Elahere

• ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis
  [see Warnings and Precautions (
  5.1 Ocular Disorders

  ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

  Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).

  [see Adverse Reactions (

  6.1

  )].

  The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients.

  Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended

  [see

  Dosage and Administration (

  2.3

  )].

  Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.

  Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

  Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

  [see Dosage and Administration (

  2.4

  )].
  ) and Adverse Reactions (
  6.1 Clinical Trials Experience

  Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

  The pooled safety population described in Warnings and Precautions reflect exposure to ELAHERE in 682 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer at 6 mg/kg AIBW administered intravenously once every 3 weeks until disease progression or unacceptable toxicity in Study 0416, Study 0417, Study 0403 (NCT02631876), and Study 0401 (NCT01609556). The median duration of treatment was 4.4 months (range: 1.0 to 30.0). In the pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.

  Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

  Study 0416

  The safety of ELAHERE was evaluated in Study 0416, a multicenter, open-label, active-controlled, randomized, two-arm, study in patients (n=453) with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer

  [see Clinical Studies (

  14

  )]

  . Patients received ELAHERE 6 mg/kg AIBW once every 3 weeks until disease progression or unacceptable toxicity. The median duration of treatment was 5 months (range: 0.69 to 27.4).

  Serious adverse reactions occurred in 24% of patients treated with ELAHERE. The most common (≥2%) serious adverse reactions were intestinal obstruction (5%), abdominal pain (3%), and pleural effusion (3%). Fatal adverse reactions occurred in 3% of patients, including intestinal obstruction, dyspnea in the setting of subileus, neutropenic sepsis, cardiopulmonary failure, respiratory failure, ischemic stroke, and pulmonary embolus.

  Permanent discontinuation of ELAHERE due to adverse reactions occurred in 9% of patients. The most common (≥1%) adverse reactions leading to permanent discontinuation were pneumonitis (2%), blurred vision (1%), and peripheral neuropathy (1%).

  Dosage delays of ELAHERE due to an adverse reaction occurred in 54% of patients treated with ELAHERE. Adverse reactions which required dosage delays in ≥3% of patients included blurred vision (22%), keratopathy (19%), dry eye (7%), neutropenia (6%), pneumonitis (6%), photophobia (5%), cataract (4%), and peripheral neuropathy (4%).

  Dose reductions of ELAHERE due to an adverse reaction occurred in 34% of patients. Adverse reactions which required dose reductions in ≥3% of patients included blurred vision (14%), keratopathy (10%), peripheral neuropathy (6%), and dry eye (5%).

  Tables 4 and 5 summarize adverse reactions and laboratory abnormalities, respectively, occurring in ≥10% of patients who received ELAHERE in Study 0416.

  Table 4: Adverse Reactions Occurring in ≥10% of Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Received ELAHERE in Study 0416

  Adverse Reaction	ELAHERE (n=218)		Chemotherapy ¥ (n=207)
  	All Grades (%)	Grades 3-4 (%)	All Grades (%)	Grades 3-4 (%)
  Gastrointestinal disorders
  Abdominal pain*	34	3	23	2
  Diarrhea	29	1	17	0.5
  Constipation	27	0	19	1
  Nausea	27	2	29	2
  Vomiting	18	3	18	1
  Eye disorders
  Blurred vision※	45	9	3	0
  Keratopathy†	37	11	0	0
  Dry eye‡	29	3	5	0
  Photophobia	18	0.5	0.5	0
  Cataract˄	16	3	0.5	0
  General disorders and administration site conditions
  Fatigue⸙	47	3	41	7
  Nervous system disorders
  Peripheral neuropathy¶	37	4	23	4
  Headache	14	0	10	0
  Musculoskel e tal and connective tissue disorders
  Musculoskeletal pain♦	31	1	21	2
  Metabolism and nutrition disorders
  Decreased appetite	18	1	14	1
  Respiratory, thoracic, and mediastinal disorders
  Pneumonitis±	10	0.5	0.5	0

  ^¥Chemotherapy: paclitaxel, pegylated liposomal doxorubicin (PLD), topotecan.

  ※ Blurred vision includes vision blurred, vitreous floaters, visual acuity reduced, diplopia, accommodation disorder, and visual impairment.

  † Keratopathy includes

  corneal disorder, corneal epithelial microcysts, keratitis, keratopathy, corneal deposits, punctate keratitis, and corneal opacity.

  ‡ Dry eye includes dry eye and lacrimation increased.

  ^˄Cataract includes cataract and cataract nuclear.

  ^⸙Fatigue includes fatigue and asthenia.

  * Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort.

  ^¶Peripheral neuropathy includes neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, hypoesthesia, polyneuropathy, neurotoxicity, and peripheral sensorimotor neuropathy.

  ^♦Musculoskeletal pain includes back pain, myalgia, neck pain, arthralgia, musculoskeletal pain, non-cardiac chest pain, bone pain, pain in extremity, musculoskeletal stiffness, musculoskeletal chest pain, and musculoskeletal discomfort.

