Phosphorous

Dosing information for PHOSPHOROUS
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
PHOSPHOROUS 250 MG TABLET	Maintenance	Adults take 1 tablet (250 mg) by oral route 4 times per day

The following drug interaction information is available for PHOSPHOROUS (sodium phosphate/potassium phosphates, monobasic and bibasic):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Burosumab/Oral Phosphates; Active Vitamin D Analogs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Both burosumab and phosphates or vitamin D may increase serum phosphate levels. This combination may lead to greater increases in serum phosphate than anticipated. CLINICAL EFFECTS: The combination of burosumab with oral phosphates or active vitamin D analogs may result in hyperphosphatemia and may increase the risk of nephrocalcinosis.(1) PREDISPOSING FACTORS: Patients with renal impairment have alterations in mineral metabolism that may increase the risk of hyperphosphatemia.(1) PATIENT MANAGEMENT: The concomitant use of burosumab with oral phosphates or active vitamin D analogs is contraindicated. Discontinue oral phosphate and/or active vitamin D analogs one week before starting burosumab.(1) DISCUSSION: Burosumab restores dysfunctional renal phosphate reabsorption and renal production of 1,25-dihydroxyvitamin D to treat X-linked hypophosphatemia. Additional oral phosphates and/or active vitamin D analogs may raise serum phosphate higher than anticipated.	CRYSVITA

Drug Interaction

Drug Names

Burosumab/Oral Phosphates; Active Vitamin D Analogs

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Both burosumab and phosphates or vitamin D may increase serum phosphate levels. This combination may lead to greater increases in serum phosphate than anticipated.

CLINICAL EFFECTS: The combination of burosumab with oral phosphates or active vitamin D analogs may result in hyperphosphatemia and may increase the risk of nephrocalcinosis.(1)

PREDISPOSING FACTORS: Patients with renal impairment have alterations in mineral metabolism that may increase the risk of hyperphosphatemia.(1)

PATIENT MANAGEMENT: The concomitant use of burosumab with oral phosphates or active vitamin D analogs is contraindicated. Discontinue oral phosphate and/or active vitamin D analogs one week before starting burosumab.(1)

DISCUSSION: Burosumab restores dysfunctional renal phosphate reabsorption and renal production of 1,25-dihydroxyvitamin D to treat X-linked hypophosphatemia. Additional oral phosphates and/or active vitamin D analogs may raise serum phosphate higher than anticipated.

