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Drug Interactions between Aralen Phosphate and Qualaquin

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

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Interactions between your drugs

Major

chloroquine quiNINE

Applies to: Aralen Phosphate (chloroquine) and Qualaquin (quinine)

GENERALLY AVOID: Chloroquine and hydroxychloroquine can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such advanced age, congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Currently available data seem to suggest a significantly higher risk of QTc prolongation (>= 60 msec increase from baseline or absolute QTc >=500 msec ) in COVID-19 patients treated with hydroxychloroquine or chloroquine, with or without azithromycin, than has been previously reported in other settings. Because COVID-19 may disproportionately affect the elderly and individuals with preexisting heart disease, and cardiac complications such as myocarditis and cardiomyopathy as well as organ failure may occur in patients with severe COVID-19, it appears likely that hospitalized patients with COVID-19 may represent a particularly susceptible and high-risk population, and other, less critically ill patients may not have the same arrhythmic risk.

MANAGEMENT: Coadministration of chloroquine or hydroxychloroquine with other drugs that can prolong the QT interval should generally be avoided, particularly in patients with baseline QT prolongation (e.g., QTc >=500 msec) or congenital long QT syndrome. Close monitoring of QTc interval, electrolyte levels, and renal and hepatic function is recommended if concomitant use is required and benefits are anticipated to outweigh the risks. Electrolyte abnormalities should be corrected prior to initiating treatment with chloroquine or hydroxychloroquine. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Because chloroquine and hydroxychloroquine are eliminated slowly from the body, the potential for drug interactions should be observed for a prolonged period following their discontinuation.

References

  1. (2022) "Product Information. Plaquenil (hydroxychloroquine)." Apothecon Inc
  2. (2005) "Product Information. Chloroquine Phosphate (chloroquine)." West Ward Pharmaceutical Corporation
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. (2017) "Product Information. Hydroxychloroquine Sulfate (hydroxychloroquine)." Prasco Laboratories
  5. US Food and Drug Administration (2020) Hydroxychloroquine or Chloroquine for COVID-19: Drug Safety Communication - FDA Cautions Against Use Outside of the Hospital Setting or a Clinical Trial Due to Risk of Heart Rhythm Problems. https://www.fda.gov/safety/medical-product-safety-information/h
  6. US Food and Drug Administration (2020) FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF HYDROXYCHLOROQUINE SULFATE SUPPLIED FROM THE STRATEGIC NATIONAL STOCKPILE FOR TREATMENT OF COVID-19 IN CERTAIN HOSPITALIZED PATIENTS. https://www.fda.gov/media/136537/download
  7. US Food and Drug Administration (2020) FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF CHLOROQUINE PHOSPHATE SUPPLIED FROM THE STRATEGIC NATIONAL STOCKPILE FOR TREATMENT OF COVID-19 IN CERTAIN HOSPITALIZED PATIENTS. https://www.fda.gov/media/136535/download
  8. National Institutes of Health (NIH) (2020) Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. https://covid19treatmentguidelines.nih.gov/
  9. Mercuro NJ, Yen CF, Shim DJ, et al. (2020) "Risk of QT interval prolongation associated with the use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19)" JAMA Cardiol, May 1:e201834, epub ahead of print
  10. Bonow RO, Hernandez AF, Turakhia M (2020) "Hydroxychloroquine, coronavirus disease 2019, and QT prolongation." JAMA Cardiol, May 1, epub ahead of print
  11. Bessiere F, Roccia H, Deliniere A, et al. (2020) "Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit." JAMA Cardiol, May 1, epub ahead of print
  12. Saleh M, Gabriels J, ChangD, et al. (2020) "The effect of chloroquine, hydroxychloroquine and azithromycin on the corrected QT interval in patients with SARS-CoV-2 infection." Circ Arrhythm Electrophysiol, Apr 29, epub ahead of print
  13. Javelot H, El-Hage W, Meyer G, Becker G, Michel B, Hingray C (2020) "COVID-19 and (hydroxy)chloroquine-azithromycin combination: should we take the risk for our patients?" Br J Clin Pharmacol, Apr 29, epub ahead of print
  14. Sacher F, Fauchier L, Boveda S, et al. (2020) "Use of drugs with potential cardiac effect in the setting of SARS-CoV-2 infection." Arch Cardiovasc Dis, Apr 24, epub ahead of print
  15. Smit C, Peeters MYM, van den Anker JN, Knibbe CAJ (2020) "Chloroquine for SARS-CoV-2: Implications of its unique pharmacokinetic and safety properties." Clin Pharmacokinet, Ar 18, epub ahead of print
  16. Roden DM, Harrington RA, Poppas A, Russo AM (2020) "Considerations for drug interactions on QTc in exploratory COVID-19 (Coroanvirus disease 2019) treatment." Heart Rhythm, Apr 14, epub ahead of print
  17. Sapp JL, Alqarawi W, MacIntyre CJ, et al. (2020) "Guidance on minimizing risk of drug-induced ventricular arrhythmia during treatment of COVID-19: A statement from the Canadian Heart Rhythm Society." Can J Cardiol, Apr 8, epub ahead of print
  18. Kapoor A, Pandurangi U, Arora V, et al. (2020) "Cardiovascular risks of hydroxychloroquine in treatment and prophylaxis of COVID-19 patients: A scientific statement from the Indian Heart Rhythm Society." Indian Pacing Electorphysiol J, Apr 8, epub ahead of print
  19. Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ (2020) "Urgent guidance for navigating and circumventing the QTc-prolonging and torsadogenic potential of possible pharmacotherapies for coronavirus disease 19 (COVID-19)" Mayo Clin Proc, Apr 7, epub ahead of print
  20. Borba MGS, Val FFA, Sampaio VS, et al. (2020) "Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 1 (SARS-CoV-2) infection: A randomized clinical trial." JAMA Netw Open, Apr 1, epub ahead of print
  21. mitra RL, Greenstein SA, Epstein lm (2020) "An algorithm for managing QT prolongation in coronavirus disease 2019 (COVID-19) patients treated with either chloroquine or hydroxychloroquine in conjunction with azithromycin; Possible benefits of intravenous lidocaine." HeartRythm Case Rep, Apr 1, epub ahead of print
View all 21 references

