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Drug overview for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl):
Generic name: GUAIFENESIN/PSEUDOEPHEDRINE HCL (gweye-FEN-eh-sin/fen-ill-EFF-rin)
Drug class: Amphetamines/Anorexiants/Stimulants
Therapeutic class: Respiratory Therapy Agents
Dextromethorphan, a derivative of levorphanol, is an antitussive agent. Guaifenesin is an expectorant. Phenylephrine hydrochloride is a sympathomimetic amine that predominantly Pseudoephedrine is a sympathomimetic agent that occurs naturally in plants acts by a direct effect on alpha1-adrenergic receptors. of the genus Ephedra; the drug acts directly on both alpha- and, to a lesser degree, beta-adrenergic receptors.
Dextromethorphan is used for the temporary relief of coughs caused by minor Pseudoephedrine is used as a nasal decongestant for self-medication for the temporary relief of nasal congestion associated with upper respiratory throat and bronchial irritation such as may occur with common colds or with allergy and to provide temporary relief of sinus congestion and pressure. inhaled irritants. Dextromethorphan is most effective in the treatment of chronic, nonproductive cough.
The drug is a common ingredient in commercial The drug also has been used for self-medication in the symptomatic cough mixtures available without prescription. prevention of otitic barotrauma+ (aerotitis ( barotitis) media). Pseudoephedrine also has been misused for clandestine synthesis of Although cough and cold preparations that contain cough suppressants methamphetamine and methcathinone for illicit use.
(including dextromethorphan), nasal decongestants, antihistamines, and/or expectorants commonly are used in pediatric patients younger than 2 years of age, systematic reviews of controlled trials have concluded that nonprescription (over-the-counter, OTC) cough and cold preparations are not more effective than placebo in reducing acute cough and other symptoms of upper respiratory tract infection in these patients. Furthermore, adverse events, including deaths, have been (and continue to be) reported in pediatric patients younger than 2 years of age receiving these preparations. (See Cautions: Pediatric Precautions and see Acute Toxicity: Manifestations.) For information on abuse of dextromethorphan, see Cautions. For use of dextromethorphan hydrobromide in fixed combination with quinidine sulfate in the treatment of pseudobulbar affect (PBA), see Dextromethorphan Hydrobromide and Quinidine Sulfate 28:92.
Generic name: GUAIFENESIN/PSEUDOEPHEDRINE HCL (gweye-FEN-eh-sin/fen-ill-EFF-rin)
Drug class: Amphetamines/Anorexiants/Stimulants
Therapeutic class: Respiratory Therapy Agents
Dextromethorphan, a derivative of levorphanol, is an antitussive agent. Guaifenesin is an expectorant. Phenylephrine hydrochloride is a sympathomimetic amine that predominantly Pseudoephedrine is a sympathomimetic agent that occurs naturally in plants acts by a direct effect on alpha1-adrenergic receptors. of the genus Ephedra; the drug acts directly on both alpha- and, to a lesser degree, beta-adrenergic receptors.
Dextromethorphan is used for the temporary relief of coughs caused by minor Pseudoephedrine is used as a nasal decongestant for self-medication for the temporary relief of nasal congestion associated with upper respiratory throat and bronchial irritation such as may occur with common colds or with allergy and to provide temporary relief of sinus congestion and pressure. inhaled irritants. Dextromethorphan is most effective in the treatment of chronic, nonproductive cough.
The drug is a common ingredient in commercial The drug also has been used for self-medication in the symptomatic cough mixtures available without prescription. prevention of otitic barotrauma+ (aerotitis ( barotitis) media). Pseudoephedrine also has been misused for clandestine synthesis of Although cough and cold preparations that contain cough suppressants methamphetamine and methcathinone for illicit use.
(including dextromethorphan), nasal decongestants, antihistamines, and/or expectorants commonly are used in pediatric patients younger than 2 years of age, systematic reviews of controlled trials have concluded that nonprescription (over-the-counter, OTC) cough and cold preparations are not more effective than placebo in reducing acute cough and other symptoms of upper respiratory tract infection in these patients. Furthermore, adverse events, including deaths, have been (and continue to be) reported in pediatric patients younger than 2 years of age receiving these preparations. (See Cautions: Pediatric Precautions and see Acute Toxicity: Manifestations.) For information on abuse of dextromethorphan, see Cautions. For use of dextromethorphan hydrobromide in fixed combination with quinidine sulfate in the treatment of pseudobulbar affect (PBA), see Dextromethorphan Hydrobromide and Quinidine Sulfate 28:92.
DRUG IMAGES
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The following indications for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl) have been approved by the FDA:
Indications:
Cold symptoms
Cough
Nasal congestion
Rhinitis
Rhinorrhea
Professional Synonyms:
Nasal stuffiness
Indications:
Cold symptoms
Cough
Nasal congestion
Rhinitis
Rhinorrhea
Professional Synonyms:
Nasal stuffiness
The following dosing information is available for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl):
Dosages of dextromethorphan hydrobromide and dextromethorphan polistirex are expressed in terms of dextromethorphan hydrobromide.
The usual dosage of dextromethorphan hydrobromide for adults and children 12 years of age or older is 10-20 mg every 4 hours or 30 mg every 6-8 hours, not to exceed 120 mg daily, or as directed by a clinician. The usual dosage for children 6 to younger than 12 years of age is 5-10 mg every 4 hours or 15 mg every 6-8 hours, not to exceed 60 mg daily, or as directed by a clinician. Children 2 to younger than 6 years of age may receive 2.5-5
mg every 4 hours or 7.5 mg every 6-8 hours, not to exceed 30 mg daily, or as directed by a clinician. Dosage in children younger than 2 years of age must be individualized.
Suggested dosages for children younger than 2 years of age+ for some cough and cold preparations have been published in various references for prescribing and parenting. Using recommended dosages for adults and older children, some clinicians have extrapolated dosages for these preparations based on the weight or age of children younger than 2 years of age. However, these extrapolations were based on assumptions that pathology of the disease and pharmacology of the drugs are similar in adults and pediatric patients.
There currently are no specific dosage recommendations (i.e., approved by the US Food and Drug Administration (FDA)) for cough and cold preparations for this patient population. (See Cautions: Pediatric Precautions.)
