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Drug overview for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320):
Generic name: pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320
Drug class:
Therapeutic class: Alternative Therapy
Folic acid is a water-soluble, B complex vitamin. Vitamin B12, a cobalt-containing B complex vitamin, is commercially Vitamin B6 (as pyridoxine, pyridoxal, and pyridoxamine) is a water-soluble, available as cyanocobalamin and hydroxocobalamin, which are synthetic forms B complex vitamin. of vitamin B12. Hydroxocobalamin (Cyanokit(R)) is an antidote for cyanide poisoning.
Folic acid is used for the treatment of megaloblastic and macrocytic anemias resulting from folate deficiency. The drug is usually indicated in the treatment of nutritional macrocytic anemia; megaloblastic anemias of pregnancy, infancy, and childhood; and megaloblastic anemia associated with primary liver disease, alcoholism and alcoholic cirrhosis, intestinal strictures, anastomoses, or sprue. Folate deficiency may also result from increased loss of folate secondary to renal dialysis or the administration of some drugs such as phenytoin, primidone, barbiturates, methotrexate, nitrofurantoin, or sulfasalazine.
Folic acid is not effective in the treatment of normocytic, refractory, or aplastic anemias or, when used alone, in the treatment of pernicious anemia. Folic acid antagonists (e.g., methotrexate, pyrimethamine, trimethoprim) inhibit folic acid reductases and prevent the formation of tetrahydrofolic acid. Therefore, folic acid is not effective as an antidote following overdosage of these drugs, and leucovorin calcium must be used.
In large doses, folic acid is used in the treatment of tropical sprue. In patients with this disease, the drug appears to exert a beneficial effect on the underlying mucosal abnormality as well as to correct folate deficiency. Although prophylactic administration of folic acid is not required in most individuals, supplemental folic acid may be required to prevent deficiency of the vitamin in patients with conditions that increase folic acid requirements such as pregnancy, nursing, or chronic hemolytic anemia.
In some patients, such as those with nutritional megaloblastic anemia associated with vitamin B12 deficiency or tropical or nontropical sprue, a simultaneous deficiency of folic acid and cyanocobalamin may exist, and combined therapy may be warranted. Likewise, combined folic acid and iron therapy may be indicated for prevention or treatment of megaloblastic anemia associated with iron deficiency as may occur in conditions such as sprue, megaloblastic anemia of pregnancy, and megaloblastic anemia of infants.
Generic name: pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320
Drug class:
Therapeutic class: Alternative Therapy
Folic acid is a water-soluble, B complex vitamin. Vitamin B12, a cobalt-containing B complex vitamin, is commercially Vitamin B6 (as pyridoxine, pyridoxal, and pyridoxamine) is a water-soluble, available as cyanocobalamin and hydroxocobalamin, which are synthetic forms B complex vitamin. of vitamin B12. Hydroxocobalamin (Cyanokit(R)) is an antidote for cyanide poisoning.
Folic acid is used for the treatment of megaloblastic and macrocytic anemias resulting from folate deficiency. The drug is usually indicated in the treatment of nutritional macrocytic anemia; megaloblastic anemias of pregnancy, infancy, and childhood; and megaloblastic anemia associated with primary liver disease, alcoholism and alcoholic cirrhosis, intestinal strictures, anastomoses, or sprue. Folate deficiency may also result from increased loss of folate secondary to renal dialysis or the administration of some drugs such as phenytoin, primidone, barbiturates, methotrexate, nitrofurantoin, or sulfasalazine.
Folic acid is not effective in the treatment of normocytic, refractory, or aplastic anemias or, when used alone, in the treatment of pernicious anemia. Folic acid antagonists (e.g., methotrexate, pyrimethamine, trimethoprim) inhibit folic acid reductases and prevent the formation of tetrahydrofolic acid. Therefore, folic acid is not effective as an antidote following overdosage of these drugs, and leucovorin calcium must be used.
In large doses, folic acid is used in the treatment of tropical sprue. In patients with this disease, the drug appears to exert a beneficial effect on the underlying mucosal abnormality as well as to correct folate deficiency. Although prophylactic administration of folic acid is not required in most individuals, supplemental folic acid may be required to prevent deficiency of the vitamin in patients with conditions that increase folic acid requirements such as pregnancy, nursing, or chronic hemolytic anemia.
