Prograf: Advanced Immunosuppression for Transplant Success
| Product dosage: 0.5mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 20 | $2.92 | $58.48 (0%) | 🛒 Add to cart |
| 30 | $2.81 | $87.72 $84.28 (4%) | 🛒 Add to cart |
| 60 | $2.58 | $175.44 $154.80 (12%) | 🛒 Add to cart |
| 90 | $2.32 | $263.16 $208.98 (21%) | 🛒 Add to cart |
| 120 | $2.15 | $350.88 $258.00 (26%) | 🛒 Add to cart |
| 180 | $1.98 | $526.32 $356.04 (32%) | 🛒 Add to cart |
| 270 | $1.81 | $789.48 $487.62 (38%) | 🛒 Add to cart |
| 360 | $1.72
Best per pill | $1052.64 $619.20 (41%) | 🛒 Add to cart |
| Product dosage: 1mg | |||
|---|---|---|---|
| Package (num) | Per pill | Price | Buy |
| 10 | $3.96 | $39.56 (0%) | 🛒 Add to cart |
| 20 | $3.14 | $79.12 $62.78 (21%) | 🛒 Add to cart |
| 30 | $2.84 | $118.68 $85.14 (28%) | 🛒 Add to cart |
| 60 | $2.62 | $237.36 $157.38 (34%) | 🛒 Add to cart |
| 90 | $2.49 | $356.04 $224.46 (37%) | 🛒 Add to cart |
| 120 | $2.41 | $474.72 $288.96 (39%) | 🛒 Add to cart |
| 180 | $2.24 | $712.08 $402.48 (43%) | 🛒 Add to cart |
| 270 | $2.06 | $1068.12 $557.28 (48%) | 🛒 Add to cart |
| 360 | $1.89
Best per pill | $1424.16 $681.12 (52%) | 🛒 Add to cart |
Synonyms | |||
Prograf (tacrolimus) is a cornerstone calcineurin inhibitor immunosuppressant medication, critically indicated for the prophylaxis of organ rejection in patients receiving allogeneic liver, kidney, or heart transplants. It is a macrolide lactone antibiotic that exerts its potent immunosuppressive effects by selectively inhibiting T-lymphocyte activation, a primary driver of the immune response against foreign graft tissue. By precisely modulating the immune system, Prograf facilitates the long-term acceptance of the transplanted organ, making it an essential component of post-transplant therapeutic regimens. Its use requires meticulous therapeutic drug monitoring and management by transplant specialists to balance efficacy with the risk of adverse effects.
Features
- Active Ingredient: Tacrolimus (as tacrolimus monohydrate).
- Available Formulations: Immediate-release capsules (0.5 mg, 1 mg, 5 mg), prolonged-release capsules, and injection for intravenous infusion.
- Mechanism of Action: Binds to the FKBP-12 protein, creating a complex that inhibits calcineurin phosphatase. This prevents the dephosphorylation and nuclear translocation of NFAT (Nuclear Factor of Activated T-cells), thereby blocking T-cell activation and the subsequent interleukin synthesis.
- High Potency: Exhibits immunosuppressive potency significantly greater than cyclosporine in vitro.
- Therapeutic Drug Monitoring (TDM) Required: Efficacy and toxicity are closely correlated with blood trough concentrations, necessitating frequent blood tests.
- Narrow Therapeutic Index: Small variations in dose or blood levels can lead to lack of efficacy or significant toxicity.
Benefits
- Superior Graft Survival: Demonstrated in clinical trials to contribute to improved short- and long-term survival rates of transplanted organs compared to older immunosuppressive regimens.
- Reduced Incidence of Acute Rejection: Provides potent and effective prophylaxis against acute cellular rejection episodes in the critical early post-transplant period.
- Flexible Dosing Formulations: Availability of both immediate and prolonged-release options allows for tailored treatment plans to improve adherence and patient convenience.
- Foundation for Combination Therapy: Effectively serves as the primary immunosuppressive agent in multi-drug regimens, often used alongside antimetabolites (e.g., mycophenolate) and corticosteroids, allowing for potential steroid sparing.
