Why are potassium phosphate-sodium phosphate tabs recommended to be taken with food?

Why are potassium phosphate-sodium phosphate tabs recommended to be taken with food?

Comment by InpharmD Researcher

There is very little research that supports the reasoning behind administering phosphate supplements with food. One review article mentions the rapid absorption of oral phosphate in the small intestine which can lead to gastrointestinal (GI) side effects and another much older study recorded the side effects from oral sodium phosphate on an empty stomach during colonoscopy prep as mainly GI related i.e. bloating, cramps, abdominal pain, nausea and vomiting. It can then be inferred that the recommendation to take sodium and potassium phosphate supplements with food is mainly to help with absorption and decrease GI related side effects. However, more research is needed to make a definite claim to this practice.

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Background

A 2020 review article on the approach to patients with hypophosphataemia noted that oral phosphate is rapidly absorbed in the small intestine and excreted in the urine within several hours. The review also mentioned that oral phosphate can cause gastrointestinal adverse effects, including diarrhea and abdominal pain, and that the rate of absorption is directly related to dietary phosphate intake. These factors may support administering phosphate tablets with food to improve absorption and help reduce gastrointestinal side effects. [1]

Relevant Prescribing Information

Dosage and Administration [2]
K-PHOS® NEUTRAL tablets should be taken with a full glass of water, with meals and at bedtime. Adults: One or two tablets four times daily; Pediatric Patients over 4 years of age: One tablet four times daily. For Pediatric Patients under 4 years of age, use only as directed by a physician.

Adverse reactions [2]
Gastrointestinal upset (diarrhea, nausea, stomach pain and vomiting) may occur with phosphate therapy. Also, bone and joint pain (possible phosphate-induced osteomalacia) could occur. The following adverse effects may be observed (primarily from sodium or potassium): headaches; dizziness; mental confusion; seizures; weakness or heaviness of legs; unusual tiredness or weakness; muscle cramps; numbness, tingling, pain, or weakness of hands or feet; numbness or tingling around lips; fast or irregular heartbeat; shortness of breath or troubled breathing; swelling of feet or lower legs; unusual weight gain; low urine output; unusual thirst.

Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Why are potassium phosphate-sodium phosphate tabs recommended to be taken with food?

Level of evidence

D - Case reports or unreliable data Read more→

Please see Table 1 for your response.

Biochemical Effects of Oral Sodium Phosphate

Design

Prospective study

N= 7

Objective

To monitor serum and urine biochemical changes after oral sodium phosphate cleansing in healthy adults

Study Groups

All participants (N= 7)

Inclusion Criteria

Healthy, asymptomatic adults aged 21-41 years without allergy to oral sodium phosphate or history of gastrointestinal surgery, heart failure, renal failure, ascites, or other chronic bowel, liver, renal, or cardiopulmonary disorders

Exclusion Criteria

Allergy or sensitivity to oral sodium phosphate, prior gastrointestinal surgery, known or suspected gastrointestinal obstruction, heart failure, renal failure, ascites, other chronic bowel, liver, renal, or cardiopulmonary disorders, pregnancy, or lactation

Methods

Sodium phosphate 45 ml diluted in 45 ml water was given orally at baseline and 12 hr later. Serum and urine samples were collected at various intervals to analyze calcium, ionized calcium, phosphorus, sodium, potassium, creatinine, PTH, and cAMP. Blood pressure, pulse, and respiratory rate were recorded every 2 hr for 24 hr. Symptom questionnaires were completed using visual analog scales at baseline, 6,12,18 and 24hrs after challenge.

Duration

24 hours after the first sodium phosphate challenge

Outcome Measures

Primary: Biochemical changes in serum and urine

Secondary: Symptoms reported by participants

Baseline Characteristics

All participants (N= 7)

Age, years

21-41

Gender

3 men, 4 women

Results

Phosphorus (mg/dl)

Calcium (mg/dl)

Ionized Calcium (mg/dl)

PTH (pg/ml)

cAMP (nmol/liter)

Baseline

3.7 ±0.2

9.4 ± 0.1

5.2 ± 0.0

189 ± 9.9

4.9 ± 1.2

Mean Peak

7.6 ± 0.1

317 ± 19.5

12.9 ± 2.4

Mean Nadir

8.4 ± 0.1

4.6 ± 0.1

P-value

0.006

<0.001

<0.001

<0.001

0.02

Symptom Score

	Baseline	6hr	12hr	18hr	24hr
Bloating	2.7 ± 0.6	19.1 ± 8.6	5.7 ± 1.7	16.6 ± 8.2	7.3±2.9
Cramps	2.9 ± 0.6	25.9 ± 8.7	3.7 ± 0.8	20.9 ± 9.2	6.6±6.8
Abdominal Pain	2.6 ± 0.4	19.0 ± 8.0	5.7 ± 1.9	16.6 ± 8.2	6.4 ± 2.7
Nausea	2.6 ± 0.5	17.9 ± 5.8	4.0 ± 0.8	26.7 ± 11.9	3.4 ± 0.6
Vomiting	2.6 ± 0.5	3.0 ± 0.8	4.0 ± 0.7	10.3 ± 5.5	3.4 ± 0.6
Dizziness	2.7 ± 0.6	4.1 ± 1.1	4.0 ± 0.7	10.3 ± 5.5	3.3 ± 0.6
Light-headedness	2.4 ± 0.7	4.4 ± 1.0	4.0 ± 0.7	12.7 ± 5.6	3.1 ± 0.6
Palpitations	2.3 ± 0.7	3.4 ± 0.9	4.1 ± 0.7	4.1 ± 0.9	3.3 ± 0.5
Weakness	2.7 ± 0.8	3.6 ± 0.8	4.3 ± 0.7	10.0 ± 5.2	4.6 ± 1.1
Rash	3.0 ± 0.8	3.3 ± 0.9	4.4 ± 0.9	4.1 ± 0.9	3.1 ± 0.7
Sweating	3.1 ± 1.0	3.0 ± 0.9	4.6 ± 0.8	11.2 ± 4.9	3.1 ± 0.7
Overall Discomfort	1.0 ± 0.0	2.0 ± 0.2	1.4 ± 0.2	2.1 ± 0.3	1.6 ± 0.2

Adverse Events

Significant symptoms included bloating, cramps, abdominal pain, and nausea. One subject passed a renal calculus 17 days after the study.

Study Author Conclusions

Significant hypocalcemia and hyperphosphatemia after oral sodium phosphate raises concern about its use in normal individuals. Oral sodium phosphate should not be administered in patients with cardiopulmonary, renal, or hepatic disease

Critique

The study's small sample size and the limited duration of monitoring may not fully capture the long-term effects or rare adverse events. The study provides valuable insights into the biochemical changes induced by oral sodium phosphate, but the findings may not be generalizable to a larger population or those with underlying health conditions.

References:
[1] DiPalma JA, Buckley SE, Warner BA, Culpepper RM. Biochemical effects of oral sodium phosphate. Dig Dis Sci. 1996;41(4):749-753. doi:10.1007/BF02213131