Aredia

pamidronate disodium

Aredia

Pharmacologic class: Bisphosphonate, hypocalcemic

Therapeutic class: Bone resorption inhibitor

Pregnancy risk category C

Action

Inhibits normal and abnormal bone resorption and decreases calcium levels

Availability

Injection: 30 mg/vial, 90 mg/vial

Indications and dosages

Hypercalcemia caused by cancer

Adults: For moderate hypercalcemia, 60 to 90 mg as a single-dose I.V. infusion over 2 to 24 hours. For severe hypercalcemia, 90 mg as a single-dose I.V. infusion over 2 to 24 hours.

Osteolytic lesions caused by multiple myeloma

Adults: 90 mg I.V. as a 4-hour infusion q month

Osteolytic bone metastases of breast cancer

Adults: 90 mg I.V. as a 2-hour infusion q 3 to 4 weeks

Paget's disease

Adults: 30 mg I.V. daily as a 4-hour infusion for 3 days

Contraindications

• Hypersensitivity to drug, its components, or other bisphosphonates

Precautions

Use cautiously in:

• renal impairment

• pregnant or breastfeeding patients

• children (safety not established).

Administration

• Hydrate patient with saline solution as needed before starting therapy.

• Because of risk of renal failure, give no more than 90 mg in single doses.

See Reconstitute vial using 10 ml of sterile water for injection. When completely dissolved, dilute in 250 to 1,000 ml of half-normal or normal saline solution or dextrose 5% in water.

See Don't mix with solutions containing calcium, such as lactated Ringer's solution.

• Administer in I.V. line separate from all other drugs and fluids.

Adverse reactions

CNS: anxiety, headache, insomnia, psychosis, drowsiness, weakness

CV: hypertension, syncope, tachycardia, atrial flutter, arrhythmias, heart failure

EENT: sinusitis

GI: nausea, vomiting, diarrhea, abdominal pain, constipation, dyspepsia, stomatitis, anorexia, GI hemorrhage

GU: urinary tract infection

Hematologic: anemia, neutropenia, leukopenia, granulocytopenia, throm-bocytopenia

Metabolic: hypothyroidism

Musculoskeletal: bone pain, joint pain, myalgia

Respiratory: crackles, coughing, dyspnea, upper respiratory infection, pleural effusion

Other: fever, generalized pain, injection site reaction

Interactions

Drug-diagnostic tests. Creatinine: increased level

Electrolytes, hemoglobin, magnesium, phosphorus, platelets, potassium, red blood cells, white blood cells: decreased levels

Patient monitoring

• Monitor hydration status carefully.

• Monitor vital signs and ECG. Evaluate cardiovascular and respiratory status closely.

• Assess hematologic studies and creatinine level before each treatment course.

• Assess electrolyte levels, especially calcium, magnesium, and phosphorus.

• Closely monitor fluid intake and output. Watch for signs and symptoms of urinary tract infection.

Patient teaching

• Instruct patient to weigh himself regularly and report sudden gains.

See Advise patient to promptly report significant respiratory problems, peripheral edema, or GI bleeding.

See Inform patient that drug lowers resistance to some infections. Tell him to immediately report fever and other signs and symptoms of infection.

• Explain importance of undergoing laboratory tests before, during, and after therapy.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration, cognition, and alertness.

• Tell patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests mentioned above.

pamidronate

(pa-mid-roe-nate) pamidronate,

Aredia

(trade name)

Classification

Therapeutic: bone resorption inhibitors
Pharmacologic: biphosphonates
Pregnancy Category: D

Indications

Moderate to severe hypercalcemia associated with malignancy.Osteolytic bone lesions associated with multiple myeloma or breast cancer.Moderate to severe Paget’s disease.

Action

Inhibits resorption of bone.

Therapeutic effects

Decreased serum calcium.Decreased skeletal destruction in multiple myeloma or breast cancer.Decreased skeletal complications in Paget’s disease.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Rapidly absorbed by bone. Reaches high concentrations in bone, liver, spleen, teeth, and tracheal cartilage. Approximately 50% of a dose is retained by bone and then slowly released.Metabolism and Excretion: 50% is excreted unchanged in the urine.Half-life: Elimination half-life from plasma is biphasic—1st phase 1.6 hr, 2nd phase 27.2 hr. Elimination half-life from bone is 300 days.

