UNASYN Sultamicillin 250mg / 5mL Powder for Oral Suspension 60mL
RXDRUG-DRP-2015
Discreet Packaging
FDA-registered Products
FDA-licensed Pharmacies
Indications/Uses
Sultamicillin is indicated for infections caused by susceptible microorganisms. Typical indications are upper respiratory tract infections including sinusitis, otitis media and tonsillitis; lower respiratory tract infections including bacterial pneumonias and bronchitis; urinary tract infections and pyelonephritis; skin and soft tissue infections; intra-abdominal infections and gonococcal infections.
Sultamicillin may also be indicated in patients requiring sulbactam/ampicillin therapy following initial treatment with sulbactam/ampicillin IM/IV.
Sultamicillin may also be indicated in patients requiring sulbactam/ampicillin therapy following initial treatment with sulbactam/ampicillin IM/IV.
Dosage/Direction for Use
The recommended dose of sultamicillin in adults (including elderly patients) is 375-750 mg orally twice daily.
In both adults and children, treatment is usually continued until 48 hours after pyrexia and other abnormal signs have resolved. Treatment is normally given for 5-14 days but the treatment period may be extended if necessary.
In the treatment of uncomplicated gonorrhea, sultamicillin can be given as a single oral dose of 2.25 g (six 375 mg tablets or three 750 mg tablets). Concomitant probenecid 1.0 g should be administered in order to prolong plasma concentrations of sulbactam and ampicillin.
Cases of gonorrhea with a suspected lesion of syphilis should have dark field examinations before receiving sultamicillin and monthly serological tests for a minimum of four months.
It is recommended that there be at least 10 days treatment for any infection caused by hemolytic streptococci to prevent the occurrence of acute rheumatic fever or glomerulonephritis.
Use in Children and Infants: The dosage for most infections in children weighing less than 30 kg is sultamicillin 25-50 mg/kg/day orally in two divided doses, depending on the severity of the infection and the physician's judgment. For children weighing 30 kg or more, the usual adult dose should be given.
Use in Patients with Renal Impairment: In patients with severe impairment of renal function (creatinine clearance ≤30 mL/min), the elimination kinetics of sulbactam and ampicillin are similarly affected and hence the plasma ratio of one to the other will remain constant. The dose of sultamicillin in such patients should be administered less frequently in accordance with usual practice for ampicillin.
In both adults and children, treatment is usually continued until 48 hours after pyrexia and other abnormal signs have resolved. Treatment is normally given for 5-14 days but the treatment period may be extended if necessary.
In the treatment of uncomplicated gonorrhea, sultamicillin can be given as a single oral dose of 2.25 g (six 375 mg tablets or three 750 mg tablets). Concomitant probenecid 1.0 g should be administered in order to prolong plasma concentrations of sulbactam and ampicillin.
Cases of gonorrhea with a suspected lesion of syphilis should have dark field examinations before receiving sultamicillin and monthly serological tests for a minimum of four months.
It is recommended that there be at least 10 days treatment for any infection caused by hemolytic streptococci to prevent the occurrence of acute rheumatic fever or glomerulonephritis.
Use in Children and Infants: The dosage for most infections in children weighing less than 30 kg is sultamicillin 25-50 mg/kg/day orally in two divided doses, depending on the severity of the infection and the physician's judgment. For children weighing 30 kg or more, the usual adult dose should be given.
Use in Patients with Renal Impairment: In patients with severe impairment of renal function (creatinine clearance ≤30 mL/min), the elimination kinetics of sulbactam and ampicillin are similarly affected and hence the plasma ratio of one to the other will remain constant. The dose of sultamicillin in such patients should be administered less frequently in accordance with usual practice for ampicillin.
Overdosage
Limited information is available on the acute toxicity of ampicillin sodium and sulbactam sodium in humans. Overdosage of the drug would be expected to produce manifestations that are principally extensions of the adverse reactions reported with the drug. The fact that high cerebrospinal fluid (CSF) concentrations of beta-lactam antibiotics may cause neurologic effects, including seizures, should be considered. Because ampicillin and sulbactam are both removed from the circulation by hemodialysis, these procedures may enhance elimination of the drug from the body if overdosage occurs in patients with impaired renal function.
Administration
May be taken with or without food.
Contraindications
The use of sultamicillin is contraindicated in individuals with a history of an allergic reaction to any of the penicillins.
