Magnesium Citrate

Drug overview for MAGNESIUM CITRATE (magnesium citrate):

Generic name: MAGNESIUM CITRATE (mag-NEE-zee-um-SYE-trate)
Drug class: Hypertonic Laxatives
Therapeutic class: Gastrointestinal Therapy Agents

Laxatives containing magnesium cations or phosphate anions are commonly termed saline laxatives.

No enhanced Uses information available for this drug.

DRUG IMAGES

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The following indications for MAGNESIUM CITRATE (magnesium citrate) have been approved by the FDA:

Indications:
Bowel evacuation
Constipation

Professional Synonyms:
None.

The following drug interaction information is available for MAGNESIUM CITRATE (magnesium citrate):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 3 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
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)	K-PHOS NO.2, K-PHOS ORIGINAL, POTASSIUM PHOSPHATE, SODIUM PHOSPHATE DIBASIC, UROQID-ACID NO.2
Trofinetide/Laxatives 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)	DAYBUE
Tenapanor/Laxatives; Stool Softeners 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)	XPHOZAH

There are 18 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
Tetracyclines/Divalent & Trivalent Cations 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) 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)	AVIDOXY, AVIDOXY DK, BENZODOX 30, BENZODOX 60, BISMUTH-METRONIDAZOLE-TETRACYC, DEMECLOCYCLINE HCL, DORYX, DORYX MPC, DOXYCYCLINE HYCLATE, DOXYCYCLINE IR-DR, DOXYCYCLINE MONOHYDRATE, EMROSI, MINOCYCLINE ER, MINOCYCLINE HCL, MINOCYCLINE HCL ER, MONDOXYNE NL, MORGIDOX, NUZYRA, ORACEA, OXYTETRACYCLINE HCL, PYLERA, SEYSARA, TARGADOX, TETRACYCLINE HCL, XIMINO
Penicillamine, Oral/Polyvalent Cations 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.	CUPRIMINE, D-PENAMINE, DEPEN, PENICILLAMINE, PENICILLAMINE(D-)
Mycophenolate/Aluminum & Magnesium Antacids; Lanthanum; Sevelamer SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum or magnesium antacids and non-calcium containing phosphate binders such as lanthanum and sevelamer decrease the absorption of mycophenolate.(1-3) CLINICAL EFFECTS: The simultaneous administration of mycophenolate with aluminum or magnesium antacids and non-calcium containing phosphate binders such as lanthanum and sevelamer may decrease the levels of mycophenolate and its clinical effects. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of mycophenolate mofetil states that calcium free phosphate binders, such as sevelamer, should not be administered simultaneously with mycophenolate mofetil. Administer sevelamer at least 2 hours after administration of mycophenolate mofetil to decrease the extent of the interaction.(1) The US manufacturer of mycophenolate sodium states that mycophenolate sodium should not be administered simultaneously with antacids. Administer aluminum or magnesium containing antacids at least 2 hours after mycophenolate.(2) Close monitoring of mycophenolic acid levels may be warranted in patients on mycophenolate mofetil therapy that are initiating or discontinuing concurrent therapy with these agents. Patients on concurrent therapies may also require higher doses of mycophenolate mofetil in order to achieve desired blood levels. DISCUSSION: In a study in 10 rheumatoid arthritis patients, the simultaneous administration of mycophenolate and Maalox TC (an antacid containing magnesium and aluminum hydroxide) resulted in decreases in the maximum concentration (Cmax) and area-under-curve (AUC) of mycophenolate by 33% and 17%, respectively.(1,2) In a study of 3 adult patients and 6 pediatric patients with stable renal graft function receiving mycophenolate mofetil, sevelamer (3-4 capsules of 403 mg twice daily) decreased the AUC and Cmax of mycophenolic acid by 26% and 36%, respectively.(1,3) In a study in 12 stable renal transplant patients, administration of magnesium-aluminum-containing antacids (30 ml) increased the Cmax and AUC of a single dose of mycophenolate sodium by 25% and 37%, respectively.(2)	CELLCEPT, MYCOPHENOLATE MOFETIL, MYCOPHENOLIC ACID, MYFORTIC, MYHIBBIN
Gabapentin/Aluminum; Magnesium-Containing Compounds SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum or magnesium containing products may reduce the bioavailability of gabapentin.(1) CLINICAL EFFECTS: Simultaneous administration of aluminum or magnesium containing products and gabapentin may result in decreased absorption of gabapentin by 20% and reduce its clinical effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If the use of both medications is unavoidable, it is recommended that gabapentin be taken at least 2 hours following the administration of aluminum or magnesium containing products.(1) DISCUSSION: In 16 subjects, Maalox reduced the bioavailability of gabapentin by about 20%. The reduction was only 5% when gabapentin was administered 2 hours after the Maalox dose. It is for this reason that the manufacturer of gabapentin recommends that it be taken at least 2 hours after the administration of aluminum or magnesium containing products.(1)	GABAPENTIN, GABAPENTIN ER, GABARONE, GRALISE, HORIZANT, NEURONTIN
