Sodium bicarbonate Bioindustria L.I.M.: detailed information

BIOINDUSTRIA Italian Medicinal Laboratory S.p.A.

ILLUSTRATED LEAFLET

Sodium Bicarbonate Bioindustria L.I.M. 1.4% infusion solution, 5% infusion solution, 7.5% infusion solution, 8.4% infusion solution

PHARMACOTHERAPEUTIC CATEGORY
Electrolytes.

THERAPEUTIC INDICATIONS
Treatment of:

Metabolic acidosis
Shock
Barbiturate, salicylate, and methanol poisoning
Hemolytic and rhabdomyolytic syndromes
Hyperuricemia
Intestinal bicarbonate losses (due to diarrhea).

CONTRAINDICATIONS

Hypersensitivity to the active substance or to any of the excipients;
Metabolic or respiratory alkalosis, especially if associated with hypochloremia (vomiting, gastrointestinal losses, diuretic therapy);
Hypocalcemia.

PRECAUTIONS FOR USE
Use with caution in patients with congestive heart failure, severe renal insufficiency, and in clinical conditions associated with edema and salt retention; in patients receiving cardiac inotropic agents or corticosteroid or corticotropin therapy.
Sodium salts should be administered cautiously in patients with hypertension, cardiac insufficiency, peripheral or pulmonary edema, reduced renal function, pre-eclampsia, or other conditions associated with sodium retention (see Interactions).
During infusion, it is advisable to monitor fluid balance, electrolytes, plasma osmolarity, and acid-base balance, correcting potassium and calcium depletion if necessary to prevent tetany.

INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicinal product,
including those without a prescription.
Corticosteroids are associated with sodium and water retention, leading to edema and hypertension: therefore, caution is required when administering sodium salts concomitantly with corticosteroids (see Precautions for Use).
Sodium bicarbonate increases the renal clearance of tetracyclines.
Concomitant administration of sodium bicarbonate and drugs promoting potassium excretion increases the risk of hypochloremic alkalosis.
Sodium bicarbonate increases the half-life and thus the duration of action of basic drugs such as quinidine, ephedrine, and pseudoephedrine.

SPECIAL WARNINGS
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
The solution must be clear, colorless, and free from visible particles. Use immediately after opening the container. The container is intended for single and uninterrupted administration; any residual solution must not be used.

Pregnancy and Lactation
Consult your doctor or pharmacist before taking any medicinal product.
No data are available on potential adverse effects of the medicinal product when administered during pregnancy or lactation, or on reproductive capacity.
Therefore, the medicinal product should not be used during pregnancy or breastfeeding unless absolutely necessary and only after careful assessment of the risk-benefit ratio.

Effects on the ability to drive and use machines
The medicinal product does not impair the ability to drive or operate machinery.

Important information about certain excipients: none

DOSAGE, ROUTE AND DURATION OF ADMINISTRATION
The 1.4% solution is isotonic with blood; the 5%, 7.5%, and 8.4% solutions are hypertonic with blood.
Solutions must be administered by intravenous infusion with caution and at a controlled infusion rate, avoiding the infusion of large volumes at high infusion rates.
The medicinal product must not be used unless specifically prescribed.
In general, dosage depends on age, weight, clinical condition, electrolyte profile, acid-base balance, and osmolarity of the patient, aiming to restore normal pH and electrolyte values (in cases of shock, hemolytic and rhabdomyolytic syndromes, and bicarbonate losses) or to alkalinize urine in cases of poisoning or hyperuricemia (urine pH of at least 7.0).

Specifically:
Acute and subacute forms of metabolic acidosis
Adults
Initial dose of 2 to 5 mEq/kg body weight over 4–8 hours, depending on the severity of acidosis. The dose should then be adjusted according to measured blood bicarbonate levels or blood gas analysis results (target increase of 20–22 mmol/L).
Children
Initial dose of 1 mEq/kg administered by slow intravenous infusion, diluted to a concentration of 0.5 mEq/ml, up to a maximum daily dose of 8 mEq/kg body weight to avoid excessive reduction in cerebrospinal pressure and possible intracranial hemorrhage.
The safety and efficacy of sodium bicarbonate in children have not been established.
Elderly
In elderly patients over 60 years of age, the maximum daily dose is 90–100 mEq of bicarbonate.
It is advisable NOT to achieve full correction of acidosis within the first 24 hours to avoid alkalosis due to excessive respiratory overcompensation.

