Ruxolitinib (Oral)

Ruxolitinib is used to treat intermediate or high-risk myelofibrosis. As a janus kinase inhibitor, Ruxolitinib is an effective treatment for myelofibrosis, a disorder which affects bone marrow.

Overview

Ruxolitinib is used to treat moderate or higher-risk myelofibrosis, which is a type of disorder that commonly causes bone marrow issues. This condition causes scar tissue to build up within the bone marrow, which results in blood cells not being produced properly. This medicine can also be used to treat polycythemia vera or PCV when it has been demonstrated that there has been a substandard response to (or an intolerance of) hydroxyurea, which is the standard treatment for this condition. PCV is a condition which causes the body to produce too many red blood cells.

As a janus kinase inhibitor complete with selectivity for JAK1 and JAK2 subtypes, Ruxolitinib helps to inhibit dysregulated JAK signalling, which is associated with illnesses like myelofibrosis. JAK1 and JAK2 typically recruit signal transducers and/or activators or transcription to the cytokine receptors which lead to modulated gene expression. Ultimately, the JAK genes are supposed to help control the level of blood cells the body produces, and when these genes become faulty, the body may produce too many blood cells. Ruxolitinib stops the signals sent by the faulty gene, reducing the number of extra cells.

This medication was approved by the US Food & Drug Administration in 2011 after extensive trials, and its use has been widespread throughout the world ever since. It may also be used "off-label"to treat other conditions which it is not currently approved for. Research suggests that Ruxolitinib may also be beneficial in the treatment of plaque psoriasis, alopecia areata, peripheral T-cell lymphoma and diffuse large B-cell lymphoma.

Conditions Treated

Type of Medicine

  • Protein kinase inhibitor

 

Side Effects

Along with the desired effects, Ruxolitinib can cause some unwanted side effects when taken orally. The likelihood of experiencing side effects while undergoing treatment with Ruxolitinib is rare-to-moderate. Some of the most common symptoms reported by individuals taking this medicine include:

  • Tarry, black stools
  • Pain in the bladder
  • Bleeding gums
  • Blood in the stools or urine
  • Bruising
  • Cloudy urine
  • Dry mouth
  • Chills
  • Coughing
  • Blood collecting under the skin
  • Dark, deep, purple bruising
  • Difficulty urinating
  • Fever
  • Frequent need to urinate
  • Lower back/side pain
  • Pale skin
  • Pinpoint red prickly spots on the skin
  • Shortness of breath
  • Sore throat
  • Difficulty breathing out
  • Ulcers, white spots or sores in the mouth
  • Unusual weakness or tiredness
  • Bloating or full feeling
  • Light-headedness or dizziness
  • Feeling of constant movement
  • Spinning sensation
  • Excess flatulence
  • Headache
  • Weight gain

As the patient continues a course of treatment with Ruxolitinib as prescribed by a doctor, most or all symptoms should lessen. If side effects persist over a prolonged period or get worse, the patient is urged to contact their physician immediately. In many instances, a doctor or healthcare professional should be able to offer advice or alternative treatments to tackle discomfort caused by side effects. For example, dry mouth can be alleviated by chewing sugar-free gum, or regularly drinking cold water with ice where possible.

In rare instances, patients may experience painful blisters on the abdomen or trunk of the body. If this side effect occurs and proves bothersome, the patient is advised to contact their doctor.

While Ruxolitinib is known to cause gastrointestinal, dermatologic, genito-urinary, hematologic, immunologic, metabolic, hepatic, and cardiovascular side effects, some effects of this medicine may not yet have been reported. Patients who experience unwanted side effects which are not yet listed are advised to contact their healthcare provider and to optionally report any findings to the FDA.

Because Ruxolitinib can cause dizziness, light-headedness and a spinning sensation, patients are advised against driving or operating heavy machinery when initially taking this drug. After it has been observed that the patient does not experience undue loss of control or concentration while undergoing treatment with this medicine, only then should they should consider driving - when they are certain that they do not pose a risk to themselves or other road users. In some instances, the spinning sensations and dizziness may dissipate as the patient's body adjusts to Ruxolitinib.