Oral Bisphosphonates/Oral Multivalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Multivalent cations may bind to and inhibit the absorption of oral bisphosphonates.(1-6) CLINICAL EFFECTS: Simultaneous administration of products containing multivalent cations may result in decreased levels of and clinical effects from oral bisphosphonates.(1-6) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Instruct patients to separate the administration times of products containing multivalent cations and oral bisphosphonates. Manufacturer recommendations regarding the separation of administration times of oral bisphosphonates and multivalent cations vary. Do NOT give multivalent cation-containing products: - until at least 30 minutes after taking alendronate(1) - within 2 hours of etidronate(2) - until at least 1 hour after taking ibandronate(3) - until at least 30 minutes after taking risedronate(4) - within 2 hours of tiludronate(5) DISCUSSION: Multivalent cations may bind to and inhibit the absorption of oral bisphosphonates, resulting in decreased levels of and clinical effects from these agents.(1-6) Administration of aluminum- or magnesium-containing antacids 1 hour before tiludronate decreased the bioavailability of tiludronate by 60%.(5)	ACTONEL, ALENDRONATE SODIUM, ATELVIA, BINOSTO, FOSAMAX, FOSAMAX PLUS D, IBANDRONATE SODIUM, RISEDRONATE SODIUM, RISEDRONATE SODIUM DR
Chloroquine; Hydroxychloroquine/Di-; Trivalent Cations 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)	CHLOROQUINE PHOSPHATE, HYDROXYCHLOROQUINE SULFATE, PLAQUENIL, SOVUNA
Oral Iron Supplements/Antacids and Selected Minerals 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.	ACCRUFER, AUROVELA 24 FE, AUROVELA FE, AURYXIA, AVERI, BALCOLTRA, BLISOVI 24 FE, BLISOVI FE, CHARLOTTE 24 FE, FEIRZA, FERRIC CITRATE, FINZALA, GALBRIELA, GEMMILY, HAILEY 24 FE, HAILEY FE, JOYEAUX, JUNEL FE, JUNEL FE 24, KAITLIB FE, LARIN 24 FE, LARIN FE, LEVONORG-ETH ESTRAD-FE BISGLYC, LO LOESTRIN FE, LOESTRIN FE, MERZEE, MIBELAS 24 FE, MICROGESTIN FE, MINZOYA, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRONE-E.ESTRADIOL-IRON, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-LEGEST FE, VELPHORO, WYMZYA FE, XARAH FE, XELRIA FE
Eltrombopag/Polyvalent Cations 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)	ALVAIZ, ELTROMBOPAG OLAMINE, PROMACTA
Selected Oral Quinolones/Selected Oral Cations 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. 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.	BAXDELA, CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, LEVOFLOXACIN, LEVOFLOXACIN HEMIHYDRATE, NALIDIXIC ACID, OFLOXACIN
Selected Oral Quinolones/Selected Oral Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Aluminum, iron, lanthanum, magnesium, and zinc may form chelation compounds with the quinolones.(1-23) CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, 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, iron, lanthanum, magnesium, and/or zinc vary: ---Do not give gatifloxacin for at least 4 hours before oral cations(1) ---Do not give gemifloxacin for at least 2 hours before or 3 hours after oral cations.(2) ---Do not give lomefloxacin for at least 2 hours before or 4 hours after oral cations.(3) ---Do not give moxifloxacin for at least 4 hours before or 8 hours after oral cations.(4) ---Do not give trovafloxacin for at least 2 hours before or after oral cations.(5) ---Do not give prulifloxacin for at least 2 hours before or 4 hours after oral cations.(23) The US manufacturer of lanthanum recommends that quinolones be taken at least 1 hour before or 4 hours after lanthanum;(6) however, it would be prudent to follow the specific quinolone manufacturers' recommendations regarding concurrent administration of cations. For quinolones not listed above, separate their administration from oral cations by as much time as feasible. DISCUSSION: Magnesium and aluminum compounds have been shown to form chelation compounds with quinolone antibiotics, resulting in decreased absorption of the quinolone.(1-22) Treatment failures during concurrent use of cations and gatifloxacin(7) and pefloxacin(8) have been reported. In a study in 24 healthy subjects, administration of an aluminum-magnesium hydroxide antacid simultaneously, 2 hours before, or 2 hours after decreased the area-under-curve (AUC) of a single dose of gatifloxacin (400 mg) by 42%, 64%, or 18%, respectively. There were no affects on gatifloxacin AUC when the antacid was administered 4 hours after gatifloxacin.(9) In a study in 16 healthy males, administration of an aluminum-magnesium hydroxide antacid 10 minutes before or 3 hours after a single dose of gemifloxacin (320 mg) decreased the gemifloxacin AUC by 85% and 15%, respectively. There was no affect when the antacid was administered 2 hours after gemifloxacin.