Thiamine HCl (Vitamin B1)

Fedratinib is used to treat intermediate-2 or high-risk primary or secondary myelofibrosis (MF) in adults, relieving night sweats, itching, pain, feeling full after eating, and spleen volume. Myelofibrosis is a rare type of bone marrow disorder. The brand name of fedratinib is Inrebic , and it is a capsule that is taken once a day. Fedratinib is a kinase inhibitor that works by blocking certain types of enzymes called kinases that are overactive in myelofibrosis: Janus-associated kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). These enzymes are involved in signaling pathways that contribute to excessive inflammation in bone marrow, an enlarged spleen, and symptoms of myelofibrosis. Fedratinib gained FDA approval on August 16, 2019, under the brand name Inrebic. There is no generic.

Fedratinib is used to treat intermediate-2 or high-risk primary or secondary myelofibrosis (MF) in adults, relieving night sweats, itching, pain, feeling full after eating, and spleen volume. Myelofibrosis is a rare type of bone marrow disorder. The brand name of fedratinib is Inrebic , and it is a capsule that is taken once a day. Fedratinib is a kinase inhibitor that works by blocking certain types of enzymes called kinases that are overactive in myelofibrosis: Janus-associated kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). These enzymes are involved in signaling pathways that contribute to excessive inflammation in bone marrow, an enlarged spleen, and symptoms of myelofibrosis. Fedratinib gained FDA approval on August 16, 2019, under the brand name Inrebic. There is no generic.

To make sure fedratinib is safe for you, tell your doctor if you: have low vitamin B1 (thiamine) levels have low red blood cell or platelet counts have or have had liver problems have or have had kidney problems have or have had eye problems are a current or past smoker have had a blood clot, heart attack, other heart problems, or stroke have or have had any other cancer are pregnant or plan to become pregnant are breastfeeding or plan to breastfeed. Fedratinib is not for use in patients under the age of 18 years.

The most common side effects of fedratinib are: diarrhea nausea low red blood cell count (anemia) vomiting.

