinergic toxicity or severe gastrointestinal adverse reactions related to hypomotility. Clozapine alone can cause life-threatening gastrointestinal adverse effects in association with its potent anticholinergic activity, ranging from constipation to paralytic ileus. Excessive parasympatholytic effects may also result in hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of clozapine in combination with other neuroleptics or anticholinergic agents may also increase the risk of tardive dyskinesia.
Management
Close monitoring for signs and symptoms of additive anticholinergic effects such as gastrointestinal hypomotility is advised when clozapine is used with other drugs that have anticholinergic properties, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Some authorities recommend avoiding this combination. Patients should be advised to notify their physician promptly if they experience constipation or symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Prompt treatment with appropriate laxatives and other measures are essential to minimize the risk of complications. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.
References (8)
- (2023) "Product Information. Clozaril (cloZAPine)." HLS Therapeutics Inc
- (2022) "Product Information. Clozaril (clozapine)." HLS Therapeutics Inc
- (2023) "Product Information. CloZAPine (cloZAPine)." Aurobindo Pharma USA Inc
- (2023) "Product Information. AA-Clozapine (clozapine)." AA Pharma Inc
- (2022) "Product Information. Denzapine (clozapine)." Britannia Pharmaceuticals Ltd
- (2022) "Product Information. Clozapine (AKM) (clozapine)." Pharmacor Pty Ltd, 03
- (2024) "Product Information. CloZAPine (cloZAPine)." Accord Healthcare, Inc.
- (2024) "Product Information. Clozapine (AKM) (clozapine)." Pharmacor Pty Ltd
Moderate drug interactions
Moderate:
cloZAPine PHENobarbital
Applies to: clozapine and Antrocol (atropine / phenobarbital)
Monitor
Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.
Management
During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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 (36)
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Food/lifestyle interactions
Major food/lifestyle interactions
Major:
PHENobarbital Alcohol (Ethanol)
Applies to: Antrocol (atropine / phenobarbital)
Generally avoid
Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.
Management
The combination of ethanol and barbiturates should be avoided.
References (5)
- Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
- Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
- Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
- Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
- Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
Moderate food/lifestyle interactions
Moderate:
cloZAPine Food/Lifestyle
Applies to: clozapine
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)
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- 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.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Moderate:
atropine Alcohol (Ethanol)
Applies to: Antrocol (atropine / phenobarbital)
Generally avoid
Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.
Management
Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.
References (1)
- Linnoila M (1973) "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol, 6, p. 107-12
Moderate:
cloZAPine Nicotine
Applies to: clozapine
Monitor
Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.
Management
Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.
References (4)
- (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
- jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
- Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
- Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38
Minor food/lifestyle interactions
Minor:
cloZAPine Caffeine
Applies to: clozapine
Caffeine may increase clozapine serum concentrations and exacerbate psychotic symptoms. The mechanism is unknown but may be related to competition for the same metabolic pathway. No specific intervention is necessary; however, if an interaction is suspected it is recommended that caffeine intake be avoided.
References (4)
- Carrillo JA, Jerling M, Bertilsson L (1995) "Interaction between caffeine and clozapine - comment." J Clin Psychopharmacol, 15, p. 376-7
- Odom-White A, de Leon J (1996) "Clozapine levels and caffeine." J Clin Psychiatry, 57, p. 175-6
- Vainer JL, Chouinard G (1994) "Interaction between caffeine and clozapine." J Clin Psychopharmacol, 14, p. 284
- Hagg S, Spiset O, Mjorndal T, Dalqvist R (2000) "Effect of caffeine on clozapine pharmacokinetics in healthy volunteers." Br J Clin Pharmacol, 49, p. 59-63
Disease interactions
82 potential interactions Applies to: 61 conditions, including High Blood Pressure, High Cholesterol, Depression, GERD, and Vitamin D Deficiency.
Abnormal Glucose Tolerance
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Abnormal Glucose Tolerance.
Severe hyperglycemia, sometimes resulting in ketoacidosis, has been reported during clozapine treatment in patients with no prior history of hyperglycemia. Glucose levels normalized in most cases following discontinuation of clozapine, and a rechallenge in one patient produced a recurrence of hyperglycemia. While a causal relationship has not been established, patients with or predisposed to hyperglycemia should be monitored during clozapine therapy. Dosage adjustments in insulin or oral hypoglycemic medications may be necessary in patients with diabetes.
Acute Alcohol Intoxication
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Acute Alcohol Intoxication.
