Tacrograf

Lupus nephritis when the effects of steroids is insufficient or administration of steroids is difficult. Prophylaxis of organ rejection in patients receiving allogeneic liver or kidney transplants concomitantly w/ adrenal corticosteroids, & w/ azathioprine or mycophenolate mofetil in kidney transplant recipients.

Individualized dosage. Adult Organ transplant: Kidney transplant Initially 0.2 mg/kg/day in combination w/ azathioprine or 0.1 mg/kg/day in combination w/ mycophenolate mofetil & interleukin-2 receptor antagonist. Administer in 2 divided doses every 12 hr & initial dose w/in 24 hr of transplantation but delay until renal function has recovered. Liver transplant Initially 0.1-0.15 mg/kg/day in 2 divided doses every 12 hr. Administer initial dose no sooner than 6 hr after transplantation. Titrate dose based on clinical assessments of rejection & tolerability. Reduce dose if nephrotoxicity develops. Lupus nephritis 3 mg once daily after dinner. Ped Organ transplant: Liver transplant Initially 0.15-0.2 mg/kg/day in 2 divided doses every 12 hr. Administer no sooner than 6 hr after transplantation. Renal & hepatic impairment Lower doses. Further dose reductions below targeted range may be required. Administer initial dose no sooner than 6 hr & w/in 24 hr but delay until renal function shows evidence of recovery in kidney transplant patients w/ post-op oliguria. Black kidney transplant patient Higher doses.

Should be taken on an empty stomach.

Hypersensitivity.

Hypersensitivity symptoms eg, dyspnea, rash, pruritus & acute resp distress syndrome. Discontinue treatment if pure red cell aplasia (PRCA) is diagnosed. Consider dose reduction or discontinuation if myocardial hypertrophy is diagnosed. Increased risk of developing lymphomas & other malignancies, particularly of the skin; infection, developing bacterial, viral including cytomegalovirus (CMV), fungal, & protozoal infections, including opportunistic infections; CMV viremia &/or CMV disease in patients who are CMV-seronegative prior to transplant & receive graft from CMV-seropositive donor. Post-transplant lymphoproliferative disorder especially in patients who are EBV seronegative. Activation of latent viral infections eg, BK virus associated w/ polyoma virus-associated nephropathy & JC virus associated w/ progressive multifocal leukoencephalopathy. Medication & dispensing errors including inadvertent or unintentional substitution between IR & ER. New-onset DM after kidney & liver transplantation. Neurotoxicities particularly when used in high doses including most severe cases [posterior reversible encephalopathy syndrome (PRES), delirium, seizure, & coma] & less severe cases (tremors, paresthesia, headache, & other changes in motor & sensory function, mental status). Hyperkalemia; HTN; QT/QTc interval prolongation & Torsades de pointes. Risk factors for PRCA eg, parvovirus B19 infection, underlying disease, or concomitant medications associated w/ PRCA. GI perforation. Black & Hispanic kidney transplant patients. Avoid use in patients w/ congenital long QT syndrome. Monitor patients for development of infection. Closely monitor blood glucose conc in patients on therapy. Maintain BP control if PRES is suspected or diagnosed. Monitor K levels; whole blood trough conc; blood levels mthly for 3 mth after start of therapy, thereafter approx 12 hr after administration periodically in patients w/ lupus nephritis. Consider obtaining ECG & monitor electrolytes (Mg, K, Ca) periodically during treatment in patients w/ CHF, bradyarrhythmias, electrolyte disturbances eg, hypokalemia, hypocalcemia, or hypomagnesemia, & those taking certain antiarrhythmics or other medicinal products that lead to QT prolongation; echocardiographic evaluation in patients who develop renal failure or clinical manifestations of ventricular dysfunction while on treatment. Regularly assess BP, serum creatinine, electrolytes (Mg, K, Ca), & blood glucose. Consider changing to another immunosuppressive therapy in patients w/ persistent elevations of serum creatinine who are unresponsive to dosage adjustments. Avoid inhalation or direct contact w/ skin or mucous membrane of powd (wash skin & eyes if it occurs); exposure to sunlight & UV light. Wear protective clothing & use sunscreen w/ high protection factor. Concomitant use w/ drugs that may be associated w/ renal dysfunction; CYP3A4 inhibitors; K-sparing diuretics, ACE inhibitors, ARBs; Ca-channel blockers. Not to be immunized w/ live vaccines during or shortly after treatment & avoid close contact w/ recently vaccinated (live vaccine) individuals. Not to be used simultaneously w/ cyclosporine; discontinue tacrolimus or cyclosporine at least 24 hr before initiating the other. Not recommended to be used w/ sirolimus in liver transplant. Acute or chronic nephrotoxicity particularly when used in high doses. Monitor patients w/ renal impairment. Close monitoring of tacrolimus trough conc in patients w/ hepatic impairment. Pregnancy. Avoid nursing during treatment. Ped kidney transplant patients. Elderly.