CRYSVITA

There are 7 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Potassium Supplements/Potassium Sparing Diuretics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Decreased renal excretion of potassium, resulting from administration of a potassium sparing diuretic. CLINICAL EFFECTS: May observe hyperkalemia which may be severe or even fatal. PREDISPOSING FACTORS: Renal function impairment. PATIENT MANAGEMENT: If both drugs are administered, monitor potassium levels. Adjust the dose of the drugs accordingly. This combination should probably be avoided if possible. DISCUSSION: The interaction is well documented. Patients with decreased renal function are especially at risk of developing hyperkalemia from this drug combination. A commonly held belief is that a potassium sparing diuretic formulated in combination with a thiazide diuretic, such as Dyazide, will not exhibit this interaction. Although the likelihood of hyperkalemia occurring may be reduced somewhat, a danger still exists.	ALDACTONE, AMILORIDE HCL, AMILORIDE-HYDROCHLOROTHIAZIDE, CAROSPIR, DYRENIUM, KERENDIA, SPIRONOLACTONE, SPIRONOLACTONE-HCTZ, TRIAMTERENE, TRIAMTERENE-HYDROCHLOROTHIAZID
Eplerenone/Potassium Supplements SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Eplerenone increases serum potassium levels.(1) CLINICAL EFFECTS: Concurrent use of eplerenone with a potassium supplement may result in hyperkalemia.(1) PREDISPOSING FACTORS: Renal impairment. PATIENT MANAGEMENT: The manufacturer of eplerenone states that the use of eplerenone for the treatment of hypertension in patients receiving potassium supplements is contraindicated.(1) DISCUSSION: The main risk of eplerenone therapy is hyperkalemia. The risk of hyperkalemia can be reduced by avoiding potassium supplements during eplerenone therapy.(1)	EPLERENONE, INSPRA
Oral Phosphate Supplements; Urinary pH Modifiers/Aluminum; Calcium; Magnesium SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Medications containing significant amounts of aluminum, calcium, or magnesium may bind to the phosphate and prevent its absorption.(1) CLINICAL EFFECTS: Concurrent use of medications containing significant amounts of aluminum, calcium, or magnesium may result in decreased effectiveness of phosphate supplements and urinary pH modifiers high in phosphate.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients receiving phosphate supplements or urinary pH modifiers high in phosphate should be instructed to avoid medications containing aluminum, calcium, or magnesium.(1) Some phosphate laxative products used as phosphate supplements may contain sufficient quantities of phosphate to interact as well. DISCUSSION: The manufacturer of K-Phos states that products containing aluminum, calcium, or magnesium may bind to the phosphate and prevent its absorption. Therefore, patients receiving phosphate supplements and urinary pH modifiers high in phosphate should be instructed to avoid products containing aluminum, calcium, or magnesium.(1)	ALUMINUM HYDROXIDE, CALCIUM ACETATE, CLENPIQ, MAGNESIUM CHLORIDE, MAGNESIUM CITRATE, MAGNESIUM OXIDE, MAGNESIUM SULFATE, SOD SULF-POTASS SULF-MAG SULF, SUFLAVE, SUPREP, SUTAB
Potassium Supplements/Potassium Binders SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Patiromer, sodium polystyrene sulfonate and sodium zirconium cyclosilicate bind to potassium.(1-3) CLINICAL EFFECTS: Concurrent use of potassium supplements and patiromer, sodium polystyrene sulfonate or sodium zirconium cyclosilicate may decrease the effectiveness of both agents. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients should normally not receive potassium supplements and patiromer, sodium polystyrene sulfonate or sodium zirconium cyclosilicate concurrently.(1-3) Patiromer, sodium polystyrene sulfonate or sodium zirconium cyclosilicate are indicated for management of hyperkalemia. Consider discontinuing or holding potassium supplements in patients who develop hyperkalemia requiring treatment. DISCUSSION: Patiromer, sodium polystyrene sulfonate and sodium zirconium cyclosilicate are indicated for hyperkalemia. Consider discontinuing or holding potassium supplements in patients receiving sodium polystyrene sulfonate or sodium zirconium cyclosilicate.	KIONEX, LOKELMA, SODIUM POLYSTYRENE SULFONATE, SPS, VELTASSA
Phosphate Supplements;Urine pH Modifiers/Phosphate Reducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lanthanum and sevelamer bind to phosphate.(1-2) Tenapanor is a sodium/hydrogen exchanger 3 (NHE3) inhibitor.(3) All three agents are used to lower phosphate absorption in the body.(1-3) CLINICAL EFFECTS: Concurrent use of phosphate supplements or urinary pH modifiers high in phosphate with agents that reduce serum phosphorus may decrease the effectiveness of both agents. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients should normally not receive phosphate supplements or urinary pH modifiers high in phosphate concurrently with agents that reduce serum phosphorus. DISCUSSION: Lanthanum, sevelamer, and tenapanor are indicated to control phosphorus levels. Consider discontinuing or holding phosphate supplements and urinary pH modifiers high in phosphate in patients receiving these agents.	FOSRENOL, LANTHANUM CARBONATE, RENVELA, SEVELAMER CARBONATE, SEVELAMER HCL, XPHOZAH
