Drug Interactions between atezolizumab and budesonide

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.

Immune-related meningoencephalitis has been reported with the use of atezolizumab therapy. Monitor patients for clinical signs and symptoms of meningitis or encephalitis. Permanently discontinue therapy for any grade of meningitis or encephalitis.

Immune-related thyroid disorders, adrenal insufficiency, and type 1 diabetes mellitus, including diabetic ketoacidosis, have been reported in patients receiving atezolizumab. It is recommended to monitor patients for clinical signs and symptoms of endocrinopathies and to institute appropriate measures as necessary. Monitor as clinically indicated prior to and periodically during treatment and withhold, reduce dose, or discontinue therapy as necessary.

Immune-mediated hepatitis occurred in patients receiving atezolizumab treatment with reported liver test abnormalities. Monitor patients for liver function test and for symptoms of hepatitis. Monitor bilirubin prior to and periodically during treatment. Therapy with atezolizumab should be administered cautiously in these patients. It is recommended to withhold atezolizumab for Grade 2 immune-mediated hepatitis and institute appropriate measures and to permanently discontinue therapy for Grade or 4 immune-mediated hepatitis

Immune-related myasthenic syndrome/myasthenia gravis, Guillain-Barré, and ocular inflammatory toxicity have been reported with the use of atezolizumab therapy. Monitor patients for symptoms of motor and sensory neuropathy. Permanently discontinue therapy for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome and institute medical intervention as appropriate.

Immune-related thyroid disorders, adrenal insufficiency, and type 1 diabetes mellitus, including diabetic ketoacidosis, have been reported in patients receiving atezolizumab. It is recommended to monitor patients for clinical signs and symptoms of endocrinopathies and to institute appropriate measures as necessary. Monitor as clinically indicated prior to and periodically during treatment and withhold, reduce dose, or discontinue therapy as necessary.

Immune-related myasthenic syndrome/myasthenia gravis, Guillain-Barré, and ocular inflammatory toxicity have been reported with the use of atezolizumab therapy. Monitor patients for symptoms of motor and sensory neuropathy. Permanently discontinue therapy for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome and institute medical intervention as appropriate.

Severe infections, including urinary tract infections, pneumonia, sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage occurred in patients treated with atezolizumab. It is recommended to monitor patients for signs and symptoms of infection and to treat with antibiotics for suspected or confirmed bacterial infections. Withhold therapy for greater than or equal to Grade 3 infections.

Immune-related myasthenic syndrome/myasthenia gravis, Guillain-Barré, and ocular inflammatory toxicity have been reported with the use of atezolizumab therapy. Monitor patients for symptoms of motor and sensory neuropathy. Permanently discontinue therapy for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome and institute medical intervention as appropriate.

Immune-related pancreatitis, including increases in serum amylase and lipase levels have been reported with the use of atezolizumab therapy. Caution is recommended and patients should be monitored for signs and symptoms of acute pancreatitis. Withhold atezolizumab for greater than or equal to Grade 3 serum amylase or lipase levels (> 2.0 ULN), or Grade 2 or 3 pancreatitis and permanently discontinue therapy for Grade 4 or any grade of recurrent pancreatitis.

Immune-related thyroid disorders, adrenal insufficiency, and type 1 diabetes mellitus, including diabetic ketoacidosis, have been reported in patients receiving atezolizumab. It is recommended to monitor patients for clinical signs and symptoms of endocrinopathies and to institute appropriate measures as necessary. Monitor as clinically indicated prior to and periodically during treatment and withhold, reduce dose, or discontinue therapy as necessary.

Programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies can cause immune-mediated adverse reactions, which may be severe or fatal. Immune-mediated adverse reactions can occur in any organ system or tissue at any time after starting therapy. This may be considered when using PD-1/PD-L1 blocking antibodies in patients with immune system disorders (e.g., ulcerative colitis, Crohn's disease, lupus) or with conditions affecting the nervous system (e.g., myasthenia gravis, Guillain-Barre syndrome). It is recommended to monitor patients closely for signs/symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions.

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. It is recommended to follow patients closely for evidence of transplant-related complications and intervene promptly. The benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody before or after an allogeneic HSCT should be considered.

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.

Immune-mediated colitis or diarrhea have been reported during atezolizumab therapy, in some cases with fatal outcomes. Monitor patients for signs and symptoms of diarrhea or colitis. It is recommended to withhold treatment with atezolizumab for Grade 2 diarrhea or colitis and if symptoms persist for longer than 5 days or recur, it is recommended to administer 1 to 2 mg/kg prednisone or equivalent per day. Withhold treatment for Grade 3 diarrhea or colitis and treat with IV methylprednisolone 1 to 2 mg/kg per day and convert to oral steroids once the patient has improved. For both Grade 2 and Grade 3 diarrhea or colitis, when symptoms improve to Grade 0 or Grade 1, taper steroids over greater than or equal to 1 month. Resume treatment if the event improves to Grade 0 or 1 within 12 weeks and corticosteroids have been reduced to the equivalent of less than or equal to 10 mg oral prednisone per day. Permanently discontinue atezolizumab for Grade 4 diarrhea or colitis.

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 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.

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.

Population pharmacokinetic analyses suggest that no dose adjustment of atezolizumab is needed for patients with mild hepatic impairment. No clinical studies were conducted with atezolizumab in patients with moderate or severe hepatic impairment. Caution is recommended when using this agent.

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.

Solid organ transplant rejection and other transplant (including corneal graft) rejection have been reported with the use of programmed death receptor-1/ligand-1 (PD-1/PD-L1) blocking antibodies. This may be considered when using PD-1/PD-L1 blocking antibodies in patients who have received a solid organ or other transplant.

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.

Immune-mediated pneumonitis, sometimes fatal, or interstitial lung disease have been reported during atezolizumab therapy. Patients should be monitored with radiographic imaging and for symptoms of pneumonitis. Therapy with atezolizumab should be administered cautiously in patients with or predisposed to pulmonary dysfunction. It is recommended to withhold atezolizumab until resolution for Grade 2 pneumonitis and to permanently discontinue therapy for Grade 3 or 4 pneumonitis.

Population pharmacokinetic analyses suggest that no dose adjustment of atezolizumab is required for patients with renal impairment. The effect of severe renal impairment on the pharmacokinetics of atezolizumab is unknown. Caution is recommended with these patients.

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.