(10) In a study in 16 subjects, simultaneous administration of calcium carbonate decreased the maximum concentration (Cmax) and AUC of a single dose of gemifloxacin (320 mg) by 17% and 21%, respectively. There was no effect of calcium carbonate when administered either 2 hours before or after gemifloxacin.(11) In a study in 27 healthy males, the administration of ferrous sulfate (325 mg) 3 hours before a single dose of gemifloxacin (320 mg) decreased the Cmax and AUC of gemifloxacin by 20% and 11%, respectively. There were no effects when ferrous sulfate was administered 2 hours after gemifloxacin.(12) In a study in 8 healthy subjects, ferrous sulfate (100 mg elemental iron) decreased the Cmax and AUC of a single dose of lomefloxacin by 26% and 13%, respectively. There were no effects with concurrent calcium carbonate (500 mg calcium).(13) Magnesium- and aluminum-containing antacids have been shown to decrease the bioavailability of lomefloxacin by 40%.(14) Administration of moxifloxacin 2 hours before, simultaneously, or 4 hours after a magnesium- and aluminum-containing antacid decreased moxifloxacin AUC by 26%, 60%, and 23%, respectively.(15) Simultaneous administration of moxifloxacin and ferrous sulfate (100 mg) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of moxifloxacin by 39% and 59%, respectively.(16) Concurrent administration of calcium had no affect on moxifloxacin pharmacokinetics.(17) In a study in 10 healthy subjects, an aluminum-magnesium hydroxide antacid decreased the bioavailability of pefloxacin (400 mg) by 44.4%.(18) The administration of an antacid containing aluminum hydroxide and magnesium hydroxide 5 minutes before rufloxacin decreased rufloxacin levels by 36%. Administration of the antacid 4 hours after rufloxacin decreased rufloxacin levels by 13%.(19) Magnesium- and aluminum-containing antacids have been shown to decrease the bioavailability of temafloxacin by 40%.(20) Aluminum hydroxide has been shown to decrease the bioavailability of tosufloxacin by 31.6%.(21) Administration of an antacid containing aluminum hydroxide and magnesium hydroxide 30 minutes before trovafloxacin decreased trovafloxacin levels by 66%.(22) 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.	GATIFLOXACIN SESQUIHYDRATE, MOXIFLOXACIN HCL
Elvitegravir/Selected Oral Cations 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, magnesium, sucralfate, and zinc may bind to elvitegravir in GI tract. CLINICAL EFFECTS: Simultaneous administration or administration of products containing aluminum, calcium, iron, 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, 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)	GENVOYA, STRIBILD
Dolutegravir/Selected Oral Cations 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)	DOVATO, TIVICAY, TIVICAY PD, TRIUMEQ, TRIUMEQ PD
Dolutegravir-Rilpivirine/Selected Oral Cations; Antacids; H2 Antagonists 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)	JULUCA
Baloxavir/Polyvalent Cations 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)	XOFLUZA
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
Cabotegravir/Polyvalent Cations 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 2 hours before or 4 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)	VOCABRIA
Amphetamines/Antacids; Urinary Alkalinizers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Antacids and urinary alkalinizers increase the absorption of amphetamines. CLINICAL EFFECTS: Concurrent use of amphetamines and antacids or urinary alkalinizers may result in increased amphetamine levels and side effects. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US and Canadian manufacturers state that coadministration of alkalinizing agents with amphetamines should be avoided.(1-3) The Canadian manufacturer states that concurrent use of proton pump inhibitors and amphetamines should be avoided.(3) The US manufacturer states that patients receiving concurrent therapy should be monitored for changes in clinical effects.(1) Monitor patients receiving concurrent therapy for changes in amphetamine effectiveness and side effects. If concurrent use cannot be avoided, separate the administration times of amphetamines and antacids. Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: Concurrent use of alkalinizing agents with amphetamines increase the absorption of amphetamines. Co-administration of these should be avoided because of the potential of increased actions of the amphetamines.(1,2)	ADDERALL, ADDERALL XR, ADZENYS XR-ODT, AMPHETAMINE SULFATE, DESOXYN, DEXEDRINE, DEXTROAMPHETAMINE SULFATE, DEXTROAMPHETAMINE SULFATE ER, DEXTROAMPHETAMINE-AMPHET ER, DEXTROAMPHETAMINE-AMPHETAMINE, DYANAVEL XR, EVEKEO, METHAMPHETAMINE HCL, MYDAYIS, PROCENTRA, ZENZEDI
Vadadustat/Polyvalent Cations and Phosphate Binders 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)	VAFSEO