The usual dosage of dextromethorphan hydrobromide as the extended-release oral suspension containing the polistirex for adults and children 12 years of age or older is 60 mg twice daily. The usual dosage as the extended-release oral suspension for children 6 to younger than 12 years of age is 30 mg twice daily; children 2 to younger than 6 years of age may receive 15 mg twice daily.
Phenylephrine hydrochloride should be administered in the lowest effective dosage for the shortest possible time. When used to increase blood pressure in patients with acute hypotensive states, dosage should be individualized based on the pressor response.
The usual dosage of dextromethorphan hydrobromide for adults and children 12 years of age or older is 10-20 mg every 4 hours or 30 mg every 6-8 hours, not to exceed 120 mg daily, or as directed by a clinician. The usual dosage for children 6 to younger than 12 years of age is 5-10 mg every 4 hours or 15 mg every 6-8 hours, not to exceed 60 mg daily, or as directed by a clinician. Children 2 to younger than 6 years of age may receive 2.5-5
mg every 4 hours or 7.5 mg every 6-8 hours, not to exceed 30 mg daily, or as directed by a clinician. Dosage in children younger than 2 years of age must be individualized.
Suggested dosages for children younger than 2 years of age+ for some cough and cold preparations have been published in various references for prescribing and parenting. Using recommended dosages for adults and older children, some clinicians have extrapolated dosages for these preparations based on the weight or age of children younger than 2 years of age. However, these extrapolations were based on assumptions that pathology of the disease and pharmacology of the drugs are similar in adults and pediatric patients.
There currently are no specific dosage recommendations (i.e., approved by the US Food and Drug Administration (FDA)) for cough and cold preparations for this patient population. (See Cautions: Pediatric Precautions.)
The usual dosage of dextromethorphan hydrobromide as the extended-release oral suspension containing the polistirex for adults and children 12 years of age or older is 60 mg twice daily. The usual dosage as the extended-release oral suspension for children 6 to younger than 12 years of age is 30 mg twice daily; children 2 to younger than 6 years of age may receive 15 mg twice daily.
Phenylephrine hydrochloride should be administered in the lowest effective dosage for the shortest possible time. When used to increase blood pressure in patients with acute hypotensive states, dosage should be individualized based on the pressor response.
Dextromethorphan preparations are administered orally. Lozenges containing dextromethorphan hydrobromide should not be used in children younger than 6 years of age and liquid-filled capsules containing the drug should not be used in children younger than 12 years of age, unless otherwise directed by a clinician. Guaifenesin is administered orally.
Mucinex(R) 600-mg extended-release tablets should not be broken, crushed, or chewed and should not be used in children younger than 12 years of age; the tablets should be kept out of reach of young children to avoid accidental swallowing and choking. Pseudoephedrine hydrochloride and sulfate are administered orally. Pseudoephedrine hydrochloride 240-mg extended-release tablets should be administered orally once daily and swallowed whole with water; the extended-release tablets should not be divided, crushed, chewed, or dissolved. Patients should be advised that the tablet does not completely dissolve and may be passed in the stool.
Mucinex(R) 600-mg extended-release tablets should not be broken, crushed, or chewed and should not be used in children younger than 12 years of age; the tablets should be kept out of reach of young children to avoid accidental swallowing and choking. Pseudoephedrine hydrochloride and sulfate are administered orally. Pseudoephedrine hydrochloride 240-mg extended-release tablets should be administered orally once daily and swallowed whole with water; the extended-release tablets should not be divided, crushed, chewed, or dissolved. Patients should be advised that the tablet does not completely dissolve and may be passed in the stool.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl):
There are 4 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Sympathomimetics (Indirect & Mixed Acting)/MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Catecholamine stores increased by MAOIs can be released by indirect acting sympathomimetics such as ephedrine and amphetamine. MAO inhibitors also interfere with gut and liver metabolism of direct acting sympathomimetics (e.g oral phenylephrine). CLINICAL EFFECTS: Concurrent use of MAOIs may result in potentiation of sympathomimetic effects, which may result in headaches, hypertensive crisis, toxic neurological effects, and malignant hyperpyrexia. Fatalities have occurred. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of monoamine oxidase inhibitors and sympathomimetics is contraindicated. The manufacturers of sympathomimetic agents recommend waiting 14 days after discontinuation of MAO inhibitors before initiating the sympathomimetic. DISCUSSION: Indirect acting sympathomimetic amines may cause abrupt elevation of blood pressure when administered to patients taking monoamine oxidase inhibitors, resulting in a potentially fatal hypertensive crisis. Mixed (direct and indirect) acting sympathomimetics have also been shown to interact with monoamine oxidase inhibitors depending on their degree of indirect action. The direct-acting sympathomimetics have not been reported to interact. Dopamine is metabolized by monoamine oxidase, and its pressor effect is enhanced by monoamine oxidase inhibitors. Since procarbazine, an antineoplastic agent, is a weak monoamine oxidase inhibitor, hypertensive reactions may result from its concurrent use with indirect and mixed acting sympathomimetics. Furazolidone, an antibacterial with monoamine oxidase inhibitor action, has also been shown to interact with indirect acting sympathomimetics. Linezolid is another antibacterial with monoamine oxidase inhibitor properties. Metaxalone is a weak inhibitor of MAO. Foods containing large amounts of tyramine have also been implicated in this interaction. Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. At recommended dosages, rasagiline, oral selegiline, and transdermal selegiline up to 6mg/day are selective for MAO-B; however, at higher dosages they have been shown to lose their selectivity. One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METAXALONE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE |
| Selected Opioids; Dextromethorphan/Selected MAOIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Selected opioids inhibit neural reuptake of serotonin. MAOIs may increase neuronal serotonin concentrations via inhibition of MAO-A.(26) CLINICAL EFFECTS: The concurrent use of selected opioids with MAOIs has resulted in hypotension, hyperpyrexia, sedation, somnolence, and death. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(26) PREDISPOSING FACTORS: Higher opioid concentrations as may occur due to inhibition of opioid clearance, patient specific genomic factors (e.g. poor metabolizer status for a P450 enzyme), or high opioid dosage may increase the risk for a severe interaction. PATIENT MANAGEMENT: Dextromethorphan, diamorphine, meperidine, and tapentadol should not be used in patients taking MAOIs. Use alternative agents for cough or pain. The US manufacturer of Nuedexta(dextromethorphan-quinidine) states Nuedexta is contraindicated within 14 days of MAOI administration.(28) Quinidine increases systemic dextromethorphan concentrations 10 to 20-fold. Other strong CYP2D6 inhibitors such as bupropion, fluoxetine and paroxetine could similarly increase dextromethorphan levels. The US manufacturer of selegiline states that concurrent use with dextromethorphan or meperidine is contraindicated. The US manufacturers of meperidine and tapentadol and the UK manufacturer of diamorphine state that they should not be used concurrently with or within 14 days of taking an MAOI. DISCUSSION: The interaction between meperidine and MAOIs has been well documented. There are at least two reports of potential interactions between MAOIs and dextromethorphan. Concomitant use of quinidine, a strong CYP2D6 inhibitor, increases systemic dextromethorphan concentrations 10 to 20-fold. Other strong CYP2D6 inhibitors such as bupropion, fluoxetine and paroxetine could similarly increase dextromethorphan levels and risk for serotonin toxicity in patients also receiving MAOIs. Furazolidone is known to be a monoamine oxidase inhibitor. Methylene blue, when administered intravenously, has been shown to reach sufficient concentrations to be a potent inhibitor of MAO-A. One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
AZILECT, EMSAM, FURAZOLIDONE, MARPLAN, MATULANE, METHYLENE BLUE, NARDIL, PARNATE, PHENELZINE SULFATE, PROCARBAZINE HCL, PROVAYBLUE, RASAGILINE MESYLATE, SELEGILINE HCL, TRANYLCYPROMINE SULFATE, XADAGO, ZELAPAR |
| Dextromethorphan/Metaxalone SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Dextromethorphan inhibits neural reuptake of serotonin. Metaxalone, a weak inhibitor of MAO, may increase neuronal serotonin concentrations.(1) CLINICAL EFFECTS: The concurrent use of dextromethorphan with MAOIs may result in hypotension, hyperpyrexia, sedation, somnolence, and death. Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(1) PREDISPOSING FACTORS: Higher opioid concentrations as may occur due to inhibition of opioid clearance, patient specific genomic factors (e.g. poor metabolizer status for a P450 enzyme), or high opioid dosage may increase the risk for a severe interaction. PATIENT MANAGEMENT: Dextromethorphan should not be used in patients taking MAOIs such as metaxalone. Use alternative agents for cough. The US manufacturer of Nuedexta (dextromethorphan-quinidine) states Nuedexta is contraindicated within 14 days of MAOI administration.(1) Quinidine increases systemic dextromethorphan concentrations 10 to 20-fold. DISCUSSION: Metaxalone is a weak inhibitor of MAO.(2,3) There are at least two reports of potential interactions between MAOIs and dextromethorphan. Concomitant use of quinidine, a strong CYP2D6 inhibitor, increases systemic dextromethorphan concentrations 10 to 20-fold. Other strong CYP2D6 inhibitors such as bupropion, fluoxetine and paroxetine could similarly increase dextromethorphan levels and risk for serotonin toxicity in patients also receiving MAOIs.(4,5) |
METAXALONE |
| Selected CYP2D6 Substrates/Mavorixafor SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Mavorixafor is a strong inhibitor of CYP2D6 and is expected to inhibit the metabolism of agents through this pathway.(1) CLINICAL EFFECTS: Concurrent use of mavorixafor may result in elevated levels of and toxicity from agents metabolized by CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2) PATIENT MANAGEMENT: The US manufacturer of mavorixafor states concurrent use with CYP2D6 substrate that are highly dependent on CYP2D6 metabolism is contraindicated.(1) DISCUSSION: Mavorixafor (400 mg) increased dextromethorphan (CYP2D6 substrate) maximum concentration (Cmax) and area-under-curve (AUC) by 6-fold and 9-fold, respectively.(1) Selected CYP2D6 substrates linked to this monograph include: aripiprazole, brexpiprazole, desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, fenfluramine, metoclopramide, methoxyphenamine, metoprolol, mexiletine, nebivolol, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, venlafaxine, and yohimbine. |
XOLREMDI |
There are 8 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Ergot Alkaloids/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of ergot alkaloids and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels. CLINICAL EFFECTS: Concurrent use of ergot alkaloids and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid the concurrent use of ergot alkaloids and sympathomimetics. If concurrent use is warranted, monitor blood pressure and for signs of vasoconstriction. Decreasing the dose of one or both drugs may be necessary. DISCUSSION: There have been reports of severe vasoconstriction resulting in gangrene in patients receiving intravenous ergonovine with dopamine or norepinephrine. |
DIHYDROERGOTAMINE MESYLATE, ERGOLOID MESYLATES, ERGOMAR, ERGOTAMINE TARTRATE, ERGOTAMINE-CAFFEINE, METHYLERGONOVINE MALEATE, METHYSERGIDE MALEATE, MIGERGOT, MIGRANAL, TRUDHESA |
| Selected Inhalation Anesthetic Agents/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. The anesthetics produce conduction changes that increase impulse re-entry into the myocardial tissue.(1) The anesthetics' ability to precipitate arrhythmias is enhanced by elevated arterial blood pressure, tachycardia, hypercapnia, and/or hypoxia, events that stimulate the release of endogenous catecholamines.(1) CLINICAL EFFECTS: Concurrent use of inhalation anesthetic agents and sympathomimetics may result in ventricular arrhythmias or sudden blood pressure and heart rate increase during surgery.(2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor blood pressure and avoid use of sympathomimetics in patients being treated with anesthetics on the day of surgery.(2) Intravenous use of epinephrine during surgery with halothane and related halogenated general anesthetics should be strongly discouraged. When intravenous epinephrine is necessary, nitrous oxide anesthesia supplemented with ether, muscle relaxants, or opioids should be used instead of halothane.(3,4) Epinephrine may safely be used subcutaneously with the following precautions: the patient is adequately ventilated to prevent hypoxia or respiratory acidosis; the total dose of epinephrine is limited to 100 mcg/10 minute period or 300 mcg/hour in adults, 3.5 mcg/Kg in infants, 2.5 mcg/Kg in children up to two years of age, and 1.45 mcg/Kg in children over two years of age; a minimum effective concentration of anesthetic is maintained; the drugs are not co-administered in patients with hypertension or other cardiovascular disorders; and the cardiac rhythm is continuously monitored during and after injection.