Sodium Bicarbonate Injection, Usp 8.4% 50 Meq/50 Ml (1 Meq/ml)

Sodium Bicarbonate Injection is indicated in the treatment of metabolic acidosis which may occur in severe renal disease, uncontrolled diabetes, circulatory insufficiency due to shock or severe dehydration, extracorporeal circulation of blood, cardiac arrest and severe primary lactic acidosis.



Sodium bicarbonate is further indicated in the treatment of certain drug intoxications, including barbiturates (where dissociation of the barbiturate-protein complex is desired), in poisoning by salicylates or methyl alcohol and in hemolytic reactions requiring alkalinization of the urine to diminish  nephrotoxicity  of  hemoglobin and  its  breakdown products.  Sodium bicarbonate  also  is  indicated  in  severe  diarrhea  which  is  often  accompanied  by  a  significant  loss  of  bicarbonate.

Treatment of  metabolic  acidosis  should,  if  possible,  be  superimposed  on measures  designed  to  control  the  basic  cause  of  the  acidosis  -  e.g., insulin in uncomplicated diabetes, blood volume  restoration in  shock. But since  an appreciable  time  interval  may elapse  before  all  of  the  ancillary effects  are  brought  about,  bicarbonate  therapy  is  indicated  to  minimize  risks  inherent  to  the  acidosis  itself.



Vigorous  bicarbonate  therapy  is  required  in  any  form  of  metabolic  acidosis  where  a  rapid  increase  in  plasma total  CO2  content is  crucial  -  e.g., cardiac  arrest, circulatory insufficiency due  to  shock or  severe  dehydration,  and  in  severe  primary  lactic  acidosis  or  severe  diabetic  acidosis.

Sodium Bicarbonate Injection is administered by the intravenous route.

In cardiac arrest,a rapid intravenous dose of one to two 50 mL vials (44.6 to 100 mEq) may be given initially and continued at a rate of 50 mL (44.6 to 50 mEq) every 5 to 10 minutes if necessary (as indicated by arterial pH and blood gas monitoring) to reverse the acidosis. Caution should be observed in emergencies where very rapid infusion of large quantities of bicarbonate is indicated. Bicarbonate solutions are hypertonic and may produce an undesirable rise in plasma sodium concentration in the process of correcting the metabolic acidosis. In cardiac arrest, however, the risks from acidosis exceed those of hypernatremia.

In less urgent forms of metabolic acidosis,Sodium Bicarbonate Injection may be added to other intravenous fluids. The amount of bicarbonate to be given to older children and adults over a four-to- eight-hour period is approximately 2 to 5 mEq/kg of body weight - depending upon the severity of the acidosis as judged by the lowering of total CO ₂ content, blood pH and clinical condition of the patient. In metabolic acidosis associated with shock, therapy should be monitored by measuring blood gases, plasma osmolarity, arterial blood lactate, hemodynamics and cardiac rhythm. Bicarbonate therapy should always be planned in a stepwise fashion since the degree of response from a given dose is not precisely predictable. Initially an infusion of 2 to 5 mEq/kg body weight over a period of 4 to 8 hours will produce a measurable improvement in the abnormal acid-base status of the blood. The next step of therapy is dependent upon the clinical response of the patient. If severe symptoms have abated, then the frequency of administration and the size of the dose may be reduced.

In general, it is unwise to attempt full correction of a low total CO ₂content during the first 24 hours of therapy, since this may be accompanied by an unrecognized alkalosis because of a delay in the readjustment of ventilation to normal. Owing to this lag, the achievement of total CO ₂content of about 20 mEq/liter at the end of the first day of therapy will usually be associated with a normal blood pH. Further modification of the acidosis to completely normal values usually occurs in the presence of normal kidney function when and if the cause of the acidosis can be controlled. Values for total CO ₂which are brought to normal or above normal within the first day of therapy are very likely to be associated with grossly alkaline values for blood pH, with ensuing undesired side effects.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.

Discard unused portion.

Sodium Bicarbonate  Injection is  contraindicated in patients  who  are  losing  chloride  by vomiting  or  from continuous  gastrointestinal suction, and in patients  receiving  diuretics  known to  produce  a  hypochloremic  alkalosis.

Overly aggressive therapy with Sodium Bicarbonate Injection, can result in metabolic alkalosis (associated with muscular twitchings, irritability and tetany) and hypernatremia.

