Acireg(Regorafenib)20Mg Cap 14’s-Potential Overview

Generic Information

• Brand Name: Acireg Cap
• Generic Name: Regorafenib
• Strength: 20 mg per capsule
• Pack Size: 14 capsules
• Pharmaceutical Class:
  • Class: Kinase Inhibitor
  • Type: Oral Cancer Therapy

Indications for Use

Acireg (Regorafenib) is used for the treatment of:

1. Metastatic Colorectal Cancer (CRC):
   • For patients with metastatic colorectal cancer who have failed prior therapies.
2. Gastrointestinal Stromal Tumors (GIST):
   • For patients with GIST after failure of prior treatment with imatinib and sunitinib.
3. Hepatocellular Carcinoma (HCC):
   • For patients with hepatocellular carcinoma who have been previously treated with sorafenib.
4. Other Tumor Types:
   • Regorafenib is also under investigation for other malignancies, including metastatic pancreatic cancer, and renal cell carcinoma.

Common Side Effects

• Gastrointestinal:
  • Diarrhea, nausea, vomiting, anorexia, abdominal pain, mouth sores.
• Skin and Hair:
  • Rash, dry skin, hair color changes, hand-foot skin reaction (redness, swelling, pain on palms/soles).
• General:
  • Fatigue, headache, weakness.
• Blood Pressure:
  • Hypertension (increased blood pressure).

Serious Side Effects (Less Common)

• Liver Toxicity:
  • Hepatotoxicity, liver failure, jaundice.
• Bleeding and Clotting:
  • Hemorrhage, including gastrointestinal bleeding, rectal bleeding, and severe nosebleeds.
• Cardiovascular:
  • Cardiac ischemia, heart attack, and arterial thromboembolism.
• Neurotoxicity:
  • Seizures, confusion, and mood changes.
• Kidney Dysfunction:
  • Renal failure or deterioration of renal function.

Dosage and Usage Instructions

1. Recommended Dosage:
   • Metastatic Colorectal Cancer (CRC):
     • 160 mg once daily for 21 days in a 28-day cycle.
   • Gastrointestinal Stromal Tumors (GIST):
     • 160 mg once daily for 21 days in a 28-day cycle.
   • Hepatocellular Carcinoma (HCC):
     • 120 mg once daily for 21 days in a 28-day cycle.
2. Administration Instructions:
   • Take Acireg capsules once daily, preferably at the same time each day.
   • Swallow the capsules whole with a glass of water.
   • Food: Can be taken with or without food, but taking with food may help reduce gastrointestinal side effects.
   • Missed Dose: If a dose is missed, skip the missed dose and take the next dose at the usual time. Do not take two doses to make up for a missed dose.

Drug Interactions

1. With Food:
   • No specific food restrictions. However, taking it with food may help reduce gastrointestinal side effects such as nausea or vomiting.
2. With Other Medications:
   • CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole): Can increase Regorafenib levels.
   • CYP3A4 Inducers (e.g., Rifampin, Phenytoin): May decrease Regorafenib levels.
   • Anticoagulants (e.g., Warfarin): Increased risk of bleeding. Monitor INR closely.
   • Tyrosine Kinase Inhibitors (e.g., Sorafenib, Sunitinib): Combining with other kinase inhibitors may increase the risk of side effects.
   • Antiplatelet Agents (e.g., Aspirin, Clopidogrel): Increased risk of bleeding.
   • Drugs that affect Blood Pressure (e.g., ACE inhibitors, beta-blockers): Monitor blood pressure closely, as regorafenib may increase blood pressure.
3. Other Interactions:
   • Grapefruit Juice: Grapefruit juice may increase the concentration of regorafenib in the blood. Avoid or limit grapefruit products.

Regulatory Approval and Manufacturer

• Regulatory Approval:
  • Acireg (Regorafenib) has been approved by the U.S. FDA and European Medicines Agency (EMA) for the treatment of colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma.
• Manufacturer:
  • Acireg is manufactured by Bayer Pharmaceuticals (known for Regorafenib under the brand name Stivarga in several regions).

Pharmacist-Related Data

Drug Name and Chemical Details

• Generic Name: Regorafenib
• Chemical Formula: C21H15ClF4N4O3S
• CAS Number: 755038-03-7
• Molecular Weight: 474.9 g/mol

Pharmacodynamics

1. Mechanism of Action:
   • Regorafenib is an oral multikinase inhibitor that targets several protein kinases involved in tumor cell growth, angiogenesis (formation of new blood vessels), and metastasis. It inhibits the activity of kinases such as VEGFR (vascular endothelial growth factor receptor), PDGFR (platelet-derived growth factor receptor), and FGFR (fibroblast growth factor receptor). This action disrupts the tumor’s blood supply and inhibits cancer cell proliferation, helping to slow down the growth of the tumor.
2. Therapeutic Effects:
   • Anticancer Effect: Regorafenib helps in the treatment of various cancers by inhibiting pathways responsible for tumor growth and metastasis. It is particularly useful in advanced or metastatic colorectal cancer, gastrointestinal stromal tumors, and hepatocellular carcinoma.

Pharmacokinetics

1. Absorption:
   • Regorafenib is well absorbed after oral administration. The absolute bioavailability is about 60%. Peak plasma concentrations are reached within 4 hours after dosing.
2. Distribution:
   • Regorafenib is widely distributed in the body and has a high protein-binding rate (approximately 99%). It is distributed into tissues including the liver, lungs, and kidneys.
3. Metabolism:
   • Regorafenib is primarily metabolized by the liver through cytochrome P450 enzymes, mainly CYP3A4. The drug undergoes extensive metabolism, producing both active and inactive metabolites.
4. Excretion:
   • The drug and its metabolites are excreted mainly via the feces (approximately 70%) and to a lesser extent through urine.
5. Half-Life:
   • The elimination half-life of regorafenib is approximately 28 hours, supporting once-daily dosing.

Drug Interactions

1. With Food:
   • Regorafenib can be taken with or without food, though taking with food may help reduce gastrointestinal side effects like nausea.
2. With Other Medications:
   • CYP3A4 Inhibitors (e.g., Ketoconazole): Can increase Regorafenib levels.
   • CYP3A4 Inducers (e.g., Rifampin): May decrease Regorafenib levels.
   • Anticoagulants (e.g., Warfarin): Increased risk of bleeding. Monitor INR closely.
   • Tyrosine Kinase Inhibitors (e.g., Sorafenib): May increase side effects.
   • Antiplatelet Drugs: Increased risk of bleeding.
3. Other Interactions:
   • Grapefruit Juice: Grapefruit may increase Regorafenib levels, so avoid or limit consumption.

Clinical Considerations

1. Pregnancy Category:
   • Category D (FDA): Regorafenib should be avoided during pregnancy due to the potential for harm to the fetus. Women of childbearing potential should use effective contraception during treatment.
2. Lactation:
   • It is not known whether Regorafenib is excreted in breast milk. Due to the potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment.
3. Pediatric Use:
   • Safety and efficacy have not been established in pediatric patients, and regorafenib is not recommended for use in children.
4. Geriatric Use:
   • No specific dosage adjustments are recommended for elderly patients, but caution is advised, especially with regard to managing side effects such as hypertension and bleeding risks.
5. Other Considerations:
   • Hepatic Impairment: Regorafenib should be used with caution in patients with moderate or severe hepatic impairment (e.g., cirrhosis). Dose adjustment may be required.
   • Cardiovascular Risk: Monitor for signs of ischemia, bleeding, and hypertension. Regular blood pressure monitoring is essential during treatment.