REGONAM

REGONAM

regorafenib 40 mg
Net Qty- 28 tablet
Self-Life- 2 Years

Regonam (Regorafenib) is an oral cancer medication used to slow the growth and spread of cancer cells by blocking multiple enzymes (kinases) that promote tumor growth and blood vessel formation (angiogenesis).

USE

Regonam (Regorafenib) is used to treat several types of advanced cancers that no longer respond to standard treatments.

Approved Uses (FDA & EMA):

  1. Metastatic Colorectal Cancer (mCRC)

    • When? After progression on standard therapies (chemotherapy + anti-VEGF/EGFR agents).

    • Evidence: CORRECT trial showed improved survival vs. placebo.

  2. Gastrointestinal Stromal Tumors (GIST)

    • When? After failure of imatinib and sunitinib.

    • Evidence: GRID trial demonstrated delayed tumor progression.

  3. Hepatocellular Carcinoma (HCC)

    • When? For patients who progressed on sorafenib.

    • Evidence: RESORCE trial showed survival benefit.

How to Use (Dosing & Administration):

  • Standard Dose: 160 mg once daily for 21 days, followed by 7 days off (28-day cycle).

  • Take with food (low-fat meal improves absorption).

  • Dose Adjustments: Required for severe side effects (e.g., liver toxicity, hand-foot syndrome).

Key Considerations:

✔ Monitor liver function (risk of hepatotoxicity).
✔ Check blood pressure (hypertension is common).
✔ Manage side effects early (e.g., skin rash, diarrhea).

Off-Label Uses (Investigational):

  • Soft tissue sarcomas

  • Thyroid cancer

  • Glioblastoma (limited evidence)

Key Benefits

🌟 Regonam (Regorafenib) – Key Benefits

Regonam (Regorafenib) offers several clinical benefits for patients with advanced cancers that have stopped responding to prior treatments. Here’s what makes it valuable in oncology:

 

✅ Slows Tumor Growth

  • Inhibits multiple kinases involved in tumor cell proliferation and angiogenesis (formation of blood vessels that feed tumors)

  • Targets VEGFR, PDGFR, KIT, RET, RAF, and others

✅ Extends Survival in Advanced Cancers

  • Colorectal Cancer (mCRC):
    ➤ Increases overall survival and progression-free survival in patients who’ve exhausted other therapies

  • GIST (Gastrointestinal Stromal Tumor):
    ➤ Effective after failure of imatinib and sunitinib
    ➤ Helps control tumor growth and delay progression

  • Hepatocellular Carcinoma (HCC):
    ➤ Shown to prolong survival in patients previously treated with sorafenib

✅ Oral Administration

  • Taken as a once-daily oral tablet, making it more convenient than IV chemotherapy

✅ Multi-Targeted Action

  • Blocks several cancer growth pathways at once

  • May help overcome resistance to single-target therapies

✅ Option When Others Fail

  • Provides a treatment path for patients with limited remaining options due to prior treatment resistance

Mechanism
of Action

🔬 Regonam (Regorafenib) – Mechanism of Action

Regonam (Regorafenib) is a multi-kinase inhibitor that works by blocking multiple proteins (kinases) involved in tumor growth, angiogenesis (formation of blood vessels), metastasis, and the tumor microenvironment.

🧬 How It Works:

Regorafenib targets several key receptor tyrosine kinases (RTKs) and intracellular kinases involved in:

1. Tumor Angiogenesis (blood vessel formation):

  • VEGFR-1, VEGFR-2, VEGFR-3

  • TIE2

✅ Blocking these receptors reduces blood supply to tumors, starving them of oxygen and nutrients.

2. Tumor Growth & Proliferation:

  • KIT (important in GIST)

  • RET

  • RAF-1, BRAF (including mutant BRAF)

  • PDGFR-α and PDGFR-β

✅ These help slow cell division and tumor progression, particularly in cancers like colorectal cancer and thyroid cancer.

