EMEND

EMEND capsules contain the active ingredient, aprepitant. Aprepitant is a substance P/neurokinin 1 (NK 1 ) receptor antagonist, an antiemetic agent, chemically described as 5-[[(2 R ,3 S )-2-[(1 R )-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3 H -1,2,4-triazol-3-one. Its empirical formula is C 23 H 21 F 7 N 4 O 3 , and its structural formula is: Aprepitant is a white to off-white crystalline solid, with a molecular weight of 534.43. It is practically insoluble in water. Aprepitant is sparingly soluble in ethanol and isopropyl acetate and slightly soluble in acetonitrile. Each capsule of EMEND for oral administration contains either 80 mg or 125 mg of aprepitant and the following inactive ingredients: sucrose, microcrystalline cellulose, hydroxypropyl cellulose and sodium lauryl sulfate. The capsule shell excipients are gelatin, titanium dioxide, and may contain sodium lauryl sulfate and silicon dioxide. The 125-mg capsule also contains red ferric oxide and yellow ferric oxide. Each pouch of EMEND for oral suspension 125 mg contains 125 mg of aprepitant and the following inactive ingredients: sucrose, lactose, hydroxypropyl cellulose, sodium lauryl sulfate, red iron oxide, and sodium stearyl fumarate. Chemical Structure

EMEND ® for oral suspension, in combination with other antiemetic agents, is indicated in patients 6 months of age and older for the prevention of: acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin. nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). EMEND ® capsules, in combination with other antiemetic agents, is indicated in patients 12 years of age and older for the prevention of: acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin. nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). EMEND ® is a substance P/neurokinin 1 (NK 1 ) receptor antagonist. EMEND for oral suspension is indicated in combination with other antiemetic agents, in patients 6 months of age and older for prevention of: acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin ( 1 ) nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) ( 1 ) EMEND capsules is indicated in combination with other antiemetic agents, in patients 12 years of age and older for prevention of: acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin ( 1 ) nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC) ( 1 ) Limitations of Use ( 1 ) EMEND has not been studied for treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended. Limitations of Use EMEND has not been studied for the treatment of established nausea and vomiting. Chronic continuous administration of EMEND is not recommended because it has not been studied, and because the drug interaction profile may change during chronic continuous use.

Recommended Dosage ( 2.1 ) EMEND capsules in adults and pediatric patients 12 years of age and older: is 125 mg on Day 1 and 80 mg on Days 2 and 3. EMEND for oral suspension in pediatric patients 6 months to less than 12 years of age or pediatric and adult patients unable to swallow capsules: see dosing recommendations in Table 3 in the Full Prescribing Information. Administer EMEND 1 hour prior to chemotherapy on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND in morning. See Full Prescribing Information for recommended dosages of concomitant dexamethasone and 5-HT 3 antagonist for HEC and MEC. Preparation and Administration ( 2.2 , 2.3 ) EMEND capsules and EMEND for oral suspension can be administered with or without food. Swallow EMEND capsules whole. EMEND for oral suspension should be prepared by healthcare provider. Once prepared, it may be administered either by a healthcare provider, patient, or caregiver. For details on preparation see Full Prescribing Information. 2.1 Recommended Dosage Adults and Pediatric Patients 12 Years of Age and Older The recommended oral dosage of EMEND capsules, dexamethasone, and a 5-HT 3 antagonist in adults and pediatric patients 12 years of age and older who can swallow oral capsules, for the prevention of nausea and vomiting associated with administration of HEC or MEC is shown in Table 1 or Table 2, respectively. For patients who cannot swallow oral capsules, EMEND for oral suspension can be used instead of EMEND capsules as shown in Table 3. Table 1: Recommended Dosing for the Prevention of Nausea and Vomiting Associated with HEC Population Day 1 Day 2 Day 3 Day 4 EMEND capsules Administer EMEND capsules 1 hour prior to chemotherapy treatment on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND capsules in the morning. Adults and Pediatric Patients 12 Years and Older 125 mg orally 80 mg orally 80 mg orally none Dexamethasone Adults 12 mg orally 8 mg orally 8 mg orally 8 mg orally Pediatric Patients 12 Years and Older If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies (14.3) ] . Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 through 4. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with EMEND [see Clinical Pharmacology (12.3) ] . 5-HT 3 antagonist Adults and Pediatric Patients 12 Years and Older See selected 5-HT 3 antagonist prescribing information for the recommended dosage none none none Table 2: Recommended Dosing for the Prevention of Nausea and Vomiting Associated with MEC Population Day 1 Day 2 Day 3 EMEND capsules Administer EMEND capsules 1 hour prior to chemotherapy treatment on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND capsules in the morning. Adults and Pediatric Patients 12 Years and Older 125 mg orally 80 mg orally 80 mg orally Dexamethasone Adults 12 mg orally none none Pediatric Patients 12 Years and Older If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies (14.3) ] . Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with EMEND [see Clinical Pharmacology (12.3) ] . 5-HT 3 antagonist Adults and Pediatric Patients 12 Years and Older See the selected 5-HT 3 antagonist prescribing information for recommended dosage none none Pediatric Patients 6 Months to less than 12 Years of Age or Pediatric and Adult Patients Unable to Swallow Capsules The recommended dose of EMEND for oral suspension to be administered with a 5-HT 3 antagonist, with or without a corticosteroid, for the prevention of nausea and vomiting associated with administration of HEC or MEC is specified in Table 3. Dosing of EMEND for oral suspension is based on weight, to a maximum of 125 mg on Day 1 and 80 mg on Days 2 and 3. Dosing in pediatric patients less than 6 kg is not recommended. Table 3: Recommended Dosing in Pediatric Patients 6 Months to Less than 12 Years of Age or Pediatric and Adult Patients Unable to Swallow Capsules Population Day 1 Day 2 Day 3 Day 4 EMEND for oral suspension After preparation, the final concentration of EMEND for oral suspension is 25 mg/mL [see Dosage and Administration (2.3) ] . Administer EMEND for oral suspension 1 hour prior to chemotherapy treatment on Days 1, 2, and 3. If no chemotherapy is given on Days 2 and 3, administer EMEND for oral suspension in the morning. Pediatric Patients 6 Months to Less than12 Years or Pediatric and Adult Patients Unable to Swallow Capsules 3 mg/kg orally Maximum dose 125 mg 2 mg/kg orally Maximum dose 80 mg 2 mg/kg orally Maximum dose 80 mg none Dexamethasone Adults Unable to Swallow Capsules See Table 1 or 2 See Table 1 or 2 See Table 1 or 2 See Table 1 or 2 Pediatric Patients 6 Months to Less than12 Years or Pediatric Patients Unable to Swallow Capsules If a corticosteroid, such as dexamethasone, is co-administered, administer 50% of the recommended corticosteroid dose on Days 1 through 4 [see Clinical Studies (14.3) ] . Administer dexamethasone 30 minutes prior to chemotherapy treatment on Day 1. A 50% dosage reduction of dexamethasone is recommended to account for a drug interaction with EMEND [see Clinical Pharmacology (12.3) ] . 5-HT 3 antagonist Pediatric Patients 6 Months to Less than12 Years or Pediatric and Adult Patients Unable to Swallow Capsules See selected 5-HT 3 antagonist prescribing information for the recommended dosage none none none 2.2 Preparation Instructions for EMEND for Oral Suspension -- for Healthcare Providers EMEND for oral suspension should be prepared by a healthcare provider. Once prepared, it may be administered either by a healthcare provider, patient, or caregiver. Before preparing EMEND: Do not open the pouch of EMEND until ready to prepare the medicine. Store the pouch at room temperature [between 68°F-77°F (20°C-25°C)]. Table 4: Instructions for Healthcare Providers on How to Prepare EMEND for Oral Suspension EMEND for oral suspension is packaged as a kit with one 1 mL oral dosing dispenser, one 5 mL oral dosing dispenser, one cap and one mixing cup. 1. Fill the mixing cup with room temperature drinking water. 2. Fill the 5 mL oral dosing dispenser with 4.6 mL of water from the mixing cup. Make sure no air is in the dispenser - if air is present, remove. 3. Discard all the unused water remaining in the mixing cup. 4. Add the 4.6 mL of water from the dispenser back into the mixing cup. 5. Each pouch of EMEND for oral suspension contains 125 mg of aprepitant which is to be suspended in 4.6 mL of water giving a final concentration of 25 mg/mL. Hold the EMEND for oral suspension pouch upright and shake the contents to the bottom before opening the pouch. 