Potassium Supplements/Trimethoprim SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Trimethoprim may increase serum potassium levels by reduction in potassium elimination.(1-3) The combination of trimethoprim and potassium supplements can have an additive effect on serum potassium resulting in potentially dangerous levels. CLINICAL EFFECTS: Concurrent use of trimethoprim and potassium supplements may result in hyperkalemia, which may be severe. PREDISPOSING FACTORS: Patients who are elderly, have any degree of renal insufficiency or heart failure have an increased risk for hyperkalemia.(1-9) Concomitant use with other drugs associated with hyperkalemia risk (e.g. ACE Inhibitors, angiotensin II receptor antagonists, aldosterone antagonists, NSAIDs) and high doses of trimethoprim further increase the risk for hyperkalemia.(1-8) Interaction risk and severity is greater in patients with multiple risk factors. PATIENT MANAGEMENT: Assure adequate monitoring for hyperkalemia.(1-9) Patients receiving trimethoprim and a potassium supplement concurrently should have their serum potassium monitored at baseline and during treatment. Potassium supplementation may need to be held during antibiotic therapy, especially when other predisposing factors for hyperkalemia are present. Peak potassium increase due to trimethoprim is delayed and generally occurs after 4 or more days of therapy.(3,5,6) When possible, alternative antibiotic therapy should be considered in patients with one or more risk factors for hyperkalemia, e.g. renal impairment, heart failure, age > 65 years, and/or receiving additional meds associated with hyperkalemia risk (e.g. ACE inhibitors, angiotensin II receptor blockers, aldosterone antagonists, NSAIDs).(6) DISCUSSION: A nested case-control study evaluated the risk for hyperkalemia in 19,194 patients with newly diagnosed heart failure. Over a mean follow-up of 3.9 years 2,176 cases of hyperkalemia (96.7% with a potassium value of => 5.5 mmol/L) were identified. Study authors found that trimethoprim independently increased the risk for hyperkalemia (OR 2.82; 95% CI 1.88-4.23).(4) A retrospective cohort study evaluated the risk for hospitalization due to hyperkalemia in 393,039 elderly women (age >65 years) treated for a urinary tract infection (UTI) with trimethoprim-sulfamethoxazole (TMP-SMX) or another antibiotic (amoxicillin, ciprofloxacin, norfloxacin, nitrofurantoin). Baseline renal function was similar in all five antibiotic groups. When compared with amoxicillin, TMP-SMX use was associated with a 3.3-fold increased risk for hospitalization due to hyperkalemia. Ciprofloxacin, norfloxacin, and nitrofurantoin were not associated with a risk for hyperkalemia.(9) A prospective study of hospitalized patients evaluated the risk for hyperkalemia in patients who received standard dose TMP-SMX (<= 320 mg trimethoprim, <= 1600 mg sulfamethoxazole daily) versus a control group who received a different antibiotic for at least 5 days. The two groups were similar in age, renal function and use of potassium altering medications. Serum potassium concentration increased in TMP-SMX patients by 1.21 mmol/L (CI 1.09 - 1.32 mmol/L), a change which was statistically significant in patients with a pretreatment serum creatinine = or > 1.2. In control patients, serum potassium decreased during antibiotic therapy (change not quantitated by authors).(5)	BACTRIM, BACTRIM DS, PRIMSOL, SULFAMETHOXAZOLE-TRIMETHOPRIM, SULFATRIM, TRIMETHOPRIM, TRIMETHOPRIM MICRONIZED
Erdafitinib/Serum Phosphate Level-Altering Drugs SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Medications that alter serum phosphate may interfere with interpretation of phosphate levels that are needed to determine initial erdafitinib dose.(1) CLINICAL EFFECTS: Serum phosphate levels that are elevated by concomitant medications may result in an inappropriately low dose and decreased effectiveness of erdafitinib. Serum phosphate levels that are decreased by concomitant medications may result in an inappropriately high dose and increased toxicity from erdafitinib. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of erdafitinib states that agents that alter serum phosphate levels should be avoided before the initial dose increase period for erdafitinib based on serum phosphate levels (days 14 to 21).(1) DISCUSSION: Concomitant administration of serum phosphate level-altering agents during the initial dose increase period of erdafitinib based on serum phosphate levels (days 14 to 21) may interfere with serum phospate levels and lead to incorrect dosing of erdafitinib.(1) Agents that may alter serum phosphate levels linked to this monograph include: aluminum carbonate, aluminum hydroxide, calcium acetate, calcium carbonate, calcium citrate, cod liver oil, ferric citrate, lanthanum, magnesium carbonate, magnesium hydroxide, potassium phosphate, sevelamer, sodium phosphate, sucroferric oxyhydroxide, tenapanor, and vitamin D.(1)	BALVERSA

