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Interactions between Fingolimod and Ultane

1 drug interaction and 17 additional warnings found for the following 2 drugs:

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Drug interactions

Major drug interactions

Major:

sevoflurane fingolimod

Applies to: Ultane (sevoflurane) and fingolimod
Monitor closely

Due to its significant bradycardic effects, the risk of QT prolongation and torsade de pointes arrhythmia may be increased during initiation of fingolimod treatment in patients receiving drugs that prolong the QT interval. Fingolimod can cause a decrease in heart rate during initiation of therapy that is apparent within an hour of the first dose and maximal at approximately 6 hours post-dose in most cases, but occasionally up to 20 hours after the first dose. Further, but smaller decreases in heart rate may occur after the second dose, although heart rate eventually returns to baseline within one month of chronic treatment. The mean decrease in heart rate in patients receiving fingolimod 0.5 mg at 6 hours after the first dose was approximately 13 beats per minute (bpm). Heart rates below 40 bpm and AV block were rarely observed. In a study evaluating the effect on QT interval of fingolimod 1.25 or 2.5 mg at steady-state, when a negative chronotropic effect of the drug was still present, fingolimod treatment resulted in a prolongation of the QTc, with an upper bound of the 90% confidence interval of 14.0 msec. There was no consistent signal of increased incidence of QTc outliers, either absolute or change from baseline, associated with fingolimod treatment. In clinical studies, investigators did not observed meaningful prolongation of the QT interval during fingolimod use, but patients at risk for QT prolongation were excluded. 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).

Management

Fingolimod has not been studied in patients receiving drugs that can prolong the QT interval. Because bradycardia and AV block are recognized risk factors for QT prolongation and torsade de pointes arrhythmia, close monitoring is recommended during initiation of fingolimod treatment in patients receiving concomitant drugs that can prolong the QT interval, patients with significant QT prolongation (QTc >470 msec in females or >450 msec in males), or patients with relevant risk factors for QT prolongation (e.g., hypokalemia, hypomagnesemia, congenital QT prolongation). Overnight continuous ECG monitoring after the first dose is recommended in accordance with the product labeling. Fingolimod should not be given if baseline QTc interval is 500 msec or greater. The same precautions are applicable if, after the first month of treatment, fingolimod is discontinued for more than two weeks and then restarted, since the effects on heart rate and AV conduction may recur on reintroduction of fingolimod. Within the first 2 weeks of treatment, first-dose procedures are also recommended after interruption of one day or more; during week 3 and 4 of treatment, first-dose procedures are recommended after treatment interruption of more than 7 days.

References (5)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2025) "Product Information. Gilenya (fingolimod)." Novartis Pharmaceuticals, 2
  5. FDA. U.S. Food and Drug Administration (2012) FDA Drug Safety Communication: Revised recommendations for cardiovascular monitoring and use of multiple sclerosis drug Gilenya (fingolimod). http://www.fda.gov/Drugs/DrugSafety/ucm303192.htm#data

Food/lifestyle interactions

No alcohol/food interactions were found. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.

Disease interactions

17 potential interactions Applies to: 16 conditions, including High Blood Pressure, Seizures, Pseudotumor Cerebri, Heart Disease, and Multiple Myeloma.

Central Nervous System Disorders

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with Central Nervous System Disorders.

Rare cases of posterior reversible encephalopathy syndrome (PRES) have been reported in patients receiving a sphingosine 1-phosphate receptor modulator. It is recommended to promptly schedule a complete physical and neurological examination and should consider an MRI, if a patient develops any unexpected neurological or psychiatric symptoms/signs, any symptom/sign suggestive of an increase of intracranial pressure, or accelerated neurological deterioration. Delay in diagnosis and treatment may lead to permanent neurological sequelae. Exercise care when using this agent in patients with a history of ischemic stroke or cerebral hemorrhage. Treatment should be discontinued if PRES is suspected.

Cerebrovascular Insufficiency

Major:

fingolimod

Fingolimod has a major potential interaction with Cerebrovascular Insufficiency.

Fingolimod is contraindicated in patients who have had a recent myocardial infarction, those with unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or Class III/IV heart failure, a history of Mobitz Type II 2nd degree or 3rd degree AV block or sick sinus syndrome, unless the patient has a pacemaker, baseline QTc interval of >= to 500 msec., or those patients being treated with Class Ia or Class III anti-arrhythmic drugs.

Diabetes Mellitus

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with Diabetes Mellitus.

Fingolimod increases the risk of macular edema. Patients with a history of uveitis, and those with diabetes mellitus are at increased risk of macular edema. It is recommended to perform an examination of the fundus including the macula in all patients before starting treatment, again 3-4 months after starting treatment, and again at any time after a patient reports visual disturbances. A decision on whether or not to discontinue therapy should include an assessment of the potential benefits and risks.

Heart Disease

Major:

fingolimod

Fingolimod has a major potential interaction with Heart Disease.

Fingolimod is contraindicated in patients who have had a recent myocardial infarction, those with unstable angina, stroke, transient ischemic attack, decompensated heart failure with hospitalization, or Class III/IV heart failure, a history of Mobitz Type II 2nd degree or 3rd degree AV block or sick sinus syndrome, unless the patient has a pacemaker, baseline QTc interval of >= to 500 msec., or those patients being treated with Class Ia or Class III anti-arrhythmic drugs.

High Blood Pressure

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with High Blood Pressure.

Hypertension was reported as an adverse reaction in patients on fingolimod. Blood pressure should be monitored during treatment with this agent as it can increase the blood pressure of patients with hypertension.

Hyperkalemia

Moderate:

Ultane

The sevoflurane in Ultane has a moderate potential interaction with Hyperkalemia.