  ^±Pneumonitis includes pneumonitis, interstitial lung disease, respiratory failure, and organizing pneumonia.

  Clinically relevant adverse reactions occurring in <10% of patients who received ELAHERE in Study 0416 included infusion related reactions/hypersensitivity (8%).

  Table 5: Select Laboratory Abnormalities ≥10% for All Grades, in Patients Who Received ELAHERE in Study 0416

  Laboratory Abnormality	ELAHERE (n=218)		Chemotherapy (n=207)
  	All Grades %	Grades 3-4 %	All Grades %	Grades 3-4 %
  Liver Function Tests
  Increased aspartate aminotransferase	57	0	14	0
  Increased alanine aminotransferase	38	1	15	1
  Increased alkaline phosphatase	30	1	13	1
  Chemistry
  Decreased albumin	21	1	27	2
  Decreased magnesium	21	1	29	2
  Decreased sodium	16	0	18	0
  Decreased potassium	15	1	11	1
  Increased calcium	12	0	5	0
  Decreased bicarbonate	11	0	11	0
  Increased creatinine	10	0	11	0
  Hematology*
  Decreased lymphocytes	27	3	42	11
  Decreased leukocytes	23	1	53	10
  Decreased neutrophils	22	1	45	17
  Decreased hemoglobin	18	1	63	8
  Decreased platelets	17	1	20	5

  * The denominator used to calculate the rate varied from 63 to 214 (ELAHERE); 63 to 194 (IC Chemo) based on the number of patients with a baseline value and at least one post-treatment value.

  Study 0417

  The safety of ELAHERE was evaluated in Study 0417, a single-arm, open-label study in patients (n=106) with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer

  [see Clinical Studies (

  14

  )]

  . Patients received ELAHERE 6 mg/kg AIBW once every 3 weeks until disease progression or unacceptable toxicity. The median duration of treatment was 4.2 months (range: 0.7 to 13.3).

  Serious adverse reactions occurred in 31% of patients treated with ELAHERE. The most common (≥2%) serious adverse reactions were intestinal obstruction (8%), ascites (4%), infection (3%), and pleural effusion (3%). Fatal adverse reactions occurred in 2% of patients, including small intestinal obstruction (1%) and pneumonitis (1%).

  Permanent discontinuation of ELAHERE due to adverse reactions occurred in 11% of patients. The most common (≥2%) adverse reactions leading to permanent discontinuation were intestinal obstruction (2%) and thrombocytopenia (2%). One patient (0.9%) permanently discontinued ELAHERE due to visual impairment (unilateral decrease to BCVA ≤ 20/200 that resolved to baseline after discontinuation).

  Dosage delays of ELAHERE due to an adverse reaction occurred in 39% of patients treated with ELAHERE. Adverse reactions which required dosage delays in ≥3% of patients included blurred vision (15%), keratopathy (11%), neutropenia (6%), dry eye (5%), cataracts (3%), and increased gamma-glutamyltransferase (3%).

  Dose reductions of ELAHERE due to an adverse reaction occurred in 20% of patients. Adverse reactions which required dose reductions in ≥3% of patients included blurred vision (9%) and keratopathy (7%).

  Table 6 summarizes the adverse reactions (≥10%) in patients treated with ELAHERE in Study 0417.

  Table 6: Adverse Reactions (≥10%) in Patients with Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Received ELAHERE in Study 0417

  Adverse Reaction	All Grades N=106 (%)	Grade 3-4 N=106 (%)
  Eye disorders
  Blurred Vision※	50	7
  Keratopathy†	37	9
  Dry eye‡	27	2
  Cataract	18	3
  Photophobia	17	0
  Eye pain§	10	0
  General disorders
  Fatigue	49	3
  Gastrointestinal disorders
  Nausea	40	0
  Abdominal pain*	36	7
  Diarrhea	31	3
  Constipation	30	1
  Vomiting	19	0
  Abdominal distension	11	0
  Nervous system disorders
  Peripheral neuropathy¶	33	2
  Metabolism and nutrition disorders
  Decreased appetite	18	1
  Musculoskeletal and connective tissue disorders
  Arthralgia	17	0
  Myalgia	10	0
  Respiratory, thoracic, and mediastinal disorders
  Dyspnea^	12	0

  ※ Blurred vision includes vision blurred, vitreous floaters, visual acuity reduced, diplopia, presbyopia, accommodation disorder, visual impairment, and refraction disorder.

  † Keratopathy includes corneal disorder, corneal epithelial microcysts, corneal epithelial defect, keratitis, keratopathy, corneal deposits, and punctate keratitis.

  ‡ Dry eye includes dry eye and lacrimation increased.

  § Eye pain includes eye pain and ocular discomfort.

  ^⸙Fatigue includes fatigue and asthenia.

  * Abdominal pain includes abdominal pain, abdominal pain upper, abdominal pain lower, and abdominal discomfort.