 

3. Tumor Microenvironment & Metastasis:

  • FGFR

  • CSF1R

✅ Affects tumor cell survival, inflammation, and the environment that supports cancer spread.

 

🧠 Summary of Action:

Regonam (Regorafenib) works by blocking multiple growth-promoting pathways at once — cutting off blood supply, reducing tumor growth, and disrupting survival signals within the cancer cells.

 

Dosage and Administration

💊 Regonam (Regorafenib) – Dosage and Administration

Regonam (Regorafenib) is taken orally, usually on a cycle of 3 weeks on, 1 week off. It’s important to follow exact dosing instructions from your oncologist or pharmacist.

 

✅ Recommended Dose (Adults):

  • 160 mg once daily

  • Taken for 21 days (3 weeks) followed by 7 days off

  • Each cycle = 28 days

This typically means: Four 40 mg tablets once a day

🕗 Timing and How to Take:

  • Take once daily at the same time each day

  • Take after a low-fat meal (containing <30% fat)

    • Example: toast, cereal, or a small sandwich

  • Swallow tablets whole with water — do not crush, split, or chew

  • If a dose is missed, skip it if it’s been more than 8 hours — do not double up

 🔄 Dose Adjustments May Be Needed If:

  • You experience serious side effects (e.g., hand-foot skin reaction, liver enzyme elevations)

  • You’re on medications that interact with regorafenib (e.g., CYP3A4 inducers/inhibitors)

  • You have liver impairment

Toxicity SeverityActionAdjusted Dose
Grade 2 (intolerable)Interrupt until ≤ Grade 1Resume at 120 mg/day
Grade 3 (severe)Interrupt until ≤ Grade 1Resume at 80 mg/day
Grade 4 (life-threatening)Discontinue permanentlyN/A

⚠️ Important Reminders:

  • Store at room temperature, in the original bottle with desiccant

  • Keep away from moisture and heat

  • Do not take during the “off week” unless told otherwise by your doctor

Common Side Effects

🤒 Regonam (Regorafenib) – Common Side Effects

Regonam (Regorafenib) is associated with frequent but manageable side effects, primarily due to its multi-kinase inhibition. Below is a breakdown of the most common adverse reactions and practical strategies to address them.

 

🔹 Most Common Side Effects:

Side EffectIncidenceManagement Tips
Fatigue~50-60%– Schedule rest periods, light exercise
– Rule out hypothyroidism or anemia
Hand-Foot Skin Reaction (HFSR)~45-60%– Preventive care: Moisturize with urea cream, avoid friction
– If severe (Grade 2-3): Dose reduction (120 mg → 80 mg)
Diarrhea~40-50%– Loperamide (Imodium®) PRN
– Hydration + electrolyte replacement
Hypertension~30-50%– Monitor BP weekly
– Start antihypertensives (e.g., ACE inhibitors, amlodipine)
Anorexia/Weight Loss~30-40%– Small, frequent meals
– Appetite stimulants (e.g., megestrol acetate) if needed

🔹Potentially Serious Side Effects (Requiring Immediate Action)

Side EffectAction Required
Severe Liver Toxicity (↑ALT/AST/bilirubin)– Hold drug if ALT/AST >5× ULN
– Discontinue if bilirubin >3× ULN
Bleeding (GI, CNS, pulmonary)– Emergency evaluation for severe hemorrhage
– Permanently discontinue if life-threatening
Heart Problems (ischemia, MI)– Hold for chest pain, ECG changes
– Discontinue if confirmed MI
Reversible Posterior Leukoencephalopathy (RPLS)– MRI confirmation
– Discontinue permanently

🔹Other Notable Side Effects (10-30% of Patients)