The use of barbiturates is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of barbiturates may be additive with those of alcohol. Severe respiratory depression and death may occur. Therapy with barbiturates should be administered cautiously in patients who might be prone to acute alcohol intake.
Adrenal Insufficiency
Moderate:
Antrocol
The PHENobarbital in Antrocol has a moderate potential interaction with Adrenal Insufficiency.
Barbiturates, especially phenobarbital, secobarbital and butabarbital, may diminish the systemic effects of exogenous and endogenous corticosteroids via induction of hepatic microsomal enzymes, thereby accelerating the metabolism of corticosteroids. In addition, barbiturates may interfere with pituitary corticotropin production. Therapy with barbiturates should be administered cautiously in patients with adrenal insufficiency. Patients with borderline hypoadrenalism should be monitored closely, and patients receiving steroid supplementation may require an adjustment in dosage when barbiturates are added to or withdrawn from their medication regimen.
Alcoholism
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Alcoholism.
Barbiturates have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use of excessive dosages. Abrupt cessation and/or a reduction in dosage may precipitate withdrawal symptoms. In patients who have developed tolerance to a barbiturate, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with barbiturates. 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 barbiturates should be undertaken gradually using a dosage-tapering schedule.
Major:
clozapine
cloZAPine has a major potential interaction with Alcoholism.
The use of neuroleptic agents is contraindicated in patients with acute alcohol intoxication exhibiting depressed vital signs. The central nervous system depressant effects of neuroleptic agents may be additive with those of alcohol. Severe respiratory depression and respiratory arrest may occur. Therapy with neuroleptic agents should be administered cautiously in patients who might be prone to acute alcohol intake.
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Alcoholism.
Antipsychotic and neuroleptic drugs can lower the seizure threshold and trigger seizures in a dose-dependent manner. This risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold. Therapy with these drugs should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism.
Altered Consciousness
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Altered Consciousness.
Barbiturates should not be administered by injection to patients in shock or coma or who have recently received another respiratory depressant. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.
Major:
clozapine
cloZAPine has a major potential interaction with Altered Consciousness.
The use of neuroleptic agents is contraindicated in comatose patients and patients with severe central nervous system depression. Neuroleptic agents may potentiate the CNS and respiratory depression in these patients.
Arrhythmia
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with Arrhythmia.
Antimuscarinic agents block vagal inhibition of the SA nodal pacemaker. These agents should be administered cautiously in patients with tachycardia, congestive heart failure, or coronary artery disease. Premature ventricular depolarization or ventricular tachycardia or fibrillation associated with antimuscarinic drugs is rare.
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with Arrhythmia.
Anticholinergics block vagal inhibition of the SA nodal pacemaker. Therapy with anticholinergics should be administered cautiously in patients with tachycardia, congestive heart failure, or coronary artery disease. Premature ventricular depolarization or ventricular tachycardia or fibrillation associated with anticholinergics is rare.
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Arrhythmia.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Asphyxia
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Asphyxia.
Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. 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 barbiturates 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. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.
Asthma
Major:
Antrocol
The atropine in Antrocol has a major potential interaction with Asthma.
The use of systemic anticholinergics is contraindicated in the treatment of lower respiratory tract symptoms including asthma. Muscarinic receptor antagonists reduce bronchial secretions, which can result in decreased fluidity and increased thickening of secretions. However, ipratropium does not produce these effects and can be used safely in treating asthma.
Autonomic Neuropathy
Major:
Antrocol
The atropine in Antrocol has a major potential interaction with Autonomic Neuropathy.
Agents with anticholinergic activity can exacerbate many of the manifestations of autonomic neuropathy, including tachycardia, anhidrosis, bladder atony, obstipation, dry mouth and eyes, cycloplegia and blurring of vision, and sexual impotence in males. Therapy with antimuscarinic agents and higher dosages of antispasmodic agents (e.g., dicyclomine or oxybutynin) should be administered cautiously in patients with autonomic neuropathy.
Bleeding Disorder
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with Bleeding Disorder.
Antimuscarinic agents may cause a delay in gastric emptying and possibly antral stasis in patients with gastric ulcer. Therapy with antimuscarinic agents should be administered cautiously to patients with gastric ulcer.
Bone Marrow Depression/Low Blood Counts
Moderate:
Antrocol
The PHENobarbital in Antrocol has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.
