Fiber Laxative (calcium polycarbophil)

Bulk-forming laxatives are usually administered 1-3 times daily. To reduce the risk of esophageal obstruction in patients receiving large (e.g., the maximum daily dosage recommended by the manufacturer) dosages of bulk-forming laxatives, these laxatives should be administered in divided doses instead of a single daily dose. The usual dosages for the individual bulk-forming laxatives are below; for dosages in children younger than the ages listed, a physician should be consulted.

Dosage of the oral calcium supplements is usually expressed in grams or mg of elemental calcium and depends on the requirements of the individual patient. Dosage of parenteral calcium replacements is usually expressed as mEq of calcium and depends on individual patient requirements. One mEq of elemental calcium is equivalent to 20 mg. See Table 1 for the approximate calcium content of the various calcium salts.

Table 1.

Calcium Salt Calcium Content calcium acetate 253 mg (12.7 mEq) per g calcium carbonate 400 mg (20 mEq) per g calcium chloride 270 mg (13.5 mEq) per g calcium citrate 211 mg (10.6 mEq) per g calcium gluceptate 82 mg (4.1 mEq) per g calcium gluconate 90 mg (4.5 mEq) per g calcium glycerophosphate 191 mg (9.6 mEq) per g calcium lactate 130 mg (6.5 mEq) per g calcium phosphate dibasic anhydrous 290 mg (14.5 mEq) per g calcium phosphate dibasic dihydrate 230 mg (11.5 mEq) per g calcium phosphate tribasic 400 mg (20 mEq) per g

Oral calcium supplements usually are administered in 3 or 4 divided doses daily. Optimum calcium absorption may require supplemental vitamin D in individuals with inadequate vitamin D intake, those with impaired renal activation of the vitamin, or those not receiving adequate exposure to sunlight.

Bulk-forming laxatives are administered orally. Commercially available powders, flakes, granules, tablets, and liquids should be dissolved and/or diluted according to the instructions of the manufacturer. In the treatment of constipation, at least one full glass (250 mL) of liquid should be administered with each laxative dose. When used to increase the bulk of stools in patients with chronic, watery diarrhea, one manufacturer suggests that one-third of a glass (80 mL) of liquid be administered with each dose.

The acetate, carbonate, citrate, gluconate, lactate, and phosphate salts of calcium are administered orally. It has been recommended that most oral calcium supplements be administered 1-1.5 hours after meals or with a demulcent (e.g., milk). However, calcium carbonate powder (i.e., CAL CARB-HD(R)) should generally be administered with meals, since the manufacturer recommends mixing the powder with food for administration. Calcium salts used to bind dietary phosphate in patients with end-stage renal disease should be administered with meals (e.g., 10-15 minutes before, or during, the meal).

Calcium chloride and calcium gluconate may be administered IV. Calcium chloride also may be administered by intraosseous (IO) injection+ in the setting of pediatric resuscitation; onset of action and systemic concentrations are comparable to those achieved with venous administration. Parenteral calcium salts may be administered in large volume IV infusion fluids.

IV calcium injections must be administered slowly at a rate not exceeding 0.7-1.8 mEq/minute, and the injection should be stopped if the patient complains of discomfort. Following IV injection, the patient should remain recumbent for a short time. Close monitoring of serum calcium concentrations is essential during IV administration of calcium. Calcium chloride should not be injected IM or into subcutaneous or perivascular tissue, since severe necrosis and sloughing may occur. Although other calcium salts may cause mild to severe local reactions, they are generally less irritating than calcium chloride. (See Cautions.) The fixed combination of calcium glycerophosphate and calcium lactate is injected IM. Although some manufacturers previously stated that calcium gluconate could be injected IM when IV administration was not possible, manufacturers of calcium gluconate currently state that the drug should not be injected IM or into subcutaneous tissue because of the potential for severe local reactions. In children, calcium salts should not be administered through scalp veins. Oral administration of calcium supplements or calcium-rich foods should replace parenteral calcium therapy as soon as possible.

The interaction of calcium and phosphate in parenteral nutrition solutions is a complex phenomenon; various factors have been identified as playing a role in the solubility or precipitation of a given combination. Calcium salts are conditionally compatible with phosphate in parenteral nutrition solutions; incompatibility is dependent on a solubility and concentration phenomenon and is not entirely predictable. Precipitation may occur during compounding or at some time after compounding is completed. Specialized references should be consulted for specific compatibility information.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Alum;Ca;Mag/Oral Phosphate Supplements; Urinary Ph Modifiers

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) If concurrent use cannot be avoided, separate the administration of phosphate containing products by as much time as possible from medications containing aluminum, calcium, or magnesium. 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 & Magnesium Antacids;Polyvalent Cations/Raltegravir

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Aluminum and/or magnesium containing antacids may alter raltegravir absorption by altering gastric pH. Magnesium antacids and supplements containing polyvalent cations may bind to raltegravir in the GI tract, preventing its absorption.(1)

CLINICAL EFFECTS: Aluminum and/or magnesium containing antacids and supplements containing polyvalent cations may reduce levels and clinical effectiveness of raltegravir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Concurrent use of any formulation of raltegravir and aluminum and/or magnesium antacids is not recommended. Instruct patients not to use aluminum and/or magnesium containing antacids. Calcium carbonate may be used in place of aluminum and/or magnesium containing antacids in patients receiving raltegravir twice daily. Calcium carbonate is not recommended for patients receiving once daily raltegravir (1,200 mg daily).(1,2) The US HIV treatment guidelines state that if coadministration of other medications that contain polyvalent cations (e.g., Mg, Al, Fe, Ca, Zn, sucralfate) is necessary, administer raltegravir at least 2 hours before or at least 6 hours after polyvalent cations. Monitor for virologic response.(2)

