Drug Interactions between budesonide and vemurafenib

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.

Vemurafenib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. It is recommended not to start treatment in patients with uncorrectable electrolyte abnormalities, QTc > 500 ms, or long QT syndrome, or in patients who are taking medicinal products known to prolong the QT interval. Evaluate patients prior to and following treatment initiation or after dose modification for QTc prolongation, evaluate ECG and electrolytes (including potassium, magnesium, and calcium) periodically, and thereafter as clinically indicated. Vemurafenib should be withhold in patients who develop QTc > 500 ms. Upon recovery to QTc <= 500 ms, restart at a reduced dose and it should be permanently discontinued if the QTc interval remains > 500 ms and increased > 60 ms from pre-treatment values after controlling cardiac risk factors for QT prolongation (e.g., electrolyte abnormalities, congestive heart failure, and bradyarrhythmias).

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.

Severe dermatologic reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and mild to severe photosensitivity can occur in patients treated with vemurafenib. Consider dose modifications for intolerable >= Grade 2 photosensitivity. It is recommended to advise patients to avoid sun exposure, wear protective clothing and use a broad-spectrum UVA/UVB sunscreen and a suitable lip balm when outdoors while on vemurafenib treatment. Permanently discontinue vemurafenib in patients who experience a severe dermatologic reaction.

Vemurafenib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. It is recommended not to start treatment in patients with uncorrectable electrolyte abnormalities, QTc > 500 ms, or long QT syndrome, or in patients who are taking medicinal products known to prolong the QT interval. Evaluate patients prior to and following treatment initiation or after dose modification for QTc prolongation, evaluate ECG and electrolytes (including potassium, magnesium, and calcium) periodically, and thereafter as clinically indicated. Vemurafenib should be withhold in patients who develop QTc > 500 ms. Upon recovery to QTc <= 500 ms, restart at a reduced dose and it should be permanently discontinued if the QTc interval remains > 500 ms and increased > 60 ms from pre-treatment values after controlling cardiac risk factors for QT prolongation (e.g., electrolyte abnormalities, congestive heart failure, and bradyarrhythmias).

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.

Cutaneous squamous cell carcinoma, keratoacanthoma, and melanoma occurred at a higher incidence in patients receiving vemurafenib. Potential risk factors associated included age (> 65 years), prior skin cancer, and chronic sun exposure. It is recommended to perform dermatologic evaluations prior to initiation of therapy and periodically thereafter as clinically indicated. Consider dermatologic monitoring for 6 months following discontinuation of vemurafenib.

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.

Liver injury leading to functional hepatic impairment, including coagulopathy or other organ dysfunction may occur with the use of vemurafenib. Based on a population pharmacokinetic analysis to evaluate the effect of hepatic impairment, no dose adjustment is recommended for patients with mild and moderate hepatic impairment. The appropriate dose of vemurafenib has not been established in patients with severe hepatic impairment. It is recommended to monitor transaminases, alkaline phosphatase, and bilirubin before initiation of treatment and monthly during treatment, or as clinically indicated; and to manage laboratory abnormalities with dose reduction, treatment interruption, or treatment discontinuation as appropriate.

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.

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.

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.

Renal failure, including acute interstitial nephritis and acute tubular necrosis may occur with the use of vemurafenib. Based on a population pharmacokinetic analysis, no dose adjustment is recommended for patients with mild and moderate renal impairment. The appropriate dose of vemurafenib has not been established in patients with severe renal impairment. It is recommended to measure serum creatinine before initiation of therapy and periodically during treatment.

Cutaneous squamous cell carcinoma, keratoacanthoma, and melanoma occurred at a higher incidence in patients receiving vemurafenib. Potential risk factors associated included age (> 65 years), prior skin cancer, and chronic sun exposure. It is recommended to perform dermatologic evaluations prior to initiation of therapy and periodically thereafter as clinically indicated. Consider dermatologic monitoring for 6 months following discontinuation of vemurafenib.

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.

Uveitis, blurry vision, and photophobia can occur in patients treated with vemurafenib. Monitor patients for signs and symptoms of uveitis. Care must be exercised when using this agent in patients with ophthalmological complications.