Composition, structure and packing
Lyophilisates for solution for infusion from white to yellow or yellowish-green.
1 vial. Pemetrexed (in the form of Pemetrexed disodium geptagidrata) 500 mg.
Excipients: mannitol, hydrochloric acid solution of 10% and / or sodium hydroxide solution 10% (to establish the required level of pH).
Clinico-pharmacological group: The antitumor drug. Antifolat.
Pharmacological action
The antitumor drug, an antimetabolite. Pemetrexed is antifolatom, inhibiting thymidylate synthase (TC), dihydrofolate reductase (DGFR) glitsinamid-ribonucleotide-formiltransferazu (GARFT), which are key folate-dependent enzymes in the biosynthesis of purine nucleotides and timidinovyh. Pemetrexed enters the cell with the vector of reduced folate and folate-binding protein transport systems. Proceeding in a cage, Pemetrexed quickly and efficiently converted into poliglutamatnye forms using the enzyme-folil poliglutamat synthase.
Poliglutamatnye form trapped in the cells and are more potent inhibitors of TS, GARFT.
Poliglutamatsiya - a process dependent on time and concentration, which is found in tumor cells and, to a lesser extent, in normal tissues. In poliglutamirovannyh metabolites increased T1 / 2, therefore increasing the duration of the drug on tumor cells.
With the combined use of Pemetrexed and cisplatin in in vitro studies observed synergistic antitumor effect.
Pharmacokinetics
Distribution
In equilibrium, Vd Pemetrexed is 16.1 liters. Binding to plasma proteins - about 81%.
Metabolism
Pemetrexed undergoes limited metabolism in the liver.
Withdrawal
In the first 24 h after administration 70-90% of output kidneys unchanged. Pemetrexed total plasma clearance is 92 ml / min, T1 / 2 from plasma is 3.5 hours in patients with normal renal function.
Pharmacokinetics in special clinical situations
In renal insufficiency, severe degree of binding to plasma proteins is not changed.
Statement
malignant pleural mesothelioma in combination with platinum drugs;
non small cell lung lung cancer (locally advanced or metastatic non small cell lung cancer of the lung) as a therapy 2 lines.
Dosage regimen
The drug is introduced into / to drip for 10 minutes.
Malignant mesothelioma of the pleura
Combination therapy with cisplatin: The recommended dose of the drug Alimta - 500 mg/m2 on the first day of each 21-day cycle. Cisplatin is introduced in a dose of 75 mg/m2 as an infusion for 2 h in approximately 30 minutes after Alimty the first day of each 21-day cycle. Patients should receive appropriate hydration prior to and / or after cisplatin administration.
Non small cell lung cancer lung
Monotherapy: The recommended dose of the drug Alimta - 500 mg/m2 on the first day of each 21-day cycle.
Recommendations before the drug
Alimta Appointment of dexamethasone (or equivalent) at a dose of 4 mg 2 times / day for 1 day before the start of treatment with Alimta, the day of administration and the next day after the introduction of Alimty reduces the frequency and severity of skin reactions. To reduce the toxicity of the drug to patients receiving Alimtu should appoint agents folic acid or multivitamins containing folic acid daily dose. Folic acid daily dose (350 mg to 1000 mg, an average of 400 micrograms) should appoint at least 5 days to 7 days before the first introduction Alimty, and the use of such doses should be continued during the entire cycle of treatment and within 21 days after the last injection Alimty. Patients also need to enter a single vitamin B12 in a dose of 1000 mcg / m in the period of 7 days before the first introduction Alimty and then every 3 cycles after the start of treatment. Subsequent administration of vitamin B12 in the same dose can be carried out on the day of introduction Alimty.
Recommendations to reduce the dose
Alimta dose adjustment to repeated courses should be given the lowest threshold of hematological parameters or at the highest expressed negematologicheskoy toxicity during the previous cycle of treatment.
Treatment may be delayed because of toxicity. As the recovery treatment should be continued in accordance with the guidelines given in Tables 1-3.
Hematological toxicity
Correction dose
With the development of negematologicheskoy toxicity (excluding neurotoxicity) ≥ grade 3 (except for transaminase elevations 3 degrees) the introduction Alimty be postponed until recovery rates appropriate to the level before treatment. Treatment Alimtoy should be removed if the patient notes and hematological toxicity negematologicheskaya 3 or 4 degrees after two dose reductions (except for transaminase elevations 3 degrees) or the immediate repeal of neurotoxicity in the presence of 3 or 4 degrees. The data on increased risk of side effects in patients aged 65 years and older are not available.
