All About Ninlaro (Ixazomib)

All about Ninlaro or Ixazomib. Ninlaro or Ixazomib is an oral proteasome inhibitor in contrast to the other proteasome inhibitors such as Velcade and Kyprolis. When is Ninlaro used? Ninlaro is approved to be given along with Revlimid and dexamethasone for the treatment of relapsed refractory multiple myeloma. It is also used occasionally for the treatment of newly diagnosed multiple myeloma when patients cannot tolerate Velcade for whatever reason. Ninlaro has also been approved for the maintenance phase of the treatment of multiple myeloma in both transplant eligible as well as non-transplant eligible. That means it is used as maintenance both in patients who get transplant or who do not go for transplant. Revlimid is the preferred drug for maintenance in multiple myeloma right now but for whatever reason patients cannot tolerate Revlimid or they have like side effects, toxicity with Revlimid, Ninlaro could be used. The NCCN guidelines list the following uses for Ninlaro. In newly diagnosed patients who are either eligible or ineligible for transplant in these combination therapies. And in relapsed and refractory myeloma patients in these combination therapies. What is the dose and schedule of Ninlaro? It is given at a dose of 4 milligrams. They are tablets which come in the dose of 4 milligrams, 3 milligrams, 2 milligrams, and 1 milligrams. Starting dose is 4 milligrams taken orally once a week for 3 weeks in a row and the fourth week is off. So in a 4 week cycle once a week for 3 weeks and the fourth week is off. It is also sometimes mentioned to the patients as day 1, 8, 15 of a 28 day cycle. That is what it means. Getting treated once a week for 3 weeks in a row and getting fourth week off. As I said it is given in combination with Revlimid and dexamethasone. What should you do if you vomit after taking Ninlaro? As I mentioned nausea and vomiting are common side effects with any chemotherapy pill. So say if you vomit right after taking the medicine and you think like you vomited the pill. Please do not take a second pill because it is one pill once a week. Please do not take a second pill. Can I put Ninlaro into my pill box to help me remember to take it? Many patients have the habit of putting their all the medications in their pill boxes for them to take on the specified days. But Ninlaro should not be taken out of its package because of the interaction with the aid, the efficiency could be reduced. So please do not take it out until you are ready to take the medication on that day at that time. Open the package, take it right away. Do not leave it exposed to air. Do not take it out and put in pill boxes. Ninlaro should be taken once a week on the same day and at approximately the same time for the first three weeks of a four week cycle. Ninlaro should not be taken with food. Food may interfere with the absorption of Ninlaro which may lower levels of the medication in the blood and possibly reduce effectiveness. Ninlaro should be taken on an empty stomach or at least one hour before or at least two hours after food. Ninlaro should be swallowed whole with water and should not be crushed, chewed, or opened. If a Ninlaro dose is delayed or missed, the dose should be taken only if the next scheduled dose is at least 72 hours or three days away. A double dose should not be taken to make up for the missed dose. If vomiting occurs after taking a dose of Ninlaro, the patient should not repeat the dose. The patient should resume dosing at the time of the next scheduled dose. What are the most common side effects of Ninlaro or Exazomib? Side effect profile of Exazomib is slightly different from Velcade. The chances of peripheral neuropathy is much lower with Exazomib which makes it a favorable option, attractive option in patients who cannot take Velcade because of existing, pre-existing peripheral neuropathy. Other side effects include diarrhea, can cause pneumonia, and it can also cause liver toxicity. It can be a little toxic to the liver. So when patients are started on Exazomib and when they are taking Ninlaro or Exazomib, the liver numbers need to be checked to monitor for the liver function. Ninlaro, like other proteasome inhibitors, can also cause shingles. So patients need to be on prophylaxis with acyclovir at a standard dose of 400 milligrams twice daily. The dosage of acyclovir can be reduced in patients with renal dysfunction. What GI toxicities are associated with Ninlaro? GI toxicity is one of the very common side effects with Ninlaro which is manifested as nausea, vomiting, and diarrhea. I usually give them a prescription for nausea medications to have them handy and to take if they start getting nauseous. And if it is a persistent complaint, I often advise patients to take the nausea medication 30 minutes before taking Ninlaro. That way they don't get sick to their stomach and vomit. In regards to the diarrhea, it's a common side effect. I usually educate patients to take