Dosage

As with all medicines, it is important for patients to take Ruxolitinib only as prescribed by a doctor or qualified healthcare professional. This means that patients must avoid taking more of this medication than advised, both in terms of dose size and frequency. In addition to this, patients should cease taking Ruxolitinib if advised to do so by their doctor - even if they still have a supply of the medication remaining.

Patients should take Ruxolitinib at the same time every day. It comes in the form of an oral tablet, which should be taken with a large (8oz) glass of water. It can be taken with or without food.

The starting dosage for Ruxolitinib will depend upon the results of the patient's blood tests, and what condition they have. A doctor may be required to make changes to the dosage levels throughout treatment and will make this decision after checking blood tests which should be taken regularly when the patient visits the hospital or clinic. Most patients continue to take Ruxolitinib for as long as it functions to keep the condition under control. Patients should not stop taking this medicine without first speaking to a doctor, as sudden cessation of treatment with Ruxolitinib can cause the patient to feel unwell. If a doctor suggests stopping treatment, they will typically do so while gradually reducing the dose over time to prevent the patient from becoming unwell.

Usual adult dose for Myelofibrosis/Myeloproliferative disorder:

As an initial dose, doctors will use the following as a guideline when prescribing Ruxolitinib:

  • If platelet count is greater than 200 x 10(9)/L, patient should receive 20mg Ruxlitinib, orally twice a day.
  • If platelet count is between 100 to 200 x 10(9)/L, patient should receive 15mg, orally, twice a day.
  • If platelet count is between 50 and 100 x 10(9)/L, patient should receive 5mg, orally, twice a day.

Doses can be adjusted based on efficacy and safety. If efficacy is not sufficient, and neutrophil and platelet counts are adequate, doses can be increased by a maximum of 5mg twice daily. However, the starting dose should not be increased within the first month or treatment; nor should it be increased any more frequently than at 2-week intervals.

Dose increases should only be considered in patients who meet the following criteria: a failure to achieve a reduction in spleen length of 50%, or a reduction in spleen length of 35% as measured by a CT or MRI scan. Treatment should be discontinued after six months if there is no discernible reduction in spleen size, or not improvement of symptoms since the initiation of therapy.

The maximum safe doses are as follows:

  • If platelet count is 100 x 10(9)/L or larger, the patient can receive a maximum of 25mg, orally, twice a day.
  • If platelet count is between 50 to 100 x 10(9)/L, the patient can receive a maximum of 10mg, orally, twice a day.

Patients experiencing platelet decline may require dose adjustments in order for Ruxolitinib to function effectively. The following information should be used as a guide only, with a qualified doctor or healthcare professional making the dosage decision based on individual factors unique to the patient.

If platelet decline occurs during treatment at 25mg twice a day:

  • 00 to less than 125 x 10(9)/L: 20 mg twice a day
  • 5 to less than 100 x 10(9)/L: 10 mg twice a day
  • 0 to less than 75 x 10(9)/L: 5 mg twice a day
  • Less than 50 x 10(9)/L: Hold

If platelet decline occurs during treatment at 20mg twice a day:

  • 00 to less than 125 x 10(9)/L: 15 mg twice a day
  • 5 to less than 100 x 10(9)/L: 10 mg twice a day
  • 0 to less than 75 x 10(9)/L: 5 mg twice a day
  • Less than 50 x 10(9)/L: Hold

If platelet decline occurs during treatment at 15mg twice a day:

  • 00 to less than 125 x 10(9)/L: no change
  • 5 to less than 100 x 10(9)/L: 10 mg twice a day
  • 0 to less than 75 x 10(9)/L: 5 mg twice a day
  • Less than 50 x 10(9)/L: Hold

If platelet decline occurs during treatment at 10mg twice a day:

  • 5 x 10 (9)/L to less than 125 x 10(9)/L: no change
  • 0 x 10(9)/L to less than 75 x 10(9)/L: 5 mg twice a day
  • Less than 50 x 10(9)/L: Hold

If platelet decline occurs during treatment at 5mg twice a day:

  • 0 to less than 125 x 10(9)/L: no change
  • Less than 50 x 10(9)/L: Hold

In certain circumstances, doses may need to be interrupted. Patients who are restarting a dose should do so at least 5mg below their daily dose at the time of interruption. Maximum restarting doses after interruption apply as follows:

  • Current platelets 125 x 10(9)/L or greater: 20 mg twice a day
  • Current platelets 100 to less than 125 x 10(9)/L: 15 mg twice a day
  • Current platelets 75 to less than 100 x 10(9)/L: 10 mg twice a day for at least 2 weeks; when stable, may increase to 15 mg twice a day
  • Current platelets 50 to less than 75 x 10(9)/L: 5 mg twice a day for at least 2 weeks; when stable, may increase to 10 mg twice a day

Interactions

All drugs have the potential to interact with other chemicals or medications within the human body, and these interactions can change how one or more of the involved medicines work. In some instances, an interaction can cause a medicine to become ineffective. Interactions can also cause potentially serious or even fatal side effects. Because of this risk, patients are advised to keep a full, detailed list of all drugs they are currently taking. This extends to vitamins, herbal supplements, over the counter remedies and complementary medicines as well as prescription medications.

Below is a partial list of medicines known to interact negatively with Ruxolitinib. Patients who are currently undergoing therapy with any of these medications are advised to inform their doctor prior to being administered with a dose of Ruxolitinib:

  • Acalabrutinib
  • ACAM2000 (smallpox vaccine)
  • Agenerase (amprenavir)
  • Amjevita (adalimumab)
  • Amoxicillin / clarithromycin / lansoprazole
  • Amoxicillin / clarithromycin / omeprazole
  • Amprenavir
  • Apixaban
  • Arava (leflunomide)
  • Ardeparin
  • Arixtra (fondaparinux)
  • Atazanavir
  • Atazanavir / cobicistat
  • Attenuvax (measles virus vaccine)
  • Aubagio (teriflunomide)
  • BCG
  • Biavax II (mumps virus vaccine / rubella vaccine)
  • Biaxin (clarithromycin)
  • Biaxin XL (clarithromycin)
  • Boceprevir
  • Cabometyx (cabozantinib)
  • Cabozantinib
  • Calquence (acalabrutinib)
  • Certolizumab
  • Cimzia (certolizumab)
  • Clarithromycin
  • Cyltezo (adalimumab)
  • Cyramza (ramucirumab)
  • Dalteparin
  • Danaparoid
  • Dasabuvir / ombitasvir / paritaprevir / ritonavir
  • Dasatinib
  • Deferasirox
  • Deferiprone
  • Delavirdine
  • Denzapine (clozapine)
  • Diflucan (fluconazole)
  • FazaClo (clozapine)
  • Iclusig (ponatinib)
  • Idelalisib
  • Imbruvica (ibrutinib)
  • Imlygic (talimogene laherparepvec)
  • In-111 Zevalin (ibritumomab)
  • Incivek (telaprevir)
  • Indinavir
  • Inflectra (infliximab)
  • Infliximab
  • Influenza virus vaccine, h1n1, live
  • Influenza virus vaccine, live, trivalent
  • Innohep (tinzaparin)
  • Invirase (saquinavir)
  • Iodine i 131 tositumomab
  • Itraconazole
  • Measles virus vaccine / mumps virus vaccine / rubella vaccine
  • Measles virus vaccine / mumps virus vaccine / rubella vaccine / varicella virus vaccine
  • Measles virus vaccine / rubella vaccine
  • Meruvax II (rubella virus vaccine)
  • Mibefradil
  • Poliovirus vaccine, live, trivalent
  • Quadramet (samarium sm 153 lexidronam)
  • Savaysa (edoxaban)
  • Serzone (nefazodone)
  • Simponi (golimumab)
  • Tao (troleandomycin)
  • Technivie (ombitasvir / paritaprevir / ritonavir)
  • Telaprevir
  • Telithromycin
  • Telzir (fosamprenavir)
  • Teriflunomide
  • TheraCys (bcg)
  • Tice BCG (bcg)
  • Tice BCG Vaccine (bcg)
  • Tinzaparin
  • Tofacitinib
  • Tositumomab
  • Troleandomycin
  • Tybost (cobicistat)
  • Typhoid vaccine, live
  • Tysabri (natalizumab)
  • Vaprisol (conivaptan)
  • Xarelto (rivaroxaban)
  • Xeljanz (tofacitinib)
  • Xeljanz XR (tofacitinib)
  • Xigris (drotrecogin alfa)
  • Y-90 Zevalin (ibritumomab)
  • yellow fever vaccine
  • YF-Vax (yellow fever vaccine)
  • Zaponex (clozapine)
  • Zevalin (ibritumomab)
  • Zostavax (zoster vaccine live)
  • Zoster vaccine live
  • Zydelig (idelalisib)

