K

ketoconazole

kee-toe-kon-a-zole

(Apo-Ketoconazole , Extina, Nizoral, Nizoral AD, Xolegel)

BLACK BOX ALERT Potentially fatal hepatotoxicity has occurred; serious cardiovascular events (QT prolongation, torsades de pointes, ventricular tachycardia, ventricular fibrillation, fatalities) have occurred.

Do not confuse Nizoral with Nasarel, Neoral, or Nitrol.

♦ CLASSIFICATION

PHARMACOTHERAPEUTIC: Imidazole derivative. CLINICAL: Antifungal.

USES

PO: Treatment of susceptible fungal infections including histoplasmosis, blastomycosis, coccidioidomycosis, paracoccidioidomycosis, chromomycosis. Shampoo: Treatment of dandruff. Treatment of tinea versicolor. Topical: Treatment of tineas, pityriasis versicolor, cutaneous candidiasis, seborrhea dermatitis, dandruff. Xolegel: Treatment of seborrheic dermatitis. OFF-LABEL: Systemic: Treatment of advanced prostate cancer.

PRECAUTIONS

Contraindications: Hypersensitivity to ketoconazole. Acute or chronic liver disease; concurrent use with alprazolam, colchicine, dofetilide, eplereone, ergot derivatives, methadone, midazolam, quinidine irinotecan, ranolazine, statins, triazolam. Cautions: Hepatic impairment, concomitant use of drugs decreasing gastric acidity (e.g., antacids, H₂ antagonists, proton pump inhibitors).

ACTION

Alters cell wall permeability, inhibits phospholipids/enzymes of fungi. Therapeutic Effect: Damages fungal cell membrane, altering its function. Fungistatic.

PHARMACOKINETICS

Well absorbed from GI tract following PO administration (absorption decreases as pH of gastric contents increases). Protein binding: 93%–96%. Metabolized in liver. Primarily excreted in bile. Negligible systemic absorption following topical absorption. Ketoconazole is not detected in plasma after shampooing, topical administration. Half-life: 8 hrs.

LIFESPAN CONSIDERATIONS

Pregnancy/Lactation: Oral form distributed in breast milk. Unknown if topical form crosses placenta or is distributed in breast milk. Children: Cream, shampoo: Safety and efficacy not established. Oral form: Safety and efficacy not established in pts younger than 2 yrs. Elderly: No age-related precautions noted.

INTERACTIONS

DRUG: May increase concentration/toxicity of cyclosporine, digoxin, ergot alkaloids, midazolam, protease inhibitors (e.g., indinavir, ritonavir, saquinavir), sirolimus, tacrolimus, triazolam, warfarin. Isoniazid, rifampin may decrease concentration/effects. Antacids, H₂ antagonists (e.g., cimetidine, famotidine), proton pump inhibitors (e.g., omeprazole) may decrease absorption. HERBAL: St. John’s wort may decrease concentration. FOOD: None known. LAB VALUES: May increase serum alkaline phosphatase, bilirubin, ALT, AST. May decrease serum corticosteroid, testosterone.

AVAILABILITY (Rx)

Foam (Extina): 2%. Gel (Xolegel): 2%. Shampoo (Nizoral AD [OTC]): 1%. Tablets (Nizoral): 200 mg.

ADMINISTRATION/HANDLING

PO

• Give with food to minimize GI irritation. • Tablets may be crushed. • Ketoconazole requires acidity; give antacids, anticholinergics, H₂ blockers at least 2 hrs following dosing.

Shampoo

• Apply to wet hair, massage for 1 min, rinse thoroughly, reapply for 3 min, rinse.

Topical

• Apply, rub gently into affected/surrounding area.

INDICATIONS/ROUTES/DOSAGE

Usual Dosage

PO: ADULTS, ELDERLY: 200–400 mg once daily. CHILDREN 2 YRS AND OLDER: 3.3–6.6 mg/kg once daily.

Topical: ADULTS, ELDERLY: Apply to affected area 1–2 times/day for 2–4 wks.

Shampoo: ADULTS, ELDERLY: Use twice wkly for 4 wks, allowing at least 3 days between shampooing. Use intermittently to maintain control.

Dosage in Renal Impairment

No dose adjustment.

Dosage in Hepatic Impairment

Use caution.

SIDE EFFECTS

Occasional (10%–3%): Nausea, vomiting. Rare (less than 2%): Abdominal pain, diarrhea, headache, dizziness, photophobia. Topical: Burning, irritation, pruritus.

ADVERSE EFFECTS/TOXIC REACTIONS

Hematologic toxicity (thrombocytopenia, hemolytic anemia, leukopenia) occurs occasionally. Hepatotoxicity may occur within first wk to several mos after starting therapy. Anaphylaxis occurs rarely.

