Drug Guide
Tacrolimus
Classification
Therapeutic: Immunosuppressant
Pharmacological: Calcineurin inhibitor
FDA Approved Indications
- Prevention of organ rejection in kidney, liver, and heart transplant patients.
- Treatment of atopic dermatitis (Protopic)
Mechanism of Action
Tacrolimus binds to the intracellular protein FKBP-12, forming a complex that inhibits calcineurin phosphatase. This inhibition prevents the activation of T-lymphocytes by blocking the transcription of IL-2 and other cytokines, thus suppressing the immune response.
Dosage and Administration
Adult: Dosing varies based on indication and formulation; typically, for transplantation, starting doses are 0.05-0.10 mg/kg/day divided into two doses. For topical use, apply a thin layer to affected skin twice daily.
Pediatric: Dosing similar to adults, adjusted for age and weight, particularly in transplant cases. Topical doses are similar to adult use.
Geriatric: Use with caution; start at lower doses due to increased sensitivity.
Renal Impairment: Use with caution; may require dose adjustments based on drug levels.
Hepatic Impairment: Use with caution; may require dose adjustments and close monitoring.
Pharmacokinetics
Absorption: Bioavailability varies; approximately 20-25%.
Distribution: Extensively protein-bound (~99%).
Metabolism: Primarily metabolized in the liver via CYP3A4/5 enzymes.
Excretion: Excreted mainly via feces (70%) and urine (~10%).
Half Life: Approximate half-life: 12-16 hours (oral).
Contraindications
- Hypersensitivity to tacrolimus or other formulation components.
Precautions
- Increased risk of infections, malignancies, impairment of wound healing, and neurotoxicity.
- Use cautiously in patients with hepatic impairment.
- Monitor for neurotoxicity, nephrotoxicity, and hypertension.
Adverse Reactions - Common
- Nephrotoxicity (Common)
- Neurotoxicity (tremors, headache, paresthesias) (Common)
- Hyperglycemia (Common)
- Hypertension (Common)
- Gastrointestinal disturbances (Common)
Adverse Reactions - Serious
- Blood dyscrasias (neutropenia, anemia) (Serious)
- Infections (viral, bacterial, fungal) (Serious)
- Malignancies (lymphomas, skin cancer) (Serious)
Drug-Drug Interactions
- CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) increase tacrolimus levels.
- CYP3A4 inducers (e.g., rifampin, carbamazepine) decrease tacrolimus levels.
- NSAIDs may increase nephrotoxicity.
Drug-Food Interactions
- Grapefruit and grapefruit juice can increase tacrolimus levels.
Drug-Herb Interactions
- St. John’s Wort may decrease tacrolimus effectiveness.
Nursing Implications
Assessment: Monitor trough blood levels to maintain therapeutic range.
Diagnoses:
- Risk for infection
- Impaired kidney function
- Risk for bleeding due to blood dyscrasias.
Implementation: Administer as prescribed; monitor for signs of toxicity; adjust dose based on blood levels.
Evaluation: Achieving desired immunosuppressive effect with acceptable side effects; maintaining therapeutic drug levels.
Patient/Family Teaching
- Take medication consistently at the same time each day.
- Report signs of infection, bleeding, or neurotoxicity immediately.
- Avoid grapefruit juice and St. John’s Wort during therapy.
- Attend regular blood level monitoring appointments.
Special Considerations
Black Box Warnings:
- Increased risk of infection and lymphoma.
- Nephrotoxicity and neurotoxicity.
Genetic Factors: Genetic polymorphisms in CYP3A5 can affect drug metabolism and dosing.
Lab Test Interference: May interfere with certain laboratory tests, and levels should be interpreted with caution.
Overdose Management
Signs/Symptoms: Severe neurotoxicity, nephrotoxicity, hypotension, tachycardia.
Treatment: Supportive care, activated charcoal if ingestion was recent, and dose withholding; no specific antidote.
Storage and Handling
Storage: Store at 20-25°C (68-77°F).
Stability: Stable for 24 months at room temperature.