Oprelvekin

Pharmacology

Mechanism of Action

Oprelvekin is a thrombopoietic growth factor that stimulates megakaryocytopoiesis and thrombopoiesis, resulting in proliferation of megakaryocyte progenitors and megakaryocyte maturation, thereby increasing platelet production.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: Adults: 112 to 152 mL/kg

Excretion

Urine (primarily; predominantly as metabolites); Clearance: Adults: 2.2 to 2.7 mL/min/kg; clearance decreases with age and is about 1.2 to 1.6 times faster in children than in adults

Onset of Action

Onset of action: 5 to 9 days; Maximum effect: 14 to 19 days

Time to Peak

Serum: 3.2 ± 2.4 hours

Duration of Action

Up to 7 days after discontinuation

Half-Life Elimination

Terminal: 6.9 ± 1.7 hours

Use in Specific Populations

Special Populations: Renal Function Impairment

Exposure to oprelvekin increases as renal function decreases.

Use: Labeled Indications

Thrombocytopenia: Prevention of severe thrombocytopenia and to reduce the need for platelet transfusions following myelosuppressive chemotherapy for nonmyeloid malignancy in adults who are at high risk for thrombocytopenia

Contraindications

Hypersensitivity to oprelvekin or any component of the formulation

Dosage and Administration

Dosing: Adult

Note: Neumega has been discontinued in the US for more than 1 year.

Thrombocytopenia: SubQ: 50 mcg/kg once daily until postnadir platelet count ≥50,000/mm³. Begin ~6 to 24 hours after the end of chemotherapy. In studies, doses were administered for 10 to 21 days (do not administer for more than 21 days). Discontinue at least 2 days prior to the next planned chemotherapy cycle.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Neumega has been discontinued in the US for more than 1 year.

Note: First dose should not be administered until 6 to 24 hours after the end of chemotherapy. Discontinue the drug at least 48 hours before beginning the next cycle of chemotherapy.

Children: SubQ: 25 to 50 mcg/kg once daily for 27 days was shown to be efficacious with decreased toxicities as compared to higher doses in one study with 47 pediatric patients (Cairo 2005); dosing should continue until postnadir platelet count ≥50,000/mm³

Note: The manufacturer states that, until efficacy/toxicity parameters are established, the use of oprelvekin in pediatric patients (particularly those <12 years of age) should be restricted to use in controlled clinical trials.

Reconstitution

Reconstitute with 1 mL provided sterile water for injection (without preservative) to a final concentration of 5 mg/mL; direct diluent down side of vial; swirl gently, avoid excessive or vigorous agitation.

Administration

SubQ: For subcutaneous administration in the abdomen, thigh, or hip; outer upper arm may also be used (if not self-injecting). Rotate injection sites each day.

Storage

Store intact vials (and prefilled diluent syringe) refrigerated between 2°C and 8°C (36°F and 46°F); do not freeze. Protect from light. Store reconstituted solution in the vial at either 2°C to 8°C (36°F to 46°F) or room temperature of ≤25°C (77°F); use within 3 hours of reconstitution. Do not freeze or shake reconstituted solution.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>10%:

Cardiovascular: Tachycardia (children: 84%; adults: 20%), edema (59%), cardiomegaly (children: 21%), vasodilation (19%), atrial arrhythmia (12% to 15%), palpitations (14%), syncope (13%)

Central nervous system: Headache (41%), dizziness (38%), insomnia (33%)

Dermatologic: Skin rash (25%)

Endocrine & metabolic: Fluid retention

Gastrointestinal: Nausea (≤77%), vomiting (≤77%), diarrhea (43%), mucositis (43%), oral candidiasis (14%)

Hematologic & oncologic: Febrile neutropenia (48%), anemia (dilutional; onset: 3 to 5 days; duration: ≤1 week)

Neuromuscular & skeletal: Severe weakness (14%), periosteal disease (children: 11%), arthralgia

Ophthalmic: Conjunctival edema (children: ≤57%; adults: ≤19%), conjunctival erythema (children: ≤57%; adults: ≤19%), conjunctival injection (children: ≤57%; adults: ≤19%), papilledema (children: 16%; adults: 1%)

Respiratory: Dyspnea (48%), rhinitis (42%), cough (29%), pharyngitis (25%)

Miscellaneous: Fever (36%)

1% to 10%: Respiratory: Pleural effusion (10%)