(3-10) If arrhythmias occur after the administration of the epinephrine, the drugs of choice are lidocaine or propranolol, depending on the type of arrhythmia.(1) DISCUSSION: Administration of epinephrine during halothane anesthesia may may lead to serious ventricular arrhythmias.(3-6,11-18) This has occurred when epinephrine was administered intravenously,(6) when it was administered with lidocaine as a dental block,(11,14) or when it was administered supraperiosteally.(5) Norepinephrine has been shown to interact with halothane in a manner similar to epinephrine.(1) In two case reports, patients were given terbutaline (0.25 to 0.35 mg) for wheezing following induction of anesthesia with halothane. One patient's heart rate increased from 68 to 100 beats/minute, and the ECG showed premature ventricular contractions and bigeminy, while the other patient developed multiple unifocal premature ventricular contractions and bigeminy. The arrhythmias resolved in both patients following lidocaine administration.(19) Although not documented, isoproterenol causes effects on the heart similar to terbutaline(20) and would probably interact with halothane in a similar manner. Other inhalation anesthetics that increase the incidence of arrhythmias with epinephrine include chloroform,(20) methoxyflurane,(20) and enflurane.(12) A similar interaction may be expected between the other inhalation anesthetics and sympathomimetics. |
DESFLURANE, FORANE, ISOFLURANE, SEVOFLURANE, SUPRANE, TERRELL, ULTANE |
| Mixed;Indirect Sympathomimetics/Selected MAOIs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Catecholamine stores increased by MAOIs can be released by indirect acting sympathomimetics such as ephedrine and amphetamine. MAO inhibitors also interfere with gut and liver metabolism of direct acting sympathomimetics (e.g oral phenylephrine). CLINICAL EFFECTS: Concurrent use of MAOIs may result in potentiation of sympathomimetic effects, which may result in headaches, hypertensive crisis, toxic neurological effects, and malignant hyperpyrexia. Fatalities have occurred with combinations of sympathomimetics and MAO-A inhibitors. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Concurrent use of MAO-A inhibitors and sympathomimetics is contraindicated. The manufacturers of sympathomimetic agents recommend waiting 14 days after discontinuation of MAO inhibitors before initiating the sympathomimetic. Patients receiving direct or indirect acting sympathomimetics should not receive linezolid unless they are monitored for potential increases in blood pressure. Initial dosages of dopamine and epinephrine should be reduced. At recommended dosages, oral selegiline and transdermal selegiline up to 6mg/day are selective for MAO-B; however, at higher dosages they have been shown to lose their selectivity. Patients receiving higher dosages of selegiline should be considered susceptive to this interaction. DISCUSSION: Indirect acting sympathomimetic amines may cause abrupt elevation of blood pressure when administered to patients taking monoamine oxidase inhibitors, resulting in a potentially fatal hypertensive crisis. Mixed (direct and indirect) acting sympathomimetics have also been shown to interact with monoamine oxidase inhibitors depending on their degree of indirect action. The direct-acting sympathomimetics have not been reported to interact. Dopamine is metabolized by monoamine oxidase, and its pressor effect is enhanced by monoamine oxidase inhibitors. Furazolidone, an antibacterial with monoamine oxidase inhibitor action, has also been shown to interact with indirect acting sympathomimetics. Foods containing large amounts of tyramine have also been implicated in this interaction. A significant pressor response was observed in normal subjects receiving linezolid and tyramine doses of more than 100 mg. Administration of linezolid (600 mg BID for 3 days) with pseudoephedrine (60 mg q 4 hours for 2 doses) increased blood pressure by 32 mmHg. Administration of linezolid (600 mg BID for 3 days) with phenylpropanolamine (25 mg q 4 hours for 2 doses) increased blood pressure by 38 mmHg. One or more of the drug pairs linked to this monograph have been included in a list of interactions that should be considered "high-priority" for inclusion and should not be inactivated in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology. |
EMSAM, LINEZOLID, LINEZOLID-0.9% NACL, LINEZOLID-D5W, SELEGILINE HCL, XADAGO, ZELAPAR, ZYVOX |
| Selected Direct-Acting Sympathomimetics/Tricyclic Compounds SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Unknown. However, it is speculated that direct-acting sympathomimetic amines have an enhanced effect due to tricyclic blockage of norepinephrine reuptake. CLINICAL EFFECTS: Increased effect of direct acting sympathomimetics. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Consider avoiding the concurrent use of direct-acting sympathomimetics and tricyclic compounds. If concurrent use of direct-acting sympathomimetics and tricyclic compounds is warranted, the initial dose of the sympathomimetic should be lowered and the patient should be monitored for adverse cardiovascular effects. Use of tricyclic compounds and other sympathomimetics should be approached with caution. DISCUSSION: Epinephrine and other direct-acting sympathomimetic amines exert enhanced cardiovascular effects (e.g., arrhythmias, hypertension, and tachycardia) in individuals concurrently receiving or previously treated with tricyclic antidepressants. Other direct and mixed acting sympathomimetic amines have also been reported to interact with tricyclic antidepressants. These include norepinephrine, phenylephrine, dopamine, and methoxamine. Protriptyline, amitriptyline, and desipramine have also been reported to interact with direct-acting sympathomimetics. |
AMITRIPTYLINE HCL, AMOXAPINE, ANAFRANIL, CHLORDIAZEPOXIDE-AMITRIPTYLINE, CLOMIPRAMINE HCL, DESIPRAMINE HCL, DOXEPIN HCL, IMIPRAMINE HCL, IMIPRAMINE PAMOATE, NORPRAMIN, NORTRIPTYLINE HCL, PAMELOR, PERPHENAZINE-AMITRIPTYLINE, PROTRIPTYLINE HCL, SILENOR, TRIMIPRAMINE MALEATE |
| Iobenguane I 123/Agents that Affect Catecholamines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1) CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1) DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine) |
ADREVIEW |
