Tacrolimus

Tacrolimus capsule is a calcineurin-inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in adult patients receiving allogeneic liver, kidney, or heart transplants, and pediatric patients receiving allogeneic liver transplants in combination with other immunosuppressants. ( 1.1 ) 1.1 Prophylaxis of Organ Rejection in Kidney, Liver or Heart Transplant Tacrolimus capsules are indicated for the prophylaxis of organ rejection, in adult patients receiving allogeneic kidney transplant [see Clinical Studies ( 14.1 )] , liver transplant [see Clinical Studies ( 14.2 )] , heart transplant [ see Clinical Studies ( 14.3 )] , and pediatric patients receiving allogeneic liver trans …

• Intravenous (IV) use recommended for patients who cannot tolerate oralformulations (capsules). • Administer capsules consistently with or without food. • Therapeutic drug monitoring is recommended. • Avoid eating grapefruit or drinking grapefruit juice. • See dosage adjustments for African-American patients , hepatic and renal impaired. • For complete dosing information, see Full Prescribing Information
• ADULT Patient Population Initial OralDosage (formulation) Whole Blood Trough Concentration Range Kidney Transplant With azathioprine 0.2 mg/kg/day capsules, divided in two doses, every 12 hours Month 1 to 3: 7 to 20 ng/mL Month 4 to 12: 5 to 15 ng/mL With MMF/IL-2 receptor antagonist 0.1 mg/kg/day capsules, divided in two doses, every 12 hours Month 1 to 12: 4 to 11 ng/mL Liver Transplant With corticosteroids only 0.1 to 0.15 mg/kg/day capsules, divided in two doses, every 12 hours Month 1 to 12: 5 to 20 ng/mL Heart Transplant With azathioprine or MMF 0.075 mg/kg/day capsules, divided in two doses, every 12 hours Month 1 to 3: 10 to 20 ng/mL Month ≥ 4: 5 to 15 ng/mL PEDIATRIC Patient Population Initial Oral Dosage (formulation) Whole Blood Trough Concerntration Range Liver Transplant 0.15 to 0.2 mg/kg/day capsules divided in two doses, every 12 hours Month 1 to 12: 5 to 20 ng/mL MMF= Mycophenolate mofetil 1 Patients with cystic fibrosis may require higher doses due to lower bioavailability. 2 Dose at 0.1 mg/kg/day if antibody induction treatment is administered. …

Tacrolimus Capsules USP, 0.5 mg are white to off white powder filled in hard gelatin capsule of size ‘4’, dark yellow opaque cap imprinted with ‘0.5 MG’ and dark yellow opaque body imprinted with ‘RDY 525’using red ink. …

• Safety and effectiveness have been established
• In pediatric liver transplant patients
• Liver Transplantation Safety and efficacy
• In pediatric de novo liver transplant patients less than 16 years of age are based on evidence from active controlled studies that included 56
• Pediatric patients, 31 of which received tacrolimus
• Additionally, 122
• Pediatric patients were studied in an uncontrolled trial of tacrolimus in living related donor liver transplantation. …

Clinical trials of tacrolimus did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. …

• Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use)
• Administration Advise the patient or caregiver to: • Inspect their tacrolimus medicine when they receive a new prescription and before taking it
• If the appearance of the capsule is not the same as usual, or if dosage instructions have changed, advise patients to contact their healthcare provider as soon as possible to make sure that they have the right medicine
• Other tacrolimus products cannot be substituted for tacrolimus capsules. • Take tacrolimus at the same 12 hour intervals every day to achieve consistent blood concentrations. …

• Tacrolimus capsules are contraindicated in patients with a hypersensitivity to tacrolimus
• Tacrolimus injection is contraindicated in patients with a hypersensitivity to HCO-60 (polyoxyl 60 hydrogenated castor oil)
• Hypersensitivity symptoms reported include dyspnea, rash, pruritus, and acute respiratory distress syndrome [seeAdverse Reactions ]
• Hypersensitivity to tacrolimus or HCO-60 (polyoxyl 60 hydrogenated castor oil)

• Mycophenolic Acid Products: Can increase MPA exposure after crossover from cyclosporine to tacrolimus; monitor for MPA-related adverse reactions and adjust MMF or MPA dose as needed. ( 7.1 ) • Nelfinavir and Grapefruit Juice: Increased tacrolimus concentrations via CYP3A inhibition; avoid concomitant use. ( 7.2 ) • CYP3A Inhibitors: Increased tacrolimus concentrations; monitor concentrations and adjust tacrolimus dose as needed. ( 5.11 , 7.2 ) • CYP3A4 Inducers: Decreased tacrolimus concentrations; monitor concentrations and adjust tacrolimus dose as needed. …

• Not Interchangeable with Extended-Release Tacrolimus Products-Medication Errors: Instruct patients or caregivers to recognize the appearance of tacrolimus capsules. ( 5.3 ) • New Onset Diabetes After Transplant: Monitor blood glucose. ( 5.4 ) • Nephrotoxicity (acute and/or chronic): Reduce the dose; use caution with other nephrotoxic drugs. ( 5.5 ) • Neurotoxicity: Including risk of Posterior Reversible Encephalopathy Syndrome (PRES); monitor for neurologic abnormalities; reduce or discontinue tacrolimus capsules. ( 5.6 ) • Hyperkalemia: Monitor serum potassium levels. Consider carefully before using with other agents also associated with hyperkalemia. …

The following serious and otherwise important adverse drug reactions are discussed in greater detail in other sections of labeling: • Lymphoma and Other Malignancies [see Warnings and Precautions (5.1) ] • Serious Infections [see Warnings and Precautions ( 5.2 )] • New Onset Diabetes After Transplant [see Warnings and Precautions ( 5.4 ) ] • Nephrotoxicity [see Warnings and Precautions ( 5.5 )] • Neurotoxicity [see Warnings and Precautions ( 5.6 )] • Hyperkalemia [see Warnings and Precautions ( 5.7 )] • Hypertension [see Warnings and Precautions ( 5.8 )] • Anaphylactic Reactions with Tacrolimus Injection [see Warnings and Precautions ( 5.9 )] • Myocardial Hypertrophy [see Warnings and Precau …

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy registry that monitors pregnancy outcomes in women exposed to tacrolimus during pregnancy. The Transplantation Pregnancy Registry International (TPRI) is a voluntary pregnancy exposure registry that monitors outcomes of pregnancy in female transplant recipients and those fathered by male transplant recipients exposed to immunosuppressants including tacrolimus. …

Limited overdosage experience is available. Acute overdosages of up to 30 times the intended dose have been reported. Almost all cases have been asymptomatic and all patients recovered with no sequelae. Acute overdosage was sometimes followed by adverse reactions consistent with those reported with the use of tacrolimus [see Adverse Reactions ( 6.1 , 6.2 )] including tremors, abnormal renal function, hypertension, and peripheral edema; in one case of acute overdosage, transient urticaria and lethargy were observed. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.