Side EffectManagement
Mucositis/Oral Pain– Saltwater rinses, topical lidocaine
– Avoid alcohol-based mouthwashes
Rash– Mild steroids (hydrocortisone cream)
– Antihistamines for itching
Nausea/Vomiting– Ondansetron (Zofran®) or prochlorperazine
– Take with a small meal
Hoarseness– Usually self-limiting; rule out hypothyroidism
Hair Color Changes– Reversible after stopping treatment

 

🔹Proactive Supportive Care Strategies
Side EffectAction Required
Severe Liver Toxicity (↑ALT/AST/bilirubin)– Hold drug if ALT/AST >5× ULN
– Discontinue if bilirubin >3× ULN
Bleeding (GI, CNS, pulmonary)– Emergency evaluation for severe hemorrhage
– Permanently discontinue if life-threatening
Heart Problems (ischemia, MI)– Hold for chest pain, ECG changes
– Discontinue if confirmed MI
Reversible Posterior Leukoencephalopathy (RPLS)– MRI confirmation
– Discontinue permanently

🧪 Lab Abnormalities That May Occur:

  • Elevated liver enzymes (ALT, AST)

  • Low platelet or white blood cell counts

  • Low calcium, phosphate, or sodium levels

⚠️ When to Contact Your Doctor Immediately:

  • Severe abdominal pain, vomiting, or bleeding

  • Signs of liver injury (yellowing of skin/eyes, dark urine)

  • Shortness of breath, chest pain

  • Uncontrolled high blood pressure

  • Signs of infection (fever, chills)

Proactive Supportive Care Strategies

✅ Before Starting Therapy:

  • Baseline tests: LFTs, BP, TSH, renal function.

  • Counseling: Educate on early signs of HFSR, diarrhea, hypertension.

✅ During Treatment:

  • Skin care: Use urea-based creams (e.g., Eucerin® 10%) + avoid tight shoes.

  • BP monitoring: Home blood pressure log for first 2 cycles.

  • Hydration: Oral rehydration solutions (e.g., Pedialyte®) for diarrhea.

✅ For Dose-Limiting Toxicities:

  • First reduction: 160 mg → 120 mg/day.

  • Second reduction: 120 mg → 80 mg/day.

  • Permanent stop: If toxicity recurs at 80 mg.

Monitoring

🩺 Regonam (Regorafenib) – Monitoring Guidelines

Patients on Regonam (Regorafenib) need regular monitoring to detect side effects early, adjust doses, and ensure safety during treatment. Here’s what healthcare providers typically keep an eye on:

 

🔍 Liver Function Tests (LFTs)

When: Before starting, weekly during the first 2 months, then at least monthly
Why: Regorafenib can cause serious liver toxicity (elevated AST/ALT, bilirubin)

➡️ Monitor: ALT, AST, bilirubin
➡️ Dose adjustment or discontinuation if significant elevations occur

 

💉 Blood Pressure

When: Before starting, weekly for the first 6 weeks, then periodically

Why: Regorafenib can cause early-onset hypertension

➡️ Control BP before starting treatment

➡️ Antihypertensives may be needed

 

🧪 Complete Blood Count (CBC)

Why: To monitor for anemia, neutropenia, thrombocytopenia
When: Periodically during treatment


🧪 Electrolytes and Renal Function

Why: Regorafenib may lower sodium, potassium, calcium, phosphate
➡️ Check BUN/creatinine and electrolytes regularly
➡️ Replace as needed


🧬 Thyroid Function

Why: Hypothyroidism can occur during therapy
➡️ TSH should be checked periodically


🦶 Skin and Mucosal Exams

Why: To monitor for Hand-Foot Skin Reaction (HFSR) and mucosal irritation
➡️ Early detection helps with prompt supportive care or dose modification


📏 Weight & Nutritional Status

Why: Weight loss and anorexia are common
➡️ Nutrition support may be necessary


🩺 Additional Assessments (if needed):

  • Cardiac evaluation if patient has heart disease or new symptoms

  • Imaging to assess tumor response (CT/MRI based on cancer type)

Precautions

⚠️ Regonam (Regorafenib) – Precautions

Patients taking Regonam (Regorafenib) need to follow certain precautions to reduce the risk of serious side effects and maximize the treatment’s effectiveness.