  ^¶Peripheral neuropathy includes neuropathy peripheral, peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, hypoesthesia, polyneuropathy, and neurotoxicity.

  ^ Dyspnea includes dyspnea and exertional dyspnea.

  Clinically relevant adverse reactions occurring in <10% of patients who received ELAHERE in Study 0417 included infusion related reactions/hypersensitivity (9%), pneumonitis (8%), and uveitis (1%).

  Table 7 summarizes the laboratory abnormalities in Study 0417.

  Table 7: Select Laboratory Abnormalities ≥10% for All Grades, or ≥2% for Grades 3-4 in Patients Who Received ELAHERE

  Laboratory Abnormality	ELAHERE*
  	All Grades (%)	Grade 3-4 (%)
  Liver Function Tests
  Increased aspartate aminotransferase	50	2
  Increased alanine aminotransferase	39	2
  Increased alkaline phosphatase	30	1
  Hematology*
  Decreased lymphocytes	35	7
  Decreased leukocytes	26	1
  Decreased neutrophils	26	3
  Decreased hemoglobin	25	3
  Decreased platelets	18	2
  Chemistry
  Decreased albumin	31	1
  Decreased magnesium	27	2
  Increased creatinine	16	0
  Decreased potassium	15	4

  * The denominator used to calculate the rate varied from 98 to 101 based on the number of patients with a baseline value and at least one post-treatment value.

  Immunogenicity: Anti-Drug Antibody-Associated Adverse Reactions

  In studies 0416, 0417, 0401, and 0403 in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer who received ELAHERE at 6 mg/kg AIBW administered intravenously once every 3 weeks, 9% (57/626) developed anti-drug antibodies. Infusion reactions (including bronchospasm, erythema, eyelid erythema, flushing, hypersensitivity, periorbital edema, rash, allergic rhinitis, face edema) occurred in 26% (15/57) of patients with anti-drug antibodies and in 7% (41/569) who did not develop anti-drug antibodies

  [see Clinical Pharmacology (

  12.6

  )]

  .
  )]
  .
  
  
  
• Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated
  [see Dosage and Administration (
  2.3 Premedication and Required Eye Care

  Premedica

  tion

  Administer the premedications in Table 1 prior to each infusion of ELAHERE to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting.

  Table 1: Premedication Prior to Each ELAHERE Infusion

  Premedication	Route of Administration	Examples (or equivalent)	Administration Time Prior to ELAHERE Infusion
  Corticosteroid	intravenous	dexamethasone 10 mg
  Antihistamine	oral or intravenous	diphenhydramine 25 mg to 50 mg	At least 30 minutes prior
  Antipyretic	oral or intravenous	acetaminophen 325 mg to 650 mg
  Antiemetic	oral or intravenous	5-HT3serotonin receptor antagonist or appropriate alternatives	Before each dose and thereafter as needed

  Consider additional premedications including corticosteroids the day prior to ELAHERE administration for patients who experienced IRRs.

  Ophthalmic Exams and Premedication

  Ophthalmic

  E

  xam

  : Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.

  Ophthalmic Topical Steroids:

  The use of ophthalmic topical steroids is recommended. The initial prescription and renewals of any corticosteroid medication should be made only after examination with a slit lamp. Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle of ELAHERE

  [see Warnings and Precautions (

  5.1

  )].

  Lubricating Eye Drops

  : The use of lubricating eye drops at least four times daily and as needed is recommended during treatment with ELAHERE. Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops

  [see Warnings and Precautions (

  5.1

  )]

  .
  )]
  .
  
  
  
• Administer prophylactic artificial tears and ophthalmic topical steroids
  [see Dosage and Administration (
  2.3 Premedication and Required Eye Care

  Premedica

  tion

  Administer the premedications in Table 1 prior to each infusion of ELAHERE to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting.

  Table 1: Premedication Prior to Each ELAHERE Infusion

  Premedication	Route of Administration	Examples (or equivalent)	Administration Time Prior to ELAHERE Infusion
  Corticosteroid	intravenous	dexamethasone 10 mg
  Antihistamine	oral or intravenous	diphenhydramine 25 mg to 50 mg	At least 30 minutes prior
  Antipyretic	oral or intravenous	acetaminophen 325 mg to 650 mg
  Antiemetic	oral or intravenous	5-HT3serotonin receptor antagonist or appropriate alternatives	Before each dose and thereafter as needed

  Consider additional premedications including corticosteroids the day prior to ELAHERE administration for patients who experienced IRRs.

  Ophthalmic Exams and Premedication

  Ophthalmic

  E

  xam

  : Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.

  Ophthalmic Topical Steroids:

  The use of ophthalmic topical steroids is recommended. The initial prescription and renewals of any corticosteroid medication should be made only after examination with a slit lamp. Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle of ELAHERE

  [see Warnings and Precautions (

  5.1

  )].

