SIROLIMUS (sir-o-li'mus)
Rapamune Classifications: immunomodulator; immunosuppressant; Therapeutic: immunosuppressant Prototype: Cyclosporine Pregnancy Category: C
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Availability
1 mg tablets; 1 mg/mL oral solution
Action
Macrolide antibiotic structurally related to tacrolimus with immunosuppressive activity. Active in reducing a transplant
rejection by inhibiting the response of helper T-lymphocytes and B-lymphocytes to cytokinesis [(interleukin) IL-2, IL-4,
and IL-5].
Therapeutic Effect
Inhibits antibody production and acute transplant rejection reaction in autoimmune disorders [e.g., systemic lupus erythematosus
(SLE)]. Indicated by nonrejection of transplanted organ.
Uses
Prophylaxis of kidney transplant rejection.
Unlabeled Uses
Treatment of psoriasis.
Contraindications
Hypersensitivity to sirolimus; lung or liver transplant patients; soya lecithin (soy fatty acids) hypersensitivity; lymphoma,
neoplastic disease; children <13 y; females of childbearing age; pregnancy (category C); lactation.
Cautious Use
Hypersensitivity to or concurrent administration with tacrolimus; impaired renal function; concurrent use of aminoglycosides,
and amphotericin B; renal transplant patients; dialysis patients, UV exposure, retransplant patients, multiorgan transplant
recipients, African American transplant patients; viral or bacterial infection; hypertriglyceridemia, hyperlipidemia, diabetic
patients, atrial fibrillation, CHF, hypervolemia, palpitations; mild to moderate hepatic disease; coronary artery disease;
myelosuppression; liver disease.
Route & Dosage
Kidney Transplant Adult: PO 6 mg loading dose immediately after transplant, then 2 mg/d. Doses will need to be much higher (up to 40 mg/d) if not on cyclosporine. Adolescent (≥13 y, <40 kg): PO 3 mg/m2 loading dose immediately after transplant, then 1 mg/m2/d. Doses will need to be much higher (up to 40 mg/d) if not on cyclosporine.
Hepatic Impairment Reduce maintenance dose by 33%.
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Administration
Oral
- Give 4 h after oral cyclosporine.
- Add prescribed amount of sirolimus to a glass containing ≥2 oz (60 mL) of
water or orange juice (do not use any other type of liquid). Stir vigorously and administer immediately. Refill glass with
≥4 oz (120 mL) of water or orange juice. Stir vigorously and administer
immediately.
- Give consistently with respect to amount and type of food.
- Refrigerate; protect from light; use multidose bottles within 1 mo of opening.
Adverse Effects (≥1%)
Body as a Whole: Asthenia, back pain, chest pain, fever, pain, arthralgia; flu-like syndrome; generalized edema; infection; lymphocele; malaise;
sepsis, arthrosis, bone necrosis, leg cramps, myalgia, osteoporosis, tetany, abscess, ascites, cellulitis, chills, face edema,
hernia, pelvic pain, peritonitis.
CNS: Insomnia, tremor, headache, anxiety, confusion,
depression, dizziness, emotional lability, hypertonia, hyperesthesia, hypotonia, neuropathy, paresthesia,
somnolence.
CV: Hypertension, atrial fibrillation, CHF, hypervolemia, hypotension, palpitation, peripheral vascular disorder, postural hypotension, syncope,
tachycardia, thrombophlebitis, thrombosis, vasodilation.
GI: Constipation, diarrhea, dyspepsia, nausea, vomiting, abdominal pain, anorexia, dysphagia, eructation, esophagitis, flatulence,
gastritis, gastroenteritis, gingivitis, gum hyperplasia, ileus,
mouth ulceration, oral moniliasis, stomatitis, abnormal liver function tests.
Hematologic: Anemia, thrombocytopenia, leukopenia, hemorrhage, ecchymosis, leukocytosis, lymphadenopathy, polycythemia, thrombotic, thrombocytopenic purpura.
Metabolic: Edema, hypercholesterolemia, hyperkalemia, hyperlipidemia, hypokalemia, hypophosphatemia, peripheral edema, weight gain, Cushing's syndrome,
diabetes, acidosis, hypercalcemia, hyperglycemia, hyperphosphatemia, hypocalcemia,
hypoglycemia, hypomagnesemia,
hyponatremia; increased LDH, alkaline phosphatase, BUN, creatine phosphokinase, ALT, or AST; weight loss.
Respiratory: Dyspnea, pharyngitis, upper respiratory tract infection, asthma, atelectasis,
bronchitis, cough, epistaxis, hypoxia, lung edema, pleural effusion,
pneumonia, rhinitis,
sinusitis.
Skin: Acne, rash, fungal dermatitis, hirsutism, pruritus, skin hypertrophy, skin ulcer, sweating.
Urogenital: UTI, albuminuria, bladder pain, dysuria, hematuria, hydronephrosis, impotence, kidney pain, nocturia, renal tubular necrosis,
oliguria, pyuria, scrotal edema, incontinence, urinary retention, glycosuria.
Special Senses: Abnormal vision,
cataract,
conjunctivitis, deafness, ear pain, otitis media, tinnitus.
Interactions
Drug: Sirolimus concentrations increased by
clarithromycin, cyclosporine, diltiazem, erythromycin, ketoconazole, itraconazole, telithromycin; sirolimus concentrations decreased by
rifabutin, rifampin; vaccines may be less effective with sirolimus;
tacrolimus increases mortality, hepatic artery thrombosis, and graft loss.
Food: Grapefruit juice significantly increases plasma levels. High fat meals increase levels.
Herbal: St. John's wort decreases efficacy.
Pharmacokinetics
Absorption: Rapidly with 14% bioavailability.
Peak: 2 h.
Distribution: 92% protein bound, distributes in high concentrations to heart, intestines, kidneys, liver, lungs, muscle, spleen, and
testes.
Metabolism: In liver (CYP3A4).
Elimination: 91% in feces, 2.2% in urine.
Half-Life: 62 h.
Nursing Implications
Assessment & Drug Effects
- Monitor for S&S of graft rejection.
- Control hyperlipidemia prior to initiating drug.
- Draw trough whole-blood sirolimus levels 1 h before a scheduled dose.
- Lab tests: Obtain periodic lipid profile, CBC with differential, fasting plasma glucose, blood chemistry, BUN, and creatinine
(especially with other drugs known to cause renal impairment).
Patient & Family Education
- Avoid grapefruit juice within 2 h of taking sirolimus.
- Limit exposure to sunlight (UV exposure).
- Note: Decreased effectiveness possible for vaccines during therapy.
- Use or add barrier contraceptive before, during, and for 12 wk after discontinuing therapy.