NURSING CONSIDERATIONS

BASELINE ASSESSMENT

Confirm culture or histologic test for accurate diagnosis; therapy may begin before results known. Receive full medication history and screen for contraindications.

INTERVENTION/EVALUATION

Monitor LFT; be alert for hepatotoxicity: dark urine, pale stools, jaundice, fatigue, anorexia, nausea, or vomiting (unrelieved by giving medication with food). Monitor CBC for hematologic toxicity. Monitor daily pattern of bowel activity, stool consistency. Assess for dizziness, provide assistance as needed. Evaluate skin for rash, urticaria, pruritus. Topical: Check for localized burning, pruritus, irritation.

PATIENT/FAMILY TEACHING

• Prolonged therapy (wks or mos) is usually necessary. • Avoid alcohol. • May cause dizziness; avoid tasks that require alertness, motor skills until response to drug is established. • Take antacids, antiulcer medications at least 2 hrs after ketoconazole. • Report dark urine, pale stool, yellow skin or eyes, vomiting, increased irritation in topical use, onset of other new symptoms. • Topical: Rub well into affected areas. • Avoid contact with eyes. • Keep skin clean, dry; wear light clothing for ventilation. • Separate personal items in direct contact with affected area. • Shampoo: Initially, use 2 times/wk for 4 wks with at least 3 days between shampooing; frequency then determined by response to medication.

ketorolac

kee-toe-role-ak

(Acular, Acular LS, Acuvail, Apo-Ketorolac , Novo-Ketorolac , Sprix, Toradol )

BLACK BOX ALERT Increased risk of serious cardiovascular thrombotic events, including myocardial infarction, CVA. Increased risk of severe GI reactions, including ulceration, bleeding, perforation.

Do not confuse Acular with Acthar or Ocular, ketorolac with Ketalar, or Toradol with Foradil, Inderal, Tegretol, or tramadol.

♦ CLASSIFICATION

PHARMACOTHERAPEUTIC: NSAID. CLINICAL: Analgesic, intraocular anti-inflammatory.

USES

PO, injection, nasal: Short-term (5 days or less) relief of mild to moderate pain. Ophthalmic: Relief of ocular itching due to seasonal allergic conjunctivitis. Treatment postop for inflammation following cataract extraction, pain following incisional refractive surgery. OFF-LABEL: Prevention, treatment of ocular inflammation (ophthalmic form).

PRECAUTIONS

Contraindications: Hypersensitivity to ketorolac, aspirin or other NSAIDs. Intracranial bleeding, hemorrhagic diathesis, high risk of bleeding; concomitant use of aspirin, NSAIDs, probenecid or pentoxifylline; labor and delivery, advanced renal impairment or risk of renal failure, active or history of peptic ulcer disease, chronic inflammation of GI tract, recent or history of GI bleeding/ulceration. Perioperative pain in setting of CABG surgery. Prophylaxis before major surgery. Cautions: Hepatic impairment, history of GI tract disease, asthma, coagulation disorders, receiving anticoagulants, fluid retention, HF, renal impairment, inflammatory bowel disease, smoking, use of alcohol, elderly, debilitated.

ACTION

Inhibits prostaglandin synthesis, reduces prostaglandin levels in aqueous humor. Therapeutic Effect: Reduces intensity of pain stimulus, reduces intraocular inflammation.

PHARMACOKINETICS

Readily absorbed from GI tract after IM administration. Protein binding: 99%. Metabolized in liver. Primarily excreted in urine. Not removed by hemodialysis. Half-life: 5–9 hrs (increased in renal impairment, in elderly).

LIFESPAN CONSIDERATIONS

Pregnancy/Lactation: Unknown if distributed in breast milk. Avoid use during third trimester (may adversely affect fetal cardiovascular system: premature closure of ductus arteriosus). Children: Safety and efficacy not established, but doses of 0.5 mg/kg have been used. Elderly: GI bleeding, ulceration more likely to cause serious adverse effects. Age-related renal impairment may increase risk of hepatic/renal toxicity; decreased dosage recommended.

INTERACTIONS

DRUG: May decrease effects of antihypertensives (e.g., amlodipine, lisinopril), diuretics (e.g., furosemide, HCTZ). Aspirin, NSAIDs, other salicylates may increase risk of GI side effects, bleeding. May increase risk of bleeding with heparin, oral anticoagulants (e.g., warfarin), thrombolytics. May increase concentration, risk of toxicity of lithium. May increase risk of methotrexate toxicity. Probenecid may increase concentration. HERBAL: Cat’s claw, dong quai, evening primrose, feverfew, garlic, ginkgo, ginseng, horse chestnut, red clover may decrease antiplatelet activity, risk of bleeding. FOOD: None known. LAB VALUES: May prolong bleeding time. May increase serum ALT, AST, BUN, potassium, creatinine.

