ADVAGRAF 1mg Capsules (Hard Gelatin)/Prolonged Release

What is ADVAGRAF 1mg

ADVAGRAF 1mg is a prolonged-release oral capsule containing tacrolimus as the active ingredient. Tacrolimus belongs to the class of immunosuppressants used primarily to prevent organ rejection in patients who have undergone transplantation, including kidney, liver, or heart transplants.

The prolonged-release formulation allows for once-daily dosing, providing a more consistent and steady blood concentration of tacrolimus compared to immediate-release forms. This steady drug level helps reduce fluctuations that might otherwise increase the risk of rejection or toxicity, thereby improving patient compliance and outcomes.

• Active Ingredient: Tacrolimus
• Dosage Form: Hard gelatin capsules, prolonged-release
• Strength: 1 mg per capsule
• Packaging: 100 capsules per pack (two pouches of 50 capsules each, blister-packed)
• Indications: Prevention of rejection in kidney, liver, and heart transplant recipients
• Drug Class: Calcineurin inhibitor immunosuppressant

How to use ADVAGRAF 1mg

Using ADVAGRAF 1mg correctly is essential to maintain effective immunosuppression while minimizing risks:

• Dosage: Take the capsules once daily, ideally at the same time every day to maintain steady blood levels.
• Swallow whole: Do not crush, chew, or open the capsules, as this will disrupt the prolonged-release mechanism.
• Food: Capsules can be taken with or without food, but consistency in diet is recommended because food can influence tacrolimus absorption.
• Monitoring: Regular blood tests to monitor tacrolimus trough levels are critical to adjust dosing and avoid toxicity or under-immunosuppression.
• Missed dose: If you miss a dose, take it as soon as you remember unless it is close to the next scheduled dose. Do not double doses.
• Do not stop abruptly: Sudden discontinuation can lead to transplant rejection; any changes must be under medical supervision.
• Inform your healthcare provider: About all other medications, supplements, or herbal products you use to avoid interactions.

Mode of Action ADVAGRAF 1mg

Tacrolimus exerts its immunosuppressive effect by selectively inhibiting T-cell activation. The detailed mechanism is:

• Binding: Tacrolimus binds to an intracellular protein called FK-binding protein (FKBP-12).
• Inhibition: The tacrolimus-FKBP-12 complex inhibits calcineurin phosphatase, a key enzyme in the activation pathway of T-cells.
• Reduced cytokine production: By blocking calcineurin, tacrolimus prevents activation of nuclear factor of activated T-cells (NF-AT), which is essential for producing interleukin-2 (IL-2) and other cytokines.
• Immune suppression: This leads to reduced T-cell proliferation and function, thereby dampening the immune response that could attack the transplanted organ.
• Selective action: Tacrolimus primarily affects T-lymphocytes, which are central to cell-mediated immunity.

ADVAGRAF 1mg Interactions ADVAGRAF 1mg

ADVAGRAF interacts with many drugs that can affect its metabolism or enhance adverse effects. Key interactions include:

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, clarithromycin, fluconazole): These can increase tacrolimus blood concentrations, raising the risk of nephrotoxicity and neurotoxicity.
• CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin, St. John’s Wort): These may reduce tacrolimus levels, increasing the risk of organ rejection.
• Nephrotoxic drugs (e.g., NSAIDs, amphotericin B, aminoglycosides): Combination may exacerbate kidney damage.
• Calcium channel blockers (e.g., diltiazem, verapamil): May increase tacrolimus levels.
• Grapefruit juice: Strong CYP3A4 inhibitor; can significantly increase blood levels of tacrolimus and should be avoided.
• Other immunosuppressants: Often given in combination but require careful monitoring to balance efficacy and toxicity.

Always inform your healthcare provider about all medications and supplements you take to manage these interactions properly.

Dosage of ADVAGRAF 1mg

Dosage must be individualized based on the type of transplant, patient weight, and blood tacrolimus levels. General dosage guidance:

• Initial dose: Typically 0.1–0.2 mg/kg/day administered once daily, beginning 12 to 24 hours post-transplantation.
• Maintenance dose: Adjusted according to blood trough levels, which typically target 5-15 ng/mL depending on time since transplant and transplant type.
• Therapeutic drug monitoring: Essential to tailor dosing and avoid toxicity or under-dosing.
• Special populations: Dose adjustments may be necessary in patients with hepatic or renal impairment, pediatric, or elderly patients.
• Missed doses: Should be taken as soon as possible but never double the dose.

Possible side effects of ADVAGRAF 1mg

Common and serious side effects of tacrolimus include:

• Nephrotoxicity: Most significant side effect, requiring frequent kidney function monitoring.
• Neurotoxicity: Manifested as tremors, headaches, seizures, insomnia, or rarely encephalopathy.
• Infections: Increased susceptibility due to immunosuppression, including bacterial, viral, and fungal infections.
• Hypertension: Elevated blood pressure is common during treatment.
• Gastrointestinal symptoms: Such as nausea, diarrhea, abdominal pain.
• Metabolic disturbances: Hyperglycemia, new-onset diabetes mellitus, hyperkalemia, hypomagnesemia.
• Other effects: Hair thinning or loss, rash, malaise, and electrolyte imbalances.
• Serious reactions: Signs of allergic reactions, severe infections, or neurological symptoms warrant immediate medical attention.

ADVAGRAF 1mg Contraindications ADVAGRAF 1mg

ADVAGRAF should not be used in:

• Known hypersensitivity: To tacrolimus or any component of the capsule.
• Active severe infections: As the immunosuppressive effect can worsen infections.
• Use with caution in severe hepatic impairment: Tacrolimus metabolism is hepatic, and impaired function may increase toxicity risk.
• Live vaccines: Contraindicated due to immunosuppression.
• Pregnancy and breastfeeding: Use only if clearly needed and under strict medical supervision due to potential fetal risks.

Storage of ADVAGRAF 1mg

Proper storage ensures the medication maintains efficacy and safety:

• Temperature: Store at controlled room temperature between 20°C and 25°C (68°F to 77°F).
• Protection: Keep capsules in original blister packs to protect from moisture and light exposure.
• Keep out of reach: Store away from children and pets.
• Do not freeze: Avoid extreme temperatures.
• Expiry: Do not use after the expiration date printed on the packaging.