Special Precautions
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy including sultamicillin. These reactions are more apt to occur in individuals with a history of penicillin hypersensitivity and/or hypersensitivity reactions to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity who have experienced severe reactions when treated with cephalosporins. Before therapy with penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, and other allergens. If an allergic reaction occurs, the drug should be discontinued and the appropriate therapy instituted.
Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids, and airway management, including intubation, should be administered as indicated.
Severe skin reactions, such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), dermatitis exfoliative, and erythema multiforme have been reported in patients on ampicillin/sulbactam therapy. If a severe skin reaction occurs, use of the product should be discontinued and appropriate therapy should be initiated (see Adverse Reactions). As with any antibiotic preparation, constant observation for signs of overgrowth of non-susceptible organisms, including fungi, is essential. Should super-infection occur, the drug should be discontinued and/or appropriate therapy instituted.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including sultamicillin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.
C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Drug induced liver injury such as cholestatic hepatitis and jaundice have been associated with the use of ampicillin/sulbactam. Patients should be advised to contact their doctor if signs and symptoms of hepatic disease develop (see Adverse Reactions).
Since infectious mononucleosis is viral in origin, ampicillin should not be used in the treatment. A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash.
It is advisable to check periodically for organ system dysfunction during prolonged therapy; this includes renal, hepatic and hematopoietic systems.
The principal route of excretion of sulbactam and ampicillin following oral administration of sultamicillin is via the urine. Because renal function is not fully developed in neonates, this should be considered when using sultamicillin in neonates.
Tablets: Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Powder for Oral Suspension: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Effects on Ability to Drive and Use Machines: None known.
Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids, and airway management, including intubation, should be administered as indicated.
Severe skin reactions, such as toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), dermatitis exfoliative, and erythema multiforme have been reported in patients on ampicillin/sulbactam therapy. If a severe skin reaction occurs, use of the product should be discontinued and appropriate therapy should be initiated (see Adverse Reactions). As with any antibiotic preparation, constant observation for signs of overgrowth of non-susceptible organisms, including fungi, is essential. Should super-infection occur, the drug should be discontinued and/or appropriate therapy instituted.
Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including sultamicillin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.
C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Drug induced liver injury such as cholestatic hepatitis and jaundice have been associated with the use of ampicillin/sulbactam. Patients should be advised to contact their doctor if signs and symptoms of hepatic disease develop (see Adverse Reactions).
Since infectious mononucleosis is viral in origin, ampicillin should not be used in the treatment. A high percentage of patients with mononucleosis who receive ampicillin develop a skin rash.
It is advisable to check periodically for organ system dysfunction during prolonged therapy; this includes renal, hepatic and hematopoietic systems.
The principal route of excretion of sulbactam and ampicillin following oral administration of sultamicillin is via the urine. Because renal function is not fully developed in neonates, this should be considered when using sultamicillin in neonates.
Tablets: Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Powder for Oral Suspension: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Effects on Ability to Drive and Use Machines: None known.
Use In Pregnancy & Lactation
Use During Pregnancy: Animal reproduction studies have revealed no evidence of impaired fertility or harm to the fetus due to sultamicillin. Sulbactam and ampicillin cross the placental barrier.
However, safety for use in human pregnancy has not been established. Therefore, sultamicillin should be used during pregnancy only if the potential benefits outweigh the potential risk.
Use During Lactation: The use of sultamicillin during lactation is not recommended. Low concentrations of ampicillin and sulbactam are excreted in the milk. This should be considered as the neonate may be exposed, particularly since renal function is not fully developed in neonates.
However, safety for use in human pregnancy has not been established. Therefore, sultamicillin should be used during pregnancy only if the potential benefits outweigh the potential risk.
Use During Lactation: The use of sultamicillin during lactation is not recommended. Low concentrations of ampicillin and sulbactam are excreted in the milk. This should be considered as the neonate may be exposed, particularly since renal function is not fully developed in neonates.
Adverse Reactions
Sultamicillin is generally well tolerated. The majority of side effects observed were of mild or moderate severity and were normally tolerated with continued treatment.
Infections and Infestations: Pseudomembranous colitis, Candida infection.
Blood and Lymphatic System Disorders: Thrombocytopenia.
Immune System Disorders: Anaphylactic shock, Anaphylactic reaction, Kounis syndrome, Hypersensitivity.
Nervous System Disorders: Dizziness, Somnolence, Sedation, Headache.
Respiratory, Thoracic and Mediastinal Disorders: Dyspnea.