Inadvertent extravasation of intravenously administered hypertonic solutions of sodium bicarbonate have been reported to cause chemical cellulitis because of their alkalinity, with tissue necrosis, ulceration or sloughing at the site of infiltration. Prompt elevation of the part, warmth and local injection of lidocaine or hyaluronidase are recommended to reduce the likelihood of tissue sloughing from extravasated I.V. solutions.

Additives  may be  incompatible; norepinephrine  and dobutamine  are  incompatible  with sodium  bicarbonate  solution.

The  addition of  sodium bicarbonate  to  parenteral  solutions  containing  calcium should be  avoided,  except  where  compatibility  has  been previously  established.  Precipitation or  haze  may  result  from  sodium  bicarbonate-calcium  admixtures.   NOTE:  Do  not  use  the  injection  if  it  contains  precipitate.

Additives  may  be  incompatible.  Consult  with  pharmacist,  if  available.  When  introducing  additives,  use  aseptic  technique,  mix  thoroughly  and  do  not  store.

Sodium Bicarbonate Injection, USP is supplied in the following dosage forms:

NDC Code: 84549-050-03

Conc %: 8.4

mg/mL (NaHCO 3): 84

mEq/mL (Na +): 1

mEq/mL (HCO 3 -): 1

mEq/Container size (mL): 50/50

mOsmol: 2/mL

The 50 mL Sodium Bicarbonate Injection are supplied as one single-dose vial.

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature].

Manufactured by:

Steriscience Sp. z o.o.

No. 10, Daniszewska Street,

Warsaw, Poland – 03-230

Sodium Bicarbonate  Injection, USP is  a sterile, nonpyrogenic, hypertonic  solution of  sodium  bicarbonate (NaHCO3) in water for injection for administration by the intravenous route as an  electrolyte  replenisher  and  systemic  alkalizer.

Solutions  are   offered  in  concentration  of  8.4%.  See  table  in   HOW  SUPPLIEDsection  for  contents  and  characteristics.

The  solutions  contain no  bacteriostat, antimicrobial  agent or  added buffer  and are  intended only for  use  as  a single-dose  injection, the  approximate  pH of  the  solutions  is  8. When smaller  doses  are  required,  the  unused  portion  should  be  discarded.

Sodium bicarbonate, 84  mg  is  equal  to  one  milliequivalent each of  Na+  and HCO3-. Sodium Bicarbonate,  USP  is  chemically  designated  NaHCO3,  a  white  crystalline  powder  soluble  in  water.

Water  for  Injection is  chemically  designated  H2O.

Do  not  use  unless  solution  is  clear  and  the  container  or  seal  is  intact.  Discard  unused  portion.

The  potentially  large  loads  of  sodium given with  bicarbonate  require  that  caution be   exercised in the  use  of  sodium bicarbonate  in patients  with congestive  heart failure  or  other  edematous  or  sodium-  retaining  states, as  well  as  in patients  with oliguria or  anuria. See  table  in HOW SUPPLIED  section for  amounts  of  sodium  present  in  solutions.

Caution must be exercised in the administration of parenteral fluids, especially those containing sodium ions, to patients receiving corticosteroids or corticotropin.

Potassium depletion may predispose to metabolic alkalosis and coexistent hypocalcemia may be associated with carpopedal spasm as the plasma pH rises. These dangers can be minimized if such electrolyte imbalances are appropriately treated prior to or concomitantly with bicarbonate infusion.

Solutions  containing  sodium  ions  should  be  used  with  great  care,  if  at  all,  in  patients  with  congestive  heart  failure,  severe  renal  insufficiency  and  in  clinical  states  in  which  there  exists  edema  with  sodium  retention.

In patients  with diminished renal  function, administration of  solutions  containing  sodium ions  may result  in  sodium  retention.



The  intravenous  administration of  these  solutions  can cause  fluid and/or  solute  overloading  resulting  in  dilution  of  serum  electrolyte  concentrations,  overhydration,  congested  states  or  pulmonary  edema.



Extravascular  infiltration  should  be  avoided,  see   ADVERSE  REACTIONS.

Clinical studies of Sodium Bicarbonate Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Rapid injection (10 mL/min) of hypertonic Sodium Bicarbonate Injection, solutions into neonates and children under two years of age may produce hypernatremia, a decrease in cerebrospinal fluid pressure and possible intracranial hemorrhage. The rate of administration in such patients should therefore be limited to no more than 8 mEq/kg/day. "A 4.2% solution may be preferred for such slow administration. "In emergencies such as cardiac arrest, the risk of rapid infusion must be weighed against the potential for fatality due to acidosis.

