si·ro·li·mus (s -r  l-ms)n. An immunosuppressive drug produced by the actinomycete Streptomyces hygroscopicus, used in combination with cyclosporine and corticosteroids to prevent rejection of transplanted tissues or organs. |
sirolimus,
sirolimus
Rapamune
Pharmacologic class: Macrocyclic lactone
Therapeutic class: Immunosuppressant
Pregnancy risk category C
FDA Boxed Warning
• Immunosuppression may increase patient's susceptibility to infection and lymphoma development. Give under supervision of physician experienced in immunosuppressive therapy and management of renal transplant patients, in facility with adequate diagnostic and treatment resources. Physician responsible for maintenance therapy should have complete information needed for patient follow-up.
Action
Inhibits early activation and proliferation of T lymphocytes and inhibits cell cycle progression at a later stage
Availability
Oral solution: 1 mg/ml
Tablets: 1 mg, 2 mg
⊘Indications and dosages
➣ Prevention of organ rejection in patients with kidney transplants
Adults and adolescents older than age 13 who weigh more than 40 kg (88 lb): Initially, 6 mg P.O. as a single dose as soon as possible after transplantation, then a maintenance dosage of 2 mg P.O. once daily. Usually given with cyclosporine and corticosteroids.
Dosage adjustment
• Mild to moderate hepatic failure
Contraindications
• Hypersensitivity to drug or its components
Precautions
Use cautiously in:
• renal or hepatic disease, cancer, diabetes mellitus, hyperlipidemia, infectious complications
• patients with liver or lung transplants (use not recommended)
• pregnant or breastfeeding patients
• children younger than age 13.
Administration
• Administer consistently either with or without food.
• Use syringe provided to withdraw prescribed amount. Dilute oral solution in a glass or plastic (not Styrofoam) cup containing at least 2 oz of water or orange juice. Don't use other fluids, especially grapefruit juice.
• Swirl cup to mix drug thoroughly; discard syringe. Administer diluted drug right away. Then fill cup with 4 oz of water or orange juice, and have patient drink fluid right away.
☞ If solution touches skin or mucous membranes, immediately wash affected area with soap and water.
• Wait 4 hours after the cyclosporine dose (if prescribed) before giving sirolimus.
| Route | Onset | Peak | Duration |
| P.O. | Unknown | 1-3 hr | Unknown |
Adverse reactions
CNS: headache, drowsiness, paresthesia, hypoesthesia, hypertonia, hypertonia, emotional lability, dizziness, confusion, syncope, malaise, asthenia, depression, anxiety, tremor, insomnia
CV: hypertension, hypotension, tachycardia, chest pain, edema, palpitations, vasodilation, peripheral edema, peripheral vascular disorders, thrombo-phlebitis, thrombosis, heart failure , atrial fibrillation, hemorrhage
EENT: abnormal vision, cataract, conjunctivitis, hearing loss, ear pain, otitis media, tinnitus, epistaxis, rhinitis, sinusitis, pharyngitis
GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, hernia, enlarged abdomen, ascites, esophagitis, eructation, flatulence, gastritis, gastroenteritis, dysphagia, stomatitis, mouth ulcers, oral candidiasis, anorexia, peritonitis
GU: dysuria, nocturia, pyuria, urinary retention, hematuria, albuminuria, urinary frequency or incontinence, urinary tract infection, pelvic pain, kidney or bladder pain, hydronephrosis, erectile dysfunction, scrotal edema, testes disorders, oliguria, GU tract hemorrhage, renal tubular necrosis, toxic nephropathy
Hematologic: anemia, bruising, polycythemia, leukocytosis, thrombocytopenia, leukopenia, thrombotic thrombocytopenia Metabolic: glycosuria, hyperglycemia, diabetes mellitus, hypokalemia, hypophosphatemia, hypovolemia, hypercalcemia, dehydration, Cushing's syndrome, acidosis
Respiratory: dyspnea, cough, upper respiratory infection, bronchitis, hypoxia, pneumonia, atelectasis, pleural effusion, pulmonary edema, asthma
Skin: skin ulcers, skin hypertrophy, pruritus, fungal dermatitis, hirsutism, rash, acne, cellulites, non-melanoma skin cancer
Other: gingivitis, gum hyperplasia, weight changes, neck pain, fever, abscess, chills, facial edema, flulike symptoms, infection, lymphadenopathy, abnormal healing, sepsis, lymphoma
Interactions
Drug-drug. Aminoglycosides, amphotericin, other nephrotoxic drugs: increased risk of nephrotoxicity
Bromocriptine, cimetidine, clarithromycin, danazol, erythromycin, fluconazole, indinavir, itraconazole, metoclopramide, nicardipine, ritonavir, verapamil, other CYP3A4 inhibitors: decreased sirolimus metabolism and increased blood level
Carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, other CYP3A4 inducers: decreased sirolimus blood level
Cyclosporine, diltiazem: increased sirolimus blood level
Live-virus vaccines: reduced vaccine efficacy
Drug-diagnostic tests. Blood urea nitrogen, cholesterol, creatinine, hepatic enzymes, lipids, red blood cells: increased levels
Calcium, glucose, phosphate, white blood cells: increased or decreased levels
Hemoglobin, magnesium, platelets, sodium: decreased levels
Drug-food. Grapefruit juice: decreased sirolimus metabolism and increased blood level
Drug-herbs. Astragalus, echinacea, melatonin, St. John's wort: decreased sirolimus efficacy
Patient monitoring
• Watch closely for signs and symptoms of infection.
• Monitor renal function tests, lipid panel, electrolyte levels, blood chemistry studies, and sirolimus blood level.
• Evaluate all body systems carefully, especially cardiovascular and renal.
• Assess neurologic status closely. Implement safety precautions as needed to prevent injury.
Patient teaching
• Teach patient correct procedure for taking drug.
• Advise patient to take consistently either with or without food, but not with grapefruit juice.
• Instruct patient to wait 4 hours after cyclosporine dose (if prescribed) before taking sirolimus.
☞ Tell patient to wash affected area with soap and water immediately if drug touches his skin or mucous membranes.
• Inform patient that drug affects almost every body system. Advise him to report significant adverse reactions.
☞ Advise patient that drug lowers resistance to infection. Instruct him to immediately report fever, cough, breathing problems, sore throat, or other signs and symptoms of infection.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
☞ Instruct patient to immediately report unusual bleeding or bruising.
☞ Advise female patient to use effective contraception before and during therapy and for 12 weeks after discontinuation.
☞ Caution patient to limit exposure to sunlight and ultraviolet light. Advise him to wear protective clothing and to use sunscreen with a high protection factor to help prevent skin cancer.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.
sirolimus
How to thank TFD for its existence? Tell a friend about us, add a link to this page, add the site to iGoogle, or visit webmaster's page for free fun content.
| ?Page tools | ||
|---|---|---|
|