Most people have no symptoms while others develop calcium deposits in the soft tissue. Severe hypophosphatemia in hospitalized patients. It appears that there is a correlation between the degree of hypophosphatemia and the severity of liver damage due to acetaminophen.87–89 The etiology of acetaminophen overdose-induced hypophosphatemia is multifactorial. Your healthcare provider will review all of your medicines with you. G. Liamis, H.J. (A) Summary of phosphate (Pi) metabolism for a normal adult in neutral phosphate balance. Herein, we review the clinical information of hypophosphatemia associated with specific drug treatment and discuss the underlying pathophysiology. Bitenc-Jasiejko A, Konior K, Gonta K, Dulęba M, Lietz-Kijak D. Pain Res Manag. In a study of normal human volunteers, it took ∼3 months for the combination of low phosphorus diet and antacids to diminish serum Pi levels to 1 mg/dl.38 Thus, prolonged high-dose therapy with these agents is associated with increased risk of hypophosphatemia even in patients with end-stage renal disease, an entity usually characterized by phosphate retention.39, Finally, hypophosphatemia related to prior antacid use is not infrequently observed in patients who undergo hepatic resection. Short-term reduction of the serum phosphorus concentration is modulated by intracellular Pi redistribution, while long-term hypophosphatemia is related to increased renal or intestinal Pi losses.3. Report of two cases, Diabetic ketoacidosis. SARS-CoV-2: influence of phosphate and magnesium, moderated by vitamin D, on energy (ATP) metabolism and on severity of COVID-19. NIH Normal total body phosphorus content in an average adult is 700 g (10 g/kg body weight), of which 85% is contained in skeleton, 14% in soft tissues, and only 1% in the extracellular fluid (Figure 1A). Musculoskeletal symptoms: weakness, bone pain. The fractional excretion of phosphate is generally in the range of 10–15%. Hypophosphatemia Is An Injectafer Side Effect With Possible Medical Complications Leading To Hospitalization Or Death (Posted by Tom Lamb at DrugInjuryWatch.com) Injectafer (ferric carboxymaltose) is an iron replacement injection approved by the FDA in 2013 for the treatment of iron deficiency anemia (IDA) in certain patients as an alternative to oral iron medications. K-Phos Neutral (phospha 250 neutral) Drug class: Phosphate Supplements. In a retrospective study, 21 out of 35 patients (67%) exhibited hypophosphatemia after major hepatic surgery. In plasma, phosphate is mainly present as inorganic phosphate (Pi), and this fraction is very small (<0.2% of total phosphate).3 However, body phosphate metabolism is regulated through plasma inorganic phosphate. Oxford University Press is a department of the University of Oxford. Awareness of this undesired effect of certain pharmaceutical agents on serum phosphorous concentrations facilitates a rational clinical management of a potentially life threatening disorder, especially in patients at high-risk for the development of hypophosphatemia, such as alcoholics. Secondary hyperparathyroidism due to diminished calcium levels might also play a contributing role in the development of hypophosphatemia in this setting.74,75, Volume expansion (e.g. If it was caused by malnutrition or lack of vitamin, you will be given the … It is related to the formation of Pi-containing intermediates of glycolytic metabolism.20 The source of this phosphate is the Pi in the extracellular fluid; as a result, serum phosphate levels fall rapidly. eCollection 2020. 2020 Sep 30;12(10):3001. doi: 10.3390/nu12103001. Indeed, hypophosphatemia occurred in 50% of patients after 48 weeks and in 61% of patients after 72 weeks of high dose (120 mg/day) adefovir therapy.65 On the contrary, adefovir at a daily dose of 10 mg, which is used for the treatment of hepatitis B, did not reduce the mean serum phosphate concentration.54, Finally, hypophosphatemia via FS has rarely been related to antibiotics (particularly tetracyclines and aminoglycosides), valproic acid and fumaric acid.66–69, The administration of both large doses of estrogens in patients with metastatic prostatic cancer and mestranol in oophorectomized women have been reported to cause hypophosphatemia due to decrease in renal phosphate reabsorption.70–72 Experimental data suggest that renal phosphate wasting and hypophosphatemia induced by estrogen are secondary to down-regulation of NaPi-IIa in the proximal tubule.73, Imatinib mesylate, a drug used in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors, causing tubulopathy and inappropriate phosphaturia can also induce hypophosphatemia. Acetazolamide is the most effective phosphaturic diuretic because phosphorus reabsorption mainly occurs in the proximal tubules.3,Thiazides and indapamide can produce an increase in the renal clearance of inorganic phosphate and hypophosphatemia.46,47 The underlying mechanisms may involve a direct effect of the diuretic on distal renal tubular reabsorption of phosphate, inhibition of carbonic anhydrase as well as changes in potassium and/or magnesium homeostasis. (B) Major determinants of serum phosphate. This review aims at a thorough understanding of the underlying pathophysiological mechanisms and risk factors of drug therapy-related hypophosphatemia thus allowing prevention and effective intervention