OUR PRODUCTS

HELPING
MEDICINES
DO MORE

Pushing healthcare forward requires us to propel medicines to their full potential. We make possible what others consider impossible. Take a look at our product portfolio to see what the right mix of technology and heart can accomplish.

VASOPRESSIN INJECTION*

*Now Available

Indications and Important Safety Information

INDICATION
Vasopressin Injection is indicated to increase blood pressure in adults with vasodilatory shock who remain hypotensive despite fluids and catecholamines.

CONTRAINDICATION
Vasopressin Injection is contraindicated in patients with known allergy or hypersensitivity to 8-L-arginine vasopressin or chlorobutanol.

WARNINGS AND PRECAUTIONS

Worsening Cardiac Functions
A decrease in cardiac index may be observed with the use of vasopressin.

Reversible Diabetes Insipidus
Patients may experience reversible diabetes insipidus, manifested by the development of polyuria, a diluted urine and hypernatremia, after cessation of treatment with vasopressin. Monitor serum electrolytes, fluid status and urine output after vasopressin discontinuation. Some patients may require readministration of vasopressin or administration of desmopressin to correct fluid and electrolyte shifts.

DRUG INTERACTIONS

Catecholamines
Use with catecholamines is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

Indomethacin
Use with indomethacin may prolong the effect of Vasopressin Injection on cardiac index and systemic vascular resistance. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

Ganglionic Blocking Agents
Use with ganglionic blocking agents may increase the effect of Vasopressin Injection on mean arterial blood pressure. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

Drugs Suspected of Causing Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
Use with drugs suspected of causing SIADH (e.g., SSRIs, tricyclic antidepressants, haloperidol, chlorpropamide, enalapril, methyldopa, pentamidine, vincristine, cyclophosphamide, ifosfamide, felbamate) may increase the pressor effect in addition to the antidiuretic effect of Vasopressin Injection. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

Drugs Suspected of Causing Diabetes Insipidus
Use with drugs suspected of causing diabetes insipidus (e.g., demeclocycline, lithium, foscarnet, clozapine) may decrease the pressor effect in addition to the antidiuretic effect of Vasopressin Injection. Hemodynamic monitoring is recommended; adjust the dose of vasopressin as needed.

ADVERSE REACTIONS
Adverse reactions associated with the use of vasopressin were identified in the literature. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

The most common adverse reactions associated with the use of vasopressin include decreased cardiac output, bradycardia, tachyarrhythmias, hyponatremia and ischemia (coronary, mesenteric, skin, digital).

USE IN SPECIFIC PATIENT POPULATIONS

Pregnancy
There are no available data on Vasopressin Injection use in pregnant women to inform a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted. Because of increased clearance of vasopressin in the second and third trimester, the dose of Vasopressin Injection may need to be increased.

Vasopressin Injection may produce tonic uterine contractions that could threaten the continuation of pregnancy.

Lactation
There are no data on the presence of vasopressin injection in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.

Pediatric Use
Safety and effectiveness of Vasopressin Injection in pediatric patients with vasodilatory shock have not been established.

Geriatric Use
Clinical studies of vasopressin did not include sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

For safety and dosing guidelines for Vasopressin Injection, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.

TO REPORT SUSPECTED ADVERSE REACTIONS, contact Eagle Pharmaceuticals, Inc. at 1-855-318-2170 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

BELRAPZO®

bendamustine hydrochloride injection

Indications and Important Safety Information

Indications
BELRAPZO® (bendamustine hydrochloride injection) is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL). Efficacy relative to first-line therapies other than chlorambucil has not been established.

BELRAPZO® (bendamustine hydrochloride injection) is indicated for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.

IMPORTANT SAFETY INFORMATION
Contraindications: BELRAPZO® is contraindicated in patients with a history of a hypersensitivity reaction to bendamustine, polyethylene glycol 400, propylene glycol, or monothioglycerol. Reactions to bendamustine HCl have included anaphylaxis and anaphylactoid reactions.

Myelosuppression: Bendamustine HCl caused severe myelosuppression (Grade 3-4) in 98% of patients in the 2 NHL studies. Three patients (2%) died from myelosuppression-related adverse reactions. In the event of treatment-related myelosuppression, monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. In the clinical trials, blood counts were monitored every week initially. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle. Prior to the initiation of the next cycle of therapy, the absolute neutrophil count (ANC) should be ≥1 x 109/L and the platelet count should be ≥75 x 109/L.