Mode dose reduction corresponds to the general recommendations.
Patients with impaired renal function in spacecraft for at least 45 ml / min dose adjustment and treatment of drug administration is not required. When QA least 45 ml / min Alimty use is not recommended (due to lack of data on the use of the drug in this patient). Insufficient data on the use of the drug in patients with impaired liver function with increased content of bilirubin more than 1.5 times from FHG, or increased activity of transaminases more than 3 times of the FHG (in the absence of metastases in the liver), or more than 5 times the FHG (in the presence of metastases in the liver).
Recommendations for solution for infusion as a solvent is used only 0.9% solution of sodium chloride. To obtain a solution for infusion vial contents (500 mg) dissolved in 20 ml 0.9% sodium chloride solution (without preservatives) to a concentration of 25 mg / ml. Each bottle is gently shaken until complete dissolution lyophilizate. The resulting solution should be transparent; permissible change the color of the solution from colorless to yellowish or greenish-yellow color. Next, additional dilution.
The corresponding amount of the solution obtained Pemetrexed should be further diluted to 100 ml 0.9% sodium chloride solution. Before the introduction of the drug solution must be inspected for the presence of particles and discoloration. Since Alimta and recommended solvent does not contain antimicrobial preservatives and the resulting solution for the introduction should be used within 24 h after reconstitution when stored at 2 ° to 8 ° C or 15 ° to 25 ° C. Unused solution should be destroyed.
Side effect
Side effects observed during monotherapy Pemetrexed with the addition of folic acid and vitamin B12 are set out below in accordance with the following frequency: Very common - ≥ 10%, often - ≥ 1% and <10%, sometimes - <1% and ≥ 0.1%, rarely - ≤ 0.1%. In brackets the frequency of toxicity in the percentage of all degrees / one grade 3-4, respectively.
On the part of the hemopoietic system: very often - leukopenia (12.1-15.2% / 4.2-5.4%), neutropenia (14.7-10.9% / 8.2-5.3%), anemia (14.9-19.2% / 3.3-4.2%), and often - thrombocytopenia (7.0-8.3% / 1.9-2.3%).
On the part of the digestive system: very often - nausea (30.9-39.2% / 2.6%), vomiting (19.6-16.2% / 1.5-2.1%), anorexia (18.6-21.9% / 1.4-1.9%), stomatitis / pharyngitis (14.7 -15.4% / 0.7-1.1%), diarrhea (12.8-15.2% / 0.4-0.9%), increased ALT levels (7.9-15.6% / 1.9-7.0%) and AST (6.8-13.1% / 1.1-4.4%), ; often - constipation, abdominal pain. Dermatological reactions: very often - rash / desquamation (14-15.9% / 0-0.2%); often - pruritus, alopecia, and sometimes - erythema multiforme.
On the part of the peripheral nervous system: frequent - sensory or motor neuropathy.
From the urinary system: often - increasing the level of creatinine.
Since the cardiovascular system: rarely - supraventricular tachycardia.
Other: very often - fatigue (34% / 4.7-5.3%), and often - fever, febrile neutropenia, allergic reactions and the accession of secondary infections without neutropenia.
Side effects
Side effects seen with combination of Pemetrexed and cisplatin with the addition of folic acid and vitamin B12 are set out below in accordance with the following frequency: Very common - ≥ 10%, often - ≥ 1% and <10%, sometimes - <1% and ≥ 0.1%, rare - ≤ 0.1%.
In brackets the frequency of toxicity in the percentage of all degrees / one grade 3-4, respectively.
On the part of the hemopoietic system: very often - leukopenia (53.0% / 14.9%), neutropenia (56.0% / 23.%), Anemia (33.0% / 5.6%), thrombocytopenia (23.2% / 5.4%).
On the part of the digestive system: very often - nausea (82.1% / 11.9%), vomiting (56.5% / 10.7%), anorexia (26.6% / 2.4%), stomatitis / pharyngitis (23.2% / 3.0%), diarrhea (16.7% / 3.6%), constipation (21.0% / 0.8%), often - dyspepsia, increased ALT, AST, GGT.