6. Pour the entire contents of the pouch into the 4.6 mL of water in the mixing cup and snap the lid shut. 7. Mix the EMEND suspension gently by swirling 20 times; then gently invert the mixing cup 5 times. To prevent foaming, do not shake the mixing cup. The mixture will be cloudy pink to light pink. 8. Check the EMEND mixture for any clumps or foaming: If any clumps are present, repeat Step 7 until there are no clumps. If there is any foam, wait for the foam to disappear before going on to Step 9. 9. Fill the dispenser with the prescribed dose shown above in Table 3. Choose the dispenser based on dose: Use 1 mL dispenser if dose is 1 mL or less. Use 5 mL dispenser if dose is more than 1 mL. Fill the dispenser with the prescribed dose from the cup. If the dose is less than 1 mL round to the nearest 0.1 mL. If the dose is more than 1 mL round to the nearest 0.2 mL. It is common to have medicine leftover in the cup. Make sure no air is in the dispenser - if air is present, remove. Make sure the dispenser contains the prescribed dose. 10. Place the cap on the dispenser until it clicks. 11. If the dose is not administered immediately after measuring, store filled oral dosing dispenser(s) in the refrigerator [between 36°F-46°F (2°C-8°C)] for up to 72 hours prior to use. When dispensing dose(s) to the patient or caregiver, instruct them to refrigerate the oral dosing dispenser(s) until they are ready to administer the dose. 12. When ready to use, the mixture can be kept at room temperature [between 68°F-77°F (20°C-25°C)] for up to 3 hours. 13. Discard the mixing cup along with any remaining suspension. Figure Figure Figure Figure Figure Figure Figure Figure Figure Figure 2.3 Administration Instructions EMEND capsules and EMEND for oral suspension can be administered with or without food. EMEND capsules Swallow capsules whole. EMEND for oral suspension The dose will be prepared by the healthcare provider and dispensed to the patient or caregiver in an oral dispenser. Keep the dispenser in the refrigerator until administered to the patient. The dose can be stored at room temperature for up to 3 hours before use. When ready to use, take the cap off the dispenser, place the dispenser in the patient's mouth along the inner cheek on either the right or left side. Slowly dispense the medicine. The dose must be used within 72 hours of preparation. Discard any doses remaining after 72 hours.

EMEND is contraindicated in patients: who are hypersensitive to any component of the product. Hypersensitivity reactions including anaphylactic reactions have been reported [see Adverse Reactions (6.2) ] . taking pimozide. Inhibition of CYP3A4 by aprepitant could result in elevated plasma concentrations of this drug which is a CYP3A4 substrate, potentially causing serious or life-threatening reactions, such as QT prolongation, a known adverse reaction of pimozide [see Warnings and Precautions (5.1) ] . Known hypersensitivity to any component of this drug. ( 4 ) Concurrent use with pimozide. ( 4 )

Most common adverse reactions (≥3%) are ( 6.1 ): Adults: fatigue, diarrhea, asthenia, dyspepsia, abdominal pain, hiccups, white blood cell count decreased, dehydration, and alanine aminotransferase increased. Pediatrics: neutropenia, headache, diarrhea, decreased appetite, cough, fatigue, hemoglobin decreased, dizziness, and hiccups. To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 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 clinical practice. The overall safety of EMEND was evaluated in approximately 6800 individuals. Adults In 2 active-controlled, double-blind clinical trials in patients receiving highly emetogenic chemotherapy (HEC) (Studies 1 and 2), EMEND in combination with ondansetron and dexamethasone (EMEND regimen) was compared to ondansetron and dexamethasone alone (standard therapy) [see Clinical Studies (14.1) ] . In 2 active-controlled clinical trials in patients receiving moderately emetogenic chemotherapy (MEC) (Studies 3 and 4), EMEND in combination with ondansetron and dexamethasone (EMEND regimen) was compared to ondansetron and dexamethasone alone (standard therapy) [see Clinical Studies (14.2) ]. The most common adverse reaction reported in patients who received MEC in pooled Studies 3 and 4 was dyspepsia (6% versus 4%). Across these 4 studies there were 1412 patients treated with the EMEND regimen during Cycle 1 of chemotherapy and 1099 of these patients continued into the Multiple-Cycle extension for up to 6 cycles of chemotherapy. The most common adverse reactions reported in patients who received HEC and MEC in pooled Studies 1, 2, 3 and 4 are listed in Table 5. Table 5: Most Common Adverse Reactions in Patients Receiving HEC and MEC from a Pooled Analysis of HEC and MEC Studies Reported in ≥ 3% of