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Drug Interactions between potassium citrate and Re-Drylex Jr

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

chlorpheniramine potassium citrate

Applies to: Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine) and potassium citrate

CONTRAINDICATED: The following interaction does not apply to all products containing potassium citrate. It is applicable to certain oral solid formulations of potassium citrate used primarily for potassium supplementation, and the prescriber should consult the individual product labeling for more specific information and guidance.

Concomitant use of agents with anticholinergic properties (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, the class IA antiarrhythmic disopyramide) may potentiate the risk of upper gastrointestinal injury associated with oral solid formulations of potassium citrate. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby creating a high localized concentration of potassium ions in the region of a dissolving tablet or capsule and increasing the contact time with GI mucosa. Solid formulations of potassium chloride have been associated with upper GI bleeding and small bowel ulceration, stenosis, perforation, and obstruction. Deaths have been reported rarely. In clinical studies, short-term coadministration of wax-matrix or microencapsulated formulations of potassium chloride and potassium citrate at high dosages in combination with an anticholinergic agent such as glycopyrrolate resulted in more frequent and more serious endoscopic lesions than potassium therapy alone. However, the lesions were not accompanied by bleeding or epigastric symptoms. Some investigators have suggested a higher risk of upper GI lesions with wax-matrix than microencapsulated formulations, although existing data are limited and conflicting.

MANAGEMENT: The use of oral solid formulations of potassium citrate is considered contraindicated in patients receiving agents with anticholinergic properties at sufficient doses to exert anticholinergic effects. A liquid formulation of potassium citrate should be considered. Patients prescribed a solid oral formulation should be advised to discontinue potassium therapy and contact their physician if they experience potential symptoms of upper GI injury such as severe vomiting, abdominal pain, distention, and gastrointestinal bleeding.

References

  1. Lambert JR, Newman A (1980) "Ulceration and stricture of the esophagus due to oral potassium chloride (slow release tablet) therapy." Am J Gastroenterol, 73, p. 508-11
  2. Farquharson-Roberts MA, Giddings AE, Nunn AJ (1975) "Perforation of small bowel due to slow release potassium chloride (slow-K)." Br Med J, 3, p. 206
  3. Wynn V (1965) "Potassium chloride and bowel ulceration." Br Med J, 5477, p. 1546
  4. McMahon FG, Ryan JR, Akdamar K, Ertan A (1984) "Effect of potassium chloride supplements on upper gastrointestinal mucosa." Clin Pharmacol Ther, 35, p. 852-5
  5. McMahon FG, Ryan JR, Akdamar K, Ertan A (1982) "Upper gastrointestinal lesions after potassium chloride supplements: a controlled clinical trial." Lancet, 2, p. 1059-61
  6. Leijonmarck CE, Raf L (1985) "Gastrointestinal lesions and potassium chloride supplements." Lancet, 1, p. 56-7
  7. Lofgren RP, Rothe PR, Carlson GJ (1982) "Jejunal perforation associated with slow-release potassium chloride therapy." South Med J, 75, p. 1154-5
  8. Leijonmarck CE, Raf L (1985) "Ulceration of the small intestine due to slow-release potassium chloride tablets." Acta Chir Scand, 151, p. 273-8
  9. Weiss SM, Rutenberg HL, Paskin DL, Zaren HA (1977) "Gut lesions due to slow-release KCI tablets." N Engl J Med, 296, p. 111-2
  10. (2001) "Product Information. K-Dur (potassium chloride)." Schering Corporation
  11. "Product Information. Urocit-K (potassium citrate)." Mission Pharmacal Company
  12. Heffernan SJ, Murphy JJ (1975) "Ulceration of small intestine and slow-release potassium tablets." Br Med J, 2, p. 746
View all 12 references

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Major

methscopolamine potassium citrate

Applies to: Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine) and potassium citrate

CONTRAINDICATED: The following interaction does not apply to all products containing potassium citrate. It is applicable to certain oral solid formulations of potassium citrate used primarily for potassium supplementation, and the prescriber should consult the individual product labeling for more specific information and guidance.

