Sirolimus

A to Z Drug Facts

 Actions Inhibits T-lymphocyte activation and proliferation that occurs in response to antigenic and cytokine stimulation; inhibits antibody production.

 Indications Prophylaxis of organ rejection in patients receiving renal transplants.

Treatment of psoriasis.

 Contraindications Standard considerations.

 Route/Dosage

Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use sirolimus.

ADULTS: PO Recommended loading dose of 6 mg with a daily maintenance dose of 2 mg (ie, loading dose 3 times the maintenance dose) in a regimen with cyclosporine and corticosteroids.

ADULTS AND CHILDREN at least 13 yr who weigh less than 40 kg: PO Adjust dose to 1 mg/m²/day based on body surface area. The loading dose should be 3 mg/m².

Hepatic Impairment: PO Reduce maintenance dose by approximately 33%; do not modify loading dose.

 Interactions

Cyclosporine: Sirolimus plasma concentrations may be increased; administer sirolimus 4 hr after cyclosporine. Cytochrome P450 3A4 inhibitors (eg, erythromycin, protease inhibitors [eg, ritonavir], verapamil): Sirolimus plasma levels may be elevated, increasing the pharmacologic and adverse effects. Cytochrome P450 3A4 inducers (eg, carbamazepine, phenytoin, St. John's wort): Sirolimus plasma levels may be reduced, decreasing the pharmacologic effects. Diltiazem, ketoconazole: Sirolimus plasma concentrations may be increased. Rifampin: Sirolimus plasma concentrations may be decreased. Vaccination: Response to vaccination may be less effective.

 Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Hypertension; hypotension; atrial fibrillation; CHF; hemorrhage; hypervolemia; palpitations; peripheral vascular disorder; postural hypotension; syncope; tachycardia; thrombophlebitis; thrombosis; vasodilation. CNS: Insomnia; tremor; headache; anxiety; confusion; depression; dizziness; emotional lability; hypertonia; hyperesthesia; hypotonia; neuropathy; paresthesia; somnolence. DERMATOLOGIC: Acne; rash; skin ulcer; fungal dermatitis; hirsutism; pruritus; skin hypertrophy; sweating. EENT: Abnormal vision; cataract; conjunctivitis; deafness; ear pain; otitis media; tinnitus. GI: Constipation; diarrhea; dyspepsia; nausea; vomiting; anorexia; dysphagia; eructation; esophagitis; flatulence; gastritis; gastroenteritis; gingivitis; gum hyperplasia; ileus; mouth ulceration; oral moniliasis; stomatitis. GU: UTI; albuminuria; bladder pain; dysuria; hematuria; hydronephrosis; impotence; kidney pain; kidney tubular necrosis; nocturia; oliguria; pyuria; scrotal edema; testis disorder; toxic nephropathy; increased urinary frequency; urinary incontinence; urinary retention. HEMATOLOGIC: Anemia; leukopenia; thrombocytopenia; ecchymosis; leukocytosis; lymphadenopathy; polycythemia. HEPATIC: Abnormal LFTs. METABOLIC: Increased serum creatinine; hypercholesterolemia; hyperkalemia; hyperlipemia; hypokalemia; increased LDH; hypophosphatemia; weight gain/loss; diabetes mellitus; glucosuria; acidosis; increased alkaline phosphatase; increased BUN; increased creatine phosphokinase; dehydration; abnormal healing; hypercalcemia; hypoglycemia; hypomagnesemia; hyponatremia. RESPIRATORY: Dyspnea; pharyngitis; upper respiratory tract infection; asthma; atelectasis; bronchitis; increased cough; epistaxis; hypoxia; lung edema; pleural effusion; pneumonia; rhinitis; sinusitis. OTHER: Edema; peripheral edema; abdominal pain; asthenia; back pain; chest pain; fever; pain; arthralgia; lymphocele; facial edema; Cushing syndrome; arthrosis; bone necrosis; leg cramps; myalgia; osteoporosis; tetany; abdominal enlargement; abscess; ascites; cellulitis; chills; flu syndrome; hernia; infection; malaise; pelvic pain; peritonitis; sepsis.

 Precautions

Pregnancy: Category C. Lactation: Undetermined. Children younger than 13 yr: Safety and efficacy not established. Infection: Increased susceptibility to infection, including Pneumocystis carinii may occur. Lipids: Increased serum cholesterol and triglycerides, requiring treatment, may occur. Lymphoma: Increased possibility of developing lymphoma. Renal function: Decreased renal function may occur; monitor closely.

 Administration/Storage

• Refrigerate and protect from light oral solution bottles and pouches at 2° to 8°C (36° to 46°F). They will be stable for 24 mo.
• Once the contents are opened, use within a short period of time. Review package inserts for specific instructions. If a slight haze appears, shake gently until the haze disappears.
• Anticipate administration in a regimen with cyclosporine and corticosteroids for prevention of renal rejection.
• Administer 4 hr after cyclosporine.
• Administer diluted as directed.
• Do not administer with grapefruit juice or use grapefruit juice for dilution.

 Assessment/Interventions

• Obtain patient history including drug history and any known allergies.
• Manage patients receiving sirolimus in facilities equipped and staffed with adequate laboratory and supportive medical resources.
• Monitor patient for potential drug interactions and side effects.
• Monitor blood sirolimus levels in pediatric patients, patients with hepatic function impairment, or during coadministration of strong CYP3A4 inducers and inhibitors, and if cyclosporine dosage is markedly reduced or discontinued.
• Monitor patient for signs and symtoms of graft rejection including increased fever, pain over transplant site, weight gain, and increased serum creatinine.
• Monitor patient for signs and symptoms of infection, bleeding, bruising, or development of lymphoma.

 Patient/Family Education

• Inform patient of the risks and benefits of sirolimus therapy.
• Give patients complete dosage instructions and review the product information with the patient.
• Instruct patient concerning signs and symptoms of renal rejection and to report them immediately to health care provider.
• Instruct patient to inform the health care provider immediately if experiencing signs and symptoms of infection.
• Caution women of childbearing potential to use effective contraception prior to the initiation of sirolimus therapy, during, and for 12 wk after therapy has been discontinued.
• Instruct patient to take medication consistently with or without food.
• Warn patient not to alter the dose or discontinue the medication without consulting the health care provider.
• Instruct patient to check with health care provider before taking any OTC or prescription medication, or receiving any vaccination.
• Caution patient to inform the health care provider if pregnant, planning to become pregnant, or planning to breastfeed.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts