Mosby's 2014 Nursing Drug Reference (119 page)

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

dasatinib (Rx)

(da-si′ti-nib)

Sprycel

Func. class.:
Antineoplastic—miscellaneous

Chem. class.:
Protein-tyrosine kinase inhibitor

ACTION:

Inhibits a tyrosine kinase enzyme, thereby reducing cell growth in leukemia

USES:

Treatment of accelerated, chronic blast phase CML or acute lymphoblastic leukemia (ALL); chronic phase CML with resistance or intolerance to prior therapy; Philadelphia chromosome–positive CML in chronic phase

CONTRAINDICATIONS:

Pregnancy (D), hypersensitivity

Precautions:
Breastfeeding, children, geriatric patients, QT prolongation, infection, thrombocytopenia, accidental exposure, edema, infertility, lactase deficiency, neutropenia, anemia, autoimmune disease with immune reconstitution syndrome

DOSAGE AND ROUTES
Calculator
Accelerated or myeloid/lymphoid blast phase CML with resistance/intolerance to prior therapy


Adult: PO
140 mg daily titrated up to 180 mg daily in those resistant to therapy

Chronic phase CML with resistance/intolerance to prior therapy


Adult: PO
100 mg daily either
AM
or
PM

Dosage reduction for those taking a strong CYP3A4 inhibitor


 
Adult: PO
20-40 mg daily

Available forms:
Tabs 20, 50, 70, 80, 100 mg

Administer:

• 
Do not break, crush, or chew tab

• 
After meal and with large glass of water

SIDE EFFECTS

CNS:
CNS hemorrhage,
headache, dizziness, insomnia, neuropathy, asthenia

CV:
Dysrhythmias,
chest pain,
CHF, pericardial effusion, congestive cardiomyopathy, decreased injection fraction, QT prolongation

GI:
Nausea
,
vomiting,
anorexia, abdominal pain
, constipation, diarrhea, GI bleeding, muscositis, stomatitis

HEMA:
Neutropenia, thrombocytopenia, bleeding

INTEG:
Rash, pruritus
, alopecia

META:
Fluid retention, edema, hypocalcemia, hypophosphatemia

MISC:
Increased/decreased weight

MS:
Pain, arthralgia, myalgia

RESP:
Cough, dyspnea, pulmonary edema/hypertension, pneumonia, upper respiratory tract infection,
pleural effusion

PHARMACOKINETICS

Metabolized by CYP3A4; 96% protein bound; peak 0.5-6 hr; excreted in feces (85%), small amount in urine (4%); terminal half-life 1.3-5 hr

INTERACTIONS

• 
Altered action of CYP3A4 substrates: alfentanil, cycloSPORINE, ergots, fentaNYL, pimozide, quiNIDine, sirolimus, tacrolimus

Increase:
dasatinib concentrations—CYP3A4 inhibitors: ketoconazole, itraconazole, erythromycin, clarithromycin, nefazodone, protease inhibitors, telithromycin

Increase:
myopathy, rhabdomyolysis-HMG-CoA reductase inhibitors (rare)

Increase:
plasma concentrations of simvastatin

Increase:
QT prolongation—class IA/III antidysrhythmics and other products that increase QT prolongation

Decrease:
dasatinib concentrations—CYP3A4 inducers (dexamethasone, phenytoin, carBAMazepine, rifampin, PHENobarbital), H
2
blockers (famotidine), proton pump inhibitors (omeprazole)

Drug/Food

• 
Grapefruit: do not use

Drug/Herb

Decrease:
dasatinib concentration—St. John’s wort

NURSING CONSIDERATIONS
Assess:


 
Myelosuppression:
ANC, platelets; in chronic phase, if ANC <1 × 10
9
/L and/or platelets <50 × 10
9
/L, stop until ANC >1.5 × 10
9
/L and platelets >75 × 10
9
/L; in accelerated phase/blast crisis, if ANC <0.5 × 10
9
/L and/or platelets <10 × 10
9
/L, determine whether cytopenia is related to biopsy/aspirate, if not, reduce dose by 200 mg, if cytopenia continues, reduce dose by another 100 mg; if cytopenia continues for 4 wk, stop product until ANC ≥1 × 10
9
/L, monitor CBC weekly × 8 wk, then monthly


 
Hepatotoxicity:
monitor LFTs before treatment and monthly; if liver transaminases >5 × IULN, withhold until transaminase levels return to <2.5 × IULN

• 
Signs of fluid retention, edema:
weigh, monitor lung sounds, assess for edema; some fluid retention is dose dependent, may result in CHF, congestive cardiomyopathy, decreased injection failure


 
QT Prolongation:
more common in those with hypokalemia, hypomagnesemia, congenital long QT syndrome, those taking products that prolong QT; correct electrolyte imbalances before use

Evaluate:

• 
Therapeutic response: decrease in leukemic cells or size of tumor

Teach patient/family:


 
To report adverse reactions immediately: SOB, swelling of extremities, bleeding, bruising

• 
About reason for treatment, expected results


 
To use contraception (pregnancy category D), to avoid breastfeeding; men should use condoms