| Selected CYP2D6 Substrates/Panobinostat SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Panobinostat is a moderate inhibitor of CYP2D6 and is expected to inhibit the metabolism of agents through this pathway.(1) CLINICAL EFFECTS: Concurrent use of panobinostat may result in elevated levels of and toxicity from agents metabolized by CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(4) PATIENT MANAGEMENT: Avoid the concurrent use of panobinostat with agents that are sensitive CYP2D6 or CYP2D6 substrates with a narrow therapeutic index. If concurrent use is warranted, monitor patients for toxicity.(1) DISCUSSION: In a study in 14 subjects with advanced cancer, panobinostat (20 mg daily on Days 3, 5, and 8) increased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of dextromethorphan (60 mg) by 20-200% and 20-130%, respectively. Dextromethorphan exposures were extremely variable.(1) Selected CYP2D6 substrates linked to this monograph include: desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, methoxyphenamine, metoprolol, nebivolol, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, venlafaxine, and yohimbine. |
FARYDAK |
| Selected CYP1A2 or CYP2D6 Substrates/Givosiran SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Givosiran interferes with the first and rate-limiting step in hepatic heme biosynthesis, which may lower hepatic heme levels and decrease production and/or activity of cytochrome P450 enzymes.(1,2) CLINICAL EFFECTS: Concurrent use of givosiran may result in elevated levels of and toxicity from agents metabolized by CYP1A2 or CYP2D6.(1) PREDISPOSING FACTORS: With tricyclic antidepressants, the risk of seizures may be increased in patients with a history of head trauma or prior seizure; CNS tumor; severe hepatic cirrhosis; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or stimulants; use of over-the-counter stimulants and anorectics; diabetics treated with oral hypoglycemics or insulin; or with concomitant medications known to lower seizure threshold (antipsychotics, theophylline, systemic steroids). With anticholinergic agents, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(3) PATIENT MANAGEMENT: Avoid the concurrent use of givosiran with agents that are sensitive substrates of CYP1A2 or CYP2D6, or CYP1A2 or CYP2D6 substrates with a narrow therapeutic index. If concurrent use is unavoidable, decrease the dose of the CYP1A2 or CYP2D6 substrate and monitor patients for toxicity. DISCUSSION: A study of 9 patients with acute intermittent porphyria found that givosiran decreased the maximum concentration (Cmax) and area-under-curve (AUC) of caffeine (a CYP1A2 substrate) by 1.3- and 3.1-fold, respectively, compared to caffeine alone. Givosiran also decreased the Cmax and AUC of dextromethorphan (a CYP2D6 substrate) by 2- and 2.4-fold, respectively, compared to dextromethorphan alone.(1,2) Selected CYP2D6 substrates linked to this monograph include: desipramine, deutetrabenazine, dextromethorphan, doxepin, encainide, methoxyphenamine, metoprolol, nebivolol, nefazodone, paroxetine, perphenazine, risperidone, tetrabenazine, trimipramine, and venlafaxine. Selected CYP1A2 substrates linked to this monograph include: agomelatine, aminophylline, rasagiline, tacrine, theophylline, tizanidine, and yohimbine. |
GIVLAARI |
| Mixed;Indirect Sympathomimetics/Rasagiline SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Catecholamine stores increased by MAOIs can be released by indirect acting sympathomimetics such as ephedrine and amphetamine. MAO inhibitors also interfere with gut and liver metabolism of direct acting sympathomimetics (e.g oral phenylephrine). CLINICAL EFFECTS: Concurrent use of MAOIs may result in potentiation of sympathomimetic effects, which may result in headaches, hypertensive crisis, toxic neurological effects, and malignant hyperpyrexia. Hypertensive crisis has been reported in patients taking recommended doses of rasagiline with sympathomimetic agents. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: At recommended dosages, rasagiline is selective for MAO-B; however, at higher dosages it has been shown to lose its selectivity. Patients receiving higher dosages of rasagiline should be considered susceptive to this interaction. Concurrent use should be approached with caution. DISCUSSION: Indirect acting sympathomimetic amines may cause abrupt elevation of blood pressure when administered to patients taking monoamine oxidase inhibitors, resulting in a potentially fatal hypertensive crisis. Mixed (direct and indirect) acting sympathomimetics have also been shown to interact with monoamine oxidase inhibitors depending on their degree of indirect action. The direct-acting sympathomimetics have not been reported to interact. Dopamine is metabolized by monoamine oxidase, and its pressor effect is enhanced by monoamine oxidase inhibitors. |
AZILECT, RASAGILINE MESYLATE |
There are 7 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Sympathomimetics (Direct, Mixed-Acting)/Guanethidine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Direct or mixed-acting sympathomimetics may inhibit uptake of guanethidine at the adrenergic neuron. CLINICAL EFFECTS: Decreased antihypertensive effectiveness. Effects may be seen for several days after discontinuation of the direct or mixed-acting sympathomimetic. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concomitant administration of these drugs. If both drugs are administered, adjust the guanethidine dose as needed based on blood pressure. DISCUSSION: Documentation supports routine monitoring of this interaction. It should be noted that this interaction can occur quickly. |
GUANETHIDINE HEMISULFATE |
| Sympathomimetics/Rauwolfia Alkaloids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Reserpine depletes catecholamine stores within the peripheral vascular adrenergic nerve endings, thus indirect acting sympathomimetics are unable to trigger the release of catecholamines. The reserpine-induced catecholamine release increases sensitivity to the effects of direct acting sympathomimetics. CLINICAL EFFECTS: Increased effects of direct acting sympathomimetics. Decreased effects of indirect acting sympathomimetics. Mixed acting sympathomimetics will show effects based on the predominance of either direct or indirect activity. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If these agents are administered concurrently, monitor blood pressure. The dose of the sympathomimetic may need to be adjusted. DISCUSSION: This interaction has been well documented in animal studies and human case reports have confirmed the interaction. Reserpine has been shown to decrease the response to epinephrine administered for hypotension. Reserpine has also been shown to decrease the effectiveness of ophthalmic epinephrine, a direct acting sympathomimetic. Ophthalmic phenylephrine has been shown to decrease the hypotensive effects of reserpine. |
RESERPINE |
| Sympathomimetics (Direct, Mixed-Acting)/Methyldopa SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. CLINICAL EFFECTS: The pressor response to sympathomimetics may be increased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Start with low doses of sympathomimetics and monitor blood pressure of patients during concurrent administration of sympathomimetics and methyldopa. DISCUSSION: The pressor response to sympathomimetics has been reported to be increased during methyldopa administration. In addition to increased duration of pressor response, severe hypertension has been reported. |