- Well-Established Safety Profile: Decades of clinical use have resulted in a deep understanding of its management, monitoring requirements, and adverse effect profile among transplant specialists.
Common use
Prograf is exclusively used in the field of transplant medicine. Its primary and approved indication is for the prophylaxis of organ rejection in patients receiving allogeneic transplants. It is most commonly prescribed for:
- Liver Transplantation: As a first-line immunosuppressant for both adult and pediatric patients.
- Kidney Transplantation: For the prevention of renal allograft rejection.
- Heart Transplantation: For the prevention of cardiac allograft rejection. Its use is initiated immediately post-transplant and is typically continued indefinitely for maintenance immunosuppression. It may also be used off-label in certain severe autoimmune conditions resistant to other therapies, though this is strictly under specialist supervision.
Dosage and direction
Dosing of Prograf is highly individualized and must be managed by a physician experienced in immunosuppressive therapy. It is never initiated without a precise dosing regimen based on patient-specific factors.
- Administration: Oral capsules should be taken consistently either with or without food, as food can affect bioavailability. The prolonged-release formulation must be taken on an empty stomach.
- Initial Dosing: For adult liver transplant patients, the initial oral dose is typically 0.10-0.15 mg/kg/day in two divided doses. Doses for kidney and heart transplant patients are often lower, usually 0.075-0.15 mg/kg/day in two divided doses.
- Pediatric Dosing: Pediatric patients often require higher doses than adults to achieve similar blood levels (e.g., 0.15-0.20 mg/kg/day for liver transplant).
- IV Administration: The intravenous formulation is reserved for patients unable to take oral medication and is dosed at approximately one-fifth of the oral dose, administered as a continuous 24-hour infusion.
- Titration: Dosage adjustments are made frequently based on regular monitoring of tacrolimus whole blood trough concentrations, clinical assessments of efficacy (e.g., organ function), and emerging adverse effects. The goal is to find the lowest effective dose.
Precautions
Extreme caution is mandatory with Prograf therapy due to its narrow therapeutic window and significant toxicities.
- Nephrotoxicity: Can cause dose-dependent and irreversible kidney damage. Renal function must be monitored closely.
- Neurotoxicity: Risk of severe neurotoxic events, including posterior reversible encephalopathy syndrome (PRES), tremor, headache, seizures, and altered mental status.
- Hyperglycemia: Can induce insulin-dependent post-transplant diabetes mellitus (PTDM), which may be irreversible. Blood glucose must be monitored.
- Hypertension: New-onset or worsening hypertension is common and requires active management.
- Hyperkalemia: Can elevate serum potassium levels; concomitant use of potassium-sparing diuretics or potassium supplements should be avoided.
- Malignancy Risk: Immunosuppression increases susceptibility to infections and the long-term risk of developing lymphoma and other malignancies, particularly skin cancer. Sun protection is critical.
- Pregnancy & Lactation: Category C. Use during pregnancy only if potential benefit justifies potential fetal risk. Tacrolimus is excreted in breast milk; a decision must be made to discontinue nursing or discontinue the drug.
Contraindications
Prograf is contraindicated in patients with:
- A known hypersensitivity to tacrolimus or any of the excipients in the formulation.
- A hypersensitivity to other macrolide antibiotics (due to potential cross-reactivity).
- Concomitant use with cyclosporine. Prograf should not be administered simultaneously with cyclosporine; cyclosporine must be discontinued at least 24 hours before initiating Prograf.
Possible side effect
A wide range of adverse effects is possible, many of which are dose-related.
- Very Common (>10%): Tremor, headache, diarrhea, nausea, hypertension, renal impairment, hyperglycemia, insomnia.
- Common (1-10%): Anemia, leukocytosis, thrombocytopenia, hyperkalemia, hypomagnesemia, anorexia, vomiting, abdominal pain, rash, pruritus, alopecia, photosensitivity, asthenia, fever, pain, peripheral edema.