Dermatological reactions: very often - rash / desquamation (16.1% / 0.6%), alopecia (11.9% / 0%).
On the part of the peripheral nervous system: very often - sensory neuropathy (10.1% / 0%), and often - a violation of taste, sometimes - motor neuropathy.
From the urinary system: very often - increasing the level of creatinine (10.7% / 0.8%), reduced QA (16.1% / 0.6%), and often - renal failure.
Since the cardiovascular system: sometimes - arrhythmia.
On the part of the respiratory system: often - pain in the chest.
Other: very often - fatigue (46.6% / 10.1%), and often - conjunctivitis, dehydration, febrile neutropenia, infection, fever, urticaria.
Post marketing surveillance data
From the respiratory system: rarely - interstitial pneumonitis.
On the part of the digestive system: rarely - colitis.
Contraindications
Pregnancy
lactation
Hypersensitivity to the drug's components.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Application for violations of liver function
To assess liver function should be periodic biochemical analysis of blood.
Application for violations of renal function
To assess kidney function should be periodically conduct biochemical analysis of blood.
Cautions
The drug Alimta should appoint a doctor with experience in the use of anticancer drugs. Alimta can inhibit the function of bone marrow, which is manifested neutropenia, thrombocytopenia and anemia, usually mielodepressiya is dozolimitiruyuschim toxicity.
Before each introduction Alimty necessary to carry out complete blood count with leukocyte counts and platelet counts.
To assess kidney and liver function should be periodically biochemical analysis of blood. Before using the product the absolute number of neutrophils should be ≥ 1500 cells / microliter, platelets ≥ 100,000 cells / ml.
Appointment of folic acid and vitamin B12 reduces the toxicity of Pemetrexed and the need for reduction of the dose in hematology and negematologicheskoy toxicity grade 3-4, such as neutropenia, febrile neutropenia and infection with neutropenia grade 3-4.
Patients with clinical manifestations of ascites and pleurisy effusion drainage was necessary before the use of Pemetrexed, because the influence of these states to the effect of Pemetrexed is not known.
Use in Pediatrics
Alimtu not recommended for use in children, because safety and efficacy in children has not been established.
Overdose
Symptoms: possible bone marrow suppression, manifested neutropenia, thrombocytopenia and anemia. There can also be observed adherence of secondary infections, diarrhea, inflammation of mucous membranes, skin rash. Treatment: symptomatic, including the immediate use of leucovorin or thymidine.
Drug Interactions
The combined use of nephrotoxic drugs and / or substances that are excreted by the kidneys, can reduce the clearance of Pemetrexed. Results of in vitro studies indicate that Pemetrexed minimally interacts with drugs that are metabolized by CYP3A, CYP2D6, CYP2C9, CYP1A2.
Pemetrexed pharmacokinetics is not altered by the use of folic acid by mouth, vitamin B12 / m and the combined use of c cisplatin. The total clearance of platinum is not violated in the application of Pemetrexed.
Pemetrexed can be used in conjunction with ibuprofen (400 mg 4 times / day) in patients with normal renal function (CC ≥ 80 ml / min).
In the appointment of ibuprofen together with Pemetrexed in patients with renal insufficiency of mild or moderate severity (CC 45-79 ml / min) should be careful. In patients with renal insufficiency mild to moderate severity is not recommended the use of NSAIDs with a short T1 / 2 for 2 days before using Alimty, on the day of application and within 2 days after application. In the absence of data on possible interactions between Alimtoy and NSAIDs with greater T1 / 2, all patients receiving NSAIDs should interrupt their use of at least 5 days before admission Alimty, in the same day and within 2 days after admission.
If you want the joint appointment of NSAIDs, patients require strict monitoring of toxicity, especially myelosuppression and toxicity from the gastrointestinal tract. Pemetrexed is incompatible with lactate Ringer's solution and Ringer's solution. Joint appointment of Pemetrexed with other drugs and fluids has not been investigated and therefore not recommended.
Terms and Conditions of storage
List B. The drug should be stored out of reach of small children at a temperature of 15 ° to 25 ° C.
Shelf life - 2 years. The prepared solution should be stored: at the temperature of 2 ° to 8 ° C or 15 ° to 25 ° C not more than 24 hours
Lyophilisates for solution for infusion from white to yellow or yellowish-green.
