What are the dosage recommendations and monitoring requirements for a patient taking PROGRAF (tacrolimus) 1 MG capsules?

Tacrolimus (PROGRAF) 1 MG Capsule Dosage and Monitoring Guidelines

The recommended dosage for tacrolimus (PROGRAF) 1 MG capsules is 0.075 mg/kg/day adjusted to achieve target whole-blood trough levels between 5-10 ng/mL, with some experts recommending a maximum trough level of 6 ng/mL to minimize toxicity while maintaining efficacy. 1

Dosage Recommendations

Initial Dosing

• For kidney transplant patients:
  • With azathioprine: 0.2 mg/kg/day divided in two doses, administered every 12 hours 2
  • With MMF/IL-2 receptor antagonist: 0.1 mg/kg/day divided in two doses, administered every 12 hours 2
• For liver transplant patients: 0.10 to 0.15 mg/kg/day divided in two doses, administered every 12 hours 2
• For heart transplant patients: 0.075 mg/kg/day divided in two doses, administered every 12 hours 2
• For patients with interstitial lung disease in systemic autoimmune rheumatic diseases: 0.075 mg/kg/day adjusted for target whole-blood trough levels between 5-10 ng/mL 1

Dosage Adjustments

• African-American patients typically require higher doses compared to Caucasian patients to achieve comparable trough concentrations 2
• Patients with renal impairment should be dosed at the lower end of the therapeutic range 2
• Patients with hepatic impairment may require lower doses due to reduced clearance and prolonged half-life 2

Target Therapeutic Levels

Transplant Patients

• Kidney transplant patients:
  • Month 1-3: 7-20 ng/mL (with azathioprine) or 4-11 ng/mL (with MMF) 2
  • Month 4-12: 5-15 ng/mL (with azathioprine) or 4-11 ng/mL (with MMF) 2
• Liver transplant patients: 5-20 ng/mL (month 1-12) 2
• Heart transplant patients:
  • Month 1-3: 10-20 ng/mL 2
  • Month ≥4: 5-15 ng/mL 2

Autoimmune Disease Patients

• For interstitial lung disease in systemic autoimmune rheumatic diseases: 5-10 ng/mL, with some experts using a maximum of 6 ng/mL 1

Monitoring Requirements

Laboratory Monitoring

• Trough tacrolimus levels:
  • 1-2 times per week for the first month 1
  • Monthly for 3 months 1
  • Every 2-3 months thereafter 1
• Comprehensive metabolic panel (CMP):
  • Same frequency as trough levels 1
• Magnesium and phosphorus:
  • Same frequency as trough levels 1
• Blood pressure monitoring regularly 1

Proper Sampling Technique

• Collect blood samples exactly 12 hours after the previous dose and immediately before the next scheduled dose 3
• For patients on twice-daily tacrolimus, the morning pre-dose level is the standard sampling time 3
• Use consistent laboratory methods for measurement 3

Special Monitoring Considerations

• Increase monitoring frequency whenever there is a change in medication or patient status that may affect blood levels 3
• Monitor levels more closely when medications that affect CYP3A4-mediated clearance are added or removed 3
• Monitor levels whenever there is a decline in kidney function 3

Administration Guidelines

Important Administration Instructions

• Tacrolimus capsules may be taken with or without food, but should be taken consistently the same way each time 2
• Patients should not eat grapefruit or drink grapefruit juice while taking tacrolimus 2
• Tacrolimus should not be used simultaneously with cyclosporine; discontinue one drug at least 24 hours before initiating the other 2
• Different tacrolimus formulations (immediate-release vs. extended-release) are not interchangeable 2

Common Pitfalls and Caveats

• Inconsistent timing of blood draws relative to dosing can lead to significant variability in results 3
• Collecting samples after a dose rather than before can result in falsely elevated readings 3
• Food significantly affects tacrolimus bioavailability - taking tacrolimus immediately after a meal or 1.5 hours after a meal reduces absorption by approximately 34% compared to the fasting state 4
• Only 48.4% of tacrolimus measurements in one study were found within the therapeutic range, with 44.5% having elevated levels, highlighting the importance of careful monitoring 5
• Drug interactions affecting CYP3A4 can significantly alter tacrolimus levels and require dose adjustments 3, 2

Notable Toxicities to Monitor

• Leukopenia 1
• Renal failure 1
• Neurotoxicity 1
• Hyperglycemia 2
• Electrolyte abnormalities, particularly hypomagnesemia 1

By following these dosage recommendations and monitoring requirements, clinicians can optimize tacrolimus therapy while minimizing the risk of toxicity and rejection in patients requiring immunosuppression.