Treatment of acute symptomatic hypocalcaemia

The normal concentration of calcium in plasma is within the range of 2.25
- 2.62 mmol per litre. Treatment should be aimed at restoring this level.
During therapy, serum calcium levels should be monitored closely.
Posology
Adults:
The usual initial dose in adults is 10 ml of 10% w/v Calcium Gluconate Inj.,
corresponding to 2.25 mmol of calcium.
If necessary, the dose may be repeated, depending on the patient's clinical
condition. Subsequent doses should be adjusted according to the actual
serum calcium level.
Paediatric population(< 18 years):
The dose and the route of administration depend on the degree of
hypocalcaemia and the nature and severity of the symptoms. In the case
of mild neuromuscular symptoms oral calcium administration should be
preferred.

The following table gives usual initial dosage values for guidance:

This corresponds approximately to:
Infants, toddlers and children up to 3 years:
. 0.4 . 1 ml/kg body weight ( 0.09 . 0.23 mmol of calcium per kg body
weight) for infants, toddlers and children up to 3 years.
Children 4 to 12 years
. 0.2 . 0.5 ml/kg body weight ( 0.05 . 0.11 mmol of calcium per kg body
weight) for children from 4 to 12 years.
In cases of severe symptoms of hypocalcaemia, e.g. cardiac symptoms,
higher initial doses (up to 2 ml per kg body weight,  0.45 mmol calcium
per kg body weight) may be necessary for a quick restoration of a normal
serum calcium level.
Also, if necessary, the dose may be repeated, depending on the patient�fs
clinical condition. Subsequent doses should be adjusted according to the
actual serum calcium level.
Intravenous therapy should be followed by oral administration if indicated,
e.g. in cases of calciferol deficiency.
Adolescents > 12 years
For patients above 12 years of age the adult dosages should be applied.
Elderly patients:
Although there is no evidence that tolerance of is directly affected by
advanced age, factors that may sometimes be associated with ageing,
such as impaired renal function and poor diet, may indirectly affect tolerance
and may require a reduction in dosage.
Method of administration
The patient should be in the lying position and should be closely observed
during injection. Monitoring should include heart rate or ECG.
Adults:
Intravenous use or intramuscular use.
Because of the risk of local irritation, deep intramuscular injections should
only be performed if slow intravenous injection is not possible.
Care should be taken to administer the intramuscular injections sufficiently
deep intramuscularly, preferably into the gluteal region (see sections
4.4 and 4.8).
In the case of adipose patients a longer needle will have to be chosen for
safe positioning of the injection into the muscle and not into the adipose
tissues.
If repeated injections are necessary, the injection site should be changed
every time.
The intravenous administration rate should not exceed 5 ml (1,13 mmol of
calcium) per minute.
Paediatric population (< 18 years):
Only slow intravenous injection or intravenous infusion (both after dilution),
in order to achieve sufficiently low administration rates and to avoid
irritation/necrosis in case of accidental extravasation.
Intramuscular injections should not be performed in children.

. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 . Hypercalcaemia (e.g. in patients with hyperparathyroidism, hypervitaminosis D, decalcifying malignancies, renal insufficiency, immobilisation osteoporosis, sarcoidosis, milk-alkali syndrome), . Hypercalciuria, . Intoxication with cardiac glycosides, . Therapy with cardiac glycosides The only exception may be that intravenous calcium administration is imperative for treatment of severe hypocalcaemia symptoms putting the patient at immediate vital risk, if safer therapeutic alternatives are not available and calcium administration via the oral route is not possible (see also sections 4.4 and 4.5). . Concomitant use of ceftriaxone and intravenous calcium-containing products is contraindicated in premature neonates and neonates (. 28 days of age). Ceftriaxone should not be used in premature neonates and neonates (. 28 days of age) if they are receiving (or are expected to receive) calcium-containing intravenous products.

Special warnings
In the exceptional case of intravenous administration of calcium gluconate
to patients receiving cardiac glycosides, adequate cardiac monitoring
is mandatory and emergency treatment of cardiac complications
such as serious arrhythmias must be available.