In some patients, such as those with nutritional megaloblastic anemia associated with vitamin B12 deficiency or tropical or nontropical sprue, a simultaneous deficiency of folic acid and cyanocobalamin may exist, and combined therapy may be warranted. Likewise, combined folic acid and iron therapy may be indicated for prevention or treatment of megaloblastic anemia associated with iron deficiency as may occur in conditions such as sprue, megaloblastic anemia of pregnancy, and megaloblastic anemia of infants.
DRUG IMAGES
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The following indications for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320) have been approved by the FDA:
Indications:
None.
Professional Synonyms:
None.
Indications:
None.
Professional Synonyms:
None.
The following dosing information is available for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320):
Dosage of folic acid injection (sodium folate) is expressed in terms of folic acid. In general, although patient response to folic acid therapy depends on the degree and nature of the deficiency, once proper corrective measures are undertaken, folate-deficient patients generally respond rapidly. During the first 24 hours of treatment, the patient experiences an improved sense of well-being, and within 48 hours, the bone marrow begins to become normoblastic.
Reticulocytosis generally begins within 2-5 days following initiation of folic acid therapy.
Although pyridoxine was previously considered nontoxic even at high dosages, current evidence indicates that chronic administration of large dosages (e.g., 2 g daily) for the management of various conditions can cause severe adverse neurologic effects, and the risk to benefit of such dosages must be carefully weighed. (See Chronic Toxicity.)
For the treatment of pernicious anemia, the usual initial IM or subcutaneous dosage of cyanocobalamin is 100 mcg daily for 6-7 days. If clinical manifestations have improved and a reticulocyte response is observed, cyanocobalamin can then be administered in a dosage of 100 mcg every other day for 7 doses and then 100 mcg every 3-4 days for 2-3 weeks. Once hematologic values have returned to normal, cyanocobalamin can be administered IM or subcutaneously in a dosage of 100 mcg once monthly for life.
Folic acid should be used concomitantly if necessary.
For the treatment of vitamin B12 deficiency in adults, the usual IM dosage of hydroxocobalamin is 30 mcg daily for 5-10 days. Once clinical symptoms have subsided and the blood components have returned to normal, monthly IM maintenance doses of 100-200 mcg appear to be sufficient to maintain a normoblastic bone marrow. For the treatment of vitamin B12 deficiency in children, the usual total IM dose of hydroxocobalamin is 1-5 mcg over 2 or more weeks, given in single doses of 100 mcg.
For maintenance, the IM or subcutaneous pediatric dosage is at least 60 mcg per month; however, smaller doses may often suffice for deficiency states not caused by pernicious anemia.
The commercially available cyanocobalamin metered-dose pump delivers 0.1 mL of solution containing 500 mcg of the drug per actuation. The recommended initial dosage of cyanocobalamin nasal spray is 500 mcg (one actuation) administered intranasally once weekly.
The dosage may need to be increased in patients who experience a decline in serum vitamin B12 concentrations after 1 month of therapy with this preparation. Therapy with a parenteral vitamin B12 preparation may be necessary in patients who do not achieve a satisfactory response to intranasal cyanocobalamin.
Reticulocytosis generally begins within 2-5 days following initiation of folic acid therapy.
Although pyridoxine was previously considered nontoxic even at high dosages, current evidence indicates that chronic administration of large dosages (e.g., 2 g daily) for the management of various conditions can cause severe adverse neurologic effects, and the risk to benefit of such dosages must be carefully weighed. (See Chronic Toxicity.)
For the treatment of pernicious anemia, the usual initial IM or subcutaneous dosage of cyanocobalamin is 100 mcg daily for 6-7 days. If clinical manifestations have improved and a reticulocyte response is observed, cyanocobalamin can then be administered in a dosage of 100 mcg every other day for 7 doses and then 100 mcg every 3-4 days for 2-3 weeks. Once hematologic values have returned to normal, cyanocobalamin can be administered IM or subcutaneously in a dosage of 100 mcg once monthly for life.
Folic acid should be used concomitantly if necessary.
For the treatment of vitamin B12 deficiency in adults, the usual IM dosage of hydroxocobalamin is 30 mcg daily for 5-10 days. Once clinical symptoms have subsided and the blood components have returned to normal, monthly IM maintenance doses of 100-200 mcg appear to be sufficient to maintain a normoblastic bone marrow. For the treatment of vitamin B12 deficiency in children, the usual total IM dose of hydroxocobalamin is 1-5 mcg over 2 or more weeks, given in single doses of 100 mcg.