🛡️ Important Precautions:

1. Liver Toxicity

  • Serious and sometimes fatal liver damage can occur.

  • Monitor liver function closely, especially in the first 2 months.

  • Dose reduction or discontinuation may be needed if liver enzymes rise significantly.

2. High Blood Pressure (Hypertension)

  • Regorafenib can cause early and severe hypertension.

  • Blood pressure should be well controlled before starting.

  • Monitor BP weekly during the first 6 weeks, then periodically.

3. Bleeding Risks

  • Increased risk of serious bleeding (gastrointestinal, pulmonary, or brain hemorrhage).

  • Use caution in patients with bleeding disorders or on anticoagulants.

  • Stop treatment for significant bleeding events.

4. Gastrointestinal Perforation or Fistula

  • Rare but serious risk.

  • Watch for severe abdominal pain, fever, vomiting — these may indicate a perforation.

  • Discontinue regorafenib if perforation occurs.

5. Hand-Foot Skin Reaction (HFSR)

  • Painful redness, swelling, and blistering of palms and soles is common.

  • Preventive measures (moisturizers, minimizing friction) are recommended.

  • Dose modifications may be needed for severe cases.

6. Cardiac Risks

  • Risk of ischemia and myocardial infarction (heart attack).

  • Use cautiously in patients with a history of heart disease.

  • Discontinue if serious cardiac events occur.

7. Infections

  • Regorafenib can increase susceptibility to infections.

  • Monitor closely for signs like fever, cough, or urinary symptoms.

8. Wound Healing

  • Can impair wound healing.

  • Hold regorafenib at least 2 weeks before and after major surgery.

  • Resume only after adequate wound healing.

9. Reproductive Precautions

  • Pregnancy: Avoid — may cause fetal harm.

  • Contraception: Effective contraception is required during treatment and for 2 months after the last dose.

  • Breastfeeding: Not recommended during treatment and for 2 weeks after the last dose.

 🚫 Use with Caution or Avoid:

  • Pregnancy and Breastfeeding:
    ➤ Regorafenib may cause harm to an unborn baby.
    ➤ Use effective contraception during treatment and for at least 2 months after the last dose.

  • Severe liver dysfunction

  • Severe renal impairment

Drug Interactions

🔄 Regonam (Regorafenib) – Drug Interactions

Regonam (Regorafenib) is metabolized mainly by liver enzymes (especially CYP3A4 and UGT1A9), so it can interact with many other drugs — potentially altering its effectiveness or increasing side effects.

⚠️ Major Drug Interactions to Know:

 

1. CYP3A4 Inhibitors

These increase regorafenib levels → higher risk of toxicity

Examples:

  • Ketoconazole

  • Clarithromycin

  • Ritonavir

  • Itraconazole

  • Grapefruit juice 🍊

➡️ Avoid or monitor closely if used together


2. CYP3A4 Inducers

These decrease regorafenib levels → reduced effectiveness

Examples:

  • Rifampin

  • Phenytoin

  • Carbamazepine

  • St. John’s Wort 🌿

➡️ Avoid combining

3. UGT1A9 Substrates

Regorafenib may inhibit UGT1A9, affecting metabolism of some drugs

Example:

  • Mycophenolate mofetil (an immunosuppressant)

4. Anticoagulants

Increased risk of bleeding when used with:

  • Warfarin

  • Apixaban

  • Rivaroxaban

➡️ Monitor INR or bleeding signs more frequently

5. Other Targeted Therapies / Chemotherapies

Concurrent use may increase toxicity or compound side effects (e.g., hand-foot syndrome, liver toxicity)

➡️ Use with caution and only if clinically necessary

Clinical Effectiveness

📊 Regonam (Regorafenib) – Clinical Effectiveness

Regonam (Regorafenib) has demonstrated significant clinical benefit in patients with advanced cancers who have progressed on standard therapies. Its broad kinase inhibition allows it to target multiple cancer pathways, which contributes to its effectiveness across several tumor types.

