Decitabine

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

This medicine can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Other drugs may interact with decitabine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Serious side effects have been reported with decitabine including the following:

• low platelet count (thrombocytopenia). Tell your doctor right away if you have any unusual bleeding, such as nosebleeds, or bruising under your skin.
• low white blood cell count (neutropenia). A low white blood cell count can cause you to get infections, which may be serious. Serious illness or death can happen if an infection is not treated right away when white blood cell counts are very low. Tell your doctor right away if you have any of the following signs or symptoms of an infection:
  • fever
  • shortness of breath
  • pain or burning on urination
  • chills
  • cough
• low red blood cell count (anemia). Tell your doctor if you have any of these symptoms of anemia during treatment with decitabine:
  • feeling weak, tired, or you get tired easily
  • you look pale
  • you feel short of breath

It is recommended to avoid pregnancy while receiving treatment with decitabine and for I month afterwards, and to use effective contraception during this time.

It is recommended for men not to father a child while receiving treatment with decitabine, and for 2 months afterwards. During these times, men with female partners of childbearing potential should use effective contraception.

Treatment Regimen - Option 1

• The starting dose of decitabine is 15 mg/m² by IV (into the vein) infusion over 3 hours repeated every 8 hours for 3 days. This cycle should be repeated every 6 weeks.
• Dosing and/or duration may be adjusted according to adverse effects that may occur.

Treatment Regimen - Option 2

• The starting dose of decitabine is 20 mg/m² by IV (into the vein) infusion over 1 hour repeated daily for 5 days. This cycle should be repeated every 4 weeks.
• Dosing and/or duration may be adjusted according to adverse effects that may occur.

Since decitabine is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Myelodysplastic Syndrome

Treatment of myelodysplastic syndrome (MDS);1 3 4 designated an orphan drug by FDA for this use.2

Used in patients with previously treated or untreated, de novo or secondary MDS of all French-American-British (FAB) subtypes (i.e., refractory anemia [RA], RA with ringed sideroblasts [RARS], RA with excess blasts [RAEB], RAEB in transformation to leukemia [RAEB-T], chronic myelomonocytic leukemia [CMML]) and International Prognostic Scoring System (IPSS) risk groups with scores of ≥0.5 (i.e., intermediate-1, intermediate-2, and high-risk groups).1 3 4

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Feeling tired or weak.
• Belly pain.
• Upset stomach or throwing up.
• Mouth irritation or mouth sores.
• Pinpoint red spots on the skin.
• Hard stools (constipation).
• Loose stools (diarrhea).
• Not hungry.
• Not able to sleep.
• Dizziness.
• Headache.
• Itching.
• Back pain.
• Muscle or joint pain.
• Anxiety.
• Hair loss.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

There are two regimens for Decitabine for Injection administration. With either regimen it is recommended that patients be treated for a minimum of 4 cycles; however, a complete or partial response may take longer than 4 cycles.

Complete blood counts and platelet counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each cycle. Liver chemistries and serum creatinine should be obtained prior to initiation of treatment.

  Treatment Regimen - Option 1

Decitabine for Injection is administered at a dose of 15 mg/m 2 by continuous intravenous infusion over 3 hours repeated every 8 hours for 3 days. This cycle should be repeated every 6 weeks. Patients may be premedicated with standard anti-emetic therapy.

If hematologic recovery (ANC ≥ 1,000/μL and platelets ≥ 50,000/μL) from a previous Decitabine for Injection treatment cycle requires more than 6 weeks, then the next cycle of Decitabine for Injection therapy should be delayed and dosing temporarily reduced by following this algorithm:

• Recovery requiring more than 6, but less than 8 weeks - Decitabine for Injection dosing to be delayed for up to 2 weeks and the dose temporarily reduced to 11 mg/m 2 every 8 hours (33 mg/m 2/day, 99 mg/m 2/cycle) upon restarting therapy.
• Recovery requiring more than 8, but less than 10 weeks - Patient should be assessed for disease progression (by bone marrow aspirates); in the absence of progression, the Decitabine for Injection dose should be delayed up to 2 more weeks and the dose reduced to 11 mg/m 2 every 8 hours (33 mg/m 2/day, 99 mg/m 2/cycle) upon restarting therapy, then maintained or increased in subsequent cycles as clinically indicated.

  Treatment Regimen - Option 2

Decitabine for Injection is administered at a dose of 20 mg/m 2 by continuous intravenous infusion over 1 hour repeated daily for 5 days. This cycle should be repeated every 4 weeks. Patients may be premedicated with standard anti-emetic therapy.

