Interactions between Chlorpheniramine and Guanfacine
1 drug interaction and 22 additional warnings found for the following 2 drugs:
- chlorpheniramine
- guanfacine
Drug interactions
Moderate drug interactions
Moderate:
chlorpheniramine guanFACINE
Applies to: chlorpheniramine and guanfacine
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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- Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
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- Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther, 36, p. 451-5
- Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF (1988) "Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic." Psychopharmacology (Berl), 96, p. 63-6
- Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I (1989) "Midazolam-morphine sedative interaction in patients." Anesth Analg, 68, p. 282-5
- "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
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- Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G (1989) "The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine." Acta Psychiatr Scand, 80 Suppl, p. 95-8
- Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
- (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
- (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
- (2001) "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc)
- (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
- (2001) "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company
- (2001) "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals
- Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
- (2001) "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical
- (2001) "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals
- Ferslew KE, Hagardorn AN, McCormick WF (1990) "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci, 35, p. 477-82
- Plushner SL (2000) "Valerian: valeriana officinalis." Am J Health Syst Pharm, 57, p. 328-35
- (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc
- (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2014) "Product Information. Belsomra (suvorexant)." Merck & Co., Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
guanFACINE Food/Lifestyle
Applies to: guanfacine
Generally avoid
Grapefruit juice may increase the plasma concentrations of guanfacine. The risk of adverse reactions such as hypotension, bradycardia, and sedation may increase. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Ketoconazole, a potent CYP450 3A4 inhibitor, has been reported to increase guanfacine peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 2- and 3-fold, respectively. A computer simulation suggests that fluconazole, a moderate CYP450 3A4 inhibitor, would increase guanfacine Cmax and AUC by about 1.5- and 2-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
Generally avoid
Alcohol may enhance the sedative and hypotensive effects of guanfacine.
Generally avoid
Administration of extended-release guanfacine with a high-fat meal may increase the bioavailability of guanfacine. When a single 4 mg dose of extended-release guanfacine was administered to adult volunteers with a high-fat breakfast, mean guanfacine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 75% and 40%, respectively, compared to dosing in a fasted state.
Management
Patients treated with guanfacine should avoid consumption of grapefruit and grapefruit juice. In addition, it is preferable to avoid or limit the use of alcohol during treatment. Patients should be advised against driving or operating hazardous machinery until they know how the medication affects them. The extended-release formulation of guanfacine should not be taken together with a high-fat meal.
References (3)
- (2001) "Product Information. Tenex (guanfacine)." Wyeth-Ayerst Laboratories
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2009) "Product Information. Intuniv (guanfacine)." Shire US Inc
Moderate food/lifestyle interactions
Moderate:
chlorpheniramine Food/Lifestyle
Applies to: chlorpheniramine
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.
Disease interactions
20 potential interactions Applies to: 17 conditions, including Depression, Asthma, COPD, Hypotension, and Hyperthyroidism.
Asthma
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Asthma.
It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.
Cardiovascular Conditions and Disorders
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Cardiovascular Conditions and Disorders.
Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.
Cerebrovascular Insufficiency
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Cerebrovascular Insufficiency.
Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system, resulting in decreases in heart rate, peripheral and renovascular resistance, and blood pressure. Therapy with these agents should be administered cautiously in patients with hypotension or conditions that may be exacerbated by decreased blood pressure and perfusion, such as coronary insufficiency, peripheral vascular disease (e.g., Raynaud's syndrome), cerebrovascular disease, or recent myocardial infarction.
COPD
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with COPD.
It has been suggested that the anticholinergic effect of antihistamines may reduce the volume and cause thickening of bronchial secretions, resulting in obstruction of respiratory tract. Some manufacturers and clinicians recommend that therapy with antihistamines be administered cautiously in patients with asthma or chronic obstructive pulmonary disease.
Depression
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Depression.
Central alpha-2 adrenoreceptor agonists may occasionally cause mental depression and should be used cautiously in patients with a history of depression.
Gastrointestinal Obstruction
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Gastrointestinal Obstruction.
Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, 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. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.
Glaucoma/Intraocular Hypertension
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Glaucoma/Intraocular Hypertension.
Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, 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. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.
Heart Block
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Heart Block.
Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system. Heart rate is decreased, which may lead to or exacerbate sinus bradycardia and atrioventricular block. Therapy with central alpha-2 adrenoreceptor agonists should be administered cautiously in patients with conduction disturbances such as sinus node dysfunction or AV nodal disease.
Hyperkinetic Syndrome of Childhood
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Hyperkinetic Syndrome of Childhood.
The safety and effectiveness of guanfacine in children under 12 years of age has not been demonstrated and its use in this age group is not recommended. However, there have been some spontaneous postmarketing reports of mania and aggressive behavioral changes in pediatric patients with attention- deficit hyperactivity disorder (ADHD) that received this drug. All patients had medical or family risks of bipolar disorder, and all of them recovered after treatment discontinuation. Hallucinations have also been reported in pediatric patients receiving guanfacine for the treatment of ADHD.
