Indications

Tacrocap (Tacrolimus) is a calcineurin-inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in adult and pediatric patients receiving allogeneic:

Liver transplantation
Kidney transplantation
Heart transplantation
Lung transplantation

It is used in combination with other immunosuppressive agents.

Pharmacology

Tacrolimus binds to an intracellular protein called FKBP-12 (FK506-binding protein-12). The tacrolimus-FKBP-12 complex subsequently binds with calcium, calmodulin, and calcineurin, resulting in inhibition of calcineurin phosphatase activity.

This action prevents the dephosphorylation and translocation of transcription factors such as:

Nuclear Factor of Activated T-cells (NF-AT)
Nuclear Factor Kappa-light-chain-enhancer of Activated B-cells (NF-κB)

Tacrolimus inhibits the expression and production of several cytokines including:

Interleukin-1β (IL-1β)
IL-2
IL-3
IL-4
IL-5
IL-6
IL-8
IL-10
Interferon-gamma
Tumor Necrosis Factor-alpha (TNF-α)
Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)

Tacrolimus also:

Inhibits IL-2 receptor expression
Reduces nitric oxide release
Induces apoptosis
Stimulates production of transforming growth factor-beta (TGF-β)

The overall result is suppression of T-lymphocyte activation and proliferation, as well as T-helper-cell-dependent B-cell responses, leading to immunosuppression.

Dosage & Administration

If patients can tolerate oral therapy, oral Tacrolimus should be initiated.

Timing of Initial Dose

Liver, heart, and lung transplant patients: administer no sooner than 6 hours after transplantation.
Kidney transplant patients: may be initiated within 24 hours after transplantation, but treatment should be delayed until renal function recovers.

Adult Patients

Kidney Transplant

With Azathioprine

0.2 mg/kg/day divided into two doses

Target Whole Blood Trough Concentration:

Months 1-3: 7-20 ng/mL
Months 4-12: 5-15 ng/mL

With MMF/IL-2 Receptor Antagonist

0.1 mg/kg/day divided into two doses

Target Trough Concentration:

Months 1-12: 4-11 ng/mL

Liver Transplant

With Corticosteroids Only

0.10-0.15 mg/kg/day divided into two doses

Target Trough Concentration:

Months 1-12: 5-20 ng/mL

Heart Transplant

With Azathioprine or MMF

0.075 mg/kg/day divided into two doses

Target Trough Concentration:

Months 1-3: 10-20 ng/mL
After Month 3: 5-15 ng/mL

Lung Transplant

With Azathioprine or MMF

0.075 mg/kg/day divided into two doses

Target Trough Concentration:

Months 1-3: 10-15 ng/mL
Months 4-12: 8-12 ng/mL

Note: Patients with cystic fibrosis may have reduced oral bioavailability and may require higher doses to achieve target tacrolimus concentrations.

Pediatric Patients

Kidney Transplant

0.3 mg/kg/day in two divided doses

Target Trough Concentration:

Months 1-12: 5-20 ng/mL

Liver Transplant

0.15-0.20 mg/kg/day in two divided doses

Target Trough Concentration:

Months 1-12: 5-20 ng/mL

Heart Transplant

0.3 mg/kg/day in two divided doses

Target Trough Concentration:

Months 1-12: 5-20 ng/mL

Lung Transplant

0.3 mg/kg/day in two divided doses

Target Trough Concentration:

Weeks 1-2: 10-20 ng/mL
Week 2 to Month 12: 10-15 ng/mL

Drug Interactions

Mycophenolic Acid Products

May increase MPA exposure following conversion from cyclosporine to Tacrocap.
Monitor for MPA-related adverse effects and adjust MMF/MPA dose if necessary.

Nelfinavir and Grapefruit Juice

Increase tacrolimus concentrations through CYP3A inhibition.
Concomitant use should be avoided.

CYP3A Inhibitors

Increase tacrolimus blood concentrations.
Monitor levels and adjust dosage accordingly.

CYP3A Inducers

Decrease tacrolimus concentrations.
Monitor levels and adjust dosage as required.

Cannabidiol

Therapeutic drug monitoring and dose reduction of Tacrocap may be required when used together.

Contraindications

Hypersensitivity to tacrolimus.
Hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil).

Side Effects

Common adverse reactions (≥15%) include:

Abnormal renal function
Hypertension
Diabetes mellitus
Fever
Cytomegalovirus (CMV) infection
Tremor
Hyperglycemia
Leukopenia
General infections
Anemia
Bronchitis
Pericardial effusion
Urinary tract infection
Constipation
Diarrhea
Headache
Abdominal pain
Insomnia
Paresthesia
Peripheral edema
Nausea
Hyperkalemia
Hypomagnesemia
Hyperlipidemia

Pregnancy & Lactation

Pregnancy

Tacrolimus may cause fetal harm. Pregnant women should be informed about the potential risk to the fetus.

Lactation

Use during breastfeeding should only be considered after careful evaluation of risks and benefits by the treating physician.

Precautions & Warnings

Not Interchangeable with Extended-Release Tacrolimus Products

Medication errors may occur. Patients and caregivers should be instructed to identify and verify the appearance of Tacrocap capsules.

New-Onset Diabetes After Transplant (NODAT)

Monitor blood glucose levels regularly.

Nephrotoxicity

Tacrolimus may cause acute or chronic kidney toxicity.

Dose reduction may be required.
Use caution when combined with other nephrotoxic medications.