Hematologic toxicity, including agranulocytosis, thrombocytopenic purpura and megaloblastic anemia, has been reported rarely during use of barbiturates. Therapy with barbiturates should be administered cautiously in patients with preexisting blood dyscrasias or bone marrow suppression. Blood counts are recommended prior to and periodically during long-term therapy, and patients should be instructed to immediately report any signs or symptoms suggestive of blood dyscrasia such as fever, sore throat, local infection, easy bruising, petechiae, bleeding, pallor, dizziness, or jaundice. Barbiturate therapy should be discontinued if blood dyscrasias occur.
Breast Cancer
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Breast Cancer.
The chronic use of neuroleptic agents can cause persistent elevations in prolactin levels due to antagonism of dopamine D2 receptors. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation with respect to long-term neuroleptic therapy is unknown. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Until further data are available, therapy with neuroleptic agents should be administered cautiously in patients with a previously detected breast cancer. Caution is also advised in patients with preexisting hyperprolactinemia. Hyperprolactinemia may suppress hypothalamic gonadotrophin releasing hormone (GnRH), resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds; however, the clinical significance of elevated serum prolactin levels is unknown for most patients. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients.
Cardiovascular Conditions and Disorders
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with Cardiovascular Conditions and Disorders.
Anticholinergics block vagal inhibition of the SA nodal pacemaker. Therapy with anticholinergics should be administered cautiously to patients with tachycardia, congestive heart failure, or coronary artery disease. Premature ventricular depolarization, ventricular tachycardia, and fibrillation associated with anticholinergics are rare.
Cerebrovascular Insufficiency
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Cerebrovascular Insufficiency.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Dehydration
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Dehydration.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Dementia
Major:
clozapine
cloZAPine 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:
Antrocol
The PHENobarbital in Antrocol 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.
Moderate:
Antrocol
The PHENobarbital in Antrocol has a moderate potential interaction with Depression.
Barbiturates depress the central nervous system and may cause or exacerbate mental depression. Therapy with barbiturates should be administered cautiously in patients with a history of depression or suicidal tendencies. It may be prudent to refrain from dispensing large quantities of medication to these patients.
Dermatitis, Drug-Induced
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Dermatitis, Drug-Induced.
Skin eruptions may precede rare but potentially fatal barbiturate-induced reactions such as systemic lupus erythematosus and exfoliative dermatitis, the latter of which may be accompanied by hepatitis and jaundice. Therapy with barbiturates should be administered cautiously in patients with preexisting drug-induced dermatitis, since it may delay the recognition of a potential reaction to barbiturates. Barbiturate therapy should be withdrawn promptly at the first sign of a dermatologic adverse effect. However, cutaneous reactions may proceed to an irreversible stage even after cessation of medication due to the slow rate of metabolism and excretion of barbiturates. Patients should be advised to promptly report signs that may indicate impending development of barbiturate-related cutaneous lesions, including high fever, severe headache, stomatitis, conjunctivitis, rhinitis, urethritis, and balanitis. Rashes may be more likely to occur with phenobarbital and mephobarbital.
Diabetes Mellitus
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Diabetes Mellitus.
Severe hyperglycemia, sometimes resulting in ketoacidosis, has been reported during clozapine treatment in patients with no prior history of hyperglycemia. Glucose levels normalized in most cases following discontinuation of clozapine, and a rechallenge in one patient produced a recurrence of hyperglycemia. While a causal relationship has not been established, patients with or predisposed to hyperglycemia should be monitored during clozapine therapy. Dosage adjustments in insulin or oral hypoglycemic medications may be necessary in patients with diabetes.
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Diabetes Mellitus.
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported with the use of atypical antipsychotic agents. Patients with diabetes should be monitored for worsening control of blood glucose when treated with these agents. It is recommended that patients with risk factors for diabetes mellitus starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment, and periodically thereafter. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when treatment with these agents was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the atypical antipsychotic drug.
Diarrhea
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Diarrhea.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Minor:
Antrocol
The atropine in Antrocol has a minor potential interaction with Diarrhea.
Diarrhea may be a symptom of incomplete intestinal obstruction, especially in patients with ileostomy or colostomy. Antimuscarinic agents may further aggravate the diarrhea. Therefore, these drugs should be administered cautiously in patients with diarrhea.
Drug Dependence
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Drug Dependence.