If myelosuppression is present, subsequent treatment cycles of Decitabine for Injection should be delayed until there is hematologic recovery (ANC ≥ 1,000/μL platelets ≥ 50,000/μL ).

  Patients with Non-hematologic Toxicity

Following the first cycle of Decitabine for Injection treatment, if any of the following non-hematologic toxicities are present, Decitabine for Injection treatment should not be restarted until the toxicity is resolved: 1) serum creatinine ≥ 2 mg/dL; 2) SGPT, total bilirubin ≥ 2 times ULN; 3) and active or uncontrolled infection.

  Instructions for Intravenous Administration

Decitabine for Injection is a cytotoxic drug and caution should be exercised when handling and preparing Decitabine for Injection. Procedures for proper handling and disposal of antineoplastic drugs should be applied. Several guidances on this subject have been published. 1-4.

Decitabine for Injection should be aseptically reconstituted with 10 mL of Sterile Water for Injection (USP); upon reconstitution, each mL contains approximately 5 mg of Decitabine at pH 6.7-7.3. Immediately after reconstitution, the solution should be further diluted with 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a final drug concentration of 0.1-1 mg/mL. Unless used within 15 minutes of reconstitution, the diluted solution must be prepared using cold (2°C - 8°C) infusion fluids and stored at 2°C - 8°C (36°F - 46°F) for up to a maximum of 4 hours until administration.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if there is evidence of particulate matter or discoloration.

• Antineoplastic Agent, Antimetabolite
• Antineoplastic Agent, DNA Methylation Inhibitor

There are no contraindications listed in the manufacturer’s labeling.

Vials should be reconstituted with 10 mL SWFI to a concentration of 5 mg/mL. Immediately further dilute with NS or D5W to a final concentration of 0.1 to 1 mg/mL. Use appropriate precautions for handling and disposal. Solutions not administered within 15 minutes of preparation should be prepared with cold (2°C to 8°C [36°F to 46°F]) infusion solutions.

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

CBC with differential and platelets (with each cycle and more frequently if needed); liver enzymes (prior to treatment initiation and periodically); serum creatinine (prior to treatment initiation and periodically)

Applies to decitabine: intravenous powder for solution

Along with its needed effects, decitabine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking decitabine:

• Black, tarry stools
• bladder pain
• bleeding after defecation
• bleeding gums
• blood in urine or stools
• bloody or cloudy urine
• blue lips and fingernails
• blurred vision
• body aches or pain
• chest pain
• chills
• coma
• congestion
• convulsions
• cough
• coughing that sometimes produces a pink frothy sputum
• decreased urination
• difficult, burning, or painful urination
• difficult, fast, noisy breathing, sometimes with wheezing
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
• drowsiness
• dry mouth
• dryness of throat
• facial swelling
• fainting
• fast or irregular heartbeat
• feeling unusually cold
• fever
• flushed, dry skin
• frequent urge to urinate
• fruit-like breath odor
• headache
• hives or welts
• hoarseness
• increased hunger
• increased sweating
• increased thirst
• increased urination
• itching, pain, redness, swelling, tenderness, or warmth on skin
• lightheadedness
• loss of appetite
• lower back or side pain
• mood or mental changes
• muscle pain or cramps
• muscle spasms or twitching
• nausea or vomiting
• nervousness
• numbness or tingling in hands, feet, or lips
• pale skin
• pinpoint red spots on skin
• redness or pain at the catheter site
• runny nose
• seizures
• shivering
• shortness of breath
• skin rash
• small clicking, bubbling, or rattling sounds in the lung when listening with a stethoscope
• small red or purple spots on skin, lips or in mouth
• sneezing
• sore mouth or tongue
• sore throat
• sores, ulcers, or white spots on lips or in mouth
• stomach pain and bloating
• sunken eyes
• swelling of face, hands, ankles, feet, or lower legs
• swollen, painful, or tender lymph glands in neck, armpit, or groin
• tightness in chest
• trembling
• trouble in swallowing
• troubled breathing with exertion
• uncomfortable swelling around anus
• unexplained weight loss
• unusual bleeding or bruising
• unusual tiredness or weakness
• voice changes
• weakness or heaviness of legs
• wheezing
• white patches in mouth and/or on tongue
• wrinkled skin
• yellow eyes or skin

• Collection of blood under skin
• deep, dark purple bruise
• diarrhea
• pain or tenderness around eyes and cheekbones
• pain, warmth, or burning in fingers, toes, and legs
• problems with vision or hearing
• skin scrape or burn
• stuffy nose
• swelling at injection site