DISCUSSION: Simultaneous administration of aluminum and magnesium hydroxide (20 ml) with raltegravir (400 mg BID) decreased raltegravir maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) by 44%, 49%, and 63%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours before raltegravir (400 mg BID) decreased raltegravir Cmax, AUC, and Cmin by 51%, 51%, and 56%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours after raltegravir (400 mg BID) decreased raltegravir Cmax, AUC, and Cmin by 22%, 30%, and 57%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 4 hours before after raltegravir (400 mg BID) decreased raltegravir Cmax, AUC, and Cmin by 22%, 19%, and 60%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 4 hours after after raltegravir (400 mg BID) decreased raltegravir Cmax, AUC, and Cmin by 30%, 32%, and 62%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 6 hours before after raltegravir (400 mg BID) decreased raltegravir Cmax, AUC, and Cmin by 10%, 13%, and 50%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 6 hours after after raltegravir (400 mg BID) decreased raltegravir Cmax, AUC, and Cmin by 10%, 11%, and 49%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 12 hours after after raltegravir (1200 mg single dose) decreased raltegravir Cmax, AUC, and Cmin by 14%, 14%, and 58%, respectively.(1,3) Data from in vitro(3) and in vivo simulations(5) suggest that magnesium's effect on raltegravir may involve chelation as well as changes in pH.

Laxatives/Trofinetide

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Trofinetide commonly causes diarrhea of mild to moderate severity. Laxatives may increase the incidence or severity of diarrhea.(1)

CLINICAL EFFECTS: Concurrent use of laxatives with trofinetide may increase the risk of severe diarrhea.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Patients should stop laxatives before starting trofinetide. If diarrhea occurs, consider anti-diarrheal treatment and monitor hydration status. If severe diarrhea or dehydration occurs, interrupt, reduce dose, or discontinue trofinetide.(1)

DISCUSSION: In clinical trials, 85% of patients on trofinetide developed diarrhea. Concurrent use of laxatives may increase this risk.(1)

Laxatives; Stool Softeners/Tenapanor

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Tenapanor commonly causes diarrhea of mild to moderate severity. Laxatives and stool softeners may increase the incidence or severity of diarrhea.(1)

CLINICAL EFFECTS: Concurrent use of laxatives or stool softeners with tenapanor may increase the risk of severe diarrhea.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of tenapanor states that patients should be instructed to avoid stool softeners and laxatives with tenapanor. If severe diarrhea occurs, tenapanor should be discontinued.(1)

DISCUSSION: In clinical trials, 43-53% of CKD patients on dialysis treated with tenapanor developed diarrhea. Diarrhea usually occurred soon after treatment initiation and was severe in 5% of patients.(1)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Aluminum-Magnesium Hydroxide; Oral Calcium/Phenytoin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aluminum hydroxide; magnesium hydroxide, and oral calcium may bind to phenytoin, preventing its absorption.(1-4)

CLINICAL EFFECTS: Simultaneous ingestion of aluminum-magnesium hydroxide and/or calcium-containing products may result in decreased levels and effectiveness of phenytoin.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of phenytoin recommends that administration times of phenytoin and antacids being staggered.(1)

DISCUSSION: In a study in 8 healthy subjects, simultaneous administration of phenytoin (600 mg) with calcium carbonate significantly decreased the area-under-curve (AUC) of phenytoin.(2) In a study in 8 healthy subjects, simultaneous administration of aluminum-magnesium hydroxide or calcium carbonate significantly decreased the AUC of phenytoin.(3) In a study in 6 patients with epilepsy, concurrent administration of an aluminum-magnesium hydroxide antacid resulted in a small but statistically significant decrease in phenytoin AUC.(4)

Antacids And Selected Minerals/Oral Iron Supplements

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Some antacids may bind to iron, preventing its absorption. Alterations in gastric pH by antacids may also play a role. Iron may bind to other minerals such as calcium, manganese, tin, and zinc in the GI tract.

CLINICAL EFFECTS: Simultaneous administration of an antacid or minerals may decrease the absorption of orally administered iron.

PREDISPOSING FACTORS: The interaction with some combinations may be affected by the presence or absence of food.

PATIENT MANAGEMENT: Iron supplements should not be taken within 1 hour before or 2 hours after antacids, calcium, manganese, or zinc.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well.

DISCUSSION: Magnesium hydroxide has been shown to inhibit the absorption of elemental iron,(2) although other studies have shown conflicting results.(3,4) Sodium bicarbonate has been shown to decrease the absorption of iron by 50%.(3) In a study in 61 healthy subjects, calcium citrate, calcium carbonate, and calcium phosphate inhibited iron absorption when taken with food. However, in the fasted state, calcium carbonate had no effect on iron absorption. In the fasted state, calcium citrate and calcium phosphate decreased iron absorption by 49% and 62%, respectively,(6) In a study in 23 healthy subjects, calcium acetate and calcium carbonate decreased the area-under-curve (AUC) of elemental iron (65 mg) by 27% and 19%, respectively.(7) In a study, manganese decreased iron absorption. A ratio of 5:1 of zinc:iron decreased iron absorption by 56%.(8) In a study, inorganic iron decreased zinc absorption.(9) In another study, ferrous sulfate decreased the absorption of zinc sulfate in a concentration dependent manner; however, heme chloride had no effect on zinc sulfate.(10) In a study in premature infants, administration of liquid zinc and iron supplements between feedings decreased iron uptake; however, no effect was seen when the supplements were mixed with feedings.(11) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.