Barbiturates have the potential to cause dependence and abuse. Tolerance as well as physical and psychological dependence can develop, particularly after prolonged use of excessive dosages. Abrupt cessation and/or a reduction in dosage may precipitate withdrawal symptoms. In patients who have developed tolerance to a barbiturate, overdosage can still produce respiratory depression and death, and cross-tolerance usually will occur with other agents in the class. Addiction-prone individuals, such as those with a history of alcohol or substance abuse, should be under careful surveillance or medical supervision when treated with barbiturates. 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 barbiturates should be undertaken gradually using a dosage-tapering schedule.
Dysphagia
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Dysphagia.
Esophageal dysmotility and aspiration have been associated with the use of antipsychotic drugs. These drugs should be administered cautiously in patients at risk for aspiration pneumonia.
Esophageal Obstruction
Major:
Antrocol
The atropine in Antrocol has a major potential interaction with Esophageal Obstruction.
Anticholinergics are contraindicated in patients with obstructive diseases such as achalasia, esophageal stricture or stenosis, pyloroduodenal stenosis, stenosing peptic ulcer, pyloric obstruction, and paralytic ileus. Anticholinergics may further suppress intestinal motility with resultant precipitation or aggravation of toxic megacolon.
Fever
Minor:
Antrocol
The atropine in Antrocol has a minor potential interaction with Fever.
Atropine-like agents may increase the risk of hyperthermia in patients with fever by producing anhidrosis. Therapy with atropine-like agents should be administered cautiously in febrile patients.
Gastrointestinal Obstruction
Major:
Antrocol
The atropine in Antrocol has a major potential interaction with Gastrointestinal Obstruction.
Anticholinergics are contraindicated in patients with obstructive diseases such as achalasia, esophageal stricture or stenosis, pyloroduodenal stenosis, stenosing peptic ulcer, pyloric obstruction, and paralytic ileus. Anticholinergics may further suppress intestinal motility with resultant precipitation or aggravation of toxic megacolon.
Major:
clozapine
cloZAPine has a major potential interaction with Gastrointestinal Obstruction.
Neuroleptic agents have anticholinergic activity, to which elderly patients are particularly sensitive. Clozapine and low-potency agents such as chlorpromazine and thioridazine tend to exhibit greater anticholinergic effects than other agents in the class. Clozapine use has been associated with impairment of intestinal peristalsis ranging from constipation to intestinal obstruction, fecal impaction, and paralytic ileus. Therapy with neuroleptic agents should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders.
GERD
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with GERD.
Antimuscarinic agents decrease gastric motility and relax the lower esophageal sphincter which promotes gastric retention and can aggravate reflux. These drugs should be administered cautiously in patients with gastroesophageal reflux or hiatal hernia associated with reflux esophagitis.
Glaucoma/Intraocular Hypertension
Major:
Antrocol
The atropine in Antrocol has a major potential interaction with Glaucoma/Intraocular Hypertension.
Anticholinergic agents are contraindicated in patients with primary glaucoma, a tendency toward glaucoma (narrow anterior chamber angle), or adhesions (synechiae) between the iris and lens, as well as for the elderly and others in whom undiagnosed glaucoma or excessive pressure in the eye may be present. Because anticholinergics cause mydriasis, they may exacerbate these conditions.
Major:
clozapine
cloZAPine has a major potential interaction with Glaucoma/Intraocular Hypertension.
Neuroleptic agents have anticholinergic activity, to which elderly patients are particularly sensitive. Clozapine and low-potency agents such as chlorpromazine and thioridazine tend to exhibit greater anticholinergic effects than other agents in the class. Clozapine use has been associated with impairment of intestinal peristalsis ranging from constipation to intestinal obstruction, fecal impaction, and paralytic ileus. Therapy with neuroleptic agents should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders.
Head Injury
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Head Injury.
Antipsychotic and neuroleptic drugs can lower the seizure threshold and trigger seizures in a dose-dependent manner. This risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold. Therapy with these drugs should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism.
Heart Disease
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Heart Disease.
The intravenous administration of barbiturates may produce severe cardiovascular reactions such as bradycardia, hypertension, or vasodilation with fall in blood pressure, particularly during rapid infusion. Parenteral therapy with barbiturates should be administered cautiously in patients with hypertension, hypotension, or cardiac disease. The intravenous administration of barbiturates should be reserved for emergency treatment of acute seizures or for anesthesia.
Heart Failure
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Heart Failure.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
High Blood Pressure
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with High Blood Pressure.
