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Afinitor, Zortress

Pharmacologic class: mTOR inhibitor

Therapeutic class: Antineoplastic, macrolide immunosuppressant

Pregnancy risk category D (Afinitor), C (Zortress)




Binds to intracellular proteins, resulting in an inhibitory (Afinitor) or immunosuppressive (Zortress) complex resulting in inhibition of mTOR kinase


Tablets (Afinitor): 2.5 mg, 5 mg, 7.5 mg, 10 mg

Tablets (Zortress): 0.25 mg, 0.5 mg, 0.75 mg

Indications and dosages

Metastatic, locally advanced, or unresectable progressive neuroendocrine tumors of pancreatic origin; advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib; renal angiomyolipoma and tuberous sclerosis complex

Adults: 10 mg (Afinitor) P.O. daily continued as long as clinical benefit is observed or until unacceptable toxicity occurs

Subependymal giant cell astrocytoma (SEGA) requiring intervention in patients who aren't candidates for surgical intervention

Adults and children age 3 and older with body surface area (BSA) of 2.2 m2 or more: 7.5 mg (Afinitor) P.O. daily

Adults and children age 3 and older with BSA of 1.3 to 2.1 m2: 5 mg (Afinitor) P.O. daily

Adults and children age 3 and older with BSA of 0.5 to 1.2 m2: 2.5 mg (Afinitor) P.O. daily

Prophylaxis of organ rejection in kidney transplant patients at low-to-moderate immunologic risk

Adults: Initially, 0.75 mg (Zortress) P.O. b.i.d. in combination with basiliximab induction and concurrently with reduced doses of cyclosporine and corticosteroids. Adjust maintenance dosage to achieve Zortress trough concentration within 3- to 8-ng/ml target range at 4- to 5-day intervals. Start doses as soon as possible after transplant.

Dosage adjustment

• Moderate hepatic impairment (Zortress)

• Mild, moderate, or severe hepatic impairment; change in hepatic status during therapy (Afinitor)

• Patients with SEGA who have severe hepatic impairment (Afinitor not recommended)

• Concurrent use of CYP3A4 inducers or inhibitors (Afinitor, Zortress)

• Concurrent use of moderate inhibitors of CYP3A4 or p-glycoprotein (PgP) (Afinitor)

• Strong CYP3A4 inducers (Afinitor)

• When switching cyclosporine formulations or when cyclosporine dosage is reduced according to recommended target concentrations (Zortress)

• Possible dosage adjustment based on everolimus blood concentrations achieved, tolerability, individual response, and change in concomitant medications (Afinitor, Zortress)


• Hypersensitivity to drug, other rapamycin derivatives, or any of its components



Use cautiously in:

• moderate hepatic impairment, renal failure

• severe hepatic impairment (use not recommended)

• noninfectious pneumonitis, infection, oral ulceration

• concurrent use of strong CYP3A4 inhibitors or inducers (avoid use)

• concurrent use of moderate CYP3A4 or PgP inhibitors

• concurrent use of live vaccines, close contact with those who have received live vaccines (avoid use)

• grapefruit, grapefruit juice, other foods known to inhibit CYP450 and PgP activity, St. John's wort

• pregnant or breastfeeding patients

• children with SEGA younger than age 3 or with BSA less than 0.58 m2 (safety and efficacy not established).


Use cautiously in:

• moderate hepatic impairment, renal dysfunction

• noninfectious pneumonitis, infection, oral ulceration

• lymphoma, other malignancies

• rare hereditary problems of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption (avoid use)

• wound healing, fluid accumulation, hyperlipidemia, proteinuria, polyoma virus infections, noninfectious pneumonitis, thrombotic microangiopathy, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, new-onset diabetes, male infertility

• prolonged exposure to ultraviolet light and sunlight (avoid use)

• concurrent use of CYP3A4 and CYP2D6 substrates with narrow therapeutic index

• concurrent use of strong CYP3A4 inducer rifampin (not recommended)

• concurrent use of ACE inhibitors

• concurrent use of standard doses of cyclosporine (avoid use)

• concurrent use of HMG-CoA reductase inhibitors (such as simvastatin, lovastatin) in transplant patients receiving cyclosporine

• concurrent use of live vaccines, close contact with those who have received live vaccines (avoid use)

• pregnant or breastfeeding patients

• children younger than age 18 (safety and efficacy not established).