Bulk Forming Laxatives/Clozapine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Clozapine has potent anticholinergic properties and inhibits serotonin receptors, including 5-HT3.(1-4) Both of these properties may cause inhibition of gastrointestinal (GI) smooth muscle contraction, resulting in decreased peristalsis.(3,4) If fluid intake is inadequate, bulk forming laxatives can increase the risk of gastrointestinal obstruction.(1-6)

CLINICAL EFFECTS: Concurrent use of clozapine and bulk forming laxatives with inadequate fluid intake may increase the risk of constipation (common) and serious bowel complications (uncommon), including complete bowel obstruction, fecal impaction, paralytic ileus and intestinal ischemia or infarction.(1-6)

PREDISPOSING FACTORS: The risk for serious bowel complications is higher with increasing age, higher frequency of constipation, and in patients on higher doses of clozapine or multiple anticholinergic agents.(1,5)

PATIENT MANAGEMENT: Concurrent use of bulk forming laxatives with clozapine may be used with caution in patients who can maintain adequate fluid intake. Evaluate the patient's bowel function regularly. If patient is unable to maintain adequate fluid intake and use bulk forming laxatives as prescribed, avoid the use of bulk forming laxatives with clozapine.(1-6) Monitor for symptoms of constipation and GI hypomotility, including having bowel movements less than three times weekly or less than usual, difficulty having a bowel movement or passing gas, nausea, vomiting, and abdominal pain or distention.(2) Consider a prophylactic laxative in those with a history of constipation or bowel obstruction.(2) Review patient medication list for anticholinergic agents which may have additive effects on decreased GI motility. When possible, decrease the dosage or number of prescribed anticholinergic agents, particularly in the elderly. Counsel the patient about the importance of maintaining adequate hydration. Encourage regular exercise and eating a high-fiber diet.(2)

DISCUSSION: The concurrent use of clozapine and bulk forming laxatives has not been studied. Use of bulk forming laxatives with inadequate fluid intake has been associated with gastrointestinal obstruction.

Calcium & Iron Containing Supplements/Bictegravir

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Calcium or iron containing supplements may bind to bictegravir in the GI tract, preventing its absorption.(1)

CLINICAL EFFECTS: Calcium or iron containing supplements may reduce levels and clinical effectiveness of bictegravir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Bictegravir and calcium or iron containing supplements may be taken together with food. Routine administration of bictegravir under fasting conditions simultaneously with, or within 2 hours after, calcium or iron containing supplements is not recommended.(1) In pregnant patients, if bictegravir is taken on an empty stomach, take bictegravir at least 2 hours before or 6 hours after calcium or iron containing supplements.(1)

DISCUSSION: Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir maximum concentration (Cmax) and area-under-curve (AUC) by 80% and 79%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours after bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 7% and 13%, respectively.(1) Administration of aluminum and magnesium hydroxide (20 ml) 2 hours before bictegravir (50 mg single dose) in a fasted state decreased bictegravir Cmax and AUC by 58% and 52%, respectively.(1) Simultaneous administration of aluminum and magnesium hydroxide (20 ml) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 49% and 47%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 42% and 33%, respectively.(1) Simultaneous administration of calcium carbonate (1200 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax by 10% and increased AUC 3%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fasted state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 71% and 63%, respectively.(1) Simultaneous administration of ferrous fumarate (324 mg single dose) in a fed state with bictegravir (50 mg single dose) decreased bictegravir Cmax and AUC by 25% and 16%, respectively.(1)

Calcium; Iron; Sucralfate/Thyroid Preparations

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism by which malabsorption of thyroid preparations occurs from calcium-containing products is presumed to be a binding of the medication to the thyroid hormone, forming an insoluble or nonabsorbable complex.(1-3) Iron may form a ferric-thyroxine complex with thyroid agents, preventing their absorption from the gastrointestinal tract.(1,4) Sucralfate binds to other agents in the gastrointestinal tract and alters absorption of other drugs, including thyroid agents.(1,5)

CLINICAL EFFECTS: The simultaneous administration of thyroid preparations with calcium, iron, or sucralfate may result in decreased levels and clinical effects of thyroid preparations.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Instruct patients to separate the administration time of thyroid preparations from calcium or iron by as much time as possible, preferably by at least four hours.(1) Administer thyroid preparations at least 2 hours before sucralfate.(5) Patients taking thyroid preparations and calcium- or iron-containing products or sucralfate should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased. Separating the administration times of the thyroid preparation and the calcium- or iron-containing products or sucralfate may decrease the effects of the interaction.(1-5)