  Lubricating Eye Drops

  : The use of lubricating eye drops at least four times daily and as needed is recommended during treatment with ELAHERE. Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops

  [see Warnings and Precautions (

  5.1

  )]

  .
  ) and Warnings and Precautions (
  5.1 Ocular Disorders

  ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

  Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).

  [see Adverse Reactions (

  6.1

  )].

  The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients.

  Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended

  [see

  Dosage and Administration (

  2.3

  )].

  Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.

  Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

  Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

  [see Dosage and Administration (

  2.4

  )].
  )]
  .
  
  
  
• Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose
  [see Dosage and Administration (
  2.4 Dosage Modifications

  Table 2 provides dose reduction levels and Table 3 provides dosage modifications for ELAHERE due to adverse reactions.

  Table 2: Dosage Reduction Schedule

  	ELAHERE Dose Levels
  First Dose Reduction	5 mg/kg AIBW once every 3 weeks (21-day cycle)
  Second Dose Reduction	4 mg/kg AIBW once every 3 weeks (21-day cycle)*

  * Permanently discontinue in patients who cannot tolerate 4 mg/kg AIBW.

  Table 3: Dosage Modifications for Adverse Reactions

  Adverse Reaction	Severity of Adverse Reaction *	Dosage Modification
  	Nonconfluent superficial keratitis	Monitor.
  Keratitis/Keratopathy [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )]	Confluent superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity	Withhold until improved or resolved, then maintain at same dose level or consider dose reduction.
  	Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse	Withhold until improved or resolved, then reduce by one dose level.
  	Corneal perforation	Permanently discontinue.
  	Grade 1/ Rare cell in anterior chamber	Monitor.
  Uveitis [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )]	Grade 2/ 1-2+ Cell or Flare in anterior chamber	Withhold until Grade 1 or less, then maintain dose at same dose level.
  	Grade 3/ 3+ Cell or Flare in anterior chamber	Withhold until Grade 1 or less, then reduce dose by one dose level.
  	Grade 4/ Hypopyon	Permanently discontinue.
  	Grade 1	Monitor.
  Pneumonitis [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 )]	Grade 2	Withhold until Grade 1 or less, then maintain at same dose level or consider dose reduction.
  	Grade 3 or 4	Permanently discontinue.
  Peripheral Neuropathy [see Warnings and Precautions ( 5.3 ) and Adverse Reactions ( 6.1 )]	Grade 2	Withhold until Grade 1 or less, then reduce by one dose level.
  	Grade 3 or 4	Permanently discontinue.
  	Grade 1	Maintain infusion rate.
  Infusion-Related Reactions/Hypersensitivity [see Adverse Reactions ( 6.1 )]	Grade 2	Interrupt infusion and administer supportive treatment. After recovery from symptoms, resume the infusion at 50% of the previous rate, and if no further symptoms appear, increase rate as appropriate until infusion is completed [see Dosage and Administration ( 2.5 )]. Administer additional premedication for future cycles [see Dosage and Administration ( 2.3 )].
  	Grade 3 or 4	Immediately stop infusion and administer supportive treatment. Advise patient to seek emergency treatment and immediately notify their healthcare provider if the infusion-related symptoms recur. Permanently discontinue.
  Hematological [see Adverse Reactions ( 6.1 )]	Grade 3 or 4	Withhold until Grade 1 or less, then resume at one lower dose level.
  Other Adverse Reactions	Grade 3	Withhold until Grade 1 or less, then resume at one lower dose level.
  [see Adverse Reactions ( 6.1 )]	Grade 4	Permanently discontinue.

  ^*Unless otherwise specified, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
  ) and Warnings and Precautions (
  5.1 Ocular Disorders

  ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

  Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).

  [see Adverse Reactions (

  6.1

  )].

  The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients.

  Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended

  [see

  Dosage and Administration (

  2.3

  )].

  Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.

  Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

  Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

  [see Dosage and Administration (

  2.4

  )].
  )]
  .
  
  
  
• Discontinue ELAHERE for Grade 4 ocular toxicities
  [see Dosage and Administration (
  2.4 Dosage Modifications

  Table 2 provides dose reduction levels and Table 3 provides dosage modifications for ELAHERE due to adverse reactions.

  Table 2: Dosage Reduction Schedule

  	ELAHERE Dose Levels
  First Dose Reduction	5 mg/kg AIBW once every 3 weeks (21-day cycle)
  Second Dose Reduction	4 mg/kg AIBW once every 3 weeks (21-day cycle)*

  * Permanently discontinue in patients who cannot tolerate 4 mg/kg AIBW.

