Panobinostat (Oral)

Panobinostat is a multiple myeloma treatment used in combination with other drugs to slow progression of the disease.

Overview

Panobinostat is a cancer treatment used specifically to treat multiple myeloma, which is a cancer of the bone marrow. It is suitable for patients who have already been treated with at least two other medications without success. Usually, it is administered in combination with bortezomib (also known as Velcade) and dexamethasone.

Panobinostat works by slowing the growth of cancer cells in the body, and clinical studies have demonstrated that it can slow progression of the disease. However, it does not necessarily improve symptoms or lengthen survival time. On average, patients experience 10.6 months without progression or worsening of multiple myeloma after treatment with panobinostat. This is almost twice as long as progression-free time when a placebo is used in place of panobinostat.

In the US, panobinostat is known by the brand name Farydak, and it is administered orally in capsule dosage form.

Conditions Treated?

Type Of Medicine?

  • Histone deacetylase (HDAC) inhibitor

Side Effects

Panobinostat can cause a variety of unwanted side effects alongside its needed effects. While it is unlikely that all of these will occur, patients must be prepared for them in order that they can recognize when it is necessary to seek medical care.

If any of the following, serious side effects occur, call your doctor immediately:

  • More common:

O Reduced appetite

O Loss of appetite

O Stomach or abdominal pain or tenderness

O Low back or side pain

O Nausea or vomiting

O Severe diarrhea

O Black, tarry stools

O Clay-colored stools

O Dark or bloody urine

O Decreased frequency of urination

O Decreased volume of urine

O Painful or difficult urination

O Muscle spasms or twitching

O Seizures

O Bloating or swelling of faces, arms, hands, legs, or feet

O Swelling of face, fingers, feet or lower legs

O Tingling of hands or feet

O Skin rash or itching

O Pinpoint red spots on skin

O Ulcers, sores, or white spots in mouth

O Unusual bruising or bleeding

O Yellow eyes or skin

O Dizziness, faintness, or lightheadedness when arising

O Unusual tiredness or weakness

O Confusion

O Nervousness

O Headache

O Increased thirst

O Fever, chills or sweating

O Sore throat or cough

O Rapid breathing

O Difficulty breathing

O Fast, pounding, racing, or irregular heartbeat or pulse

O Slow or fast heartbeat

O Pounding in ears

O Sudden, unusual weight gain or loss

  • Less common

O Difficulty swallowing

O Paralysis

O Pain in shoulders, arms, jaw, or neck

O Chest pain or discomfort

O Coughing up blood

O Nosebleeds

O Vaginal bleeding or increased menstrual flow

The following side effects are minor and do not require medical attention unless they become very severe or persistent. If they are particularly bothersome or you are struggling to cope with them, you could speak to your doctor about them. Sometimes they dissipate once the body adjusts to the medicine.

  • Acidic or sour stomach
  • Belching or passing gas
  • Heartburn or indigestion
  • Loss of or change in taste
  • Dry mouth
  • Hoarseness or husky voice
  • Redness of the skin
  • Hair loss
  • Unusual fatigue or lethargy
  • Depressed mood

If you notice any other side effects not listed here, consult your doctor about them. You could also report new side effects to the FDA, or your doctor may do this on your behalf.

Dosage

The amount of panobinostat that you take will vary depending on your medical history, the stage of your illness, and other factors such as the cancer treatments you have received in the past or those which will be combined with panobinostat. Always follow your doctors dosing instructions and schedule closely to ensure the medicine has the best chance of working correctly.

The average dose of panobinostat, when taken in combination with bortezomib and dexamethasone for the treatment of multiple myeloma in adults, is, at first, 20 mg taken once every other day (for three doses each week) for two weeks in a 21-day cycle. Patients will typically take the drug on days 1, 3, 5, 8, 10 and 12, and then will stop taking it for another 9 days to complete a cycle. The 21-day cycle is usually repeated for 8 cycles. Sometimes, doctors will request that treatment continues for an additional 8 cycles after this, meaning that total treatment time will be 16 cycles over 48 weeks. Doses may be increased throughout this process depending on how well the drug appears to be working.

How to take panobinostat

You will receive a medication guide with panobinostat and you should read this carefully in order that you understand exactly how to take it. If you're unsure about how to take panobinostat correctly, consult your doctor before you start taking it. Always take the medicine as directed by your doctor, as taking more of it or taking it more often could cause harmful effects, and taking less of it or taking it less often may make it less effective.

Panobinostat is administered orally in the form of capsules. The capsules should be swallowed whole without crushing, chewing, or opening them. You should take them with a whole cup of water, but you do not have to take them with food unless you prefer. Do note, however, that other medicines which may be used in combination with panobinostat may need to be taken with food, so check the instructions of all the medicines you take. You should try to take panobinostat at around the same time each day that you are scheduled a dose of the drug.

