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Drug Interactions between Cotrim and Halfan

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

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Interactions between your drugs

Minor

sulfamethoxazole halofantrine

Applies to: Cotrim (sulfamethoxazole / trimethoprim) and Halfan (halofantrine)

Limited data suggest that sulfamethoxazole-trimethoprim (SMX-TMP) may rarely prolong the QT interval of the electrocardiogram. 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. There have been isolated reports of QT prolongation and ventricular arrhythmias occurring in patients treated with SMX-TMP intravenously. However, a causal relationship has not been established, and the risk of clinically significant QT prolongation is unlikely at recommended dosages of SMX-TMP. 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 as 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). 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.

References

  1. Wiener I, Rubin D, Martinez E, et al. "QT prolongation and paroxysmal ventricular tachycardia occurring during fever following trimethoprim-sulfamethoxazole administration." Mt Sinai J Med 48 (1981): 53-5
  2. Crouch MA, Limon L, Cassano AT "Clinical relevance and management of drug-related QT interval prolongation." Pharmacotherapy 23 (2003): 881-908
  3. Lopez JA, Harold JG, Rosenthal MC, Oseran DS, Schapira JN, Peter T "QT prolongation and torsades de pointes after administration of trimethoprin-sulfamethoxazole." Am J Cardiol 59 (1987): 376-7
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Darpo B "Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes." Eur Heart J Suppl 3(Suppl K) (2001): K70-80
View all 7 references

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Drug and food interactions

Major

halofantrine food

Applies to: Halfan (halofantrine)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentration of halofantrine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. After administration of 500 mg with 250 mL regular-strength grapefruit juice daily for 3 days, average halofantrine AUC increased 2.8-fold and peak plasma concentrations increased 3.2-fold, compared to water, in healthy subjects (n=12). QT interval prolongation increased from an average of 17 ms with water to 31 ms with grapefruit juice. Halofantrine, even at recommended doses, can cause dose-related prolongation of the QT interval, resulting in an elevated risk of potentially fatal ventricular arrhythmias including ventricular tachycardia and torsade de pointes.

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of halofantrine. Peak plasma concentrations increased seven-fold and AUC increased three-fold in healthy subjects when halofantrine was administered with high-fat food.

MANAGEMENT: The authors of the study recommend that grapefruit juice be avoided during halofantrine therapy. The manufacturer recommends performing an ECG before initiating halofantrine therapy and cardiac monitoring during and for 8 to 12 hours after completion of therapy. Halofantrine should be taken on an empty stomach at least 1 hour before or 2 hours after food.

References

  1. Giao PT, de Vries PJ "Pharmacokinetic interactions of antimalarial agents." Clin Pharmacokinet 40 (2001): 343-73
  2. "Product Information. Halfan (halofantrine)." GlaxoSmithKline (2003):
  3. Charbit B, Becquemont L, Lepere B, Peytavin G, Funck-Bretano C "Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine." Clin Pharmacol Ther 72 (2002): 514-23
  4. Abernethy DR, Wesche DL, Barbey JT, et al. "Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation." Br J Clin Pharmacol 51 (2001): 231-7
View all 4 references

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Moderate

sulfamethoxazole food

Applies to: Cotrim (sulfamethoxazole / trimethoprim)

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

References

  1. Heelon MW, White M "Disulfiram-cotrimoxazole reaction." Pharmacotherapy 18 (1998): 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother 64 (2020): e02167-19

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

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

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

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