Calcium salts should only be used with caution and after careful establishment
of the indication in patients with nephrocalcinosis, heart diseases,
sarcoidosis (Boeck's disease), in patients receiving epinephrine (see
section 4.5), or in the elderly.
Renal impairment may be associated with hypercalcaemia and secondary
hyperparathyroidism. Therefore, in patients with renal impairment, parenteral
calcium should be administered only after careful assessment of
the indication and the calcium-phosphate balance should be monitored.
Patients receiving ceftriaxone
In patients of any age ceftriaxone must not be mixed or administered
simultaneously with any calcium-containing intravenous solutions even
via different infusion lines or different infusion sites (see section 6.2).
Cases of fatal reactions with calcium-ceftriaxone precipitates in lungs and
kidneys in premature and full-term newborns aged less than 1 month have
been described.
However, in patients older than 28 days of age ceftriaxone and calciumcontaining
solutions may be administered sequentially one after another
if infusion lines at different sites are used or if the infusion lines are
replaced or thoroughly flushed between infusions with physiological saltsolution
to avoid precipitation.
Sequential infusions of ceftriaxone and calcium-containing products must
be avoided in case of hypovolaemia.
Precautions for use
Solutions containing calcium should be administered slowly to minimise
peripheral vasodilation and cardiac depression.
Intravenous injections should be accompanied by heart rate or ECG control
because bradycardia with vasodilatation or arrhythmia can occur
when calcium is administered too quickly.
In paediatric patients, 10% w/v Calcium Gluconate Inj. should not be
injected intramuscularly but only slowly intravenously.
Patients receiving calcium salts should be monitored carefully to ensure
maintenance of correct calcium balance without tissue deposition.
Plasma levels and urinary excretion of calcium should be monitored when
high-dose parenteral calcium is administered.
Calcium is insoluble in adipose tissue and may therefore cause infiltration
and subsequent abscess formation, tissue indurations and necrosis if accidently
injected into the adipose tissue.
After perivascular or superficial intramuscular injection local irritation,
possibly followed by skin ablation or tissue necrosis, may occur (see also
section 4.8). Extravasation must be avoided; the injection site should be
monitored carefully.
High Vitamin D intake should be avoided.

Cardiac glycosides
The effects of digoxin and other cardiac glycosides may be potentiated by
calcium, which may result in serious toxicity. Therefore, intravenous
administration of calcium preparations to patients under therapy with
cardiac glycosides is contraindicated. The only exception may be that
intravenous calcium administration is imperative for treatment of severe
hypocalcaemia symptoms putting the patient at immediate vital risk, if
safer therapeutic alternatives are not available and calcium administration
via the oral route is not possible (see sections 4.3 and 4.4).
Epinephrine
Co-administration of calcium and epinephrine attenuate epinephrine's �adrenergic
effects in postoperative heart surgery patients (see section
4.4).
Magnesium
Calcium and magnesium mutually antagonise their effects.
Calcium antagonists
Calcium may antagonise the effect of calcium antagonists (calcium channel
blockers).
Thiazide diuretics
Combination with thiazide diuretics may induce hypercalcaemia as these
medicinal products reduce renal calcium excretion.
Interaction with ceftriaxone
See sections 4.4 and 6.2

Pregnancy
Calcium passes across the placental barrier and its concentration in foetal
blood is higher than in maternal blood.
10% w/v Calcium Gluconate Inj. should not be used during pregnancy
unless clearly necessary. The administered dose should be carefully calculated,
and the serum calcium level regularly evaluated in order to avoid
hypercalcaemia, which may be deleterious for the foetus.
Breast-feeding
Calcium is excreted in breast milk This should be borne in mind when
administering calcium to women who are breast-feeding their infants.fS

Not relevant.

The frequency of undesirable effects listed below is defined using the following convention:
Very common .1/10
Common .1/100 to <1/10
Uncommon .1/1,000 to <1/100
Rare .1/10,000 to <1/1,000
Very rare < 1/10,000
Not known Frequency cannot be estimated from the available
data
Cardiovascular and other systemic undesirable effects are likely to occur
as symptoms of acute hypercalcaemia resulting from intravenous overdose
or too rapid intravenous injection. Their occurrence and frequency is
directly related to the administration rate and the administered dose.
Cardiac disorders
Not known: Bradycardia, cardiac arrhythmia
Vascular disorders
Not known: Hypotension, vasodilatation, circulatory collapse (possibly
fatal), flushing, mainly after too rapid injection.
Gastrointestinal disorders
Not known: Nausea, vomiting
General disorders and administration site conditions
Not known: Heat sensations, sweating
Not known: Intramuscular injection may be accompanied by pain sensations
or erythema
Adverse reactions only occurring with improper administration technique:
If intramuscular injection is not performed sufficiently deep intramuscularly,
infiltration into the adipose tissue may occur with subsequent
abscess formation, tissue induration, and necrosis.
Calcinosis cutis, possibly followed by skin ablation and necrosis, due to
extravasation, has been reported.
Reddening of skin, burning sensation or pain during intravenous injection
may indicate accidental perivascular injection, which may lead to tissue necrosis.

Reporting of suspected adverse reactions:
Reporting of suspected adverse reactions after authorisation of the medicinal
product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected
adverse reactions via the national reporting system:
Vigilance and Crisis Management Executive Directorate
Saudi Arabia
Fax : 011 2057662
Email : npc.drug@sfda.gov.sa
Website : www.sfda.gov.sa/npcling

Symptoms
Symptoms of hypercalcaemia may include: anorexia, nausea, vomiting,
constipation, abdominal pain, polyuria, polydipsia, dehydration, muscle
weakness, renal calcification, drowsiness, confusion, hypertension and, in
severe cases, cardiac arrhythmia up to cardiac arrest, and coma.
If intravenous injection is too rapid, symptoms of hypercalcaemia may
occur as well as a chalky taste, hot flushes and hypotension.
Emergency treatment, antidotes
Treatment should be aimed at lowering the elevated plasma calcium concentration.
Initial management should include rehydration and, in severe hypercalcaemia,
it may be necessary to administer isotonic sodium chloride solution
by intravenous infusion to expand the extracellular fluid. Calcitonin
may be given to lower the elevated serum calcium concentration.
Furosemide may be administered to increase calcium excretion but thiazide
diuretics should be avoided as they may increase renal absorption of
calcium.
Haemodialysis or peritoneal dialysis may be considered where other measures
have failed and where the patient remains acutely symptomatic.
Serum electrolytes should be carefully monitored throughout treatment of
overdose.