• Administer tablets whole with a glass of water and food (not grapefruit juice or grapefruit products) or give consistently without food.

• Administer Zortress consistently approximately 12 hours apart to minimize variability in absorption and at same time as cyclosporine.

• For patient unable to swallow Afinitor tablets: Immediately before administering, disperse tablets completely in a glass of water (containing approximately 30 ml) by gently stirring. Rinse glass with same volume of water and have patient completely swallow rinse to ensure entire dose is administered.

• Before starting Afinitor, obtain CBC, renal function tests (including BUN, serum creatinine, or urinary protein), and fasting serum glucose and lipid profile (when possible ensure optimal glucose and lipid control).

Discontinue Afinitor therapy in patients with signs and symptoms of severe noninfectious pneumonitis.

Before starting Afinitor, complete treatment of preexisting invasive fungal infections. During treatment, be vigilant for signs and symptoms of infection. If diagnosis of infection is made, institute appropriate treatment promptly and consider interrupting or discontinuing therapy. If diagnosis of invasive systemic fungal infection is made, discontinue drug and treat with appropriate antifungal therapy.

• Be aware that Afinitor isn't recommended for use in patients with SEGA who have severe hepatic impairment.

• Be aware that patients with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption shouldn't take Zortress as this may result in diarrhea and malabsorption of drug.

Adverse reactions


CNS: headache, migraine headache, fatigue, malaise, asthenia, dizziness, insomnia, paresthesia, personality change, somnolence, anxiety, seizures

CV: hypertension, tachycardia, deep vein thrombosis, cardiac arrest, congestive heart failure

EENT: eyelid edema, conjunctivitis, ocular hyperemia, otitis media, otitis externa, nasopharyngitis, rhinitis, allergic rhinitis, epistaxis, sinusitis, oropharyngeal pain, pharyngolaryngeal pain, rhinorrhea, pharyngitis, pharyngeal inflammation, nasal congestion

GI: nausea, vomiting, diarrhea, abdominal pain, stomatitis, oral ulcers, constipation, dry mouth, anorexia, hemorrhoids, dysphagia, gastroenteritis, gastric infection, gastritis

GU: urinary tract infection, proteinuria, nephrotoxicity, acute renal failure

Hematologic: anemia, decreased hemoglobin, leukopenia, lymphopenia, neutropenia, pancytopenia, thrombocytopenia, hemorrhage

Hepatic: hepatic failure

Metabolic: hyperglycemia, increased ALP, hypercholesterolemia, decreased bicarbonate, hypophosphatemia, increased AST and ALT, hypertriglyceridemia, hypocalcemia, hypokalemia, hyperkalemia, hyponatremia, increased serum creatinine, decreased albumin, increased bilirubin, new-onset exacerbation of preexisting diabetes mellitus

Musculoskeletal: arthralgia, back pain, extremity pain, muscle spasms, jaw pain

Respiratory: cough, upper respiratory tract infection, dyspnea, exertional dyspnea, pneumonia, noninfectious pneumonitis, acute respiratory distress, pulmonary embolus, respiratory failure, pleural effusion

Skin: rash, nail disorders, pruritus, dry skin, impaired wound healing, erythema, skin lesion, acneiform dermatitis, cellulitis, tinea, skin infection, contact dermatitis, acne, excoriation, pityriasis rosea

Other: mucosal inflammation, edema, peripheral edema, fluid accumulation, dehydration, fever, infections, weight loss, decreased appetite, dysgeusia, chest pain, chills, abnormal chest Xray, palmar-plantar erythrodysesthesia syndrome, sepsis, death (cause unknown), hypersensitivity reactions (including, but not limited to, anaphylaxis, dyspnea, flushing, chest pain, angioedema)