1 vial. Pemetrexed (in the form of Pemetrexed disodium geptagidrata) 500 mg.
Excipients: mannitol, hydrochloric acid solution of 10% and / or sodium hydroxide solution 10% (to establish the required level of pH).
Clinico-pharmacological group: The antitumor drug. Antifolat.
Pharmacological action
The antitumor drug, an antimetabolite. Pemetrexed is antifolatom, inhibiting thymidylate synthase (TC), dihydrofolate reductase (DGFR) glitsinamid-ribonucleotide-formiltransferazu (GARFT), which are key folate-dependent enzymes in the biosynthesis of purine nucleotides and timidinovyh. Pemetrexed enters the cell with the vector of reduced folate and folate-binding protein transport systems. Proceeding in a cage, Pemetrexed quickly and efficiently converted into poliglutamatnye forms using the enzyme-folil poliglutamat synthase.
Poliglutamatnye form trapped in the cells and are more potent inhibitors of TS, GARFT.
Poliglutamatsiya - a process dependent on time and concentration, which is found in tumor cells and, to a lesser extent, in normal tissues. In poliglutamirovannyh metabolites increased T1 / 2, therefore increasing the duration of the drug on tumor cells.
With the combined use of Pemetrexed and cisplatin in in vitro studies observed synergistic antitumor effect.
Pharmacokinetics
Distribution
In equilibrium, Vd Pemetrexed is 16.1 liters. Binding to plasma proteins - about 81%.
Metabolism
Pemetrexed undergoes limited metabolism in the liver.
Withdrawal
In the first 24 h after administration 70-90% of output kidneys unchanged. Pemetrexed total plasma clearance is 92 ml / min, T1 / 2 from plasma is 3.5 hours in patients with normal renal function.
Pharmacokinetics in special clinical situations
In renal insufficiency, severe degree of binding to plasma proteins is not changed.
Statement
malignant pleural mesothelioma in combination with platinum drugs;
non small cell lung lung cancer (locally advanced or metastatic non small cell lung cancer of the lung) as a therapy 2 lines.
Dosage regimen
The drug is introduced into / to drip for 10 minutes.
Malignant mesothelioma of the pleura
Combination therapy with cisplatin: The recommended dose of the drug Alimta - 500 mg/m2 on the first day of each 21-day cycle. Cisplatin is introduced in a dose of 75 mg/m2 as an infusion for 2 h in approximately 30 minutes after Alimty the first day of each 21-day cycle. Patients should receive appropriate hydration prior to and / or after cisplatin administration.
Non small cell lung cancer lung
Monotherapy: The recommended dose of the drug Alimta - 500 mg/m2 on the first day of each 21-day cycle.
Recommendations before the drug
Alimta Appointment of dexamethasone (or equivalent) at a dose of 4 mg 2 times / day for 1 day before the start of treatment with Alimta, the day of administration and the next day after the introduction of Alimty reduces the frequency and severity of skin reactions. To reduce the toxicity of the drug to patients receiving Alimtu should appoint agents folic acid or multivitamins containing folic acid daily dose. Folic acid daily dose (350 mg to 1000 mg, an average of 400 micrograms) should appoint at least 5 days to 7 days before the first introduction Alimty, and the use of such doses should be continued during the entire cycle of treatment and within 21 days after the last injection Alimty. Patients also need to enter a single vitamin B12 in a dose of 1000 mcg / m in the period of 7 days before the first introduction Alimty and then every 3 cycles after the start of treatment. Subsequent administration of vitamin B12 in the same dose can be carried out on the day of introduction Alimty.
Recommendations to reduce the dose
Alimta dose adjustment to repeated courses should be given the lowest threshold of hematological parameters or at the highest expressed negematologicheskoy toxicity during the previous cycle of treatment.
Treatment may be delayed because of toxicity. As the recovery treatment should be continued in accordance with the guidelines given in Tables 1-3.
Hematological toxicity
Correction dose
With the development of negematologicheskoy toxicity (excluding neurotoxicity) ≥ grade 3 (except for transaminase elevations 3 degrees) the introduction Alimty be postponed until recovery rates appropriate to the level before treatment. Treatment Alimtoy should be removed if the patient notes and hematological toxicity negematologicheskaya 3 or 4 degrees after two dose reductions (except for transaminase elevations 3 degrees) or the immediate repeal of neurotoxicity in the presence of 3 or 4 degrees. The data on increased risk of side effects in patients aged 65 years and older are not available.
