Tacromus Capsule

Tacromus Capsule is used for: Prophylaxis of organ rejection in patients receiving allogeneic liver, kidney or heart transplants Use concomitantly with adrenal corticosteroids; in kidney and heart transplant Use in conjunction with azathioprine or mycophenolate mofetil (MMF)

Adult Kidney transplant In combination with azathioprine 0.2 mg/kg/day divided q12hr initially In combination with MMF/IL-2 receptor antagonist 0.1 mg/kg/day divided q12hr initially Adult Liver transplant 0.10-0.15 mg/kg/day divided q12hr initially Administer initial dose no sooner than 6 hr after transplantation Adult Heart transplant 0.075 mg/kg/day divided q12hr initially Administer the initial dose no sooner than 6 hr after transplantation Adult Lung Transplant Prophylaxis of organ rejection in patients receiving lung transplants in combination with other immunosuppressants (with azathioprine or MMF): 0.075 mg/kg/day divided q12hr initially Patients with cystic fibrosis may require higher doses owing to lower bioavailability Hepatic Impairment The mean clearance of tacrolimus was substantially lower in patients with severe hepatic impairment (mean Child-Pugh score: >10) compared to healthy volunteers with normal hepatic function. Close monitoring of tacrolimus trough concentrations is warranted in patients with hepatic impairment. Hepatic impaired patients should receive doses at the lowest value of the recommended initial oral dosing range.

Pediatric Liver transplant 0.15-0.20 mg/kg/day

Renal impaired patients should receive doses at the lowest value of the recommended initial oral dosing range. Monitor renal function in patients with impaired renal function.

Administer capsules consistently with or without food; do not drink grapefruit juice

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

Lymphoma and Other Malignancies: Risk of lymphomas, including post-transplant lymphoproliferative disorder (PLTD); appears related to intensity and duration of use. Avoid prolonged exposure to UV light and sunlight Serious infections: Increased risk of bacterial, viral, fungal and protozoal infections, including opportunistic infections: combination immunosuppression should be used with caution Polyoma Virus Infections: Serious, sometimes fatal outcomes, including polyoma virus-associated nephropathy (PVAN), mostly due to BK virus, and JC virus-associated progressive multifocal leukoencephalopathy (PML); consider reducing immunosuppression Cytomegalovirus (CMV) Infections: Increased risk of CMV viremia and disease; consider reducing immunosuppression New Onset Diabetes After Transplant: Monitor blood glucose Nephrotoxicity: Acute and/or chronic; reduce the dose; use caution with other nephrotoxic drugs Neurotoxicity: Risk of Posterior Reversible Encephalopathy Syndrome, monitor for neurologic abnormalities; reduce or discontinue Prograf and other immunosuppressants Hyperkalemia: Monitor serum potassium levels. Careful consideration should be given prior to use of other agents also associated with hyperkalemia Hypertension: May require antihypertensive therapy. Monitor relevant drug-drug interactions Anaphylactic Reactions with IV formulation: Observe patients receiving Prograf injection for signs and symptoms of anaphylaxis Use with Sirolimus: Not recommended in liver and heart transplant due to increased risk of serious adverse reactions Myocardial Hypertrophy: Consider dosage reduction or discontinuation Immunizations: Use of live vaccines should be avoided Pure Red Cell Aplasia: Discontinuation should be considered