strategies. Check the full list of possible causes and conditions now! Megapanou E, Florentin M, Milionis H, Elisaf M, Liamis G. Drug Saf. 2021 Jan 1;320(1):E2-E6. Mild-to-moderate use of such phosphate binders generally poses no threat to phosphate homeostasis because dietary ingestion greatly exceeds body needs. Interestingly, hypophosphatemia is the most frequent electrolyte disorder in patients with hyponatremia due to SIADH.48 Taking into account that numerous drugs can induce SIADH, they should also be considered as a potential cause of hypophosphatemia.77, Finally, increased renal phosphate excretion due to downregulation of Na–Pi-IIa co-transporter has been proposed as the possible explanation of acyclovir-induced hypophosphatemia.78,79, Metabolic acidosis induces renal wasting of phosphate disproportionate to its effect on mobilization of tissue phosphorus. Causes include alcoholism, refeeding in those with malnutrition, diabetic ketoacidosis, burns, hyperventilation, and certain medications. For example, parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF-23) decrease the absorption of phosphate in the proximal tubule, while 1,25-dihydroxyvitamin D3 increases tubular phosphate reabsorption. Mannitol is a non-reabsorbable polysaccharide that acts as an osmotic diuretic. It is known that the concurrent use of sodium 2-mercapto-ethanesulfonate (mesna), a synthetic thiol compound that detoxifies reactive ifosfamide metabolites, reduces the incidence of ifosfamide-induced hemorrhagic cystitis. But their use requires close monitoring because of the possibility of excessive calcium × phosphate product causing vascular calcification in dialysis patients taking calcium-containing binders. Complications may include seizures, coma, rhabdomyolysis, or softening of the bones. Cardiac symptoms: dyspnea, and orthopnea. The clinical manifestations of drug-induced hypophosphatemia are usually mild but might also be severe and potentially life-threatening. This review aims at a thorough understanding of the underlying pathophysiological mechanisms and risk factors of drug therapy-related hypophosphatemia thus allowing prevention and effective intervention strategies. The serum Pi concentration should be measured every 6 h because the response to phosphate supplementation is not predictable.8,98,99. Clinically significant toxicity appears to occur at a total dose above 100 g/m2.61 On the contrary, renal toxicity is moderate with a moderate dose of ifosfamide.62 Since ifosfamide-related phosphaturia is frequently observed, it should be considered as a herald of severe renal dysfunction.60 This renal phosphate loss, though, usually reversible may be chronic lasting up to 5 years).63, Clinically significant risk factors for ifosfamide-induced hypophosphatemia include the concurrent administration of another nephrotoxic agent, previous treatment with cisplatin, and the increased total dose of ifosfamide. 2005 Oct;118(10):1094-101. doi: 10.1016/j.amjmed.2005.02.014. Clinical features include muscle weakness, respiratory failure, and heart failure; seizures and coma can occur. Talk to our Chatbot to narrow down your search. Phosphorus is the sixth most abundant element in the body. In a series of 62 children who received ifosfamide 10 (16.1%) developed hypophosphatemia. Hypophosphatemia has repeatedly been associated with phosphate-binding antacids.38,39 In fact, absorption of phosphate can be blocked by commonly used over-the-counter aluminum-, calcium- and magnesium-containing antacids. Proper diagnostic approach of patients with low serum phosphorus concentrations should involve a detailed medical history with special attention to the recent use of medications. Phosphate is required by the red blood cells for producing 2,3-diphosphoglycerate which is used for releasing oxygen from the hemoglobin. The safest mode of therapy is oral given that overzealous intravenous phosphate therapy for hypophosphatemia has been reported to cause a precipitous fall in serum calcium concentration resulting in tetany, hypotension, renal failure and potentially fatal arrhythmias.95–97 Phosphate salts are available in skim milk (∼1g/l). NLM Hypophosphatemia: an update on its etiology and treatment. Hypophosphatemia is defined as a serum phosphate level of less than 2.5 mg/dL (0.8 mmol/L) in adults. This site needs JavaScript to work properly. Prophylaxis of Pain and Fractures within Feet in the Course of Osteoporosis: The Issue of Diagnosing. Am J Physiol Endocrinol Metab. Looking for medication to treat hypophosphatemia? It is well known that the increase in intracellular pH stimulates phosphofructokinase activity which in turn stimulates glycolysis.20 Taking into consideration that for a given extracellular pH, carbon dioxide penetrates cell membrane more readily than bicarbonate, respiratory alkalosis which raises intracellular pH more than similar degrees of metabolic alkalosis may lead to a more profound effect on serum Pi concentration.21. Renal and intestinal phosphate reabsorption is also mediated by multiple hormonal and non-hormonal factors. USA.gov. It has been reported that several drugs can cause vitamin D deficiency and hypocalcemia.84. Taking into account that mannitol exerts only a weak phosphaturic effect is highly unlikely that its administration per se can cause significant hypophosphatemia.