• 
To take at same time of day, not to crush or chew, do not use grapefruit juice

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

HIGH ALERT
DAUNOrubicin (Rx)

(daw-noe-roo′bi-sin)

Cerubidine

DAUNOrubicin citrate
liposomal (Rx)

DaunoXome

Func. class.:
Antineoplastic, antibiotic

Chem. class.:
Anthracycline glycoside

Do not confuse:
DAUNOrubicin
/DOXOrubicin

ACTION:

Inhibits DNA synthesis, primarily; derived from
Streptomyces coerulorubidus;
replication is decreased by binding to DNA, which causes strand splitting; cell-cycle specific (S phase); a vesicant

USES:

Acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML);
liposomal:
Kaposi’s sarcoma

Unlabeled uses:
Liposomal:
multiple myeloma, AML, breast cancer, non-Hodgkin’s lymphoma

CONTRAINDICATIONS:

Pregnancy (D), breastfeeding, hypersensitivity, systemic infections, cardiac disease, bone marrow depression

 

Black Box Warning:

IM/SUBCUT use

Precautions:
Tumor lysis syndrome, MI, infection, thrombocytopenia, renal/hepatic disease; gout

 

Black Box Warning:

Bone marrow suppression, cardiac disease, extravasation, renal failure, hepatic disease; requires a specialized care setting and an experienced clinician

DOSAGE AND ROUTES
Calculator

Use decreased dose for those >60 yr

DAUNOrubicin


Adult: IV
45-60 mg/m
2
/day × 3 days then 2 days of subsequent courses in combination, max 400-600 mg/m
2
total cumulative dose


Child: IV
30-40 mg/m
2
/day depending on cycle (AML); ≤2 yr or <0.5 m
2
: 1 mg/kg on day 1 weekly in combination with vinCRIStine and predniSONE, base dose on body weight not surface area (ALL); >2 yr or 0.5 m
2
: 25 mg/m
2
day 1 weekly in combination with vinCRIStine and predniSONE (ALL)

DAUNOrubicin citrate liposomal


Adult: IV
40 mg/m
2
q2wk (Kaposi’s sarcoma); 100 mg/m
2
q3wk (multiple myeloma, unlabeled);
IV
100-140 mg/m
2
q3wk (non-Hodgkin’s lymphoma, unlabeled; metastatic breast cancer, unlabeled); IV escalating doses of 75, 100, 125, 135, 150 mg/m
2
/day × 3 days (AML, unlabeled)

Renal dose


Adult: IV
serum CCr >3 mg/dl, reduce dose by 50%

Hepatic dose


Adult: IV
serum bilirubin 1.2-3 mg/dl, reduce dose by 50%; bilirubin >3 mg/dl, reduce dose by 75%; bilirubin >5 mg/dl, omit dose

Available forms:
Inj 20 mg powder/vial,
liposomal:
solution for inj 2 mg/ml

Administer:

• 
Antiemetic 30-60 min before giving product and 6-10 hr after treatment to prevent vomiting

 

Black Box Warning:

To be used in a care setting with emergency equipment available

 

Black Box Warning:

To be used by a clinician knowledgeable in cytotoxic therapy

 

Black Box Warning:

Do not give by IM/subcut injection

IV route (Cerubidine)
Do not confuse with liposome

• 
Use cytotoxic handling precautions

• 
After diluting 20 mg/4 ml sterile water for inj (5 mg/ml), rotate, further dilute in 10-15 ml 0.9% NaCl; give over 3-5 min by direct IV through
Y
-tube or 3-way stopcock of inf of D
5
or 0.9% NaCl; or dilute in 50 ml 0.9% NaCl and give over 10-15 min; or dilute in 100 ml and give over 30 min

• 
Hydrocortisone for extravasation; apply ice compress after stopping inf

Solution compatibilities:
D
3.3
%/0.3% NaCl, D
5
W, Normosol R, LR, 0.9% NaCl

Y-site compatibilities:
Amifostine, anidulafungin, atenolol, bivalirudin, bleomycin, CARBOplatin, caspofungin, CISplatin, codeine, cyclophosphamide, cytarabine, DACTINomycin, DAPTOmycin, dexmedetomidine, etoposide, fenoldopam, filgrastim, gemcitabine, gemtuzumab, granisetron, melphalan, meperidine, methotrexate, nesiritide, octreotide, ondansetron, oxaliplatin, PACLitaxel,
palonosetron, quinupristin-dalfopristin, riTUXimab, sodium acetate/bicarbonate, teniposide, thiotepa, tigecycline, trastuzumab, vinCRIStine, vinorelbine, voriconazole, zoledronic acid

IV route (DaunoXome)

• 
Dilute with D
5
W to (1 mg/ml), give over 1-2 hr, do not use in-line filter, reconstituted sol may be stored ≤6 hr refrigerated; do not admix

IV compatibilities:
Anidulafungin, bivalirudin, meperidine, octreotide, sodium acetate, tirofiban, trastuzumab

SIDE EFFECTS
DAUNOrubicin

CNS:
Fever, chills

CV:
CHF, pericarditis, myocarditis,
peripheral edema,
fatal myocarditis, left ventricular failure, QT prolongation, ST-T wave changes, QRS voltage changes, tachycardia, SVT, PVCs

