Drug Interactions between budesonide and ceritinib

Do not consume grapefruit or grapefruit juice during treatment with ceritinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of ceritinib to dangerous levels, increasing the risk of an irregular heart rhythm that may be serious. Other, more common side effects such as diarrhea, nausea, vomiting, abdominal pain, and hyperglycemia (high blood sugar) may also increase. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart palpitations during treatment with ceritinib. Food may also increase the blood levels of ceritinib. Therefore, you should take ceritinib on an empty stomach, meaning no food should be eaten for at least two hours before or after taking ceritinib. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

You should avoid the regular consumption of large amounts of grapefruits and grapefruit juice while taking budesonide. Grapefruit can raise the levels of budesonide in your body and lead to increased side effects. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor.

Ceritinib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. When possible, avoid use of ceritinib in patients with congenital long QT syndrome. It is recommended to conduct periodic monitoring with electrocardiograms (ECGs) in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval. Withhold ceritinib in patients who develop a QTc interval greater than 500 msec on at least 2 separate ECGs until the QTc interval is less than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then resume therapy at a reduced dose as clinically indicated. Permanently discontinue ceritinib in patients who develop QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia. This drug should be used with caution in patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.

Ceritinib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. When possible, avoid use of ceritinib in patients with congenital long QT syndrome. It is recommended to conduct periodic monitoring with electrocardiograms (ECGs) in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval. Withhold ceritinib in patients who develop a QTc interval greater than 500 msec on at least 2 separate ECGs until the QTc interval is less than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then resume therapy at a reduced dose as clinically indicated. Permanently discontinue ceritinib in patients who develop QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia. This drug should be used with caution in patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Therapy with corticosteroids should be administered cautiously nonetheless in patients with a history of cataracts, glaucoma, or increased intraocular pressure. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

The use of ceritinib causes hyperglycemia. It is recommended to monitor fasting serum glucose prior to the start of therapy and periodically thereafter as clinically indicated. Initiate or optimize antihyperglycemic medications as clinically appropriate, and withhold therapy until hyperglycemia is adequately controlled, then resume at a reduced dose as clinically appropriate. If adequate hyperglycemic control cannot be achieved with optimal medical management, permanently discontinue treatment with ceritinib. Care should be exercised when using this agent in diabetic patients.

Severe gastrointestinal toxicity has been reported in patients treated with ceritinib. It is recommended to monitor and manage patients using standards of care, or withhold ceritinib with resumption at a reduced dose as per clinical guidelines. Care and close monitoring is recommended in patients reporting diarrhea, vomiting, or abdominal pain.

Prolonged use of corticosteroids may cause posterior subcapsular cataracts and elevated intraocular pressure, the latter of which may lead to glaucoma and/or damage to the optic nerves. Therapy with corticosteroids should be administered cautiously nonetheless in patients with a history of cataracts, glaucoma, or increased intraocular pressure. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

The use of ceritinib may cause bradycardia. It is recommended to monitor heart rate and blood pressure regularly and in cases of symptomatic bradycardia that is not life-threatening, withhold therapy until recovery and adjust the dose of ceritinib. It might be necessary to permanently discontinue ceritinib for life-threatening bradycardia if no contributing concomitant medication is identified; however, if associated with a concomitant medication known to cause bradycardia or hypotension, withhold therapy until recovery and resume therapy at a reduced dose with frequent monitoring. Care and close monitoring is recommended.

The use of corticosteroids may rarely precipitate or aggravate conditions of hyperadrenocorticism. Although adverse effects of corticosteroids may be minimized by local rather than systemic administration, the risks are not entirely abolished. Inhaled and nasally applied drug may be absorbed into the circulation, especially when large doses are used. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used. The development of symptoms such as menstrual irregularities, acneiform lesions, cataracts and cushingoid features during inhaled or nasal corticosteroid therapy may indicate excessive use.