Mode dose reduction corresponds to the general recommendations.
Patients with impaired renal function in spacecraft for at least 45 ml / min dose adjustment and treatment of drug administration is not required. When QA least 45 ml / min Alimty use is not recommended (due to lack of data on the use of the drug in this patient). Insufficient data on the use of the drug in patients with impaired liver function with increased content of bilirubin more than 1.5 times from FHG, or increased activity of transaminases more than 3 times of the FHG (in the absence of metastases in the liver), or more than 5 times the FHG (in the presence of metastases in the liver).
Recommendations for solution for infusion as a solvent is used only 0.9% solution of sodium chloride. To obtain a solution for infusion vial contents (500 mg) dissolved in 20 ml 0.9% sodium chloride solution (without preservatives) to a concentration of 25 mg / ml. Each bottle is gently shaken until complete dissolution lyophilizate. The resulting solution should be transparent; permissible change the color of the solution from colorless to yellowish or greenish-yellow color. Next, additional dilution.
The corresponding amount of the solution obtained Pemetrexed should be further diluted to 100 ml 0.9% sodium chloride solution. Before the introduction of the drug solution must be inspected for the presence of particles and discoloration. Since Alimta and recommended solvent does not contain antimicrobial preservatives and the resulting solution for the introduction should be used within 24 h after reconstitution when stored at 2 ° to 8 ° C or 15 ° to 25 ° C. Unused solution should be destroyed.
Side effect
Side effects observed during monotherapy Pemetrexed with the addition of folic acid and vitamin B12 are set out below in accordance with the following frequency: Very common - ≥ 10%, often - ≥ 1% and <10%, sometimes - <1% and ≥ 0.1%, rarely - ≤ 0.1%. In brackets the frequency of toxicity in the percentage of all degrees / one grade 3-4, respectively.
On the part of the hemopoietic system: very often - leukopenia (12.1-15.2% / 4.2-5.4%), neutropenia (14.7-10.9% / 8.2-5.3%), anemia (14.9-19.2% / 3.3-4.2%), and often - thrombocytopenia (7.0-8.3% / 1.9-2.3%).
On the part of the digestive system: very often - nausea (30.9-39.2% / 2.6%), vomiting (19.6-16.2% / 1.5-2.1%), anorexia (18.6-21.9% / 1.4-1.9%), stomatitis / pharyngitis (14.7 -15.4% / 0.7-1.1%), diarrhea (12.8-15.2% / 0.4-0.9%), increased ALT levels (7.9-15.6% / 1.9-7.0%) and AST (6.8-13.1% / 1.1-4.4%), ; often - constipation, abdominal pain. Dermatological reactions: very often - rash / desquamation (14-15.9% / 0-0.2%); often - pruritus, alopecia, and sometimes - erythema multiforme.
On the part of the peripheral nervous system: frequent - sensory or motor neuropathy.
From the urinary system: often - increasing the level of creatinine.
Since the cardiovascular system: rarely - supraventricular tachycardia.
Other: very often - fatigue (34% / 4.7-5.3%), and often - fever, febrile neutropenia, allergic reactions and the accession of secondary infections without neutropenia.
Side effects
Side effects seen with combination of Pemetrexed and cisplatin with the addition of folic acid and vitamin B12 are set out below in accordance with the following frequency: Very common - ≥ 10%, often - ≥ 1% and <10%, sometimes - <1% and ≥ 0.1%, rare - ≤ 0.1%.
In brackets the frequency of toxicity in the percentage of all degrees / one grade 3-4, respectively.
On the part of the hemopoietic system: very often - leukopenia (53.0% / 14.9%), neutropenia (56.0% / 23.%), Anemia (33.0% / 5.6%), thrombocytopenia (23.2% / 5.4%).
On the part of the digestive system: very often - nausea (82.1% / 11.9%), vomiting (56.5% / 10.7%), anorexia (26.6% / 2.4%), stomatitis / pharyngitis (23.2% / 3.0%), diarrhea (16.7% / 3.6%), constipation (21.0% / 0.8%), often - dyspepsia, increased ALT, AST, GGT.