Cancer medicines like panobinostat are incredibly strong and can cause serious side effects. Do not handle crushed or broken capsules or allow anyone else to do so. If the contents of a capsule do come into contact with the skin, wash the skin thoroughly with soap and water. If the medicine gets in the eyes, rinse thoroughly with water and consult your doctor.

Panobinostat can cause stomach irritation. If you vomit after taking a dose, do not take another capsule, but instead simply take the next dose at the usual time. You should consult your doctor if you are regularly vomiting after each dose of panobinostat.

If you miss a dose of panobinostat, you can take it within 12 hours of the time at which you were supposed to take it. If more than 12 hours have passed since the scheduled time, do not take the missed dose, and simply continue with your normal dosing schedule. Never double doses of panobinostat, as doing so could increase the risk or severity of serious side effects.

Interactions

There are many medicines which interact with panobinostat and could cause any of the following effects:

  • Increase the risk of certain side effects
  • Make panobinostat or other medicines less effective
  • Cause secondary health complications

It is vital that your doctor knows about all the medicines you take in order that they can check for harmful interactions. Be sure to mention medicines which are prescribed to you, those which have been purchased over the counter, and any herbal supplements or vitamins that you take, particularly St. John's Wort. It may be helpful to keep a full list of medicines which you can present to each doctor or pharmacist that you see. It is particularly important to mention any antifungal medicines or HIV medicines that you take.

If interactions do occur with your existing medicines, your doctor will consider changing some of the medicines you take, or they may not prescribe panobinostat. If both medicines are deemed important and potential interactions are relatively minor, your doctor may continue to prescribe both medicines, sometimes with dosage adjustments, or perhaps with new instructions as to how you take the medicines. Always follow your doctor's instructions closely.

The following medicines should never be taken at the same time as panobinostat:

  • Amifampridine (Firdapse)
  • Amisulpride
  • Bepridil (Vascor)
  • Cisapride (Propulsid)
  • Dronedarone (Multaq)
  • Fluconazole (Diflucan)
  • Ketoconazole (Nizoral)
  • Mesoridazine (Serentil)
  • Pimozide (Orap)
  • Piperaquine
  • Saquinavir (Invirase, Fortovase)
  • Sparfloxacin (Zagam)
  • Terfenadine (Seldane)
  • Thioridazine (Mellaril, Mellaril-S)
  • Ziprasidone (Geodon)

Food interactions

Do not eat grapefruit, star fruit, or pomegranate, or drink grapefruit or pomegranate juice while using panobinostat. If you have questions about these food interactions, consult your doctor.

Warnings

Interactions with other medical conditions

Make sure your doctor knows about all the medical conditions you currently suffer from, as well as those you have suffered from in the past. Some conditions may interact with panobinostat and cause complications.

The following conditions may be worsened by panobinostat:

  • Bleeding or blood clotting problems
  • Neutropenia (low white blood cells)
  • Thrombocytopenia (low blood platelets)
  • Anemia
  • Electrolyte imbalance
  • Heart disease
  • Heart rhythm problems, such as QT prolongation or arrhythmia
  • Liver disease
  • Diarrhea

People with the following conditions are not recommended to take panobinostat:

  • Recent heart attack
  • Angina (severe chest pain)
  • Severe liver disease

Panobinostat may reduce the body's ability to fight infection. If you are suffering from an infection, your doctor may avoid prescribing panobinostat until the infection has cleared. If you develop an infection while taking panobinostat, tell your doctor right away. Signs of infection include:

  • Fever
  • Redness and swelling in infected area
  • Pus or fluid drainage in infected area
  • Warmth or heat in infected area
  • Sore throat
  • General feeling of malaise (feeling unwell)

Risk of diarrhea and GI problems

Panobinostat can cause diarrhea and other symptoms affecting the gastrointestinal (GI) region, which is the stomach and intestines. If these effects are left untreated, they could lead to dehydration, electrolyte imbalance, and other serious problems. Tell your doctor if you experience persistent diarrhea or any of the following symptoms of GI problems or dehydration:

  • Stomach cramps
  • Loose stools
  • Vomiting
  • Dry mouth
  • Decreased sweating
  • Dry skin
  • Dark urine

You should also avoid taking laxatives or other stool softeners during your treatment with panobinostat without first speaking to your doctor.