METHYLDOPA, METHYLDOPA-HYDROCHLOROTHIAZIDE, METHYLDOPATE HCL |
| Dextromethorphan/Selected SSRIs that Inhibit CYP2D6 SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Fluoxetine and paroxetine, strong inhibitors of CYP2D6, may inhibit the metabolism of dextromethorphan.(1-4) CLINICAL EFFECTS: Patients may experience increased adverse effects of dextromethorphan due to elevated systemic concentrations. Concomitant use of two or more serotonergic agents increases the risk for serotonin syndrome. Serotonin syndrome constitutes a range of toxicities from mild to life threatening.(5) Mild serotonin symptoms may include: shivering, diaphoresis, mydriasis, intermittent tremor, and/or myoclonus.(5) Moderate serotonin symptoms may include: tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis, hyperactive bowel sounds, hyperreflexia, and/OR clonus.(5) Severe serotonin symptoms may include: severe hypertension and tachycardia, shock, agitated delirium, muscular rigidity, and/or hypertonicity.(5) PREDISPOSING FACTORS: Concurrent use of additional drugs which increase CNS serotonin levels would be expected to further increase risk for serotonin syndrome.(5) PATIENT MANAGEMENT: Monitor patients on multiple serotonergic agents for symptoms of serotonin toxicity. Patients in whom serotonin syndrome is suspected should receive immediate medical attention. If the interacting agents are prescribed by different providers, it would be prudent to assure that both are aware of concomitant therapy and monitoring the patient for serotonin toxicities. Advise patients not to exceed recommended dosages of dextromethorphan. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: An open label parallel group trial evaluated the interaction between dextromethorphan-quinidine 30 mg-30 mg (higher than marketed strength of 20 mg-10 mg) and paroxetine 20 mg in 27 healthy volunteers with a mean age of 33.6 years. Subjects were randomly divided into 2 groups: - Group 1 received paroxetine 20 mg once daily for 12 days, followed by the addition of dextromethorphan-quinidine twice daily for 8 days. - Group 2 received dextromethorphan-quinidine twice daily for 8 days, followed by paroxetine 20 mg daily for 12 days. Results: overall, adverse effects were reported in 19 of 26 subjects who received combination therapy (73%) and 15 of 27 subjects who received monotherapy (56%). Adverse effects from the combination differed somewhat between groups and were more closely associated with the second drug product administered. Group 1 reported dizziness, headache, somnolence, euphoria, nausea, and vomiting after the addition of dextromethorphan-quinidine to paroxetine. Group 2 adverse events were dizziness, headache, nausea, vomiting, insomnia, anxiety, and hyperhidrosis after the addition of paroxetine to dextromethorphan.(1) Two weeks of fluoxetine therapy increased the area-under-curve (AUC) of dextromethorphan by 27-fold.(4) Serotonin syndrome has been reported in patients following the addition of dextromethorphan containing cough syrups to fluoxetine(6,7) and paroxetine.(8) |
FLUOXETINE DR, FLUOXETINE HCL, OLANZAPINE-FLUOXETINE HCL, PAROXETINE CR, PAROXETINE ER, PAROXETINE HCL, PAROXETINE MESYLATE, PAXIL, PAXIL CR, PROZAC, SYMBYAX |
| Selected CYP2D6 Substrates/Desvenlafaxine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Desvenlafaxine is considered a weak inhibitor of CYP2D6.(1) CLINICAL EFFECTS: Concurrent use of desvenlafaxine may lead to increased serum levels and adverse effects of drugs sensitive to inhibition of the CYP2D6 pathway.(1) Agents linked to this monograph are: atomoxetine, dapoxetine, deutetrabenazine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, and yohimbine. PREDISPOSING FACTORS: With perphenazine and tolterodine, the risk of anticholinergic toxicities including cognitive decline, delirium, falls and fractures is increased in geriatric patients using more than one medicine with anticholinergic properties.(2) PATIENT MANAGEMENT: Reduce the dose of CYP2D6 substrates by up to one-half when coadministered with desvenlafaxine 400 mg.(1) Studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 metabolism at the dose of 100 mg daily. CYP2D6 substrates should be dosed at the original level when coadministered with desvenlafaxine 100 mg or lower or when desvenlafaxine is discontinued.(1) DISCUSSION: In a study, coadministration of desvenlafaxine 100 mg daily with desipramine (single dose 50 mg) increased desipramine's maximum concentration (Cmax) and area-under-the-curve (AUC)by 25% and 17%.(1) In a study, coadministration of desvenlafaxine 400 mg daily with desipramine (single dose 50 mg) increased desipramine's maximum concentration (Cmax) and area-under-the-curve (AUC)by 50% and 90%.(1) Selected CYP2D6 substrates linked to this monograph are: atomoxetine, dapoxetine, deutetrabenazine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, and yohimbine. |
DESVENLAFAXINE ER, DESVENLAFAXINE SUCCINATE ER, PRISTIQ |
| Dextromethorphan/Selected Serotonergic Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Dextromethorphan inhibits neuronal reuptake of serotonin. Concurrent administration with one or more serotonergic agents may increase serotonin effects, leading to serotonin toxicity.(1-11) CLINICAL EFFECTS: The concurrent use of dextromethorphan with serotonergic agents may increase the risk for serotonin syndrome. Serotonin syndrome constitutes a range of toxicities from mild to life threatening.(3) Mild serotonin symptoms may include: shivering, diaphoresis, mydriasis, intermittent tremor, and/or myoclonus.(3) Moderate serotonin symptoms may include: tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis, hyperactive bowel sounds, hyperreflexia, and/OR clonus.(3) Severe serotonin symptoms may include: severe hypertension and tachycardia, shock, agitated delirium, muscular rigidity, and/or hypertonicity.(3) PREDISPOSING FACTORS: Concurrent use of additional drugs which increase CNS serotonin levels would be expected to further increase risk for serotonin syndrome.(1-11) PATIENT MANAGEMENT: Monitor patients on multiple serotonergic agents for symptoms of serotonin toxicity. Patients in whom serotonin syndrome is suspected should receive immediate medical attention. If the interacting agents are prescribed by different providers, it would be prudent to assure that both are aware of concomitant therapy and monitoring the patient for serotonin toxicities. Advise patients not to exceed recommended dosages of dextromethorphan. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: Dextromethorphan inhibits neuronal reuptake of serotonin and may potentially precipitate dose-dependant serotonin toxicity in conjunction with other serotonergic agents.(4,5) Serotonin syndrome has been reported in patients following the addition of dextromethorphan containing cough syrups to duloxetine,(6) escitalopram,(7) fluoxetine,(8,9) paroxetine,(10) and sertraline.(11) Selected serotonergic agents linked to this monograph include: citalopram, clomipramine, duloxetine, escitalopram, fluvoxamine, imipramine, levomilnacipran, milnacipran, sertraline, venlafaxine, vilazodone and vortioxetine. |
