D

dabigatran

Availability (Rx)

Capsules: 75 mg, 150 mg.

Administration/handling

PO

• May be given without regard to food. Administer with water. • Do not break, cut, open capsules.

Indications/routes/dosage

◀ ALERT ▶ Medication should be discontinued prior to invasive or surgical procedures.

Nonvalvular atrial fibrillation

PO: ADULTS, ELDERLY: 150 mg twice daily.

Renal impairment

Creatinine Clearance 15–30 ml/min: 75 mg twice daily. Creatinine clearance less than 15, or HD: Use not recommended (removes ∼60% over 2–3 hrs).

Side effects

Frequent (less than 16%): Dyspepsia (heartburn, nausea, indigestion), diarrhea, upper abdominal pain.

Adverse effects/toxic reactions

Gastrointestinal bleeding occurs rarely.

Nursing considerations

Baseline assessment

Assess CBC, including platelet count. Check PT, PTT. Determine initial B/P.

Intervention/evaluation

Assess for any sign of bleeding (hematuria, melena, bleeding from gums, petechiae, bruising). Do not obtain B/P in lower extremities (possible deep vein thrombosis). Assess for decrease in B/P, increase in pulse rate, complaint of abdominal pain, diarrhea. Obtain aPTT, PT, platelet count. Question for increase in discharge during menses. Monitor for hematoma. Use care in removing any dressing, tape.

Patient/family teaching

• Do not break, open, chew capsules. • Use electric razor, soft toothbrush to prevent bleeding. • Report any sign of red or dark urine, black or red stool, coffee-ground vomitus, red-speckled mucus from cough. • Keep in original container. Do not transfer to pill box/organizer. • Once bottle is opened, must be used within 60 days. • Open blister pack at time of use.

dabrafenib

da-braf-e-nib

(Tafinlar)

Do not confuse dabrafenib with dasatinib.

classification

PHARMACOTHERAPEUTIC: Kinase inhibitor. CLINICAL: Antineoplastic.

Action

Inhibits BRAF kinase gene mutation, a main cause of tumor cell growth, in the absence of growth factors that are normally required for proliferation. Therapeutic Effect: Inhibits tumor cell growth and metastasis.

Pharmacokinetics

Readily absorbed after PO administration. Protein binding: 99.7%. Peak plasma concentration: 2 hrs. Metabolized in liver. Excreted in feces (71%), urine (23%). Half-life: 8 hrs.

Uses

Treatment of unresectable or metastatic melanoma with BRAF V600E mutation as detected by FDA-approved test.

◀ ALERT ▶ Not indicated for treatment of wild-type BRAF melanomas.

Precautions

Contraindications: None known. Cautions: Diabetes mellitus, hepatic/renal impairment, dehydration, glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Lifespan considerations

Pregnancy/Lactation: Avoid pregnancy. May cause fetal harm. Must use effective nonhormonal contraception during treatment and for at least 4 wks after treatment (intrauterine device, barrier methods). Unknown if distributed in breast milk. Must either discontinue breastfeeding or discontinue therapy. Pregnancy Category D. Children: Safety and efficacy not established. Elderly: May have increased risk of adverse effects, skin lesions.

Interactions

DRUG: Antacids, H₂-receptors blockers, proton pump inhibitors may decrease concentration/effect. CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) may decrease concentration/effect. CYP3A4 inhibitors (e.g., clarithromycin, gemfibrozil, ketoconazole) may increase concentration. May decrease effectiveness of hormonal contraceptives, warfarin. HERBAL: St John’s wort may decrease concentration/effect. FOOD: High-fat meals may decrease absorption/effect. LAB VALUES: May increase serum glucose, alkaline phosphatase. May decrease serum phosphate, sodium.

Availability (Rx)

Capsules: 50 mg, 75 mg.

Administration/handling

PO

• Give at least 1 hr before or at least 2 hrs after meal. Do not crush, cut, or open capsule.

Indications/routes/dosage

Metastatic melanoma

PO: ADULTS/ELDERLY: 150 mg twice daily (about 12 hrs apart).

Dose modification

Based on Common Terminology Criteria for Adverse Events (CTCAE) grading 1–4.

Reduction Levels	Dose
1st dose reduction	100 mg twice daily
2nd dose reduction	75 mg twice daily
3rd dose reduction	50 mg twice daily

Fever greater than 101.3°F or any grade 2 or grade 3 adverse event

Withhold until fever or adverse event resolves to grade 1 or less, then reduce dose by one level. May further decrease each dose level based on tolerability.

Recurrent grade 4 adverse event or 50-mg dose intolerability or hemodynamic instability

Permanently discontinue.

Side effects

Frequent (37%–17%): Hyperkeratosis, headache, pyrexia, arthalgia, alopecia, rash. Occasional (12%–10%): Back pain, cough, myalgia, constipation, nasopharyngitis, fatigue.

Adverse effects/toxic reactions

Cutaneous squamous cell carcinoma (cuSCC) and keratocanthomas reported in 11% of pts (esp. elderly, prior skin cancer, chronic sun exposure). Skin reactions including palmar-plantar erythrodysesthesia syndrome (PPES), papilloma have occurred. May increase cell proliferation of wild-type BRAF melanoma or new malignant melanomas. Eye conditions including uveitis, iritis reported. Hyperglycemia reported in 6% of pts. Serious febrile drug reactions including hypotension, rigors, dehydration reported in 4% of pts. Pts with G6PD deficiency have increased risk of hemolytic anemia. Pancreatitis, interstitial nephritis, bullous rash reported in less than 10% of pts.

Nursing considerations

Baseline assessment

Obtain baseline serum CMP, magnesium, phosphate, capillary glucose level. Confirm presence of BRAF V600E mutation, negative urine pregnancy before initiating treatment. Assess skin for moles, lesions, papillomas. Baseline ophthalmologic exam, visual acuity. Question current breastfeeding status. Receive full medication history including herbal products.

