Decitabine is a chemotherapeutic agent used primarily for the treatment of certain types of myelodysplastic syndromes (MDS), which are a group of bone marrow disorders that can progress to acute myeloid leukemia (AML). It's an analogue of cytidine, and its mechanism of action involves the inhibition of DNA methyltransferases, leading to hypomethylation of DNA. This can lead to the reactivation of tumor suppressor genes that had been previously silenced by hypermethylation.

Decitabine (Dacogen) is a nucleic acid synthesis inhibitor. It is used in the treatment of myelodysplastic syndrome and acute myeloid leukemia.

Decitabine Uses:

• Myelodysplastic syndromes:
  • Used in the treatment of myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System (IPSS) groups.
• Off Label Use of Decitabine in Adults:
  • Acute myeloid leukemia

Decitabine (Dacogen) Dose in Adults

Decitabine (Dacogen) Dose in the treatment of Acute myeloid leukemia (AML) (off-label):

• In the treatment of Acute Myeloid Leukemia (AML) in adults who are 60 years or older, the recommended dose of Decitabine is given through a vein (intravenous or IV)
• The dose is calculated based on the person's body surface area, and it's usually 20 milligrams per square meter of body surface
• This dose is given over a period of 1 hour each day for 5 days in a row, and this treatment cycle is repeated every 28 days
• The treatment continues until there is a relapse of the disease, the disease progresses, or if the person experiences side effects that are too severe to continue the treatment
• This use of Decitabine for AML might not be officially approved, meaning it's considered "off-label," but it has been studied and used by doctors based on the research findings.

Decitabine (Dacogen) Dose in the treatment of Myelodysplastic syndromes (MDS): IV:

3-day regimen:

• Dosage: Patients receive 15 mg of Decitabine for every square meter of their body surface. This dose is given over 3 hours.
• Frequency: This dosage is given three times a day, adding up to a total of 45 mg for every square meter each day.
• Duration: This treatment is given for 3 consecutive days, so over those days, the total dosage is 135 mg for every square meter of the patient's body surface.
• Repeat: After the 3-day treatment, there's a break. The treatment cycle is repeated every 6 weeks, but only once the patient's blood counts recover. Recovery is defined as having a certain level of white blood cells (specifically, an ANC of 1,000/mm^3 or more) and a platelet count of 50,000/mm^3 or more.
• Duration of Treatment: At least 4 of these treatment cycles are recommended, but it might take longer than 4 cycles to see whether the treatment is working (either a full or partial response).

5-day regimen:

• Dosage: Patients receive 20 mg of Decitabine for every square meter of their body surface. This dose is given over 1 hour.
• Frequency: This is done once a day.
• Duration: The treatment lasts for 5 consecutive days.
• Repeat: After the 5-day treatment, there's a break. The cycle starts again every 4 weeks, but like the 3-day regimen, this only happens once the patient's blood counts recover to the levels mentioned earlier.
• Duration of Treatment: Again, a minimum of 4 treatment cycles is recommended. And, as before, determining the effectiveness might require more than 4 cycles.

Use in Children:

Not indicated.

Decitabine (Dacogen) Pregnancy Risk Category:

• Fetal Harm Risk: Decitabine has the potential to harm the developing fetus if a pregnant person is exposed to it. This means that if a pregnant person takes Decitabine, it could negatively affect the baby's growth and development.
• Limited Pregnancy Data: There isn't a lot of information available about how safe Decitabine is to use during pregnancy. This lack of information means that doctors don't have a clear understanding of its effects on pregnant individuals and their babies.
• Before Treatment: If someone is considering Decitabine treatment, it's important for the doctor to check if they're pregnant. This helps make sure that if the person is pregnant, steps can be taken to avoid using the drug.
• Contraception: If a person of reproductive age (meaning they could have children) is going to take Decitabine, they should use effective birth control methods during the treatment period. For females, this contraception should continue for 6 months after the last dose of Decitabine. For males with female partners who could become pregnant, effective contraception should be used for 3 months after the last dose of Decitabine. This is to prevent unintended pregnancies while the drug might still be in the body.

Use of decitabine during breastfeeding

• It's unclear if Decitabine gets into breast milk.
• Because there's a chance that the baby could experience severe side effects if they ingest Decitabine through breast milk, the company that makes the drug advises not to breastfeed during the treatment.
• To be on the safe side, it's also recommended not to breastfeed for at least 1 week after the last dose of Decitabine.

Decitabine (Dacogen) Dose in Kidney Disease:

For people with existing health issues:

• The drug manufacturer hasn't provided specific instructions for adjusting the dose of Decitabine.
• This is because they haven't thoroughly studied its effects in people with certain pre-existing conditions.
• If someone with a known health issue is taking Decitabine, they should be watched more closely to ensure they don't experience harmful side effects.