The intravenous administration of barbiturates may produce severe cardiovascular reactions such as bradycardia, hypertension, or vasodilation with fall in blood pressure, particularly during rapid infusion. Parenteral therapy with barbiturates should be administered cautiously in patients with hypertension, hypotension, or cardiac disease. The intravenous administration of barbiturates should be reserved for emergency treatment of acute seizures or for anesthesia.
Minor:
Antrocol
The atropine in Antrocol has a minor potential interaction with High Blood Pressure.
Cardiovascular effects of anticholinergics may exacerbate hypertension. Therapy with anticholinergic agents should be administered cautiously in patients with hypertension.
High Cholesterol
Moderate:
clozapine
cloZAPine has a moderate potential interaction with High Cholesterol.
Atypical antipsychotic drugs have been associated with undesirable alterations in lipid levels. While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile. Before or soon after initiation of antipsychotic medications, a fasting lipid profile should be obtained at baseline and monitored periodically during treatment.
History - Myocardial Infarction
Moderate:
clozapine
cloZAPine has a moderate potential interaction with History - Myocardial Infarction.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Hyperkinetic Syndrome of Childhood
Moderate:
Antrocol
The PHENobarbital in Antrocol has a moderate potential interaction with Hyperkinetic Syndrome of Childhood.
Paradoxical reactions characterized by excitability and restlessness may occur in pediatric patients with hyperactive aggressive disorders. Such patients should be monitored for signs of paradoxical stimulation during therapy with barbiturates.
Hyperprolactinemia
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Hyperprolactinemia.
The chronic use of neuroleptic agents can cause persistent elevations in prolactin levels due to antagonism of dopamine D2 receptors. Based on in vitro data, approximately one-third of human breast cancers are thought to be prolactin-dependent. The clinical significance of this observation with respect to long-term neuroleptic therapy is unknown. Chronic administration of neuroleptic drugs has been associated with mammary tumorigenesis in rodent studies but not in human clinical or epidemiologic studies. Until further data are available, therapy with neuroleptic agents should be administered cautiously in patients with a previously detected breast cancer. Caution is also advised in patients with preexisting hyperprolactinemia. Hyperprolactinemia may suppress hypothalamic gonadotrophin releasing hormone (GnRH), resulting in reduced pituitary gonadotropin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds; however, the clinical significance of elevated serum prolactin levels is unknown for most patients. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male patients.
Hyperthyroidism
Minor:
Antrocol
The atropine in Antrocol has a minor potential interaction with Hyperthyroidism.
In general, agents with anticholinergic activity may exacerbate hyperthyroidism. Therapy with anticholinergics should be administered cautiously in patients with hyperthyroidism. Thyroid levels should be monitored if usage is prolonged.
Hypotension
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Hypotension.
The intravenous administration of barbiturates may produce severe cardiovascular reactions such as bradycardia, hypertension, or vasodilation with fall in blood pressure, particularly during rapid infusion. Parenteral therapy with barbiturates should be administered cautiously in patients with hypertension, hypotension, or cardiac disease. The intravenous administration of barbiturates should be reserved for emergency treatment of acute seizures or for anesthesia.
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Hypotension.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Infectious Gastroenteritis
Major:
Antrocol
The atropine in Antrocol has a major potential interaction with Infectious Gastroenteritis.
The use of drugs with antiperistaltic activity (primarily antidiarrheal and antimuscarinic agents, but also antispasmodic agents such as dicyclomine or oxybutynin at high dosages) is contraindicated in patients with diarrhea due to pseudomembranous enterocolitis or enterotoxin-producing bacteria. These drugs may prolong and/or worsen diarrhea associated with organisms that invade the intestinal mucosa, such as toxigenic E. coli, Salmonella and Shigella, and pseudomembranous colitis due to broad-spectrum antibiotics. Other symptoms and complications such as fever, shedding of organisms and extraintestinal illness may also be increased or prolonged. In general, because antiperistaltic agents decrease gastrointestinal motility, they may delay the excretion of infective gastroenteric organisms or toxins and should be used cautiously in patients with any infectious diarrhea, particularly if accompanied by high fever or pus or blood in the stool. Some cough and cold and other combination products may occasionally include antimuscarinic agents for their drying effects and may, therefore, require careful selection when necessary.
Ischemic Heart Disease
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with Ischemic Heart Disease.
Antimuscarinic agents block vagal inhibition of the SA nodal pacemaker. These agents should be administered cautiously in patients with tachycardia, congestive heart failure, or coronary artery disease. Premature ventricular depolarization or ventricular tachycardia or fibrillation associated with antimuscarinic drugs is rare.