There are 7 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Angiotensin II Receptor Blocker (ARB)/Potassium Supplements SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Angiotensin II receptor blockers (ARBs) may decrease the renal excretion of potassium. CLINICAL EFFECTS: Concurrent use of potassium supplements with ARBs may result in hyperkalemia. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and ARBs. DISCUSSION: Several studies have indicated that serum potassium levels increase when ARB therapy is initiated and decrease when the drug is lowered. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with ARBs.	AMLODIPINE-OLMESARTAN, AMLODIPINE-VALSARTAN, AMLODIPINE-VALSARTAN-HCTZ, ARBLI, ATACAND, ATACAND HCT, AVALIDE, AVAPRO, AZOR, BENICAR, BENICAR HCT, CANDESARTAN CILEXETIL, CANDESARTAN-HYDROCHLOROTHIAZID, COZAAR, DIOVAN, DIOVAN HCT, EDARBI, EDARBYCLOR, ENTRESTO, ENTRESTO SPRINKLE, EPROSARTAN MESYLATE, EXFORGE, EXFORGE HCT, FILSPARI, HYZAAR, IRBESARTAN, IRBESARTAN-HYDROCHLOROTHIAZIDE, LOSARTAN POTASSIUM, LOSARTAN-HYDROCHLOROTHIAZIDE, MICARDIS, MICARDIS HCT, OLMESARTAN MEDOXOMIL, OLMESARTAN-AMLODIPINE-HCTZ, OLMESARTAN-HYDROCHLOROTHIAZIDE, TELMISARTAN, TELMISARTAN-AMLODIPINE, TELMISARTAN-HYDROCHLOROTHIAZID, TRIBENZOR, VALSARTAN, VALSARTAN-HYDROCHLOROTHIAZIDE
Drospirenone/Potassium Supplements SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Drospirenone has antimineralocorticoid activity and may cause hyperkalemia. Potassium supplements also increase potassium levels.(1) CLINICAL EFFECTS: Concurrent use of drospirenone and potassium supplements may result in hyperkalemia.(1) PREDISPOSING FACTORS: Renal insufficiency, hepatic dysfunction, adrenal insufficiency, and use of potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, heparin, and NSAIDs may increase potassium levels.(1) PATIENT MANAGEMENT: Patients receiving drospirenone with a potassium supplement should have their serum potassium level checked during the first treatment cycle.(1) DISCUSSION: Drospirenone has antimineralocorticoid activity comparable to 25 mg of spironolactone and may result in hyperkalemia. Concurrent use of potassium-supplements also increase potassium levels.(1)	ANGELIQ, BEYAZ, DROSPIRENONE-ETH ESTRA-LEVOMEF, DROSPIRENONE-ETHINYL ESTRADIOL, JASMIEL, LO-ZUMANDIMINE, LORYNA, NEXTSTELLIS, NIKKI, OCELLA, SAFYRAL, SLYND, SYEDA, VESTURA, YASMIN 28, YAZ, ZARAH, ZUMANDIMINE
Memantine; Amantadine/Urinary Alkalinizers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Memantine and amantadine elimination is impaired by urinary alkalinization.(1,2) CLINICAL EFFECTS: Potentiation of memantine or amantadine effects may be observed. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor patient for adverse reactions such as dizziness, headache, or confusion if a urinary alkalinizer is required. The memantine or amantadine dose may need to be adjusted when a urinary alkalinizer is started or stopped.(1,2) DISCUSSION: The clearance of memantine was reduced by about 80% under alkaline urine conditions at pH 8. Urine alkalinization may lead to an accumulation of memantine with a possible increase in adverse effects. Urine pH is also altered by diet and clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract). Hence, memantine should be used with caution under these conditions.(1) A study in rats showed that concomitant administration of sodium bicarbonate with amantadine caused a decrease in amantadine renal clearance (1.16 vs. 0.76). Amantadine's area-under-the-curve (AUC) was increased approximately 78%.(3) A study in 12 healthy subjects showed that plasma concentrations of memantine are dependent on urine pH. Alkaline urine pH caused a 79% reduction in renal clearance.(4)	AMANTADINE, AMANTADINE HCL, GOCOVRI, MEMANTINE HCL, MEMANTINE HCL ER, MEMANTINE HCL-DONEPEZIL HCL ER, NAMENDA, NAMENDA XR, NAMZARIC, OSMOLEX ER
