Treatment of Hypocalcemia

Acute hypocalcemia is an emergency that requires prompt attention. If symptoms of

neuromuscular irritability are present and carpopedal spasm is elicited on physical examination,
treatment with intravenous calcium is indicated until the signs and symptoms of hypocalcemia
subside. Approximately 100 mg of elemental calcium should be infused over a period of 10 to 20
minutes (Table 28-6). If this is not sufficient to alleviate the clinical findings of hypocalcemia, an
infusion of 100 mg/hour can be given to adults for several hours, with close monitoring of
calcium levels. In hypocalcemia associated with hypomagnesemia, magnesium replacement also
is required. Magnesium should be given intravenously, 100 mEq over 24 hours in the acute
setting. Because most of the parenteral magnesium is excreted in the urine, oral magnesium
oxide should be instituted as soon as possible to replete body stores. Special caution and reduced
doses are necessary when administering magnesium to patients in renal failure (see Disorders of
Magnesium Metabolism).
TABLE 28-6 -- Therapeutic Mineral Ion Preparations
AVAILABLE FORMULATIONS
Mineral Ion
Content
Compound

MW
*

mg/g mmol/g

Oral Preprations

Parenteral Preparations

Compoun
d

Mineral Ion
Mineral Ion
Compoun
Content
Content
d
mg/g mmol/g
mg/g
mmol/g

Calcium
Ca carbonate 100

400

10.0

1250 mg[]

500
mg

12.5
mmol

Ca
phosphate

310

383

9.6

1565 mg

600
mg

15.0
mmol

Ca acetate

158

253

6.3

668 mg[]

167
mg

4.2
mmol

Ca citrate

498

210

6.0

950 mg[]

200
mg

5.0
mmol

Ca lactate

218

130

4.6

650 mg[]

84
mg

2.1
mmol

Ca
glubionate

64

1.7

5 mL

115
mg

2.0
mmol

Ca gluconate 430

93

2.3

1000 mg[]

93
mg

2.3
mmol

Ca
gluceptate

82

2.0

488

10% soln

93
mg/10
mL

2.3
mmol/10
mL

22% soln

2.3
90 mg/5
mmol/10
mL
mL

AVAILABLE FORMULATIONS
Mineral Ion
Content
Compound

Ca chloride

MW
*

mg/g mmol/g

Oral Preprations
Compoun
d

Parenteral Preparations

Mineral Ion
Mineral Ion
Compoun
Content
Content
d
mg/g mmol/g
mg/g
mmol/g

147

273

6.8

Mg oxide

40

603

24.8

400 mg[]

241
mg

9.9
mmol

Mg
gluconate

450

54

2.2

500 mg

27
mg

1.1
mmol

Mg chloride 203

120

4.9

535 mg

64
mg

2.6
mmol

Mg sulfate

99

4.1

10% soln

273
mg/10
mL

20% soln

24
1.0
mg/mL mmol/mL

50% soln[]

49
2.0
mg/mL mmol/mL

soln

94
3.0
mg/mL mmol/mL

soln

94
3.0
mg/mL mmol/mL

11.2
mmol/mL

Magnesium

246

Phosphorus
Na/K
phosphate
(neutral)

Capsule

250
mg

8.1
mmol

K phosphate
(neutral)

Capsule

250
mg

8.1
mmol

Na
phosphate
(neutral)

Data from Drug Facts and Comparisons, 1995 ed. St. Louis: Facts and Comparisons.
MW, molecular weight; soln, solution.
*

Molecular weights (MW) shown are for the usual chemical form, including water molecules
(e.g., MgSO4 7 H2O).
Other formulations exist. Those shown are among those approved in the United States.
Phosphate preparations contain buffered mixtures of monobasic (H2PO4) and dibasic (HPO4)
ions; the phosphorus content therefore is specified in millimoles. Oral phosphates contain 7
mEq sodium and potassium per capsule (Na/K form) or 14 mEq potassium per capsule (K
form). Parenteral solutions typically contain 4 mEq of sodium or potassium per milliliter.

