ADVAGRAF 5mg Capsules (Hard Gelatin)/Prolonged Release

What is ADVAGRAF 5mg

ADVAGRAF 5mg is a prolonged-release oral capsule containing tacrolimus, a potent immunosuppressant drug. It is prescribed primarily to prevent organ rejection in patients who have undergone solid organ transplantation, such as kidney, liver, or heart transplants.

The prolonged-release formulation enables once-daily dosing, providing a steady and controlled release of tacrolimus into the bloodstream. This consistent delivery helps maintain therapeutic drug levels, improving transplant outcomes and patient compliance by simplifying the medication regimen.

• Active Ingredient: Tacrolimus
• Dosage Form: Hard gelatin capsule, prolonged-release
• Strength: 5 mg per capsule
• Packaging: 100 capsules (2 pouches of 50 capsules, blister-packed)
• Therapeutic Class: Calcineurin inhibitor immunosuppressant
• Indications: Prevention of rejection in kidney, liver, and heart transplantation

How to use ADVAGRAF 5mg

Proper administration of ADVAGRAF 5mg is critical for optimal efficacy and safety:

• Dosage Schedule: Taken once daily at the same time every day to maintain steady blood levels.
• Administration: Swallow capsules whole with water. Do not crush, chew, or open the capsules to preserve the prolonged-release properties.
• Food Intake: Can be taken with or without food, but it is important to maintain consistency in relation to meals to avoid fluctuations in drug absorption.
• Monitoring: Regular blood level monitoring is essential to adjust doses and minimize toxicity or risk of rejection.
• Missed Dose: If a dose is missed, take it as soon as possible unless it is close to the time for the next dose. Do not double the dose.
• Do Not Stop Abruptly: Discontinuing the drug suddenly may lead to transplant rejection; always consult a healthcare professional before changing the dose or stopping.
• Inform Healthcare Provider: Always inform your doctor of all medications, supplements, and changes in health status.

Mode of Action ADVAGRAF 5mg

ADVAGRAF contains tacrolimus, which works by suppressing the immune response that causes organ rejection:

• Intracellular Binding: Tacrolimus binds to a protein called FKBP-12 inside T-lymphocytes.
• Calcineurin Inhibition: The tacrolimus-FKBP-12 complex inhibits calcineurin, an enzyme essential for activating T-cells.
• Suppression of Cytokines: This inhibition prevents the transcription of interleukin-2 (IL-2) and other cytokines that promote T-cell activation and proliferation.
• Reduced Immune Response: By inhibiting T-cell activation, tacrolimus lowers the body's immune response to the transplanted organ, preventing rejection.
• Selective Action: Tacrolimus primarily targets T-cell mediated immunity, reducing overall immune activity with a focused effect on preventing organ rejection.

ADVAGRAF 5mg Interactions ADVAGRAF 5mg

Tacrolimus is metabolized by the CYP3A4 enzyme and P-glycoprotein transport system, making it susceptible to numerous drug interactions:

• CYP3A4 Inhibitors: Drugs like ketoconazole, erythromycin, clarithromycin, fluconazole, and protease inhibitors can raise tacrolimus blood levels, increasing toxicity risk.
• CYP3A4 Inducers: Rifampicin, carbamazepine, phenytoin, and St. John's Wort can reduce tacrolimus levels, potentially leading to transplant rejection.
• Nephrotoxic Agents: Use caution with NSAIDs, aminoglycosides, and amphotericin B as they may exacerbate kidney damage.
• Calcium Channel Blockers: Verapamil and diltiazem may increase tacrolimus levels.
• Grapefruit Juice: Can increase tacrolimus blood concentrations by inhibiting CYP3A4; should be avoided.
• Other Immunosuppressants: Often co-administered but require careful dose adjustments and monitoring to avoid additive adverse effects.

Always consult a healthcare provider before starting or stopping any medication while on ADVAGRAF.

Dosage of ADVAGRAF 5mg

The dosing of ADVAGRAF 5mg is individualized based on patient weight, transplant type, and therapeutic drug monitoring:

• Initial Dose: Generally 0.1-0.2 mg/kg body weight once daily, started within 12 to 24 hours post-transplantation.
• Maintenance Dose: Adjusted according to blood tacrolimus trough levels, with typical target ranges of 5-15 ng/mL depending on transplant type and time since surgery.
• Therapeutic Drug Monitoring: Essential to prevent toxicity and rejection by frequent blood level checks, especially during dose adjustments.
• Special Populations: Dose modifications may be necessary in elderly patients, those with hepatic impairment, or concomitant medications affecting metabolism.
• Missed Dose: Take as soon as possible, but do not double doses to compensate.

Possible side effects of ADVAGRAF 5mg

Like all immunosuppressants, ADVAGRAF can cause a range of side effects, from mild to serious:

• Nephrotoxicity: Kidney dysfunction or damage is a common and serious adverse effect requiring monitoring.
• Neurotoxicity: Tremors, headaches, insomnia, dizziness, and in severe cases, seizures.
• Infections: Increased susceptibility to bacterial, viral, and fungal infections due to immune suppression.
• Hypertension: Elevated blood pressure is frequently observed.
• Metabolic Changes: Hyperglycemia, new-onset diabetes, hyperkalemia, and hypomagnesemia may occur.
• Gastrointestinal Symptoms: Nausea, vomiting, diarrhea, and abdominal discomfort.
• Other Effects: Alopecia, fatigue, rash, electrolyte imbalances.
• Severe Reactions: Rarely, serious allergic reactions or neurologic complications may develop and require immediate medical attention.

ADVAGRAF 5mg Contraindications ADVAGRAF 5mg

ADVAGRAF should not be used or used with caution in the following cases:

• Known Hypersensitivity: Allergy to tacrolimus or any capsule component.
• Active Serious Infections: Immunosuppressive therapy may worsen infections.
• Live Vaccines: Contraindicated as immune response may be insufficient and risk of infection is higher.
• Pregnancy and Lactation: Use only if benefits justify risks; tacrolimus crosses the placenta and is excreted in breast milk.
• Severe Hepatic Impairment: Use cautiously with dose adjustments due to altered metabolism.

Storage of ADVAGRAF 5mg

Proper storage of ADVAGRAF ensures medication efficacy and safety:

• Temperature: Store at controlled room temperature between 20°C and 25°C (68°F to 77°F).
• Packaging: Keep capsules in original blister packs to protect from moisture and light exposure.
• Keep Out of Reach: Store in a safe place, away from children and pets.
• Avoid Extremes: Do not freeze or expose to excessive heat or humidity.
• Expiry Date: Do not use after the expiration date printed on the packaging.