CNS: fatigue, headache, tremor, insomnia

CV: hypertension

GI: nausea, vomiting, constipation, diarrhea, abdominal pain, dyspepsia

GU: urinary tract infection, proteinuria, male infertility, hematuria, dysuria

Hematologic: anemia, leukopenia, graft thrombosis, thrombotic microangiopathy, TTP, hemolytic uremic syndrome

Hepatic: increased hepatic enzymes and bilirubin

Metabolic: hyperlipidemia, increased serum creatinine, new-onset diabetes mellitus, exacerbation of preexisting diabetes mellitus, hyperkalemia, hypokalemia, hypercholesterolemia, dyslipidemia, hypomagnesemia, hypophosphatemia, hyperglycemia

Musculoskeletal: back pain, extremity pain

Respiratory: cough, upper respiratory tract infection, noninfectious pneumonitis

Skin: impaired wound healing

Other: peripheral edema, incision and procedural pain, fluid accumulation, fever, serious infections, polyoma virus infections, lymphomas and other malignancies, angioedema, hypersensitivity



Drug-drug. Depot octreotide: increased octreotide Cmin

Moderate CYP3A4 and PgP inhibitors (such as amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, verapamil): significantly increased everolimus exposure

Strong CYP3A4 inducers (such as carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine): decreased everolimus exposure

Strong CYP3A4 inhibitors (such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole): significantly increased everolimus exposure

Drug-diagnostic tests. ALP, ALT, AST, blood glucose, cholesterol, serum bilirubin, serum creatinine, lipids, triglycerides, urine proteins: increased levels

Bicarbonates, calcium, hemoglobin, platelets, serum albumin, serum phosphorus, sodium, WBCs: decreased levels

Potassium: decreased or increased level

Drug-food. Grapefruit, grapefruit juice, other foods known to inhibit CYP450 and PgP: increased everolimus exposure

Drug-herbs. St. John's wort: decreased everolimus exposure


Drug-drug. CYP3A substrates (such as cyclosporine) and CYP2D6 substrates with narrow therapeutic indices: potentially increased concentrations of these drugs

CYP3A4 and PgP substrates (verapamil): significantly increased everolimus Cmax and area under the curve

Moderate CYP3A4 and PgP inhibitors (such as amprenavir, diltiazem, fluconazole, indinavir, macrolide antibiotics, nicardipine): increased everolimus blood concentration

PgP inhibitors (such as cyclosporine, digoxin): increased everolimus blood concentration

Strong CYP3A4 inducers (such as carbamazepine, efavirenz, nevirapine, phenobarbital, phenytoin, rifampin): decreased everolimus exposure

Strong CYP3A4 inhibitors (such as clarithromycin, itraconazole, ketoconazole, ritonavir, telithromycin, voriconazole): significantly increased everolimus exposure

Drug-diagnostic tests. Blood glucose, cholesterol, lipids, magnesium, hepatic enzymes, serum bilirubin, serum creatinine, serum phosphorus: increased levels

Hemoglobin, platelets: decreased levels

Potassium: decreased or increased level

Drug-food. Grapefruit, grapefruit juice: increased everolimus exposure

Drug-herbs. St. John's wort: decreased everolimus exposure

Patient monitoring

• Closely monitor CBC with differential.

Monitor renal function, including BUN, urinary protein, and serum creatinine, closely.

• Closely monitor drug blood concentration in patients with hepatic impairment; during concomitant administration of CYP3A4 inducers/inhibitors, or PgP substrates; when switching cyclosporine formulations; and when cyclosporine dosage is reduced according to recommended target concentrations.

• Watch for increases in serum cholesterol, triglyceride, and blood glucose levels.

Closely monitor patients for hypersensitivity reactions, serious infections, respiratory or cardiac signs and symptoms, signs or symptoms of bleeding or thrombosis, seizures, and palmar-plantar erythrodysesthesia.

• Be aware that patients are at increased risk for delayed wound healing and fluid accumulation; particularly monitor incision sites to minimize complications.

Patient teaching

• Tell patient to take drug at same time each day with a whole glass of water, either consistently with food or without food.