Intervention/evaluation

Offer emotional support. Monitor serum electrolytes, capillary blood glucose routinely. Obtain CBC if hemolytic anemia suspected. Monitor for signs of hyperglycemia (thirst, polyuria, confusion, dehydration). Assess for skin lesions every 2 mos during treatment and at least 6 mos after treatment. Immediately report any vision changes, eye pain/swelling, febrile events, renal impairment.

Patient/family teaching

• Treatment may cause hair loss. • Do not breastfeed. • Avoid pregnancy; nonhormonal contraception should be used during treatment and up to 4 wks after treatment. • Take capsule at least 1 hr before or at least 2 hrs after meal. Swallow whole; do not crush or chew. • Report any increased urination, thirst, confusion, vision changes, eye pain, fever, skin changes including moles or lesions. • Minimize exposure to sunlight. • Males may experience a decreased sperm count. • Report any newly prescribed medications.

dacarbazine

da-kar-bah-zeen

(DTIC )

BLACK BOX ALERT Myelosuppression is most common toxicity. May cause hepatic necrosis, hepatic vein thrombosis. May be carcinogenic or teratogenic. Administer only under supervision of an experienced cancer chemotherapy physician.

Do not confuse dacarbazine with Dicarbosil or procarbazine.

classification

PHARMACOTHERAPEUTIC: Alkylating agent. CLINICAL: Antineoplastic (see p. 84C).

Action

Forms methyldiazonium ions, which attack nucleophilic groups in DNA. Cross-links DNA strands. Therapeutic Effect: Inhibits DNA, RNA, protein synthesis.

Pharmacokinetics

Minimally crosses blood-brain barrier. Protein binding: 5%. Metabolized in liver. Excreted in urine. Half-life: 5 hrs (increased in renal impairment).

Uses

Treatment of metastatic malignant melanoma, second-line therapy of Hodgkin’s disease. OFF-LABEL: Treatment of islet cell carcinoma, soft-tissue sarcoma, pheochromocytoma, medullary carcinoma of thyroid.

Precautions

Contraindications: Hypersensitivity to dacarbazine. Cautions: Renal/hepatic impairment, bone marrow suppression.

Lifespan considerations

Pregnancy/Lactation: If possible, avoid use during pregnancy, esp. first trimester. Breastfeeding not recommended. Pregnancy Category C. Children: Safety and efficacy not established. Elderly: Age-related renal impairment may require dosage adjustment.

Interactions

DRUG: Bone marrow depressants may enhance myelosuppression. CYP1A2 inducers (e.g., rifampin) may decrease effects. CYP1A2 inhibitors (e.g., fluoxetine, amlodipine) may increase levels/effects. Live virus vaccines may potentiate virus replication, increase vaccine side effects, decrease pt’s antibody response to the vaccine. HERBAL: Dong quai, St. John’s wort may increase photosensitization. Echinacea may decrease effects. FOOD: None known. LAB VALUES: May increase BUN, serum alkaline phosphatase, AST, ALT.

Availability (Rx)

Injection, Powder for Reconstitution: 100-mg vial, 200-mg vial.

Administration/handling

◀ ALERT ▶ Give by IV push or IV infusion. May be carcinogenic, mutagenic, teratogenic. Handle with extreme care during preparation/administration.

IV

Reconstitution • Reconstitute 100-mg vial with 9.9 ml Sterile Water for Injection (19.7 ml for 200-mg vial) to provide concentration of 10 mg/ml.

Rate of Administration • Give IV push over 2–3 min. • For IV infusion, further dilute with 250–1,000 ml D₅W or 0.9% NaCl at a concentration not to exceed 10 mg/ml. Infuse over 15–120 min. • Apply hot packs if local pain, burning sensation, irritation at injection site occur. • Avoid extravasation (stinging, swelling, coolness, slight or no blood return at injection site).

Storage • Protect from light; refrigerate vials. • Color change from ivory to pink indicates decomposition; discard. • Solution containing 10 mg/ml is stable for 8 hrs at room temperature or 72 hrs if refrigerated. • Solution diluted with D₅W or 0.9% NaCl is stable for at least 24 hrs at room temperature.

IV incompatibilities

Allopurinol (Aloprim), hydrocortisone (Solu-Cortef), heparin, piperacillin and tazobactam (Zosyn).

IV compatibilities

Granisetron (Kytril), ondansetron (Zofran), palonosetron (Aloxi).

Indications/routes/dosage

Refer to individual protocols.

Metastatic melanoma

IV: ADULTS, ELDERLY: 250 mg/m²/day for 5 days, repeat q3wks.

Hodgkin’s disease

IV: ADULTS, ELDERLY, CHILDREN: 375 mg/m² once, repeat in 15 days (as combination therapy) of every 28-day cycle.

Dosage in renal impairment

Creatinine Clearance	Dose
46–60 ml/min	80% of dose
31–45 ml/min	75% of dose
30 or less ml/min	70% of dose

Side effects

Frequent (90%): Nausea, vomiting, anorexia (occurs within 1 hr of initial dose, may last up to 12 hrs). Occasional: Facial flushing, paresthesia, alopecia, flu-like symptoms (fever, myalgia, malaise), dermatologic reactions, confusion, blurred vision, headache, lethargy. Rare: Diarrhea, stomatitis, photosensitivity.

Adverse effects/toxic reactions

Myelosuppression resulting in blood dyscrasias (leukopenia, thrombocytopenia) generally appears 2–4 wks after last dacarbazine dose. Hepatotoxicity occurs rarely.

Nursing considerations

Baseline assessment

Obtain baseline CBC, serum chemistries, esp. hepatic function tests. Conflicting reports of antiemetic effectiveness for nausea, vomiting. Some clinicians recommend food, fluid restriction 4–6 hrs before treatment; other clinicians believe good hydration to within 1 hr of treatment will prevent dehydration due to vomiting.