Angina pectoris, atrial fibrillation & flutter, bradycardia, cardiac arrest, arrhythmia & failure, cardioresp arrest, cerebral infarction & ischemia, chest pain, decreased heart rate, deep vein thrombophlebitis, DVT, ECG abnormality (QRS or ST segment or T wave), edema, flushing, hemorrhagic stroke, HTN, hypertrophic cardiomyopathy, hypotension, ischemic heart disease, localized phlebitis, MI, orthostatic hypotension, pericardial effusion, peripheral edema & vascular disease, phlebitis, syncope, tachycardia, thrombosis, vasodilatation, ventricular premature contractions; abnormal dreams, abnormality in thinking, agitation, amnesia, anxiety, aphasia, ataxia, brain disease, carpal tunnel syndrome, chills, confusion, convulsions, depression, dizziness, drowsiness, emotional lability, excessive crying, falling, fatigue, flaccid paralysis, hallucination, headache, hypertonia, hypoesthesia, insomnia, mental status changes, mood elevation, myasthenia, myoclonus, nervousness, neuropathy (including compression), neurotoxicity, nightmares, pain, paresis, paresthesia, peripheral neuropathy, psychosis, seizure, vertigo, voice disorder, writing difficulty; acne vulgaris, alopecia, cellulitis, condyloma acuminatum, dermal ulcer, dermatitis (including fungal), dermatological reaction, diaphoresis, exfoliative dermatitis, hypotrichosis, pruritus, skin discoloration, photosensitivity & rash, tinea versicolor; acidosis, albuminuria, alkalosis, anasarca, Cushing's syndrome, decreased serum bicarbonate & Fe, dehydration, DM, gout, hirsutism, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipidemia, hypertriglyceridemia, hyperuricemia, hypervolemia, hypocalcemia, hypoglycemia, hypomagnesemia, hyponatremia, hypophosphatemia, increased γ-glutamyl transferase & LDH, wt changes & gain; abdominal pain, anorexia, aphthous stomatitis, cholangitis, colitis, constipation, delayed gastric emptying, diarrhea, duodenitis, dyspepsia, dysphagia, enlargement of abdomen, esophagitis (including ulcerative), flatulence, gastric ulcer, gastritis, GERD, GI hemorrhage & perforation, hernia, hiccups, increased appetite, intestinal obstruction, nausea, oral candidiasis, pancreatic & rectal disease (pseudocyst), pancreatitis (including hemorrhagic & necrotizing), peritonitis, stomach cramps, stomatitis, vomiting; anuria, bladder spasm, cystitis, dysuria, hematuria, nocturia, oliguria, proteinuria, toxic nephrosis, urinary frequency, incontinence, retention & urgency, UTI, vaginitis; anemia (Hb <10 g/dL), blood coagulation disorder, bruise, decreased prothrombin time, hemolytic & hypochromic anemia, hemorrhage, hypoproteinemia, increased hematocrit & INR, Kaposi's sarcoma, leukocytosis, leukopenia, malignant bladder & thyroid neoplasm, neutropenia, pancytopenia, polycythemia, skin neoplasm, thrombocytopenia; abnormal hepatic function tests, ascites, cholestatic jaundice, hepatic injury, hepatitis (including acute, chronic, & granulomatous), hyperbilirubinemia, increased liver enzymes & serum alkaline phosphatase, jaundice; hypersensitivity reaction; graft complications (kidney transplant); abscess, bacterial, herpes simplex, Epstein-Barr & serious infection, CMV disease, infection, sepsis; fever, post-op pain & wound complication, wound healing impairment; arthralgia, arthropathy, back pain, leg cramps, muscle spasm & weakness of extremities, myalgia, osteopenia, osteoporosis, tremor, weakness; amblyopia, blurred vision, conjunctivitis, visual disturbance; hearing loss, otalgia, otitis externa & media, tinnitus; acute renal failure, hydronephrosis, increased BUN & serum creatinine, renal disease (BK nephropathy), renal function abnormality, renal tubular necrosis; allergic rhinitis, asthma, atelectasis, bronchitis, cough, dyspnea, emphysema, flu-like symptoms, pharyngitis, pleural effusion, pneumonia, pneumothorax, pulmonary disease, edema & infiltrates, resp depression, failure & tract infection, rhinitis, sinusitis. Gastroenteritis; polyoma virus infection. SJS, TEN.