<1%, postmarketing, and/or case reports: Amblyopia, anaphylactoid reaction, anaphylaxis, blindness, blurred vision, capillary leak syndrome, cardiac failure, cerebrovascular accident, chest pain, decreased visual acuity, dehydration, dysarthria, exfoliative dermatitis, facial edema, hemophthalmos, hypersensitivity reaction, hypervolemia, hypoalbuminemia, hypocalcemia, hypokalemia, hypotension, increased clotting factors (von Willebrand factor), increased serum fibrinogen, injection site reaction (dermatitis, local discoloration, pain at injection site), loss of consciousness, mental status changes, optic neuropathy, paresthesia, pericardial effusion, peripheral edema, pneumonia, pulmonary edema, renal failure, shock, skin discoloration, urticaria, ventricular arrhythmia, visual field defect, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Anemia (dilutional): Dilutional anemia may occur due to increased plasma volume, presenting as moderate decreases in hemoglobin concentration, hematocrit, and red blood cells without a decrease in red blood cell mass; effect generally appears within 3 to 5 days of initiation of therapy and resolves over ~1 week following oprelvekin discontinuation.
• Cardiovascular effects: Arrhythmias (usually brief in duration), pulmonary edema, and cardiac arrest have been reported; use in patients with a history of atrial arrhythmia only if the potential benefit exceeds possible risks. Stroke has been reported in patients who develop atrial fibrillation/flutter while receiving oprelvekin (patients with a history of stroke or transient ischemic attack may be at risk for atrial fibrillation/flutter). Ventricular arrhythmia has also been reported, occurring within 2 to 7 days of treatment initiation.
• Fluid retention: May cause serious fluid retention (reversible within several days after discontinuation), which may result in peripheral edema, dyspnea, pulmonary edema, capillary leak syndrome, atrial arrhythmias, and exacerbation of preexisting pleural effusion. Serious fluid retention (sometimes fatal) has been reported. Use with caution in patients with clinically evident heart failure or who may be susceptible to developing heart failure, patients receiving aggressive hydration, patients with a history of heart failure who are well compensated and receiving appropriate medical therapy, and patients who may develop fluid retention as a result of associated medical conditions or whose medical condition may be exacerbated by fluid retention. Monitor fluid and electrolyte status; preexisting fluid collections, including pericardial effusions or ascites, should also be monitored (may require drainage).
• Hypersensitivity reactions: [US Boxed Warning]: Allergic or hypersensitivity reactions, including anaphylaxis, have been reported. Permanently discontinue in any patient developing an allergic or hypersensitivity reaction. Reaction may occur with the first or with subsequent doses. Allergic reactions included facial/tongue/larynx edema, dyspnea, wheezing, chest pain, hypotension (including shock), rash, urticaria, flushing, fever, loss of consciousness, mental status changes, and/or dysarthria.
• Papilledema: Papilledema has occurred, usually following repeated cycles. The incidence of papilledema occurred more frequently in children. Use with caution in patients with preexisting papilledema or with CNS tumors; may worsen or develop during treatment. Patients experiencing oprelvekin-related papilledema may be at risk for visual acuity changes and/or visual field defects, ranging from blurred vision to blindness.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment (oprelvekin is renally eliminated); dosage adjustment required in severe renal impairment. Monitor fluid balance.

Other warnings/precautions:

• Appropriate use: Begin 6 to 24 hours following completion of chemotherapy; safety and efficacy of oprelvekin administered immediately before or during cytotoxic chemotherapy or initiated at the time of expected nadir has not been established. Not indicated following myeloablative chemotherapy; increased toxicities (hypotension, tachycardia, edema, and conjunctival bleeding) were reported and efficacy was not demonstrated. A higher incidence of adverse events (fluid retention/overload, facial/pulmonary edema, capillary leak syndrome) has also been reported when used following bone marrow transplantation. Efficacy has not been evaluated with chemotherapy regimens >5 days' duration or with regimens associated with delayed myelosuppression (eg, nitrosoureas, mitomycin). Safety and efficacy have not been established with chronic administration.

Monitoring Parameters

Monitor electrolytes and fluid balance during therapy (including persisting fluid collections [pericardial effusions or ascites]); obtain a complete blood cell count (CBC) at baseline and at regular intervals during therapy; monitor platelet counts during the time of expected nadir and until adequate recovery has occurred; renal function (at baseline)

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience mouth sores, trouble sleeping, or runny nose. Have patient report immediately to prescriber rash, severe fatigue, severe nausea, vomiting, severe diarrhea, severe abdominal pain, flu-like symptoms, sore throat, difficulty breathing, signs of severe cerebrovascular disease (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight), shortness of breath, excessive weight gain, swelling of arms or legs, chest pain, fast heartbeat, severe dizziness, passing out, flushing, arrhythmia, severe headache, bruising, bleeding, vision changes, eye pain, severe eye irritation, blindness, loss of strength and energy, unable to pass urine, change in amount of urine passed, dysphagia, or illogical thinking (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.