Tyronib 400mg Tablet 10pcs

✔️

✔️ Dosage & Administration

Adult Dosages:

• Ph+ CML (Chronic Phase): 400 mg/day.
• Ph+ CML (Accelerated/Blast Crisis): 600 mg/day.
• Ph+ ALL: 600 mg/day.
• MDS/MPD: 400 mg/day.
• ASM & HES/CEL: 100 mg/day or 400 mg/day.
• DFSP: 800 mg/day.
• Metastatic/Unresectable GIST: 400 mg/day.
• Adjuvant GIST Therapy: 400 mg/day.
• Hepatic Impairment:
  • Mild/Moderate: 400 mg/day.
  • Severe: 300 mg/day.

Pediatric Dosages:

• Ph+ CML (Chronic Phase): 340 mg/m²/day.
• Ph+ ALL: 340 mg/m²/day.

✔️ Administration Instructions:

• Take it with a meal and a large glass of water.
• Doses of 400 mg or 600 mg: Once daily.
• Doses of 800 mg: 400 mg twice daily.
• Tablets can be dissolved in water or apple juice for swallowing difficulties.
• Use 400 mg tablets for higher doses to minimize iron exposure.

✔️ Interactions

Agents Affecting CYP3A Metabolism

CYP3A4 Inducers:

• Strong inducers (e.g., rifampin, phenytoin, carbamazepine, St. John’s Wort) may reduce imatinib exposure significantly.
• Consider alternative agents to maintain efficacy.

CYP3A4 Inhibitors:

• Strong inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) may increase imatinib exposure.
• Avoid grapefruit juice, as it can raise plasma imatinib levels.

Interactions with CYP3A4 Substrates

• Imatinib increases the plasma concentrations of drugs metabolized by CYP3A4 (e.g., triazole-benzodiazepines, dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors).
• Use caution with drugs that have a narrow therapeutic window.

Warfarin:

• As warfarin is metabolized by CYP2C9 and CYP3A4, it can lead to significant interactions.
• Use low-molecular weight or standard heparin as an alternative anticoagulant in patients on Tyronib.

CYP2D6 Substrates:

• Tyronib may alter the plasma concentration of drugs metabolized by CYP2D6.
• Use caution with narrow therapeutic window substrates (e.g., metoprolol, antidepressants).

✔️ Side Effects

Fluid Retention & Edema:

• Common in patients; monitor for significant weight gain or swelling.

Hematologic Toxicity:

• Includes neutropenia, thrombocytopenia, and anemia; requires frequent blood count monitoring.

Cardiac Toxicity:

• Risk of congestive heart failure and left ventricular dysfunction; monitor cardiac function in patients with prior cardiac conditions.

Hepatotoxicity:

• Elevations in liver enzymes; rare cases of liver failure reported.

Hemorrhage:

• Serious bleeding events were reported, particularly in the gastrointestinal tract.

Gastrointestinal Disorders:

• Nausea, diarrhea, abdominal pain, and vomiting.

Hypereosinophilic Cardiac Toxicity:

• Rare but potentially fatal; monitor cardiac function in patients with HES or CEL.

Dermatologic Toxicities:

• Skin rash, severe bullous reactions, and Stevens-Johnson syndrome may occur.

Hypothyroidism:

• Can occur in thyroidectomy patients on levothyroxine; monitor thyroid hormone levels.

Growth Retardation:

• Seen in pediatric patients; monitor growth parameters regularly.

Tumor Lysis Syndrome:

• Rare but serious metabolic imbalance following rapid tumor cell lysis; ensure proper hydration and uric acid control.

Driving and Machinery Impairment:

• Imatinib may cause fatigue, dizziness, and visual disturbances, affecting performance in tasks requiring alertness.

Renal Toxicity:

• Elevated creatinine levels and cases of renal failure have been observed; monitor renal function periodically.

✔️ Pregnancy & Lactation

• Women of childbearing potential must be advised to use effective contraception during treatment and for at least 15 days after stopping Imatinib.