Infections: Infection, including pneumonia, sepsis, septic shock, hepatitis, and death has occurred in adult and pediatric patients in clinical trials and in postmarketing reports for bendamustine HCl. Patients with myelosuppression following treatment with bendamustine HCl are more susceptible to infections. Advise patients with myelosuppression following BELRAPZO® treatment to contact a physician immediately if they have symptoms or signs of infection. Patients treated with bendamustine HCl are at risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster. Patients should undergo appropriate measures (including clinical and laboratory monitoring, prophylaxis, and treatment) for infection and infection reactivation prior to administration.

Anaphylaxis and Infusion Reactions: Infusion reactions to bendamustine HCl have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus, and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Patients who experience Grade 3 or worse allergic-type reactions should not be rechallenged. Consider measures to prevent severe reactions, including antihistamines, antipyretics, and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions. Discontinue BELRAPZO® for patients with Grade 4 infusion reactions. Consider discontinuation for Grade 3 infusion reactions as clinically appropriate considering individual benefits, risks, and supportive care.

Tumor Lysis Syndrome: Tumor lysis syndrome associated with bendamustine HCl has occurred in patients in clinical trials and in postmarketing reports. The onset tends to be within the first treatment cycle of bendamustine HCl and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. Allopurinol has also been used during the beginning of bendamustine HCl therapy. However, there may be an increased risk of severe skin toxicity when bendamustine HCl and allopurinol are administered concomitantly.

Skin Reactions: Fatal and serious skin reactions have been reported with bendamustine HCl treatment in clinical trials and postmarketing safety reports, including toxic skin reactions [Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS)], bullous exanthema, and rash. Events occurred when bendamustine HCl was given as a single agent and in combination with other anticancer agents or allopurinol.

Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold, or discontinue BELRAPZO®.

Hepatotoxicity: Fatal and serious cases of liver injury have been reported with bendamustine HCl. Combination therapy, progressive disease, or reactivation of hepatitis B were confounding factors in some patients. Most cases were reported within the first 3 months of starting therapy. Monitor liver chemistry tests prior to and during BELRAPZO® therapy.

Other Malignancies: There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with bendamustine HCl, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma.

Extravasation Injury: Bendamustine HCl extravasations resulting in hospitalizations from erythema, marked swelling, and pain has been reported in postmarketing. Ensure good venous access prior to starting BELRAPZO® infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of BELRAPZO®.

Embryo-fetal Toxicity: Bendamustine HCl can cause fetal harm when administered to a pregnant woman. Single intraperitoneal doses of bendamustine in mice and rats administered during organogenesis caused an increase in resorptions, skeletal and visceral malformations, and decreased fetal body weights. Advise women to avoid becoming pregnant while using BELRAPZO®.

Most Common Adverse Reactions

  • Most common non-hematologic adverse reactions for CLL (frequency ≥ 15%) are pyrexia, nausea, and vomiting.
  • Most common non-hematologic adverse reactions for NHL (frequency ≥ 15%) are nausea, fatigue, vomiting, diarrhea, pyrexia, constipation, anorexia, cough, headache, weight decreased, dyspnea, rash, and stomatitis.
  • Most common hematologic abnormalities (frequency ≥15%) are lymphopenia, anemia, leukopenia, thrombocytopenia, and neutropenia.

TO REPORT ADVERSE REACTIONS, contact Eagle Pharmaceuticals, Inc. at 1-855-318-2170 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch.

PEMFEXY™

(pemetrexed injection)

Indications and Important Safety Information

INDICATION
PEMFEXY is indicated in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).

PEMFEXY is indicated as a single agent for the maintenance treatment of patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.

PEMFEXY is indicated as a single agent for the treatment of patients with recurrent, metastatic non-squamous non-small cell lung cancer (NSCLC) after prior chemotherapy.

Limitation of Use: PEMFEXY is not indicated for the treatment of patients with squamous cell non-small cell lung cancer.

PEMFEXY is indicated in combination with cisplatin for the initial treatment of patients with malignant pleural mesothelioma (MPM), whose disease is unresectable or who are otherwise not candidates for curative surgery.

CONTRAINDICATION
PEMFEXY is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed.

WARNINGS AND PRECAUTIONS

Myelosuppression and Increased Risk of Myelosuppression Without Vitamin Supplementation

PEMFEXY can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation.