May prolong QT interval & increased risk of life-threatening cardiac arrhythmias including Torsades de pointes of antiarrhythmic agents (eg, disopyramide, dofetilide, procainamide, quinidine, sotalol), arsenic trioxide, chlorpromazine, cisapride, citalopram, clarithromycin, dolasetron, droperidol, erythromycin, fluoxetine, levofloxacin, mesoridazine, moxifloxacin, pentamidine, pimozide, thioridazine, ziprasidone. Increased serum conc of afatinib; bosutinib; brentuximab vedotin; colchicine; systemic cyclosporine; active metabolite(s) of dabigatran etexilate; conventional doxorubicin; edoxaban; everolimus; fosphenytoin; edipasvir; naloxegol; pazopanib; prucalopride; rifaximin; silodosin; topotecan; venetoclax; lipos vincristine. Increased serum conc w/ aprepitant; systemic azithromycin, cyclosporine, erythromycin, fusidic acid, ketoconazole & levofloxacin; boceprevir; dihydropyridine Ca channel blockers (except clevidipine); chloramphenicol; oral & topical clotrimazole; conivaptan; crizotinib; strong CYP3A4 inhibitors; danazol; dasatanib; dronedarone; efonidipine; ertapenem; fluconazole; fosaprepitant; grazoprevir; idelalisib; itraconazole; ivacaftor; luliconazole; mifepristone; nelfinavir; netupitant; ombitasvir, paritaprevir, ritonavir, dasabuvir; osimertinib; palbociclib; P-gp/ABCB1 inhibitors; posaconazole; PPIs; ranolazine; schisandra; stiripentol; telaprevir; tofisopam; voriconazole. Increased absorption w/ ethyl alcohol. Decreased metabolism w/ serotonin reuptake inhibitor/antagonist antidepressants (except trazodone); non-dihydropyridine Ca channel blockers (except bepridil); moderate CYP3A4 inhibitors; grapefruit juice; PIs. Diminished therapeutic effect of antidiabetics; intravesical BCG; nivolumab; sipuleucel-T; inactivated & live vaccines. Diminished therapeutic effect w/ echinacea. Decreased serum conc w/ bosentan; caspofungin; cinacalcet; moderate CYP3A4 inducers; dabrafenib; deferasirox; efavirenz; enzalutamide; fosphenytoin; mitotane; P-gp/ABCB1 inducers; phenytoin; PIs; rifamycin derivatives; sevelamer; siltuximab; St. John's wort; temsirolimus; tocilizumab. Enhanced adverse/toxic effect of clozapine; leflunomide; natalizumab; live vaccines. Enhanced adverse/toxic effect w/ denosumab; dipyrone; pimecrolimus; topical tacrolimus. Enhanced adverse/toxic effect of & w/ sirolimus; temsirolimus. Diminished diagnostic effect of Coccidioides immitis skin test. Enhanced nephrotoxic effect of & w/ systemic cyclosporine. Enhanced nephrotoxic effect of fenofibrate & derivatives. Enhanced nephrotoxic effect w/ foscarnet; NSAIDs. Increased metabolism w/ strong CYP3A4 inducers. Enhanced QTc-prolonging effect of dronedarone; highest/moderate risk QTc-prolonging agents. Enhanced QTc-prolonging effect w/ systemic levofloxacin; mifepristone. Enhanced hyperkalemic effect w/ eplerenone; K-sparing diuretics. Enhanced immunosuppressive effect of fingolimod; tofacitinib. Enhanced immunosuppressive effect w/ roflumilast. Enhanced neutropenic effect of deferiprone. Enhanced neutropenic effect w/ trastuzumab. Increased serum level &/or toxicity w/ grapefruit juice.

Immunosuppressants

L04AD02 - tacrolimus ; Belongs to the class of calcineurin inhibitors. Used as immunosuppressants.

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