Classifications: immunomodulator; immunosuppressant; Therapeutic: immunosuppressant
Pregnancy Category: C
1 mg tablets; 1 mg/mL oral solution
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,
Inhibits antibody production and acute transplant rejection reaction in autoimmune disorders [e.g., systemic lupus erythematosus
(SLE)]. Indicated by nonrejection of transplanted organ.
Prophylaxis of kidney transplant rejection.
Treatment of psoriasis.
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.
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
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.
Reduce maintenance dose by 33%.
- 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
- 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
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
, deafness, ear pain, otitis media, tinnitus.
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
Rapidly with 14% bioavailability. Peak:
2 h. Distribution:
92% protein bound, distributes in high concentrations to heart, intestines, kidneys, liver, lungs, muscle, spleen, and
In liver (CYP3A4). Elimination:
91% in feces, 2.2% in urine. Half-Life:
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.