Imodium. And Imodium can be taken like sometimes if it is bad diarrhea with every bowel movement or every two hours, Imodium helps with the diarrhea. In rare cases, when Imodium is not able to control it, we give something stronger like Lomotil. Imodium with Lomotil if needed usually controls the diarrhea. Caution must be taken to prevent dehydration caused by vomiting and diarrhea. You should drink sufficient amounts of water and fluids and seek medical help if you are experiencing dizziness, lightheadedness, or fainting. Your doctor should monitor your electrolytes, especially potassium, if you are experiencing GI side effects. Additionally, Ninlaro can cause thrombocytopenia, low platelet counts, edema or fluid retention, rash, eye disorders such as dry eye, blurred vision, pink eye, and fetal harm. Share all side effects you are experiencing with your healthcare team so they can decide the best way to manage them. What is the mechanism of action of Ninlaro? How does it work? As I mentioned, it is an oral proteasome inhibitor. What are proteasomes? Proteasomes are protein complexes which have enzymes. Enzymes means chemicals to remove the defective proteins in the body. When this function is inhibited, it leads to disruption of the cell cycle. Cell cycle means the life cycle of cells wherein the cells are produced, they grow, and they die. By inhibiting the proteasomes, more cells are disrupted in their cell cycle which leads to the death. Which is a good thing because here we are talking about cancer cells. So proteasome inhibitors, with this mechanism of action, they lead to disruption of the cell cycle and eventually cell death. How do you make sure individuals are taking their oral therapy correctly and not missing or skipping doses because of forgetfulness or side effects? Whenever chemotherapy is given orally as pills, patients are in control of it. So patient education is paramount. And of course compliance is very important. That means like remembering to take the medication and taking it the same day, trying to take it around the same time. So let's talk about all those details. First thing to remember is Ninlaro has to be taken once a week. It is taken once a week for three weeks, not three days in a row. Because I've had patients in spite of like being educated, in spite of having written instructions have taken three days in a row. Please don't do that. Only one pill once a week for three weeks and fourth week is break. Now how to take it? It is good to take the medication at around the same time to make it a habit to take it around the same time that that way like you are more likely to take it. What I tell patients is like to maintain pocket calendars to mark off the day that they are taking it. That way like when they come to see me, I can look at the calendar and see where they are in their cycle. But also by maintaining a calendar, they tend to remember better. Of course nowadays like with the smartphones like there are reminders and some of the companies actually are sending reminders to the patients once a week to take their medication. Having said that, if patients forget to take the medication like in the morning like where they are when they are supposed to be, they can take it later too. It is recommended to take it with plenty of fluids. Now sometimes patients do get nausea or vomiting with these medications. So we usually give them a prescription for anti-emetics which are medications to treat the nausea and vomiting which they can take when they have those symptoms. And if it is a persistent problem, I usually tell patients to take the nausea pill 30 minutes before they have to take the chemotherapy pill. That way they don't get sick to their stomach. Other side effect is diarrhea. So what do patients do because they are at home on their own. I usually educate them to take Imodium if they have diarrhea when they are taking Ninlarob which is a common side effect and drink plenty of fluids to maintain the fluid balance. So different medications have different absorption patterns. Some medications should be taken with meals. Some medications cannot be taken with meals. So Ninlaro usually has to be the package instead. The instructions are to take it like one hour before eating or two hours after. Whereas dexamethasone is to be taken with meals. So do not take both medications at the same time. More information about Ninlaro. And anytime you are having symptoms that you are not able to manage at home with the medications, with the prescribed medications that you have, please contact your doctor immediately. Please call the clinic, please call the doctor, let them know what's going on and get evaluated and managed in time. Takeda Oncology's Here to Assist program works with your healthcare provider and your insurance company to help you get started on your medication. It identifies available financial assistance that may be right for you and connects you to additional support services and resources.