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Drug Interactions between ezetimibe / rosuvastatin and safinamide

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

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Interactions between your drugs

Moderate

ezetimibe rosuvastatin

Applies to: ezetimibe / rosuvastatin and ezetimibe / rosuvastatin

MONITOR: Coadministration with ezetimibe may rarely increase the risk of myopathy and serum transaminase elevations associated with HMG-CoA reductase inhibitors (i.e., statins). The mechanism of interaction is unknown. A case report describes two patients whose serum creatine kinase increased after ezetimibe was added to their statin therapy (atorvastatin and fluvastatin, respectively). One of the patients also developed myalgia and tendinopathy, which resolved promptly after withdrawal of both drugs. Statin therapy was subsequently reintroduced at the previous dosage without incident. In the other patient, serum creatine kinase returned to normal within 4 weeks after discontinuation of ezetimibe while the statin was continued. On the contrary, no cases of myopathy or tendinopathy occurred in a study of 33 hypercholesterolemic patients treated with ezetimibe and atorvastatin or simvastatin. There were also no reports of myopathy or significant increases in serum creatine kinase in a study of 32 subjects treated with ezetimibe and fluvastatin. In controlled clinical studies, the incidence of consecutive elevations (greater than 3 times the upper limit of normal) in serum transaminases was 1.3% for patients treated with ezetimibe in combination with a statin versus 0.4% for patients treated with a statin alone. These elevations were generally asymptomatic, not associated with cholestasis, and returned to baseline after discontinuation of therapy or with continued treatment.

MANAGEMENT: Until further information is available, use of a statin in combination with ezetimibe should be approached with caution. Patients should be advised to promptly report to their physician any unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever. The drugs should be discontinued if creatine kinase is markedly elevated in the absence of strenuous exercise or if myopathy is otherwise suspected or diagnosed. In addition, liver function tests should be performed at initiation of therapy and according to the recommendations of the HMG-CoA reductase inhibitor.

References

  1. Gagne C, Gaudet D, Bruckert E (2002) "Efficacy and safety of ezetimibe coadministered with atorvastatin or simvastatin in patients with homozygous familial hypercholesterolemia." Circulation, 105, p. 2469-75
  2. Fux R, Morike K, Gundel UF, Hartmann R, Gleiter CH (2004) "Ezetimibe and statin-associated myopathy." Ann Intern Med, 140, p. 671-2

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Moderate

rosuvastatin safinamide

Applies to: ezetimibe / rosuvastatin and safinamide

MONITOR: Coadministration with safinamide may increase the plasma concentrations of drugs that are substrates of the breast cancer resistance protein (BCRP) transporter. The proposed mechanism is decreased clearance due to intestinal BCRP-inhibition by safinamide.

MANAGEMENT: Caution is advised when safinamide is prescribed with drugs that are BCRP substrates, particularly those with a narrow therapeutic range such as methotrexate, topotecan, and irinotecan. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever safinamide is added to or withdrawn from therapy.

References

  1. (2017) "Product Information. Xadago (safinamide)." US WorldMeds LLC

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Drug and food interactions

Moderate

safinamide food

Applies to: safinamide

GENERALLY AVOID: Foods that contain large amounts of tyramine may precipitate a hypertensive crisis in patients treated with safinamide. The proposed mechanism involves potentiation of the tyramine pressor effect due to inhibition of monoamine oxidase (MAO) by safinamide. Monoamine oxidase in the gastrointestinal tract and liver, primarily type A (MAO-A), is the enzyme responsible for metabolizing exogenous amines such as tyramine and preventing them from being absorbed intact. Once absorbed, tyramine is metabolized to octopamine, a substance that is believed to displace norepinephrine from storage granules causing a rise in blood pressure. In vitro, safinamide inhibits MAO-B with greater than 1000-fold selectivity over MAO-A, and neither safinamide nor its major metabolites inhibit MAO-A at clinically relevant concentrations. Results from an oral tyramine challenge study also suggest that safinamide is a selective inhibitor of MAO-B at the recommended dosages of 50 or 100 mg/day. However, this selectivity is not absolute and may diminish in a dose-related manner above the maximum recommended daily dosage. In clinical trials, the incidence of hypertension was 7% and 5% for safinamide 50 mg and 100 mg, respectively, versus 4% for placebo. There were no reported cases of hypertensive crisis.

Administration of safinamide following intake of a high-fat, high-caloric breakfast resulted in a slight delay in the absorption of safinamide, but had no effects on safinamide peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration under fasted conditions.

MANAGEMENT: Dietary restriction is not ordinarily required during safinamide treatment with respect to most foods and beverages that contain tyramine, which usually include aged, fermented, cured, smoked, or pickled foods (e.g., air-dried and fermented meats or fish, aged cheeses, most soybean products, yeast extracts, red wine, beer, sauerkraut). However, certain foods like some of the aged cheeses (e.g., Boursault, Liederkrantz, Mycella, Stilton) and pickled herring may contain very high amounts of tyramine and could potentially cause a hypertensive reaction in patients taking safinamide, even at recommended dosages, due to increased sensitivity to tyramine. Patients should be advised to avoid the intake of very high levels of tyramine (e.g., greater than 150 mg) and to promptly seek medical attention if they experience potential signs and symptoms of a hypertensive crisis such as severe headache, visual disturbances, confusion, stupor, seizures, chest pain, unexplained nausea or vomiting, and stroke-like symptoms. Blood pressure should be regularly monitored and managed accordingly. Medication adjustment may be necessary if blood pressure elevations are sustained or not adequately controlled. Safinamide should not be used at dosages exceeding 100 mg/day, or 50 mg/day in patients with moderate hepatic impairment (Child-Pugh B, 7-9), as it may increase the risk of hypertensive crisis and other adverse reactions associated with nonselective inhibition of MAO. Safinamide can be administered with or without food.

References

  1. (2023) "Product Information. Xadago (safinamide)." US WorldMeds LLC
  2. (2020) "Product Information. Onstryv (safinamide)." Valeo Pharma Inc
  3. (2022) "Product Information. Xadago (safinamide)." Seqirus Pty Ltd
  4. (2021) "Product Information. Xadago (safinamide)." Zambon UK Ltd
View all 4 references

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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

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