Title 13. TDM OF DRUGS USED IN ORGAN TRANSPLANTATIONS.pdf ✅

PHARMD GURU Page 3  Gastrointestinal: Nausea, diarrhea, gingival hyperplasia, abdominal distress, and dyspepsia  Genitourinary: Urinary tract infection  Infection: Increased susceptibility to infection and viral infection  Neuromuscular and skeletal: Tremor and leg cramps  Renal: Increased serum creatinine level and renal insufficiency  Respiratory: Upper respiratory tract infection. DRUG INTERACTIONS:  Cyclosporine level increases when used with diltiazem, doxycycline, erythromycin, ketoconazole, methylprednisolone (high doses), nicardipine, verapamil, or oral contraceptives; concomitant use should be avoided.  Cyclosporine level decreases when used with carbamazepine, isoniazid, phenobarbitone, phenytoin, or rifampicin; concomitant use should be avoided.  Risk of convulsion increases when Cyclosporine is used concurrently with high-dose methylprednisolone; concomitant use should be avoided.  Additive nephrotoxicity is observed when Cyclosporine is used with aminoglycosides, amphotericin B, ciprofloxacin, colchicine, melphalan, co- trimoxazole, or NSAIDs; concomitant use should be avoided. TOXIC RANGE: The oral LD50 in rats is 1480 mg/kg and the TDLO in humans is 12 mg/kg. CONTRAINDICATIONS: Contraindicated in • Hypersensitivity to Cyclosporine or any component of the formulation. • Hypersensitivity to polyoxyethylated castor oil. • Rheumatoid arthritis and psoriasis patients with abnormal renal function, uncontrolled hypertension, primary or secondary immunodeficiency other than that associated with autoimmune disease, uncontrolled infection, or malignancy (excluding non-melanoma skin cancer). • Concomitant administration with PUVA or UVB therapy, methotrexate or other immunosuppressive agents, coal tar, or radiation therapy in patients with psoriasis. • Concurrent use with bosentan.
PHARMD GURU Page 4 MONITORING PARAMETERS:  Monitor plasma concentrations of Cyclosporine.  Renal function tests (serum levels of creatinine and BUN).  BP (periodically and following the addition, modification, or deletion of other medications).  Monitor for hypersensitivity reactions (IV cyclosporine).  Signs and symptoms of hepatotoxicity, secondary malignancy, diabetes mellitus, and infection.  Monitor for progressive cognitive or motor deficits.  Magnetic resonance imaging may be required for the diagnosis of posterior reversible encephalopathy syndrome (PRES). TRANSPLANT PATIENTS:  Cyclosporine trough levels.  Serum electrolyte levels.  Renal and hepatic function tests.  BP.  Lipid profile.  Blood sugar level.  HbA1c. DOSAGE ADJUSTMENTS: HEPATIC IMPAIRMENT:  Mild-to-moderate impairment:  No dosage adjustments provided in the manufacturer's labeling; monitor blood concentrations.  Severe impairment:  No dosage adjustments provided in the manufacturer's labeling; however, metabolism is extensively hepatic (exposure is increased). Monitor blood concentrations; may require dose reduction. RENAL IMPAIRMENT:  Hemodialysis: Supplemental dose is not necessary. Dialysis does not significantly alter Cyclosporine clearance.  Peritoneal dialysis: Supplemental dose is not necessary.