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Ischemic Heart Disease.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Liver Disease
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Liver Disease.
Barbiturates are extensively metabolized by the liver. The plasma clearance of barbiturates may be decreased and the half-lives prolonged in patients with impaired hepatic function. Therapy with barbiturates should be administered cautiously and initiated at reduced dosages in patients with liver disease. Barbiturates are not recommended for use in patients with cirrhosis, hepatic failure, hepatic coma, or other severe hepatic impairment.
Major:
clozapine
cloZAPine has a major potential interaction with Liver Disease.
Hepatitis has been reported in association with the use of clozapine, both in patients with and without underlying liver function abnormalities. Therapy with clozapine should be administered cautiously in patients with preexisting liver disease. The drug should be discontinued if clinically significant elevations of liver function tests or symptoms of jaundice occur.
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with Liver Disease.
Atropine-like agents undergo significant hepatic metabolism. Therapy with atropine-like agents should be administered cautiously to patients with liver disease.
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Liver Disease.
Most neuroleptic agents are extensively metabolized by the liver. The plasma concentrations of these agents may be increased and the half-lives prolonged in patients with impaired hepatic function. Therapy with neuroleptic agents should be administered cautiously in patients with significant liver disease. Lower initial dosages and slower titration may be appropriate.
Myasthenia Gravis
Major:
Antrocol
The atropine in Antrocol has a major potential interaction with Myasthenia Gravis.
Because antimuscarinic agents have anticholinergic effects, they are contraindicated in patients with myasthenia gravis. Their use may be appropriate to reduce adverse muscarinic effects caused by an anticholinesterase agent.
Neuroleptic Malignant Syndrome
Major:
clozapine
cloZAPine has a major potential interaction with Neuroleptic Malignant Syndrome.
The central dopaminergic blocking effects of neuroleptic agents may precipitate or aggravate a potentially fatal symptom complex known as neuroleptic malignant syndrome (NMS). NMS is observed most frequently when high-potency agents like haloperidol are administered intramuscularly, but may occur with any neuroleptic agent given for any length of time. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, altered mental status and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). Additional signs may include elevated creatine phosphokinase, myoglobinuria, and acute renal failure. Neuroleptic agents should not be given to patients with active NMS and should be immediately discontinued if currently being administered in such patients. In patients with a history of NMS, introduction or reintroduction of neuroleptic agents should be carefully considered, since NMS may recur.
Neutropenia
Major:
clozapine
cloZAPine has a major potential interaction with Neutropenia.
The use of clozapine is contraindicated in patients with myeloproliferative disorders, preexisting bone marrow depression, or a history of clozapine-induced agranulocytosis or severe granulocytopenia. Clozapine therapy is associated with the development of agranulocytosis, defined as an absolute neutrophil count (ANC) below 500/mm3. The cumulative incidence is estimated at 1% to 2% after one year of use. The onset is generally between 4 to 16 weeks following initiation of therapy, and it is usually reversible if detected early and the drug discontinued promptly. All patients should have a white blood cell (WBC) count prior to initiating therapy, and clozapine should not be administered if baseline WBC count is less than 3500/mm3. WBC counts and differential should be monitored closely during therapy and for 4 weeks after end of therapy according to product labeling. Also, patients should be advised to immediately report signs of infection such as fever, sore throat, malaise, lethargy, and flu-like symptoms. Individuals who develop clozapine-induced agranulocytosis or severe granulocytopenia (WBC count < 2000/mm3 or ANC < 1000/mm3) should not be rechallenged following recovery, since the condition may recur, often with a shorter latency on reexposure. If continued neuroleptic therapy is necessary, other agents may be used with little apparent risk of cross-sensitivity.
Panhypopituitarism
Moderate:
Antrocol
The PHENobarbital in Antrocol has a moderate potential interaction with Panhypopituitarism.
Barbiturates, especially phenobarbital, secobarbital and butabarbital, may diminish the systemic effects of exogenous and endogenous corticosteroids via induction of hepatic microsomal enzymes, thereby accelerating the metabolism of corticosteroids. In addition, barbiturates may interfere with pituitary corticotropin production. Therapy with barbiturates should be administered cautiously in patients with adrenal insufficiency. Patients with borderline hypoadrenalism should be monitored closely, and patients receiving steroid supplementation may require an adjustment in dosage when barbiturates are added to or withdrawn from their medication regimen.