Should alkalosis result, the bicarbonate should be stopped and the patient managed according to the degree of alkalosis present. 0.9% sodium chloride injection intravenous may be given; potassium chloride also may be indicated if there is hypokalemia. Severe alkalosis may be accompanied by hyperirritability or tetany and these symptoms may be controlled by calcium gluconate. An acidifying agent such as ammonium chloride may also be indicated in severe alkalosis. See WARNINGSand PRECAUTIONS.

The aim of all bicarbonate therapy is to produce a substantial correction of the low total CO2 content and blood pH, but the risks of overdosage and alkalosis should be avoided. Hence, repeated fractional doses and periodic monitoring by appropriate laboratory tests are recommended to minimize the possibility of overdosage.

Intravenous sodium bicarbonate therapy increases plasma bicarbonate, buffers excess hydrogen ion concentration, raises blood pH and reverses the clinical manifestations of acidosis. Sodium bicarbonate in water dissociates to provide sodium (Na ⁺) and bicarbonate (HCO ₃ ^-) ions. Sodium (Na ⁺) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Bicarbonate (HCO ₃ ^-) is a normal constituent of body fluids and the normal plasma level ranges from 24 to 31 mEq/liter. Plasma concentration is regulated by the kidney through acidification of the urine when there is a deficit or by alkalinization of the urine when there is an excess. Bicarbonate anion is considered "labile" since at a proper concentration of hydrogen ion (H ⁺) it may be converted to carbonic acid (H ₂CO ₃) and thence to its volatile form, carbon dioxide (CO ₂) excreted by the lung. Normally a ratio of 1:20 (carbonic acid: bicarbonate) is present in the extracellular fluid. In a healthy adult with normal kidney function, practically all the glomerular filtered bicarbonate ion is reabsorbed; less than 1% is excreted in the urine.

Pregnancy

Animal reproduction studies have not been conducted with sodium bicarbonate. It is also not known whether sodium bicarbonate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium bicarbonate should be given to a pregnant woman only if clearly needed.

Do  not  use  unless  solution  is  clear  and  the  container  or  seal  is  intact.  Discard  unused  portion.

The  potentially  large  loads  of  sodium given with  bicarbonate  require  that  caution be   exercised in the  use  of  sodium bicarbonate  in patients  with congestive  heart failure  or  other  edematous  or  sodium-  retaining  states, as  well  as  in patients  with oliguria or  anuria. See  table  in HOW SUPPLIED  section for  amounts  of  sodium  present  in  solutions.

Caution must be exercised in the administration of parenteral fluids, especially those containing sodium ions, to patients receiving corticosteroids or corticotropin.

Potassium depletion may predispose to metabolic alkalosis and coexistent hypocalcemia may be associated with carpopedal spasm as the plasma pH rises. These dangers can be minimized if such electrolyte imbalances are appropriately treated prior to or concomitantly with bicarbonate infusion.

Solutions  containing  sodium  ions  should  be  used  with  great  care,  if  at  all,  in  patients  with  congestive  heart  failure,  severe  renal  insufficiency  and  in  clinical  states  in  which  there  exists  edema  with  sodium  retention.

In patients  with diminished renal  function, administration of  solutions  containing  sodium ions  may result  in  sodium  retention.



The  intravenous  administration of  these  solutions  can cause  fluid and/or  solute  overloading  resulting  in  dilution  of  serum  electrolyte  concentrations,  overhydration,  congested  states  or  pulmonary  edema.



Extravascular  infiltration  should  be  avoided,  see   ADVERSE  REACTIONS.

Clinical studies of Sodium Bicarbonate Injection did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Rapid injection (10 mL/min) of hypertonic Sodium Bicarbonate Injection, solutions into neonates and children under two years of age may produce hypernatremia, a decrease in cerebrospinal fluid pressure and possible intracranial hemorrhage. The rate of administration in such patients should therefore be limited to no more than 8 mEq/kg/day. "A 4.2% solution may be preferred for such slow administration. "In emergencies such as cardiac arrest, the risk of rapid infusion must be weighed against the potential for fatality due to acidosis.