• For patient taking Afinitor: Instruct patient to swallow tablets whole and not to chew or crush them. Tell patient unable to swallow tablets to disperse drug completely (by gently stirring) in a glass of water (containing approximately 1 ounce) immediately before drinking, then rinse with same volume of water and completely swallow rinse to ensure entire dose is taken.

• Tell patient to avoid grapefruit juice and grapefruit products during therapy.

• Inform patient of the need to monitor blood chemistry and hematologic values before starting therapy and periodically thereafter.

Instruct patient to immediately seek medical attention for difficulty breathing or new or worsening respiratory signs or symptoms, flushing, chest pain, swelling of airway or tongue, fever or other signs or symptoms of infection, urinary problems, or bleeding.

• For patient taking Afinitor: Instruct patient to report signs and symptoms of palmar-plantar erythrodysesthesia (such as redness, swelling, tenderness, or tingling of palms of hands or soles of feet).

For patient taking Zortress: Inform patient of increased risk of developing lymphomas and other malignancies, particularly of the skin. Tell patient to avoid prolonged exposure to ultraviolet light and sunlight during therapy.

For patient taking Zortress: Inform patient of risk of a clot in the blood vessels of the transplanted kidney and to immediately seek medical attention if pain in the groin, lower back, side, or abdomen; change in urination; blood in urine or dark-colored urine; fever; nausea; or vomiting occurs.

• Advise patient to manage oral ulcerations with mouthwashes (without alcohol or peroxide) and topical treatments, as prescribed.

• Instruct patient to tell prescriber about all drugs he's taking, because some drugs have potential for serious drug interactions and shouldn't be taken with everolimus.

• Tell patient to avoid live vaccines and close contact with those who have received live vaccines during therapy.

• Advise patient to avoid use of St. John's wort during therapy.

• For patient taking Zortress: Advise female patient of childbearing age that drug may cause fetal harm and to use an effective method of contraception during therapy and for 8 weeks after treatment ends.

• For patient taking Afinitor: Advise breastfeeding patient that she should decide whether to discontinue breastfeeding or discontinue drug, taking into account importance of the drug for her treatment.

• For patient taking Zortress: Advise female patient of childbearing age to avoid breastfeeding during therapy.

• For patient taking Zortress: Inform male patient of potential risk of infertility with therapy.

• 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.

McGraw-Hill Nurse's Drug Handbook, 7th Ed. Copyright © 2013 by The McGraw-Hill Companies, Inc. All rights reserved


A compound that is a derivative of sirolimus, used as an immunosuppresant after transplant surgery, in the treatment of certain types of advanced breast, kidney, and pancreatic cancers, and in the treatment of some tumors associated with tuberous sclerosis complex.
The American Heritage® Medical Dictionary Copyright © 2007, 2004 by Houghton Mifflin Company. Published by Houghton Mifflin Company. All rights reserved.


A new immunosuppressive agent intended for use in heart transplantation. The drug has been found more effective than AZATHIOPRINE in reducing the severity of coronary artery narrowing and occlusion in the grafted organ (cardiac-allograft vasculopathy).
Collins Dictionary of Medicine © Robert M. Youngson 2004, 2005

Immunosuppressants: Cyclosporine, Methotrexate, Everolimus, Sirolimus, and Tacrolimus

Synonym/acronym: Cyclosporine (Sandimmune), methotrexate (MTX, amethopterin, Folex, Rheumatrex), methotrexate sodium (Mexate), everolimus (Afinitor, Certican, Zortress), sirolimus (Rapamycin), tacrolimus (Prograf).

Common use

To monitor appropriate drug dosage of immunosuppressant related to organ transplant maintenance.