Pregnancy

• Limited data are available on the use of Imatinib during pregnancy.
• Risks identified:
  • Post-marketing reports indicate cases of spontaneous abortions and congenital anomalies in infants exposed to Imatinib in utero.
  • Animal studies have shown reproductive toxicity, indicating potential fetal risk.
• Recommendation:
  • Imatinib should only be used during pregnancy if necessary.
  • Patients must be informed of the potential risks to the fetus.

Breastfeeding

• Imatinib and its active metabolite are distributed in human milk:
  • Milk-plasma ratio: 0.5 for Imatinib and 0.9 for the metabolite.
  • Estimated infant exposure through breast milk is low (approx. 10% of a therapeutic dose).
• Due to the unknown effects of low-dose exposure, women should not breastfeed during treatment and for at least 15 days after stopping Imatinib.

Fertility

• Non-clinical studies:
  • Fertility in male and female rats was unaffected, but effects on reproductive parameters were observed.
• Human studies:
  • No studies have been conducted on the effects of Imatinib on human fertility or gametogenesis.
• Patients with concerns about fertility should consult their physician for further guidance.

✔️ Overdose Effects

Adult Population:

• 1200–1600 mg (1–10 days): Nausea, vomiting, diarrhea, rash, fatigue, muscle spasms, cytopenias, abdominal pain.
• 1800–3200 mg (up to 6 days): Weakness, myalgia, increased creatine phosphokinase, and bilirubin.
• 6400 mg (single dose): Nausea, vomiting, facial swelling, and increased liver enzymes.
• 8000–10,000 mg (single dose): GI pain and vomiting.

Pediatric Population:

• 400 mg (single dose in a 3-year-old): Vomiting, diarrhea, anorexia.
• 980 mg (single dose in a 3-year-old): Diarrhea, low WBC count.

Management:

• In the event of an overdose, observe patients and provide appropriate symptomatic and supportive care.

✔️ Precautions & Warnings

Edema & Fluid Retention

• Severe cases were reported.
• Regularly weigh patients; manage rapid weight gain with drug interruption and diuretics.

Cytopenias

• Anemia, neutropenia, and thrombocytopenia may occur.
• Perform weekly blood counts for the first month, biweekly for the second month, and periodically afterward.
• Manage with dose reduction, interruption, or discontinuation.

Cardiac Events

• Risk of congestive heart failure (CHF) and left ventricular dysfunction, especially in patients with comorbidities.
• Monitor and treat patients with cardiac disease or risk factors.

Hepatotoxicity

• Severe liver toxicity, including fatalities, may occur.
• Assess liver function before treatment and monthly thereafter. Monitor closely if combined with chemotherapy.

Hemorrhage and GI Perforation

• Grade 3/4 hemorrhages have been reported in CML and GIST patients.
• Some GI bleeds originate from tumor sites in GIST patients. GI perforations (some fatal) have occurred.

Cardiogenic Shock/Left Ventricular Dysfunction

• Associated with conditions involving high eosinophil levels (HES, MDS/MPD, ASM). Monitor closely.

Bullous Dermatologic Reactions

• Conditions like erythema multiforme and Stevens-Johnson syndrome have been reported.

Hypothyroidism

• Monitor TSH levels closely in thyroidectomy patients receiving levothyroxine replacement therapy.

Pregnancy

• Can harm the fetus. Advise women of reproductive age to avoid pregnancy during treatment.

Growth Retardation in Children

• Monitor growth regularly in pediatric patients on Tyronib.

Tumor Lysis Syndrome

• Monitor patients at risk closely.

Motor Impairment

• Advise caution while driving or operating machinery due to risks of accidents.

Renal Toxicity

• Risk of declined renal function. Evaluate renal function before and during therapy, especially in patients with risk factors for renal dysfunction.

✔️ Storage:

• Store below 30°C, in a cool, dry place, and protect from light.
• Keep out of reach of children.