Mosby's 2014 Nursing Drug Reference (431 page)

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carfilzomib

(car-fil′zoe-mib)

Kyprolis

Func. class.:
Antineoplastic biologic response modifiers

Chem. class.:
Signal transduction inhibitors (STIs)

ACTION:

Antiproliferative and proapoptotic activity

USES:

Multiple myeloma in those who have received ≥2 therapies (including bortezomib and immunomodulatory agents)

CONTRAINDICATIONS:

Pregnancy (D), hypersensitivity

Precautions:
Breastfeeding, children, cardiac disease, cardiac arrest, dysrhythmias, MI, infusion-related reactions, pulmonary/hepatic disease, edema, thrombocytopenia, neutropenia, tumor lysis syndrome

DOSAGE AND ROUTES
Calculator

• Adult:
IV
20 mg/m
2
over 2-10 min on days 1, 2, 8, 9, 15, 16, then 12 day rest (days 17-28), then may increase to 27 mg/m
2
on days 1, 2, 8, 9, 15, 16 repeated every 28 days

 
Refer to package insert for dosage adjustments for treatment-related toxicity

Available forms:
Powder for injection 60 mg

Administer:

• 
Premedicate with dexamethasone 4 mg PO/IV before all carfilzomib 20-mg/m
2
doses during cycle 1 and before all carfilzomib 27-mg/m
2
doses in cycle 2; dexamethasone may be given in subsequent cycles if infusion-related reactions occur

• 
Hydration with 250–500 ml of NS or other IV fluids before each dose in cycle 1; additional hydration with 250–500 ml may be given after the carfilzomib infusion in cycle 1, continue hydration as needed

• 
Do not mix with other products

• 
Flush IV line with NS or D
5
for injection, before and after use

Reconstitution:

• 
Add 29 ml of sterile water for injection to the inside wall of the vial to minimize foaming (2 mg/mL); to mix, gently swirl and/or invert the vial slowly for about 1 min or until the cake or powder completely dissolves; do not shake; if foaming occurs, allow the solution to rest for 2 to 5 min or until foaming subsides; visually inspect for particulate and discoloration before use

IV injection route

• 
Give over 2-10 min; do not give as an IV bolus; the reconstituted sol may be stored in the vial/syringe at room temperature × 4 hr or ≤24 hr refrigerated

IV infusion route

• 
May further dilute in D
5
W; measure and inject the correct dose from the reconstituted vial into 50 ml D
5
W

• 
Administer IV over 2-10 min

• 
The diluted solution may be stored at room temperature × 4 hr or ≤24 hr refrigerated

SIDE EFFECTS

CNS:
Headache, dizziness, insomnia

CV:
Heart failure

GI:
Nausea, vomiting, dyspepsia, anorexia, diarrhea

HEMA:
Neutropenia, thrombocytopenia

META:
Hyperglycemia, hypercalcemia, hypomagnesemia, hyponatremia, hypophosphatemia

MISC:
Fatigue

MS:
Arthralgia, myalgia

PHARMACOKINETICS

Protein binding 97%

NURSING CONSIDERATIONS
Assess:

 
Tumor lysis syndrome (TLS):
hydrate well; assess for hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, uremia

 
Hematologic toxicity
grade 3 and 4 neutropenia and thrombocytopenia; platelet nadirs occur day 8 of each 28-day cycle; counts return to baseline before the start of the next cycle; monitor blood and platelet counts frequently; hold dose for grade 3 or 4 neutropenia or grade 4 thrombocytopenia, may require dosage reduction

 
Serious liver toxicity:
AST/ALT and bilirubin elevations and rare cases of fatal hepatic failure have occurred; monitor hepatic enzymes frequently; withhold doses until resolution or return to baseline in grade 3 or 4AST/ALT or bilirubin elevations