Gastrointestinal Disorders: Enterocolitis, Melena, Diarrhea, Vomiting, Abdominal pain, Dyspepsia, Nausea, Stomatitis, Dysgeusia, Tongue discoloration.
Hepatobiliary Disorders: Jaundice, Hepatic function abnormal (see Precautions).
Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, Erythema multiforme (see Precautions), Angioedema, Urticaria, Dermatitis, Rash, Pruritus.
Musculoskeletal and Connective Tissue Disorders: Arthralgia.
General Disorders and Administration Site Conditions: Fatigue, Malaise.
Investigations: Alanine aminotransferase increased, Aspartate aminotransferase increased (see Precautions).
Adverse reactions associated with the use of ampicillin alone and/or sulbactam/ampicillin IM/IV may be observed with sultamicillin. These include: Blood and Lymphatic System Disorders: Agranulocytosis, Hemolytic anemia, Thrombocytopenic purpura, Leukopenia, Neutropenia, Eosinophilia, Anemia.
Immune System Disorders: Anaphylactoid shock, Anaphylactoid reaction.
Nervous System Disorders: Convulsion.
Gastrointestinal Disorders: Glossitis.
Hepatobiliary Disorders: Hepatitis cholestatic, Cholestasis, Hyperbilirubinemia (see Precautions).
Skin and Subcutaneous Tissue Disorders: Dermatitis exfoliative, Acute generalized exanthematous pustulosis (see Precautions).
Renal and Urinary Disorders: Tubulointerstitial nephritis.
Investigations: Platelet aggregation abnormal.
Seek medical attention immediately at the first sign of any adverse drug reaction.
Infections and Infestations: Pseudomembranous colitis, Candida infection.
Blood and Lymphatic System Disorders: Thrombocytopenia.
Immune System Disorders: Anaphylactic shock, Anaphylactic reaction, Kounis syndrome, Hypersensitivity.
Nervous System Disorders: Dizziness, Somnolence, Sedation, Headache.
Respiratory, Thoracic and Mediastinal Disorders: Dyspnea.
Gastrointestinal Disorders: Enterocolitis, Melena, Diarrhea, Vomiting, Abdominal pain, Dyspepsia, Nausea, Stomatitis, Dysgeusia, Tongue discoloration.
Hepatobiliary Disorders: Jaundice, Hepatic function abnormal (see Precautions).
Skin and Subcutaneous Tissue Disorders: Toxic epidermal necrolysis, Stevens-Johnson syndrome, Erythema multiforme (see Precautions), Angioedema, Urticaria, Dermatitis, Rash, Pruritus.
Musculoskeletal and Connective Tissue Disorders: Arthralgia.
General Disorders and Administration Site Conditions: Fatigue, Malaise.
Investigations: Alanine aminotransferase increased, Aspartate aminotransferase increased (see Precautions).
Adverse reactions associated with the use of ampicillin alone and/or sulbactam/ampicillin IM/IV may be observed with sultamicillin. These include: Blood and Lymphatic System Disorders: Agranulocytosis, Hemolytic anemia, Thrombocytopenic purpura, Leukopenia, Neutropenia, Eosinophilia, Anemia.
Immune System Disorders: Anaphylactoid shock, Anaphylactoid reaction.
Nervous System Disorders: Convulsion.
Gastrointestinal Disorders: Glossitis.
Hepatobiliary Disorders: Hepatitis cholestatic, Cholestasis, Hyperbilirubinemia (see Precautions).
Skin and Subcutaneous Tissue Disorders: Dermatitis exfoliative, Acute generalized exanthematous pustulosis (see Precautions).
Renal and Urinary Disorders: Tubulointerstitial nephritis.
Investigations: Platelet aggregation abnormal.
Seek medical attention immediately at the first sign of any adverse drug reaction.
Drug Interactions
Allopurinol: The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone.
Anticoagulants: Penicillins can produce alterations in platelet aggregation and coagulation tests. These effects may be additive with anticoagulants.
Bacteriostatic drugs (chloramphenicol, erythromycin, sulfonamides and tetracyclines): Bacteriostatic drugs may interfere with the bactericidal effect of penicillins; it is best to avoid concurrent therapy.
Estrogen-containing oral contraceptives: There have been case reports of reduced oral contraceptive effectiveness in women taking ampicillin, resulting in unplanned pregnancy. Although the association is weak, patients should be given the option to use an alternate or additional method of contraception while taking ampicillin.
