Indications

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

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. A tacrolimus-FKBP-12 complex is formed, which subsequently binds with calcium, calmodulin, and calcineurin. This inhibits the phosphatase activity of calcineurin.

As a result, dephosphorylation and translocation of transcription factors such as:

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

are prevented.

Tacrolimus inhibits the expression and/or 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
Suppresses nitric oxide release
Induces apoptosis
Stimulates transforming growth factor-beta (TGF-β) production

The overall effect is inhibition of T-lymphocyte activation and proliferation, along with suppression of T-helper-cell-dependent B-cell responses, resulting in immunosuppression.

Dosage & Administration

For patients who can tolerate oral therapy, oral Tacrolimus should be initiated.

Initial Administration

Liver, Heart, and Lung Transplant Patients: Start no earlier than 6 hours after transplantation.
Kidney Transplant Patients: May start within 24 hours after transplantation, but administration should be delayed until renal function has recovered.

Adult Dosage

Kidney Transplant

With Azathioprine

0.2 mg/kg/day in two divided doses

Target Trough Level:

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 in two divided doses

Target Trough Level:

Months 1-12: 4-11 ng/mL

Liver Transplant

With Corticosteroids Only

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

Target Trough Level:

Months 1-12: 5-20 ng/mL

Heart Transplant

With Azathioprine or MMF

0.075 mg/kg/day in two divided doses

Target Trough Level:

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 in two divided doses

Target Trough Level:

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

Note: Patients with cystic fibrosis may require higher doses because oral bioavailability may be reduced. Tacrolimus trough concentrations should be monitored regularly.

Pediatric Dosage

Kidney Transplant

0.3 mg/kg/day in two divided doses
Target trough level: 5-20 ng/mL

Liver Transplant

0.15-0.2 mg/kg/day in two divided doses
Target trough level: 5-20 ng/mL

Heart Transplant

0.3 mg/kg/day in two divided doses
Target trough level: 5-20 ng/mL

Lung Transplant

0.3 mg/kg/day in two divided doses
Week 1-2: 10-20 ng/mL
Week 2-Month 12: 10-15 ng/mL

Drug Interactions

Mycophenolic Acid Products

May increase exposure to mycophenolic acid (MPA) after conversion from cyclosporine to Tacrocap.
Monitor for MPA-related adverse reactions and adjust MMF or MPA dosage if necessary.

Nelfinavir and Grapefruit Juice

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

CYP3A Inhibitors

Increase tacrolimus blood concentrations.
Monitor drug levels and adjust dose accordingly.

CYP3A Inducers

Decrease tacrolimus concentrations.
Monitor drug levels and adjust dose as needed.

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
Infections
Anemia
Bronchitis
Pericardial effusion
Urinary tract infection
Constipation
Diarrhea
Headache
Abdominal pain
Insomnia
Paresthesia
Peripheral edema
Nausea
Hyperkalemia
Hypomagnesemia
Hyperlipidemia