Dibasic pot phosphate
Adverse Effects and Treatment
Excessive administration of intravenous phosphate
causes hyperphosphataemia, particularly in patients
with renal failure. Hyperphosphataemia leads in
turn to hypocalcaemia, which may be severe, and to
ectopic calcification, particularly in patients with in-
itial hypercalcaemia. Tissue calcification may cause
hypotension and organ damage and result in acute
renal failure. Hyperphosphataemia, hypocalcaemia,
and tissue calcification are rare after oral or rectal
phosphate administration (but see also below).
Adverse effects that may occur with the use of oral
phosphates include nausea, vomiting, diarrhoea, and
abdominal pain. When oral phosphates are being
used for indications other than their laxative effects.
diarrhoea may necessitate a reduction in dosage.
When administered rectally for bowel evacuation,
sodium phosphates may cause local irritation.
Phosphates are administered as the potassium or so-
dium salts or both: therefore, additional electrolyte
disturbances that may be expected on excessive ad-
ministration include hyperkalaemia, and hypemat-
raemia and dehydration.
Treatment of adverse effects involves withdrawal of
phosphate, general supportive measures, and correc-
tion of serum-electrolyte concentrations, especially
calcium. Measures to remove excess phosphate such
as oral phosphate binders and haemodialysis may be
required .
Effects on electrolytes. Although less common than after
intravenous therapy, hyperphosphataemia accompanied by
hypocalcaemia or other severe electrolyte disturbances and
resulting in tetany and even death has been reported on a
number of occasions following the use of phosphate enemas.
Similar effects have also been reported with the use of oral
phosphate laxatives in Infants or children and those with
renal impairment, have often been the subjects of these ad-
verse effects. Soft tissue calcification appears to occur rarely
with oral phosphate, but nephrocalcinosis has been reported
in children with hypophosphataemic rickets treated with cal-
citriol and phosphate supplements, and was found to be asso-
ciated with the phosphate dose.
Local toxicity. Rectal gangrene has been associated with the
use of phosphate enemas in elderly patients and was believed
to be due to a direct necrotising effect of the phosphate on the
rectum.
Precautions
Phosphates should not generally be administered to
patients with severely impaired renal function. They
should be avoided in patients who may have low
serum-calcium concentrations, as these may de-
crease further, and in patients with infected phos-
phate renal calculi. Potassium phosphates should be
avoided in patients with hyperkalaemia and sodium
with congestive heart failure, hypertension, and
oedema. Serum electrolytes and renal function
should be monitored during therapy, particularly if
phosphates are administered parenterally.
Oral or rectal sodium phosphate preparations for
bowel evacuation should not be used in patients with
gastro-intestinal obstruction, inflammatory bowel
disease, and conditions where there is likely to be
increased colonic absorption. They should be used
cautiously in elderly and debilitated patients, and in
those with pre-existing electrolyte disturbances.
Interactions
Oral phosphate supplements should not be adminis-
tered concomitantly with aluminium, calcium, or
magnesium salts as these will bind phosphate and
reduce its absorption. Vitamin D increases the gas-
tro-intestinal absorption of phosphates and therefore
increases the potential for hyperphosphataemia.
Hyperphosphataemia, hypocalcaemia, and hyper-
natraemia are more likely to occur with phosphate
enemas or oral laxatives if these are administered to
patients receiving diuretics or other drugs that may
affect serum electrolytes. The risk of ectopic calcifi-
cation may be increased by concurrent use of calci-
um supplements or calcium-containing antacids.
The risk of hyperkalaemia is increased if potassium
phosphates are coadministered with drugs that can
increase serum-potassium concentrations.
Pharmacokinetics
Approximately two-thirds of ingested phosphate is
absorbed from the gastro-intestinal tract. Excess
phosphate is predominantly excreted in the urine,
the remainder being excreted in the faeces.
Human Requirements
Phosphorus requirements are usually regarded to be
equal to those of calcium.
Most foods contain adequate amounts of phosphate,
particularly meat and dairy products, hence defi-
ciency is virtually unknown except in certain disease
states, in patients receiving total parenteral nutrition.
or in those who have received phosphate-binding
agents for prolonged periods: for further details see
under Hypophosphataemia.