  Table 3: Dosage Modifications for Adverse Reactions

  Adverse Reaction	Severity of Adverse Reaction *	Dosage Modification
  	Nonconfluent superficial keratitis	Monitor.
  Keratitis/Keratopathy [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )]	Confluent superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity	Withhold until improved or resolved, then maintain at same dose level or consider dose reduction.
  	Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse	Withhold until improved or resolved, then reduce by one dose level.
  	Corneal perforation	Permanently discontinue.
  	Grade 1/ Rare cell in anterior chamber	Monitor.
  Uveitis [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )]	Grade 2/ 1-2+ Cell or Flare in anterior chamber	Withhold until Grade 1 or less, then maintain dose at same dose level.
  	Grade 3/ 3+ Cell or Flare in anterior chamber	Withhold until Grade 1 or less, then reduce dose by one dose level.
  	Grade 4/ Hypopyon	Permanently discontinue.
  	Grade 1	Monitor.
  Pneumonitis [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 )]	Grade 2	Withhold until Grade 1 or less, then maintain at same dose level or consider dose reduction.
  	Grade 3 or 4	Permanently discontinue.
  Peripheral Neuropathy [see Warnings and Precautions ( 5.3 ) and Adverse Reactions ( 6.1 )]	Grade 2	Withhold until Grade 1 or less, then reduce by one dose level.
  	Grade 3 or 4	Permanently discontinue.
  	Grade 1	Maintain infusion rate.
  Infusion-Related Reactions/Hypersensitivity [see Adverse Reactions ( 6.1 )]	Grade 2	Interrupt infusion and administer supportive treatment. After recovery from symptoms, resume the infusion at 50% of the previous rate, and if no further symptoms appear, increase rate as appropriate until infusion is completed [see Dosage and Administration ( 2.5 )]. Administer additional premedication for future cycles [see Dosage and Administration ( 2.3 )].
  	Grade 3 or 4	Immediately stop infusion and administer supportive treatment. Advise patient to seek emergency treatment and immediately notify their healthcare provider if the infusion-related symptoms recur. Permanently discontinue.
  Hematological [see Adverse Reactions ( 6.1 )]	Grade 3 or 4	Withhold until Grade 1 or less, then resume at one lower dose level.
  Other Adverse Reactions	Grade 3	Withhold until Grade 1 or less, then resume at one lower dose level.
  [see Adverse Reactions ( 6.1 )]	Grade 4	Permanently discontinue.

  ^*Unless otherwise specified, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
  ) and Warnings and Precautions (
  5.1 Ocular Disorders

  ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

  Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).

  [see Adverse Reactions (

  6.1

  )].

  The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients.

  Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended

  [see

  Dosage and Administration (

  2.3

  )].

  Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.

  Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

  Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

  [see Dosage and Administration (

  2.4

  )].
  )]
  .

ELAHERE^® is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test

• Administer ELAHERE as an intravenous infusion only after dilution in 5% Dextrose Injection, USP. ELAHERE is incompatible with normal saline. (
  2.5 Instructions for Preparation and Administration

  Preparation

  • ELAHERE is a hazardous drug. Follow applicable special handling and disposal procedures¹.
    
    
  • Calculate the dose (mg) (based on the patient’s AIBW), total volume (mL) of solution required, and the number of vials of ELAHERE needed
    [see Recommended Dosage (
    2.2
    ) and Dose Modifications (
    2.4
    )]
    . More than one vial will be needed for a full dose.
    
    
  • Remove the vials of ELAHERE from the refrigerator and allow to warm to room temperature.
    
    
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. ELAHERE is a clear to slightly opalescent, colorless solution.
    
    
  • Gently swirl and inspect each vial prior to withdrawing the calculated dose volume of ELAHERE.
    Do not shake
    the vial.
    
    
  • Using aseptic technique, withdraw the calculated dose volume of ELAHERE for subsequent dilution.
    
    
  • ELAHERE contains no preservatives and is intended for single-dose only. Discard any unused drug remaining in the vial.

  Dilution

  • ELAHERE must be diluted prior to administration with 5% Dextrose Injection, USP to a final concentration of 1 mg/mL to 2 mg/mL.
    
    
  • ELAHERE is incompatible with 0.9% Sodium Chloride Injection. ELAHERE must not be mixed with any other drugs or intravenous fluids.
    
    
  • Determine the volume of 5% Dextrose Injection, USP required to achieve the final diluted drug concentration. Either remove excess 5% Dextrose Injection, USP from a prefilled intravenous bag or add the calculated volume of 5% Dextrose Injection, USP to a sterile empty intravenous bag. Then add the calculated dose volume of ELAHERE to the intravenous bag.
    
    
  • Gently mix the diluted drug solution by slowly inverting the bag several times to assure uniform mixing.
    Do not shake or agitate.

  • If the diluted infusion solution is not used immediately, store solution either at ambient temperature [(18°C to 25°C (64.4°F to 77°F)] for no more than 8 hours (including infusion time), or under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours. If refrigerated, allow the infusion bag to reach room temperature prior to administration. After refrigeration, administer diluted infusion solutions within 8 hours (including infusion time).

  • Do not freeze
    prepared infusion solution.

  Administration

  • Inspect the ELAHERE intravenous infusion bag visually for particulate matter and discoloration prior to administration.
    
    
  • Administer pre-medications prior to ELAHERE administration
    [see Premedication and Prophylactic Regimen (
    2.3
    )]
    .
    