 
Serious cardiac toxicity:
fatal cardiac arrest, CHF with decreased left ventricular function/ejection fraction, myocardial ischemia, and pulmonary edema; those with NYHA class III/ IV CHF, MI within 6 mo, cardiac arrhythmias (conduction abnormalities) may be at increased risk; monitor for cardiac complications; withhold doses until resolution or return to baseline for grade 3 or 4 cardiac toxicity

 
Infusion-related reactions:
may occur ≤24 hr after dose; premedication with dexamethasone is recommended; assess for fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, angina

Evaluate:

• 
Decreased spread of multiple myeloma

Teach patient/family:

• 
To promptly report infusion-related symptoms (fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, angina)

Canada only   Side effects:
italics
= common;
bold
= life-threatening   
Nurse Alert

enzalutamide

(en-zal-u′ta-mide)

Xtandi

Func. class.:
Antineoplastic hormone

Chem. class.:
Nonsteroidal antiandrogen

ACTION:

Binds to cytosolic androgen receptors in target tissue, which competitively inhibits the action to androgens

USES:

Metastatic castration-resistant prostate cancer in those who have received docetaxel

CONTRAINDICATIONS:

Pregnancy (X), women, hypersensitivity

Precautions:
Breastfeeding, brain tumor, head trauma, infertility, seizures, stroke, male-mediated teratogenicity

DOSAGE AND ROUTES
Calculator

• Adult:
PO
160 mg (4 × 40-mg caps) daily

• 
If a patient experiences a grade 3 or higher toxicity or an intolerable adverse effect, withhold dosing for 1 wk or until symptoms improve to grade 2 or less, then resume at the same or a reduced dosage (120 or 80 mg), if warranted

• 
The concomitant use of strong cytochrome P450 (CYP-450) 2C8 inhibitors should be avoided if possible; if a strong CYP2C8 inhibitor must be coadministered, reduce the enzalutamide dosage to 80 mg once daily

Available forms:
Tabs 40 mg

Administer:

• 
At same time each day, without regard to food

• 
Swallow whole

SIDE EFFECTS

CNS:
Dizziness, paresthesias, insomnia, anxiety, headache

CV:
Hot flashes, hypertension

GU:
Urinary frequency

INTEG:
Dry skin, pruritus

MISC:
Infection, asthenia

PHARMACOKINETICS

Terminal half-life 2.8 to 10.2 days, 97% to 98% protein binding

INTERACTIONS

Increase:
anticoagulation—anticoagulants

Increase:
enzalutamide effects—CYP3A4 inhibitors (amiodarone, antiretrovirals, protease inhibitors, clarithromycin, dalfopristin, quinupristin, delavirdine, efavirenz, erythromycin, FLUoxetine, fluvoxaMINE, imatinib, mifepristone, RU-486, nefazodone, some azole antifungals)

Decrease:
enzalutamide effects—CYP3A4 inducers (barbiturates, bosentan, carBAMazepine, dexamethasone, nevirapine, OXcarbazepine, phenytoin, rifabutin, rifampin, rifapentine)

Drug/Lab Test

Might require dosage change when used with St. John’s wort

NURSING CONSIDERATIONS
Assess:

 
Male-mediated teratogenicity:
a condom and another effective birth control method should be used if patient is having sex with a woman of childbearing potential during and 3 mo after end of therapy

 
Seizures:
those with a history of seizures, underlying head trauma with loss of consciousness, TIA within 12 mo, stroke, brain tumor, or drugs lowering seizure threshold, should be told about danger of loss of consciousness when engaging in activities

 
For hot flashes, assure patient that these are common side effects

Evaluate:

• 
Therapeutic response: decreased tumor size, decreased spread of malignancy

Teach patient/family:

• 
That infertility can occur

 
To use a condom and another form of birth control during and for 3 mo after end of therapy if female sex partner is of child bearing potential

 
That those with seizure disorders might experience seizures because seizure threshold is decreased

• 
Not to use other products unless approved by prescriber

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