For maintenance, the IM or subcutaneous pediatric dosage is at least 60 mcg per month; however, smaller doses may often suffice for deficiency states not caused by pernicious anemia.
The commercially available cyanocobalamin metered-dose pump delivers 0.1 mL of solution containing 500 mcg of the drug per actuation. The recommended initial dosage of cyanocobalamin nasal spray is 500 mcg (one actuation) administered intranasally once weekly.
The dosage may need to be increased in patients who experience a decline in serum vitamin B12 concentrations after 1 month of therapy with this preparation. Therapy with a parenteral vitamin B12 preparation may be necessary in patients who do not achieve a satisfactory response to intranasal cyanocobalamin.
Folic acid is usually administered orally. When oral administration is not feasible or when malabsorption is suspected, the drug may be administered by deep IM, subcutaneous, or IV injection. However, most patients with malabsorption are able to absorb oral folic acid.
Cyanocobalamin is administered by IM or deep subcutaneous injection. Cyanocobalamin also is administered orally and intranasally. Hydroxocobalamin is administered by IM injection or IV infusion.
Oral therapy with vitamin B12 preparations is markedly inferior to parenteral therapy and should be used only for the treatment of dietary vitamin B12 deficiency in patients with normal GI absorption. Pyridoxine hydrochloride is usually administered orally; however, the drug may be given by IM, IV, or subcutaneous injection when oral administration is not feasible. In infants with seizures, pyridoxine hydrochloride should be administered by IM or IV injection.
Cyanocobalamin is administered by IM or deep subcutaneous injection. Cyanocobalamin also is administered orally and intranasally. Hydroxocobalamin is administered by IM injection or IV infusion.
Oral therapy with vitamin B12 preparations is markedly inferior to parenteral therapy and should be used only for the treatment of dietary vitamin B12 deficiency in patients with normal GI absorption. Pyridoxine hydrochloride is usually administered orally; however, the drug may be given by IM, IV, or subcutaneous injection when oral administration is not feasible. In infants with seizures, pyridoxine hydrochloride should be administered by IM or IV injection.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320):
There are 1 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
Drug Interaction | Drug Names |
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Deuruxolitinib/Strong & Moderate CYP2C9 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Strong or moderate CYP2C9 inhibitors may inhibit the metabolism of deuruxolitinib.(1) CLINICAL EFFECTS: Concurrent use of deuruxolitinib with a strong or moderate inhibitor of CYP2C9 may result in elevated levels of and toxicity from deuruxolitinib, including hematologic toxicities (neutropenia, lymphopenia, anemia), lipid abnormalities, infection, and thrombosis.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of deuruxolitinib states that concomitant treatment with a strong or moderate CYP2C9 inhibitor is contraindicated.(1) DISCUSSION: Concurrent use with strong CYP2C9 inhibitors has not been studied. Based on pharmacokinetic modelling, deuruxolitinib area-under-curve (AUC) is predicted to be increased by 200% and maximum concentration (Cmax) by 25% following concomitant use of multiple dosages of a strong CYP2C9 inhibitor with a single dose of 12 mg deuruxolitinib (1.5 times the licensed 8 mg dose).(1) Deuruxolitinib AUC increased by 140% and Cmax by 21% following concomitant use of multiple dosages of 200 mg fluconazole (dual moderate CYP3A4 and CYP2C9 inhibitor) with a single dose of 12 mg deuruxolitinib (1.5 times the licensed 8 mg dose).(1) Strong CYP2C9 inhibitors linked to this monograph include: sulfaphenazole.(2-3) Moderate CY2C9 inhibitors linked to this monograph include: amiodarone, apazone, benzbromarone, fluconazole, miconazole, mifepristone, milk thistle, nitisinone, oxandrolone, phenylbutazone, and piperine.(2-3) |
LEQSELVI |
There are 5 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 |