DISCUSSION: In a pharmacokinetic study 8 healthy, euthyroid adults were given levothyroxine alone and levothyroxine coadministered with calcium carbonate, calcium citrate, or calcium acetate in doses containing 500 mg elemental calcium. The coadministration of each of the three calcium preparations significantly reduced levothyroxine absorption by about 20%-25% compared with levothyroxine given alone.(3) In a study in 14 subjects, the simultaneous administration of thyroxine with ferrous sulfate for 12 weeks resulted in an increase in the mean level of thyroid stimulating hormone (TSH) from 1.6+/-0.4 mU/L to 5.4+/-2.8 mU/L. Mixing thyroxine with ferrous sulfate in vitro resulted in a poorly soluble complex.(4) In a study in 20 hypothyroid patients, the simultaneous administration of levothyroxine and calcium carbonate (1200 mg) daily for three months resulted in reductions in the mean free T4 and total T4 levels. These values increased in most patients following the discontinuation of calcium carbonate. A concurrent in-vitro study found that calcium carbonate adsorbed levothyroxine in solution at a pH of 2, gastric pH, but not at a pH of 7.4.(6) One author reported three cases of decreased levothyroxine efficacy following the addition of calcium carbonate to therapy.(7) In a study in 5 healthy subjects, levothyroxine (five 200 mcg tablets) was administered in 3 different dosing regimens: after an overnight fast, with the fifth and final dose of sucralfate (1 gram every 6 hours) and 8 hours after the second and final dose of sucralfate (2 grams every 12 hours). When administered alone, 80% of levothyroxine was absorbed within 6 hours of administration, compared to 23% when administered concurrently with sucralfate. There was no difference in levothyroxine absorption when administered alone or 8 hours after sucralfate.(8) There are several case reports documenting decreased effects of thyroid supplementation as the result of simultaneous administration of sucralfate.(9,10) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.

Calcium; Iron; Sucralfate/Tiratricol

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism by which malabsorption of thyroid preparations such as tiratricol occurs from calcium-containing products is presumed to be a binding of the medication to the thyroid hormone, forming an insoluble or nonabsorbable complex.(1,2) Iron may form a ferric-thyroxine complex with thyroid agents such as tiratricol, preventing their absorption from the gastrointestinal tract.(1,2) Sucralfate binds to other agents in the gastrointestinal tract and alters absorption of other drugs, including thyroid agents such as tiratricol.(1-3)

CLINICAL EFFECTS: The simultaneous administration of thyroid preparations with calcium, iron, or sucralfate may result in decreased levels and clinical effects of thyroid preparations.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Instruct patients to take iron and calcium supplements at the same time every day relative to tiratricol dosing.(6,7) Patients taking thyroid preparations and calcium- or iron-containing products or sucralfate should be monitored for changes in thyroid function. The dosage of the thyroid preparation may need to be increased. Separating the administration times of the thyroid preparation and the calcium- or iron-containing products or sucralfate may decrease the effects of the interaction.(1-3)

DISCUSSION: Iron and calcium may interfere with the absorption of tiratricol.(1,2)

Di-; Trivalent Cations/Chloroquine; Hydroxychloroquine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Di- and trivalent cations such as aluminum, calcium, lanthanum, and magnesium may adsorb chloroquine and hydroxychloroquine; preventing their absorption.(1-5) The adsorption may also limit the effectiveness of the di- or trivalent cation.(1)

CLINICAL EFFECTS: Simultaneous administration of di- or trivalent cations may result in decreased levels and effectiveness of chloroquine and hydroxychloroquine(2-5) and decreased effectiveness of the di- or trivalent cation.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Instruct patients to separate the administration times of these medicines by 2 to 4 hours.(2,3)

DISCUSSION: Adsorption of chloroquine by magnesium trisilicate was found to decrease hydrochloric acid uptake and decrease the amount of magnesium released in an acidic environment.(1) In a study, calcium carbonate, kaolin, and magnesium trisilicate were found to decrease the absorption of chloroquine by 52.8%, 46.5%, and 31.3%, respectively.(3) Magnesium trisilicate and magnesium oxide have been shown to decrease the release of chloroquine from tablets and to adsorb chloroquine after its release.(4) In a study in 6 subjects, magnesium trisilicate and kaolin decreased the area-under-curve (AUC) of chloroquine by 18.2% and 28.6%, respectively.(5)

Divalent & Trivalent Cations/Tetracyclines

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Di- and trivalent cations may form chelation complexes with tetracyclines, preventing their absorption.(1,2)

CLINICAL EFFECTS: Simultaneous administration of di- or trivalent cations may result in decreased levels of and therapeutics effects from tetracyclines.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Administer tetracyclines at least two hours before or after the di- or trivalent cations. When used for the treatment of H. pylori infection, tetracyclines and bismuth should be given simultaneously. The US manufacturer of omadacycline states to fast for at least four hours, administer omadacycline, and then wait four hours before taking di- or trivalent cations.(21) The US manufacturer of ferric maltose recommends separation of ferric maltose by at least 4 hours.(22)