In the United Kingdom dietary reference values (DRV)' and
in the United States dietary reference intakes including rec-
ommended dietary allowances (RDA)' have been published
for phosphorus. In the UK the reference nutrient intake (RNI)
for adults is approximately 550 mg (17.5 mmol) daily; no ad-
ditional amount is recommended for pregnancy although an
additional amount of about 440 mg (14.3 mmol) daily is ad-
vised during lactation. In the USA the RDA is 1250 mg daily
for those aged 9 to 18 years and 700 mg daily in adults, no
increase in RDA is recommended during pregnancy and lac-
tation.
Uses and Administration
Phosphates are used in the management of hy
phosphataemia caused by phosphate deficiency
hypophosphataemic states . Doses of up to
100 mmol of phosphate daily may be given
mouth. The intravenous route is seldom necessary.
but a dose of up to 9 mmol of monobasic potassium
phosphate may be given over 12 hours and repeated
every 12 hours as necessary for severe hypophos
phataemia (see also below). Plasma-electrolyte con
centrations, especially phosphate and calcium, and
renal function should be carefully monitored. Re
duced doses may be necessary in patients with im-
paired renal function. Phosphate supplements are
used in total parenteral nutrition regimens; typical
daily requirements are 20 to 30 mmol of phosphate.
Phosphates act as mild osmotic laxatives
when administered by mouth as dilute solutions or
by the rectal route. Phosphate enemas or concentrat-
ed oral solutions are used for bowel cleansing prior
to surgery or endoscopy procedures. Preparations
typically combine monobasic and dibasic sodium
phosphates but the composition and dosage do vary
slightly. Phosphate enemas act within 2 to 5 min-
utes, whereas the oral solutions act within 30 min-
utes to 6 hours.
Phosphates have also been employed for other uses.
They lower the pH of urine and have been given as
adjuncts to urinary antimicrobials that depend on an
acid urine for their activity. Phosphates have also
been employed for the prophylaxis of calcium renal
calculi; the phosphates reduce urinary excretion of
calcium thus preventing calcium deposition. A sug-
gested dose for both uses is 7.4 mmol of phosphate
four times daily by mouth,
Hypercalcaemia. Intravenous phosphates have been used
to lower plasma-calcium concentrations in hypercalcaemic
emergencies , but because of their potential to cause
serious adverse effects other drugs are now preferred. Oral
phosphates may be used to prevent gastro-intestinal absorp-
tion of calcium in the treatment of hypercalcaemia.
Hypophosphatemia. Phosphate salts are given in the
management of hypophosphataemia when a phosphate defi-
ciency is identified, as discussed in Uses and
Administration.
above. Intravenous phosphates are associated with serious
ad-
verse effects if hypophosphataemia is over-corrected, and
the
rise in serum-phosphorus concentration cannot be predicted
from a given dose. Consequently, it has been recommended
that intravenous phosphate be used cautiously in the treat-
ment of severe hypophosphataemia. However, some advo-
cate a more aggressive fixed-dose regimen in critically ill
patients
Ostomalacia. Vitamin D deficiency, or its abnormal me-
tabolism, is the most usual cause of osteomalacia and rickets
however, phosphate depletion may also contribute,
and phosphate supplementation may be given as appropriate.
RICKETS of PREMATURITY. Dietary deficiency of phosphorus is
unusual, but can occur in small premature infants fed exclu-
sively on human breast milk. The phosphate intake in
these infants appears to be inadequate to meet the needs of bone
mineralisation, and hypophosphataemic rickets can develop.
It has been proposed that this condition, variably called met-
abolic bone disease of prematurity, or rickets of prematurity.
could be prevented by giving phosphorus supplements to very
low-birth-weight babies ( less than about 1000 g) fed on breast
milk alone.' A suggested regimen is to add 10 to 15 mg of
phosphorus per 100 mL of feed (as buffered sodium phos-
phate) until the infant reached 2000 g. Concomitant calcium
and vitamin D supplementation are also recommended.' A
placebo-controlled study' in infants weighing less than
1250 g at birth confirmed that phosphate supplements (50 mg
daily) could prevent the development of the bone defects of
rickets of prematurity.