Parkinsonism
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Parkinsonism.
The use of neuroleptic agents is associated with pseudo-parkinsonian symptoms such as akinesia, bradykinesia, tremors, pill-rolling motion, cogwheel rigidity, and postural abnormalities including stooped posture and shuffling gait. The onset is usually 1 to 2 weeks following initiation of therapy or an increase in dosage. Older neuroleptic agents such as haloperidol are more likely to induce these effects, and their use may be contraindicated in patients with Parkinson's disease or parkinsonian symptoms.
Porphyria
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Porphyria.
The use of barbiturates is contraindicated in patients with a history of porphyria. Barbiturates may exacerbate acute intermittent porphyria or porphyria variegata by inducing the enzymes responsible for porphyrin synthesis.
Psychosis
Moderate:
Antrocol
The PHENobarbital in Antrocol 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.
Pulmonary Embolism
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Pulmonary Embolism.
Thromboembolic events such as deep-vein thrombosis and pulmonary embolism have been noted during clozapine therapy. Therapy with clozapine should be administered cautiously in patients with an active or past history of thromboembolic events.
Pulmonary Impairment
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Pulmonary Impairment.
Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. 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 barbiturates 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. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.
Renal Dysfunction
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Renal Dysfunction.
The long-acting barbiturate, phenobarbital, is partially eliminated by the kidney. The plasma clearance of phenobarbital may be decreased and the half-life prolonged in patients with impaired renal function. Therapy with phenobarbital should be administered cautiously and initiated at reduced dosages in patients with renal impairment. Since approximately 75% of a mephobarbital dose is metabolized to phenobarbital, the same precaution should be observed with mephobarbital. The remaining barbiturates, which are short- and intermediate-acting, are all negligibly excreted in the urine and may be appropriate alternatives in these patients.
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with Renal Dysfunction.
Atropine-like agents are primarily eliminated by the kidney. Therapy with atropine-like agents should be administered cautiously to patients with renal disease.
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Renal Dysfunction.
Clozapine is extensively metabolized by the liver and subsequently excreted in the urine (50%) and feces (35%), primarily as metabolites. One of the metabolites appears to have only limited pharmacologic activity, while the others are inactive. However, the effects of possible metabolite accumulation have not been studied. The manufacturer recommends that therapy with clozapine be administered cautiously in patients with impaired renal function.
Respiratory Arrest
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Respiratory Arrest.
Barbiturates may produce severe respiratory depression, apnea, laryngospasm, bronchospasm and cough, particularly during rapid intravenous administration. In usual hypnotic dosages, the degree of respiratory depression produced is similar to that which occurs during physiologic sleep, while at higher dosages, the rate, depth and volume of respiration may be markedly decreased. 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 barbiturates 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. Barbiturates, especially injectable formulations, should generally be avoided in patients with sleep apnea, hypoxia, or severe pulmonary diseases in which dyspnea or obstruction is evident.
Major:
clozapine
cloZAPine has a major potential interaction with Respiratory Arrest.
The use of neuroleptic agents is contraindicated in comatose patients and patients with severe central nervous system depression. Neuroleptic agents may potentiate the CNS and respiratory depression in these patients.
Seizures
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Seizures.
Antipsychotic and neuroleptic drugs can lower the seizure threshold and trigger seizures in a dose-dependent manner. This risk is greatest in patients with a history of seizures or with conditions that lower the seizure threshold. Therapy with these drugs should be administered cautiously in patients with a history of seizures or other predisposing factors, such as head trauma, CNS abnormalities, and alcoholism.
Shock
Major:
Antrocol
The PHENobarbital in Antrocol has a major potential interaction with Shock.
Barbiturates should not be administered by injection to patients in shock or coma or who have recently received another respiratory depressant. The hypnotic and hypotensive effects of these agents may be prolonged and intensified in such patients.
Syncope
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Syncope.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Tardive Dyskinesia
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Tardive Dyskinesia.