For those experiencing kidney issues while on Decitabine:

• If a blood test shows a person's serum creatinine level (a marker of kidney function) is 2 mg/dL or higher, this suggests there might be an issue with their kidneys.
• In such cases, the use of Decitabine should be paused.
• The treatment should only be restarted once the kidney issue has been addressed and resolved.

Decitabine (Dacogen) Dose in Liver disease:

For people with existing health problems:

• The drug company hasn't given specific instructions about changing the dose of Decitabine for those with certain pre-existing conditions, because they haven't researched its effects on this group of people.
• So, if someone with a known health problem is taking Decitabine, they should be checked more often to make sure the drug isn't causing harmful side effects.

For those experiencing liver issues while on Decitabine:

• If a blood test shows either the ALT level (a liver enzyme) or bilirubin level (a substance the liver produces) is 2 times higher than the normal range's upper limit, it suggests there could be a problem with the liver.
• In this case, Decitabine use should be paused. The drug should only be taken again once the liver issue is cleared up.

Common Side Effects of Decitabine (Dacogen):

• Cardiovascular:
  • Peripheral Edema
  • Edema
  • Heart Murmur
  • Hypotension
• Central Nervous System:
  • Fatigue
  • Headache
  • Insomnia
  • Rigors
  • Dizziness
  • Chills
  • Pain
  • Confusion
  • Lethargy
  • Hypoesthesia
  • Anxiety
• Dermatologic:
  • Pallor
  • Skin Rash
  • Erythema
  • Cellulitis
  • Pruritus
• Endocrine & Metabolic:
  • Hyperglycemia
  • Hypoalbuminemia
  • Hypomagnesemia
  • Hypokalemia
  • Hyponatremia
  • Hyperkalemia
• Gastrointestinal:
  • Nausea
  • Constipation
  • Diarrhea
  • Vomiting
  • Anorexia
  • Decreased Appetite
  • Abdominal Pain
  • Stomatitis
  • Dyspepsia
• Hematologic & Oncologic:
  • Neutropenia
  • Thrombocytopenia
  • Anemia
  • Petechia
  • Febrile Neutropenia
  • Leukopenia
  • Bruise
  • Oral Mucosal Petechiae
  • Lymphadenopathy
• Hepatic:
  • Hyperbilirubinemia
  • Increased Serum Alkaline Phosphatase
• Local:
  • Localized Tenderness
• Neuromuscular & Skeletal:
  • Arthralgia
  • Limb Pain
  • Back Pain
  • Weakness
• Respiratory:
  • Cough
  • Dyspnea
  • Pneumonia
  • Pharyngitis
  • Rales
  • Epistaxis
• Miscellaneous:
  • Fever
  • Lesion

Less Common Side Effects Of Decitabine (Dacogen):

• Cardiovascular:
  • Tachycardia
  • Chest Wall Pain
  • Chest Pain
  • Chest Discomfort
  • Facial Edema
  • Hypertension
  • Cardiac Failure
• Central Nervous System:
  • Depression
  • Falling
  • Malaise
  • Mouth Pain
• Dermatologic:
  • Alopecia
  • Xeroderma
  • Urticaria
  • Catheter Site Erythema
  • Night Sweats
• Endocrine & Metabolic:
  • Hyperuricemia
  • Weight Loss
  • Increased Lactate Dehydrogenase
  • Dehydration
  • Hypochloremia
  • Increased Serum Bicarbonate
  • Decreased Serum Bicarbonate
  • Hypoproteinemia
• Gastrointestinal:
  • Mucosal Inflammation
  • Gingival Hemorrhage
  • Hemorrhoids
  • Loose Stools
  • Tongue Ulcer
  • Oral Candidiasis
  • Toothache
  • Dysphagia
  • Abdominal Distention
  • Gastroesophageal Reflux Disease
  • Glossalgia
  • Oral Mucosa Ulcer
• Genitourinary:
  • Urinary Tract Infection
  • Dysuria
• Hematologic & Oncologic:
  • Hematoma
  • Pancytopenia
  • Thrombocythemia
• Hepatic:
  • Ascites
  • Increased Serum AST
  • Decreased Serum Bilirubin
• Hypersensitivity:
  • Transfusion Reaction
• Infection:
  • Candidiasis
  • Bacteremia
  • Staphylococcal Infection
  • Tooth Abscess
• Local:
  • Catheter Infection
  • Catheter Pain
  • Swelling At Injection Site
• Neuromuscular & Skeletal:
  • Myalgia
  • Muscle Spasm
  • Ostealgia
  • Musculoskeletal Pain
• Ophthalmic:
  • Blurred Vision
• Otic:
  • Otalgia
• Renal:
  • Polyuria
• Respiratory:
  • Hypoxia
  • Upper Respiratory Tract Infection
  • Abnormal Breath Sounds
  • Pharyngolaryngeal Pain
  • Pulmonary Edema
  • Sinusitis
  • Pleural Effusion
  • Post Nasal Drip
  • Pulmonary Signs And Symptoms
  • Sinus Congestion

Contraindications to Decitabine (Dacogen):

The company that makes the drug hasn't listed any specific situations or conditions where the drug should definitely not be used.