    
  • Administer ELAHERE as an intravenous infusion only, using a 0.2 or 0.22 µm polyethersulfone (PES) in-line filter. Do not substitute other membrane materials.
    
    
  • Administer the initial dose as an intravenous infusion at the rate of 1 mg/min. If well tolerated after 30 minutes at 1 mg/min, the infusion rate can be increased to 3 mg/min. If well tolerated after 30 minutes at 3 mg/min, the infusion rate can be increased to 5 mg/min.
    
    
  • If no infusion-related reactions occur with the previous dose, subsequent infusions should be started at the maximally tolerated rate and may be increased up to a maximum infusion rate of 5 mg/min, as tolerated.
    
    
  • Following the infusion, flush the intravenous line with 5% Dextrose Injection, USP to ensure delivery of the full dose. Do not use any other intravenous fluids for flushing.
  )
  
  
• The recommended dose of ELAHERE is 6 mg/kg adjusted ideal body weight administered as an intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. (
  2.2 Recommended Dosage

  The recommended dosage of ELAHERE is 6 mg/kg adjusted ideal body weight (AIBW) administered once every 3 weeks (21-day cycle) as an intravenous infusion until disease progression or unacceptable toxicity

  [see Dosage and Administration (

  2.5

  )].

  Dosing based on AIBW reduces exposure variability for patients who are either under or overweight.

  The total dose of ELAHERE is calculated based on each patient’s AIBW using the following formula:

  AIBW = Ideal Body Weight (IBW [kg]) + 0.4*(Actual weight [kg] – IBW)

  Female IBW [kg] = 0.9*height[cm] – 92
  )
  
  
• Premedicate with a corticosteroid, antihistamine, and antipyretic. (
  2.3 Premedication and Required Eye Care

  Premedica

  tion

  Administer the premedications in Table 1 prior to each infusion of ELAHERE to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting.

  Table 1: Premedication Prior to Each ELAHERE Infusion

  Premedication	Route of Administration	Examples (or equivalent)	Administration Time Prior to ELAHERE Infusion
  Corticosteroid	intravenous	dexamethasone 10 mg
  Antihistamine	oral or intravenous	diphenhydramine 25 mg to 50 mg	At least 30 minutes prior
  Antipyretic	oral or intravenous	acetaminophen 325 mg to 650 mg
  Antiemetic	oral or intravenous	5-HT3serotonin receptor antagonist or appropriate alternatives	Before each dose and thereafter as needed

  Consider additional premedications including corticosteroids the day prior to ELAHERE administration for patients who experienced IRRs.

  Ophthalmic Exams and Premedication

  Ophthalmic

  E

  xam

  : Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.

  Ophthalmic Topical Steroids:

  The use of ophthalmic topical steroids is recommended. The initial prescription and renewals of any corticosteroid medication should be made only after examination with a slit lamp. Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle of ELAHERE

  [see Warnings and Precautions (

  5.1

  )].

  Lubricating Eye Drops

  : The use of lubricating eye drops at least four times daily and as needed is recommended during treatment with ELAHERE. Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops

  [see Warnings and Precautions (

  5.1

  )]

  .
  )
  
  
• Premedicate with an antiemetic, ophthalmic topical steroids, and lubricating eye drops. (
  2.3 Premedication and Required Eye Care

  Premedica

  tion

  Administer the premedications in Table 1 prior to each infusion of ELAHERE to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting.

  Table 1: Premedication Prior to Each ELAHERE Infusion

  Premedication	Route of Administration	Examples (or equivalent)	Administration Time Prior to ELAHERE Infusion
  Corticosteroid	intravenous	dexamethasone 10 mg
  Antihistamine	oral or intravenous	diphenhydramine 25 mg to 50 mg	At least 30 minutes prior
  Antipyretic	oral or intravenous	acetaminophen 325 mg to 650 mg
  Antiemetic	oral or intravenous	5-HT3serotonin receptor antagonist or appropriate alternatives	Before each dose and thereafter as needed

  Consider additional premedications including corticosteroids the day prior to ELAHERE administration for patients who experienced IRRs.

  Ophthalmic Exams and Premedication

  Ophthalmic

  E

  xam

  : Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.

  Ophthalmic Topical Steroids:

  The use of ophthalmic topical steroids is recommended. The initial prescription and renewals of any corticosteroid medication should be made only after examination with a slit lamp. Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle of ELAHERE

  [see Warnings and Precautions (

  5.1

  )].

  Lubricating Eye Drops

  : The use of lubricating eye drops at least four times daily and as needed is recommended during treatment with ELAHERE. Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops

  [see Warnings and Precautions (

  5.1

  )]

  .
  ,
  5.1 Ocular Disorders

  ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

  Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).

  [see Adverse Reactions (

  6.1

  )].

  The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up. Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients.

  Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended

  [see

  Dosage and Administration (

  2.3

  )].

  Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider.

  Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

  Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

  [see Dosage and Administration (

  2.4

  )].
  )
  
  
• See full Prescribing Information for preparation and administration instructions and dose modifications for adverse reactions. (
  2 DOSAGE AND ADMINISTRATION

  • Administer ELAHERE as an intravenous infusion only after dilution in 5% Dextrose Injection, USP. ELAHERE is incompatible with normal saline.
    
    
  • The recommended dose of ELAHERE is 6 mg/kg adjusted ideal body weight administered as an intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.
    
    
  • Premedicate with a corticosteroid, antihistamine, and antipyretic.
    
    
  • Premedicate with an antiemetic, ophthalmic topical steroids, and lubricating eye drops.
    
    
  • See full Prescribing Information for preparation and administration instructions and dose modifications for adverse reactions.

  2.1 Patient Selection

  Select patients for the treatment of platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer with ELAHERE based on the presence of FRα tumor expression

  [see Indications & Usage (

  1

  ) and Clinical Studies (

  14

  )]

  using an FDA-approved test.

  Information on FDA-approved tests for the measurement of FRα tumor expression is available at http://www.fda.gov/CompanionDiagnostics.

  2.2 Recommended Dosage

  The recommended dosage of ELAHERE is 6 mg/kg adjusted ideal body weight (AIBW) administered once every 3 weeks (21-day cycle) as an intravenous infusion until disease progression or unacceptable toxicity

  [see Dosage and Administration (

  2.5

  )].

  Dosing based on AIBW reduces exposure variability for patients who are either under or overweight.

  The total dose of ELAHERE is calculated based on each patient’s AIBW using the following formula:

  AIBW = Ideal Body Weight (IBW [kg]) + 0.4*(Actual weight [kg] – IBW)

  Female IBW [kg] = 0.9*height[cm] – 92

  2.3 Premedication and Required Eye Care

  Premedica

  tion

  Administer the premedications in Table 1 prior to each infusion of ELAHERE to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting.

  Table 1: Premedication Prior to Each ELAHERE Infusion

  Premedication	Route of Administration	Examples (or equivalent)	Administration Time Prior to ELAHERE Infusion
  Corticosteroid	intravenous	dexamethasone 10 mg
  Antihistamine	oral or intravenous	diphenhydramine 25 mg to 50 mg	At least 30 minutes prior
  Antipyretic	oral or intravenous	acetaminophen 325 mg to 650 mg
  Antiemetic	oral or intravenous	5-HT3serotonin receptor antagonist or appropriate alternatives	Before each dose and thereafter as needed

  Consider additional premedications including corticosteroids the day prior to ELAHERE administration for patients who experienced IRRs.

  Ophthalmic Exams and Premedication

  Ophthalmic

  E

  xam

  : Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.

  Ophthalmic Topical Steroids:

  The use of ophthalmic topical steroids is recommended. The initial prescription and renewals of any corticosteroid medication should be made only after examination with a slit lamp. Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle of ELAHERE

  [see Warnings and Precautions (

  5.1

  )].

  Lubricating Eye Drops

  : The use of lubricating eye drops at least four times daily and as needed is recommended during treatment with ELAHERE. Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops

  [see Warnings and Precautions (

  5.1

  )]

  .

  2.4 Dosage Modifications

  Table 2 provides dose reduction levels and Table 3 provides dosage modifications for ELAHERE due to adverse reactions.

  Table 2: Dosage Reduction Schedule

  	ELAHERE Dose Levels
  First Dose Reduction	5 mg/kg AIBW once every 3 weeks (21-day cycle)
  Second Dose Reduction	4 mg/kg AIBW once every 3 weeks (21-day cycle)*

  * Permanently discontinue in patients who cannot tolerate 4 mg/kg AIBW.

  Table 3: Dosage Modifications for Adverse Reactions

  Adverse Reaction	Severity of Adverse Reaction *	Dosage Modification
  	Nonconfluent superficial keratitis	Monitor.
  Keratitis/Keratopathy [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )]	Confluent superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity	Withhold until improved or resolved, then maintain at same dose level or consider dose reduction.
  	Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse	Withhold until improved or resolved, then reduce by one dose level.
  	Corneal perforation	Permanently discontinue.
  	Grade 1/ Rare cell in anterior chamber	Monitor.
  Uveitis [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )]	Grade 2/ 1-2+ Cell or Flare in anterior chamber	Withhold until Grade 1 or less, then maintain dose at same dose level.
  	Grade 3/ 3+ Cell or Flare in anterior chamber	Withhold until Grade 1 or less, then reduce dose by one dose level.
  	Grade 4/ Hypopyon	Permanently discontinue.
  	Grade 1	Monitor.
  Pneumonitis [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.1 )]	Grade 2	Withhold until Grade 1 or less, then maintain at same dose level or consider dose reduction.
  	Grade 3 or 4	Permanently discontinue.
  Peripheral Neuropathy [see Warnings and Precautions ( 5.3 ) and Adverse Reactions ( 6.1 )]	Grade 2	Withhold until Grade 1 or less, then reduce by one dose level.
  	Grade 3 or 4	Permanently discontinue.
  	Grade 1	Maintain infusion rate.
  Infusion-Related Reactions/Hypersensitivity [see Adverse Reactions ( 6.1 )]	Grade 2	Interrupt infusion and administer supportive treatment. After recovery from symptoms, resume the infusion at 50% of the previous rate, and if no further symptoms appear, increase rate as appropriate until infusion is completed [see Dosage and Administration ( 2.5 )]. Administer additional premedication for future cycles [see Dosage and Administration ( 2.3 )].
  	Grade 3 or 4	Immediately stop infusion and administer supportive treatment. Advise patient to seek emergency treatment and immediately notify their healthcare provider if the infusion-related symptoms recur. Permanently discontinue.
  Hematological [see Adverse Reactions ( 6.1 )]	Grade 3 or 4	Withhold until Grade 1 or less, then resume at one lower dose level.
  Other Adverse Reactions	Grade 3	Withhold until Grade 1 or less, then resume at one lower dose level.
  [see Adverse Reactions ( 6.1 )]	Grade 4	Permanently discontinue.