Intervention/evaluation

Monitor CBC for evidence of myelosuppression. Monitor for hematologic toxicity (fever, sore throat, signs of local infection, unusual bruising/bleeding from any site).

Patient/family teaching

• Tolerance to GI effects occurs rapidly (generally after 1–2 days of treatment). • Do not have immunizations without physician’s approval (drug lowers resistance). • Avoid contact with those who have recently received live virus vaccine. • Promptly report fever, sore throat, signs of local infection, unusual bruising/bleeding from any site. • Notify physician of persistent nausea, vomiting.

dalfampridine

dal-fam-pri-deen

(Ampyra)

Do not confuse Ampyra with anakinra, or dalfampridine with desipramine.

classification

PHARMACOTHERAPEUTIC: Potassium channel blocker. CLINICAL: Multiple sclerosis agent.

Action

Increases conduction of action potentials in demyelinated axons, inhibiting potassium channels. Therapeutic Effect: Improves ambulation in those with multiple sclerosis (MS).

Pharmacokinetics

Rapidly absorbed from GI tract. Minimally metabolized in liver. Primarily excreted in urine. Half-life: 5.2–6.5 hrs.

Uses

Indicated to improve ambulation in pts with MS, as demonstrated by increase in walking speed.

Precautions

Contraindications: History of seizures, moderate to severe renal impairment (creatinine clearance [CrCl] equal to or less than 50 ml/min). Cautions: Mild renal impairment (CrCl equal to 51–80 ml/min).

Lifespan considerations

Pregnancy/Lactation: Unknown if drug crosses placenta or is distributed in breast milk. Pregnancy Category C. Children: Safety and efficacy not established in those younger than 18 years. Elderly: Age-related renal impairment may require dosage adjustment.

Interactions

DRUG: None significant. HERBAL: None significant. FOOD: None known. LAB VALUES: May increase creatinine clearance.

Availability (Rx)

Tablet, Film-Coated, Extended-Release: 10 mg.

Administration/handling

PO

• May give without regard to food. • Do not break, cut, crush, or divide tablets.

Indications/routes/dosage

Multiple sclerosis

PO: ADULTS 18 YEARS AND OLDER, ELDERLY: 10 mg twice daily.

Dosage in renal impairment

Creatinine Clearance 50 ml/min or Less: Contraindicated.

Side effects

Frequent (9%–5%): Insomnia, dizziness, headache, nausea, asthenia (loss of strength, energy), back pain.

Rare (4%–2%): Paresthesia, nasopharyngitis, constipation, dyspepsia, pharyngolaryngeal pain.

Adverse effects/toxic reactions

Urinary tract infection occurs in 12% of pts.

Nursing considerations

Baseline assessment

Obtain CBC, BUN, creatinine clearance, serum chemistries prior to treatment and routinely thereafter. Offer emotional support.

Intervention/evaluation

Monitor CBC, serum chemistries, renal function tests, particularly creatinine clearance. Monitor for urinary, respiratory infection. Assess for therapeutic response (improvement in walking as demonstrated by increase in walking speed).

Patient/family teaching

• Avoid tasks that require alertness, motor skills until response to drug is established. • Report difficulty in sleeping, dizziness, headache, nausea, back pain, loss of strength or energy. • Do not break, chew, crush, or divide tablets.

dalteparin

dal-te-par-in

(Fragmin)

BLACK BOX ALERT Epidural or spinal anesthesia greatly increases potential for spinal or epidural hematoma, subsequent long-term or permanent paralysis.

classification

PHARMACOTHERAPEUTIC: Low molecular weight heparin. CLINICAL: Anticoagulant (see p. 32C).

Action

Antithrombin in presence of low molecular weight heparin inhibits factor Xa, thrombin. Only slightly influences platelet aggregation, PT, aPTT. Therapeutic Effect: Produces anticoagulation.

Pharmacokinetics

Route	Onset	Peak	Duration
Subcutaneous	N/A	4 hrs	N/A

Protein binding: less than 10%. Half-life: 3–5 hrs.

Uses

Treatment of unstable angina, non–Q-wave MI to prevent ischemic events. Prevention of deep vein thrombosis (DVT) in pts undergoing hip replacement or abdominal surgery who are at risk for thromboembolic complications. Extended treatment of symptomatic venous thromboembolism (VTE) to reduce recurrence of VTE in cancer pts. Prevention of DVT or pulmonary embolism in acutely ill pts with severely restricted mobility. Those at risk are 40 yrs and older, obese, undergoing surgery under general anesthesia lasting longer than 30 min, malignancy, history of DVT, pulmonary embolism. OFF-LABEL: Treatment of DVT in noncancer pts.

Precautions

Contraindications: Active major bleeding; concurrent heparin therapy; hypersensitivity to dalteparin, heparin, pork products; unstable angina; history of heparin-induced thrombocytopenia; non–Q-wave MI; prolonged venous thromboembolism undergoing epidural/neuraxial anesthesia. Cautions: Conditions with increased risk for hemorrhage, bacterial endocarditis, renal/hepatic impairment, uncontrolled hypertension, history of recent GI ulceration/hemorrhage, peptic ulcer disease, pericarditis, preexisting thrombocytopenia, recent childbirth, concurrent use of aspirin.

Lifespan considerations

Pregnancy/Lactation: Use with caution, particularly during last trimester, immediate postpartum period (increased risk of maternal hemorrhage). Unknown if distributed in breast milk. Pregnancy Category B. Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

Interactions

DRUG: Anticoagulants, NSAIDs, platelet inhibitors, thrombolytic agents may increase risk of bleeding. HERBAL: Cat’s claw, dong quai, evening primrose, garlic, ginseng, other herbs with anticoagulant/antiplatelet activity may increase antiplatelet activity. FOOD: None known. LAB VALUES: May increase serum AST, ALT. May decrease serum triglycerides.

Availability (Rx)

Injection, Solution: 2,500 international units/0.2 ml, 5,000 international units/0.2 ml, 7,500 international units/0.3 ml, 10,000 international units/ml, 25,000 international units/ml, 12,500 international units/0.5 ml, 15,000 international units/0.6 ml, 18,000 international units/0.72 ml.

Administration/handling

Subcutaneous

• Store at room temperature. • Inject in U-shaped area around the navel, upper outer side of thigh, upper outer quadrangle of buttock. • Use fine needle (25–26 gauge) to minimize tissue trauma. • Introduce entire length of needle (½ inch) into skin fold held between thumb and forefinger, holding needle during injection at 45°–90° angle. • Do not rub injection site after administration (prevents bruising). • Alternate administration site with each injection. • New injections should be administered at least 1 inch from the old site. Never inject into an area where skin is tender, bruised, red, or hard.

Indications/routes/dosage

Abdominal surgery, low to moderate DVT risk

Subcutaneous: ADULTS, ELDERLY: 2,500 international units 1–2 hrs before surgery, then daily for 5–10 days.

Abdominal surgery, high DVT risk

Subcutaneous: ADULTS, ELDERLY: 5,000 international units 1–2 hrs before surgery, then daily for 5–10 days.

Total hip surgery

Subcutaneous: ADULTS, ELDERLY: 2,500 international units 1–2 hrs before surgery, then 2,500 units 4–8 hrs after surgery, then 5,000 units/day (starting at least 6 hrs after postsurgical dose) for 7–10 days.

Unstable angina, non–Q-wave MI

Subcutaneous: ADULTS, ELDERLY: 120 international units/kg q12h (maximum: 10,000 international units/dose) given with aspirin until clinically stable.

Venous thromboembolism (cancer pts)

Subcutaneous: ADULTS, ELDERLY: Initially (1 mo), 200 international units/kg (maximum: 18,000 international units) daily for 30 days. Maintenance (2–6 mos): 150 international units/kg once daily (maximum: 18,000 international units). If platelet count 50,000–100,000/mm³, reduce dose by 2,500 units until platelet count recovers to 100,000/mm³ or more. If platelet count less than 50,000/mm³, discontinue until platelet count recovers to more than 50,000/mm³.

Prevention of deep vein thrombosis (DVT), acutely ill PT, immobile PT

Subcutaneous: ADULTS, ELDERLY: 5,000 international units once a day.

Dosage in renal impairment

For creatinine clearance less than 30 ml/min, monitor anti-Xa levels to determine appropriate dose.

Side effects

Occasional (7%–3%): Hematoma at injection site. Rare (less than 1%): Hypersensitivity reaction (chills, fever, pruritus, urticaria, asthma, rhinitis, lacrimation, headache); mild, local skin irritation.

Adverse effects/toxic reactions

Overdose may lead to bleeding complications ranging from local ecchymoses to major hemorrhage. Thrombocytopenia occurs rarely.

Nursing considerations

Baseline assessment

Obtain baseline coagulation studies, CBC, esp. platelet count. Determine baseline B/P.

Intervention/evaluation

Periodically monitor CBC, platelet count, stool for occult blood (no need for daily monitoring in pts with normal presurgical coagulation parameters). Assess for any sign of bleeding (bleeding at surgical site, hematuria, blood in stool, bleeding from gums, petechiae, bruising/bleeding at injection sites).

Patient/family teaching

• Usual length of therapy is 5–10 days. • Do not take any OTC medication (esp. aspirin) without consulting physician. • Report bleeding, bruising, dizziness, light-headedness, rash, itching, fever, swelling, breathing difficulty. • Rotate injection sites daily. • Teach proper injection technique. • Excessive bruising at injection site may be lessened by ice massage before injection.

dantrolene

dan-troe-leen

(Dantrium, Revontro)

BLACK BOX ALERT Potential for hepatotoxicity.

Do not confuse Dantrium with danazol or Daraprim, Revontro with Revatio.

classification

CLINICAL: Skeletal muscle relaxant (see p. 151C).

Action

Reduces muscle contraction by interfering with release of calcium ion. Reduces calcium ion concentration. Therapeutic Effect: Dissociates excitation-contraction coupling. Interferes with catabolic process associated with malignant hyperthermia.

Pharmacokinetics

Poorly absorbed from GI tract. Protein binding: High. Metabolized in liver. Primarily excreted in urine. Half-life: IV: 4–8 hrs; PO: 8.7 hrs.

Uses

PO: Relief of symptoms of spasticity due to spinal cord injuries, stroke, cerebral palsy, multiple sclerosis, esp. flexor spasms, concomitant pain, clonus, muscular rigidity. Parenteral: Management of fulminant hypermetabolism of skeletal muscle due to malignant hyperthermia crisis. Prevention of malignant hyperthermia (pre- or postoperative administration). OFF-LABEL: Neuroleptic malignant syndrome.

Precautions

Contraindications: IV: None known. PO: When spasticity used to maintain posture/balance during locomotion or to obtain increased motor function. Active hepatic disease. Cautions: Cardiac/pulmonary impairment, history of previous hepatic disease.

Lifespan considerations

Pregnancy/Lactation: Readily crosses placenta. Breastfeeding not recommended. Pregnancy Category C. Children: No age-related precautions noted in those 5 yrs and older. Elderly: No precautions specified.

Interactions

DRUG: CNS depressants may increase CNS depression with short-term use. Hepatotoxic medications may increase risk of hepatic toxicity with chronic use. CYP3A4 inhibitors (e.g., clarithromycin) may increase concentration. HERBAL: Gotu kola, kava kava, St. John’s wort, valerian may increase CNS depression. FOOD: None known. LAB VALUES: May alter serum hepatic function test.

Availability (Rx)

Capsules (Dantrium): 25 mg, 50 mg, 100 mg. Injection, Powder for Reconstitution (Dantrium, Revontro): 20-mg vial.

Administration/handling

IV

Reconstitution • Reconstitute 20-mg vial with 60 ml Sterile Water for Injection (not Bacteriostatic Water for Injection).

Rate of Administration • For therapeutic or emergency dose, give IV over 2–3 min. • For IV infusion, administer over 1 hr. • Diligently monitor for extravasation (high pH of IV preparation). May produce severe complications.

Storage • Store at room temperature. • Use within 6 hrs after reconstitution. • Solution is clear, colorless. Discard if cloudy, precipitate forms.

PO

• Give without regard to food.

IV incompatibility

D₅W, 0.9% NaCl.

Indications/routes/dosage

Spasticity

PO: ADULTS, ELDERLY: Initially, 25 mg once daily for 7 days; then 25 mg 3 times/day for 7 days; then 50 mg 3 times/day for 7 days; then 100 mg 3 times/day. Maximum: 400 mg/day. CHILDREN: Initially, 0.5 mg/kg/dose once daily for 7 days; then 0.5 mg/kg/dose 3 times/day for 7 days; then 1 mg/kg/dose 3 times/day for 7 days; then 2 mg/kg/dose 3 times/day. Maximum: 400 mg/day.

Perioperative prophylaxis for malignant hyperthermic crisis

PO: ADULTS, ELDERLY, CHILDREN: 4–8 mg/kg/day in 3–4 divided doses beginning 1–2 days before surgery; give last dose 3–4 hrs before surgery.

IV: ADULTS, ELDERLY, CHILDREN: 2.5 mg/kg about 1.25 hrs before surgery with additional doses as needed.

Management of malignant hyperthermic crisis

IV: ADULTS, ELDERLY, CHILDREN: Initially, a minimum of 2.5 mg/kg rapid IV; may repeat up to total cumulative dose of 10 mg/kg. May follow with 4–8 mg/kg/day PO in 4 divided doses up to 3 days after crisis.

Side effects

Frequent: Drowsiness, dizziness, weakness, general malaise, diarrhea (mild). Occasional: Confusion, diarrhea (severe), headache, insomnia, constipation, urinary frequency. Rare: Paradoxical CNS excitement or restlessness, paresthesia, tinnitus, slurred speech, tremor, blurred vision, dry mouth, nocturia, impotence, rash, pruritus.

Adverse effects/toxic reactions

Risk of hepatotoxicity, most notably in females, pts 35 yrs and older, those taking other hepatotoxic medications concurrently. Overt hepatitis noted most frequently between 3rd and 12th mo of therapy. Overdose results in vomiting, muscular hypotonia, muscle twitching, respiratory depression, seizures.

Nursing considerations

Baseline assessment

Obtain baseline hepatic function tests (AST, ALT, alkaline phosphatase, total bilirubin). Record onset, type, location, duration of muscular spasm. Check for immobility, stiffness, swelling.

Intervention/evaluation

Assist with ambulation. For pts on long-term therapy, hepatic/renal function tests, CBC should be performed periodically. Assess for therapeutic response: relief of pain, stiffness, spasm.

Patient/family teaching

• Drowsiness usually diminishes with continued therapy. • Avoid tasks that require alertness, motor skills until response to drug is established. • Avoid alcohol/other depressants. • Report continued weakness, fatigue, nausea, diarrhea, skin rash, itching, bloody/tarry stools.

daptomycin

dap-toe-mye-sin

(Cubicin)

Do not confuse Cubicin with Cleocin, or daptomycin with dactinomycin.

classification

PHARMACOTHERAPEUTIC: Lipopeptide antibacterial agent. CLINICAL: Antibiotic.

Action

Binds to bacterial membranes and causes rapid depolarization of membrane potential. Inhibits protein, DNA, RNA synthesis. Therapeutic Effect: Bactericidal.

Pharmacokinetics

Widely distributed. Protein binding: 90%. Primarily excreted unchanged in urine. Moderately removed by hemodialysis. Half-life: 7–8 hrs (increased in renal impairment).

Uses

Treatment of complicated skin/skin structure infections caused by susceptible strains of gram-positive pathogens, including Staphyloccus aureus (methicillin susceptible and methicillin resistant), Streptococcus pyogenes, Streptococcus agalactiae. Treatment of S. aureus systemic infections caused by methicillin susceptible and resistant S. aureus.

Precautions

Contraindications: None known. Cautions: Severe renal impairment (creatinine clearance less than 30 ml/min), concurrent use of other medications associated with myopathy (e.g., statins).

Lifespan considerations

Pregnancy/Lactation: Unknown if drug is distributed in breast milk. Pregnancy Category B. Children: Safety and efficacy not established in those younger than 18 yrs. Elderly: No age-related precautions noted.

Interactions

DRUG: Concurrent use with HMG-CoA reductase inhibitors (statins) may cause myopathy (discontinue use). HERBAL: None significant. FOOD: None known. LAB VALUES: May increase serum CPK, potassium. May alter serum hepatic function test results.

Availability (Rx)

Injection, Powder for Reconstitution: 500 mg/vial.

Administration/handling

IV

Reconstitution • Reconstitute 500-mg vial with 10 ml 0.9% NaCl to provide a concentration of 50 mg/ml. May further dilute in 0.9% NaCl. • Do not shake or agitate vial.

Rate of Administration • For IV injection, give over 2 min (concentration: 50 mg/ml). • For intermittent IV infusion (piggyback), infuse over 30 min.

Storage • Refrigerate. • Appears as pale yellow to light brown lyophilized cake. • Reconstituted solution is stable for 12 hrs at room temperature or up to 48 hrs if refrigerated. • Discard if particulate forms.

IV incompatibilities

Diluents containing dextrose. If same IV line is used to administer different drugs, flush line with 0.9% NaCl.

IV compatibilities

0.9% NaCl, Lactated Ringer’s, aztreonam (Azactam), dopamine, fluconazole (Diflucan), gentamicin, heparin, levofloxacin (Levaquin).

Indications/routes/dosage

Complicated skin/skin structure infections

IV: ADULTS, ELDERLY: 4 mg/kg every 24 hrs for 7–14 days.

Systemic infections

IV: ADULTS, ELDERLY: 6 mg/kg once daily for 2–6 wks.

Dosage in renal impairment

Creatinine clearance less than 30 ml/min, (HD) hemodialysis, (PD) peritoneal dialysis: Dosage is 4 mg/kg q48h for skin and soft tissue infections, 6 mg/kg q48h for staphylococcal bacteremia. (HD) hemodialysis: Give dose after dialysis. (CRRT) continuous renal replacement therapy (CVVHD): 8 mg/kg q48h, (CVVH or CVVHDF): 8 mg/kg q48h or 4–6 mg/kg q24h.

Side effects

Frequent (6%–5%): Constipation, nausea, peripheral injection site reactions, headache, diarrhea. Occasional (4%–3%): Insomnia, rash, vomiting. Rare (less than 3%): Pruritus, dizziness, hypotension.

Adverse effects/toxic reactions

Skeletal muscle myopathy (muscle pain/weakness, particularly of distal extremities) occurs rarely. Antibiotic-associated colitis, other superinfections (abdominal cramps, severe diarrhea, fever) may result from altered bacterial balance in GI tract.

Nursing considerations

Baseline assessment

Obtain CPK, blood culture, sensitivity test before first dose (therapy may begin before results are known).

Intervention/evaluation

Assess oral cavity for white patches on mucous membranes, tongue (thrush). Monitor for myopathy (muscle pain, weakness), CPK levels, renal function tests. Monitor daily pattern of bowel activity, stool consistency. Mild GI effects may be tolerable, but increasing severity may indicate onset of antibiotic-associated colitis. Be alert for superinfection: fever, vomiting, diarrhea, anal/genital pruritus, oral mucosal changes (ulceration, pain, erythema). Monitor for dizziness, institute appropriate measures.

Patient/family teaching

• Report rash, headache, nausea, dizziness, constipation, diarrhea, muscle pain, or any other new symptom.

darbepoetin alfa

dar-be-poe-e-tin al-fa

(Aranesp)

BLACK BOX ALERT Increased risk of serious cardiovascular events, thromboembolic events, mortality, time-to-tumor progression when administered to a target hemoglobin greater than 11 g/dl. Shortened overall survival and/or increased risk of tumor progression has been reported with breast, cervical, head/neck, NSCL cancers.

Do not confuse Aranesp with Aricept, or darbepoetin with dalteparin or epoetin.

classification

PHARMACOTHERAPEUTIC: Glycoprotein. CLINICAL: Hematopoietic agent.

Action

Stimulates formation of RBCs in bone marrow; increases serum half-life of epoetin. Therapeutic Effect: Induces erythropoiesis, release of reticulocytes from bone marrow.

Pharmacokinetics

Well absorbed after subcutaneous administration. Half-life: 48.5 hrs.

Uses

Treatment of anemia associated with chronic renal failure (including pts on dialysis and pts not on dialysis), treatment of anemia caused by concurrent myelosuppressive chemotherapy in pts planned to receive chemotherapy for minimum of 2 additional months. OFF-LABEL: Treatment of symptomatic anemia in myelodysplastic syndrome (MDS).

Precautions

Contraindications: Pure red cell aplasia, uncontrolled hypertension. Cautions: History of seizures, hypertension.

Lifespan considerations

Pregnancy/Lactation: Unknown if drug crosses placenta or is distributed in breast milk. Pregnancy Category C. Children: Safety and efficacy not established. Elderly: Age-related renal impairment may require dosage adjustment.

Interactions

DRUG: None significant. HERBAL: None significant. FOOD: None known. LAB VALUES: May decrease serum ferritin, serum transferrin saturation.

Availability (Rx)

Injection Solution: 25 mcg/ml, 40 mcg/ml, 60 mcg/ml, 100 mcg/ml, 150 mcg/0.75 ml, 200 mcg/ml, 300 mcg/ml. Prefilled Syringe: 25 mcg/0.42 ml, 40 mcg/0.4 ml, 60 mcg/0.3 ml, 100 mcg/0.5 ml, 150 mcg/0.3 ml, 200 mcg/0.4 ml, 300 mcg/0.6 ml, 500 mcg/ml.

Administration/handling

◀ ALERT ▶ Avoid excessive agitation of vial; do not shake (will cause foaming).

IV

Reconstitution • No reconstitution necessary. Do not dilute.

Rate of Administration • May be given as IV bolus.

Storage • Refrigerate vials. • Do not shake. Vigorous shaking may denature medication, rendering it inactive.

Subcutaneous

• Use 1 dose per vial; do not reenter vial. Discard unused portion.

IV incompatibilities

Do not mix with other medications.

Indications/routes/dosage

Anemia in chronic renal failure

◀ ALERT ▶ Individualize dosing and use lowest dose to reduce need for RBC transfusions. ON DIALYSIS: Initiate when Hgb less than 10 g/dl; reduce or stop dose when Hgb approaches or exceeds 11 g/dl. NOT ON DIALYSIS: Initiate when Hgb less than 10 g/dl and Hgb decline would likely result in RBC transfusion; reduce dose or stop if Hgb exceeds 10 g/dl.

IV, Subcutaneous: ADULTS, ELDERLY: ON DIALYSIS: Initially, 0.45 mcg/kg once weekly. Alternate for nondialysis pts: 0.75 mcg/kg once q2wks. NOT ON DIALYSIS: 0.45 mcg/kg q4wks.

Decrease dose by 25%: If Hgb approaches 12 g/dl or increases greater than 1 g/dl in any 2-wk period.

Increase dose by 25%: If Hgb does not increase by 1 g/dl after 4 wks of therapy and Hgb is below target range (with adequate iron stores), do not increase dose more frequently than every 4 wks.

Note: If pt does not attain Hgb range of 10–12 g/dl after appropriate dosing over 12 wks, do not increase dose and use minimum effective dose to maintain Hgb level that will avoid red blood cell transfusions.