The immunosuppressant and anti-inflammatory effects of corticosteroids, particularly in higher dosages, may decrease host resistance to infectious agents, decrease the ability to localize infections, and mask the symptoms of infection. Secondary infections may be more likely to develop. Therapy with corticosteroids should be administered cautiously in patients with an infection, particularly active or quiescent tuberculosis or in hepatitis B carriers. Monitor patients for any new or worsening infection and use with caution in these patients. A serious or even fatal course of chickenpox and measles can occur in susceptible patients. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

Some inhaled corticosteroid formulations contain lactose and may cause adverse reactions including cough, wheezing and bronchospasm in patients with severe milk protein allergy or intolerance. Caution is advised.

Corticosteroids are predominantly cleared by hepatic metabolism and impairment of the liver function may lead to their accumulation. Patients with hepatic disease should be closely monitored.

Ceritinib is eliminated primarily via the liver. Patients with hepatic impairment may have increased exposure and drug-induced hepatotoxicity. Based on results of population pharmacokinetic analysis no dose adjustment is needed for patients with mild hepatic impairment. The pharmacokinetics of ceritinib has not been studied in patients with moderate to severe hepatic impairment; therefore, a recommended dose has not been determined for these patients. It is recommended to monitor liver function tests including ALT, AST, and total bilirubin once a month and as clinically indicated, with more frequent testing in patients who develop transaminase elevations. In some cases, it might be necessary to withhold ceritinib and resume therapy at a reduced dose, or permanently discontinue treatment.

Pharmacologic dosages of corticosteroids may increase the risk of corneal perforation in patients with ocular herpes simplex. Therapy with inhaled and nasal corticosteroids should be administered cautiously in such patients.

Prolonged use of inhaled corticosteroids may be associated with a reduction in bone density. This effect appears to be dose-related and has been reported primarily with high dosages (800 mcg/day or more of beclomethasone or equivalent for 1 year or greater). Reduced levels of total body calcium have also been demonstrated in patients receiving lower dosages. Long-term therapy with inhaled and nasal corticosteroids should be administered cautiously in patients with osteoporosis. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Pancreatitis, including a fatal case has occurred in patients receiving ceritinib. It is recommended to monitor lipase and amylase prior to the start of therapy with ceritinib and periodically thereafter as clinically indicated. It might be necessary to withhold the dose of ceritinib based on the severity of the laboratory abnormalities and resume therapy at a reduced dose per clinical guidelines. Care is recommended when using this agent in patients at risk.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

Based on results of population pharmacokinetic analyses ceritinib exposures are similar between patients with mild to moderate renal impairment and patients with normal renal function. No dose adjustment is needed for these patients. Caution and monitoring is needed when using this agent in patients with severe renal impairment as no information is available.

The use of ceritinib may cause bradycardia. It is recommended to monitor heart rate and blood pressure regularly and in cases of symptomatic bradycardia that is not life-threatening, withhold therapy until recovery and adjust the dose of ceritinib. It might be necessary to permanently discontinue ceritinib for life-threatening bradycardia if no contributing concomitant medication is identified; however, if associated with a concomitant medication known to cause bradycardia or hypotension, withhold therapy until recovery and resume therapy at a reduced dose with frequent monitoring. Care and close monitoring is recommended.

The immunosuppressant and anti-inflammatory effects of corticosteroids, particularly in higher dosages, may decrease host resistance to infectious agents, decrease the ability to localize infections, and mask the symptoms of infection. Secondary infections may be more likely to develop. Therapy with corticosteroids should be administered cautiously in patients with an infection, particularly active or quiescent tuberculosis or in hepatitis B carriers. Monitor patients for any new or worsening infection and use with caution in these patients. A serious or even fatal course of chickenpox and measles can occur in susceptible patients. It is important that the recommended dosages of the individual products not be exceeded and that the lowest effective dosage be used.

Severe gastrointestinal toxicity has been reported in patients treated with ceritinib. It is recommended to monitor and manage patients using standards of care, or withhold ceritinib with resumption at a reduced dose as per clinical guidelines. Care and close monitoring is recommended in patients reporting diarrhea, vomiting, or abdominal pain.