SUSTOL
Generic: GRANISETRON
Basic Information
Manufacturer
Heron Therapeutics, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
SUBCUTANEOUS
FDA Set ID
f7c7ffdd-8270-4030-bc1e-a1cb28a6de56
Indications & Usage
1 INDICATIONS AND USAGE SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.
SUSTOL is a serotonin-3 (5-HT 3 ) receptor antagonist indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.
( 1 )
SUSTOL is a serotonin-3 (5-HT 3 ) receptor antagonist indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Injection Site Reactions [see Warnings and Precautions ( 5.1 )] Gastrointestinal Disorders [see Warnings and Precautions ( 5.2 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] Serotonin Syndrome [see Warnings and Precautions ( 5.4 )] Most common adverse reactions (≥ 3%) are injection site reactions, constipation, fatigue, headache, diarrhea, abdominal pain, insomnia, dyspepsia, dizziness, asthenia, and gastroesophageal reflux.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Heron Therapeutics, Inc.
at 844-HERON11 (1-844-437-6611) and www.SUSTOL.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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.
Studies 1 and 2 The safety of a 10 mg subcutaneous dose of SUSTOL was evaluated in two double-blind, randomized, active-controlled studies, in which 210 patients (23%) received MEC and 467 patients (51%) received AC combination chemotherapy (Studies 1 and 2) [see Clinical Studies ( 14 )] .
The data described below reflect exposure to a single 10 mg dose of SUSTOL in 924 patients whose mean age was 56 years (range 19 to 91 years); 76% of patients were female; 70% of patients were Caucasian, 16% Asian, 10% Black, and 4% other races.
Dexamethasone was co-administered with SUSTOL in Study 1 and Study 2 and an NK 1 receptor antagonist was co-administered with SUSTOL in Study 2.
Table 1 lists the most common adverse reactions reported in at least 3% of patients following a single dose of SUSTOL 10 mg in Study 1 and/or Study 2.
Overall, injection site reactions (ISRs) were the most common group of adverse reactions in SUSTOL-treated patients.
Specific types of ISRs reported by SUSTOL-treated patients are shown in Table 2 .
Table 1.
Adverse Reactions Occurring in at Least 3% of Patients Treated with SUSTOL 10 mg in Study 1 and/or Study 2 Study 1 Study 2 Adverse Reaction SUSTOL 10 mg subcutaneous (N=468) % Palonosetron hydrochloride 0.25 mg intravenous (N=463) % SUSTOL 10 mg subcutaneous (N=456) % Ondansetron 0.15 mg/kg intravenous (N=459) % Injection Site Reactions, any Rates of individual injection site reactions (ISRs) are shown in Table 2 37 15 The placebo subcutaneous injection for Study 1 was normal saline and for Study 2 was a SUSTOL-matched control consisting of the SUSTOL polymer vehicle without active drug.
62 See footnote Constipation 14 11 22 15 Fatigue 11 10 21 24 Headache 9 9 13 19 Diarrhea 8 7 9 8 Abdominal Pain 7 7 7 4 Insomnia 4 2 5 6 Dyspepsia 3 3 6 7 Dizziness 3 2 5 5 Asthenia 4 6 2 2 Gastroesophageal Reflux 1 1 5 4 Injection Site Reactions (ISRs) in Studies 1 and 2 Injection site reactions occurred in 37% (175/468) in Study 1, Cycle 1 only, and 62% (281/456) in Study 2 of SUSTOL-treated patients.
The ISR manifestations included pain, erythema, mass/nodule, swelling/induration, and bleeding.
The incidence of individual ISRs is shown in Table 2 .
Patients may have experienced one or more types of injection site reactions; a total of 213 of 924 patients had three or more.
ISR reporting procedures included both investigator- and patient-reported outcomes in Study 2, while Study 1 used only investigator reporting.
Table 2.
Injection Site Adverse Reactions Following a Single 10 mg SUSTOL Dose Injection Site Reaction Study 1 Treatment Arm (Subcutaneous Injection) Study 2 Patient diary was used in Study 2 to collect ISR information daily.
, The placebo subcutaneous injection for Study 2 was a SUSTOL-matched control consisting of the SUSTOL polymer vehicle without active drug.
ISR data for this group are not shown.
SUSTOL (N=456) % SUSTOL (N=468) % Saline Control (N=463) % Total Subjects with at least 1 ISR 37 15 62 Pain 3 1 20 Tenderness 4 1 27 Bruising/Hematoma 22 10 45 Bleeding 2 1 4 Erythema/Redness 11 3 17 Swelling/Induration 1 0 10 Mass/Nodule 11 1 18 Infection at injection site <1 0 1 Other Other includes injection site discoloration, vesicles, irritation, lipoma, paresthesia, pruritus, rash, reaction, scab, scar, and warmth.