Methotrexate: Concurrent use with penicillins has resulted in decreased clearance of methotrexate and a corresponding increase in methotrexate toxicity. Patients should be closely monitored. Leucovorin dosages may need to be increased and administered for longer periods of time.
Probenecid: Probenecid decreases renal tubular secretion of ampicillin and sulbactam when used concurrently; this effect results in increased and prolonged serum concentrations, prolonged elimination half-life, and increased risk of toxicity.
Laboratory test interactions: False-positive glycosuria may be observed in urinalysis using Benedict reagent, Fehling reagent, and Clinitest. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol glucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with sulbactam sodium/ampicillin sodium IM/IV.
Anticoagulants: Penicillins can produce alterations in platelet aggregation and coagulation tests. These effects may be additive with anticoagulants.
Bacteriostatic drugs (chloramphenicol, erythromycin, sulfonamides and tetracyclines): Bacteriostatic drugs may interfere with the bactericidal effect of penicillins; it is best to avoid concurrent therapy.
Estrogen-containing oral contraceptives: There have been case reports of reduced oral contraceptive effectiveness in women taking ampicillin, resulting in unplanned pregnancy. Although the association is weak, patients should be given the option to use an alternate or additional method of contraception while taking ampicillin.
Methotrexate: Concurrent use with penicillins has resulted in decreased clearance of methotrexate and a corresponding increase in methotrexate toxicity. Patients should be closely monitored. Leucovorin dosages may need to be increased and administered for longer periods of time.
Probenecid: Probenecid decreases renal tubular secretion of ampicillin and sulbactam when used concurrently; this effect results in increased and prolonged serum concentrations, prolonged elimination half-life, and increased risk of toxicity.
Laboratory test interactions: False-positive glycosuria may be observed in urinalysis using Benedict reagent, Fehling reagent, and Clinitest. Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated estriol, estriol glucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with sulbactam sodium/ampicillin sodium IM/IV.
Caution For Usage
Directions for Reconstitution for Sultamicillin Powder for Oral Suspension: Ingest only after preparation of a suspension. The bottle with the powder for oral suspension should be filled with water up to the marking line. It should then be shaken until the content is uniformly mixed; then subsequently fill again with water up to the same marking line and shake again. The suspension now can be used for 14 days if stored in the refrigerator. Shake before each use.
Storage
375 mg Tablet: Store at temperatures not exceeding 30°C.
250 mg/5 mL Powder for Oral Suspension and 750 mg Tablet: Store at temperatures not exceeding 25°C.
The reconstituted oral suspension must be stored under refrigeration and discarded after 14 days.
250 mg/5 mL Powder for Oral Suspension and 750 mg Tablet: Store at temperatures not exceeding 25°C.
The reconstituted oral suspension must be stored under refrigeration and discarded after 14 days.
Action
Pharmacologic Category: Antibacterial.
Pharmacology: Pharmacodynamics: Biochemical studies with cell-free bacterial systems have shown sulbactam to be an irreversible inhibitor of most important beta-lactamases that occur in penicillin-resistant organisms. While sulbactam antibacterial activity is mainly limited to Neisseriaceae, the potential for sulbactam sodium in preventing the destruction of penicillins and cephalosporins by resistant organisms was confirmed in whole-organism studies using resistant strains, in which sulbactam sodium exhibited marked synergistic effects with penicillins and cephalosporins. Since sulbactam also binds to some penicillin-binding proteins, some sensitive strains are rendered more susceptible to the combination than to the beta-lactam antibiotic alone.
The bactericidal component of this product is ampicillin, which, like benzyl penicillin, acts against sensitive organisms during the stage of active multiplication by the inhibition of biosynthesis of cell wall mucopeptide.
Sultamicillin is effective against a wide range of gram-positive and gram-negative bacteria including: Staphylococcus aureus and Staphylococcus epidermidis (including penicillin-resistant and some methicillin-resistant strains); Streptococcus pneumoniae, Streptococcus faecalis and other Streptococcus species; Haemophilus influenzae and Haemophilus parainfluenzae (both beta-lactamase-positive and -negative strains); Moraxella catarrhalis; anaerobes including Bacteroides fragilis and related species; Escherichia coli; Klebsiella species; Proteus species (both indole-positive and indole-negative); Enterobacter species; Morganella morganii; Citrobacter species; Neisseria meningitidis and Neisseria gonorrhoeae.