The following contraindication information is available for MAGNESIUM CITRATE (magnesium citrate):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

No enhanced Contraindications information available for this drug.

There are 3 contraindications. Absolute contraindication.

Contraindication List
Appendicitis
Gastrointestinal obstruction
Hypermagnesemia

There are 2 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Dehydration
Hyponatremia

There are 2 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Kidney disease with reduction in glomerular filtration rate (GFr)
Seizure disorder

The following adverse reaction information is available for MAGNESIUM CITRATE (magnesium citrate):

Overview
Severe
Less Severe

Adverse reaction overview.

No enhanced Common Adverse Effects information available for this drug.

There are 8 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Anaphylaxis Angioedema Cardiac arrhythmia Dyspnea Hypermagnesemia Hyponatremia Seizure disorder Ulceration of colon

There are 10 less severe adverse reactions.

More Frequent	Less Frequent
None.	Abdominal pain with cramps Diarrhea Flatulence Headache disorder Nausea Polydipsia Vomiting

Rare/Very Rare
Pruritus of skin Skin rash Urticaria

The following precautions are available for MAGNESIUM CITRATE (magnesium citrate):

Pediatric
Pregnant
Lactation
Geriatric

No enhanced Pediatric Use information available for this drug.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

No enhanced Pregnancy information available for this drug.

No enhanced Lactation information available for this drug.

No enhanced Geriatric Use information available for this drug.

Constipation
K59.0	Constipation
K59.00	Constipation, unspecified
K59.01	Slow transit constipation
K59.03	Drug induced constipation
K59.04	Chronic idiopathic constipation
K59.09	Other constipation