(Onmel, Sporanox)

BLACK BOX ALERT Serious cardiovascular events, including HF, ventricular tachycardia, torsade de pointes, death, have occurred due to concurrent use with pimozide, quinidine, dofetilide, ergot alkaloids, felodipine, lovastatin, methadone, midazolam (oral), simvastatin, triazolam, or levomethadyl. Negative inotropic effects observed following IV administration. Contraindicated for treatment of onychomycosis in pts with HF, ventricular dysfunction.

Do not confuse itraconazole with fluconazole, or Sporanox with Suprax or Topamax.

♦ CLASSIFICATION

PHARMACOTHERAPEUTIC: Imidazole/triazole type antifungal. CLINICAL: Antifungal.

USES

Oral capsules: Treatment of aspergillosis, blastomycosis, esophageal and oropharyngeal candidiasis, empiric treatment in febrile neutropenia, histoplasmosis, onychomycosis. Oral solution: Treatment of oral and esophageal candidiasis. Oral tablet: Treatment of onychomycosis of toenail.

PRECAUTIONS

Contraindications: Hypersensitivity to itraconazole, other azoles. Treatment of onychomycosis in pts with evidence of ventricular dysfunction (e.g., HF or history of HF); concurrent use of dofetilide, dronedarone, eplerenone, ergot derivatives, felodipine, irinotecan, lovastatin, lurasidone, methadone, midazolam (oral), pimozide, ranolazine, simvastatin, ticagrelor, triazolam, quinidine; concurrent use with colchicine, fesoterodine, solifenacin in pts with renal/hepatic impairment; treatment of onychomycosis in women who are pregnant or are intending to become pregnant. Cautions: Preexisting hepatic impairment (not recommended in pts with active hepatic disease, elevated LFTs), renal impairment, pts with risk factors for HF (e.g., COPD, myocardial ischemia).

ACTION

Inhibits synthesis of ergosterol (vital component of fungal cell formation). Therapeutic Effect: Damages fungal cell membrane, altering its function. Fungistatic.

PHARMACOKINETICS

Moderately absorbed from GI tract. Absorption is increased when taken with food. Protein binding: 99%. Widely distributed, primarily in fatty tissue, liver, kidneys. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis. Half-life: 16–26 hrs.

 LIFESPAN CONSIDERATIONS

Pregnancy/Lactation: Distributed in breast milk. Children: Safety and efficacy not established. Elderly: Age-related renal impairment may require dosage adjustment.

INTERACTIONS

DRUG: May increase concentration/toxicity of calcium channel–blocking agents (e.g., felodipine, nifedipine), carbamazepine, cyclosporine, digoxin, ergot alkaloids, HMG-CoA reductase inhibitors (e.g., lovastatin, simvastatin), midazolam, oral antidiabetic agents (e.g., glyburide, glipizide), protease inhibitors (e.g., indinavir, ritonavir, saquinavir), sirolimus, tacrolimus, triazolam, warfarin. CYP3A4 inducers (e.g., carbamazepine, isoniazid, phenobarbital, phenytoin, rifampin) may decrease concentration/effects. May inhibit metabolism of busulfan, docetaxel, vinca alkaloids. Erythromycin may increase risk of cardiac toxicity. Antacids, H₂ antagonists, proton pump inhibitors may decrease absorption. HERBAL: St. John’s wort may decrease concentration. FOOD: Grapefruit products may alter absorption. LAB VALUES: May increase serum alkaline phosphatase, bilirubin, ALT, AST, LDH. May decrease serum potassium.

AVAILABILITY (Rx)

Capsules: 100 mg. Oral Solution: 10 mg/ml. Tablet: 200 mg.

ADMINISTRATION/HANDLING

PO

• Give capsules and tablets with food (increases absorption). • Give solution on empty stomach. Swish vigorously in mouth, then swallow.

INDICATIONS/ROUTES/DOSAGE

Note: Capsules/tablets are not bioequivalent with oral solution.

Blastomycosis, Histoplasmosis

PO: ADULTS, ELDERLY: Initially, 200 mg once daily. May increase in increments of 100 mg/day up to 400 mg/day. Life-threatening infections: 200 mg 3 times/day for first 3 days of therapy. Continue for at least 3 mos.

Aspergillosis

PO: ADULTS, ELDERLY: 200–400 mg daily for 3 mos. Life-threatening infections: 200 mg 3 times/day for first 3 days of therapy. Continue 200–400 mg/day for at least 3 mos.

Esophageal Candidiasis

PO: ADULTS, ELDERLY: Swish 100–200 mg (10–20 ml) in mouth for several seconds, then swallow once daily for a minimum of 3 wks. Continue for 2 wks after resolution of symptoms. Maximum: 200 mg/day.

Oropharyngeal Candidiasis

PO: ADULTS, ELDERLY: 200 mg (10 ml) oral solution, swish and swallow once daily for 7–14 days.

Onychomycosis (Fingernail)

PO: ADULTS, ELDERLY: 200 mg twice daily for 7 days, off for 21 days, repeat 200 mg twice daily for 7 days.

Onychomycosis (Toenail)

PO: ADULTS, ELDERLY: 200 mg once daily for 12 wks.

Dosage in Renal/Hepatic Impairment

Use caution.

SIDE EFFECTS

Frequent (11%–9%): Nausea, rash. Occasional (5%–3%): Vomiting, headache, diarrhea, hypertension, peripheral edema, fatigue, fever. Rare (2% or less): Abdominal pain, dizziness, anorexia, pruritus.

ADVERSE EFFECTS/TOXIC REACTIONS

Hepatitis (anorexia, abdominal pain, unusual fatigue/weakness, jaundiced skin/sclera, dark urine) occurs rarely.

NURSING CONSIDERATIONS

BASELINE ASSESSMENT

Determine baseline temperature, LFT. Assess allergies. Receive full medication history (numerous contrainidications/cautions).

INTERVENTION/EVALUATION

Assess for signs, symptoms of hepatic dysfunction. Monitor LFT in pts with preexisting hepatic impairment.

PATIENT/ FAMILY TEACHING

• Take capsules with food, liquids if GI distress occurs. • Therapy will continue for at least 3 mos, until lab tests, clinical presentation indicate infection is controlled. • Immediately report unusual fatigue, yellow skin, dark urine, pale stool, anorexia, nausea, vomiting. • Avoid grapefruit products.

ivabradine

eye-vab-ra-deen

(Corlanor)

♦ CLASSIFICATION

PHARMACOTHERAPEUTIC: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel blocker. CLINICAL: Reduces risk of worsening HF.

USES

To reduce the risk of hospitalization for worsening HF in pts with stable, symptomatic chronic HF with left ventricular ejection fraction less than or equal to 35%, who are in sinus rhythm with a resting heart rate greater than or equal to 70 bpm, and either are on maximally tolerated dose of beta blockers or have a contraindication to beta blocker use.

PRECAUTIONS

Contraindications: Hypersensitivity to ivabradine. Acute decompensated HF, B/P less than 90/50 mm Hg, sick sinus syndrome; sinoatrial block or third-degree AV block (unless a functional pacemaker is present), resting heart rate less than 60 bpm prior to initiation, severe hepatic impairment, pacemaker dependence (heart rate maintained exclusively by a pacemaker), concomitant use of strong CYP3A4 inhibitors. Cautions: History of atrial fibrillation, hypertension. Avoid concomitant use of diltiazem or verapamil. Avoid use in pts with second-degree heart block (unless a functioning pacemaker is present). Pts at risk for bradycardia. Not recommended with pacemakers set to rate of 60 bpm or greater.

ACTION

Reduces spontaneous pacemaker activity of the cardiac sinus node by blocking HCN channels that are responsible for cardiac current, which regulates heart rate. Does not affect ventricular repolarization or myocardial contractility. Also inhibits retinal current involved in reducing bright light in retina. Therapeutic Effect: Reduces heart rate.

PHARMACOKINETICS

Widely distributed. Metabolized in liver and intestines. Protein binding: 70%. Peak plasma concentration: 1 hr. Eliminated in feces, urine (% not specified). Half-life: 6 hrs.

 ​LIFESPAN CONSIDERATIONS

Pregnancy/Lactation: May cause fetal harm. Females of reproductive potential should use effective contraception. Unknown if distributed in breast milk. Must either discontinue drug or discontinue breastfeeding. If treatment is decided to be absolutely necessary, pregnant pts should be closely monitored for destabilizing HF, esp. during the first trimester. Pregnant women with chronic HF in the third trimester should be closely monitored for preterm birth. Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

INTERACTIONS

DRUG: Beta blockers (e.g., labetolol, metoprolol), negative chronotropes (e.g., amiodarone, digoxin, diltiazem, verapamil) may increase risk of bradycardia. Diltiazem, verapamil may increase concentration/effect; may further increase risk of bradycardia. Strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole) may increase concentration/effect. CYP3A4 inducers (e.g., phenytoin, rifampin) may decrease concentration/effect. HERBAL: St. John’s wort may decrease concentration/effect. FOOD: Grapefruit products may increase concentration/effect. LAB VALUES: None significant.

AVAILABILITY (Rx)

Tablets: 5 mg, 7.5 mg.

ADMINISTRATION/HANDLING

PO

• Give with meals. May divide 5-mg tablet, providing 2.5-mg dose.

INDICATIONS/ROUTES/DOSAGE

HF

PO: ADULTS, ELDERLY: Initially, 5 mg twice daily for 14 days, then adjust dose to resting heart rate of 50–60 bpm. Further adjustments based on resting heart rate and tolerability. Maximum dose: 7.5 mg twice daily. Pts with history of conduction defects, pts in whom bradycardia could lead to hemodynamic compromise: Initiate therapy at 2.5 mg twice daily.

Dose Modification

Adjust dose to maintain a resting heart between 50–60 bpm as follows:

Heart rate	Dose Adjustment
Greater than 60 bpm	Increase by 2.5 mg (given twice daily) up to maximum dose of 7.5 mg daily.
50–60 bpm	Maintain dose.
Less than 50 bpm or symptomatic bradycardia	Decrease by 2.5 mg (given twice daily); if current dose is 2.5 mg twice daily, permanently discontinue.

Dosage in Renal Impairment

Mild to moderate impairment: No dose adjustment. Severe impairment: Use caution.

Dosage in Hepatic Impairment

Mild to moderate impairment: No dose adjustment. Severe impairment: Contraindicated.

SIDE EFFECTS

Occasional (10%–3%): Bradycardia, hypertension, phosphenes (visual disturbances, luminous phenomena), visual brightness.

ADVERSE EFFECTS/TOXIC REACTIONS

May increase risk of atrial fibrillation (8.3% of pts). Bradycardia, sinus arrest, or heart block may occur. Bradycardia occurred in 10% of pts. Risk factors for bradycardia may include sinus node dysfunction, conduction defects (e.g., first- or second-degree AV block, bundle branch block), ventricular dyssynchrony, or use of negative chronotropic drugs. Phosphenes, a transient enhanced brightness in the visual field (which may include halos, stroboscopic or kaleidoscopic effect, colored bright lights, or multiple images) may occur. Phosphenes are usually triggered by sudden variations in light intensity and generally occur within the first 2 mos of treatment. Other adverse reactions such as angioedema, diplopia, erythema, hypotension, pruritus, rash, syncope, urticaria, vertigo, visual impairment occur rarely. Overdose may lead to severe and prolonged bradycardia requiring temporary cardiac pacing or infusion of IV beta-stimulating agents.

NURSING CONSIDERATIONS

BASELINE ASSESSMENT

Obtain baseline HR, B/P. Confirm negative pregnancy test before initiating therapy. Receive full medication history and screen for interactions. Screen for contraindications as listed in Precautions. Question history of atrial fibrillation, bradycardia, hypertension.

INTERVENTION/EVALUATION

Frequently monitor HR, B/P. Diligently monitor for atrial fibrillation, bradycardia, syncope. If symptomatic bradycardia occurs, temporary cardiac pacing or infusion of beta-stimulating agents may be warranted. Immediately report suspected pregnancy. Monitor for hypersensitivity reaction. Monitor for visual changes. Initiate fall precautions.

PATIENT/FAMILY TEACHING

• Take medication with meals. • Avoid grapefruit products, herbal supplements such as St. John’s wort. • Treatment may cause fetal harm. Female pts of reproductive potential should use effective contraception during treatment. • Report symptoms of low heart rate such as confusion, dizziness, fatigue, fainting, low blood pressure, pallor. • Report symptoms of atrial fibrillation such as chest pressure, palpitations, shortness of breath. • Treatment may cause luminous phenomena (phosphenes), a transient visual brightness that may include halos, light sensitivity, or colored bright lights. • Avoid tasks that require alertness, motor skills until response to drug is established. • Report allergic reactions such as hives, itching, rash, tongue swelling.

ivacaftor

eye-va-kaf-tor

(Kalydeco)

FIXED COMBINATION(S)

Orkambi: ivacaftor/lumacaftor (cystic fibrosis transmembrane conductance regulator): 125 mg/200 mg.

♦ CLASSIFICATION

PHARMACOTHERAPEUTIC: Cystic fibrosis transmembrane conductance regulator potentiator. CLINICAL: Cystic fibrosis agent.

USES

Treatment of cystic fibrosis in pts age 2 yrs and older who have a G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

PRECAUTIONS

Contraindications: Hypersensitivity to ivacaftor. Cautions: Moderate to severe hepatic/renal impairment.

ACTION

Potentiates a specific protein to facilitate, regulate chloride ions, water transport. In cystic fibrosis pts with a specific gene mutation (G551D), a defect in chloride and water transport results in formation of thick mucus in lungs. Therapeutic Effect: Improves lung function, fewer respiratory exacerbations.

PHARMACOKINETICS

Readily absorbed. Peak concentration occurs in 4 hrs. Metabolized in liver. Protein binding: 99%. Primarily excreted in feces. Half-life: 12 hrs.

 LIFESPAN CONSIDERATIONS

Pregnancy/Lactation: Distributed in breast milk. Children: Safety and efficacy in children younger than 6 yrs not established. Elderly: No age-related precautions noted.

INTERACTIONS

DRUG: Strong CYP3A4 inducers (e.g., carbamazepine, rifampin) substantially decreases concentration/effects. Concurrent use not recommended. Strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole) significantly increases concentration. Moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole) may increase concentration and should not be given concurrently. HERBAL: St. John’s wort decreases concentration/effects. FOOD: Grapefruit products, Seville oranges should be avoided (increases concentration). High-fat meals increase absorption. LAB VALUES: May increase serum ALT, AST.

AVAILABILITY (Rx)

Oral Granules: 50 mg, 75 mg. Tablets, Film-Coated: 150 mg.

ADMINISTRATION/HANDLING

PO

• Give with a high-fat meal (e.g., eggs, butter, peanut butter, cheese pizza).

INDICATIONS/ROUTES/DOSAGE

Cystic Fibrosis

PO: ADULTS, CHILDREN 6 YRS AND OLDER: One 150-mg tablet q12h with fat-containing food. Total daily dose: 300 mg. CHILDREN 2–6 YRS, WEIGHING 14 KG OR MORE: 75-mg packet q12hr. CHILDREN 2–6 YRS, WEIGHING LESS THAN 14 KG: 50-mg packet q12hr.

Concurrent Use with Moderate CYP3A4 Inhibitors (e.g., fluconazole)

PO: ADULTS, CHILDREN 6 YRS AND OLDER: 150 mg once daily.

Concurrent Use with Strong CYP3A4 Inhibitors (e.g., clarithromycin, ketoconazole)

PO: ADULTS, CHILDREN 6 YRS AND OLDER: 150 mg twice wkly.

Dosage in Renal Impairment

Mild to moderate impairment: No dose adjustment. Severe impairment, ESRD: Use caution.

Dosage in Hepatic Impairment

Mild impairment: No dose adjustment. Moderate impairment: ADULTS, ELDERLY: 150 mg once daily. CHILDREN WEIGHING 14 KG OR MORE: 75 mg once daily. CHILDREN WEIGHING LESS THAN 14 KG: 50 mg once daily. Severe impairment: 150 mg once daily or q48h. Use caution.

SIDE EFFECTS

Frequent (24%–10%): Headache, nasal congestion, abdominal discomfort, diarrhea, nausea, rash. Occasional (6%–5%): Rhinitis, dizziness, arthralgia, bacteria in sputum. Rare (4% and Less): Myalgia, wheezing, acne.

ADVERSE EFFECTS/TOXIC REACTIONS

Upper respiratory infections occurs in 22% of pts, nasopharyngitis in 15%. Increase in ALT, AST occurs in 6% of pts.

NURSING CONSIDERATIONS

BASELINE ASSESSMENT

If the pt’s genotype is unknown, an FDA-cleared CF mutation test should be used to detect presence of the G551D mutation. Assess hepatic function prior to and periodically during therapy.

INTERVENTION/EVALUATION

Patients who develop increased ALT, AST levels should be closely monitored until the abnormalities resolve. Dosing should be interrupted if transaminases (ALT or AST) are greater than 5 times upper limit of normal. Transaminases should be obtained every 3 mos during the first year of treatment, and annually thereafter.

PATIENT/FAMILY TEACHING

• Always take medication with fatty food. • Avoid grapefruit products and Seville oranges. • Adhere to routine laboratory testing as a part of treatment regimen. • Report headache, diarrhea, rash, signs and symptoms of respiratory infection.

ixabepilone

ix-ab-ep-i-lone

(Ixempra)

BLACK BOX ALERT Combination therapy with capecitabine is contraindicated in pts with ALT or AST greater than 2.5 times upper limit of normal (ULN) or bilirubin greater than 1 times ULN. Increased risk of toxicity, neutropenia-related mortality.

♦ CLASSIFICATION

PHARMACOTHERAPEUTIC: Epothilone microtubule inhibitor, antimitotic agent. CLINICAL: Antineoplastic.

USES

Combination therapy with capecitabine for treatment of metastatic or locally advanced breast cancer in pts after failure of anthracycline, taxane therapy. As monotherapy, treatment of metastatic or locally advanced breast cancer in pts after failure of anthracycline, taxane, and capecitabine therapy. OFF-LABEL: Treatment of endometrial cancer.

PRECAUTIONS

Contraindications: Hypersensitivity to ixabepilone. Severe hypersensitivity reaction (grade 3 or 4) to Cremophor, baseline neutrophil count less than 1,500/mm³ or platelet count less than 100,000 cells/mm³. Combination Capecitabine Therapy: ALT or AST greater than 2.5 times normal range, bilirubin greater than 1 times normal range. Cautions: Diabetes mellitus, existing moderate to severe neuropathy, history of cardiovascular disease. Monotherapy: ALT or AST greater than 5 times normal range, bilirubin greater than 3 times normal range.

ACTION

Binds directly on microtubules during active stage of G2 and M phases of cell cycle, preventing formation of microtubules, an essential part of the process of separation of chromosomes. Therapeutic Effect: Blocks cells in mitotic phase of cell division, leading to cell death.

PHARMACOKINETICS

Metabolized in liver. Protein binding: 77%. Excreted in feces (65%), urine (21%). Half-life: 52 hrs.

 LIFESPAN CONSIDERATIONS

Pregnancy/Lactation: May cause fetal harm. Unknown if distributed in breast milk. Children: Safety and efficacy not established. Elderly: Higher incidence of severe adverse reactions in those older than 65 yrs.

INTERACTIONS

DRUG: CYP3A4 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, ritonavir, voriconazole) may increase concentration. CYP3A4 inducers (e.g., carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentin) may decrease concentration. HERBAL: St. John’s wort may decrease plasma concentration. FOOD: Grapefruit products may increase plasma concentration. LAB VALUES: May increase serum ALT, AST, bilirubin. May decrease WBCs, Hgb, platelets.

AVAILABILITY (Rx)

Injection, Solution: Kit: 15 mg kit supplied with diluent for Ixempra, 8 ml; 45 mg supplied with diluent for Ixempra, 23.5 ml.

ADMINISTRATION/HANDLING

IV

Reconstitution • Withdraw diluent and slowly inject into vial. • Gently swirl and invert until powder is completely dissolved. • Further dilute with 250 ml lactated Ringer’s. • Solution may be stored in vial for a maximum of 1 hr at room temperature. • Final concentration for infusion must be between 0.2 mg/ml and 0.6 mg/ml. • Mix infusion bag by manual rotation.

Rate of Administration • Administer through an in-line filter of 0.2 to 1.2 microns. • Infuse over 3 hrs. Administration must be completed within 6 hrs of reconstitution.

Storage • Refrigerate kit. • Prior to reconstitution, kit should be removed from refrigerator and allowed to stand at room temperature for approximately 30 min. • When vials are initially removed from refrigerator, a white precipitate may be observed in the diluent vial. • This precipitate will dissolve to form a clear solution once diluent warms to room temperature. • Once diluted with lactated Ringer’s, solution is stable at room temperature and room light for a maximum of 6 hrs.

INDICATIONS/ROUTES/DOSAGE

◀ ALERT ▶ An H₁ antagonist (diphenhydramine 50 mg PO or equivalent) and an H₂ antagonist (ranitidine 150–300 mg PO or equivalent) must be given prior to beginning treatment with ixabepilone. Pts who experienced a previous hypersensitivity reaction to ixabepilone require pretreatment with corticosteroids (e.g., dexamethasone 20 mg IV, 30 min before infusion or PO, 1 hr before infusion) in addition to pretreatment with H₁ and H₂ antagonists.

Breast Cancer

IV: ADULTS, ELDERLY: 40 mg/m² infused over 3 hrs q3 wks. Maximum: 88 mg.

Monotherapy Dosage Adjustments for Hepatic Impairment

Mild Hepatic Impairment (ALT and AST Less Than 2.5 Times Upper Limit of Normal (ULN) and Bilirubin Less Than 1 Time ULN)

IV: ADULTS, ELDERLY: 40 mg/m² infused over 3 hrs q3 wks.

Mild Hepatic Impairment (ALT and AST Greater Than 2.5 Times ULN and Less Than 10 Times ULN and Bilirubin Greater Than 1 Time ULN and Less Than 1.5 Times ULN)

IV: ADULTS, ELDERLY: 32 mg/m² infused over 3 hrs q3 wks.

Moderate Hepatic Impairment (ALT and AST Less Than 10 Times ULN and Bilirubin Greater Than 1.5 Times ULN and Less Than 3 Times ULN)

IV Infusion: ADULTS, ELDERLY: 20–30 mg/m² infused over 3 hrs q3 wks.

Dosage with Strong CYP3A4 Inhibitors/Inducers

Inhibitors: Consider dose reduction to 20 mg/m².

Inducers: Consider dose increase to 60 mg/m².

Dosage in Renal Impairment

No dose adjustment.

Dose Modification

Dosage adjustment based on grade of neuropathy, hematologic conditions.

Hematologic

Neutrophils Less Than 500/mm³ for 7 Days or Longer: Reduce dose by 20%. Neutropenic Fever: Reduce dose by 20%. Platelets Less Than 25,000/mm³ (Less Than 50,000/mm³ with Bleeding): Reduce dose by 20%.

Neuropathy

Grade 2 for 7 Days or Longer or Grade 3 for Less Than 7 Days: Reduce dose by 20%. Grade 3 for 7 Days or Longer: Discontinue treatment. Grade 3 (Other Than Neuropathy): Reduce dose by 20%. Grade 4: Discontinue treatment.

SIDE EFFECTS

Common (62%): Peripheral sensory neuropathy. Frequent (56%–46%): Fatigue, asthenia, myalgia, arthralgia, alopecia, nausea. Occasional (29%–11%): Vomiting, stomatitis, mucositis, diarrhea, musculoskeletal pain, anorexia, constipation, abdominal pain, headache. Rare (9%–5%): Skin rash, nail disorder, edema, hand-foot syndrome (blistering/rash/peeling of skin on palms of hands, soles of feet), pyrexia, dizziness, pruritus, gastroesophageal reflux disease (GERD), hot flashes, taste disorder, insomnia.

ADVERSE EFFECTS/TOXIC REACTIONS

Neuropathy occurs early during treatment; 75% of new onset or worsening neuropathy occurred during first 3 cycles. Diabetics may be at increased risk for severe neuropathy manifested as grade 4 neutropenia. Neutropenia, leukopenia occurs commonly; anemia, thrombocytopenia occur rarely.

NURSING CONSIDERATIONS

BASELINE ASSESSMENT

Question possibility of pregnancy. Obtain baseline CBC, serum chemistries, LFT before treatment begins as baseline and monitor for hepatotoxicity, peripheral neuropathy (most frequent cause of drug discontinuation).

INTERVENTION/EVALUATION

Monitor for symptoms of neuropathy (burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain). Assess hands and feet for erythema. Monitor CBC for evidence of neutropenia, thrombocytopenia; LFT for hepatotoxicity. Assess mouth for stomatitis, mucositis.

PATIENT/FAMILY TEACHING

• Avoid crowds, those with known infection. • Avoid contact with those who have recently received live virus vaccine. • Do not have immunizations without physician’s approval (drug lowers resistance). • Promptly report fever over 100.5°F, chills, numbness, tingling, burning sensation, erythema of hands/feet.

ixazomib

ix-az-oh-mib

(Ninlaro)

Do not confuse ixazomib with bortezomib, carfilzomib, idelalisib, or ixekizumab.

♦ CLASSIFICATION

PHARMACOTHERAPEUTIC: Proteasome inhibitor. CLINICAL: Antineoplastic.

USES

Treatment of multiple myeloma (in combination with lenalidomide and dexamethasone) in pts who have received at least 1 prior therapy.

PRECAUTIONS

Contraindications: Severe hypersensitivity to ixazomib. Cautions: Baseline neutropenia, thrombocytopenia; hepatic/renal impairment, chronic peripheral edema, predisposing factors to infection (e.g., diabetes, renal failure, open wounds). Concomitant use of strong CYP3A inducers not recommended.

ACTION

Inhibits activity of beta 5 subunit of the 20S proteasome, leading to cell cycle arrest and tumor cell death (apoptosis). Therapeutic Effect: Inhibits tumor cells growth and metastasis.

PHARMACOKINETICS

Well absorbed following oral administration. Widely distributed. Metabolized in liver. Protein binding: 99%. Peak plasma concentration: 1 hr. Eliminated in urine (62%), feces (22%). Not removed by hemodialysis. Half-life: 9.5 days.

 LIFESPAN CONSIDERATIONS

Pregnancy/Lactation: Avoid pregnancy; may cause fetal harm/malformations. Female and male pts of reproductive potential should use effective contraception during treatment and up to 3 mos after discontinuation. Unknown if distributed in breast milk. Breastfeeding not recommended. Children: Safety and efficacy not established. Elderly: No age-related precautions noted.

INTERACTIONS

DRUG: Strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin) may decrease concentration/effect; avoid use. HERBAL: St. John’s wort may decrease concentration/effect. FOOD: High-fat meals may decrease absorption/concentration. LAB VALUES: Expected to decrease neutrophils, platelets.

AVAILABILITY (Rx)

Capsules: 2.3 mg, 3 mg, 4 mg.

ADMINISTRATION/HANDLING

PO

• Capsule contents are hazardous; use cytotoxic precautions during handling and disposal. • Administer capsule whole; do not break, cut, crush, or open. • Give at least 1 hr before or 2 hrs after food. • Give on the same day each wk and at the same time that day. If a dose is missed, do not administer within 72 hrs of next scheduled dose. • If vomiting occurs after dosing, do not readminister; give dose at next scheduled time.

INDICATIONS/ROUTES/DOSAGE

Multiple Myeloma

PO: ADULTS, ELDERLY: 4 mg once wkly on days 1, 8, and 15 of 28-day cycle, in combination with lenalidomide 25 mg daily (on days 1–21 of 28-day cycle) and dexamethasone 40 mg (on days 1, 8, 15, and 22 of 28-day cycle). Continue until disease progression or unacceptable toxicity.

Dose Reduction Schedule

Initial dose: 4 mg. First dose reduction: 3 mg. Second dose reduction:

2.3 mg. Unable to tolerate 2.3-mg dose: Permanently discontinue.

Dose Modification

Based on Common Terminology Criteria for Adverse Events (CTCAE).

Thrombocytopenia

Platelet count less than 30,000 cells/mm³: Withhold ixazomib and lenalidomide until platelet count is 30,000 cells/mm3 or greater, then resume ixazomib at the same dose and resume lenalidomide at reduced dose level (see manufacturer guidelines).

Recurrence of platelet count less than 30,000 cells/mm³: Withhold ixazomib and lenalidomide until platelet count is 30,000 cells/mm3 or greater, then resume ixazomib at reduced dose level and resume lenalidomide at the same dose.

Additional occurrences: Alternate dose modification of ixazomib and lenalidomide.

Neutropenia

Absolute neutrophil count (ANC) less than 500 cells/mm³: Withhold ixazomib and lenalidomide until ANC is 500 cells/mm3 or greater, then resume ixazomib at the same dose and resume lenalidomide at reduced dose level (see manufacturer guidelines).

Recurrence of ANC less than 500 cells/mm³: Withhold ixazomib and lenalidomide until ANC is 500 cells/mm3 or greater, then resume ixazomib at reduced dose level and resume lenalidomide at the same dose.

Additional occurrences: Alternate dose modification of ixazomib and lenalidomide.

Rash

Grade 2 or 3 rash: Withhold lenalidomide until resolved to grade 1 or 0, then resume lenalidomide at next lower dose level (see manufacturer guidelines) and resume ixazomib at the same dose.

Recurrence of grade 2 or 3 rash: Withhold ixazomib and lenalidomide until recovery to grade 1 or 0, then resume ixazomib at reduced dose level and resume lenalidomide at the same dose.

Grade 4 rash: Permanently discontinue.

Additional occurrences: Alternate dose modification of ixazomib and lenalidomide.

Peripheral Neuropathy

Grade 1 (with pain) or grade 2: Withhold ixazomib until resolved to baseline or improved to grade 1 or 0 without pain (at prescriber’s discretion), then resume ixazomib at the same dose.

Grade 2 (with pain) or grade 3: Withhold ixazomib until resolved to baseline or improved to grade 1 or 0 without pain (at prescriber’s discretion), then resume ixazomib at reduced dose level.

Grade 4: Permanently discontinue.

Any Other Nonhematologic Toxicity

Grade 3 or 4: Withhold ixazomib until resolved to baseline or improved to grade 1 or 0 (at physician’s discretion), then resume ixazomib at reduced dose level.

Dosage in Renal Impairment

Mild to moderate impairment: Not specified; use caution. Severe impairment, end-stage renal disease: Reduce starting dose to 3 mg.

Dosage in Hepatic Impairment

Mild impairment: No dose adjustment. Moderate to severe impairment: Reduce starting dose to 3 mg.

SIDE EFFECTS

Frequent (42%–26%): Diarrhea, constipation, nausea. Occasional (22%–5%): Vomiting, back pain, blurry vision, dry eye.

ADVERSE EFFECTS/TOXIC REACTIONS

Neutropenia, thrombocytopenia are expected responses to therapy. Thrombocytopenia reported in 78% of pts; neutropenia in 67% of pts. Severe diarrhea may lead to discontinuation of treatment. Peripheral neuropathy reported in 28% of pts (sensory neuropathies were the most common type). Peripheral edema occurred in 28% of pts. Dermatologic toxicities including maculopapular and macular rash may occur. Infectious processes including upper respiratory tract infection (19% of pts), conjunctivitis (6% of pts) may occur. Other toxic reactions including neutrophilic dermatosis, posterior reversible encephalopathy, Stevens-Johnson syndrome, thrombotic thrombocytopenic purpura, transverse myelitis, treatment-induced hepatotoxicity, tumor lysis syndrome, occur rarely.

NURSING CONSIDERATIONS

BASELINE ASSESSMENT

Obtain ANC, CBC (esp. platelet count), renal function test (in pts with renal impairment), LFT; pregnancy test in female pts of reproductive potential. Screen for active infection. Question history of peripheral neuropathy, peripheral edema, hepatic/renal impairment, current hemodialysis status. Receive full medication history including herbal supplements. Offer emotional support. Assess hydration status. Obtain baseline visual acuity. Obtain dietary consult for nutritional support.

INTERVENTION/EVALUATION

Monitor ANC, platelet count at least monthly; more frequently during first 3 cycles; LFT in pts with hepatic impairment. Consider concomitant granulocyte colony-stimulating factor (e.g., filgrastim, pegfilgrastim) in pts with neutropenia. Monitor for dehydration, electrolyte imbalance if diarrhea occurs. Offer antiemetics for nausea; antidiarrheals for diarrhea. Monitor for infection (esp. in pts with neutropenia); dermal toxicity, skin rashes, petechiae; peripheral neuropathy (with or without pain); peripheral edema. Monitor daily pattern bowel activity, stool consistency. Monitor for side effects of dexamethasone (e.g., hyperglycemia, weight loss, decreased appetite), lenalidomide (see prescribing information). Reversible posterior leukoencephalopathy syndrome should be considered in pts with altered mental status, confusion, headache, seizures, visual disturbances. Obtain visual acuity if vision becomes blurry.

PATIENT/FAMILY TEACHING

• Treatment may depress your immune system and reduce your ability to fight infection. Report symptoms of infection such as body aches, chills, cough, fatigue, fever. Avoid those with active infection. • Female and male pts of reproductive potential should use effective contraception during treatment and up to 3 mos after last dose. Do not breastfeed. Immediately report suspected pregnancy. • Do not take ixazomib and dexamethasone at the same time. Take dexamethasone with food to minimize GI upset. • Swallow capsules whole; do not chew, crush, or open. Take dose at least 1 hr before or 2 hrs after any food. • Do not expose the capsule contents to the skin or eyes. If eyes are exposed to the capsule powder, thoroughly flush eyes with water. If skin is exposed to the capsule powder, thoroughly wash skin with soap and water. • Treatment may cause nerve pain; extreme sensitivity to touch; muscle weakness; or prickling, tingling, numbness in your hands and feet. • Report swelling of the legs, ankles, feet. • Report neurologic changes such as blurry vision, confusion, headache, seizures; may indicate life-threatening brain swelling. • Treatment may increase risk of bleeding. • Do not take herbal supplements, esp. St. John’s wort.

ixekizumab

ix-ee-kiz-ue-mab

(Taltz)

Do not confuse ixekizumab with daclizumab, eculizumab, gevokizumab, secukinumab, or ustekinumab.

♦ CLASSIFICATION

PHARMACOTHERAPEUTIC: Human interleukin-17A antagonist. Monoclonal antibody. CLINICAL: Antipsoriasis agent.

USES

Treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

PRECAUTIONS

Contraindications: Hypersensitivity to ixekizumab. Cautions: Baseline neutropenia, thrombocytopenia; inflammatory bowel disease (Crohn’s disease, ulcerative colitis), HIV infection, concomitant immunosuppressant therapy, conditions predisposing to infection (e.g., diabetes, renal failure, open wounds), pts who have been exposed to tuberculosis. Concomitant use of live vaccines not recommended.

ACTION

Binds to and inhibits interaction of interleukin-17A receptor, a cytokine that is involved in inflammatory and immune response. May reduce epidermal neutrophils in psoriatic plaques. Therapeutic Effect: Alters biologic immune response; reduces inflammation.

PHARMACOKINETICS

Widely distributed. Degraded into small peptides and amino acids via catabolic pathway. Peak plasma concentration: 4 days. Steady state reached in 8–10 wks. Elimination not specified. Half-life: 13 days.

 LIFESPAN CONSIDERATIONS

Pregnancy/Lactation: Unknown if distributed in breast milk. However, human immunoglobulin G is present in breastmilk and is known to cross placenta. Children: Safety and efficacy not established in pts younger than 18 yrs. Elderly: No age-related precautions noted.

INTERACTIONS

DRUG: Avoid use of live vaccines. May decrease therapeutic response. HERBAL: Echinacea may decrease effect. FOOD: None known. LAB VALUES: May decrease neutrophil, platelets. May decrease diagnostic effect of Coccidioides immitis skin test.

AVAILABILITY (Rx)

Auto-injector Pen: 80 mg/ml. Prefilled Syringe: 80 mg/ml.

ADMINISTRATION/HANDLING

Subcutaneous

• Follow instructions for preparation according to manufacturer guidelines. • Remove autoinjector or prefilled syringe from refrigerator and allow to warm to room temperature (approx. 30 mins) with needle cap intact. • Visually inspect for particulate matter or discoloration. Solution should appear clear, colorless to slightly yellow in color. Do not use if solution is cloudy, discolored, or if visible particles are observed.

Administration • Insert needle subcutaneously into upper arms, outer thigh, or abdomen and inject solution. • Do not inject into areas of active skin disease or injury such as sunburns, skin rashes, inflammation, skin infections, or active psoriasis. • Rotate injection sites.

Storage • Refrigerate until time of use. • Do not freeze. • Do not shake. • Protect from light.

INDICATIONS/ROUTES/DOSAGE

Plaque Psoriasis

SQ: ADULTS, ELDERLY: Initially, 160 mg (two injections of 80 mg) once, then 80 mg at wks 2, 4, 6, 8, 10, 12, then 80 mg once q4wks.

Dosage in Renal Impairment

Not specified; use caution.

Dosage in Hepatic Impairment

Not specified; use caution.

SIDE EFFECTS

Occasional (17%): Injections site reactions (pain, erythema). Rare (2%): Nausea.

ADVERSE EFFECTS/TOXIC REACTIONS

May increase risk of infection including tuberculosis. Infections including upper respiratory tract infection (14% of pts), nasopharyngitis (14% of pts), tinea infections (2% of pts) have occurred. Cytopenias including neutropenia (11% of pts), thrombocytopenia (3% of pts) were reported. May cause exacerbation of Crohn’s disease and ulcerative colitis. Hypersensitivity reactions, including angioedema, occur rarely. Immunogenicity (auto-ixekizumab antibodies) occurred in less than 9% of pts.

NURSING CONSIDERATIONS

BASELINE ASSESSMENT

Obtain CBC in pts with known history of neutropenia, thrombocytopenia. Screen for active infection. Pts should be evaluated for active tuberculosis and tested for latent infection prior to initiating treatment and periodically during therapy. Induration of 5 mm or greater with tuberculin skin testing should be considered a positive test result when assessing if treatment for latent tuberculosis is necessary. Consider administration of age-appropriate immunizations (if applicable) before initiation. Question history of Crohn’s disease, ulcerative colitis, hypersensitivity reaction. Conduct dermatologic exam; record characteristics of psoriatic lesions.

INTERVENTION/EVALUATION

Monitor for symptoms of tuberculosis, including pts who tested negative for latent tuberculosis infection prior to initiating therapy. Interrupt or discontinue treatment if serious infection, opportunistic infection, or sepsis occurs and initiate appropriate antimicrobial therapy. Assess skin for improvement of lesions. Monitor for hypersensitivity reaction, symptoms of inflammatory bowel disease.

PATIENT/FAMILY TEACHING

• A healthcare provider will show you how to properly prepare and inject your medication. You must demonstrate correct preparation and injection techniques before using medication at home. • Treatment may depress your immune system response and reduce your ability to fight infection. Report symptoms of infection such as body aches, chills, cough, fatigue, fever. Avoid people with active infection. • Do not receive live vaccines. • Expect frequent tuberculosis screening. • Report travel plans to possible endemic areas. • Immediately report difficulty breathing, itching, hives, rash, swelling of the face or tongue; may indicate allergic reaction. • Treatment may cause worsening of Crohn’s disease or cause inflammatory bowel disease. Report abdominal pain, diarrhea, weight loss.