Whole blood (1 mL) collected in lavender-top tube for cyclosporine, everolimus; sirolimus; tacrolimus. Serum (1 mL) collected in a red-top tube for methotrexate; specimen must be protected from light.
ImmunosuppressantRoute of AdministrationRecommended Collection Time
CyclosporineOral or intravenous12 hr after dose or immediately prior to next dose
MethotrexateOralVaries according to dosing protocol
IntramuscularVaries according to dosing protocol
EverolimusOralImmediately prior to next dose
SirolimusOralImmediately prior to next dose
TacrolimusOralImmediately prior to next dose
Leucovorin therapy, also called leucovorin rescue, is used in conjunction with administration of methotrexate. Leucovorin, a fast-acting form of folic acid, protects healthy cells from the toxic effects of methotrexate

Normal findings

(Method: Immunoassay for cyclosporine and methotrexate; liquid chromatography with tandem mass spectrometry for everolimus, sirolimus, and tacrolimus)
Therapeutic DoseHalf-Life (hr)Volume of Distribution (L/kg)Protein Binding (%)Excretion
Conventional UnitsSI Units (Conventional Units × 0.832)
Cyclosporine100–300 ng/mL renal transplant83–250 nmol/L8–244–690Renal
200–350 ng/mL cardiac, hepatic, pancreatic transplant166–291 nmol/L8–244–690Renal
100–300 ng/mL bone marrow transplant83–250 nmol/L8–244–690Renal
MethotrexateDependent on therapeutic approach5–90.4–150–70Renal
Low dose: 0.5–1 micromol/L
High dose: Less than 5 micromol/L at 24 h; less than 0.5 micromol/L at 48 h; less than 0.1 micromol/L at 72 h
Conventional UnitsSI Units (Conventional Units × 0.832)
EverolimusTransplant: 3–8 ng/mL18–35 (kidney); 30–35 (liver)128–58975Biliary
Oncology: 5–10 ng/mL18–35128–58975Biliary
SirolimusMaintenance phase: renal transplant: 4–12 ng/mL; liver transplant: 12–20 ng/mL46–784–2092Biliary
TacrolimusMaintenance phase: renal transplant: 6–12 ng/mL; liver transplant: 4–10 ng/mL; pancreas transplant: 10–18 ng/mL; bone marrow transplant: 10–20 ng/mL10–141.599Biliary
Therapeutic targets for the initial phase post-transplantation are slightly higher than during the maintenance phase and are influenced by the specific therapy chosen for each patient with respect to coordination of treatment for other conditions and corresponding therapies. Therapeutic ranges for everolimus, sirolimus, and tacrolimus assume concomitant administration of cyclosporine and steroids.


Cyclosporine is an immunosuppressive drug used in the management of organ rejection, especially rejection of heart, liver, pancreas, and kidney transplants. Its most serious side effect is renal impairment or renal failure. Cyclosporine is often administered in conjunction with corticosteroids (e.g., prednisone) for its anti-inflammatory or immune-suppres-sing properties and with other drugs (e.g., everolimus, sirolimus, tacrolimus) to reduce graft-versus-host disease. Methotrexate is a highly toxic drug that causes cell death by disrupting DNA synthesis. Methotrexate is also used in the treatment of rheumatoid arthritis, psoriasis, polymyositis, and Reiter’s syndrome. These drugs are metabolized by the cytochrome enzyme, CYP3A4 or CYP3A5, which is essential to achieve the desired therapeutic effect. Testing for specific CYP450 genotype defects can be performed in some laboratories on blood and buccal specimens. Counseling and informed written consent are generally required for genetic testing. Test results can identify poor and ultrasensitive drug metabolizers. This allows for the possibility of personalized adjustments to their medication regimen or decisions to seek alternative drugs which in turn results in safer, more effective treatment.

Many factors must be considered in effective dosing and monitoring of therapeutic drugs, including patient age; weight; interacting medications; electrolyte balance; protein levels; water balance; conditions that affect absorption and excretion; as well as foods, herbals, vitamins, and minerals that can either potentiate or inhibit the intended target concentration.

Important note: These medications are metabolized and excreted by the kidneys and are therefore contra-indicated in patients with renal disease and cautiously advised in patients with renal impairment. Information regarding medications must be clearly and accurately communicated to avoid misunderstanding of the dose time in relation to the collection time. Miscommunication between the individual administering the medication and the individual collecting the specimen is the most frequent cause of subtherapeutic levels, toxic levels, and misleading information used in the calculation of future doses. Some pharmacies use a computerized pharma-cokinetics approach to dosing that eliminates the need to be concerned about peak and trough collections; random specimens are adequate. If administration of the drug is delayed, notify the appropriate department(s) to reschedule the blood draw and notify the requesting health-care provider (HCP) if the delay has caused any real or perceived therapeutic harm.