Incompatibilities with Sodium Bicarbonate Bioindustria L.I.M.
If used to dilute medicinal products, consult a pharmacist if available before adding any additives; consider the characteristics of the products to be added; use aseptic techniques. In case of adverse reaction, discontinue administration.
Do not use with solutions containing noradrenaline, dobutamine, or calcium.
Use the solution immediately after opening the container. It is intended for single and uninterrupted administration; any residual solution must not be used.
Do not use the medicinal product if the solution is not clear and colorless or if it contains particles.
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Adopt all standard precautions to maintain sterility before and during intravenous infusion.

OVERDOSE
Symptoms
Excessive administration of sodium bicarbonate solutions may lead, depending on the patient's clinical condition, to alkalemia, hypernatremia, and/or hypervolemia.
Hypernatremia and excessive sodium retention, especially in the presence of impaired renal sodium excretion, may cause dehydration of internal organs, particularly the brain, and accumulation of extracellular fluid leading to edema affecting cerebral, pulmonary, and peripheral circulation, including pulmonary and peripheral edema.
Symptoms of alkalosis include muscle weakness associated with potassium depletion, increased muscle tone, muscle spasms, and tetany, particularly in hypocalcemic patients.

Treatment
Immediately discontinue the infusion and initiate corrective therapy to reduce plasma levels of excess ions and restore, if necessary, acid-base balance (see Precautions for Use).
The patient should be closely monitored for signs and symptoms related to the administered medicinal product, with appropriate symptomatic and supportive measures provided as needed.
In cases of severe hypernatremia, loop diuretics may be used.
Serum sodium levels exceeding 200 mmol/L may require dialysis.
Hyperirritability and tetany associated with alkalosis may be managed with administration of adequate doses of calcium gluconate. In cases of severe alkalosis, ammonium chloride administration is recommended, except in patients with liver disease.

In case of accidental ingestion/overdose of Sodium Bicarbonate Bioindustria L.I.M., contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Sodium Bicarbonate Bioindustria L.I.M., consult your doctor or pharmacist.

UNDESIRABLE EFFECTS
Like all medicinal products, Sodium Bicarbonate may cause adverse effects, although not everyone experiences them.
The following are adverse effects associated with Sodium Bicarbonate. There are insufficient data to determine the frequency of individual listed effects.
Disorders of water and electrolyte balance
Alkalemia, hypernatremia, hypervolemia, hyperosmolarity.
Systemic disorders and administration site conditions
Fever episodes, infusion site infection, pain or local reaction, venous irritation, thrombosis or phlebitis, chemical cellulitis with tissue necrosis due to accidental extravasation into soft tissues.
Following the instructions in this leaflet reduces the risk of adverse effects.
If any of the adverse effects worsens, or if you notice any adverse effect not listed in this leaflet, inform your doctor or pharmacist.
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.

EXPIRY DATE AND STORAGE
Expiry date: see the date on the packaging.
The expiry date refers to the product stored unopened and under recommended conditions.
Caution: Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions
Store in the original packaging and in a tightly closed container. Do not refrigerate or freeze.
Medicinal products must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of unused medicinal products. This will help protect the environment.
Keep the medicinal product out of the reach and sight of children.

COMPOSITION
Sodium Bicarbonate Bioindustria L.I.M. 1.4% infusion solution
1000 ml of solution contains:
Active substance: sodium bicarbonate 14.0 g
Excipients: edetate disodium, water for injections.
mEq/liter Na 167
HCO₃⁻ 167
Theoretical osmolarity (mOsm/liter) 334
pH: 7.0 – 8.5

Sodium Bicarbonate Bioindustria L.I.M. 5% infusion solution
1000 ml of solution contains:
Active substance: sodium bicarbonate 50.0 g
Excipients: edetate disodium, water for injections.
mEq/liter Na 595
HCO₃⁻ 595
Theoretical osmolarity (mOsm/liter) 1190
pH: 7.0 – 8.5

Sodium Bicarbonate Bioindustria L.I.M. 7.5% infusion solution
1000 ml of solution contains:
Active substance: sodium bicarbonate 75.0 g
Excipients: edetate disodium, water for injections.
mEq/liter Na 893
HCO₃⁻ 893
Theoretical osmolarity (mOsm/liter) 1785
pH: 7.0 – 8.5

Sodium Bicarbonate Bioindustria L.I.M. 8.4% infusion solution
1000 ml of solution contains:
Active substance: sodium bicarbonate 84.0 g
Excipients: edetate disodium, water for injections.
mEq/liter Na 1000
HCO₃⁻ 1000
Theoretical osmolarity (mOsm/liter) 2000
pH: 7.0 – 8.5

BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.

PHARMACEUTICAL FORM AND CONTENT
Sterile, pyrogen-free infusion solution.
Type I glass vial (Ph. Eur.), with butyl rubber stopper and aluminum flip-off seal.
Capacities:
50 ml vial;
100 ml vial;
250 ml vial;
500 ml vial;
50 ml in 100 ml vial;
100 ml in 250 ml vial;
250 ml in 500 ml vial.