Risk of heart problems

Panobinostat can cause very serious, life-threatening heart problems. The risk of these heart problems is higher in people with a history of conditions affecting the heart or heart rhythm. Your doctor may request ECG (electrocardiogram) tests to assess the activity of the heart both before and during treatment with panobinostat. If you notice any of the following signs of heart problems while taking panobinostat, call your doctor immediately:

  • Chest pain
  • Fast, slow or irregular pulse
  • Shortness of breath
  • Blue lips, fingernails, or skin
  • Dizziness and feeling faint
  • Swelling of the limbs (edema)

Keep all appointments

Your doctor will want to monitor you closely throughout your treatment with panobinostat to check how well the drug is working and to look out for unwanted side effects or complications. It is vital that you keep all appointments and undergo all tests that your doctor requests. The most common tests required are blood tests, but depending on your medical history and the side effects that you experience, you may need to have ECG or EKG tests too.

Pediatric use

Panobinostat has not been studied in the pediatric population. The safety and efficacy of the drug for children has not therefore not been established. Doctors are likely to administer alternative cancer treatments where possible.

Geriatric use

There is no evidence that panobinostat is any less effective in elderly patients than it is in younger adults. However, elderly patients are more likely to be sensitive to the drug and experience unwanted side effects. Doctors are therefore more cautious when prescribing the drug to the geriatric population and they may administer lower doses initially to avoid harmful effects.

Pregnancy and breastfeeding

Animal studies have demonstrated evidence of fetal harm when panobinostat is taken during pregnancy. There have not been adequate human studies to understand what effects the drug may have on the fetus. However, it is known that the drug could impair both male and female fertility. The drug is therefore not recommended for use during pregnancy due to potential fetal harm.

Women are advised to use birth control throughout treatment with panobinostat and for up to 3 months after their last dose. Men are advised to use condoms throughout treatment and for 6 months after their last dose. Women of childbearing potential are usually tested for pregnancy before treatment with panobinostat begins. If you become pregnant while taking panobinostat, consult your doctor immediately.

It is not known whether panobinostat is excreted in human breast milk and, if so, what effects it may have on a nursing infant. However, it is assumed that the drug could be harmful. Breastfeeding women should either avoid panobinostat treatment or discontinue breastfeeding, taking into account the usefulness of the treatment to the mother.

Allergy

If you have had an allergic reaction to panobinostat or to drugs like it, tell your doctor. You should also tell them about any other allergies you suffer from, including food, drug, chemical, pollen, and animal allergies, so that they can check whether you are allergic to any of the ingredients in panobinostat capsules.

Storage

Panobinostat should be stored at room temperature and in the packaging it was provided to you in. Do not allow it to freeze, and keep it away from heat, direct light, and moisture. Do not store it in the bathroom. Keep it out of reach and sight of children.

Do not keep unused panobinostat capsules. Ask your healthcare provider how to dispose of them. There may be a medicine take-back program offered by your healthcare provider, your pharmacy, or your local garbage or recycling department. Do not throw panobinostat in the trash or flush it down the toilet, as it may come to harm other people or the environment.

Summary

Panobinostat is a cancer treatment which can slow down the progression of multiple myeloma, a cancer which affects the bone marrow. It is only used if patients have already undergone at least two other treatments which have been unsuccessful. It is used in combination with other medicines, usually bortezomib (brand name Velcade) and dexamethasone. In the US, panobinostat is known by the brand name Farydak.

The more common, minor side effects associated with panobinostat are acidic stomach, heartburn or indigestion, belching or passing gas, hoarse or husky voice, hair loss, lethargy, and depressed mood. These do not usually require medical attention. If patients experience diarrhea or severe gastrointestinal (GI) problems such as stomach cramps or vomiting, they should consult their doctor right away. If diarrhea or GI problems result in signs of dehydration, such as dry mouth, dry skin, reduced sweating, and dark urine, they should also consult their doctor.

Panobinostat can also cause serious heart and heart rhythm problems. People with a history of medical conditions affecting the heart may not be able to take panobinostat for this reason. If patients experience chest pain, fast, slow or irregular pulse, shortness of breath, blue lips or skin, dizziness, lightheadedness or fainting, or edema in the limbs, they should tell their doctor right away.

Designed to be taken orally, panobinostat is provided in capsule form. Capsules should be swallowed whole either with or without food. Typically, patients take one dose every other day (or three times each week) for two weeks, following by a week-long break. This cycle is repeated eight times. Doctors may then request the cycles to be repeated once more, making a total treatment time of 16 cycles or 48 weeks.

Panobinostat is not recommended for use in children because the safety and efficacy of the drug in this population has not been established. It is suitable for elderly patients, but smaller dosages may be administered initially as they may be more sensitive to side effects. The drug is not suitable for use during pregnancy or while breastfeeding. Women should use birth control throughout treatment with the drug and for three months after treatment has ended. Men should use condoms throughout treatment and for six months after treatment has ended because the drug is thought to cause fertility problems in both men and women.