Tardive dyskinesia (TD) has occurred in patients treated with antipsychotic drugs; the syndrome consists of potentially irreversible, involuntary, dyskinetic movements. The risk appears highest in older patients (particularly older women) but it is not possible to predict which patients are likely to develop TD; whether antipsychotic drugs differ in their potential to cause TD is unknown. The risk of TD and the likelihood that it will become irreversible increase with the duration of therapy and the total cumulative dose. The syndrome can develop after relatively brief treatment periods, even at low dosages; it may also occur after discontinuation of therapy. TD may remit (partially or completely) upon discontinuation of antipsychotic therapy, although antipsychotic therapy itself may suppress (or partially suppress) signs/symptoms of TD, possibly masking the underlying process; the effect of symptomatic suppression on the long-term course of TD is unknown. In patients with preexisting drug-induced TD, initiating or increasing the dosage of antipsychotic therapy may temporarily mask the symptoms of TD but could eventually worsen the condition. In patients requiring chronic therapy, the lowest dose and shortest duration of therapy producing a satisfactory clinical response are recommended; the need for continued therapy should be reassessed periodically. If signs/symptoms of TD occur during antipsychotic therapy, discontinuation of the offending agent should be considered; however, some patients may require treatment despite the presence of TD.
Thrombotic/Thromboembolic Disorder
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.
Thromboembolic events such as deep-vein thrombosis and pulmonary embolism have been noted during clozapine therapy. Therapy with clozapine should be administered cautiously in patients with an active or past history of thromboembolic events.
Ulcerative Colitis
Moderate:
Antrocol
The atropine in Antrocol has a moderate potential interaction with Ulcerative Colitis.
Antimuscarinic agents may suppress intestinal motility and produce paralytic ileus with resultant precipitation of toxic megacolon. These drugs should be administered cautiously to patients with ulcerative colitis.
Urinary Retention
Major:
Antrocol
The atropine in Antrocol has a major potential interaction with Urinary Retention.
In general, the use of anticholinergic agents is contraindicated in patients with urinary retention and bladder neck obstruction caused by prostatic hypertrophy. Dysuria may occur and may require catheterization. Also, anticholinergic drugs may aggravate partial obstructive uropathy. Caution is advised even when using agents with mild to moderate anticholinergic activity, particularly in elderly patients.
Major:
clozapine
cloZAPine has a major potential interaction with Urinary Retention.
Neuroleptic agents have anticholinergic activity, to which elderly patients are particularly sensitive. Clozapine and low-potency agents such as chlorpromazine and thioridazine tend to exhibit greater anticholinergic effects than other agents in the class. Clozapine use has been associated with impairment of intestinal peristalsis ranging from constipation to intestinal obstruction, fecal impaction, and paralytic ileus. Therapy with neuroleptic agents should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders.
Vitamin D Deficiency
Moderate:
Antrocol
The PHENobarbital in Antrocol has a moderate potential interaction with Vitamin D Deficiency.
Rickets and osteomalacia have rarely been reported following prolonged use of barbiturates, possibly due to increased metabolism of vitamin D as a result of enzyme induction by barbiturates. Long-term therapy with barbiturates should be administered cautiously in patients with vitamin D deficiency.
Vomiting
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Vomiting.
The use of atypical antipsychotic agents has been associated with orthostatic hypotension and syncope. Therapy with atypical antipsychotics should be administered cautiously in patients with hypotension or conditions that could be exacerbated by hypotension, such as a history of myocardial infarction, angina, or ischemic stroke. Patients with dehydration (e.g., due to severe diarrhea or vomiting) may be predisposed to hypotension and should also be managed carefully during therapy with atypical antipsychotics. Blood pressure should be monitored at regular intervals, particularly during dosage escalation or whenever dosage has been altered, and patients should be advised not to rise abruptly from a sitting or recumbent position.
Weight Loss
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Weight Loss.
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported with the use of atypical antipsychotic agents. Patients with diabetes should be monitored for worsening control of blood glucose when treated with these agents. It is recommended that patients with risk factors for diabetes mellitus starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment, and periodically thereafter. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when treatment with these agents was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the atypical antipsychotic drug.
Moderate:
clozapine
cloZAPine has a moderate potential interaction with Weight Loss.
Weight gain has been observed with atypical antipsychotic use. While all agents in the class have been shown to produce some changes, each drug has its own specific risk profile. When treating pediatric patients with atypical antipsychotic agents, weight gain should be monitored and assessed against that expected for normal growth. Monitor weight at baseline and frequently thereafter.
More resources
Antrocol
A total of 934 drugs are known to interact with Antrocol.
- Antrocol is in the drug class anticholinergics/antispasmodics.
clozapine
A total of 985 drugs are known to interact with clozapine.
- Clozapine is in the drug class atypical antipsychotics.
-
Clozapine is used to treat the following conditions:
- Borderline Personality Disorder (off-label)
- Paranoid Disorder (off-label)
- Schizophrenia
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. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.