7 Days prior to treatment with PEMFEXY, patients must be instructed to initiate supplementation with oral folic acid. Intramuscular injections of vitamin B 12  are also required 7 days prior to PEMFEXY treatment. Continue vitamin supplementation during treatment and for 21 days after the last dose of PEMFEXY to reduce the severity of treatment-related hematologic and gastrointestinal toxicities. Obtain a complete blood count at the beginning of each cycle. Do not administer PEMFEXY until the ANC is at least 1500 cells/mm 3 and platelet count is at least 100,000 cells/mm 3 . Permanently reduce PEMFEXY in patients with an ANC of less than 500 cells/mm 3 or platelet count of less than 50,000 cells/mm 3  in previous cycles.
In Studies JMDB and JMCH, among patients who received vitamin supplementation, incidence of Grade 3-4 neutropenia was 15% and 23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In Study JMCH, 18% of patients in the pemetrexed arm required red blood cell transfusions compared to 7% of patients in the cisplatin arm. In Studies JMEN, PARAMOUNT, and JMEI, where all patients received vitamin supplementation, incidence of Grade 3-4 neutropenia ranged from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to 5%.

Renal Failure
Pemetrexed can cause severe, and sometimes fatal, renal toxicity. Determine creatinine clearance before each dose and periodically monitor renal function during treatment with PEMFEXY. The incidences of renal failure in clinical studies in which patients received pemetrexed with cisplatin were 2.1% in Study JMDB and 2.2% in Study JMCH. The incidence of renal failure in clinical studies in which patients received pemetrexed as a single agent ranged from 0.4% to 0.6% (Studies JMEN, PARAMOUNT, and JMEI). Withhold PEMFEXY in patients with a creatinine clearance of less than 45 mL/min.

Bullous and Exfoliative Skin Toxicity
Serious and sometimes fatal, bullous, blistering, and exfoliative skin toxicity, including cases suggestive of Stevens-Johnson Syndrome/toxic epidermal necrolysis, can occur with pemetrexed. Permanently discontinue PEMFEXY for severe and life-threatening bullous, blistering, or exfoliating skin toxicity.

Interstitial Pneumonitis
Serious interstitial pneumonitis, including fatal cases, can occur with pemetrexed. Withhold PEMFEXY for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation. If pneumonitis is confirmed, permanently discontinue PEMFEXY.

Radiation Recall
Radiation recall can occur with pemetrexed in patients who have received radiation weeks to years previously. Monitor patients for inflammation or blistering in areas of previous radiation treatment. Permanently discontinue PEMFEXY for signs of radiation recall.

Increased Risk of Toxicity with Ibuprofen in Patients with Renal Impairment
Exposure to pemetrexed is increased in patients with mild to moderate renal impairment who take concomitant ibuprofen, increasing the risks of adverse reactions of pemetrexed. In patients with creatinine clearances between 45 mL/min and 79 mL/min, avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of PEMFEXY. If concomitant ibuprofen use cannot be avoided, monitor patients more frequently for pemetrexed adverse reactions, including myelosuppression, renal, and gastrointestinal toxicity.

Embryo-Fetal Toxicity
Based on findings from animal studies and its mechanism of action, PEMFEXY can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and increased malformations at doses lower than the recommended human dose of 500 mg/m 2 . Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with PEMFEXY and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMFEXY and for 3 months after the final dose.

DRUG INTERACTIONS
Ibuprofen increases exposure (AUC) of pemetrexed. In patients with creatinine clearance between 45 mL/min and 79 mL/min:

  • Avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of PEMFEXY.
  • Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided.

ADVERSE REACTIONS
Severe adverse reactions (Grade 3-4) occurring in fully vitamin supplemented patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed in combination with cisplatin versus gemcitabine in combination with cisplatin for initial treatment (JMDB),respectively, were neutropenia (15% vs 27%); fatigue (7% vs 5%); nausea (7% vs 4%); anemi(6% vs 10%); vomiting (6% vs 6%); thrombocytopenia (4% vs 13%); anorexia (2% vs 1%); diarrhea (1% vs 2%); elevated creatinine (1% vs 1%); stomatitis/pharyngitis (1% vs 0%); and constipation (1% vs 0%).

Common adverse reactions (all grades) occurring in ≥5% fully vitamin supplemented patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed in combination with cisplatin versus gemcitabine in combination with cisplatin for initial treatment (JMDB), respectively, were nausea (56% vs 53%); fatigue (43% vs 45%); vomiting (40% vs 36%); anemia (33% vs 46%); neutropenia (29% vs 38%); anorexia (27% vs 24%); constipation (21% vs 20%); stomatitis/pharyngitis (14% vs 12%); alopecia (12% vs 21%); diarrhea (12% vs 13%); thrombocytopenia (10% vs 27%); elevated creatinine (10% vs 7%), sensory neuropathy (9% vs 12%); taste disturbance (8% vs 9%); rash/desquamation (7% vs 8%); and dyspepsia/heartburn (5% vs 6%).