MARKETING AUTHORIZATION HOLDER
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Via De Ambrosiis, 2
Novi Ligure (AL) - Italy

MANUFACTURER
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Via De Ambrosiis, 2
Novi Ligure (AL) - Italy
AIFA determination of 20/02/2013.
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.

INSTRUCTIONS FOR USE

Sodio Bicarbonato Bioindustria L.I.M. 10 mEq/10 ml concentrate for solution for infusion

PHARMACOTHERAPEUTIC CATEGORY
Electrolyte solutions.

THERAPEUTIC INDICATIONS
Treatment of:

Cardiac arrest
Metabolic acidosis
Shock
Poisoning due to barbiturates, salicylates, and methanol
Hemolytic and rhabdomyolytic syndromes
Hyperuricemia
Intestinal bicarbonate losses (due to diarrhea).

CONTRAINDICATIONS

Hypersensitivity to the active substance or to any of the excipients;
metabolic or respiratory alkalosis, especially if hypochloremic (vomiting, gastrointestinal losses, diuretic therapy);
hypocalcemia.

PRECAUTIONS FOR USE
Use with caution in patients with congestive heart failure, severe renal insufficiency, and in clinical conditions associated with edema and salt retention; in patients receiving cardiac inotropic drugs or corticosteroid or corticotropin therapy.
Sodium salts should be administered cautiously in patients with hypertension, cardiac insufficiency, peripheral or pulmonary edema, reduced renal function, pre-eclampsia, or other conditions associated with sodium retention (see Interactions).
During infusion, it is advisable to monitor fluid balance, electrolytes, plasma osmolarity, and acid-base balance, correcting, if necessary, any potassium or calcium depletion to prevent tetany.

INTERACTIONS
Inform your doctor or pharmacist if you have recently taken any other medicines,
including those without a prescription.
Corticosteroids are associated with sodium and water retention, leading to edema and hypertension: therefore, caution is required when administering sodium salts concomitantly with corticosteroids (see Precautions for Use).
Sodium bicarbonate increases the renal clearance of tetracyclines.
Concomitant administration of sodium bicarbonate and drugs promoting potassium excretion increases the risk of hypochloremic alkalosis.
Sodium bicarbonate increases the half-life and thus the duration of action of basic drugs such as quinidine, ephedrine, and pseudoephedrine.

SPECIAL WARNINGS
The solution must be clear, colorless, and free from visible particles. Use immediately after opening the container. The container is intended for single, uninterrupted administration; any residual solution must not be used.

Pregnancy and breastfeeding
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Consult your doctor or pharmacist before taking any medicine.
There are no available data on possible adverse effects of the medicine when administered during pregnancy or breastfeeding, or on reproductive capacity.
Therefore, the medicine should not be used during pregnancy or breastfeeding unless strictly necessary and only after careful assessment of the risk/benefit ratio.

Effects on ability to drive vehicles and use machinery
The medicine does not impair the ability to drive vehicles or operate machinery.
Important information about certain excipients: none.

DOSAGE, ROUTE AND DURATION OF ADMINISTRATION
The medicine is a hypertonic solution relative to blood and must be administered intravenously with caution and at a controlled infusion rate only after dilution to isotonicity (approximately 1.5% sodium bicarbonate, corresponding to about 16 mEq of bicarbonate per 100 ml) with compatible solutions (see end of this section).
The solution may be administered undiluted intravenously only in cases of cardiac arrest.
The medicine must not be used unless specifically prescribed.
In general, dosage depends on age, weight, clinical condition, electrolyte profile, acid-base balance, and osmolarity of the patient, aiming to restore normal pH and electrolyte values (in shock, hemolytic and rhabdomyolytic syndromes, and bicarbonate losses) or to alkalinize urine in cases of poisoning or hyperuricemia (urine pH of at least 7.0).

Specifically:

Cardiac arrest
50 to 100 mEq as bolus, followed by 50 mEq every 5–10 minutes according to acid-base monitoring results.

Acute and subacute forms of metabolic acidosis

Adults
Initial dose of 2 to 5 mEq/kg body weight over 4–8 hours, depending on severity of acidosis. The dose should then be adjusted based on blood bicarbonate levels or blood gas analysis results (increase of 20–22 mmol/L).

Children
Initial dose of 1 mEq/kg administered by slow intravenous infusion, diluting the solution to 0.5 mEq/ml, up to a maximum dosage of 8 mEq/kg body weight per day, to avoid excessive reduction in cerebrospinal pressure and possible intracranial hemorrhage.
The safety and efficacy of sodium bicarbonate in children have not been established.

