Neumega

Colony-stimulating Factors
Interleukins

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Ask patients about any adverse reactions to a previous dose of oprelvekin. If an allergic or hypersensitivity reaction occurred, another dose of oprelvekin is contraindicated. Oprelvekin should only be administered in a facility that can appropriately address a severe anaphylactic reaction, including anaphylactic shock.
Administer oprelvekin subcutaneously in the abdomen, thigh, or hip (or upper arm if not self-injecting). Take care not to inject intradermally or intravascularly.
Dosing with oprelvekin should begin 6—24 hours after completion of chemotherapy; the safety and efficacy of oprelvekin immediately prior to or concurrently with cytotoxic chemotherapy or initiated at the time of the expected nadir have not been established. The effectiveness of oprelvekin has not been evaluated in patients receiving chemotherapy regimens of > 5 days duration or regimens with delayed myelosuppression.
Administer at roughly the same time daily.
Fluid and electrolyte balance should be monitored during oprelvekin therapy.
 
Reconstitution:
Reconstitute aseptically with 1 ml of sterile water for injection, USP (without preservative). The sterile water for injection should be directed at the side of the vial and the contents gently swirled; AVOID EXCESSIVE OR VIGOROUS AGITATION. The reconstituted injection should be clear, colorless, and contain 5 mg/ml of oprelvekin.
Do not re-enter or reuse the single-use vial. The reconstituted injection should be used as soon as possible following reconstitution because neither the commercially available product nor the sterile water for injection, USP contain preservatives.
The reconstituted injection may be used within 3 hours of reconstitution when stored either at 2—8 degrees C (36—46 degrees F) or at room temperature up to 25 degrees C (77 degrees F). DO NOT FREEZE OR SHAKE THE RECONSTITUTED INJECTION SOLUTION. Discard any unused portion of either the reconstituted injection or sterile water for injection, USP.

atrial flutter / Early / 12.0-12.0
atrial fibrillation / Early / 12.0-12.0
pleural effusion / Delayed / 10.0-10.0
papilledema / Delayed / 2.0-2.0
heart failure / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
pulmonary edema / Early / Incidence not known
capillary leak syndrome / Early / Incidence not known
visual impairment / Early / Incidence not known
ocular hemorrhage / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
laryngeal edema / Rapid / Incidence not known
stroke / Early / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known

edema / Delayed / 59.0-59.0
dyspnea / Early / 48.0-48.0
sinus tachycardia / Rapid / 20.0-20.0
ocular infection / Delayed / 19.0-19.0
anemia / Delayed / 10.0-15.0
palpitations / Early / 14.0-14.0
candidiasis / Delayed / 14.0-14.0
antibody formation / Delayed / 1.0-1.0
hypokalemia / Delayed / 0-1.0
constipation / Delayed / 10.0
bone pain / Delayed / 10.0
peripheral edema / Delayed / Incidence not known
fluid retention / Delayed / Incidence not known
blurred vision / Early / Incidence not known
wheezing / Rapid / Incidence not known
dysarthria / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
chest pain (unspecified) / Early / Incidence not known
dehydration / Delayed / Incidence not known
hypoalbuminemia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known

nausea / Early / 77.0-77.0
vomiting / Early / 77.0-77.0
diarrhea / Early / 43.0-43.0
fever / Early / 43.0-43.0
rhinitis / Early / 42.0-42.0
headache / Early / 41.0-41.0
dizziness / Early / 38.0-38.0
insomnia / Early / 33.0-33.0
cough / Delayed / 29.0-29.0
rash (unspecified) / Early / 25.0-25.0
pharyngitis / Delayed / 25.0-25.0
asthenia / Delayed / 14.0-14.0
syncope / Early / 13.0-13.0
anorexia / Delayed / 10.0
abdominal pain / Early / 10.0
dyspepsia / Early / 10.0
ecchymosis / Delayed / 10.0
alopecia / Delayed / 10.0
infection / Delayed / 10.0
myalgia / Early / 10.0
chills / Rapid / 10.0
urticaria / Rapid / Incidence not known
flushing / Rapid / Incidence not known
paresthesias / Delayed / Incidence not known
skin discoloration / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known

Neumega

Rx

Recombinant human IL-11; biological activity is essentially the similar to native protein; used as a platelet growth factor; wide spectrum of activity involving the hematopoietic, lymphopoietic, hepatic, adipose, neuronal and osteoclast systems.

The recommended dose is 50 mcg/kg subcutaneously once daily. Dosing should be initiated 6—24 hours after the completion of chemotherapy and continued until the postnadir platelet count is 50,000/mm3 or higher. Platelet counts should be monitored periodically to assess the optimal duration of therapy. In controlled clinical trials, doses were administered for 10—21 days. Dosing beyond 21 days per treatment course is not recommended. Oprelvekin has not been evaluated in patients receiving regimens longer than 5 days duration or with agents associated with delayed myelosuppression (e.g., nitrosoureas, mitomycin C). Treatment should be discontinued at least 2 days before the start of the next planned cycle of chemotherapy.