Severe adverse reactions (Grade 3-4) occurring in patients with non-progressive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed as a single agent versus placebo as maintenance treatment (JMEN), respectively, following non-pemetrexed containing, platinum-based induction therapy were fatigue (5% vs 1%); anemia (3% vs 1%); neutropenia (3% vs 0%); infection (2% vs 0%); anorexia (2% vs 0%); nausea (1% vs 1%); mucositis/stomatitis (1% vs 0%); diarrhea (1% vs 0%); and sensory neuropathy (1% vs 0%).

Common adverse reactions (all grades) occurring in ≥5% patients with non-progressive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed as a single agent versus placebo as maintenance treatment (JMEN), respectively, following non-pemetrexed containing, platinum-based induction therapy were fatigue (25% vs 11%); nausea (19% vs 6%); anorexia (19% vs 5%); anemia (15% vs 6%); increased ALT (10% vs 4%); rash/desquamation (10% vs 3%); sensory neuropathy (9% vs 4%); vomiting (9% vs 1%); increased AST (8% vs 4%); mucositis/stomatitis (7% vs 2%); neutropenia (6% vs 0%); diarrhea (5% vs 3%); and infection (5% vs 2%).

Severe adverse reactions (Grade 3-4) occurring in patients with non-progressive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed as a single agent versus placebo as maintenance treatment (PARAMOUNT), respectively, following pemetrexed plus cisplatin induction therapy were anemia (4.8% vs 0.6%); fatigue (4.5% vs 0.6%); neutropenia (3.9% vs 0%); nausea (0.3% vs 0%); and mucositis/stomatitis (0.3% vs 0%).

Common adverse reactions (all grades) occurring in ≥5% patients with non-progressive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed as a single agent versus placebo as maintenance treatment (PARAMOUNT),respectively, following pemetrexed plus cisplatin induction therapy were fatigue (18% vs 11%); anemia (15% vs 4.8%); nausea (12% vs 2.4%); neutropenia (9% vs 0.6%); vomiting (6% vs 1.8%); edema (5% vs 3.6%); and mucositis/stomatitis (5% vs 2.4%).

Severe adverse reactions (Grade 3-4) occurring in fully supplemented patients with recurrent metastatic non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed as a single agent versus docetaxel as 2nd-line treatment after prior chemotherapy (JMEI), respectively, were
neutropenia (5% vs 40%); fatigue (5% vs 5%); anemia (4% vs 4%); nausea (3% vs 2%); anorexia (2% vs 3%); vomiting (2% vs 1%); thrombocytopenia (2% vs 0%); increased ALT (2% vs 0%); alopecia (1% vs 2%); stomatitis/pharyngitis (1% vs 1%); and increased AST (1% vs 0%).

Common adverse reactions (all grades) occurring in ≥5% of fully supplemented patients with recurrent metastatic non-squamous non-small cell lung cancer (NSCLC) receiving pemetrexed as a single agent versus docetaxel as 2nd-line treatment after prior chemotherapy (JMEI), respectively, were fatigue (34% vs 36%); nausea (31% vs 17%); anorexia (22% vs 24%); anemia (19% vs 22%); vomiting (16% vs 12%); stomatitis/pharyngitis (15% vs 17%); rash/desquamation (14% vs 6%); diarrhea (13% vs 24%); neutropenia (11% vs 45%); fever (8% vs 8%); thrombocytopenia (8% vs 1%); increased ALT (8% vs 1%); pruritus (7% vs 2%); increased AST (7% vs 1%); alopecia (6% vs 38%); and constipation (6% vs 4%).

Severe adverse reactions (Grade 3-4) occurring in fully supplemented subgroup of patients with malignant pleural mesothelioma (MPM) receiving pemetrexed in combination with cisplatin versus cisplatin alone (JMCH), respectively, were neutropenia (23% vs 3%); nausea (12% vs 6%); vomiting (11% vs 4%); fatigue (10% vs 9%); thrombocytopenia (5% vs 0%); dehydration (4% vs 1%); anemia (4% vs 0%); diarrhea (4% vs 0%); stomatitis/pharyngitis (3% vs 0%); decreased creatinine clearance (1% vs 2%); elevated creatinine (1% vs 1%); anorexia (1% vs 1%); constipation (1% vs 1%); dyspepsia (1% vs 0%); and rash (1% vs 0%).

