Drug Interactions between Abraxane and atezolizumab

Grapefruits and grapefruit juice may increase the blood levels and effects of PACLitaxel protein-bound. This can increase the risk of side effects such as nausea, diarrhea, hair loss, muscle pain or weakness, nerve damage, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. Contact your doctor if you experience paleness, fatigue, dizziness, fainting, unusual bruising or bleeding, fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, pain or burning during urination, vision problems, and/or numbness, burning or tingling in your hands and feet. You may need a dose adjustment and/or more frequent monitoring by your doctor to safely use both medications. 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.

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.

Severe conduction abnormalities, some requiring pacemaker placement, have been reported during paclitaxel therapy. Therapy with paclitaxel should be administered cautiously in patients with or predisposed to conduction disorders. Clinical monitoring of cardiac function is recommended during subsequent paclitaxel therapy.

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.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

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.

Paclitaxel induces dose-dependent myelosuppression, primarily affecting neutrophils. Anemia characterized as a red blood cell count <11 g/dl has been reported in 78% of patients administered paclitaxel. Thrombocytopenia is uncommon and rarely severe. Therapy with paclitaxel should be administered cautiously in patients whose bone marrow reserve may be severely depressed and should be withheld when neutrophil counts fall below 1500/mm3 and/or platelet counts fall below 100,000/mm3. Paclitaxel injection should not be used in patients with solid tumors with baseline neutrophil counts less than 1500/mm3 or in patients with AIDS-related Kaposi's sarcoma with baseline neutrophil counts of less than 1000/mm3. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Close clinical monitoring of hematopoietic function is recommended.

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.

Paclitaxel is extensively metabolized by the liver. Patients with moderate to severe hepatic impairment may be at increased risk for hepatotoxicity. Additionally, myelotoxicity of paclitaxel may be exacerbated in patients with serum total bilirubin >2 times ULN. Therapy with paclitaxel should be administered cautiously and at a reduced dosage in patients with compromised hepatic function.

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.

Dose-dependent peripheral neuropathy has been reported in 60% of patients during paclitaxel therapy. Severe peripheral neuropathy is rare and requires a 20% reduction in dosage of paclitaxel. Therapy with paclitaxel should be administered cautiously in patients with or predisposed to peripheral neuropathy.

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.

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.

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.

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.

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.