Dermatological reactions: very often - rash / desquamation (16.1% / 0.6%), alopecia (11.9% / 0%).
On the part of the peripheral nervous system: very often - sensory neuropathy (10.1% / 0%), and often - a violation of taste, sometimes - motor neuropathy.
From the urinary system: very often - increasing the level of creatinine (10.7% / 0.8%), reduced QA (16.1% / 0.6%), and often - renal failure.
Since the cardiovascular system: sometimes - arrhythmia.
On the part of the respiratory system: often - pain in the chest.
Other: very often - fatigue (46.6% / 10.1%), and often - conjunctivitis, dehydration, febrile neutropenia, infection, fever, urticaria.
Post marketing surveillance data
From the respiratory system: rarely - interstitial pneumonitis.
On the part of the digestive system: rarely - colitis.
Contraindications
Pregnancy
lactation
Hypersensitivity to the drug's components.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Application for violations of liver function
To assess liver function should be periodic biochemical analysis of blood.
Application for violations of renal function
To assess kidney function should be periodically conduct biochemical analysis of blood.
Cautions
The drug Alimta should appoint a doctor with experience in the use of anticancer drugs. Alimta can inhibit the function of bone marrow, which is manifested neutropenia, thrombocytopenia and anemia, usually mielodepressiya is dozolimitiruyuschim toxicity.
Before each introduction Alimty necessary to carry out complete blood count with leukocyte counts and platelet counts.
To assess kidney and liver function should be periodically biochemical analysis of blood. Before using the product the absolute number of neutrophils should be ≥ 1500 cells / microliter, platelets ≥ 100,000 cells / ml.
Appointment of folic acid and vitamin B12 reduces the toxicity of Pemetrexed and the need for reduction of the dose in hematology and negematologicheskoy toxicity grade 3-4, such as neutropenia, febrile neutropenia and infection with neutropenia grade 3-4.
Patients with clinical manifestations of ascites and pleurisy effusion drainage was necessary before the use of Pemetrexed, because the influence of these states to the effect of Pemetrexed is not known.
Use in Pediatrics
Alimtu not recommended for use in children, because safety and efficacy in children has not been established.
Overdose
Symptoms: possible bone marrow suppression, manifested neutropenia, thrombocytopenia and anemia. There can also be observed adherence of secondary infections, diarrhea, inflammation of mucous membranes, skin rash. Treatment: symptomatic, including the immediate use of leucovorin or thymidine.
Drug Interactions
The combined use of nephrotoxic drugs and / or substances that are excreted by the kidneys, can reduce the clearance of Pemetrexed. Results of in vitro studies indicate that Pemetrexed minimally interacts with drugs that are metabolized by CYP3A, CYP2D6, CYP2C9, CYP1A2.
Pemetrexed pharmacokinetics is not altered by the use of folic acid by mouth, vitamin B12 / m and the combined use of c cisplatin. The total clearance of platinum is not violated in the application of Pemetrexed.
Pemetrexed can be used in conjunction with ibuprofen (400 mg 4 times / day) in patients with normal renal function (CC ≥ 80 ml / min).
In the appointment of ibuprofen together with Pemetrexed in patients with renal insufficiency of mild or moderate severity (CC 45-79 ml / min) should be careful. In patients with renal insufficiency mild to moderate severity is not recommended the use of NSAIDs with a short T1 / 2 for 2 days before using Alimty, on the day of application and within 2 days after application. In the absence of data on possible interactions between Alimtoy and NSAIDs with greater T1 / 2, all patients receiving NSAIDs should interrupt their use of at least 5 days before admission Alimty, in the same day and within 2 days after admission.
If you want the joint appointment of NSAIDs, patients require strict monitoring of toxicity, especially myelosuppression and toxicity from the gastrointestinal tract. Pemetrexed is incompatible with lactate Ringer's solution and Ringer's solution. Joint appointment of Pemetrexed with other drugs and fluids has not been investigated and therefore not recommended.
Terms and Conditions of storage
List B. The drug should be stored out of reach of small children at a temperature of 15 ° to 25 ° C.
Shelf life - 2 years. The prepared solution should be stored: at the temperature of 2 ° to 8 ° C or 15 ° to 25 ° C not more than 24 hours
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