Fedratinib carries a Boxed Warning for encephalopathy, including Wernicke's encephalopathy. Encephalopathy ( including Wernicke's encephalopathy). A serious and sometimes fatal neurological problem called encephalopathy (including Wernicke's encephalopathy) has happened in some people who take fedratinib. Wernicke’s encephalopathy is a neurologic emergency that can happen if you do not have enough Vitamin B1 (thiamine) in your body. Your healthcare provider will do a blood test to check your Vitamin B1 level and treat you with Vitamin B1 if your level is too low before starting treatment with fedratinib. Your healthcare provider may also check your Vitamin B1 level during treatment and you should take a Vitamin B1 supplement (100 mg of thiamine) throughout treatment with fedratinib. Get emergency medical help right away if you develop the following: confusion, memory problems, or drowsiness problems with balance and movement, such as difficulty walking eye problems, such as double or blurred vision, or abnormal eye movements. Call your healthcare provider right away if you experience diarrhea, nausea, vomiting, and weight loss that does not get better with treatment. Low blood cell counts . Fedratinib may cause new or worsening low red blood cell counts (anemia) and low platelet counts (thrombocytopenia) in some people. You may need a blood transfusion if your blood counts drop too low. Your healthcare provider will do blood tests to check your blood counts before you start and during treatment with fedratinib. Tell your healthcare provider if you develop any bleeding or bruising during treatment with fedratinib. Diarrhea, nausea, and vomiting . Your healthcare provider may give you certain medicines to help treat diarrhea, nausea, and vomiting caused by fedratinib. Call your healthcare provider or get emergency medical help right away if you have diarrhea, nausea, or vomiting that does not get better with treatment. Liver problems . Fedratinib may cause increased liver enzymes. Your healthcare provider will do blood tests to check your liver function before starting and during treatment with fedratinib. Amylase and lipase increases . You may have increases in your blood amylase or lipase levels that may indicate a problem with your pancreas. Your healthcare provider will do blood tests to check your amylase or lipase levels before starting and during treatment with fedratinib. Uveitis . Inrebic may cause inflammation of the middle layer of the eyeball (uvea) called uveitis. Tell your healthcare provider if you develop any symptoms, including eye pain, redness, sensitivity to light, new or increased floaters (specks or threads that float in your vision), or a decrease in your vision. You may need to see an eye specialist to check your eyes if you develop any signs and symptoms of eye problems. Major cardiac events such as a heart attack, stroke, or death . An increased risk of major cardiac events has occurred in people, especially those who have cardiovascular risk factors and who are current or past smokers, while taking another Janus Kinase (JAK) inhibitor to treat rheumatoid arthritis. Get emergency help right away if you have any symptoms of a heart attack or stroke while taking fedratinib, including: discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw pain or discomfort in your arms, back, neck, jaw, or stomach shortness of breath with or without chest discomfort breaking out in a cold sweat nausea or vomiting feeling lightheaded weakness in one part or on one side of your body slurred speech. Blood clots . Increased risk of blood clots in the veins of the legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) has happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening. Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with fedratinib, including: swelling, pain, or tenderness in one or both legs sudden unexplained chest or upper back pain shortness of breath, or difficulty breathing. New (secondary) cancers . People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers, except nonmelanoma skin cancer. People who smoke or who smoked in the past have an increased risk of new cancers. Fedratinib may cause an allergic reaction . Get emergency medical help if you have signs of an allergic reaction to fedratinib: hives , difficulty breathing, swelling of your face, lips, tongue, or throat. Driving and using machines : While using this medicine, you may feel weak, tired, dizzy, or confused. You may have blurred vision. Before driving a vehicle or using machinery, wait to see how you feel after taking fedratinib. Call your doctor at once if you have: severe or ongoing nausea, vomiting, or diarrhea (even while you are taking medication to prevent these effects); easy bruising, unusual bleeding, purple or red spots under your skin; low red blood cells (anemia) - pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet; or low white blood cell counts - fever, mouth sores, skin sores, sore throat , cough, trouble breathing. You may need a blood transfusion if your blood counts get too low. This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Fedratinib carries a Boxed Warning for encephalopathy, including Wernicke's encephalopathy. Encephalopathy ( including Wernicke's encephalopathy). A serious and sometimes fatal neurological problem called encephalopathy (including Wernicke's encephalopathy) has happened in some people who take fedratinib. Wernicke’s encephalopathy is a neurologic emergency that can happen if you do not have enough Vitamin B1 (thiamine) in your body. Your healthcare provider will do a blood test to check your Vitamin B1 level and treat you with Vitamin B1 if your level is too low before starting treatment with fedratinib. Your healthcare provider may also check your Vitamin B1 level during treatment and you should take a Vitamin B1 supplement (100 mg of thiamine) throughout treatment with fedratinib. Get emergency medical help right away if you develop the following: confusion, memory problems, or drowsiness problems with balance and movement, such as difficulty walking eye problems, such as double or blurred vision, or abnormal eye movements. Call your healthcare provider right away if you experience diarrhea, nausea, vomiting, and weight loss that does not get better with treatment. Low blood cell counts . Fedratinib may cause new or worsening low red blood cell counts (anemia) and low platelet counts (thrombocytopenia) in some people. You may need a blood transfusion if your blood counts drop too low. Your healthcare provider will do blood tests to check your blood counts before you start and during treatment with fedratinib. Tell your healthcare provider if you develop any bleeding or bruising during treatment with fedratinib. Diarrhea, nausea, and vomiting . Your healthcare provider may give you certain medicines to help treat diarrhea, nausea, and vomiting caused by fedratinib. Call your healthcare provider or get emergency medical help right away if you have diarrhea, nausea, or vomiting that does not get better with treatment. Liver problems . Fedratinib may cause increased liver enzymes. Your healthcare provider will do blood tests to check your liver function before starting and during treatment with fedratinib. Amylase and lipase increases . You may have increases in your blood amylase or lipase levels that may indicate a problem with your pancreas. Your healthcare provider will do blood tests to check your amylase or lipase levels before starting and during treatment with fedratinib. Uveitis . Inrebic may cause inflammation of the middle layer of the eyeball (uvea) called uveitis. Tell your healthcare provider if you develop any symptoms, including eye pain, redness, sensitivity to light, new or increased floaters (specks or threads that float in your vision), or a decrease in your vision. You may need to see an eye specialist to check your eyes if you develop any signs and symptoms of eye problems. Major cardiac events such as a heart attack, stroke, or death . An increased risk of major cardiac events has occurred in people, especially those who have cardiovascular risk factors and who are current or past smokers, while taking another Janus Kinase (JAK) inhibitor to treat rheumatoid arthritis. Get emergency help right away if you have any symptoms of a heart attack or stroke while taking fedratinib, including: discomfort in the center of your chest that lasts for more than a few minutes, or that goes away and comes back severe tightness, pain, pressure, or heaviness in your chest, throat, neck, or jaw pain or discomfort in your arms, back, neck, jaw, or stomach shortness of breath with or without chest discomfort breaking out in a cold sweat nausea or vomiting feeling lightheaded weakness in one part or on one side of your body slurred speech. Blood clots . Increased risk of blood clots in the veins of the legs (deep vein thrombosis, DVT) or lungs (pulmonary embolism, PE) has happened in people taking another JAK inhibitor for rheumatoid arthritis and may be life-threatening. Tell your healthcare provider right away if you have any signs and symptoms of blood clots during treatment with fedratinib, including: swelling, pain, or tenderness in one or both legs sudden unexplained chest or upper back pain shortness of breath, or difficulty breathing. New (secondary) cancers . People who take another JAK inhibitor for rheumatoid arthritis have an increased risk of new (secondary) cancers, including lymphoma and other cancers, except nonmelanoma skin cancer. People who smoke or who smoked in the past have an increased risk of new cancers. Fedratinib may cause an allergic reaction . Get emergency medical help if you have signs of an allergic reaction to fedratinib: hives , difficulty breathing, swelling of your face, lips, tongue, or throat. Driving and using machines : While using this medicine, you may feel weak, tired, dizzy, or confused. You may have blurred vision. Before driving a vehicle or using machinery, wait to see how you feel after taking fedratinib. Call your doctor at once if you have: severe or ongoing nausea, vomiting, or diarrhea (even while you are taking medication to prevent these effects); easy bruising, unusual bleeding, purple or red spots under your skin; low red blood cells (anemia) - pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet; or low white blood cell counts - fever, mouth sores, skin sores, sore throat , cough, trouble breathing. You may need a blood transfusion if your blood counts get too low. This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