Time/action profile (effect on serum calcium)

ROUTEONSETPEAKDURATION
IV24 hr7 daysunknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity to pamidronate, other biphosphonates, or mannitol; Obstetric / Lactation: Pregnancy or lactation.Use Cautiously in: Underlying cardiovascular disease, especially HF (initiate saline hydration cautiously);Invasive dental procedures, cancer, receiving chemotherapy or corticosteroids, poor oral hygiene, periodontal disease, dental disease, anemia, coagulopathy, infection, or poorly-fitting dentures (may ↑ risk of jaw osteonecrosis);History of thyroid surgery (may be at ↑ risk for hypocalcemia);Renal impairment (dose ↓ recommended); Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • fatigue

Ear, Eye, Nose, Throat

  • conjunctivitis
  • blurred vision
  • eye pain/inflammation
  • rhinitis

Respiratory

  • rales

Cardiovascular

  • arrhythmias
  • hypertension
  • syncope
  • tachycardia

Gastrointestinal

  • nausea (most frequent)
  • abdominal pain
  • anorexia
  • constipation
  • vomiting

Fluid and Electrolyte

  • hypocalcemia (most frequent)
  • hypokalemia (most frequent)
  • hypomagnesemia (most frequent)
  • hypophosphatemia (most frequent)
  • fluid overload

Genitourinary

  • nephrotoxicity

Hematologic

  • leukopenia (most frequent)
  • anemia

Local

  • phlebitis at injection site (most frequent)

Metabolic

  • hypothyroidism

Musculoskeletal

  • muscle stiffness (most frequent)
  • musculoskeletal pain (most frequent)
  • femur fractures
  • osteonecrosis (primarily of jaw)

Miscellaneous

  • fever (most frequent)
  • generalized pain (most frequent)

Interactions

Drug-Drug interaction

Hypokalemia and hypomagnesemia may ↑ risk of digoxin toxicity.Calcium and vitamin D will antagonize the beneficial effects of pamidronate.Concurrent use of thalidomide may ↑ risk of renal dysfunction.

Route/Dosage

Single doses should not exceed 90 mgHypercalcemia of MalignancyIntravenous (Adults) Moderate hypercalcemia—30–90 mg; may be repeated after 7 days.Osteolytic Lesions from Multiple MyelomaIntravenous (Adults) 90 mg monthly.Osteolytic Lesions from Metastatic Breast CancerIntravenous (Adults) 90 mg q 3–4 wk.Paget’s DiseaseIntravenous (Adults) 90–180 mg/treatment; may be given as 30 mg daily for 3 days up to 30 mg/wk for 6 wk. Single doses of 60–90 mg may also be effective.

Availability (generic available)

Powder for injection: 30 mg/vial, 90 mg/vial

Nursing implications

Nursing assessment

  • Monitor intake/output ratios and BP frequently during therapy. Assess for signs of fluid overload (edema, rales/crackles).
  • Monitor symptoms of hypercalcemia (nausea, vomiting, anorexia, weakness, constipation, thirst, and cardiac arrhythmias).
  • Observe for evidence of hypocalcemia (paresthesia, muscle twitching, laryngospasm, and Chvostek’s or Trousseau’s sign). Protect symptomatic patients by elevating and padding side rails; keep bed in low position.
  • Monitor IV site for phlebitis (pain, redness, swelling). Symptomatic treatment should be used if this occurs.
  • Assess for bone pain. Treatment with nonopioid or opioid analgesics may be necessary.
  • Lab Test Considerations: Assess serum creatinine prior to each treatment. Withhold dose if renal function has deteriorated in patients treated for bone metastases.
    • Monitor serum electrolytes (including calcium, phosphate, potassium, and magnesium), hemoglobin, and creatinine closely. Monitor CBC and platelet count during the first 2 wk of therapy. May cause hyperkalemia or hypokalemia, hypernatremia, and hematuria.
    • Monitor renal function periodically during therapy.