2 1 1 Less common adverse reactions reported in less than 3% of SUSTOL-treated patients in clinical trials are syncope, elevation of serum transaminase levels, pancreatitis, atrial fibrillation, somnolence, flushing, and hypersensitivity reactions (e.g., anaphylaxis, urticaria).
Injection Site Reactions in the Safety Database Reactions at the injection site were assessed in 1814 patients with cancer treated with SUSTOL for one or multiple cycles across four studies (dosing-ranging, open-label, and/or active-controlled), including Study 1 and Study 2.
Of the 1814 patients with cancer, 1131 patients were treated with the SUSTOL 10 mg dose.
Additionally, infections at the injection site were assessed in 412 healthy subjects treated with any dose of SUSTOL across single- or multiple-dose studies.
Infections : occurred in 7 of 1814 (0.4%) patients with cancer and 1 of 412 (0.2%) healthy subjects in clinical trials.
Injection site infections had a median onset of 9 days (range 7 to 16 days) following SUSTOL administration.
One patient who was neutropenic at the time of the infection was hospitalized.
All patients with infection were treated with antibiotics and had complete resolution.
Bruising and/or hematomas : occurred in 426 of 1131 (38%) patients treated with SUSTOL 10 mg with a median time to onset of 2 days.
Injection site bruising and/or hematomas with a delayed onset (onset 5 or more days following SUSTOL administration) were reported in 175 (15%) patients.
Severe bruising or hematoma (e.g., greater than 4 cm bruise or hematoma) occurred in 3% of patients.
Patients receiving concomitant anticoagulant and antiplatelet medications were at greater risk for severe injection site bruising and hematomas.
Bleeding : occurred in 70 of 1814 (4%) patients treated with SUSTOL.
One patient required emergency management.
Injection site bleeding for longer than 5 days was reported in 23 (1%) patients.
Pain and tenderness : In a clinical trial that collected information about injection site pain and tenderness from patient diaries, pain with or without tenderness at the injection site was reported by 91 of 456 (20%) patients treated with SUSTOL 10 mg, and an additional 50 of 456 (11%) patients reported tenderness without pain.
Pain and/or tenderness severe enough to require taking pain medication, interfere with patient activity level, or cause significant discomfort at rest was reported in 2% of patients.
Among all patients who reported pain and/or tenderness with SUSTOL 10 mg, the median duration was 5 days, and pain lasting longer than 7 days occurred in 6% of patients.
Nodules : occurred in 203 of 1131 (18%) patients treated with SUSTOL 10 mg and persisted for a median of 15 days; 73 patients (6%) had nodules with durations longer than 21 days.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of other formulations of granisetron.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
System Organ Class Adverse Reactions Cardiovascular bradycardia, chest pain, palpitations, sick sinus syndrome
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Heron Therapeutics, Inc.
at 844-HERON11 (1-844-437-6611) and www.SUSTOL.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 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.
Studies 1 and 2 The safety of a 10 mg subcutaneous dose of SUSTOL was evaluated in two double-blind, randomized, active-controlled studies, in which 210 patients (23%) received MEC and 467 patients (51%) received AC combination chemotherapy (Studies 1 and 2) [see Clinical Studies ( 14 )] .
The data described below reflect exposure to a single 10 mg dose of SUSTOL in 924 patients whose mean age was 56 years (range 19 to 91 years); 76% of patients were female; 70% of patients were Caucasian, 16% Asian, 10% Black, and 4% other races.
Dexamethasone was co-administered with SUSTOL in Study 1 and Study 2 and an NK 1 receptor antagonist was co-administered with SUSTOL in Study 2.
Table 1 lists the most common adverse reactions reported in at least 3% of patients following a single dose of SUSTOL 10 mg in Study 1 and/or Study 2.
Overall, injection site reactions (ISRs) were the most common group of adverse reactions in SUSTOL-treated patients.
Specific types of ISRs reported by SUSTOL-treated patients are shown in Table 2 .
Table 1.
Adverse Reactions Occurring in at Least 3% of Patients Treated with SUSTOL 10 mg in Study 1 and/or Study 2 Study 1 Study 2 Adverse Reaction SUSTOL 10 mg subcutaneous (N=468) % Palonosetron hydrochloride 0.25 mg intravenous (N=463) % SUSTOL 10 mg subcutaneous (N=456) % Ondansetron 0.15 mg/kg intravenous (N=459) % Injection Site Reactions, any Rates of individual injection site reactions (ISRs) are shown in Table 2 37 15 The placebo subcutaneous injection for Study 1 was normal saline and for Study 2 was a SUSTOL-matched control consisting of the SUSTOL polymer vehicle without active drug.