DISCUSSION: Concurrent administration of aluminum hydroxide or divalent cations (such as calcium, magnesium, or zinc) has been shown to significantly decrease the gastrointestinal absorption of tetracycline.(3-5) Concurrent administration of tetracycline and magnesium-aluminum hydroxide gel has been shown to decrease the tetracycline area-under-curve (AUC) by 90%.(6) Magnesium-aluminum silicate has been shown to decrease the AUC of tetracycline by 27%.(7) Demeclocycline(8,9) methacycline,(10) chlortetracycline,(11) and oxytetracycline(10,12) have been shown to interact with aluminum hydroxide and/or dairy products. Doxycycline has been reported to interact with aluminum hydroxide gel.(13) Aluminum magnesium hydroxide has been shown to decrease doxycycline absorption by 84%.(14) Minocycline absorption has been shown to be impaired by aluminum, calcium, and magnesium.(15) Bismuth subsalicylate has been shown to decrease absorption of doxycycline and tetracycline by 37%(16) and 34%,(17) respectively. Since sucralfate is an aluminum salt of a sulfated disaccharide, it may also prevent absorption of tetracyclines. This complex has been used to provide site-specific delivery of tetracycline to gastric ulcers in the treatment of Helicobacter pylori gastric ulcer disease and may be useful in some indications.(18) Quinapril tablets contain a high percentage of magnesium and have been shown to decrease the absorption of tetracycline by 28-37%.(19) Lanthanum is expected to interact with tetracyclines as well.(20)

Oral Calcium Products/Estramustine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Calcium may bind to estramustine in the gastro-intestinal tract, preventing its absorption.(1-4)

CLINICAL EFFECTS: Simultaneous administration of oral calcium products may result in decreased levels and clinical effectiveness of estramustine.(1-4)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The UK(1) and US(2) manufacturers of estramustine state that calcium containing products should not be taken simultaneously with estramustine. One Australian manufacturer of calcium carbonate recommends separating administration by at least 3 hours.(3)

DISCUSSION: In a randomized, cross-over study in 6 patients, simultaneous administration of estramustine (420 mg) with milk (200 ml containing 120 mg calcium) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of estromustine (a metabolite of estramustine) by 59% and 68%, respectively. The AUC of estrone (another estramustine metabolite) was decreased by 63%.(4)

Oral Calcium Products/Strontium

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Calcium may prevent the absorption of strontium.(1,2)

CLINICAL EFFECTS: Simultaneous administration of strontium with oral calcium products may result in decreased levels and effectiveness of strontium.(1,2)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The administration of strontium and oral calcium products should be separated by at least 2 hours.(1,2)

DISCUSSION: Simultaneous administration of strontium with calcium or food decreased the bioavailability of strontium by 60-70% when compared to administration 3 hours after a meal.(1,2)

Polyvalent Cations And Phosphate Binders/Vadadustat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Vadadustat may form a chelate with iron supplements, phosphate binders, and other medicinal products whose primary component consists of polyvalent cations such as aluminum, calcium, magnesium, selenium, and zinc.(1)

CLINICAL EFFECTS: Simultaneous administration of vadadustat and polyvalent cations and phosphate binders decreases the exposure and effectiveness of vadadustat.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of vadadustat states that it should be administered at least 1 hour before or 2 hours after any medications or products whose primary component consists of iron, phosphate binders and polyvalent cations.(1)

DISCUSSION: Two studies evaluating the pharmacokinetics, safety, and tolerability of a single oral dose of vadadustat coadministered with a phosphate binder or iron supplement were conducted in healthy adult participants. Vadadustat exposure was reduced by coadministration with sevelamer carbonate, calcium acetate, ferric citrate, and ferrous sulfate. Geometric least squares mean ratios for area under the concentration-time curve (AUC) were reduced 37% to 55% by phosphate binders and 46% by ferrous sulfate. However, when vadadustat was administered 1 hour before phosphate binders, 90% confidence intervals for vadadustat exposure were within the no-effect boundaries of +50% to -33%, indicating that drug-drug interactions can be reduced by administering vadadustat 1 hour before phosphate binders.(2)

Polyvalent Cations/Baloxavir

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aluminum, calcium, iron, magnesium, selenium, and zinc may form chelation compounds with baloxavir.(1)

CLINICAL EFFECTS: Simultaneous administration of products containing aluminum, calcium, iron, magnesium, selenium, and zinc may result in decreased levels of and clinical effects from baloxavir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Avoid concurrent administration of baloxavir with cation-containing products.(1)

DISCUSSION: A significant decrease in baloxavir exposure was observed when baloxavir was coadministered with calcium, aluminum, magnesium, or iron in monkeys. No studies have been conducted in humans.(1)

Polyvalent Cations/Cabotegravir

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Cabotegravir chelates polyvalent cations such as aluminum, calcium, iron, magnesium, selenium, and zinc.(1)

CLINICAL EFFECTS: Simultaneous administration of cabotegravir and polyvalent cations may decrease the absorption and clinical effects of cabotegravir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of cabotegravir states that it should be administered at least 4 hours before or 2 hours after any medications or products containing polyvalent cations such as antacids or mineral supplements.(1)

DISCUSSION: Clinical studies have not been conducted. Prescribing information states cabotegravir levels may be decreased when coadministered with antacids containing polyvalent cations (examples include aluminum or magnesium hydroxide, calcium carbonate) suggesting cabotegravir is susceptible to chelation.(1)

Polyvalent Cations/Eltrombopag

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Eltrombopag chelates polyvalent cations such as aluminum, calcium, iron, magnesium, selenium, and zinc.(1)

CLINICAL EFFECTS: Simultaneous administration of eltrombopag and polyvalent cations may decrease the absorption and clinical effects of eltrombopag.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The US manufacturer of eltrombopag states that it should be administered at least 2 hours before or 4 hours after any medications or products containing polyvalent cations such as antacids or mineral supplements.(1)

DISCUSSION: In a crossover study in 25 healthy subjects, administration of eltrombopag with an antacid (1524 mg aluminum hydroxide/1425 mg magnesium carbonate/sodium alginate) decreased eltrombopag levels by 70%.(1,2)

Polyvalent Cations/Penicillamine, Oral

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Penicillamine chelates with polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc in the GI tract reducing the absorption of the penicillamine.

