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Drug Interactions between levomethadyl acetate and Ranexa

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

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Interactions between your drugs

Major

levomethadyl acetate ranolazine

Applies to: levomethadyl acetate and Ranexa (ranolazine)

CONTRAINDICATED: Levomethadyl acetate may 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. High dosages of levomethadyl acetate alone have been associated with QT interval prolongation and torsade de pointes. 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). The extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In addition, central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking levomethadyl acetate with certain other drugs that cause these effects, especially in elderly or debilitated patients.

MANAGEMENT: Coadministration of levomethadyl acetate with other drugs that can prolong the QT interval is considered contraindicated.

References

  1. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc PROD (2001):
  2. Deamer RL, Wilson DR, Clark DS, Prichard JG "Torsades de pointes associated with high dose levomethadyl acetate (ORLAAM)." J Addict Dis 20 (2001): 7-14
  3. Krantz MJ, Mehler PS "Synthetic opioids and QT prolongation." Arch Intern Med 163 (2003): 1615; author reply 1615
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852" (2013):
View all 5 references

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Drug and food interactions

Major

levomethadyl acetate food

Applies to: levomethadyl acetate

GENERALLY AVOID: The concurrent use of levomethadyl acetate and alcohol may result in additive CNS and respiratory depression, hypotension, sedation, or coma. Grapefruit juice may increase the plasma concentrations of orally administered drugs which are substrates of the CYP450 3A4 isoenzyme, such as levomethadyl acetate. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who are known to abuse alcohol should be warned of the risk of potentially fatal overdose if these substances are taken concurrently. Patients who regularly consume grapefruits and grapefruit juice should be monitored for adverse effects and altered plasma concentrations of levomethadyl acetate. A 12-lead ECG should be performed before initiating therapy, 12 to 14 days after initiating therapy, and periodically thereafter. Patients should be advised to immediately seek medical attention if they experience palpitations, dizziness, lightheadedness, fainting, or seizures. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

References

  1. "Product Information. Orlaam (levomethadyl acetate)." Roxane Laboratories Inc PROD (2001):

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Major

ranolazine food

Applies to: Ranexa (ranolazine)

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of orally administered ranolazine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes.

MANAGEMENT: Patients treated with ranolazine should avoid consumption of grapefruit juice and other grapefruit products if possible. Otherwise, the dosage of ranolazine should be limited to 500 mg twice a day.

References

  1. "Product Information. Ranexa (ranolazine)." Calmoseptine Inc (2006):

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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.

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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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