62 See footnote Constipation 14 11 22 15 Fatigue 11 10 21 24 Headache 9 9 13 19 Diarrhea 8 7 9 8 Abdominal Pain 7 7 7 4 Insomnia 4 2 5 6 Dyspepsia 3 3 6 7 Dizziness 3 2 5 5 Asthenia 4 6 2 2 Gastroesophageal Reflux 1 1 5 4 Injection Site Reactions (ISRs) in Studies 1 and 2 Injection site reactions occurred in 37% (175/468) in Study 1, Cycle 1 only, and 62% (281/456) in Study 2 of SUSTOL-treated patients.
The ISR manifestations included pain, erythema, mass/nodule, swelling/induration, and bleeding.
The incidence of individual ISRs is shown in Table 2 .
Patients may have experienced one or more types of injection site reactions; a total of 213 of 924 patients had three or more.
ISR reporting procedures included both investigator- and patient-reported outcomes in Study 2, while Study 1 used only investigator reporting.
Table 2.
Injection Site Adverse Reactions Following a Single 10 mg SUSTOL Dose Injection Site Reaction Study 1 Treatment Arm (Subcutaneous Injection) Study 2 Patient diary was used in Study 2 to collect ISR information daily.
, The placebo subcutaneous injection for Study 2 was a SUSTOL-matched control consisting of the SUSTOL polymer vehicle without active drug.
ISR data for this group are not shown.
SUSTOL (N=456) % SUSTOL (N=468) % Saline Control (N=463) % Total Subjects with at least 1 ISR 37 15 62 Pain 3 1 20 Tenderness 4 1 27 Bruising/Hematoma 22 10 45 Bleeding 2 1 4 Erythema/Redness 11 3 17 Swelling/Induration 1 0 10 Mass/Nodule 11 1 18 Infection at injection site <1 0 1 Other Other includes injection site discoloration, vesicles, irritation, lipoma, paresthesia, pruritus, rash, reaction, scab, scar, and warmth.
2 1 1 Less common adverse reactions reported in less than 3% of SUSTOL-treated patients in clinical trials are syncope, elevation of serum transaminase levels, pancreatitis, atrial fibrillation, somnolence, flushing, and hypersensitivity reactions (e.g., anaphylaxis, urticaria).
Injection Site Reactions in the Safety Database Reactions at the injection site were assessed in 1814 patients with cancer treated with SUSTOL for one or multiple cycles across four studies (dosing-ranging, open-label, and/or active-controlled), including Study 1 and Study 2.
Of the 1814 patients with cancer, 1131 patients were treated with the SUSTOL 10 mg dose.
Additionally, infections at the injection site were assessed in 412 healthy subjects treated with any dose of SUSTOL across single- or multiple-dose studies.
Infections : occurred in 7 of 1814 (0.4%) patients with cancer and 1 of 412 (0.2%) healthy subjects in clinical trials.
Injection site infections had a median onset of 9 days (range 7 to 16 days) following SUSTOL administration.
One patient who was neutropenic at the time of the infection was hospitalized.
All patients with infection were treated with antibiotics and had complete resolution.
Bruising and/or hematomas : occurred in 426 of 1131 (38%) patients treated with SUSTOL 10 mg with a median time to onset of 2 days.
Injection site bruising and/or hematomas with a delayed onset (onset 5 or more days following SUSTOL administration) were reported in 175 (15%) patients.
Severe bruising or hematoma (e.g., greater than 4 cm bruise or hematoma) occurred in 3% of patients.
Patients receiving concomitant anticoagulant and antiplatelet medications were at greater risk for severe injection site bruising and hematomas.
Bleeding : occurred in 70 of 1814 (4%) patients treated with SUSTOL.
One patient required emergency management.
Injection site bleeding for longer than 5 days was reported in 23 (1%) patients.
Pain and tenderness : In a clinical trial that collected information about injection site pain and tenderness from patient diaries, pain with or without tenderness at the injection site was reported by 91 of 456 (20%) patients treated with SUSTOL 10 mg, and an additional 50 of 456 (11%) patients reported tenderness without pain.
Pain and/or tenderness severe enough to require taking pain medication, interfere with patient activity level, or cause significant discomfort at rest was reported in 2% of patients.
Among all patients who reported pain and/or tenderness with SUSTOL 10 mg, the median duration was 5 days, and pain lasting longer than 7 days occurred in 6% of patients.
Nodules : occurred in 203 of 1131 (18%) patients treated with SUSTOL 10 mg and persisted for a median of 15 days; 73 patients (6%) had nodules with durations longer than 21 days.
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of other formulations of granisetron.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
System Organ Class Adverse Reactions Cardiovascular bradycardia, chest pain, palpitations, sick sinus syndrome