This procedure is contraindicated for



    Cyclosporine, Sirolimus, Tacrolimus

  • Assist in the management of treatments to prevent organ rejection
  • Monitor for toxicity
  • Everolimus

  • Assist in the management of treatments to prevent organ rejection
  • Assist in the management of treatments for subependymal giant cell astrocytoma
  • Monitor effectiveness of treatment of renal cell carcinoma
  • Monitor for toxicity
  • Methotrexate

  • Monitor effectiveness of treatment of cancer and some autoimmune disorders
  • Monitor for toxicity

Potential diagnosis

Normal levelsTherapeutic effect
Toxic levelsAdjust dose as indicated
 CyclosporineRenal impairment
 MethotrexateRenal impairment
 Everolimus, sirolimus, tacrolimusHepatic impairment

Critical findings

  • It is important to note the adverse effects of toxic and subtherapeutic levels. Care must be taken to investigate signs and symptoms of too little and too much medication.

  • Note and immediately report to the health-care provider (HCP) any critically increased or decreased values and related symptoms.

  • It is essential that a critical finding be communicated immediately to the requesting health-care provider (HCP). A listing of these findings varies among facilities.

  • Timely notification of a critical finding for lab or diagnostic studies is a role expectation of the professional nurse. Notification processes will vary among facilities. Upon receipt of the critical value the information should be read back to the caller to verify accuracy. Most policies require immediate notification of the primary HCP, Hospitalist, or on-call HCP. Reported information includes the patient’s name, unique identifiers, critical value, name of the person giving the report, and name of the person receiving the report. Documentation of notification should be made in the medical record with the name of the HCP notified, time and date of notification, and any orders received. Any delay in a timely report of a critical finding may require completion of a notification form with review by Risk Management.

  • Cyclosporine: Greater Than 500 ng/mL (SI: Greater Than 416 nmol/L)

  • Signs and symptoms of cyclosporine toxicity include increased severity of expected side effects, which include nausea, stomatitis, vomiting, anorexia, hypertension, infection, fluid retention, hypercalcemic metabolic acidosis, tremor, seizures, headache, and flushing. Possible interventions include close monitoring of blood levels to make dosing adjustments, inducing emesis (if orally ingested), performing gastric lavage (if orally ingested), withholding the drug, and initiating alternative therapy for a short time until the patient is stabilized.

  • Methotrexate: Greater Than 1 micromol/L After 48 Hr With High-Dose Therapy; Greater Than 0.02 micromol/L After 48 Hr With Low-Dose Therapy

  • Signs and symptoms of methotrexate toxicity include increased severity of expected side effects, which include nausea, stomatitis, vomiting, anorexia, bleeding, infection, bone marrow depression, and, over a prolonged period of use, hepatotoxicity. The effect of methotrexate on normal cells can be reversed by administration of 5-formyltetrahydrofolate (citrovorum or leucovorin). 5-Formyltetrahydrofolate allows higher doses of methotrexate to be given.

  • Everolimus: Greater Than 15 ng/mL (SI: Greater than 15 mcg/L)

  • Signs and symptoms of everolimus pulmonary toxicity include hypoxia, pleural effusion, cough, and dyspnea. Possible interventions include dosing adjustments, administration of corticosteroids, and monitoring of pulmonary function with chest x-ray. Use of everolimus is contraindicated in patients with severe hepatic impairment. Concomitant administration of strong CYP3A4 inhibitors may significantly increase everolimus levels.

  • Sirolimus: Greater Than 25 ng/mL (SI: Greater than 25 mcg/L)

  • Signs and symptoms of sirolimus pulmonary toxicity include cough, shortness of breath, chest pain, and rapid heart rate. Possible interventions include dosing adjustments, administration of corticosteroids, and monitoring of pulmonary function with chest x-ray.