CLINICAL EFFECTS: Reduced (to 30% of fasting) bioavailability of penicillamine with decreased pharmacologic response.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In order to assure systemic absorption and maximal effectiveness from penicillamine, counsel patient to separate penicillamine by at least 1 hour before or 1 hours after any medications or products containing polyvalent cations such as antacids or mineral supplements. Monitor clinical status for decreased effectiveness and adjust the penicillamine dose if necessary.

DISCUSSION: Clinical studies with polyvalent cations have not been conducted. Multivitamins with low doses of cations including iron and zinc may decrease penicillamine absorption so insure patient is aware of the risks.

Polyvalent Cations/Roxadustat

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Roxadustat chelates polyvalent cations such as aluminum, calcium, iron, magnesium, selenium, and zinc.(1)

CLINICAL EFFECTS: Simultaneous administration of roxadustat and polyvalent cations may decrease the absorption and clinical effects of roxadustat.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of roxadustat states that it should be administered at least 1 hour before or 1 hour after any medications or products containing polyvalent cations such as antacids or mineral supplements.(1)

DISCUSSION: Clinical studies with polyvalent cations have not been conducted. In a study in health subjects, concurrent use of roxadustat with sevelamer carbonate or calcium acetate decreased roxadustat area-under-curve (AUC) by 67% and 46% and concentration maximum (Cmax) by 66% and 52%, respectively.(1)

Sel Oral Cations; Antacids; H2 Antag/Dolutegravir-Rilpivirin

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aluminum, calcium, iron, lanthanum, magnesium, sucralfate, and zinc may form chelation compounds with dolutegravir.(1) Rilpivirine requires an acidic medium for absorption. Antacid or H2 antagonist induced decrease in gastric pH may result in decrease in rilpivirine absorption.(1)

CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or sucralfate close to the administration time of dolutegravir may result in decreased absorption and clinical effectiveness of dolutegravir.(1) Simultaneous administration of an antacid or a H2 antagonist may result in decreased levels and effectiveness of rilpivirine, as well as the development of resistance.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, avoid concurrent therapy with dolutegravir-rilpivirine and cation-containing products. If it is necessary to use these agents concurrently, dolutegravir-rilpivirine should be administered 4 hours before or 6 hours after taking these medications.(1) Alternatively, dolutegravir-rilpivirine and supplements containing calcium or iron can be taken together with food.(1) In patients maintained on dolutegravir-rilpivirine, administer dolutegravir-rilpivirine at least 4 hours before or 6 hours after antacids .(1) In patients maintained on dolutegravir-rilpivirine, administer dolutegravir-rilpivirine at least 4 hours before or 12 hours after H2 antagonists.(1) Concurrent use of proton pump inhibitors will dolutegravir-rilpivirine is contraindicated.(1)

DISCUSSION: In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) simultaneously with dolutegravir (50 mg single dose) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of dolutegravir by 72%, 74%, and 74%, respectively.(1) In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) 2 hours after dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 18%, 26%, and 30%, respectively.(1) In a study in 16 subjects, the administration of a multiple vitamin (One-A-Day) simultaneously with dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 35%, 33%, and 32%, respectively.(1) In a study in 16 subjects, omeprazole (20 mg daily) decreased the Cmax, AUC, and Cmin of rilpivirine (150 mg daily) by 40%, 40%, and 33%, respectively. The Cmax and AUC of omeprazole decreased by 14% and 14%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 12 hours before a single dose of rilpivirine (150 mg) had no significant effect on rilpivirine Cmax or AUC.(1) In a study in 23 subjects, famotidine (40 mg single dose) administered 2 hours before a single dose of rilpivirine (150 mg) decreased the rilpivirine Cmax and AUC by 85% and 76%, respectively.(1) In a study in 24 subjects, famotidine (40 mg single dose) administered 4 hours before a single dose of rilpivirine (150 mg) increased the rilpivirine Cmax and AUC by 21% and 13%, respectively.(1)

Selected Oral Cations/Dolutegravir

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aluminum, calcium, iron, lanthanum, magnesium, sucralfate, and zinc may form chelation compounds with dolutegravir.(1)

CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or sucralfate close to the administration time of dolutegravir may result in decreased absorption and clinical effectiveness of dolutegravir.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, avoid concurrent therapy with dolutegravir and cation-containing products. If it is necessary to use these agents concurrently, dolutegravir should be administered 2 hours before or 6 hours after taking these medications.(1) Alternatively, dolutegravir and supplements containing calcium or iron can be taken together with food.(1)

DISCUSSION: In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) simultaneously with dolutegravir (50 mg single dose) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of dolutegravir by 72%, 74%, and 74%, respectively.(1) In a study in 16 subjects, the administration of an antacid (Maalox - aluminum and magnesium hydroxide) 2 hours after dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 18%, 26%, and 30%, respectively.(1) In a study in 16 subjects, the administration of a multiple vitamin (One-A-Day) simultaneously with dolutegravir (50 mg single dose) decreased dolutegravir Cmax, AUC, and Cmin by 35%, 33%, and 32%, respectively.(1)

Selected Oral Cations/Elvitegravir

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The exact mechanism is unknown, but aluminum, calcium, iron, lanthanum, magnesium, sucralfate, and zinc may bind to elvitegravir in GI tract.

CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or sucralfate may result in decreased levels and effectiveness of elvitegravir, as well as the development of resistance.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Separate the administration of elvitegravir and products containing aluminum, calcium, iron, lanthanum, magnesium, and/or sucralfate by at least 2 hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well.

DISCUSSION: Administration of an antacid (exact formulation not stated) 2 hours before elvitegravir (50 mg) decreased the maximum concentration (Cmax), area-under-curve (AUC), or minimum concentration (Cmin) of elvitegravir by 18%, 15%, and 10%, respectively.(1) Administration of an antacid 2 hours after elvitegravir (50 mg) decreased the Cmax, AUC, or Cmin of elvitegravir by 21%, 20%, and 20%, respectively.(1) Administration of an antacid 4 hours before elvitegravir (50 mg) decreased the Cmax and AUC of elvitegravir by 5%, and 4%, respectively.(1) Administration of an antacid 4 hours before elvitegravir (50 mg) decreased both the Cmax and AUC of elvitegravir by 2%.(1)

Selected Oral Cations/Selected Oral Quinolones

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Aluminum, calcium, iron, lanthanum, magnesium, and zinc may form chelation compounds with the quinolones.(1-40)

CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, lanthanum, magnesium, and/or zinc close to the administration time of an oral quinolone may result in decreased absorption and clinical effectiveness of the quinolone.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: If possible, avoid concurrent therapy with quinolones and cation-containing products. If it is necessary to administer these agents concurrently, follow the manufacturers' recommendations regarding timing of administration of the quinolone and cation-containing products. Manufacturer recommendations regarding the separation of administration times of quinolones and products containing aluminum, calcium, iron, lanthanum, magnesium, and/or zinc vary: ---Do not give ciprofloxacin for at least 2 hours before or 6 hours after oral cations.(1) ---Do not give delafloxacin for at least 2 hours before or 6 hours after oral cations.(2) ---Do not give enoxacin for at least 2 hours before or 8 hours after oral cations.(3) ---Do not give levofloxacin for at least 2 hours before or 2 hours after oral cations.(4) ---Do not give nalidixic acid for at least 2 hours before or 2 hours after oral cations.(5) ---Do not give norfloxacin for at least 2 hours before or 2 hours after oral cations.(6) ---Do not give ofloxacin for at least 2 hours before or 2 hours after oral cations.(7) ---Do not give sparfloxacin for at least 4 hours before oral cations.(8) ---Do not give sitafloxacin for at least 2 hours before or 2 hours after oral cations.(9) The US manufacturer of lanthanum recommends that quinolones be taken at least 1 hour before or 4 hours after lanthanum;(10) however, it would be prudent to follow the specific quinolone manufacturers' recommendations regarding concurrent administration of cations. The US manufacturer of ferric maltose recommends separation of ferric maltose by at least 4 hours. For quinolones not listed above, separate their administration from oral cations by as much time as feasible.