AVAILABILITY (Rx)

Injection Solution (Toradol): 15 mg/ml, 30 mg/ml. Nasal Spray (Sprix): 1.7-g bottle provides 8 sprays (15.75 mg/spray). Ophthalmic Solution: 0.4% (Acular LS), 0.45% (Acuvail), 0.5% (Acular). Tablets (Toradol): 10 mg.

ADMINISTRATION/HANDLING

IV

• Give undiluted as IV push. • Give over at least 15 sec.

IM

• Give deep IM slowly into large muscle mass.

PO

• Give with food, milk, antacids if GI distress occurs.

Ophthalmic

• Place gloved finger on lower eyelid and pull out until pocket is formed between eye and lower lid. Place prescribed number of drops into pocket. • Instruct pt to close eye gently for 1–2 min (so medication will not be squeezed out of the sac) and to apply digital pressure to lacrimal sac at inner canthus for 1 min to minimize system absorption.

IV INCOMPATIBILITY

Promethazine (Phenergan).

IV COMPATIBILITIES

Fentanyl (Sublimaze), hydromorphone (Dilaudid), morphine, nalbuphine (Nubain).

INDICATIONS/ROUTES/DOSAGE

Pain Management

PO: ADULTS, ELDERLY: Initially, 20 mg (10 mg for elderly), then 10 mg q4–6h. Maximum: 40 mg/24 hrs.

IM: ADULTS YOUNGER THAN 65 YRS: 60 mg once or 30 mg q6h. Maximum: 120 mg/24 hrs. ADULTS 65 YRS AND OLDER, PTS WITH RENAL IMPAIRMENT, PTS WEIGHING LESS THAN 50 KG: 30 mg once or 15 mg q6h. Maximum: 60 mg/24 hrs.

IV: ADULTS YOUNGER THAN 65 YRS: 30 mg once or 30 mg q6h. Maximum: 120 mg/24 hrs. ADULTS 65 YRS AND OLDER, PTS WITH RENAL IMPAIRMENT, PTS WEIGHING LESS THAN 50 KG: 15 mg once or 15 mg q6h. Maximum: 60 mg/24 hrs.

Nasal Spray: ADULTS, ELDERLY YOUNGER THAN 65 YRS: 31.5 mg (1 spray each nostril) q6–8h. Maximum daily dose: 126 mg. ADULTS 65 YRS AND OLDER, PTS WEIGHING LESS THAN 50 KG: 15.75 (1 spray in one nostril) mg q6–8h. Maximum daily dose: 63 mg.

Allergic Conjunctivitis

Ophthalmic: ADULTS, ELDERLY, CHILDREN 3 YRS AND OLDER: 1 drop 4 times/day.

Cataract Extraction

Ophthalmic: ADULTS, ELDERLY: 1 drop 4 times/day. Begin 24 hrs after surgery and continue for 2 wks.

Refractive Surgery

Ophthalmic: ADULTS, ELDERLY: 1 drop 4 times/day for 3 days.

Dosage in Renal Impairment

See dosage section.

Dosage in Hepatic Impairment

Use caution.

SIDE EFFECTS

Frequent (17%–12%): Headache, nausea, abdominal cramps/pain, dyspepsia. Occasional (9%–3%): Diarrhea. Nasal: Nasal discomfort, rhinalgia, increased lacrimation, throat irritation, rhinitis. Ophthalmic: Transient stinging, burning. Rare (3%–1%): Constipation, vomiting, flatulence, stomatitis. Ophthalmic: Ocular irritation, allergic reactions (manifested by pruritus, stinging), superficial ocular infection, keratitis.

ADVERSE EFFECTS/TOXIC REACTIONS

Peptic ulcer, GI bleeding, gastritis, severe hepatic reaction (cholestasis, jaundice) occur rarely. Nephrotoxicity (glomerular nephritis, interstitial nephritis, nephrotic syndrome) may occur in pts with preexisting renal impairment. Acute hypersensitivity reaction (fever, chills, joint pain) occurs rarely.

NURSING CONSIDERATIONS

BASELINE ASSESSMENT

Assess onset, type, location, duration of pain. Obtain baseline renal/hepatic function tests.

INTERVENTION/EVALUATION

Monitor renal function, LFT, urinary output. Monitor daily pattern of bowel activity, stool consistency. Observe for occult blood loss. Assess for therapeutic response: relief of pain, stiffness, swelling; increased joint mobility; reduced joint tenderness; improved grip strength. Monitor for bleeding (may also occur with ophthalmic route due to systemic absorption).

PATIENT/ FAMILY TEACHING

• Avoid aspirin, alcohol. • Report abdominal pain, bloody stools, or vomiting blood. • If GI upset occurs, take with food, milk. • Ophthalmic: Transient stinging, burning may occur upon instillation. • Do not administer while wearing soft contact lenses.