  • Tacrolimus: Greater Than 25 ng/mL (SI: Greater than 25 mcg/L)

  • Signs and symptoms of tacrolimus toxicity include tremors, seizures, headache, high blood pressure, hyperkalemia, tinnitus, nausea, and vomiting. Possible interventions include treatment of hypertension, administration of antiemetics for nausea and vomiting, and dosing adjustments.

Interfering factors

  • Numerous drugs interact with cyclosporine and either increase cyclosporine levels or increase the risk of toxicity. These drugs include acyclovir, aminoglycosides, amiodarone, amphotericin B, anabolic steroids, cephalosporins, cimetidine, danazol, erythromycin, furosemide, ketoconazole, melphalan, methylprednisolone, miconazole, NSAIDs, oral contraceptives, and trimethoprim- sulfamethoxazole.
  • Drugs that may decrease cyclosporine levels include carbamazepine, ethotoin, mephenytoin, phenobarbital, phenytoin, primidone, and rifampin.
  • Drugs that may increase methotrexate levels or increase the risk of toxicity include NSAIDs, probenecid, salicylate, and sulfonamides.
  • Antibiotics may decrease the absorption of methotrexate.
  • Drugs and foods that may increase everolimus levels include ketoconazole, amprenavir, aprepitant, atazanavir, clarithromycin, delavirdine, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, verapamil, and voriconazole.
  • Drugs and herbs that may decrease everolimus levels include carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, and St. John’s Wort.
  • Drugs and foods that may increase sirolimus levels include bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, indinavir, metoclopramide, nicardipine, ritonavir, troleandomycin, and verapamil.
  • Drugs and herbs that may increase sirolimus levels include carbamazepine, phenobarbital, phenytoin, rifapentine, and St. John’s Wort.
  • Drugs and foods that may increase tacrolimus levels include bromocriptine, chloramphenicol, cimetidine, cisapride, clarithromycin, clotrimazole, cyclosporine, danazol, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole, methylprednisolone, metoclopramide, nelfinavir, nicardipine, nifedipine, torinavir, troleandomycin, verapamil, and voriconazole.
  • Drugs and herbs that may decrease tacrolimus levels include carbamazepine, ethotoin, mephenytoin, octreotide, phenobarbital, primidone, rifabutin, rifampin, sirolimus, and St. John’s Wort.

Nursing Implications and Procedure


  • Positively identify the patient using at least two unique identifiers before providing care, treatment, or services.
  • Patient Teaching: Inform the patient this test can assess in monitoring therapeutic and toxic drug levels.
  • Obtain a history of the patient’s complaints, including a list of known allergens, especially allergies or sensitivities to latex.
  • Obtain a history of the patient’s genitourinary and immune systems, symptoms, and results of previously performed laboratory tests and diagnostic and surgical procedures. Some considerations prior to medication administration include documentation of adequate renal function with creatinine and BUN levels, documentation of adequate hepatic function with alanine aminotransferase (ALT) and bilirubin levels, and documentation of adequate hematological and immune function with platelet and white blood cell (WBC) count. Patients receiving methotrexate must be well hydrated and, depending on the therapy, may be treated with sodium bicarbonate for urinary alkalinization to enhance drug excretion. Leucovorin calcium rescue therapy may also be part of the protocol.
  • Obtain a list of the patient’s current medications, including herbs, nutritional supplements, and nutraceuticals (see Effects of Natural Products on Laboratory Values online at DavisPlus).
  • Review the procedure with the patient. Inform the patient that specimen collection takes approximately 5 to 10 min. Address concerns about pain and explain that there may be some discomfort during the venipuncture.
  • Sensitivity to social and cultural issues, as well as concern for modesty, is important in providing psychological support before, during, and after the procedure.
  • Note that there are no food, fluid, or medication restrictions unless by medical direction.


  • Potential complications:
  • Note that lack of consideration for the proper collection time in relation to the dosing schedule can provide misleading information that may result in an erroneous interpretation of levels, creating the potential for a medication-error-related injury to the patient.