Aliskiren/Potassium Supplements SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aliskiren may decrease the renal excretion of potassium. CLINICAL EFFECTS: Concurrent use of potassium supplements with aliskiren may result in hyperkalemia. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and aliskiren. DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors and ARB therapy is initiated and decrease when the drug is lowered. Increased potassium levels have also been seen with aliskiren. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with aliskiren.	ALISKIREN, TEKTURNA
Selected ACE Inhibitors/Potassium Supplements SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: ACE inhibitors may decrease the renal excretion of potassium. CLINICAL EFFECTS: Concurrent use of potassium supplements with ACE inhibitors may result in hyperkalemia. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and ACE inhibitors. DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors is initiated and decrease when the drug is lowered. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with ACE inhibitors. Selected ACE inhibitors linked to this monograph include: alacepril, cilazapril, delapril, imidapril, perindopril, spirapril, temocapril, and zofenopril.	PERINDOPRIL ERBUMINE, PRESTALIA
Selected ACE Inhibitors/Potassium Supplements SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: ACE inhibitors may decrease the renal excretion of potassium. CLINICAL EFFECTS: Concurrent use of potassium supplements with ACE inhibitors may result in hyperkalemia. PREDISPOSING FACTORS: Impaired renal function; diabetes mellitus. PATIENT MANAGEMENT: Monitor serum potassium and adjust the dosage accordingly in patients receiving concurrent therapy with potassium supplements and ACE inhibitors. DISCUSSION: Several studies have indicated that serum potassium levels increase when ACE inhibitors is initiated and decrease when the drug is lowered. Based on this data, serum potassium levels should be monitored in patients receiving potassium supplements with ACE inhibitors. Selected ACE inhibitors linked to this monograph include: benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, quinapril, ramipril, and trandolapril.	ACCUPRIL, ACCURETIC, ALTACE, AMLODIPINE BESYLATE-BENAZEPRIL, BENAZEPRIL HCL, BENAZEPRIL-HYDROCHLOROTHIAZIDE, CAPTOPRIL, CAPTOPRIL-HYDROCHLOROTHIAZIDE, ENALAPRIL MALEATE, ENALAPRIL-HYDROCHLOROTHIAZIDE, ENALAPRILAT, EPANED, FOSINOPRIL SODIUM, FOSINOPRIL-HYDROCHLOROTHIAZIDE, LISINOPRIL, LISINOPRIL-HYDROCHLOROTHIAZIDE, LOTENSIN, LOTENSIN HCT, LOTREL, MOEXIPRIL HCL, QBRELIS, QUINAPRIL HCL, QUINAPRIL-HYDROCHLOROTHIAZIDE, RAMIPRIL, TRANDOLAPRIL, TRANDOLAPRIL-VERAPAMIL ER, VASERETIC, VASOTEC, ZESTORETIC, ZESTRIL
Trientine/Selected Minerals, Oral SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Mineral supplements may bind to trientine and block its absorption. CLINICAL EFFECTS: The levels and clinical effects of trientine may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of trientine states that mineral supplements should not be given with trientine. If concomitant therapy is necessary, take trientine on an empty stomach and separate administration at least one hour apart from any other drug. Monitor clinical status for decreased effectiveness and adjust the trientine dose if necessary. DISCUSSION: Multivitamins with minerals may decrease trientine absorption so ensure patient is aware of the risks.	CUVRIOR, SYPRINE, TRIENTINE HCL

Contraindication List
Hypernatremia
Hyperphosphatemia
Hypocalcemia

Severe List
Anuria
Azotemia
Chronic heart failure
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Dehydration
Edema
Hyporeninemic hypoaldosteronism
Myotonia congenita - autosomal dominant form

Moderate List
Hepatic cirrhosis
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Severe hepatic disease

Hypophosphatemia
E83.31	Familial hypophosphatemia