Warnings and precautions

Suppression of bone marrow

Decitabine can commonly cause a drop in blood cell counts, which is known as myelosuppression. This can lead to:

• Neutropenia: A decrease in a type of white blood cell called neutrophils.
• Thrombocytopenia: A decrease in platelets, which help with blood clotting.
• Anemia: A decrease in the overall number of red blood cells.

These reductions can be severe, and in some cases, can cause serious problems like fever due to neutropenia. This fever is particularly concerning because neutrophils play a major role in fighting infections. In some rare cases, these effects can even be fatal.

Monitoring and Management:

• Blood counts, including platelets, should be checked:
  • Before starting treatment.
  • Before each treatment cycle.
  • Whenever needed to keep an eye on how the patient is responding to the drug and to watch for any harmful effects.
• During the first two cycles of treatment with Decitabine, it's more common to see drops in blood cell counts. However, this doesn't necessarily mean the underlying bone marrow condition (like MDS) is getting worse.
• If blood cell counts get too low, the following might be needed:
  • Reducing the dose of Decitabine.
  • Delaying the next dose.
  • Stopping the drug.
  • Using drugs that help boost blood cell growth.
  • Using antibiotics or other drugs to prevent or treat infections.

Always be alert for signs of infection since the body will be less equipped to fight off germs.

Decitabine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Blood Counts:

• Check a Complete Blood Count (CBC) with a breakdown of the different types of blood cells (differential) and platelet count:
  • Before starting treatment.
  • At the start of each treatment cycle.
  • More often if needed.

Liver Health:

• Check liver enzymes to see how the liver is working:
  • Before starting treatment.
  • From time to time while on treatment.

Kidney Health:

• Test serum creatinine to see how the kidneys are functioning:
  • Before starting treatment.
  • Periodically during treatment.

Pregnancy Test:

• For women who can become pregnant:
  • Check a pregnancy test before starting treatment to ensure they're not pregnant.

How to administer Decitabine (Dacogen)?

Duration of Infusion:

• The time it takes to give Decitabine through an IV varies from 1 to 3 hours. The exact time depends on the specific dose and the reason for the treatment.

For Myelodysplastic Syndromes:

• If the dose is 15 mg/m^2: Infuse over 3 hours.
• If the dose is 20 mg/m^2: Infuse over 1 hour.

For Acute Myeloid Leukemia (Off-label Use):

• As per research references (Cashen 2010; Kantarjian 2012), the drug should be given over 1 hour.

Before Starting the Infusion:

• It's recommended by the drug manufacturer to give medications to prevent nausea and vomiting (antiemetics) before starting the Decitabine infusion.

Mechanism of action of Decitabine (Dacogen):

Decitabine works as a hypomethylating agent, which means it reduces the level of methylation in DNA. Here's how it happens:

• Phosphorylation: First, decitabine gets modified by adding a phosphate group to it. This helps it become active.
• Incorporation into DNA: Once it's active, decitabine is added into the DNA during the process of DNA replication.
• Blocking Methylation: When decitabine is part of the DNA, it interferes with the work of an enzyme called DNA methyltransferase. This enzyme is responsible for adding methyl groups to the DNA, which usually results in "silencing" certain genes, or turning them off.
• Hypomethylation: By stopping DNA methyltransferase, decitabine leads to a decrease in the level of methylation in the DNA. This is called hypomethylation. It's like lifting the "silence" button from some genes.
• Cell Cycle Impact: Decitabine's most effective when cells are replicating their DNA (S-phase of the cell cycle). It affects the DNA copying process and can cause errors that lead to cell death.

So, in a nutshell, decitabine messes with the DNA methylation process, which can cause cells to die, particularly when they're replicating. This is one way it's used to treat certain conditions like myelodysplastic syndromes and even off-label for acute myeloid leukemia.

Distribution:

• After being administered, decitabine spreads throughout the body and has a distribution volume of about 63 to 89 liters for every square meter of body surface area, as per research from 2008 by Cashen.

Metabolism:

• It's believed that decitabine is changed and broken down (or metabolized) through a process where it loses an amino group.
• This is done by an enzyme called cytidine deaminase.

How Long It Lasts:

• Decitabine doesn't stay in the body very long.
• Its half-life, which is the time it takes for half of the drug to be removed from the body, is between 0.5 to 0.6 hours.
• So, in less than an hour, half the amount of the drug will be gone.

International Brand Names of Decitabine:

• Dacogen
• Xalibo
• Decbine

Decitabine Brand Names in Pakistan:

Update soon.