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Siponimod/Selected Moderate CYP2C9 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inhibitors of CYP2C9 may inhibit the metabolism of siponimod.(1) CLINICAL EFFECTS: Concurrent use of an inhibitor of CYP2C9 may result in elevated levels of and clinical effects of siponimod, including immunosuppression and increased risk of infection.(1) Concurrent use of siponimod with immunosuppressive or immune-modulating agents, such as asciminib, may result in an additive risk and increased risk of serious infections. PREDISPOSING FACTORS: Concurrent use of a strong or moderate inhibitor of CYP3A4 may increase the effects of the interaction. PATIENT MANAGEMENT: Concurrent use of an inhibitor of CYP2C9 with siponimod is not recommended in patients also taking a strong or moderate inhibitor of CYP3A4.(1) Review the patient's therapy for concurrent use of strong or moderate inhibitors of CYP3A4 prior to initiating siponimod. If concurrent use is necessary, the manufacturer of nitisinone recommends reducing the dosage of a CYP2C9 substrate like siponimod by one-half.(2) DISCUSSION: Siponimod is metabolized by CYP2C9 (79.3%) and CYP3A4 (18.5%). Concurrent use of fluconazole (a dual moderate inhibitor of CYP2C9 and CYP3A4, 200 mg at steady state) in healthy subjects with the CYP2C9*1/*1 genotype increased the area-under-curve (AUC) of siponimod (4 mg single dose) by 2-fold. Siponimod half-life increased by 50%. Fluconazole increased siponimod AUC by 2-fold to 4-fold across all CYP2C9 genotypes.(1) Selected moderate CYP2C9 inhibitors linked to this monograph include: apazone, asciminib, benzbromarone, felbamate, miconazole, milk thistle, nitisinone, oxandrolone, phenylbutazone, piperine, silibinin, and sulfaphenazole.(3) |
MAYZENT |
Erdafitinib/Strong CYP3A4 or Moderate CYP2C9 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Erdafitinib is metabolized by CYP3A4 and CYP2C9. Strong inhibitors of CYP3A4 or moderate inhibitors of CYP2C9 may inhibit the metabolism of erdafitinib.(1) CLINICAL EFFECTS: Concurrent use of strong CYP3A4 or moderate CYP2C9 inhibitors may increase the levels and effects of erdafitinib, including retinopathy and hyperphosphatemia.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US prescribing information states that concurrent use of erdafitinib with strong CYP3A4 inhibitors or moderate CYPC9 inhibitors should be avoided. If concurrent use cannot be avoided, monitor closely for adverse reactions and consider a dose modification based on prescribing information. If the strong CYP3A4 or moderate CYP2C9 inhibitor is discontinued, consider increasing the erdafitinib dose if patient does not have any drug-related toxicity.(1) If concurrent use with nitisinone cannot be avoided, the manufacturer of nitisinone recommends reducing the dosage of a CYP2C9 substrate like erdafitinib by one-half.(2) DISCUSSION: In PKPB models, concurrent use of fluconazole (a moderate CYP2C9 and CYP3A4 inhibitor) resulted in erdafitinib mean ratios for concentration maximum (Cmax) and area-under-curve (AUC) of 121% and 148% , respectively, compared to erdafitinib alone.(1) In PKPB models, concurrent use of itraconazole (a strong CYP3A4 inhibitor and P-gp inhibitor) resulted in erdafitinib mean ratios for Cmax and AUC of 105% and 134%, respectively, compared to erdafitinib alone.(1) Strong inhibitors of CYP3A4 include: adagrasib, boceprevir, ceritinib, clarithromycin, cobicistat, idelalisib, indinavir, itraconazole, josamycin, ketoconazole, levoketoconazole, lonafarnib, lopinavir, mibefradil, mifepristone, nefazodone, nelfinavir, nirmatrelvir, paritaprevir, posaconazole, ribociclib, saquinavir, telaprevir, telithromycin, tipranavir, troleandomycin, tucatinib, and voriconazole.(3,4) Moderate inhibitors of CYP2C9 include: adagrasib, amiodarone, apazone, asciminib, benzbromarone, fluconazole, miconazole, mifepristone, milk thistle, nitisinone, oxandrolone, phenylbutazone, and sulfaphenazole.(2,3) |
BALVERSA |
Vincristine/P-glycoprotein (P-gp) Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inducers of P-glycoprotein (P-gp) may reduce systemic exposure to vincristine.(1) CLINICAL EFFECTS: Concurrent or recent use of P-gp inducers may result in decreased effectiveness of vincristine.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of vincristine states that concurrent use of P-gp inducers should be avoided.(1) Consider the use of agents with no or minimal induction potential if possible. Monitor patients for decreased response to therapy. DISCUSSION: Vincristine is transported by P-gp and inducers of this transporter are expected to decrease levels of vincristine.(1) Inducers of P-gp include linked to this monograph include: efavirenz, green tea, and lorlatinib.(2,3) |
VINCASAR PFS, VINCRISTINE SULFATE |
