Merpurin Mercaptopurine sitotoksik kocak farma

I. Basic Drug Information

Generic Name: Mercaptopurine

Brand Names: Merpurin, Puri-nethol, Xaluprine

Dosage Form: Tablets (10 mg, 50 mg)

Pharmacological Class: Purine Analog; Antimetabolite Antineoplastic Agent

Manufacturer: Koçak Farma İlaç

Storage Requirements: Store in a dry environment at 20°C–25°C (allowable range: 15°C–30°C).

II. Indications

1. Leukemia

Acute Lymphocytic Leukemia (ALL): Remission induction and maintenance therapy

Acute Nonlymphocytic Leukemia (ANLL)

Chronic Granulocytic Leukemia (CGL): Blast crisis phase

2. Solid Tumors

- Choriocarcinoma, Malignant Hydatidiform Mole

Off-label Uses (Requires Physician Assessment)

Crohn's Disease: For patients unresponsive to corticosteroids or salicylates; 1–1.5 mg/kg daily; treatment course ≥ 3–6 months.

Ulcerative Colitis: Initial dose of 50 mg daily; adjust dosage based on tolerability; used to reduce corticosteroid dependence.

III. Mechanism of Action

Inhibition of Purine Synthesis: As a purine analog, it interferes with DNA/RNA synthesis, thereby blocking tumor cell proliferation.

Immunosuppression: Inhibits T-cell activity; used in the treatment of inflammatory bowel disease.

IV. Dosage and Administration

| Patient Population | Dosage                                                                 | Adjustment Principles

| Adults/Children   | 2.5 mg/kg daily OR 50–70 mg/m² of body surface area | Individualize dosage based on blood counts, hepatic function, and renal function; maintenance dose is typically 1.5–2.5 mg/kg daily.

| Elderly Patients  | Same as adults, but requires close monitoring of hepatic and renal function | Reduce dosage in patients with renal impairment (CrCl < 50 mL/min) or hepatic impairment.

| Concomitant Use with Allopurinol | Reduce dosage to 25%–33% of the original dose | Allopurinol inhibits the metabolism of mercaptopurine, thereby increasing the risk of toxicity.

Key Points: Timing of Administration: Take on an empty stomach or at a fixed time after meals; avoid concurrent intake with dairy products (allow an interval of at least 1 hour).

Duration of Treatment: Maintenance therapy for leukemia requires long-term use; for inflammatory bowel disease, therapeutic effects typically become apparent after at least 3 to 6 months.

Basis for Dosage Adjustment: Monitor complete blood counts (white blood cells and platelets) weekly, and assess liver function monthly.

V. Contraindications

Absolute Contraindications:

- Hypersensitivity to mercaptopurine;

- Pregnancy (risk of fetal malformation or death);

- Breastfeeding;

- Homozygous mutations in the *TPMT* or *NUDT15* genes (risk of severe myelosuppression). VI. Adverse Reactions

| Type          | Common Manifestations                                     | Serious Risks

| Hematologic | ↓ Leukocytes, ↓ Platelets, Anemia (>30%)                | Severe Myelosuppression (requiring blood transfusion intervention)

| Hepatic     | ↑ Transaminases, ↑ Bilirubin (10%–20%)                  | Hepatic Necrosis (rare but potentially fatal)

| Gastrointestinal | Nausea, Vomiting, Diarrhea (5%–15%)                     | Pancreatitis, Oral Ulceration

| Infectious  | Increased susceptibility to bacterial/viral infections | Severe Infections (e.g., EBV-associated lymphoproliferative disease)

| Other       | Skin Hyperpigmentation, Alopecia, Hyperuricemia         | Macrophage Activation Syndrome (MAS), Secondary Malignancies (e.g., Lymphoma)

VII. Precautions

1. Genetic Testing:

- Test for *TPMT* and *NUDT15* genotypes prior to treatment; patients with low enzyme activity require significant dose reduction.