patients treated with the EMEND regimen and at a greater incidence than standard therapy. EMEND, ondansetron, and dexamethasone EMEND regimen (N=1412) Ondansetron and dexamethasone Standard therapy (N=1396) fatigue 13% 12% diarrhea 9% 8% asthenia 7% 6% dyspepsia 7% 5% abdominal pain 6% 5% hiccups 5% 3% white blood cell count decreased 4% 3% dehydration 3% 2% alanine aminotransferase increased 3% 2% In a pooled analysis of the HEC and MEC studies, less common adverse reactions reported in patients treated with the EMEND regimen are listed in Table 6. Table 6: Less Common Adverse Reactions in EMEND-Treated Patients from a Pooled Analysis of HEC and MEC Studies Reported in > 0.5% of patients treated with the EMEND regimen, at a greater incidence than standard therapy and not previously described in Table 5. Infection and Infestations oral candidiasis, pharyngitis Blood and the Lymphatic System Disorders anemia, febrile neutropenia, neutropenia, thrombocytopenia Metabolism and Nutrition Disorders decreased appetite, hypokalemia Psychiatric Disorders anxiety Nervous System Disorders dizziness, dysgeusia, peripheral neuropathy Cardiac Disorders palpitations Vascular Disorders flushing, hot flush Respiratory, Thoracic and Mediastinal Disorders cough, dyspnea, oropharyngeal pain Gastrointestinal Disorders dry mouth, eructation, flatulence, gastritis, gastroesophageal reflux disease, nausea, vomiting Skin and Subcutaneous Tissue Disorders alopecia, hyperhidrosis, rash Musculoskeletal and Connective Tissue Disorders musculoskeletal pain General Disorders and Administration Site Condition edema peripheral, malaise Investigations aspartate aminotransferase increased, blood alkaline phosphatase increased, blood sodium decreased, blood urea increased, proteinuria, weight decreased In an additional active-controlled clinical study in 1169 patients receiving EMEND and HEC, the adverse reactions were generally similar to that seen in the other HEC studies with EMEND. In another CINV study, Stevens-Johnson syndrome was reported as a serious adverse reaction in a patient receiving the EMEND regimen with cancer chemotherapy. Adverse reactions in the Multiple-Cycle extensions of HEC and MEC studies for up to 6 cycles of chemotherapy were generally similar to that observed in Cycle 1. Pediatric Patients 6 Months to 17 Years of Age In a pooled analysis of 2 active-controlled clinical trials in pediatric patients aged 6 months to 17 years who received highly or moderately emetogenic cancer chemotherapy (Study 5 and a safety study, Study 6), EMEND in combination with ondansetron with or without dexamethasone (EMEND regimen) was compared to ondansetron with or without dexamethasone (control regimen). There were 184 patients treated with the EMEND regimen during Cycle 1 and 215 patients received open-label EMEND for up to 9 additional cycles of chemotherapy. In Cycle 1, the most common adverse reactions reported in pediatric patients treated with the EMEND regimen in pooled Studies 5 and 6 are listed in Table 7. Table 7: Most Common Adverse Reactions in EMEND-Treated Pediatric Patients in HEC and MEC Pooled Studies 5 and 6 Reported in ≥3% of patients treated with the EMEND regimen and at a greater incidence than control regimen. EMEND and ondansetron EMEND regimen (N=184) Ondansetron Control regimen (N=168) neutropenia 13% 11% headache 9% 5% diarrhea 6% 5% decreased appetite 5% 4% cough 5% 3% fatigue 5% 2% hemoglobin decreased 5% 4% dizziness 5% 1% hiccups 4% 1% Forty-nine patients were treated with ifosfamide chemotherapy in each arm. Two of the patients treated with ifosfamide in the aprepitant arm developed behavioral changes (agitation = 1; abnormal behavior = 1), whereas no patient treated with ifosfamide in the control arm developed behavioral changes. Aprepitant has the potential for increasing ifosfamide-mediated neurotoxicity through induction of CYP3A4 [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . Non-CINV Studies Serious adverse reactions reported in adult patients receiving a non-recommended dosage of EMEND in non-CINV studies include single cases of each of the following: angioedema and urticaria, constipation, and sub-ileus. EMEND is only approved in the CINV population. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of EMEND. 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. Skin and subcutaneous tissue disorders: pruritus, rash, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis. Immune system disorders: hypersensitivity reactions including anaphylactic reactions [see Contraindications (4) ] . Nervous system disorders: ifosfamide-induced neurotoxicity reported after EMEND and ifosfamide coadministration.