Vincristine/P-glycoprotein (P-gp) Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: P-glycoprotein (P-gp) inhibitors may inhibit cellular efflux of vincristine.(1) CLINICAL EFFECTS: Concurrent administration of a P-gp inhibitor may result in elevated levels of and toxicity from vincristine including myelosuppression, neurologic toxicity, tumor lysis syndrome, hepatotoxicity, constipation, or bowel obstruction.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of P-gp inhibitors in patients undergoing therapy with vincristine.(1) Consider alternatives with no or minimal P-gp inhibition. The manufacturer of vincristine states that concomitant use of P-gp inhibitors should be avoided.(1) The manufacturer of lopinavir/ritonavir states that patients who develop significant hematological or gastrointestinal toxicity on concomitant vincristine should temporarily hold lopinavir/ritonavir, or use alternative medications that do not inhibit CYP3A4 or P-gp.(2) DISCUSSION: Vincristine is a substrate of P-gp. Inhibitors of P-gp may increase toxicity of vincristine.(1) There are several case reports of neurotoxicity with concurrent administration of vincristine and itraconazole.(3-5) There is a case report of neurotoxicity with concurrent administration of lopinavir-ritonavir with vincristine.(6) In a prospective study in 22 children receiving various chemotherapy with prophylactic itraconazole oral solution (0.5 ml/kg per day), two children receiving vincristine developed non-alcoholic steatohepatitis (NASH) and one child developed syndrome of inappropriate anti-diuretic hormone secretion (SIADH).(7) Strong inhibitors of P-gp linked to this monograph include: abrocitinib, amiodarone, Asian ginseng (Panax ginseng), asunaprevir, azithromycin, belumosudil, capmatinib, carvedilol, cimetidine, cyclosporine, danicopan, daridorexant, diltiazem, diosmin, dronedarone, elagolix, eliglustat, erythromycin, flibanserin, fluvoxamine, fostamatinib, ginkgo biloba, glecaprevir and pibrentasvir, isavuconazonium, ivacaftor, lapatinib, mavorixafor, milk thistle (Silybum marianum), neratinib, osimertinib, pirtobrutinib, propafenone, quercetin, quinidine, ranolazine, rolapitant, Schisandra chinensis, selpercatinib, sofosbuvir, sotorasib, tepotinib, tezacaftor, valbenazine, velpatasvir, vemurafenib, venetoclax, verapamil, vilazodone, vimseltinib, and voclosporin.(8,9) |
VINCASAR PFS, VINCRISTINE SULFATE |
Ensartinib/Selected P-glycoprotein (P-gp) Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ensartinib is a P-glycoprotein (P-gp) substrate. P-gp inhibitors may increase the levels of ensartinib.(1) CLINICAL EFFECTS: The concurrent administration of a P-glycoprotein (P-gp) inhibitor may result in elevated levels of and toxicity from ensartinib.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of ensartinib states that concurrent use of P-glycoprotein (P-gp) inhibitors should be avoided.(1) DISCUSSION: Ensartinib is a substrate of P-gp. Inhibitors of P-gp may increase toxicity of ensartinib.(1) Inhibitors of P-gp linked to this monograph include: abrocitinib, amiodarone, Asian ginseng (Panax ginseng), asunaprevir, azithromycin, belumosudil, capmatinib, carvedilol, cimetidine, cyclosporine, danicopan, daridorexant, diosmin, eliglustat, flibanserin, fostamatinib, ginkgo biloba, glecaprevir and pibrentasvir, hydroquinidine, ivacaftor, lapatinib, mavorixafor, milk thistle (Silybum marianum), neratinib, osimertinib, propafenone, quercetin, quinidine, ranolazine, rolapitant, silibinin, silymarin, sotagliflozin, tepotinib, tezacaftor, valbenazine, velpatasvir, vemurafenib, venetoclax, vilazodone, vimseltinib, and voclosporin.(2,3) |
ENSACOVE |
There are 35 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 |
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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-) |
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. |
KIONEX, SODIUM POLYSTYRENE SULFONATE, SPS |
Levodopa/Pyridoxine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Pyridoxine increases levodopa metabolism, decreasing the amount of levodopa available to the central nervous system. CLINICAL EFFECTS: The pharmacologic effects of levodopa may be decreased. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid pyridoxine in patients receiving levodopa alone; however, the interaction can be minimized by giving levodopa with a peripheral decarboxylase inhibitor (e.g. carbidopa, benserazide). DISCUSSION: In patients with Parkinson's disease, as little as 10 mg of pyridoxine may reverse the clinical benefits as well as the adverse effects of levodopa. Coadministration of levodopa with either carbidopa or benserazide has minimized the effects of this interaction. |