ANAFRANIL, CELEXA, CITALOPRAM HBR, CLOMIPRAMINE HCL, CYMBALTA, DRIZALMA SPRINKLE, DULOXETINE HCL, DULOXICAINE, EFFEXOR XR, ESCITALOPRAM OXALATE, FETZIMA, FLUVOXAMINE MALEATE, FLUVOXAMINE MALEATE ER, IMIPRAMINE HCL, IMIPRAMINE PAMOATE, LEXAPRO, SAVELLA, SERTRALINE HCL, TRINTELLIX, VENLAFAXINE BESYLATE ER, VENLAFAXINE HCL, VENLAFAXINE HCL ER, VIIBRYD, VILAZODONE HCL, ZOLOFT |
| Dextromethorphan/Selected Strong CYP2D6 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong inhibitors of CYP2D6 may inhibit the metabolism of dextromethorphan.(1-4) CLINICAL EFFECTS: Patients may experience increased adverse effects of dextromethorphan due to elevated systemic concentrations. Elevated levels of dextromethorphan or concomitant use of two or more serotonergic agents increases the risk for serotonin syndrome. Serotonin syndrome constitutes a range of toxicities from mild to life threatening.(5) Mild serotonin symptoms may include: shivering, diaphoresis, mydriasis, intermittent tremor, and/or myoclonus.(5) Moderate serotonin symptoms may include: tachycardia, hypertension, hyperthermia, mydriasis, diaphoresis, hyperactive bowel sounds, hyperreflexia, and/OR clonus.(5) Severe serotonin symptoms may include: severe hypertension and tachycardia, shock, agitated delirium, muscular rigidity, and/or hypertonicity.(5) PREDISPOSING FACTORS: Concurrent use of additional drugs which increase CNS serotonin levels would be expected to further increase risk for serotonin syndrome.(5) PATIENT MANAGEMENT: Monitor patients for elevated dextromethorphan levels or on multiple serotonergic agents for symptoms of serotonin toxicity. Patients in whom serotonin syndrome is suspected should receive immediate medical attention. If the interacting agents are prescribed by different providers, it would be prudent to assure that both are aware of concomitant therapy and monitoring the patient for serotonin toxicities. Advise patients not to exceed recommended dosages of dextromethorphan. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: An open label parallel group trial evaluated the interaction between dextromethorphan-quinidine 30 mg-30 mg (higher than marketed strength of 20 mg-10 mg) and paroxetine 20 mg in 27 healthy volunteers with a mean age of 33.6 years. Subjects were randomly divided into 2 groups: - Group 1 received paroxetine 20 mg once daily for 12 days, followed by the addition of dextromethorphan-quinidine twice daily for 8 days. - Group 2 received dextromethorphan-quinidine twice daily for 8 days, followed by paroxetine 20 mg daily for 12 days. Results: overall, adverse effects were reported in 19 of 26 subjects who received combination therapy (73%) and 15 of 27 subjects who received monotherapy (56%). Adverse effects from the combination differed somewhat between groups and were more closely associated with the second drug product administered. Group 1 reported dizziness, headache, somnolence, euphoria, nausea, and vomiting after the addition of dextromethorphan-quinidine to paroxetine. Group 2 adverse events were dizziness, headache, nausea, vomiting, insomnia, anxiety, and hyperhidrosis after the addition of paroxetine to dextromethorphan.(1) Two weeks of fluoxetine therapy increased the area-under-curve (AUC) of dextromethorphan by 27-fold.(4) Serotonin syndrome has been reported in patients following the addition of dextromethorphan containing cough syrups to fluoxetine(6,7) and paroxetine.(8) Selected strong CYP2D6 inhibitors linked to this monograph include: bupropion, dacomitinib, hydroquinidine, quinidine, and terbinafine.(8) |
APLENZIN, AUVELITY, BUPROPION HCL, BUPROPION HCL SR, BUPROPION XL, CONTRAVE, FORFIVO XL, NUEDEXTA, QUINIDINE GLUCONATE, QUINIDINE SULFATE, TERBINAFINE HCL, VIZIMPRO, WELLBUTRIN SR, WELLBUTRIN XL |
The following contraindication information is available for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 3 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Severe coronary artery disease |
| Severe uncontrolled hypertension |
| Urinary retention |
There are 8 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Angle-closure glaucoma |
| Benign prostatic hyperplasia |
| Coronary artery disease |
| Diabetes mellitus |
| Hypertension |
| Hyperthyroidism |
| Pheochromocytoma |
| Systemic mastocytosis |
There are 4 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Chronic heart failure |
| Kidney disease with reduction in glomerular filtration rate (GFr) |
| No disease contraindications |
| Severe hepatic disease |
The following adverse reaction information is available for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 18 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. | None. |
| Rare/Very Rare |
|---|
|
Acute generalized exanthematous pustulosis Cardiac arrhythmia Dizziness Dyspnea Hallucinations Headache disorder Hyperhidrosis Hypertension Insomnia Ischemic colitis Nervousness Pallor Posterior reversible encephalopathy syndrome Reversible cerebral vasoconstriction syndrome Seizure disorder Tachycardia Tremor Vomiting |
There are 28 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Headache disorder Insomnia |
Agitation Anorexia Dizziness Drowsy Dysuria General weakness Nausea Nervousness Pallor Tachycardia Tremor |
| Rare/Very Rare |
|---|
|
Abdominal pain with cramps Anticholinergic toxicity Cardiac arrhythmia Chest tightness Dizziness Drowsy Dyspepsia Excitement Gastrointestinal irritation Hyperhidrosis Nausea Palpitations Symptoms of anxiety Syncope Vomiting |
The following precautions are available for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Contraindicated
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
| Dextromethorphan (OTC, Select) | 1 Day – 6 Years | Do not use in pediatrics <6 years of age unless clinician consultation. |
Contraindicated
| Phenylephrine (oral) | 1 Day – 6 Years | Risk of CNS excitation. Do not use age <6 years without clinician consult. |
Contraindicated
| Pseudoephedrine (Immed. Release) | 1 Day – 6 Years | High risk of adverse CNS effects. Not recommended for use age < 6 years. |
Severe Precaution
| Guaifenesin (Liquid) | 1 Day – 2 Years | No established efficacy for cough and cold products age < 2 years. Do not use unless directed by clinician consultation. |
Management or Monitoring Precaution
| None |
It is not known whether phenylephrine hydrochloride can cause fetal harm when administered to pregnant women; the drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal studies suggest a potential for adverse cardiovascular effects to the fetus if the drug is administered IV during pregnancy. Administration of phenylephrine to patients in late pregnancy or labor may cause fetal anoxia and bradycardia by increasing contractility of the uterus and decreasing uterine blood flow.