Concomitant use of agents with anticholinergic properties (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, the class IA antiarrhythmic disopyramide) may potentiate the risk of upper gastrointestinal injury associated with oral solid formulations of potassium citrate. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby creating a high localized concentration of potassium ions in the region of a dissolving tablet or capsule and increasing the contact time with GI mucosa. Solid formulations of potassium chloride have been associated with upper GI bleeding and small bowel ulceration, stenosis, perforation, and obstruction. Deaths have been reported rarely. In clinical studies, short-term coadministration of wax-matrix or microencapsulated formulations of potassium chloride and potassium citrate at high dosages in combination with an anticholinergic agent such as glycopyrrolate resulted in more frequent and more serious endoscopic lesions than potassium therapy alone. However, the lesions were not accompanied by bleeding or epigastric symptoms. Some investigators have suggested a higher risk of upper GI lesions with wax-matrix than microencapsulated formulations, although existing data are limited and conflicting.

MANAGEMENT: The use of oral solid formulations of potassium citrate is considered contraindicated in patients receiving agents with anticholinergic properties at sufficient doses to exert anticholinergic effects. A liquid formulation of potassium citrate should be considered. Patients prescribed a solid oral formulation should be advised to discontinue potassium therapy and contact their physician if they experience potential symptoms of upper GI injury such as severe vomiting, abdominal pain, distention, and gastrointestinal bleeding.

References

  1. Lambert JR, Newman A (1980) "Ulceration and stricture of the esophagus due to oral potassium chloride (slow release tablet) therapy." Am J Gastroenterol, 73, p. 508-11
  2. Farquharson-Roberts MA, Giddings AE, Nunn AJ (1975) "Perforation of small bowel due to slow release potassium chloride (slow-K)." Br Med J, 3, p. 206
  3. Wynn V (1965) "Potassium chloride and bowel ulceration." Br Med J, 5477, p. 1546
  4. McMahon FG, Ryan JR, Akdamar K, Ertan A (1984) "Effect of potassium chloride supplements on upper gastrointestinal mucosa." Clin Pharmacol Ther, 35, p. 852-5
  5. McMahon FG, Ryan JR, Akdamar K, Ertan A (1982) "Upper gastrointestinal lesions after potassium chloride supplements: a controlled clinical trial." Lancet, 2, p. 1059-61
  6. Leijonmarck CE, Raf L (1985) "Gastrointestinal lesions and potassium chloride supplements." Lancet, 1, p. 56-7
  7. Lofgren RP, Rothe PR, Carlson GJ (1982) "Jejunal perforation associated with slow-release potassium chloride therapy." South Med J, 75, p. 1154-5
  8. Leijonmarck CE, Raf L (1985) "Ulceration of the small intestine due to slow-release potassium chloride tablets." Acta Chir Scand, 151, p. 273-8
  9. Weiss SM, Rutenberg HL, Paskin DL, Zaren HA (1977) "Gut lesions due to slow-release KCI tablets." N Engl J Med, 296, p. 111-2
  10. (2001) "Product Information. K-Dur (potassium chloride)." Schering Corporation
  11. "Product Information. Urocit-K (potassium citrate)." Mission Pharmacal Company
  12. Heffernan SJ, Murphy JJ (1975) "Ulceration of small intestine and slow-release potassium tablets." Br Med J, 2, p. 746
View all 12 references

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Moderate

chlorpheniramine methscopolamine

Applies to: Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine) and Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine)

MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, 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 symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. 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 neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, 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. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