DISCUSSION: Aluminum, calcium, iron, magnesium, and zinc products have been shown to form chelation compounds with quinolone antibiotics, resulting in decreased absorption of the quinolone.(1-40) Treatment failures have been reported.(11-12) In a study in 12 healthy subjects, simultaneous administration of didanosine chewable tablets, which contain aluminum and magnesium, decreased ciprofloxacin area-under-curve (AUC) and maximum concentration (Cmax) by 92% and 98%, respectively.(14) The administration of ciprofloxacin 2 hours prior to Videx chewable/dispersible tablets decreased ciprofloxacin concentrations by 26%.(15,16) In a study in healthy subjects, pretreatment with an antacid containing aluminum-magnesium hydroxide at 5-10 minutes, 2 hours, and 4 hours before a single dose of ciprofloxacin decreased ciprofloxacin AUC by 84.9%, 76.8%, and 30%, respectively. There was no effect when the antacid was administered 6 hours before or 2 hours after.(17) In a study in 12 healthy subjects, aluminum hydroxide decreased ciprofloxacin AUC by 85%.(18) In a study in patients on continuous ambulatory peritoneal dialysis, peak levels of ciprofloxacin were decreased by 67% to 92% in patients receiving aluminum-containing antacids.(19) In a study in 15 healthy subjects, simultaneous administration of calcium acetate decreased the bioavailability of ciprofloxacin by 51%.(20) In a study in 6 healthy males, simultaneous administration of calcium carbonate decreased ciprofloxacin Cmax and AUC by 40% and 43%, respectively.(21) In a study in 12 healthy subjects, calcium carbonate decreased ciprofloxacin AUC by 40%.(18) In a study in 13 healthy males, calcium carbonate had no effect on ciprofloxacin bioavailability when administered 2 hours prior to the antibiotic.(22,23) In a study in healthy males, simultaneous administration of calcium polycarbophil decreased ciprofloxacin AUC by 50%.(24) In a study in 8 healthy males, simultaneous administration of ferrous fumarate (200 mg) decreased ciprofloxacin AUC by 70%.(25) In a study in healthy subjects, ferrous gluconate decreased ciprofloxacin bioavailability by 50%; however, no significant effects were seen with iron-ovotransferrin.(26) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered ciprofloxacin by 54% and 57%, respectively.(27) In a study in 8 healthy subjects, administration of ferrous sulfate decreased the Cmax and AUC of ciprofloxacin by 33% and 46%, respectively. Administration of ferrous gluconate decreased the Cmax and AUC of ciprofloxacin by 57% and 67%, respectively. Administration of a multivitamin product containing calcium, copper, iron, magnesium, manganese, and zinc decreased the Cmax and AUC of ciprofloxacin by 53% and 56%, respectively.(28) In a study in 12 healthy males, ferrous sulfate decreased ciprofloxacin AUC by 63%.(29) In a study in 12 healthy subjects, lanthanum carbonate decreased the area-under-curve (AUC) and maximum concentration (Cmax) of concurrently administered ciprofloxacin by 54% and 56%, respectively.(30) In a study in 12 healthy males, a multivitamin containing zinc decreased ciprofloxacin AUC by 22%.(29) In a study in 12 healthy subjects, an antacid containing aluminum-magnesium hydroxide had no effect on the pharmacokinetics of intravenous enoxacin.(31) In a study in 10 healthy subjects, administration of an aluminum-magnesium hydroxide antacid 0.5 hours or 2 hours before oral enoxacin (400 mg single dose) decreased the AUC of enoxacin by 73% and 43%, respectively. There were no significant effects on enoxacin AUC when the antacid was administered 8 hours before or 2 hours after enoxacin.(32) In a study in 9 healthy subjects, colloidal aluminum phosphate had no effect on the amount of enoxacin absorbed; however, ferrous sulfate (1050 mg) decreased the amount of enoxacin absorption by 10%.(33) In a study in 5 healthy subjects and 5 patients with cystic fibrosis, separation of levofloxacin (750 mg) and calcium carbonate (500 mg 3 times daily with meals) by 2 hours resulted in no interaction in healthy subjects; however, levofloxacin levels were not bioequivalent in patients with cystic fibrosis.(34) Concurrent magnesium-aluminum hydroxide or calcium have been shown to decrease the bioavailability of norfloxacin by 91.0% and 63.5%, respectively.(35) Concurrent zinc has been shown to decrease the bioavailability of norfloxacin.(36) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered norfloxacin by 75% and 73%, respectively.(27) Simultaneous aluminum phosphate was found to decrease the rate, but not the extent, of absorption of ofloxacin.(37) In a study in 8 healthy subjects, ferrous sulfate decreased the Cmax and AUC of simultaneously administered norfloxacin by 36% and 25%, respectively.(27) In an in vitro study, ferrous sulfate, aluminum hydroxide, and calcium carbonate decreased ofloxacin availability by 32.6%, 30.7%, and 26.2%, respectively. However, in vivo tests showed a significant effect with only aluminum hydroxide.(38) In a study in 9 healthy subjects, simultaneous administration colloidal aluminum phosphate had no effect on ofloxacin (200 mg) absorption; however, ferrous sulfate (1050 mg) decreased the ofloxacin fraction of dose absorbed by 10.85%.(33) In a study in 16 subjects, administration of either aluminum-magnesium hydroxide or calcium carbonate at least 2 hours before or after ofloxacin administration had no significant effects on ofloxacin levels.(39) The administration of an antacid containing aluminum hydroxide and magnesium hydroxide 2 hours before, 2 hours after, and 4 hours after sparfloxacin decreased sparfloxacin levels by 23%, 17%, and 5%, respectively.(40) One or more of the drug pairs linked to this monograph have been included in a list of interactions that could be considered for classification as "non-interruptive" in EHR systems. This DDI subset was vetted by an expert panel commissioned by the U.S. Office of the National Coordinator (ONC) for Health Information Technology.

Slt Cation-Donating Antacids/Polystyrene Sulfonate

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Polystyrene sulfonate may bind the cation from the antacid, resulting in increased intestinal absorption of non-neutralized bicarbonate, which may result in systemic alkalosis and decreased potassium binding by polystyrene sulfonate. Intestinal obstruction has occurred with aluminum hydroxide because of concretion.

CLINICAL EFFECTS: Simultaneous oral use may result in metabolic alkalosis and a decrease in the potassium lowering effect of polystyrene sulfonate. Intestinal obstruction has been reported with aluminum hydroxide.

PREDISPOSING FACTORS: Patients with renal failure may be at a higher risk of systemic alkalosis.

PATIENT MANAGEMENT: Consider the use of alternative agents to cation-donating antacids in patients receiving oral polystyrene sulfonate when possible. If concurrent use is required, separate the dosing by several hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well.

DISCUSSION: In a study in 11 patients with decreased renal function, the administration of magnesium hydroxide and sodium polystyrene sulfonate produced moderate to moderately severe metabolic alkalosis.(2) There are case reports documenting this affect as well.(3-7) Intestinal obstruction has been reported with aluminum hydroxide and sodium polystyrene sulfonate.(8) If the polystyrene sulfonate is administered rectally, a clinically significant interaction is not likely to occur.

There is no enhanced messaging for this drug.

• Appendicitis
• Esophageal obstruction
• Gastrointestinal obstruction

• Dysphagia

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

Less Frequent

• Allergic dermatitis
• Esophageal obstruction
• Intestinal impaction
• Pruritus of skin
• Skin rash

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.

No enhanced messaging available.