Pharmacokinetics: Following oral administration in humans, sultamicillin is hydrolyzed during absorption to provide sulbactam and ampicillin in a 1:1 molar ratio in the systemic circulation. The bioavailability of an oral dose is 80% of an equal intravenous dose of sulbactam and ampicillin. Administration following food does not affect the systemic bioavailability of sultamicillin. Peak serum levels of ampicillin, following administration of sultamicillin, are approximately twice those of an equal dose of oral ampicillin. Elimination half-lives are approximately 0.75 and 1 hour for sulbactam and ampicillin, respectively, in healthy volunteers, with 50%-75% of each agent being excreted unchanged in the urine.
Elimination half-lives are increased in the elderly and in patients with renal dysfunction. Probenecid decreases the renal tubular secretion of both ampicillin and sulbactam. Concurrent use of probenecid with sultamicillin results in increased and prolonged blood levels of ampicillin and sulbactam (see Interactions).
Toxicology: Preclinical Safety Data: While reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in humans.
Long-term studies in animals have not been performed to evaluate the carcinogenic potential. The individual components of sultamicillin (ampicillin/sulbactam) tested negative for mutagenicity.
Reproduction studies have been performed in mice and rats at doses in excess of the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to sultamicillin.
Pharmacology: Pharmacodynamics: Biochemical studies with cell-free bacterial systems have shown sulbactam to be an irreversible inhibitor of most important beta-lactamases that occur in penicillin-resistant organisms. While sulbactam antibacterial activity is mainly limited to Neisseriaceae, the potential for sulbactam sodium in preventing the destruction of penicillins and cephalosporins by resistant organisms was confirmed in whole-organism studies using resistant strains, in which sulbactam sodium exhibited marked synergistic effects with penicillins and cephalosporins. Since sulbactam also binds to some penicillin-binding proteins, some sensitive strains are rendered more susceptible to the combination than to the beta-lactam antibiotic alone.
The bactericidal component of this product is ampicillin, which, like benzyl penicillin, acts against sensitive organisms during the stage of active multiplication by the inhibition of biosynthesis of cell wall mucopeptide.
Sultamicillin is effective against a wide range of gram-positive and gram-negative bacteria including: Staphylococcus aureus and Staphylococcus epidermidis (including penicillin-resistant and some methicillin-resistant strains); Streptococcus pneumoniae, Streptococcus faecalis and other Streptococcus species; Haemophilus influenzae and Haemophilus parainfluenzae (both beta-lactamase-positive and -negative strains); Moraxella catarrhalis; anaerobes including Bacteroides fragilis and related species; Escherichia coli; Klebsiella species; Proteus species (both indole-positive and indole-negative); Enterobacter species; Morganella morganii; Citrobacter species; Neisseria meningitidis and Neisseria gonorrhoeae.
Pharmacokinetics: Following oral administration in humans, sultamicillin is hydrolyzed during absorption to provide sulbactam and ampicillin in a 1:1 molar ratio in the systemic circulation. The bioavailability of an oral dose is 80% of an equal intravenous dose of sulbactam and ampicillin. Administration following food does not affect the systemic bioavailability of sultamicillin. Peak serum levels of ampicillin, following administration of sultamicillin, are approximately twice those of an equal dose of oral ampicillin. Elimination half-lives are approximately 0.75 and 1 hour for sulbactam and ampicillin, respectively, in healthy volunteers, with 50%-75% of each agent being excreted unchanged in the urine.
Elimination half-lives are increased in the elderly and in patients with renal dysfunction. Probenecid decreases the renal tubular secretion of both ampicillin and sulbactam. Concurrent use of probenecid with sultamicillin results in increased and prolonged blood levels of ampicillin and sulbactam (see Interactions).
Toxicology: Preclinical Safety Data: While reversible glycogenosis was observed in laboratory animals, this phenomenon was dose- and time-dependent and is not expected to develop at the therapeutic doses and corresponding plasma levels attained during the relatively short periods of combined ampicillin/sulbactam therapy in humans.
Long-term studies in animals have not been performed to evaluate the carcinogenic potential. The individual components of sultamicillin (ampicillin/sulbactam) tested negative for mutagenicity.
Reproduction studies have been performed in mice and rats at doses in excess of the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to sultamicillin.
MedsGo Class
Penicillins
Features
Brand
Unasyn
Full Details
Dosage Strength
250mg / 5ml
Drug Ingredients
- Sultamicillin
Drug Packaging
Powder for Oral Suspension 60ml
Generic Name
Sultamicillin
Dosage Form
Powder for Oral Suspension
Registration Number
DRP-2015
Drug Classification
Prescription Drug (RX)
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