- Uncommon (<1%): Hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, pancreatitis, hearing loss, cardiac arrhythmias, QT prolongation, torsades de pointes, pure red cell aplasia, anaphylactic reactions.
- Post-Marketing Reports: Posterior reversible encephalopathy syndrome (PRES), Stevens-Johnson syndrome, toxic epidermal necrolysis.
Drug interaction
Prograf is a major substrate of CYP3A4 and P-glycoprotein. Concomitant use with drugs that inhibit or induce these pathways can dramatically alter its blood concentration.
- Increased Tacrolimus Levels (Risk of Toxicity):
- Strong CYP3A4 Inhibitors: Ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin.
- Moderate/Weak Inhibitors: Fluconazole, erythromycin, diltiazem, verapamil, nicardipine, cimetidine, chloramphenicol.
- Others: Grapefruit juice, danazol, methylprednisolone (high dose), nefazodone.
- Decreased Tacrolimus Levels (Risk of Rejection):
- Strong CYP3A4 Inducers: Rifampin, rifabutin, phenytoin, phenobarbital, carbamazepine, St. John’s Wort.
- Additive Nephrotoxicity: Concomitant use with other nephrotoxic agents (e.g., aminoglycosides, amphotericin B, cisplatin, ganciclovir, NSAIDs) should be avoided.
- Additive Neurotoxicity: Caution with other neurotoxic drugs.
- Potassium: Avoid potassium-sparing diuretics and potassium supplements due to risk of hyperkalemia.
- Vaccines: Live vaccines are contraindicated during treatment.
Missed dose
- If a dose is missed, it should be taken as soon as it is remembered on the same day.
- If it is close to the time for the next dose, the missed dose should be skipped. The patient should never take a double dose to make up for the forgotten one.
- The prescribing physician or transplant coordinator should be informed of the missed dose, as it may necessitate a check of tacrolimus trough levels.
Overdose
Overdose with Prograf is a medical emergency due to the high risk of severe nephrotoxicity, neurotoxicity, hyperkalemia, and QT prolongation.
- Symptoms: Exaggerated adverse reactions, including severe renal impairment, tremor, headache, nausea, vomiting, infections, lethargy, seizures, and cardiac arrhythmias.
- Management: There is no specific antidote. Treatment is supportive and symptomatic. Immediate gastric lavage may be considered if ingestion was recent. Management focuses on maintaining electrolyte balance, supporting renal function, and managing neurological and cardiac symptoms. Hemodialysis is not effective in removing tacrolimus from the blood due to its high protein binding and extensive distribution in erythrocytes. Charcoal hemoperfusion may be considered in severe cases.
Storage
- Store at room temperature between 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F and 86°F).
- Keep in the original container to protect from moisture and light.
- Keep out of reach of children and pets.
Disclaimer
This information is for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content has been compiled from various resources but may not be exhaustive or fully updated. Dosing and usage must be determined solely by a qualified healthcare professional.
Reviews
- Transplant Hepatologist, 15 years experience: “Prograf remains the gold standard in our liver transplant immunosuppression protocols. Its potency is unmatched, but it demands respect. Our entire team is built around meticulous TDM to harness its benefits while mitigating risks. The introduction of prolonged-release formulations has been a game-changer for adherence.”
- Renal Transplant Pharmacist: “Managing a patient on tacrolimus is a dynamic process. The number of drug interactions is staggering, and we spend significant time counseling patients on what to avoid. However, its efficacy in preventing acute rejection in kidney transplants is well worth the intensive management it requires.”
- Heart Transplant Recipient, 5 years post-op: “It’s a love-hate relationship. I know this medication is keeping me alive, but the tremors and the constant blood draws are a reminder. My team is excellent at adjusting the dose to keep side effects manageable. You learn to live with it for the gift you’ve been given.”
- Clinical Researcher: “The data from long-term registries continues to show the superior graft survival associated with tacrolimus-based regimens compared to previous standards of care. Ongoing research focuses on protocols to minimize long-term nephrotoxicity while maintaining efficacy.”