Potential Nursing Diagnoses

Acute pain (Indications, Side Effects)
Risk for injury (Indications)

Implementation

  • Initiate a vigorous saline hydration, maintaining a urine output of 2000 mL/24 hr, concurrently with pamidronate therapy. Patients should be adequately hydrated, but avoid overhydration. Use caution in patients with underlying cardiovascular disease, especially HF. Do not use diuretics prior to treatment of hypovolemia.
    • Patients with severe hypercalcemia should be started at the 90-mg dose.
  • Intravenous: Reconstitute by adding 10 mL of sterile water for injection to each vial. Concentration: 30 mg/10 mL or 90 mg/10 mL. Allow drug to dissolve before withdrawing. Solution is stable for 24 hr if refrigerated.
  • Hypercalcemia: Diluent: Dilute further in 1000 mL of 0.45% NaCl, 0.9% NaCl, or D5W. Solution is stable for 24 hr at room temperature.
  • Rate: Administer 60-mg infusion over at least 4 hr and 90-mg infusion over 24 hr.
  • Multiple Myeloma: Diluent: Dilute reconstituted solution in 500 mL of 0.45% NaCl, 0.9% NaCl, or D5W.
  • Rate: Administer over 4 hr.
  • Paget’s Disease: Dilute reconstituted solution in 500 mL of 0.45% NaCl, 0.9% NaCl, or D5W.
  • Rate: Administer over 4 hr.
  • Y-Site Compatibility: acyclovir, alemtuzumab, alfentanil, allopurinol, amifostine, amikacin, aminiophylline, amphotericin B lipid complex, amphotericin B liposome, ampillicin, ampicillin/sulbactam, anidulafungin, argatroban, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, carboplatin, carmustine, cefazolin, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, chlorpromazine, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, daptomycin, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doxacurium, doxorubicin, doxorubicin liposomal, doxycycline, droperidol, enelaprilat, ephedrine, epinephrine, epirubicin, ertapenem, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hydralazine, hydrocortisone, hydromorphone, ifosfamide, imipenem/cilastatin, insulin, isoproterenol, ketorolac, labetalol, levofloxacin, levorphanol, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, melphalan, meperidine, meropenem, mesna, metaraminol, methotrexate, methyldopate, methylprednisolone, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitoxantrone, morphine, moxifloxacin, mycophenolate, nafcillin, nalbuphine, naloxone, nesiritide, nicardipine, nitroglycerin, nitroprusside, norepinephrine, octreotide, ondansetron, oxytocin, paclitaxel, palonosetron, pancuronium, pemetrexed, pentamidine, pentazocine, pentobarbital, phenobarbital, phentolamine, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, prochlorperazine, promethazine, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, topotecan, trimethoprim/sulfamethoxazole, vancomycin, vasopressin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, voriconazole, zidovudine
  • Y-Site Incompatibility: amphotericin B colloidal, caspofungin, dantrolene, diazepam, leucovorin, phenytoin
  • Additive Incompatibility: Calcium-containing solutions, such as Ringer’s solution.

Patient/Family Teaching

  • Advise patient to report signs of hypercalcemic relapse (bone pain, anorexia, nausea, vomiting, thirst, lethargy) or eye problems (pain, inflammation, blurred vision, conjunctivitis) to health care professional promptly.
  • Advise patient to notify nurse of pain at the infusion site.
  • Encourage patient to comply with dietary recommendations. Diet should contain adequate amounts of calcium and vitamin D.
  • Advise patient to notify health care professional if bone pain is severe or persistent.
  • Advise patient to maintain good oral hygiene and have regular dental examinations. Instruct patient to inform health care professional of pamidronate therapy prior to dental surgery.
  • Emphasize the need for keeping follow-up exams to monitor progress, even after medication is discontinued, to detect relapse.

Evaluation/Desired Outcomes

  • Lowered serum calcium levels.
  • Decreased pain from lytic lesions.

Aredia®

Pamidronate, see there.

Aredia

A brand name for PAMIDRONATE.