  • Avoid the use of equipment containing latex if the patient has a history of allergic reaction to latex.
  • Instruct the patient to cooperate fully and to follow directions. Direct the patient to breathe normally and to avoid unnecessary movement.
  • Observe standard precautions, and follow the general guidelines in Patient Preparation and Specimen Collection. Consider recommended collection time in relation to the dosing schedule. Positively identify the patient, and label the appropriate specimen container with the corresponding patient demographics, initials of the person collecting the specimen, date, and time of collection, noting the last dose of medication taken. Perform a venipuncture.
  • Remove the needle and apply direct pressure with dry gauze to stop bleeding. Observe/assess venipuncture site for bleeding or hematoma formation and secure gauze with adhesive bandage.
  • Promptly transport the specimen to the laboratory for processing and analysis.


  • Inform the patient that a report of the results will be made available to the requesting HCP, who will discuss the results with the patient.
  • Nutritional Considerations: Patients taking immunosuppressant therapy tend to have decreased appetites due to the side effects of the medication. Instruct patients to consume a variety of foods within the basic food groups, maintain a healthy weight, be physically active, limit salt intake, limit alcohol intake, and be a nonsmoker.
  • Recognize anxiety related to test results, and offer support. Patients receiving these drugs usually have conditions that can be intermittently moderately to severely debilitating, resulting in significant lifestyle changes. Educate the patient regarding access to counseling services, as appropriate.
  • Reinforce information given by the patient’s HCP regarding further testing, treatment, or referral to another HCP. Explain to the patient the importance of following the medication regimen and give instructions regarding drug interactions. Answer any questions or address any concerns voiced by the patient or family.
  • Instruct the patient to be prepared to provide the pharmacist with a list of other medications he or she is already taking in the event that the requesting HCP prescribes a medication.
  • Depending on the results of this procedure, additional testing may be performed to evaluate or monitor progression of the disease process and determine the need for a change in therapy. Evaluate test results in relation to the patient’s symptoms and other tests performed.

Related Monographs

  • Related tests include ALT, AST, bilirubin, BUN, CBC platelet count, CBC WBC count and differential, and creatinine.
  • Refer to the Genitourinary and Immune systems tables at the end of the book for related tests by body system.
Handbook of Laboratory and Diagnostic Tests, © 2013 Farlex and Partners
References in periodicals archive ?
Issuing its final guidance, Nice said Everolimus - which is marketed as Afinitor and Novartis - "does not provide enough benefit to patients to justify its high cost".
The study compared the safety and effectiveness of three types of stent: bare-metal stents, stents that eluted the drug sirolimus and those that eluted the drug everolimus. The drugs help prevent tissue inside the arteries from growing over the mesh structure of the stent.
The National Institute for Health and Clinical Excellence (Nice) confirmed it was turning down everolimus (Afinitor) despite a new risk-sharing scheme proposed by manufacturer Novartis.
The Institute of Medical Genetics, which is based in the city, will examine the effect of the drug everolimus (Afinitor) on kidney tumours.
The Xience V Everolimus Eluting Coronary Stent System was approved for "improving coronary luminal diameter in patients with symptomatic heart disease due to de novo native coronary artery lesions (length 28 mm or less) with reference vessel diameters of 2.5 mm to 4.5 mm."
With the introduction of the novel immunosuppressive agents sirolimus and everolimus, new, potentially more effective immunosuppressive regimens
SNX-5422 was studied in combination with everolimus and showed promising signs of clinical activity in subjects with advanced NETs.
The rate of progression-free survival with everolimus and letrozole treatment is very impressive, compared with traditional chemotherapy using carboplatin and paclitaxel.
This trial concluded that PCI with everolimus eluting stents was non inferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years.
NICE recommends lenvatinib, also known as kisplyx, be given in conjunction with another drug called everolimus. This drug-duo is recommended as an option for patients who have previously been treated for advanced renal cell carcinoma.
Although there are currently two clinical trials evaluating ibrutinib in combination with nivolumab (programmed cell death protein 1, PD-1, inhibitor) or everolimus (mammalian target of rapamycin, mTOR, inhibitor) for metastatic renal cell carcinoma (RCC), there are no reports of RCC (metastatic or non-metastatic) showing response to a BTK inhibitor in humans.