References

  1. Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
  2. Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
  3. Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
  4. Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
  5. Gershon S, Neubauer H, Sundland DM (1965) "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther, 6, p. 749-56
  6. Sarnquist F, Larson CP Jr (1973) "Drug-induced heat stroke." Anesthesiology, 39, p. 348-50
  7. Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
  8. Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
  9. Forester D (1978) "Fatal drug-induced heat stroke." JACEP, 7, p. 243-4
  10. Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
  11. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
  12. Cohen MA, Alfonso CA, Mosquera M (1994) "Development of urinary retention during treatment with clozapine and meclizine [published erratum appears in Am J Psychiatry 1994 Jun;151(6):952]." Am J Psychiatry, 151, p. 619-20
  13. (2001) "Product Information. Cogentin (benztropine)." Merck & Co., Inc
  14. Kulik AV, Wilbur R (1982) "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry, 6, p. 75-82
  15. (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
View all 15 references

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Moderate

phenylephrine methscopolamine

Applies to: Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine) and Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine)

MONITOR: The pressor response to phenylephrine may be potentiated by the vagolytic effect of atropine, which inhibits the reflex bradycardia that would normally accompany any increases in blood pressure induced by phenylephrine. Other antimuscarinic agents may also participate in this interaction, although clinical data are lacking. In one report, pseudo-pheochromocytoma (i.e., significant increases in blood pressure and tachycardia) occurred in seven patients who underwent eye surgery and were given phenylephrine 10% ophthalmic solution and systemic atropine, three of whom subsequently developed left ventricular failure and pulmonary edema that required intensive care monitoring. Two patients had preexisting hypertension, while others had no known history of cardiovascular disease. All had received general anesthesia with propofol, phenoperidine, and vecuronium. Since phenylephrine use alone may be associated with cardiovascular toxicities including hypertension, arrhythmia, myocardial infarction and cardiac failure, the extent of involvement by atropine is uncertain. The authors reported no further cardiovascular events following implementation of various measures that reduced phenylephrine dosage and systemic exposure, including: use of a milder strength of phenylephrine ophthalmic solution; swabbing to minimize drainage into the nasolachrymal duct to the nasal mucosa; and use of a cannula to reduce drop size. In a study of six healthy volunteers, diastolic and systolic blood pressure increased by 4 mmHg following administration of phenylephrine (0.42 mcg/kg/min), compared to 17 mmHg when phenylephrine was given after three doses of atropine (0.02, 0.01 and 0.01 mg/kg at 30 minute intervals).

MANAGEMENT: Caution is advised if phenylephrine (systemic or ophthalmic) is used in combination with atropine or other antimuscarinic agents. Cardiovascular status, including blood pressure and heart rate, should be closely monitored. When using ophthalmic formulations, measures to minimize systemic absorption should be employed, such as digital compression of the lacrimal sac or lid closure after instillation. A milder strength (< 10%) is preferable if phenylephrine ophthalmic solution is given.

References

  1. Daelman F, Andrejak M, Rajaonarivony D, Bryselbout E, Jezraoui P, Ossart M (1994) "Phenylephrine eyedrops, systemic atropine and cardiovascular adverse events." Therapie, 49, p. 467
  2. Fraunfelder FT, Fraunfelder FW; Randall JA (2001) "Drug-Induced Ocular Side Effects" Boston, MA: Butterworth-Heinemann
  3. Lai YK (1989) "Adverse effect of intraoperative phenylephrine 10%: case report." Br J Ophthalmol, 73, p. 468-9
  4. Van Der Spek AF, Hantler CB (1986) "Phenylephrine eyedrops and anesthesia." Anesthesiology, 64, p. 812-4
  5. Levine MA, Leenen FH (1992) "Role of vagal activity in the cardiovascular responses to phenylephrine in man." Br J Clin Pharmacol, 33, p. 333-6
View all 5 references

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Drug and food interactions

Moderate

chlorpheniramine food

Applies to: Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine)

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

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

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Moderate

methscopolamine food

Applies to: Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine)

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

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Moderate

phenylephrine food

Applies to: Re-Drylex Jr (chlorpheniramine / methscopolamine / phenylephrine)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
View all 7 references

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Therapeutic duplication warnings

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Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

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

Further information

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