Should alkalosis result, the bicarbonate should be stopped and the patient managed according to the degree of alkalosis present. 0.9% sodium chloride injection intravenous may be given; potassium chloride also may be indicated if there is hypokalemia. Severe alkalosis may be accompanied by hyperirritability or tetany and these symptoms may be controlled by calcium gluconate. An acidifying agent such as ammonium chloride may also be indicated in severe alkalosis. See WARNINGSand PRECAUTIONS.

Sodium Bicarbonate  Injection, USP is  a sterile, nonpyrogenic, hypertonic  solution of  sodium  bicarbonate (NaHCO3) in water for injection for administration by the intravenous route as an  electrolyte  replenisher  and  systemic  alkalizer.

Solutions  are   offered  in  concentration  of  8.4%.  See  table  in   HOW  SUPPLIEDsection  for  contents  and  characteristics.

The  solutions  contain no  bacteriostat, antimicrobial  agent or  added buffer  and are  intended only for  use  as  a single-dose  injection, the  approximate  pH of  the  solutions  is  8. When smaller  doses  are  required,  the  unused  portion  should  be  discarded.

Sodium bicarbonate, 84  mg  is  equal  to  one  milliequivalent each of  Na+  and HCO3-. Sodium Bicarbonate,  USP  is  chemically  designated  NaHCO3,  a  white  crystalline  powder  soluble  in  water.

Water  for  Injection is  chemically  designated  H2O.

Sodium Bicarbonate Injection, USP is supplied in the following dosage forms:

NDC Code: 84549-050-03

Conc %: 8.4

mg/mL (NaHCO 3): 84

mEq/mL (Na +): 1

mEq/mL (HCO 3 -): 1

mEq/Container size (mL): 50/50

mOsmol: 2/mL

The 50 mL Sodium Bicarbonate Injection are supplied as one single-dose vial.

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. Store at 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature].

Manufactured by:

Steriscience Sp. z o.o.

No. 10, Daniszewska Street,

Warsaw, Poland – 03-230

The aim of all bicarbonate therapy is to produce a substantial correction of the low total CO2 content and blood pH, but the risks of overdosage and alkalosis should be avoided. Hence, repeated fractional doses and periodic monitoring by appropriate laboratory tests are recommended to minimize the possibility of overdosage.

Overly aggressive therapy with Sodium Bicarbonate Injection, can result in metabolic alkalosis (associated with muscular twitchings, irritability and tetany) and hypernatremia.

Inadvertent extravasation of intravenously administered hypertonic solutions of sodium bicarbonate have been reported to cause chemical cellulitis because of their alkalinity, with tissue necrosis, ulceration or sloughing at the site of infiltration. Prompt elevation of the part, warmth and local injection of lidocaine or hyaluronidase are recommended to reduce the likelihood of tissue sloughing from extravasated I.V. solutions.

Sodium Bicarbonate  Injection is  contraindicated in patients  who  are  losing  chloride  by vomiting  or  from continuous  gastrointestinal suction, and in patients  receiving  diuretics  known to  produce  a  hypochloremic  alkalosis.

Additives  may be  incompatible; norepinephrine  and dobutamine  are  incompatible  with sodium  bicarbonate  solution.

The  addition of  sodium bicarbonate  to  parenteral  solutions  containing  calcium should be  avoided,  except  where  compatibility  has  been previously  established.  Precipitation or  haze  may  result  from  sodium  bicarbonate-calcium  admixtures.   NOTE:  Do  not  use  the  injection  if  it  contains  precipitate.

Additives  may  be  incompatible.  Consult  with  pharmacist,  if  available.  When  introducing  additives,  use  aseptic  technique,  mix  thoroughly  and  do  not  store.

Intravenous sodium bicarbonate therapy increases plasma bicarbonate, buffers excess hydrogen ion concentration, raises blood pH and reverses the clinical manifestations of acidosis. Sodium bicarbonate in water dissociates to provide sodium (Na ⁺) and bicarbonate (HCO ₃ ^-) ions. Sodium (Na ⁺) is the principal cation of the extracellular fluid and plays a large part in the therapy of fluid and electrolyte disturbances. Bicarbonate (HCO ₃ ^-) is a normal constituent of body fluids and the normal plasma level ranges from 24 to 31 mEq/liter. Plasma concentration is regulated by the kidney through acidification of the urine when there is a deficit or by alkalinization of the urine when there is an excess. Bicarbonate anion is considered "labile" since at a proper concentration of hydrogen ion (H ⁺) it may be converted to carbonic acid (H ₂CO ₃) and thence to its volatile form, carbon dioxide (CO ₂) excreted by the lung. Normally a ratio of 1:20 (carbonic acid: bicarbonate) is present in the extracellular fluid. In a healthy adult with normal kidney function, practically all the glomerular filtered bicarbonate ion is reabsorbed; less than 1% is excreted in the urine.