  ^*Unless otherwise specified, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

  2.5 Instructions for Preparation and Administration

  Preparation

  • ELAHERE is a hazardous drug. Follow applicable special handling and disposal procedures¹.
    
    
  • Calculate the dose (mg) (based on the patient’s AIBW), total volume (mL) of solution required, and the number of vials of ELAHERE needed
    [see Recommended Dosage (
    2.2
    ) and Dose Modifications (
    2.4
    )]
    . More than one vial will be needed for a full dose.
    
    
  • Remove the vials of ELAHERE from the refrigerator and allow to warm to room temperature.
    
    
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. ELAHERE is a clear to slightly opalescent, colorless solution.
    
    
  • Gently swirl and inspect each vial prior to withdrawing the calculated dose volume of ELAHERE.
    Do not shake
    the vial.
    
    
  • Using aseptic technique, withdraw the calculated dose volume of ELAHERE for subsequent dilution.
    
    
  • ELAHERE contains no preservatives and is intended for single-dose only. Discard any unused drug remaining in the vial.

  Dilution

  • ELAHERE must be diluted prior to administration with 5% Dextrose Injection, USP to a final concentration of 1 mg/mL to 2 mg/mL.
    
    
  • ELAHERE is incompatible with 0.9% Sodium Chloride Injection. ELAHERE must not be mixed with any other drugs or intravenous fluids.
    
    
  • Determine the volume of 5% Dextrose Injection, USP required to achieve the final diluted drug concentration. Either remove excess 5% Dextrose Injection, USP from a prefilled intravenous bag or add the calculated volume of 5% Dextrose Injection, USP to a sterile empty intravenous bag. Then add the calculated dose volume of ELAHERE to the intravenous bag.
    
    
  • Gently mix the diluted drug solution by slowly inverting the bag several times to assure uniform mixing.
    Do not shake or agitate.

  • If the diluted infusion solution is not used immediately, store solution either at ambient temperature [(18°C to 25°C (64.4°F to 77°F)] for no more than 8 hours (including infusion time), or under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours. If refrigerated, allow the infusion bag to reach room temperature prior to administration. After refrigeration, administer diluted infusion solutions within 8 hours (including infusion time).

  • Do not freeze
    prepared infusion solution.

  Administration

  • Inspect the ELAHERE intravenous infusion bag visually for particulate matter and discoloration prior to administration.
    
    
  • Administer pre-medications prior to ELAHERE administration
    [see Premedication and Prophylactic Regimen (
    2.3
    )]
    .
    
    
  • Administer ELAHERE as an intravenous infusion only, using a 0.2 or 0.22 µm polyethersulfone (PES) in-line filter. Do not substitute other membrane materials.
    
    
  • Administer the initial dose as an intravenous infusion at the rate of 1 mg/min. If well tolerated after 30 minutes at 1 mg/min, the infusion rate can be increased to 3 mg/min. If well tolerated after 30 minutes at 3 mg/min, the infusion rate can be increased to 5 mg/min.
    
    
  • If no infusion-related reactions occur with the previous dose, subsequent infusions should be started at the maximally tolerated rate and may be increased up to a maximum infusion rate of 5 mg/min, as tolerated.
    
    
  • Following the infusion, flush the intravenous line with 5% Dextrose Injection, USP to ensure delivery of the full dose. Do not use any other intravenous fluids for flushing.
  )

Injection: 100 mg/20 mL (5 mg/mL) clear to slightly opalescent, colorless solution in a single-dose vial.

• Lactation: Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  There are no data on the presence of mirvetuximab soravtansine-gynx in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ELAHERE and for 1 month after the last dose.
  )
  
  
• Moderate or severe hepatic impairment: Avoid use. (
  8.7 Hepatic Impairment

  Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).

  No dosage adjustment of ELAHERE is recommended for patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST)

  [see Clinical Pharmacology (

  12.3

  )]

  .
  )