The use of inhaled anesthetic agents has been associated with rare increases in serum potassium levels that have resulted in cardiac arrhythmias and death in pediatric patients during the postoperative period. Patients with latent as well as overt neuromuscular disease, particularly Duchenne muscular dystrophy, appear to be most vulnerable. Early and aggressive intervention to treat the hyperkalemia and resistant arrhythmias is recommended; as is subsequent evaluation for latent neuromuscular disease. Caution and close monitoring is recommended when using this agent in these patients.

Infection

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with Infection.

Fingolimod may increase the risk of infections, and some serious infections with opportunistic pathogens including viruses have been reported. Prior to treatment, a recent CBC (i.e., within 6 months or after discontinuation of prior therapy) should be available. Consider withholding treatment if a patient develops a serious infection, and reassess the benefits and risks prior to reinitiation of therapy.

Liver Disease

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with Liver Disease.

Cases of liver injury with hepatocellular and/or cholestatic hepatitis have been reported with fingolimod in the postmarketing setting. Patients with preexisting liver disease may be at increased risk of developing elevated liver enzymes when taking fingolimod. It is recommended to obtain liver enzyme results before initiation of therapy. No dose adjustment is needed in patients with mild or moderate hepatic impairment. Closely monitor patients with severe hepatic impairment as this agent exposure is doubled in these patients and the risk of adverse reactions is greater. Discontinue if significant liver injury occurs.

Moderate:

Ultane

The sevoflurane in Ultane has a moderate potential interaction with Liver Disease.

In a multicenter study to compare the safety of sevoflurane and isoflurane in patients with mild to moderate hepatic impairment, sevoflurane patients had prolonged terminal disposition of fluoride, as evidenced by longer inorganic fluoride half-life than patients with normal hepatic function. Results of evaluations of laboratory parameters (e.g., ALT, AST, alkaline phosphatase, and total bilirubin, etc.), as well as investigator-reported incidence of adverse events relating to liver function, demonstrate that sevoflurane can be administered to patients with normal or mild-to-moderately impaired hepatic function. The use of this agent in patients with severe hepatic dysfunction has not been investigated. Clinical judgment should be exercised when sevoflurane is used in patients with underlying hepatic conditions or under treatment with drugs known to cause hepatic dysfunction.

Malignant Hyperthermia

Major:

Ultane

The sevoflurane in Ultane has a major potential interaction with Malignant Hyperthermia.

The use of sevoflurane is contraindicated in patients with known or suspected susceptibility to malignant hyperthermia.

Multiple Myeloma

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with Multiple Myeloma.

Rare cases of severe exacerbation of multiple sclerosis (MS), including disease rebound, have been reported after discontinuation of sphingosine 1-phosphate receptor modulator in MS treated patients. The possibility of severe exacerbation of disease should be considered after stopping treatment with these agents. Patients should be observed for a severe increase in disability upon discontinuation and appropriate treatment should be instituted, as required.

Pseudotumor Cerebri

Moderate:

Ultane

The sevoflurane in Ultane has a moderate potential interaction with Pseudotumor Cerebri.

Studies comparing sevoflurane to isoflurane for maintenance of anesthesia during neurosurgical procedures found no difference between sevoflurane and isoflurane with regard to recovery from anesthesia. In patients at risk for elevations of intracranial pressure (ICP), sevoflurane should be administered cautiously in conjunction with ICP-reducing maneuvers such as hyperventilation.

Pulmonary Impairment

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with Pulmonary Impairment.

Cases of dyspnea in patients using fingolimod have been reported during clinical trials. Dose-dependent reductions in forced expiratory volume over 1 second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) were observed in patients treated with fingolimod as early as 1 month after treatment initiation. Caution with patients at risk of dyspnea and spirometric evaluation of respiratory function and evaluation of DLCO should be performed during therapy if clinically indicated.

Renal Dysfunction

Moderate:

Ultane

The sevoflurane in Ultane has a moderate potential interaction with Renal Dysfunction.

Limited data are available on the use of oral sevoflurane in patients with renal insufficiency. Sevoflurane may be associated with glycosuria and proteinuria when used for long procedures at low flow rates. Caution is advised when using sevoflurane in these patients as the safety has not been fully established.

Seizures

Moderate:

Ultane

The sevoflurane in Ultane has a moderate potential interaction with Seizures.

The use of sevoflurane has been associated with seizures. The majority of cases were in children and young adults, most of whom had no medical history of seizures. Seizures have occurred during, or soon after sevoflurane induction, during emergence, and during post-operative recovery up to a day following anesthesia. Caution and clinical judgment should be exercised when using sevoflurane in patients who may be at risk for seizures.

Skin Cancer

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with Skin Cancer.

Cases of malignancies, including skin malignancies have been reported in patients treated with some sphingosine -1-receptor (S1P) receptor modulators. Skin examinations are recommended prior and during treatment in all patients, particularly in those with risk factors for skin cancer. Suspicious skin lesions should be promptly evaluated, and patients at increased risk should wear protective clothing and use sunscreen with high protection factor.

Uveitis

Moderate:

fingolimod

Fingolimod has a moderate potential interaction with Uveitis.

Fingolimod increases the risk of macular edema. Patients with a history of uveitis, and those with diabetes mellitus are at increased risk of macular edema. It is recommended to perform an examination of the fundus including the macula in all patients before starting treatment, again 3-4 months after starting treatment, and again at any time after a patient reports visual disturbances. A decision on whether or not to discontinue therapy should include an assessment of the potential benefits and risks.

More resources

fingolimod

A total of 688 drugs are known to interact with fingolimod.

Ultane

A total of 361 drugs are known to interact with Ultane.

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.