2. Infection Prevention and Control:

- Live vaccines (e.g., measles, BCG) are contraindicated; discontinue medication for ≥3 months before vaccination.

- Avoid contact with patients suffering from varicella (chickenpox) or herpes zoster (shingles).

3. Carcinogenic Risk:

- Long-term use may increase the risk of lymphoma and skin cancer; practice sun protection and undergo regular skin examinations.

4. Impact on Fertility:

- Both male and female patients must use effective contraception for 6 months after discontinuing the medication (due to teratogenic risks). VIII. Drug Interactions

| Concomitant Drug      | Mechanism of Interaction                     | Management Recommendations

| Allopurinol           | Inhibits xanthine oxidase → Toxicity accumulation | Reduce mercaptopurine dosage to 25%–33% of the original dose

| Aminosalicylates      | Inhibits TPMT enzyme → Exacerbated myelosuppression | Avoid concomitant use, or reduce dosage and monitor closely

| Warfarin              | Reduces anticoagulant effect                 | Increase Warfarin dosage and monitor INR

| Hepatotoxic Drugs     | Additive risk of liver injury                | Avoid concomitant use (e.g., Isoniazid, antifungal agents)

IX. Use in Specific Populations

Pregnant Women: Contraindicated (clear evidence of teratogenicity);

Breastfeeding Women: Drug is excreted into breast milk; breastfeeding is contraindicated;

Children:

- Calculate dosage based on body weight; monitor closely for hypoglycemia (especially in low-weight children <6 years of age);

- Effective for maintenance therapy in leukemia, but requires intensified infection prevention and control measures;

Hepatic and Renal Impairment:

- For patients with hepatic impairment: reduce dosage or use is contraindicated (Child-Pugh Class C);

- For patients with renal insufficiency (CrCl <50 mL/min): reduce dosage by 30%–50%.

X. Storage and Handling

Temperature: 20°C–25°C (excursions permitted between 15°C and 30°C);

Environment: Protect from light and moisture; store in the original sealed packaging;

Shelf Life: Refer to the expiration date marked on the original packaging; expired medication requires professional disposal.

Disclaimer: Specific medication use must be in accordance with a physician's instructions. Product Specifications

Product Name: Mercaptopurine Tablets 50mg * 25 Tablets/Box (Merpurin)

Common Name: Mercaptopurine Tablets

Composition: Mercaptopurine

Dosage Form: Tablets

Specification: 50mg/tablet; 25 tablets/box

Manufacturer: Koçak Farma İlaç

Indications: 1. Hematological Disorders

Acute Lymphocytic Leukemia (ALL): Remission induction and maintenance therapy

Acute Non-Lymphocytic Leukemia (ANLL)

Chronic Myeloid Leukemia (in blast crisis phase)

2. Solid Tumors

Choriocarcinoma, Malignant Hydatidiform Mole

Usage and Dosage: I. Treatment of Hematological Disorders

1. Acute Leukemia (Remission Induction and Maintenance Therapy)

Adults:

Remission Induction: Oral administration of 1.5–3 mg/kg daily, taken in 1–2 divided doses; treatment course is 2–4 weeks.

Maintenance Therapy: 1–3 mg/kg daily; for long-term use.

Children:

Remission Induction: 1.5–2.5 mg/kg daily, taken in 1–2 divided doses.

Maintenance Therapy: 1–2 mg/kg daily, calculated based on body surface area (1.5–3 mg/m²).

2. Chronic Myeloid Leukemia (Adjuvant Therapy)

1.5–3 mg/kg daily, taken in divided doses; dosage should be adjusted based on blood counts.

II. Inflammatory Bowel Disease (e.g., Crohn's Disease, Ulcerative Colitis)

Adults: Initial dose of 0.5–1 mg/kg daily, gradually increased to 1.5–2.5 mg/kg daily, taken in 1–2 divided doses; onset of action typically takes 3–6 months.

Children: 1–1.5 mg/kg daily; maximum dose not to exceed 2.5 mg/kg daily.