As well as drug interactions, various food interactions also exist with Ruxolitimib. Patients undergoing treatment with this medicine are advised against consuming Seville oranges or grapefruit, as these fruits contain enzymes which can cause the medicine to be absorbed into the body at a much greater rate.

Warnings

Patients are advised to inform their doctor if they have ever had tuberculosis, if anyone in their household has had tuberculosis, or if they have recently traveled to or from an area where tuberculosis is common. This is because conditions caused by this infection can cause serious complications in those receiving treatment with Ruxolitinib.

Prior to starting a course of treatment with this medicine, patients are advised to inform their doctor if they are currently suffering from any of the following conditions:

In some patients, Ruxolitinib use could increase the risk of developing skin cancers. For further information on the risks, patients should consult their doctor or healthcare provider.

This medicine is classed in pregnancy category C by the FDA. This means that it is not known whether treatment with this drug will cause any undue harm to an unborn baby, although women who are pregnant or intending on becoming pregnant in the near future are advised to discuss the risks and benefits of this medicine with their doctor.

Ruxolitinib is thought to be excreted into human breastmilk. No conclusive studies have been performed to ascertain whether Ruxolitinib has the potential to harm nursing babies, although official advice states that women should discontinue breastfeeding while undergoing treatment with this medicine.

The number of red blood cells in the blood may be reduced as a result of undergoing treatment with Ruxolitinib. Red blood cells carry oxygen around the body, and a lack of oxygen as a result of reduced red blood cell count (anemia) can cause the patient to feel breathless and tired. Patients are advised to inform their nurse or doctor if they feel like this, as they may need an IV drip to provide them with additional red blood cells (blood transfusion).

Storage

Ruxolitinib should be kept in its original packaging, at room temperature (below 30C) and away from sources of heat and moisture. This medication is not suitable for storage in a bathroom and should be kept in a dedicated, locked medicine cabinet if possible. Patients are advised to store Ruxolitinib out of reach of children and pets. If treatment is discontinued, the patient should dispose of any unwanted medicine safely and hygienically. The best way to dispose of unused medication is to return to a pharmacy which participates in a take-back scheme.

Summary

Ruxolitinib is an effective treatment for myelofibrosis, a type of cancer which affects the bone marrow and the ability to produce white blood cells. It can also be used to treat polycythemia vera (PCV) when patients do not respond to hydroxyurea therapy. While it is an incredibly beneficial medication, it can also pose a risk to patients who fail to communicate fully with their doctor.

In order to get the most out of this medication, patients are advised to take their tablets precisely as advised by a doctor or nurse. This medicine should be taken at the same time every day, preferably with a glass of water.