100 to 300 mg (200 (200)) 24 hourly PO,IM — IV doses should be administered slowly atleast over 20 min to reduce Idiosyncratic reactions Scraped Dose — Take fedratinib exactly as prescribed by your doctor. Follow all directions on your Inrebic (fedratinib) Package Insert and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Fedratinib is taken 1 time a day. You may take fedratinib capsules with or without food. Taking fedratinib with a high-fat meal may help to reduce nausea and vomiting symptoms. Take Vitamin B1 (thiamine 100 mg) by mouth daily to prevent low Vitamin B1 levels during treatment with fedratinib. If you cannot swallow fedratinib capsules whole or have a nasogastric tube , the capsules can be opened, and the contents can be mixed with Ensure Plus liquid nutritional supplement. Carefully open your prescribed dose into a glass container and mix with about 180 mL (6 oz) of liquid nutritional supplement at room temperature, between 68°F to 77°F (20°C to 25°C). Swallow the mixture right away or give it through a nasogastric (NG) tube (French size 14 or 16) within 2 hours of preparation. If using an NG tube, flush the NG tube with 60 mL (2 oz) of water after giving the Inrebic mixture. Throw away the prepared dose if not given within 2 hours and mix a new dose. You may be given other medications to help prevent nausea , vomiting , and diarrhea . Keep using these medicines for as long as your doctor has prescribed. Call your doctor if you are sick with vomiting or diarrhea, even while taking medications to prevent these side effects. You can easily become malnourished from vomiting and diarrhea. This can lead to low vitamin B1 levels. Fedratinib can lower your blood cell counts and affect liver function. Your blood will need to be tested often. Your treatments may be delayed based on the results. Do not change your dose or stop taking fedratinib without your doctor's advice.

1 mg/kg (1 (1)) 24 hourly Intra Muscular — - 1 mg/kg (1 (1)) 24 hourly Oral — -

0.625 mg/kg (0.62 (0.625)) 24 hourly Intramuscular — 0.625 mg/kg (0.62 (0.625)) 24 hourly Oral —

Sometimes it is not safe to use certain medications at the same time. Some drugs can affect your blood levels of other drugs you take, which may increase side effects or make the medications less effective. Other drugs may interact with fedratinib, including prescription and over-the-counter medicines, vitamins , and herbal products . Tell your doctor about all your current medicines and any medicine you start or stop using. Especially tell your doctor if you are taking any of the following medicines: macrolide antibiotics (clarithromycin, erythromycin) antifungal medicines (itraconazole, ketoconazole, posaconazole, voriconazole) HIV medicines that contain atazanavir, darunavir, efavirenz, etravirine, indinavir, nelfinavir, nevirapine, ritonavir, saquinavir, or cobicistat heart or blood pressure medicines (quinidine, amiodarone, diltiazem, verapamil) cimetidine mifepristone nefazodone cannabidiol cyclosporine phenytoin rifampin St. John's wort ; ondansetron apalutamide , enzalutamide , mitotane sumatriptan methadone; carbamazepine , oxcarbazepine , phenytoin, primidone dexamethasone , prednisone. Not all possible interactions are listed here. Know the medicines you take. Keep a list of the medicines you take to show your healthcare provider and pharmacist when you get a new medicine.

Inj Store Below 40°C. Do not Freeze. Protect from Sunlight. Tab Store in a well closed container, Below 40°C. Protect from Sunlight.