Common adverse reactions (all grades) occurring in ≥5% of fully supplemented subgroup of patients with malignant pleural mesothelioma (MPM) receiving pemetrexed in combination with cisplatin versus cisplatin alone (JMCH), respectively, were nausea (82% vs 77%); vomiting (57% vs 50%); neutropenia (56% vs 13%); fatigue (48% vs 42%); anemia (26% vs 10%); thrombocytopenia (23% vs 9%); stomatitis/pharyngitis (23% vs 6%); anorexia (20% vs 14%); diarrhea (17% vs 8%); decreased creatinine clearance (16% vs 18%); rash (16% vs 5%); constipation (12% vs 7%); elevated creatinine (11% vs 10%); alopecia (11% vs 6%); sensory neuropathy (10% vs 10%); taste disturbance (8% vs 6%); dehydration (7% vs 1%); conjunctivitis (5% vs 1%); and dyspepsia (5% vs 1%).

USE IN SPECIFIC PATIENT POPULATIONS

Pregnancy
There are no available data on pemetrexed use in pregnant women. Based on findings from animal studies and its mechanism of action, PEMFEXY can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and malformations at doses lower than the recommended human dose of 500 mg/m 2. Advise pregnant women on the potential risk to a fetus.

Lactation
There is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from PEMFEXY, advise women not to breastfeed during treatment with PEMFEXY and for one week after last dose.

Females and Males of Reproductive Potential
Verify pregnancy status of females of reproductive potential prior to initiating PEMFEXY. PEMFEXY can cause fetal harm when administered to a pregnant woman. Because of the potential for genotoxicity, advise females of reproductive potential to use effective contraception during treatment with PEMFEXY and for 6 months after the final dose. Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use effective contraception during treatment with PEMFEXY and for 3 months after the final dose. PEMFEXY may impair fertility in males of reproductive potential. It is not known whether these effects on fertility are reversible.

Pediatric Use
The safety and effectiveness of PEMFEXY in pediatric patients have not been established. Adverse reactions observed in pediatric patients studied were similar to those observed in adults.

Geriatric Use
The incidences of Grade 3-4 anemia, fatigue, thrombocytopenia, hypertension, and neutropenia were higher in patients 65 years of age and older as compared to younger patients in at least one of five randomized clinical trials.

Renal Impairment
PEMFEXY is primarily excreted by the kidneys. Decreased renal function results in reduced clearance and greater exposure (AUC) to pemetrexed compared with patients with normal renal function. No dosage is recommended for patients with creatinine clearance less than 45 mL/min.

For safety and dosing guidelines for PEMFEXY, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information.
To report SUSPECTED ADVERSE REACTIONS, contact Eagle Pharmaceuticals, Inc. at 1-855-318-2170 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

RYANODEX®

(dantrolene sodium) for injectable suspension

Indications and Important Safety Information

Indications
RYANODEX® (dantrolene sodium) for injectable suspension is indicated for the treatment of malignant hyperthermia in conjunction with appropriate supportive measures, and for the prevention of malignant hyperthermia in patients at high risk.

Important Safety Information
RYANODEX® is not a substitute for appropriate supportive measures in the treatment of malignant hyperthermia (MH), including discontinuing use of MH-triggering anesthetic agents, managing the metabolic acidosis, instituting cooling when necessary, and administering diuretics to prevent late kidney injury due to myoglobinuria (the amount of mannitol in RYANODEX® is insufficient to maintain diuresis).

RYANODEX® is associated with skeletal muscle weakness such as loss of grip strength and weakness in the legs, as well as drowsiness, dizziness, dysphagia, dyspnea, and decreased inspiratory capacity. Patients should not be permitted to ambulate without assistance until they have normal strength and balance. Care must be taken to prevent extravasation of RYANODEX® into the surrounding tissue due to the high pH of the reconstituted RYANODEX® suspension and potential for tissue necrosis.

BENDEKA®

(bendamustine hydrochloride) Injection

Indications and Important Safety Information

Indications
BENDEKA® is indicated for the treatment of patients with Chronic lymphocytic leukemia (CLL). Efficacy relative to first-line therapies other than chlorambucil has not been established.

Indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.

Important Safety Information
Contraindication: BENDEKA® (bendamustine HCI) injection is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine HCl, polyethylene glycol 400, propylene glycol, or monothioglycerol.