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Drug and food interactions

Moderate

chloroquine food

Applies to: Aralen Phosphate (chloroquine)

GENERALLY AVOID: Theoretically, grapefruit and grapefruit juice may increase the plasma concentrations of hydroxychloroquine or chloroquine and the risk of toxicities such as QT interval prolongation and ventricular arrhythmias. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. Following coadministration with cimetidine, a weak to moderate CYP450 3A4 inhibitor, a 2-fold increase in chloroquine exposure occurred. Since chloroquine and hydroxychloroquine have similar structures and metabolic elimination pathways, a similar interaction may be observed with hydroxychloroquine. 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract during hydroxychloroquine or chloroquine therapy.

References

  1. Cerner Multum, Inc. "Australian Product Information."

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Minor

quiNINE food

Applies to: Qualaquin (quinine)

Coadministration with grapefruit juice does not appear to affect the pharmacokinetics of quinine in a clinically relevant manner. Although grapefruit juice is an inhibitor of CYP450 3A4 and quinine is metabolized by this pathway to its major metabolite, 3-hydroxyquinine, a study of ten healthy volunteers found no significant differences in quinine peak plasma concentration (Cmax), time to reach Cmax (Tmax), terminal elimination half-life, systemic exposure (AUC), or apparent oral clearance (Cl/F) when a single 600 mg oral dose of quinine sulfate was administered in combination with 200 mL of orange juice (control), half-strength grapefruit juice, and full-strength grapefruit juice twice daily for 6 days each, separated by a 2-week washout period. Relative to the control period, the apparent renal clearance of quinine was markedly increased by 81% during treatment with half-strength grapefruit juice. However, since renal clearance accounts for approximately 6% of the total clearance of quinine, this change would likely have minimal clinical impact. The lack of a significant interaction is probably due to the fact that grapefruit juice primarily inhibits intestinal rather than hepatic CYP450 3A4, and quinine is not known to undergo significant presystemic metabolism as evidenced by its relatively high oral bioavailability (76% to 88%). Nevertheless, excessive consumption of grapefruit juice and tonic water (which contains quinine) was suspected as the cause of torsade de pointes arrhythmia in a patient with a history of asymptomatic long QT syndrome. Treatment with magnesium sulfate and metoprolol had no effect, but the arrhythmia resolved spontaneously 48 hours after discontinuation of the drinks. Based on current data, moderate grapefruit juice consumption is probably safe for the majority of patients taking quinine.

References

  1. Ho PC, Chalcroft SC, Coville PF, Wanwimolruk S (1999) "Grapefruit juice has no effect on quinine pharmacokinetics." Eur J Clin Pharmacol, 55, p. 393-8
  2. Hermans K, Stockman D, Van den Branden F (2003) "Grapefruit and tonic: a deadly combination in a patient with the long QT syndrome." Am J Med, 114, p. 511-2
  3. (2006) "Product Information. Qualaquin (quinine)." AR Scientific Inc
  4. Zhang H, Coville PF, Walker RJ, Miners JO, Birkett DJ, Wanwimolruk S (1997) "Evidence for involvement of human CYP3A in the 3-hydroxylation of quinine." Br J Clin Pharmacol, 43, p. 245-52
  5. Mirghani RA, Yasar U, Zheng T, et al. (2002) "Enzyme kinetics for the formation of 3-hydroxyquinine and three new metabolites of quinine in vitro; 3-hydroxylation by CYP3A4 is indeed the major metabolic pathway." Drug Metab Dispos, 30, p. 1368-71
View all 5 references

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antimalarials

Therapeutic duplication

The recommended maximum number of medicines in the 'antimalarials' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antimalarials' category:

  • Aralen Phosphate (chloroquine)
  • Qualaquin (quinine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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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.

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