Hyperthyroidism
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Hyperthyroidism.
Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.
Hypotension
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Hypotension.
Antihistamines may infrequently cause cardiovascular adverse effects related to their anticholinergic and local anesthetic (quinidine-like) activities. Tachycardia, palpitation, ECG changes, arrhythmias, hypotension, and hypertension have been reported. Although these effects are uncommon and usually limited to overdosage situations, the manufacturers and some clinicians recommend that therapy with antihistamines be administered cautiously in patients with cardiovascular disease, hypertension, and/or hyperthyroidism.
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Hypotension.
Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system, resulting in decreases in heart rate, peripheral and renovascular resistance, and blood pressure. Therapy with these agents should be administered cautiously in patients with hypotension or conditions that may be exacerbated by decreased blood pressure and perfusion, such as coronary insufficiency, peripheral vascular disease (e.g., Raynaud's syndrome), cerebrovascular disease, or recent myocardial infarction.
Ischemic Heart Disease
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Ischemic Heart Disease.
Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system, resulting in decreases in heart rate, peripheral and renovascular resistance, and blood pressure. Therapy with these agents should be administered cautiously in patients with hypotension or conditions that may be exacerbated by decreased blood pressure and perfusion, such as coronary insufficiency, peripheral vascular disease (e.g., Raynaud's syndrome), cerebrovascular disease, or recent myocardial infarction.
Liver Disease
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Liver Disease.
Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Liver Disease.
Normally, approximately 50% of a guanfacine dose is eliminated unchanged by the kidney and the rest metabolized by the liver. However, neither the parent drug nor its metabolites accumulate significantly during chronic dosing in patients with severe renal impairment due to increased hepatic metabolism of the drug in these patients. Thus, initial dosage adjustments are generally not necessary in renal impairment. Dosage titration, however, should be made cautiously if hepatic function is also compromised. The pharmacokinetics of guanfacine has not been studied in patients with liver disease. The manufacturer recommends caution when the drug is used in such patients.
Peripheral Arterial Disease
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Peripheral Arterial Disease.
Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system, resulting in decreases in heart rate, peripheral and renovascular resistance, and blood pressure. Therapy with these agents should be administered cautiously in patients with hypotension or conditions that may be exacerbated by decreased blood pressure and perfusion, such as coronary insufficiency, peripheral vascular disease (e.g., Raynaud's syndrome), cerebrovascular disease, or recent myocardial infarction.
Renal Dysfunction
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Renal Dysfunction.
Limited pharmacokinetic data are available for the older, first-generation antihistamines. Many appear to be primarily metabolized by the liver, and both parent drugs and metabolites are excreted in the urine. Patients with renal and/or liver disease may be at greater risk for adverse effects from antihistamines due to drug and metabolite accumulation. Therapy with antihistamines should be administered cautiously in such patients. Lower initial dosages may be appropriate.
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Renal Dysfunction.
Normally, approximately 50% of a guanfacine dose is eliminated unchanged by the kidney and the rest metabolized by the liver. However, neither the parent drug nor its metabolites accumulate significantly during chronic dosing in patients with severe renal impairment due to increased hepatic metabolism of the drug in these patients. Thus, initial dosage adjustments are generally not necessary in renal impairment. Dosage titration, however, should be made cautiously if hepatic function is also compromised. The pharmacokinetics of guanfacine has not been studied in patients with liver disease. The manufacturer recommends caution when the drug is used in such patients.
Sinus Node Dysfunction
Moderate:
guanfacine
guanFACINE has a moderate potential interaction with Sinus Node Dysfunction.
Central alpha-2 adrenoreceptor agonists reduce sympathetic outflow from the central nervous system. Heart rate is decreased, which may lead to or exacerbate sinus bradycardia and atrioventricular block. Therapy with central alpha-2 adrenoreceptor agonists should be administered cautiously in patients with conduction disturbances such as sinus node dysfunction or AV nodal disease.
Urinary Retention
Moderate:
chlorpheniramine
Chlorpheniramine has a moderate potential interaction with Urinary Retention.
Antihistamines often have anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with antihistamines should be administered cautiously, if at all, 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. Conventional, first-generation antihistamines such as the ethanolamines (bromodiphenhydramine, carbinoxamine, clemastine, dimenhydrinate, diphenhydramine, doxylamine, phenyltoloxamine) tend to exhibit substantial anticholinergic effects. In contrast, the newer, relatively nonsedating antihistamines (e.g., cetirizine, fexofenadine, loratadine) reportedly have low to minimal anticholinergic activity at normally recommended dosages and may be appropriate alternatives.
More resources
chlorpheniramine
A total of 358 drugs are known to interact with chlorpheniramine.
- Chlorpheniramine is in the drug class antihistamines.
- Chlorpheniramine is used to treat the following conditions:
guanfacine
A total of 534 drugs are known to interact with guanfacine.
- Guanfacine is in the drug class antiadrenergic agents, centrally acting.
-
Guanfacine is used to treat the following conditions:
- ADHD
- High Blood Pressure
- Tourette's Syndrome (off-label)
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
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