Some side effects of decitabine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• anxiety
• back pain
• belching
• bumps on skin
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest discomfort
• constipation
• difficulty swallowing
• fall
• hair loss, thinning of hair
• heartburn
• indigestion
• loose stools
• muscle stiffness
• pain in arms or legs
• pain in joints
• sleeplessness
• stomach discomfort or upset
• swelling or inflammation of the mouth
• trouble sleeping
• unable to sleep
• unusual drowsiness, dullness, or feeling of sluggishness

• Difficulty in moving
• general feeling of discomfort or illness
• muscle aching
• pain in the tongue
• postnasal drip
• pressure in the stomach
• swollen joints

Applies to decitabine: intravenous powder for injection

Hematologic

Very common (10% or more): Neutropenia (90%), thrombocytopenia (89%), anemia (68%), febrile neutropenia (29%), leukopenia (28%), lymphadenopathy (12%)
Common (1% to 10%): Thrombocythemia
Uncommon (0.1% to 1%): Pancytopenia[Ref]

Gastrointestinal

Very common (10% or more): Nausea (42%), constipation (35%), diarrhea (34%), vomiting (25%), abdominal pain (14%), oral mucosal petechiae (13%), stomatitis (12%), dyspepsia (12%), ascites (10%)
Common (1% to 10%): Gingival bleeding, hemorrhoids, loose stools, tongue ulceration, dysphagia, oral soft tissue disorder, lip ulceration, abdominal distension, upper abdominal pain, gastroesophageal reflux disease, glossodynia
Frequency not reported: Enterocolitis (including neutropenic colitis, cecitis)[Ref]

Respiratory

Very common (10% or more): Cough (40%), pneumonia (24%), pharyngitis (16%), epistaxis (14%), lung crackles (14%), breath sounds decreased (10%), hypoxia (10%)
Common (1% to 10%): Sinusitis, rales, postnasal drip
Frequency not reported: Interstitial lung disease[Ref]

Other

Very common (10% or more): Pyrexia (53%), peripheral edema (25%), rigors (22%), edema (18%), pain (13%), lethargy (12%), tenderness (11%), blood alkaline phosphatase increased (11%), blood urea increased (10%)
Common (1% to 10%): Fall, chest wall pain, intermittent pyrexia, malaise, crepitations, blood lactate dehydrogenase increased, blood albumin decreased, blood bicarbonate increased, blood chloride decreased, decreased total protein, blood bilirubin decreased[Ref]

Metabolic

Very common (10% or more): Hyperglycemia (33%), hypoalbuminemia (24%), hypomagnesemia (24%), hypokalemia (22%), hyponatremia (19%), appetite decreased (16%), anorexia (16%), hyperkalemia (13%)
Common (1% to 10%): Dehydration[Ref]

Nervous system

Very common (10% or more): Headache (28%), dizziness (18%), hypoesthesia (11%)[Ref]

Psychiatric

Very common (10% or more): Insomnia (28%), confusion (12%), anxiety (11%)[Ref]

Immunologic

Very common (10% or more): Bacterial, viral, fungal infections (63%), candida infection (10%)
Common (1% to 10%): Septic shock, sepsis, staphylococcal infection, oral candidiasis, bacteremia[Ref]

Dermatologic

Very common (10% or more): Ecchymosis (22%), rash (19%), erythema (14%), cellulitis (12%) skin lesion (11%), pruritus (11%)
Common (1% to 10%): Alopecia, urticaria, swelling face
Uncommon (0.1% to 1%): Acute febrile neutrophilic dermatosis (Sweet's syndrome)[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (20%), pain in limb (19%), back pain (17%)
Common (1% to 10%): Chest wall pain, musculoskeletal discomfort, myalgia[Ref]

Cardiovascular

Very common (10% or more): Petechiae (39%), pallor (23%), cardiac murmur (16%)
Common (1% to 10%): Pulmonary edema, hypotension, hematoma[Ref]

Hepatic

Very common (10% or more): Hyperbilirubinemia (14%)[Ref]

Hypersensitivity

Common (1% to 10%): Hypersensitivity including anaphylaxis[Ref]

Ocular

Common (1% to 10%): Blurred vision[Ref]

Genitourinary

Very common (10% or more): Urinary tract infection (15%)
Common (1% to 10%): Dysuria, urinary frequency
.[Ref]

Local

Common (1% to 10%): Injection site erythema, injection site pain, injection site swelling[Ref]

Some side effects of decitabine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Data not available