Anemia associated with chemotherapy

◀ ALERT ▶ Initiate only if Hgb less than 10 g/dl and anticipated duration of myelosuppression is 2 months or longer. Titrate dose to maintain Hgb level and avoid RBC transfusions. Discontinue upon completion of chemotherapy.

Subcutaneous: ADULTS, ELDERLY: 2.25 mcg/kg once weekly or 500 mcg every 3 wks.

Increase dose: If Hgb does not increase by 1 g/dl after 6 wks and Hgb is below target range, increase dose to 4.5 mcg/kg once weekly.

Decrease dose: Decrease dose by 40% if Hgb increases greater than 1 g/dl in any 2-wk period or Hgb reaches level that will avoid red blood cell transfusions. Note: Withhold dose when Hgb exceeds a level needed to avoid RBC transfusions, resume at dose 40% lower when Hgb approaches a level where transfusions may be required.

Side effects

Frequent: Myalgia, hypertension/hypotension, headache, diarrhea. Occasional: Fatigue, edema, vomiting, reaction at injection site, asthenia (loss of strength, energy), dizziness.

Adverse effects/toxic reactions

Vascular access thrombosis, HF, sepsis, arrhythmias, anaphylactic reaction occur rarely.

Nursing considerations

Baseline assessment

Assess B/P before drug administration. B/P often rises during early therapy in pts with history of hypertension. Assess serum iron (transferrin saturation should be greater than 20%), serum ferritin (greater than 100 ng/ml) before and during therapy. Consider supplemental iron therapy. Establish baseline CBC (esp. note Hct).

Intervention/evaluation

Monitor serum ferritin, CBC with differential, serum creatinine, BUN, potassium, phosphorus, reticulocyte count. Monitor B/P aggressively for increase (25% of pts taking medication require antihypertension therapy, dietary restrictions).

Patient/family teaching

• Frequent blood tests needed to determine correct dose. • Report swollen extremities, breathing difficulty, extreme fatigue, or severe headache. • Avoid tasks requiring alertness, motor skills until response to drug is established.

darifenacin

dare-i-fen-a-sin

(Enablex)

classification

PHARMACOTHERAPEUTIC: Muscarinic receptor antagonist. CLINICAL: Urinary antispasmodic.

Action

Acts as a direct antagonist at muscarinic receptor sites in cholinergically innervated organs; limits bladder contractions. Therapeutic Effect: Reduces symptoms of bladder irritability/overactivity (urge incontinence, urinary urgency/frequency), improves bladder capacity.

Pharmacokinetics

Well absorbed following PO administration. Protein binding: 98%. Metabolized in liver. Excreted in urine (60%), feces (40%). Half-life: 13–19 hrs.

Uses

Management of symptoms of bladder overactivity (urge incontinence, urinary urgency/frequency).

Precautions

Contraindications: Uncontrolled narrow-angle glaucoma, paralytic ileus, GI/GU obstruction, urine retention. Cautions: Bladder outflow obstruction, hepatic impairment, nonobstructive prostatic hyperplasia, decreased GI motility, constipation, hiatal hernia, reflux esophagitis, ulcerative colitis, controlled narrow-angle glaucoma, myasthenia gravis, concurrent use of CYP3A4 inhibitors.

Lifespan considerations

Interactions

DRUG: CYP3A4 inhibitors (clarithromycin, erythromycin, isoniazid, protease inhibitors) may increase concentration/effects. Anticholinergics may increase side effects (e.g., dry mouth, constipation). HERBAL: St. John’s wort may decrease concentration/effects. FOOD: None known. LAB VALUES: Grapefruit may increase potential for urinary retention; constipation.

Availability (Rx)

Tablets (Extended-Release): 7.5 mg, 15 mg.

Administration/handling

PO

• Give without regard to food. • Administer extended-release tablets whole; do not break, crush, or divide tablet.

Indications/routes/dosage

Overactive bladder

PO: ADULTS, ELDERLY: Initially, 7.5 mg once daily. If response is not adequate after at least 2 wks, may increase to 15 mg once daily. Do not exceed 7.5 mg once daily in moderate hepatic impairment or concurrent use with CYP3A4 inhibitors (clarithromycin, fluconazole, protease inhibitors, isoniazid).

Dosage hepatic impairment

Moderate impairment	Maximum dose: 7.5 mg
Severe impairment	Not recommended

Side effects

Frequent (35%–21%): Dry mouth, constipation. Occasional (8%–4%): Dyspepsia, headache, nausea, abdominal pain. Rare (3%–2%): Asthenia (loss of strength, energy), diarrhea, dizziness, ocular dryness.

Adverse effects/toxic reactions

UTI occurs occasionally.

Nursing considerations

Baseline assessment

Monitor voiding pattern, assess signs/symptoms of overactive bladder prior to therapy as baseline.

Intervention/evaluation

Monitor I&O. Palpate bladder for urine retention. Monitor daily pattern of bowel activity, stool consistency for evidence of constipation. Dry mouth may be relieved with sips of tepid water. Assess for relief of symptoms of overactive bladder (urge incontinence, urinary frequency/urgency).

Patient/family teaching

• Swallow tablet whole; do not break, chew, crush, or divide. • Increase fluid intake to reduce risk of constipation. • Avoid tasks that require alertness, motor skills until response to drug is established.

darunavir

dar-ue-na-veer

(Prezista)

classification

PHARMACOTHERAPEUTIC: Protease inhibitor. CLINICAL: Antiretroviral (see pp. 69C, 119C).

Action

Prevents virus-specific processing of polyproteins, HIV-1 protease infected cells. Therapeutic Effect: Prevents formation of mature viral cells.

Pharmacokinetics

Readily absorbed following PO administration. Protein binding: 95%. Metabolized in liver. Eliminated in feces (79.5%), urine (13.9%). Not significantly removed by hemodialysis. Half-life: 15 hrs.