Pregnancy: Based on animal data may cause fetal harm. Use only if the potential benefit justifies the risk. Nursing Mothers: Discontinue nursing taking into consideration importance of drug to mother. Pregnancy Tacrolimus can cause fetal harm when administered to a pregnant woman; data from postmarketing surveillance and TPRI suggest that infants exposed to tacrolimus in utero are at a risk of prematurity, birth defects/congenital anomalies, low birth weight, and fetal distress; advise pregnant women of potential risk to fetus; administration of oral tacrolimus to pregnant rabbits and rats throughout the period of organogenesis was associated with maternal toxicity/lethality, and an increased incidence of abortion, malformation and embryofetal death at clinically relevant doses (0.5 to 6.9 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m2 basis) Risks during pregnancy are increased in organ transplant recipients; the risk of premature delivery following transplantation is increased; pre-existing hypertension and diabetes confer additional risk to the pregnancy of an organ transplant recipient; pre-gestational and gestational diabetes are associated with birth defects/congenital anomalies, hypertension, low birth weight and fetal death; cholestasis of pregnancy (COP) was reported in 7% of liver or liver-kidney (LK) transplant recipients, compared with approximately 1% of pregnancies in the general population; however, COP symptoms resolved postpartum and no long term effect on offsprings was reported Tacrolimus may increase hyperglycemia in pregnant women with diabetes (including gestational diabetes); monitor maternal blood glucose levels regularly Therapy may exacerbate hypertension in pregnant women and increase pre-eclampsia; monitor and control blood pressure Renal dysfunction, transient neonatal hyperkalemia and low birth weight have been reported at time of delivery in infants of mothers taking drug There is an increased risk for premature delivery (< 37 weeks) following transplantation and maternal exposure to drug. Contraception Therapy can cause fetal harm when administered to pregnant women; advise female and male patients of reproductive potential to speak to their healthcare provider on family planning options including appropriate contraception prior to starting treatment Infertility Based on findings in animals, male and female fertility may be compromised by treatment Lactation Controlled lactation studies have not been conducted in humans; however tacrolimus has been reported to be present in human milk; effects of tacrolimus on breastfed infant, or on milk production have not been assessed Tacrolimus is excreted in rat milk and in peri-/postnatal rat studies, exposure to tacrolimus during postnatal period was associated with developmental toxicity in offspring at clinically relevant doses The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for drug and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Mycophenolic Acid Products: Can increase MPA exposure after crossover from cyclosporine to Prograf; monitor for MPA-related adverse reactions and adjust MMF or MPA-dose as needed Nelfinavir and Grapefruit Juice: Increased tacrolimus concentrations via CYP3A inhibition; avoid concomitant use CYP3A Inhibitors: Increased tacrolimus concentrations; monitor concentrations and adjust tacrolimus dose as needed with concomitant use CYP3A4 Inducers: Decreased tacrolimus concentrations; monitor concentrations and adjust tacrolimus dose as needed with concomitant use

Side effects of Tacrolimus : >10% Tremor (54%) Hypertension (50%) Hypophosphatemia (49%) Increased creatinine (45%) Infection (45%) Headache (44%) Diarrhea (44%) Nausea (38%) Peripheral edema (36%) Constipation (35%) Urinary tract infection (34%) Hypomagnesemia (34%) Asthenia (34%) Abdominal pain (33%) Pain (32%) Insomnia (32%) Hyperlipemia (31%) Hyperkalemia (31%) Anemia (30%) Vomiting (29%) Dyspepsia (28%) Fever (29%) Arthralgia (25%) Back pain (24%) Diabetes mellitus (24%) Paresthesia (23%) Hypokalemia (22%) Hyperglycemia (22%) Dyspnea (22%) Dizziness (19%) Chest Pain (19%) Increased cough (18%) Edema (18%) Skin rash (17%) Pruritus (15%) Leukopenia (15%)

Calcineurin inhibitor; inhibits T-cell activation and proliferation, humoral immunity Tacrolimus is a potent macrolide which suppresses T-cell activation and T-helper-cell dependent B-cell proliferation, as well as the formation of lymphokines [e.g. interleukin (IL)-2, IL-3, and γ-interferon] and the expression of the IL-2 receptor. It inhibits calcineurin activity by binding to an intracellular protein, FKBP-12; forming complex w/ Ca, calmodulin and calcineurin.

Tacromus 0.5 mg Capsule manufactured by UniMed UniHealth Pharmaceuticals Ltd.. Its generic name is Tacrolimus. Tacromus is availble in Bangladesh. Farmaco BD drug index information on Tacromus Capsule is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.