Pharmacotherapeutic group: Solutions affecting the electrolyte balance,
electrolytes.
ATC-code: B05B B01.
Calcium is the most abundant mineral in the human organism (approx. 1.5
% of the entire body weight). More than 99% of the body�s total calcium
are located in bones and teeth, approx. 1% are dissolved in intra- and
extracellular fluid.
Calcium is necessary for the functional integrity of nerves and muscles. It
is essential for the muscle contraction, cardiac function and blood coagulation.
The physiological level of the plasma calcium concentration is maintained
at 2.25 � 2.62 mmol/l. As about 40-50 % of the plasma calcium is bound
to albumin, total plasma calcium is coupled to the plasma protein concentration.
The concentration of ionised calcium is between 1.23 and 1.43
mmol/l, regulated by calcitonin and parathormone.
Hypocalcaemia (total calcium below 2.25 mmol/l or ionised calcium below
1.23 mmol/l, respectively) may be caused by renal failure, vitamin D deficiency,
magnesium deficiency, massive blood transfusion, osteoblastic
malignant tumours, hypoparathyroidism, or intoxication with phosphates,
oxalates, fluorides, strontium or radium.
Hypocalcaemia may be accompanied by the following symptoms:
increased neuromuscular excitability up to tetany, paraesthesiae, carpopedal
spasms, spasms of smooth muscles e.g. in the form of intestinal
colic, muscle weakness, confusion, cerebral convulsive seizures and cardiac
symptoms like prolonged QT interval, arrhythmia and even acute
myocardial failure.
The therapeutic effect of parenteral calcium substitution is normalisation
of pathologically low serum calcium levels and thus relief of the symptoms
of hypocalcaemia.

Distribution
After injection the administered calcium shows the same distribution
behaviour as the endogenous calcium. About 45-50% of the total plasma
calcium is in the physiologically active ionised form, about 40-50% is
bound to proteins, mainly albumin, and 8-10% is complexed with anions.
Biotransformation
After injection the administered calcium adds to the intravascular calcium
pool and is handled by the organism in the same manner as the
endogenous calcium.
Elimination
Excretion of calcium occurs in the urine although a large proportion
undergoes renal tubular reabsorption.

 

Non-clinical data reveal no special hazard for humans based on conventional
studies of safety pharmacology, repeated dose toxicity, genotoxicity,
carcinogenic potential, toxicity to reproduction and development.�

Calcium-d-saccharate 4 H2O,
Water for injections@

Calcium salts can form complexes with many drugs and this may result in
a precipitate.
Calcium salts are incompatible with oxidising agents, citrates, soluble carbonates,
bicarbonates, oxalates, phosphates, tartrates and sulphates.
Physical incompatibility has also been reported with amphotericin,
cephalothin sodium, ceftriaxone (see section 4.4), novobiocin sodium,
prochlorperazine and tetracyclines.
This medicinal product must not be mixed with other medicinal products
except those mentioned in section 6.6 or unless compatibility has been
satisfactorily demonstrated.zirPCGJz

Unopened 3 years After dilution When diluted to 10 mg/ml, according to directions, with the recommended infusion fluids (i.e. sodium chloride 9 mg/ml (0,9%) solution for injection or glucose 50 mg/ml (5%) solution for injection) physical in-use stability has been demonstrated for 48 hours, when stored at room temperature. From a microbiological point of view, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8� C, unless dilution has taken place in controlled and validated aseptic conditions.

Do not store above 25�C
For storage conditions of the diluted medicinal product, see section 6.3.//translate.go

10 ml LDPE ampoule packed in cardboard box.
Pack size: 20 ampoules.
Not all pack sizes may be marketed.core�

Disposal
No special requirements for disposal.
Handling
The product is intended for single use only. Discard any unused solution.
The medicinal product should be visually inspected for particulate matter,
discolouration and the integrity of the container prior to use.
The solution should only be used if it is clear, colourless to light brown
aqueous solution, practically free from particles and the container is
undamaged.
Dilution
For intravenous infusion, 10% w/v Calcium Gluconate Inj. may be diluted
1:10 to a concentration of 10 mg/ml with the following two infusion fluids:
sodium chloride 9 mg/ml (0.9%) solution for injection or glucose 50
mg/ml (5%) solution for injection. When diluted with these recommended
infusion fluids, the resulting solutions are intended for immediate single
use. Dilution should be performed under controlled and validated
aseptic conditions. After mixing, the container should be gently agitated
to ensure homogeneity.