 

✅ 1. Metastatic Colorectal Cancer (mCRC)

Study: CORRECT Trial

  • Patients previously treated with chemotherapy and targeted therapies

  • Regonam (Regorafenib) vs. Placebo

  • Results:

    • Overall survival (OS): 6.4 vs. 5.0 months

    • Progression-free survival (PFS): 1.9 vs. 1.7 months

    • Disease control rate: 41% vs. 15%
      🔹 Conclusion: Regorafenib modestly improves survival in treatment-refractory mCRC.

✅ 2. Gastrointestinal Stromal Tumor (GIST)

Study: GRID Trial

  • Patients resistant to imatinib and sunitinib

  • Regorafenib vs. Placebo

  • Results:

    • PFS: 4.8 vs. 0.9 months

    • Disease control: 53% vs. 9%
      🔹 Conclusion: Regorafenib significantly delays progression in drug-resistant GIST.

✅ 3. Hepatocellular Carcinoma (HCC)

Study: RESORCE Trial

  • Patients who progressed on sorafenib

  • Regorafenib vs. Placebo

  • Results:

    • OS: 10.6 vs. 7.8 months

    • PFS: 3.1 vs. 1.5 months
      🔹 Conclusion: Regorafenib provides a survival benefit as a second-line therapy in liver cancer.

🔬 Mechanistic Strength

  • Multi-target kinase inhibition allows it to overcome resistance to prior treatments

  • Especially beneficial in refractory or metastatic settings

💡 Clinical Summary:

Regorafenib is not a first-line treatment but offers meaningful clinical benefits in:

  • Extending survival

  • Delaying disease progression

  • Controlling symptoms in advanced, previously treated cancers

Tips for Patients

🧘‍♀️ Regonam (Regorafenib) – Tips for Patients

If you’re starting Regonam (Regorafenib), here are some key tips to help you stay safe, manage side effects, and get the most benefit from your treatment.

 

💊 1. How to Take the Medication

  • Take 160 mg once daily (usually 4 tablets) for 21 days, then stop for 7 days (28-day cycle)

  • Always take after a low-fat meal (less than 30% fat) — this helps absorption and reduces stomach upset

  • Take at the same time every day

  • Swallow tablets whole — don’t crush, chew, or split them

🕒 2. If You Miss a Dose

  • If you remember within 8 hours, take it

  • If it’s been more than 8 hours, skip the dose — don’t double up

⚠️ 3. Monitor for Side Effects

  • Report early signs of hand-foot skin reaction (redness, pain, blisters)

  • Watch for high blood pressure (headaches, dizziness)

  • Monitor for liver issues (yellowing skin/eyes, dark urine, fatigue)

  • Keep track of bowel movements (diarrhea is common)

  • Let your doctor know if you have mouth sores, rash, or unusual bleeding

💧 4. Self-Care During Treatment

  • Use moisturizers daily to prevent hand-foot reactions

  • Wear comfortable shoes and avoid friction on hands/feet

  • Hydrate well and eat small, frequent meals

  • Maintain a healthy, balanced diet — consider seeing a dietitian

  • Use a soft toothbrush and avoid alcohol-based mouthwashes

🧾 5. General Reminders

  • Keep all appointments for blood tests and checkups

  • Do not take with grapefruit juice — it may increase side effects

  • Avoid pregnancy — both men and women should use effective birth control during and for 2 months after treatment

  • Store in original bottle with desiccant — away from moisture and heat

🧠 6. Stay Organized

  • Use a medication calendar or pillbox

  • Keep a side effect journal to track symptoms and report patterns