Myelosuppression: Bendamustine HCl caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies. Three patients (2%) died from myelosuppression-related adverse reactions. Monitor leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle.

Infections: Infection, including pneumonia, sepsis, septic shock, hepatitis and death has occurred. Patients with myelosuppression following treatment with BENDEKA® are more susceptible to infections. Patients treated with bendamustine HCl are at risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster. Patients should undergo appropriate monitoring, prophylaxis, and treatment measures prior to administration.

Anaphylaxis and Infusion Reactions: Infusion reactions to bendamustine HCl have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus, and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy. Monitor clinically and discontinue drug for severe (Grade 3-4) reactions. Ask patients about symptoms suggestive of infusion reactions after their first cycle of therapy. Consider measures to prevent severe reactions, including antihistamines, antipyretics, and corticosteroids in subsequent cycles in patients who have experienced Grade 1 or 2 infusion reactions.

Tumor Lysis Syndrome: Tumor lysis syndrome associated with bendamustine HCl has occurred. The onset tends to be within the first treatment cycle with bendamustine HCl and, without intervention, may lead to acute renal failure and death. Preventive measures include vigorous hydration and close monitoring of blood chemistry, particularly potassium and uric acid levels. There may be an increased risk of severe skin toxicity when bendamustine HCl and allopurinol are administered concomitantly.

Skin Reactions: Fatal and serious skin reactions have been reported with bendamustine HCl and include, toxic skin reactions, [Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS)], bullous exanthema and rash. Events occurred when bendamustine HCl was given as a single agent and in combination with other anticancer agents or allopurinol. Where skin reactions occur, they may be progressive and increase in severity with further treatment. Monitor patients with skin reactions closely. If skin reactions are severe or progressive, withhold, or discontinue BENDEKA®.

Hepatotoxicity: Fatal and serious cases of liver injury have been reported with bendamustine HCl. Combination therapy, progressive disease, or reactivation of hepatitis B were confounding factors in some patients. Most cases were reported within the first three months of starting therapy. Monitor liver chemistry tests prior to and during BENDEKA® therapy.

Other Malignancies: There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with bendamustine HCl, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia, and bronchial carcinoma. The association with BENDEKA® has not been determined.

Extravasation Injury: Bendamustine HCl extravasations have been reported in post-marketing resulting in hospitalizations from erythema, marked swelling, and pain. Assure good venous access prior to starting BENDEKA infusion and monitor the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of BENDEKA®.

Embryo-fetal Toxicity: Bendamustine HCl can cause fetal harm when administered to a pregnant woman. Women should be advised to avoid becoming pregnant while using BENDEKA®.

Most Common Adverse Reactions:
Adverse reactions (frequency >5%) during infusion and within 24 hours post-infusion are nausea and fatigue.
The most common non-hematologic adverse reactions for CLL (frequency ≥15%) are pyrexia, nausea, and vomiting.
The most common non-hematologic adverse reactions for NHL (frequency ≥15%) are nausea, fatigue, vomiting, diarrhea, pyrexia, constipation, anorexia, cough, headache, weight decreased, dyspnea, rash, and stomatitis.
The most common hematologic abnormalities (frequency ≥15%) are lymphopenia, anemia, leukopenia, thrombocytopenia, and neutropenia.

DOCETAXEL INJECTION

(non-alcohol formula)

Please see full Prescribing Information for boxed warning.

ARGATROBAN

(Argatroban Injection)

WHERE OTHERS SEE A
STOPPING POINT,
WE SEE UNTAPPED
POTENTIAL.

We believe that making the best end product
starts at the beginning. This is why we use our
3-step process of reinvention to see products
through from start to finish.

1

Identify medicines that can benefit from second generation advancements

2

Improve products by determining the technology requirements to address unmet needs

3

Impact patients’ lives with improved medicines brought to market primarily through the 505(b)(2) regulatory pathway

Through a fully integrated commercial team, we have the flexibility to market our products with or without a partner.

REFERENCES:

  1. RYANODEX® (dantrolene sodium) for injectable suspension [prescribing information]. Woodcliff Lake, NJ: Eagle Pharmaceuticals, Inc.; 2020.
  2. BENDEKA® (bendamustine hydrochloride) injection [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2021.
  3. BELRAPZO® (bendamustine hydrochloride injection) [prescribing information]. Woodcliff Lake, NJ: Eagle Pharmaceuticals, Inc.; 2021.