ADVAGRAF 0.5mg Capsules (Hard Gelatin)/Prolonged Release

What is ADVAGRAF 0.5mg

ADVAGRAF 0.5mg is a prolonged-release oral capsule containing tacrolimus as its active ingredient. Tacrolimus is an immunosuppressant medication primarily prescribed to prevent organ rejection in patients who have undergone kidney, liver, or heart transplantation. By modulating the immune system, it reduces the risk that the body will reject the transplanted organ.

The prolonged-release formulation ensures a gradual release of the drug, allowing once-daily dosing and more stable blood levels. This improves patient adherence and reduces fluctuations in drug concentration, which can help minimize side effects and maintain therapeutic efficacy.

• Active Ingredient: Tacrolimus
• Dosage Form: Hard gelatin capsules, prolonged-release
• Strength: 0.5 mg per capsule
• Packaging: 100 capsules per package (two pouches of 50 capsules each, in blister packs)
• Therapeutic Use: Prevention of transplant rejection (kidney, liver, heart)
• Drug Class: Calcineurin inhibitor immunosuppressant

How to use ADVAGRAF 0.5mg

ADVAGRAF 0.5mg should be taken exactly as prescribed by your transplant specialist or healthcare provider. Proper usage is critical to prevent transplant rejection and reduce the risk of side effects.

• Administration: Take the capsules orally once daily, preferably at the same time each day to maintain consistent blood levels.
• Swallow whole: Do not crush, chew, or open the capsules as this can alter the drug release and absorption.
• Food interaction: The capsules can be taken with or without food, but high-fat meals may affect absorption; try to maintain a consistent diet.
• Monitoring: Regular blood tests are essential to monitor tacrolimus levels and adjust dosage to keep drug levels within the therapeutic range and avoid toxicity.
• Missed dose: If you miss a dose, take it as soon as you remember unless it is close to the next dose. Do not double dose to make up for a missed one.
• Avoid abrupt discontinuation: Stopping tacrolimus suddenly can lead to transplant rejection; always consult your healthcare provider before making any changes.

Mode of Action ADVAGRAF 0.5mg

Tacrolimus, the active substance in ADVAGRAF, works by suppressing the immune system through inhibition of calcineurin, a critical enzyme in T-cell activation. Here's how it works:

• Calcineurin inhibition: Tacrolimus binds to an intracellular protein called FK-binding protein (FKBP-12) to form a complex.
• Block T-cell activation: This complex inhibits calcineurin phosphatase activity, which is essential for the activation of nuclear factor of activated T-cells (NF-AT).
• Reduced cytokine production: Without NF-AT activation, T-cells cannot produce interleukin-2 (IL-2) and other cytokines vital for T-cell proliferation and immune response.
• Immunosuppression: The result is a suppression of cell-mediated immune responses, which lowers the risk of the immune system attacking the transplanted organ.
• Selective action: Tacrolimus selectively targets T-lymphocytes, preserving other immune functions to some degree compared to broader immunosuppressants.

ADVAGRAF 0.5mg Interactions ADVAGRAF 0.5mg

Tacrolimus has several clinically significant drug interactions that may affect its blood levels or increase the risk of adverse effects. Some notable interactions include:

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, clarithromycin): These drugs can increase tacrolimus blood levels, raising the risk of toxicity such as nephrotoxicity and neurotoxicity.
• CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin): These may decrease tacrolimus levels, potentially leading to transplant rejection due to inadequate immunosuppression.
• Nephrotoxic agents (e.g., NSAIDs, amphotericin B): Concurrent use can enhance the risk of kidney damage.
• Calcium channel blockers (e.g., diltiazem, verapamil): May increase tacrolimus blood concentrations.
• Grapefruit juice: Can inhibit CYP3A4 enzymes and increase tacrolimus blood levels; should be avoided.
• Other immunosuppressants: Combination with drugs like corticosteroids or mycophenolate mofetil is common but requires close monitoring.

Inform your healthcare provider about all medications and supplements to manage potential interactions effectively.

Dosage of ADVAGRAF 0.5mg

The dosage of ADVAGRAF 0.5mg is individualized based on the type of transplant, patient weight, kidney and liver function, and blood tacrolimus levels. General dosing considerations include:

• Initial dose: Typically ranges from 0.1 to 0.2 mg/kg/day taken once daily, usually starting 12-24 hours after transplantation.
• Maintenance dose: Adjusted according to therapeutic drug monitoring to maintain trough blood levels within the target range.
• Therapeutic blood levels: Usually between 5–15 ng/mL, but targets vary by transplant type and time post-transplant.
• Renal or hepatic impairment: Dose adjustment may be necessary, guided by blood level monitoring.
• Special populations: Pediatric and elderly patients may require dose adjustments due to differences in metabolism.

Possible side effects of ADVAGRAF 0.5mg

While ADVAGRAF effectively prevents organ rejection, it can cause a range of side effects, some of which can be serious. Common and notable side effects include:

• Nephrotoxicity: Kidney damage is a common adverse effect requiring close monitoring of kidney function.
• Neurotoxicity: Symptoms may include tremors, headache, insomnia, seizures, and rarely encephalopathy.
• Infections: Due to immunosuppression, patients are at higher risk of bacterial, viral, and fungal infections.
• Hypertension: High blood pressure can develop during therapy.
• Gastrointestinal disturbances: Nausea, diarrhea, abdominal pain, and constipation.
• Hyperglycemia and diabetes mellitus: Tacrolimus can impair glucose tolerance.
• Electrolyte imbalances: Such as hyperkalemia and hypomagnesemia.
• Others: Hair loss, rash, and malaise.

Immediate medical attention is required if you experience signs of allergic reactions, severe infection, or neurological symptoms.

ADVAGRAF 0.5mg Contraindications ADVAGRAF 0.5mg

ADVAGRAF 0.5mg should not be used in patients with the following conditions or history:

• Known hypersensitivity: Allergy to tacrolimus or any component of the formulation.
• Uncontrolled infections: Active serious infections may worsen due to immunosuppression.
• Severe hepatic impairment: Use with caution as metabolism is primarily hepatic.
• Live vaccines: Contraindicated during tacrolimus therapy due to immunosuppression.
• Pregnancy and breastfeeding: Should be used only if clearly needed and under strict medical supervision due to potential risks.

Storage of ADVAGRAF 0.5mg

Proper storage of ADVAGRAF 0.5mg is essential to maintain its stability and effectiveness:

• Temperature: Store capsules at controlled room temperature between 20°C and 25°C (68°F to 77°F).
• Protection: Keep the capsules in their original blister packaging to protect from moisture and light.
• Keep out of reach of children: To prevent accidental ingestion.
• Do not freeze: Avoid storing in very cold conditions or freezing.
• Expiry: Do not use the medication beyond the expiration date printed on the packaging.