The treatment of hypocalcemia should be directed at the underlying disorder. In all cases,
replacement with exogenous calcium (1 to 3 g of elemental calcium daily, given orally) should
be instituted. Calcium carbonate is the least expensive formulation, but it requires acidification
for efficient absorption. This becomes important for patients with achlorhydria and for those in
whom gastric acid production is being suppressed with pharmacologic agents. Notable in this
respect is the acid-buffering capacity of calcium carbonate. It is recommended that patients take
their calcium carbonate supplements in divided doses of 1 g or less. The calcium should be taken
with food or citrus drinks to promote maximal absorption.
In cases of vitamin D deficiency or resistance, the metabolite of vitamin D chosen depends on
the underlying disorder. If impaired renal 1 hydroxylation is present, such as in renal failure,
hypoparathyroidism (or PTH resistance), or the vitamin Ddependent rickets syndromes,
metabolites that do not require this modification should be administered (calcitriol 0.25 to 1 ?
g/day or dihydrotachysterol 0.2 to 1 mg/day). If decreased intake or increased losses are the
problem, vitamin D should be administered and the treatment directed at the underlying disorder.
Initial repletion of stores can be undertaken with 50,000 IU of vitamin D daily for 2 to 3 weeks,
followed by weekly or bimonthly administration until the underlying disorder has been treated.
In patients with resistance to vitamin D, such as those taking phenytoin, high doses (50,000 IU
one to three times weekly) should be used as maintenance therapy. In other patients, once
treatment of the underlying disorder and repletion of body stores have been addressed, two
multivitamins (i.e., 800 IU) per day should provide sufficient maintenance therapy. In cases of
severe malabsorption, vitamin D can be administered parenterally.
Patients should be monitored closely, both to assess response to therapy and to prevent
therapeutic complications. Serum calcium should be monitored frequently (daily in profound
hypocalcemia, weekly in moderate hypocalcemia) for the first month of therapy. Concomitant
with resolution of the hypocalcemia, a decline in serum PTH should be observed as the
secondary hyperparathyroidism resolves. Measurement of serum PTH and assessment of 24-hour
urinary calcium excretion should be performed within 2 to 4 weeks after institution of therapy.
The urinary calcium measurement reflects the effect of therapy on the patient's ability to absorb
calcium and the net uptake of calcium by bone. A low urine calcium concentration indicates poor
adherence to a regimen, poor absorption of calcium, or increased uptake by bone. In addition, the
urine calcium level provides important information on which to base therapeutic modifications to
avoid nephrolithiasis.
Once normalization of serum and urinary calcium and a decrease in PTH levels have been
observed, a transition from aggressive replacement therapy to maintenance therapy should be
undertaken to prevent hypercalcemia and nephrolithiasis. These same parameters should be
monitored at 1 and 3 months after a dose change to assess the effect of the therapeutic
intervention. Monitoring of the alkaline phosphatase concentration can also be performed at this
time. Alkaline phosphatase levels may actually increase soon after treatment is started, because
of healing of the osteomalacic lesions; however, by 3 to 4 months after institution of therapy, a
clear downward trend should be observed. Alkaline phosphatase and PTH values may remain
elevated for 6 to 12 months after therapy begins; this should not be a cause for alarm, provided
that the levels are declining and that monitoring of the other parameters indicates that therapy is
effective.

The treatment of hypoparathyroidism is similar to that of vitamin D deficiency, with the

exception that these patients have impaired renal 1 hydroxylation of 25(OH)D and therefore
require treatment with 1-hydroxylated metabolites. PTH has been used experimentally for the
treatment of hypoparathyroidism, with twice-daily injections providing a better result than oncedaily administration.[453] This therapy controls hypocalcemia with lower urine calcium excretion
compared with calcium and calcitriol therapy, but it is expensive and requires parenteral
administration. Therefore, oral calcium and 1-hydroxylated vitamin D metabolites remain the
mainstay of therapy. Monitoring of serum and urinary calcium should be performed as in the
treatment of vitamin D deficiency.
Therapy in these patients is lifelong, and careful monitoring is required to avoid renal or
hypercalcemic complications. The aim of therapy should be to maintain serum calcium in the
low-normal range without causing frank hypercalciuria, to avoid nephrolithiasis and decrease in
GFR. Because PTH plays an important role in renal calcium reabsorption, difficulties are often
encountered in attaining these therapeutic goals. In such cases, renal calcium losses can be
minimized by the addition of a thiazide diuretic to the treatment regimen. As stated earlier, in
patients with PHP, the intact distal tubular reabsorption of calcium leads less often to
hypercalciuria and allows more aggressive treatment aimed at normalizing PTH levels, to protect
bones from the hyperparathyroid bone disease sometimes seen in PHP.
One of the frustrations often encountered in treating patients with hypoparathyroidism is the
fluctuating response to a seemingly stable therapeutic regimen. Episodes of hypercalcemia are
occasionally observed without any discernible cause. Because of this, serum calcium should be
monitored every 3 months to permit temporary withdrawal of calcitriol, should a hypercalcemic
trend be observed. The half-life of this metabolite is short, so that discontinuation for a few days
to 1 week, with subsequent resumption at a lower dose, is usually efficacious.
All patients receiving vitamin D metabolites and calcium need to be aware of potential
therapeutic complications. Importantly, the mild symptoms of hypercalcemia should be
emphasized to the patient. It is essential that these patients be aware that their calcium level
should be monitored more frequently during intercurrent illnesses that may affect their
absorption of calcium or their hydration status, and also on introduction of drugs such as
thiazides or loop diuretics that might change the dosing requirement, to prevent the development
of hypocalcemia or severe hypercalcemia.