Sodium Bicarbonate Injection is indicated in the treatment of metabolic acidosis which may occur in severe renal disease, uncontrolled diabetes, circulatory insufficiency due to shock or severe dehydration, extracorporeal circulation of blood, cardiac arrest and severe primary lactic acidosis.



Sodium bicarbonate is further indicated in the treatment of certain drug intoxications, including barbiturates (where dissociation of the barbiturate-protein complex is desired), in poisoning by salicylates or methyl alcohol and in hemolytic reactions requiring alkalinization of the urine to diminish  nephrotoxicity  of  hemoglobin and  its  breakdown products.  Sodium bicarbonate  also  is  indicated  in  severe  diarrhea  which  is  often  accompanied  by  a  significant  loss  of  bicarbonate.

Treatment of  metabolic  acidosis  should,  if  possible,  be  superimposed  on measures  designed  to  control  the  basic  cause  of  the  acidosis  -  e.g., insulin in uncomplicated diabetes, blood volume  restoration in  shock. But since  an appreciable  time  interval  may elapse  before  all  of  the  ancillary effects  are  brought  about,  bicarbonate  therapy  is  indicated  to  minimize  risks  inherent  to  the  acidosis  itself.



Vigorous  bicarbonate  therapy  is  required  in  any  form  of  metabolic  acidosis  where  a  rapid  increase  in  plasma total  CO2  content is  crucial  -  e.g., cardiac  arrest, circulatory insufficiency due  to  shock or  severe  dehydration,  and  in  severe  primary  lactic  acidosis  or  severe  diabetic  acidosis.

Sodium Bicarbonate Injection is administered by the intravenous route.

In cardiac arrest,a rapid intravenous dose of one to two 50 mL vials (44.6 to 100 mEq) may be given initially and continued at a rate of 50 mL (44.6 to 50 mEq) every 5 to 10 minutes if necessary (as indicated by arterial pH and blood gas monitoring) to reverse the acidosis. Caution should be observed in emergencies where very rapid infusion of large quantities of bicarbonate is indicated. Bicarbonate solutions are hypertonic and may produce an undesirable rise in plasma sodium concentration in the process of correcting the metabolic acidosis. In cardiac arrest, however, the risks from acidosis exceed those of hypernatremia.

In less urgent forms of metabolic acidosis,Sodium Bicarbonate Injection may be added to other intravenous fluids. The amount of bicarbonate to be given to older children and adults over a four-to- eight-hour period is approximately 2 to 5 mEq/kg of body weight - depending upon the severity of the acidosis as judged by the lowering of total CO ₂ content, blood pH and clinical condition of the patient. In metabolic acidosis associated with shock, therapy should be monitored by measuring blood gases, plasma osmolarity, arterial blood lactate, hemodynamics and cardiac rhythm. Bicarbonate therapy should always be planned in a stepwise fashion since the degree of response from a given dose is not precisely predictable. Initially an infusion of 2 to 5 mEq/kg body weight over a period of 4 to 8 hours will produce a measurable improvement in the abnormal acid-base status of the blood. The next step of therapy is dependent upon the clinical response of the patient. If severe symptoms have abated, then the frequency of administration and the size of the dose may be reduced.

In general, it is unwise to attempt full correction of a low total CO ₂content during the first 24 hours of therapy, since this may be accompanied by an unrecognized alkalosis because of a delay in the readjustment of ventilation to normal. Owing to this lag, the achievement of total CO ₂content of about 20 mEq/liter at the end of the first day of therapy will usually be associated with a normal blood pH. Further modification of the acidosis to completely normal values usually occurs in the presence of normal kidney function when and if the cause of the acidosis can be controlled. Values for total CO ₂which are brought to normal or above normal within the first day of therapy are very likely to be associated with grossly alkaline values for blood pH, with ensuing undesired side effects.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.

Discard unused portion.

Pregnancy

Animal reproduction studies have not been conducted with sodium bicarbonate. It is also not known whether sodium bicarbonate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Sodium bicarbonate should be given to a pregnant woman only if clearly needed.