ADVAGRAF 3mg Capsules (Hard Gelatin)/Prolonged Release

What is ADVAGRAF 3mg

ADVAGRAF 3mg is a prolonged-release oral capsule formulation containing tacrolimus, an immunosuppressant drug. It is primarily prescribed to prevent organ rejection in patients who have undergone solid organ transplantation, including kidney, liver, or heart transplants.

ADVAGRAF’s prolonged-release design allows for once-daily administration, providing a consistent and steady blood concentration of tacrolimus. This steadiness enhances patient adherence by simplifying the dosing schedule and helps maintain optimal immunosuppressive levels to protect the transplanted organ from immune system attacks.

• Active ingredient: Tacrolimus
• Dosage form: Hard gelatin capsule, prolonged-release
• Strength: 3 mg per capsule
• Packaging: 100 capsules (2 pouches of 50 capsules each, blister packed)
• Therapeutic class: Calcineurin inhibitor immunosuppressant
• Indications: Prevention of rejection in kidney, liver, and heart transplantation

How to use ADVAGRAF 3mg

Correct usage of ADVAGRAF 3mg is essential to ensure effective immunosuppression while minimizing adverse effects:

• Dosage schedule: Taken once daily, preferably at the same time each day to maintain steady blood levels.
• Swallow whole: Capsules should be swallowed intact; do not crush, chew, or open them as this will disrupt the prolonged-release mechanism.
• Food considerations: It can be taken with or without food. However, consistency is important, since food intake can affect absorption.
• Monitoring: Regular blood tests are necessary to monitor tacrolimus trough levels and adjust the dose accordingly.
• Missed dose: If a dose is missed, take it as soon as possible unless it is close to the next dose. Do not double the dose.
• Do not stop abruptly: Stopping tacrolimus suddenly can lead to transplant rejection; any changes must be made under medical supervision.
• Inform healthcare provider: Always inform your doctor about all medications and supplements you are taking.

Mode of Action ADVAGRAF 3mg

Tacrolimus, the active ingredient in ADVAGRAF, suppresses the immune system by specifically targeting T-lymphocytes, which play a central role in organ rejection:

• Intracellular binding: Tacrolimus binds to FK-binding protein 12 (FKBP-12) inside T-cells.
• Calcineurin inhibition: The tacrolimus-FKBP-12 complex inhibits calcineurin, an enzyme critical for activating nuclear factor of activated T-cells (NF-AT).
• Prevention of cytokine production: This inhibition blocks transcription of interleukin-2 (IL-2) and other cytokines necessary for T-cell activation and proliferation.
• Immunosuppression: The net effect is reduced T-cell response and prevention of immune-mediated attack on the transplanted organ.
• Selective mechanism: Tacrolimus targets cell-mediated immunity while sparing other immune functions to some extent.

ADVAGRAF 3mg Interactions ADVAGRAF 3mg

ADVAGRAF has significant interactions with many medications, primarily due to its metabolism via the CYP3A4 enzyme system:

• CYP3A4 inhibitors: Drugs such as ketoconazole, erythromycin, clarithromycin, fluconazole, and protease inhibitors can increase tacrolimus blood levels, increasing toxicity risk.
• CYP3A4 inducers: Rifampicin, carbamazepine, phenytoin, St. John's Wort can lower tacrolimus levels, risking transplant rejection.
• Nephrotoxic agents: Concurrent use with NSAIDs, amphotericin B, aminoglycosides may exacerbate kidney damage.
• Calcium channel blockers: Verapamil and diltiazem can increase tacrolimus levels.
• Grapefruit juice: Inhibits CYP3A4 and may elevate tacrolimus levels; consumption should be avoided.
• Other immunosuppressants: Often co-administered, requiring careful dose adjustment and monitoring to avoid additive toxicity.

Patients should always disclose their full medication list to their healthcare provider to manage interactions properly.

Dosage of ADVAGRAF 3mg

Dosage of ADVAGRAF 3mg must be individualized and carefully monitored:

• Initial dosing: Usually starts at 0.1-0.2 mg/kg body weight once daily, initiated within 12 to 24 hours after transplantation.
• Maintenance dose: Adjusted based on blood trough levels, aiming for 5-15 ng/mL depending on time post-transplant and type of organ transplanted.
• Therapeutic drug monitoring: Essential to tailor dosing, minimize toxicity, and prevent under-immunosuppression.
• Special populations: Dose adjustments may be required for patients with hepatic or renal impairment, elderly patients, or pediatrics.
• Missed dose: Take as soon as remembered unless it is almost time for the next dose; never double dose.

Possible side effects of ADVAGRAF 3mg

p>ADVAGRAF has a range of potential side effects, which require close monitoring:

• Nephrotoxicity: Most common and serious; may manifest as elevated serum creatinine or reduced kidney function.
• Neurotoxicity: Tremors, headaches, insomnia, dizziness, seizures in severe cases.
• Increased infection risk: Due to immunosuppression, patients may develop bacterial, viral, or fungal infections.
• Hypertension: High blood pressure is frequently reported.
• Metabolic disturbances: Hyperglycemia, new-onset diabetes, hyperkalemia, hypomagnesemia.
• Gastrointestinal effects: Nausea, diarrhea, abdominal discomfort.
• Other: Alopecia, rash, fatigue, electrolyte imbalances.
• Serious adverse events: Allergic reactions, severe infections, and neurologic complications require urgent medical attention.

ADVAGRAF 3mg Contraindications ADVAGRAF 3mg

ADVAGRAF should be avoided or used with extreme caution in the following situations:

• Hypersensitivity: Known allergy to tacrolimus or any capsule components.
• Active infections: Severe infections are contraindications due to immunosuppressive effects.
• Live vaccines: Contraindicated because of impaired immune response.
• Pregnancy and breastfeeding: Use only if benefits outweigh risks, as tacrolimus may harm the fetus or infant.
• Severe hepatic impairment: Dose adjustments needed; caution required due to altered metabolism.

Storage of ADVAGRAF 3mg

Proper storage conditions ensure medication stability and safety:

• Temperature: Store at controlled room temperature (20°C to 25°C or 68°F to 77°F).
• Packaging: Keep capsules in original blister packs to protect from moisture and light.
• Keep out of reach: Store away from children and pets.
• Avoid extreme conditions: Do not freeze or expose to excessive heat.
• Expiry date: Do not use after the printed expiry date.