Uses

Treatment of HIV infection in combination with ritonavir and other antiretroviral agents in adults and children 3 yrs and older.

Precautions

Contraindications: Concurrent therapy with alfuzosin, dihydroergotamine, ergonovine, ergotamine, lovastatin, methylergonovine, oral midazolam, pimozide, rifampin, sildenafil (for treatment of PAH), simvastatin, St. John’s wort, triazolam. Cautions: Diabetes mellitus, hemophilia, known sulfonamide allergy, hepatic impairment.

Lifespan considerations

Pregnancy/Lactation: Unknown if drug crosses placenta or is distributed in breast milk. Breastfeeding not recommended. Pregnancy Category B. Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

Interactions

DRUG: May increase concentration/effects of amiodarone, bepredil, lidocaine, desipramine, colchicine, beta blockers, midazolam, paroxetine, sertraline, atorvastatin, clarithromycin, cyclosporine, felodipine, inhaled fluticasone, lovastatin, nicardipine, nifedipine, pravastatin, simvastatin, sirolimus, tacrolimus, trazodone, sildenafil, tadalafil, vardenafil. CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, voriconazole) may increase concentration. May decrease effect of methadone, oral contraceptives. HERBAL: St. John’s wort may lead to loss of virologic response, potential resistance to darunavir. FOOD: Food increases plasma concentration. LAB VALUES: May increase aPTT, PT, serum alkaline phosphatase, bilirubin, amylase, lipase, cholesterol, triglycerides, uric acid. May decrease lymphocytes/neutrophil count, platelets, WBC count, serum bicarbonate, albumin, calcium. May alter serum glucose, sodium.

Availability (Rx)

Tablets (Prezista): 75 mg, 150 mg, 400 mg, 600 mg, 800 mg.

Administration/handling

PO

• Give with food (increases plasma concentration). • Coadministration with ritonavir required. • Do not crush or cut film-coated tablets.

Indications/routes/dosage

HIV infection, treatment experienced

PO: ADULTS, ELDERLY: 600 mg administered with 100 mg ritonavir with food twice daily or 800 mg (two 400-mg tablets) with 100 mg ritonavir with food once daily.

HIV infection, treatment naive

PO: ADULTS, ELDERLY: 800 mg (two 400-mg tablets) administered with 100 mg ritonavir with food once daily.

Usual pediatric dose

◀ ALERT ▶ Do not use once-daily dosing in pediaric pts.

PO: CHILDREN 3 YRS OF AGE OR OLDER: 20 mg/kg twice daily.

Use tablet or solution

PO: CHILDREN WEIGHING 40 KG OR MORE: 600 mg twice daily with 100 mg ritonavir. WEIGHING 30–39 KG: 450 mg twice daily with 60 mg ritonavir. WEIGHING 15–29 KG: 375 mg twice daily with 50 mg ritonavir.

Use oral solution only

14 KG TO < 15 KG: 280 mg (48 mg ritonavir) twice daily. 13 KG TO < 14 KG: 250 mg (40 mg ritonavir) twice daily. 12 KG TO < 13 KG: 240 mg (40 mg ritonavir) twice daily. 11 KG TO < 12 KG: 220 mg (32 mg ritonavir) twice daily. 10 KG TO < 11 KG: 200 mg (32 mg ritonavir) twice daily.

Side effects

Frequent (19%–13%): Diarrhea, nausea, headache, nasopharyngitis. Occasional (3%–2%): Constipation, abdominal pain, vomiting. Rare (less than 2%): Allergic dermatitis, dyspepsia, flatulence, abdominal distention, anorexia, arthralgia, myalgia, paresthesia, memory impairment.

Adverse effects/toxic reactions

Hypertension, MI, transient ischemic attack occur in less than 2% of pts. Acute renal failure, diabetes mellitus, dyspnea, worsening of hepatic impairment, skin reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis occur rarely.

Nursing considerations

Baseline assessment

Obtain baseline hepatic function tests before beginning therapy and at periodic intervals during therapy. Offer emotional support. Obtain full medication history.

Intervention/evaluation

Closely monitor for GI discomfort. Monitor daily pattern of bowel activity, stool consistency. Assess skin for rash, other skin reactions, chemistries, laboratory abnormalities, particularly hepatic profile, glucose, cholesterol, triglycerides. Assess for opportunistic infections (onset of fever, oral mucosa changes, cough, other respiratory symptoms).

Patient/family teaching

• Take medication with food. • Continue therapy for full length of treatment. • Doses should be evenly spaced. • Darunavir is not a cure for HIV infection, nor does it reduce risk of transmission to others. • Pt may continue to experience illnesses, including opportunistic infections. • Diarrhea can be controlled with OTC medication. • Report any skin reactions.

dasatinib

da-sa-ti-nib

(Sprycel)

Do not confuse dasatinib with erlotinib, imatinib, or lapatinib.

classification

PHARMACOTHERAPEUTIC: Protein-tyrosine kinase inhibitor. CLINICAL: Antineoplastic (see p. 84C).

Action

Reduces activity of proteins responsible for uncontrolled growth of leukemia cells by binding to most imatinib-resistant BCR-ABL mutations of pts with chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL). Therapeutic Effect: Inhibits proliferation, tumor growth of CML and ALL cancer cell lines.

Pharmacokinetics

Extensively distributed in extravascular space. Protein binding: 96%. Metabolized in liver. Eliminated primarily in feces. Half-life: 3–5 hrs.

Uses

Treatment of adults with chronic, accelerated, myeloid or lymphoid blast phase of chronic myelogenous leukemia (CML) with resistance, intolerance to prior therapy, including imatinib. Treatment of adults with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy. Treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase of newly diagnosed pts. OFF-LABEL: Post stem cell transplant follow-up treatment of CML. Treatment of GI stromal tumor.

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Tags: Saunders Nursing Drug Handbook 2015

Mar 8, 2017 | Posted by admin in NURSING | Comments Off

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