The manufacturer recommends that oprelvekin use in children, especially those younger than 12 years, be restricted to controlled clinical trials with closely monitored safety assessments. In a phase I, single-arm, dose escalation study, 43 pediatric patients were treated with oprelvekin at doses ranging from 25—125 mcg/kg/day subcutaneously following ICE chemotherapy. All patients required platelet transfusions and the lack of a comparator arm made the study design inadequate to assess efficacy. The projected effective dose in children (based on comparable AUC observed for the effective dose in healthy adults) appears to exceed the maximum tolerated pediatric dose of 50 mcg/kg/day.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

CrCl < 30 ml/min: Reduce dose to 25 mcg/kg SC once daily.

Bumetanide: (Major) Patients receiving loop diuretics during oprelvekin, rh-IL-11 therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy.
Ethacrynic Acid: (Major) Patients receiving loop diuretics during oprelvekin, rh-IL-11 therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy.
Furosemide: (Major) Patients receiving loop diuretics during oprelvekin, rh-IL-11 therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy.
Loop diuretics: (Major) Patients receiving loop diuretics during oprelvekin, rh-IL-11 therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy.
Thiazide diuretics: (Major) Patients receiving thiazide diuretics during oprelvekin, rh-IL-11 therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy.
Torsemide: (Major) Patients receiving loop diuretics during oprelvekin, rh-IL-11 therapy are at increased risk for developing severe hypokalemia; close monitoring of fluid and electrolyte status is warranted during concurrent diuretic and oprelvekin therapy.
Vinblastine: (Moderate) Interleukins are inhibitors of cytochrome P450 (CYP) isoenzyme 3A4. Vinblastine is a CYP3A4 substrate. Increased concentrations of vinblastine are likely if it is coadministered with aldesleukin or other interleukins; exercise caution. Enhanced vinblastine toxicity has been reported in patients receiving a concomitant CYP3A4 inhibitor. In addition, myelosuppressive or other side effects may be additive. For example, due to the thrombocytopenic effects of vinblastine and many of the interleukins, an additive risk of infection or bleeding may be seen.

50 mcg/kg/day SC. Doses > 50 mcg/kg/day have been given but are associated with an increased incidence of cardiovascular events.

50 mcg/kg/day SC. Doses > 50 mcg/kg/day have been given but are associated with an increased incidence of cardiovascular events.

50 mcg/kg/day SC has been studied.

50 mcg/kg/day SC has been studied.

>= 8 months: 50 mcg/kg/day SC has been studied.

Mechanism of Action: Oprelvekin functions similarly to endogenous interleukin (IL)-11 and stimulates platelet production. The primary hematopoietic activity of oprelvekin is stimulation of megakaryocytopoiesis and thrombopoiesis. At the molecular level, IL-11 binds to the IL-11 receptor (IL-11Ralpha) on megakaryocytes and megakaryocyte progenitor cells. The IL-11 receptor belongs to a family of cytokine receptors which includes the receptors for IL-6, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M (OSM), which are all capable of interacting with the signal transducing receptor gp130 after ligand binding. Binding of IL-11 to IL-11Ralpha stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production. Platelets produced in response to oprelvekin are morphologically and functionally normal and possess a normal life-span. Oprelvekin has also been shown to have non-hematopoietic activities in animals including regulation of intestinal epithelium growth (enhanced healing of gastrointestinal lesions), inhibition of adipogenesis, induction of acute phase protein synthesis, inhibition of pro-inflammatory cytokine production by macrophages, and stimulation of osteoclastogenesis and neurogenesis.

Oprelvekin is administered subcutaneously. The kidney is the primary route of elimination. Metabolism of the drug does occur; however, the mechanisms involved have not been determined. The amount of intact drug in urine is low. The terminal half life is about 7 hours.

Mean peak serum concentrations (Cmax) of 17.4 ng/mL are reached at approximately 3.2 hours (Tmax) following a single 50 mcg/kg subcutaneous dose. The absolute bioavailability of oprelvekin is > 80%. Oprelvekin is rapidly cleared from the serum and distributed to highly perfused organs. Following multiple dosing, accumulation does not occur and clearance is not impaired.

Oprelvekin is classified as FDA pregnancy risk category C and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal data have shown that oprelvekin has embryocidal effects when given in doses of 0.2- to 20-times the human dose. There are no adequate and well-controlled studies of oprelvekin in pregnant women.

According to the manufacturer, a decision should be made whether to discontinue breast-feeding or to discontinue oprelvekin therapy, taking into account the importance of the drug to the mother. It is not known if oprelvekin is excreted in human milk. However, if the drug is excreted into breast-milk, minimal risk to the nursing infant would be expected, because the drug would likely be digested by the infant's gastrointestinal tract. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.