See Full Prescribing Information for a list of clinically significant drug interactions. ( 4 , 5.1 , 5.2 , 5.3 , 7.1 , 7.2 ) 7.1 Effect of Aprepitant on the Pharmacokinetics of Other Drugs Aprepitant is a substrate, a weak-to-moderate (dose-dependent) inhibitor, and an inducer of CYP3A4. Aprepitant is also an inducer of CYP2C9 [see Clinical Pharmacology (12.3) ] . Aprepitant acts as a moderate inhibitor of CYP3A4 when administered as a 3-day regimen (125-mg/80-mg/80-mg) and can increase plasma concentrations of concomitant drugs that are substrates for CYP3A4. Some substrates of CYP3A4 are contraindicated with EMEND [see Contraindications (4) ] . Dosage adjustment of some CYP3A4 and CYP2C9 substrates may be warranted, as shown in Table 8. Table 8: Effects of Aprepitant on the Pharmacokinetics of Other Drugs CYP3A4 Substrates Pimozide Clinical Impact Increased pimozide exposure. Intervention EMEND is contraindicated [see Contraindications (4) ] . Benzodiazepines Clinical Impact Increased exposure to midazolam or other benzodiazepines metabolized via CYP3A4 (alprazolam, triazolam) may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ]. Intervention Monitor for benzodiazepine-related adverse reactions. Depending on the clinical situation (e.g., elderly patients) and degree of monitoring available, reduce the dose of intravenous midazolam Dexamethasone Clinical Impact Increased dexamethasone exposure [see Clinical Pharmacology (12.3) ]. Intervention Reduce the dose of oral dexamethasone by approximately 50% [see Dosage and Administration (2.1) ]. Methylprednisolone Clinical Impact Increased methylprednisolone exposure [see Clinical Pharmacology (12.3) ]. Intervention Reduce the dose of intravenous methylprednisolone by approximately 25% Reduce the dose of oral methylprednisolone by approximately 50% Chemotherapeutic agents that are metabolized by CYP3A4 Clinical Impact Increased exposure of the chemotherapeutic agent may increase the risk of adverse reactions [see Clinical Pharmacology (12.3) ] . Intervention Vinblastine, vincristine, or ifosfamide or other chemotherapeutic agents Monitor for chemotherapeutic-related adverse reactions. Etoposide, vinorelbine, paclitaxel, and docetaxel No dosage adjustment needed. Hormonal Contraceptives Clinical Impact Decreased hormonal exposure during administration of and for 28 days after administration of the last dose of EMEND [see Warnings and Precautions (5.3) , Use in Specific Populations (8.3) , Clinical Pharmacology (12.3) ] . Intervention Effective alternative or back-up methods of contraception (such as condoms and spermicides) should be used during treatment with EMEND and for 1 month following the last dose of EMEND. Examples birth control pills, skin patches, implants, and certain IUDs CYP2C9 Substrates Warfarin Clinical Impact Decreased warfarin exposure and decreased prothrombin time (INR) [see Warnings and Precautions (5.2) , Clinical Pharmacology (12.3) ] . Intervention In patients on chronic warfarin therapy, monitor the prothrombin time (INR) in the 2-week period, particularly at 7 to 10 days, following initiation of the 3-day EMEND regimen with each chemotherapy cycle. Other 5-HT 3 Antagonists Clinical Impact No change in the exposure of the 5-HT 3 antagonist [see Clinical Pharmacology (12.3) ] . Intervention No dosage adjustment needed Examples ondansetron, granisetron, dolasetron 7.2 Effect of Other Drugs on the Pharmacokinetics of Aprepitant Aprepitant is a CYP3A4 substrate [see Clinical Pharmacology (12.3) ] . Co-administration of EMEND with drugs that are inhibitors or inducers of CYP3A4 may result in increased or decreased plasma concentrations of aprepitant, respectively, as shown in Table 9. Table 9: Effects of Other Drugs on Pharmacokinetics of Aprepitant Moderate to Strong CYP3A4 Inhibitors Clinical Impact Significantly increased exposure of aprepitant may increase the risk of adverse reactions associated with EMEND [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ] . Intervention Avoid concomitant use of EMEND. Examples Moderate inhibitor: diltiazem Strong inhibitors: ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir Strong CYP3A4 Inducers Clinical Impact Substantially decreased exposure of aprepitant in patients chronically taking a strong CYP3A4 inducer may decrease the efficacy of EMEND [see Clinical Pharmacology (12.3) ] . Intervention Avoid concomitant use of EMEND. Examples rifampin, carbamazepine, phenytoin

Storage and Handling Capsules Store at 20-25°C (68-77°F) [see USP Controlled Room Temperature]. For Oral Suspension Store unopened pouch at 20-25°C (68-77°F); excursions permitted between 15-30°C (between 59-86°F). Store in the original container. Do not open pouch until ready for use. Once prepared, if suspension is not used immediately, store refrigerated [between 36°F-46°F (2°C-8°C)] for up to 72 hours prior to use. When ready to use, the mixture can be kept at room temperature [between 68°F-77°F (20°C-25°C)] for up to 3 hours.