GI:
Nausea, vomiting, anorexia, mucositis
,
hepatotoxicity

GU:
Impotence, sterility, amenorrhea, gynecomastia

HEMA:
Thrombocytopenia, leukopenia, anemia

INTEG:
Rash
,
extravasation,
dermatitis, reversible alopecia, cellulitis, thrombophlebitis at inj site

SYST:
Anaphylaxis, tumor lysis syndrome

DAUNOrubicin citrate liposomal

CNS:
Fatigue, headache
, depression, insomnia, dizziness,
malaise, neuropathy

CV:
Chest pain, edema

GI:
Abdominal pain, stomatitis,
nausea, vomiting, diarrhea
, constipation

INTEG:
Alopecia, pruritus
, sweating

MISC:
Allergic reactions, chest pain, fever
, edema, flulike symptoms

MS:
Rigors
, arthralgia, back pain

RESP:
Cough, dyspnea, rhinitis, sinusitis

PHARMACOKINETICS

Half-life 18½ hr, liposome 55½ hr; metabolized by liver; crosses placenta; excreted in breast milk, urine, bile

INTERACTIONS

Increase:
QT prolongation, torsades de pointes—arsenic trioxide, chloroquine, clarithromycin, class IA, class III antidysrhythmics, dasatinib, dolasetron, droperidol, erythromycin, flecainide, halofantrine, haloperidol, levomethadyl, methadone, ondansetron, palonosetron, pentamidine, some phenothiazines, propafenone, risperiDONE, sparfloxacin; tricyclic antidepressants (high doses); vorinostat, ziprasidone

Increase:
bleeding risk—NSAIDs, salicylates, anticoagulants, platelet inhibitors, thrombolytics

Increase:
toxicity—other antineoplastics, radiation, cyclophosphamide

Decrease:
DAUNOrubicin effects—hematopoietic progenitor cells given within 24 hr

Decrease:
antibody reaction—live virus vaccines

Drug/Lab Test

Increase:
uric acid

NURSING CONSIDERATIONS
Assess:

 

Black Box Warning:

Bone marrow suppression:
CBC, differential, platelet count weekly, leukocyte nadir within 2 wk after administration, recovery within 3 wk; do not administer if absolute granulocyte count is <750/mm
3
(liposome)


 
Acute renal failure, uric acid nephropathy:
renal studies: BUN, urine CCr, electrolytes, uric acid baseline before each dose; I&O ratio; report fall in urine output to <30 ml/hr; provide aggressive alkalinization of urine and use of allopurinol; can prevent urate nephropathy

• 
Monitor temp q4hr; fever may indicate beginning infection

• 
Hepatotoxicity:
monitor hepatic studies baseline before each dose: bilirubin, AST, ALT, alk phos; check for jaundice of skin, sclera; dark urine, clay-colored stools; itchy skin, abdominal pain, fever; diarrhea

 

Black Box Warning:

Cardiac toxicity:
chest x-ray, echocardiography, radionuclide angiography, MUGA, ECG; watch for ST-T wave changes, low QRS and QT prolongation, possible dysrhythmias (sinus tachycardia, heart block, PVCs); watch for CHF (jugular vein distention, weight gain, edema, crackles), may occur after 2-6 mo of treatment, cumulative dose (400-550 mg/m
2
), 450 mg/m
2
if used in combination with radiation, cyclophosphamide

• 
Bleeding: hematuria, guaiac stools, bruising, petechiae, mucosa or orifices q8hr

• 
Effects of alopecia on body image; discuss feelings about body changes

• 
Buccal cavity q8hr for dryness, sores, ulceration, white patches, oral pain, bleeding, dysphagia, rinse mouth tid-qid with water, club soda; brush teeth bid-qid with soft brush or cotton-tipped applicators for stomatitis; use unwaxed dental floss


 
Tumor lysis syndrome:
hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia

 

Black Box Warning:

Extravasation:
swelling, pain, decreased blood return; if extravasation occurs, stop infusion, remove tubing, attempt to aspirate the drug prior to removing the needle, elevate area, treat with ice pack

• 
GI symptoms: frequency of stools, cramping

Perform/provide:

• 
Increased fluid intake to 2-3 L/day to prevent urate and calculi formation

Evaluate:

• 
Therapeutic response: decreased tumor size, spread of malignancy

Teach patient/family:


 
To report signs of infection, bleeding, bruising, SOB, swelling, change in heart rate

• 
That hair may be lost during treatment; that wig or hairpiece may make patient feel better; that new hair may be different in color, texture


 
To avoid pregnancy (D) while taking product and for 4 mo thereafter; not to breastfeed

• 
To avoid foods with citric acid, hot or rough texture if stomatitis is present

• 
To report any bleeding, white spots, ulcerations in mouth; to examine mouth daily

• 
That urine and other body fluids may be red-orange for 48 hr

• 
To avoid vaccines, alcohol, aspirin, NSAIDs while taking this product

• 
To avoid crowds, those with known infections

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