Elderly
In elderly patients over 60 years of age, the maximum daily dose is 90–100 mEq of bicarbonate.
It is advisable NOT to achieve full correction of acidosis within the first 24 hours to avoid alkalosis due to excessive respiratory overcompensation.

Incompatibilities with Sodio Bicarbonato Bioindustria L.I.M.
If used to dilute drugs, consult the pharmacist, if available, before adding any additive drugs; always consider the characteristics of the products to be added; use aseptic techniques. In case of adverse reaction, discontinue administration.
Do not use with solutions containing noradrenaline, dobutamine, or calcium.

Solutions suitable for dilution of Sodio Bicarbonato Bioindustria L.I.M.
5% Glucose – 0.9% Sodium chloride (physiological saline) or other compatible solutions.

BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Dilute the solution immediately after opening the container; the diluted solution must be used immediately. The solution must be clear, colorless, and free from visible particles. The container is intended for single, uninterrupted administration; any residual solution must not be used.
Do not use the medicine if the solution is not clear and colorless or contains particles.
Adopt all usual precautions to maintain sterility before and during intravenous infusion.

OVERDOSE
Symptoms
Excessive administration of sodium bicarbonate solutions may lead, depending on the patient's clinical condition, to alkalemia, hypernatremia, and/or hypervolemia.
Hypernatremia and excessive sodium retention, especially when renal sodium excretion is impaired, may cause dehydration of internal organs, particularly the brain, and accumulation of extracellular fluid leading to edema affecting cerebral, pulmonary, and peripheral circulation, possibly resulting in pulmonary and peripheral edema.
Symptoms of alkalosis include muscle weakness associated with potassium depletion, muscle hypertonia, muscle spasms, and tetany, which may be particularly evident in hypocalcemic patients.

Treatment
Immediately discontinue the infusion and initiate corrective therapy to reduce plasma levels of excess ions and restore, if necessary, acid-base balance (see Precautions for Use).
The patient should be closely monitored for the onset of any signs and symptoms related to the administered drug, with appropriate symptomatic and supportive measures provided as needed.
In cases of severe hypernatremia, loop diuretics may be used.
Serum sodium levels exceeding 200 mmol/L may require dialysis.
Hyperirritability and tetany associated with alkalosis may be controlled by administration of adequate doses of calcium gluconate. In cases of severe alkalosis, administration of ammonium chloride is recommended, except in patients with liver disease.
In case of accidental ingestion/overdose of Sodio Bicarbonato Bioindustria L.I.M., contact a doctor immediately or go to the nearest hospital.
If you have any doubts about the use of Sodio Bicarbonato Bioindustria L.I.M., consult your doctor or pharmacist.

UNDESIRABLE EFFECTS
Like all medicines, Sodio Bicarbonato may cause adverse effects, although not everyone experiences them.
The following are adverse effects associated with Sodio Bicarbonato. There are insufficient data to determine the frequency of individual listed effects.

Disorders of water and electrolyte balance
Alkalemia, hypernatremia, hypervolemia, hyperosmolarity.

Systemic disorders and administration site conditions
Fever, infusion site infection, pain or local reaction, venous irritation, venous thrombosis or phlebitis, chemical cellulitis with tissue necrosis due to accidental extravasation into soft tissues.

BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Following the instructions in this leaflet reduces the risk of adverse effects.
If any of the adverse effects worsens, or if you notice any adverse effect not listed in this leaflet, inform your doctor or pharmacist.

EXPIRY DATE AND STORAGE
Expiry date: see the date printed on the packaging.
The expiry date refers to the product stored unopened and under recommended conditions.
Caution: do not use the medicine after the expiry date stated on the packaging.

Storage conditions
Store in the original packaging and in a tightly closed container. Do not refrigerate or freeze.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.
Keep the medicine out of the reach and sight of children.

COMPOSITION
10 ml of solution contain:
Active substance: sodium bicarbonate 0.84 g
mEq/10 ml Na 10
HCO₃⁻ 10
Excipients: water for injections
pH: 7.0 – 8.5

PHARMACEUTICAL FORM AND CONTENT
Concentrate for solution for infusion, sterile and pyrogen-free.
Type I neutral glass vials of 10 ml.
Carton containing 10 vials.

MARKETING AUTHORIZATION HOLDER
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Via De Ambrosiis, 2
Novi Ligure (AL) – Italy

MANUFACTURER
BIOINDUSTRIA Laboratorio Italiano Medicinali S.p.A.
Via De Ambrosiis, 2
Novi Ligure (AL) – Italy
AIFA determination of 20/02/2013