In studies of IV phenylephrine in pregnant women undergoing cesarean delivery with neuraxial anesthesia, common adverse effects reported in the mother included nausea and vomiting, bradycardia, reactive hypertension, and transient arrhythmias. The drug did not appear to affect neonatal Apgar scores or umbilical artery blood-gas status. If a vasopressor is used in conjunction with oxytocic drugs, the vasopressor effect is potentiated and may result in potentially serious adverse effects. (See Drug Interactions: Oxytocic Drugs.)
In studies of IV phenylephrine in pregnant women undergoing cesarean delivery with neuraxial anesthesia, common adverse effects reported in the mother included nausea and vomiting, bradycardia, reactive hypertension, and transient arrhythmias. The drug did not appear to affect neonatal Apgar scores or umbilical artery blood-gas status. If a vasopressor is used in conjunction with oxytocic drugs, the vasopressor effect is potentiated and may result in potentially serious adverse effects. (See Drug Interactions: Oxytocic Drugs.)
| Drug/Drug Class | Severity | Precaution Description | Pregnancy Category Description |
|---|---|---|---|
| Dextromethorphan | 2 | Available human data show no increased risk for major birth defects | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
| Guaifenesin | 2 | Available human data show no increased risk for major birth defects | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
| Phenylephrine | 2 | Insufficient human data available | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
| Pseudoephedrine | 2 | Limited human data are inconclusive on developmental toxicity risk | No fda rating but may have precautions or warnings; may have animal and/or human studies or pre or post marketing information. |
It is not known whether phenylephrine is distributed into human milk following parenteral administration. The drug should be used with caution in nursing women.
Precaution Exists
Precaution exists. (No data or inconclusive human data.) Use of this drug by breast feeding mothers should be evaluated carefully.
Precaution Exists
Precaution exists. (No data or inconclusive human data.) Use of this drug by breast feeding mothers should be evaluated carefully.
| Drug Name | Excretion Potential | Effect on Infant | Notes |
|---|---|---|---|
| Dextromethorphan | Unknown. It is unknown whether the drug is excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Insufficient data available; molecular wt low enough for possible excretion |
| Guaifenesin | Unknown. It is unknown whether the drug is excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Insufficient human data available |
| Phenylephrine | Excreted.This drug is known to be excreted in human breast milk. | It is not known whether this drug has an adverse effect on the nursing infant. (No data or inconclusive human data) | Oral bioavailability low; infant exposure may be minimal |
| Pseudoephedrine | Excreted.This drug is known to be excreted in human breast milk. | This drug has been shown to have an adverse effect on the nursing infant. | May decrease milk supply and cause irritability |
No enhanced Geriatric Use information available for this drug.
Precaution Exists
Geriatric management or monitoring precaution exists.
Precaution Exists
Geriatric management or monitoring precaution exists.
| Drug Name | Narrative | REN | HEP | CARDIO | NEURO | PULM | ENDO |
|---|---|---|---|---|---|---|---|
| Phenylephrine | Cardiovascular-Elderly are more sensitive to tachycardia and hypertensive effects. May exacerbate symptomatic coronary insufficiency. Genitourinary-May cause urinary retention. Neuro/Psych-May worsen cognitive impairment in some elderly with dementia. Insomnia risk. | N | N | Y | Y | N | N |
| Pseudoephedrine | Cardiovascular-Elderly are more sensitive to tachycardia and hypertensive effects. May exacerbate symptomatic coronary insufficiency. Genitourinary-May cause urinary retention. Neuro/Psych-May worsen cognitive impairment in some elderly with dementia. Insomnia risk. | Y | N | Y | Y | N | N |
The following prioritized warning is available for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for TUSNEL PEDIATRIC (guaifenesin/pseudoephedrine hcl)'s list of indications:
| Cold symptoms | |
| J00 | Acute nasopharyngitis [common cold] |
| Cough | |
| R05 | Cough |
| R05.1 | Acute cough |
| R05.2 | Subacute cough |
| R05.3 | Chronic cough |
| R05.9 | Cough, unspecified |
| Nasal congestion | |
| R09.81 | Nasal congestion |
| Rhinitis | |
| J30 | Vasomotor and allergic rhinitis |
| J30.0 | Vasomotor rhinitis |
| J30.1 | Allergic rhinitis due to pollen |
| J30.2 | Other seasonal allergic rhinitis |
| J30.5 | Allergic rhinitis due to food |
| J30.8 | Other allergic rhinitis |
| J30.81 | Allergic rhinitis due to animal (cat) (dog) hair and dander |
| J30.89 | Other allergic rhinitis |
| J30.9 | Allergic rhinitis, unspecified |
| J31.0 | Chronic rhinitis |
| Rhinorrhea | |
| R09.82 | Postnasal drip |
Formulary Reference Tool