INBRIJA, LEVODOPA |
Itraconazole; Ketoconazole/Agents Affecting Gastric pH SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Antacids, buffers in didanosine products, H2 antagonists, and proton-pump inhibitors increase the stomach pH. Quinapril tablets may contain a high percentage of magnesium. Since some orally administered azole antifungal agents require an acidic medium for optimal absorption, agents may decrease the absorption of azole antifungal agents. CLINICAL EFFECTS: Simultaneous administration of an antacid, buffered didanosine, a H2 antagonist, or a proton-pump inhibitor may result in decreased therapeutic effects of the azole antifungal. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If the concurrent administration of these two agents cannot be avoided, consider administering two capsules of glutamic acid hydrochloride 15 minutes before administering the antifungal and separate the administration times of the antifungal and the agent affecting gastric pH by at least two hours. DISCUSSION: Itraconazole, ketoconazole, and posaconazole require an acidic medium for predictable dissolution and absorption decreases as pH increases and proton pump inhibitors are expected to decrease their absorption.(1-4) In a study in 11 healthy subjects, omeprazole (40 mg daily) decreased the maximum concentration (Cmax) and area-under-curve (AUC) of itraconazole (200 mg single dose) by 66% and 64%, respectively.(5) In a study in 15 healthy subjects, omeprazole (40 mg daily) had no effect on the pharmacokinetics of itraconazole solution.(6) In a study in 9 healthy subjects, omeprazole (60 mg) decreased the AUC of ketoconazole (200 mg single dose) by 83.4% compared to control (ketoconazole alone). Administration of Coca-Cola (240 ml) with ketoconazole and omeprazole raised ketoconazole AUC to 65% of control values.(7) Omeprazole has been shown to have no significant effect on the absorption of fluconazole(8) or voriconazole.(9) Case reports and in-vivo studies have documented significant decreases in ketoconazole levels during concurrent therapy with H-2 antagonists, including cimetidine and ranitidine. Concurrent administration of itraconazole and famotidine resulted in a significant decrease in itraconazole levels, but no significant changes in famotidine levels. An interaction should be expected to occur between both ketoconazole or itraconazole and the other H-2 antagonists.(10-14) In randomized, open-labeled, cross-over study in 12 healthy subjects, simultaneous administration of an antacid decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of itraconazole (200 mg) by 66% and 70%, respectively. Time to Cmax (Tmax) increased by 70%.(15) This interaction has also been reported in a case report.(16) In a study in 3 subjects, simultaneous administration of a combination aluminum hydroxide/magnesium hydroxide (30 ml) decreased the AUC of a single dose of ketoconazole (200 mg) by 41%.(172) In a case report, a patient receiving concurrent ketoconazole with aluminum hydroxide, cimetidine, and sodium bicarbonate did not respond to therapy until cimetidine was discontinued and the administration time of aluminum hydroxide and cimetidine was changed to 2 hours after ketoconazole. In a follow-up study in 2 subjects, concurrent cimetidine and sodium hydroxide lowered ketoconazole levels.(18) In a study in 14 subjects, simultaneous administration of aluminum hydroxide/magnesium hydroxide (20 ml, 1800 mg/1200 mg) had no significant effects on fluconazole pharmacokinetics.(3) In a randomized, open-label, cross-over study in 6 subjects, simultaneous administration of itraconazole with buffered didanosine tablets resulted in undetectable levels of itraconazole.(19) In a randomized cross-over study in 12 HIV-positive subjects, administration of buffered didanosine tablets 2 hours after ketoconazole had no effects on ketoconazole levels.(20) In a randomized, cross-over, open-label study in 24 healthy subjects, simultaneous administration of enteric-coated didanosine had no effect on ketoconazole pharmacokinetics.(21) 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. |
ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KETOCONAZOLE, SPORANOX, TOLSURA |
Thyroid Preparations/Calcium; Iron; Sucralfate 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. |
ADTHYZA, ARMOUR THYROID, CYTOMEL, ERMEZA, EUTHYROX, LEVO-T, LEVOTHYROXINE SODIUM, LEVOTHYROXINE SODIUM DILUTION, LEVOXYL, LIOTHYRONINE SODIUM, NIVA THYROID, NP THYROID, PCCA T3 SODIUM DILUTION, PCCA T4 SODIUM DILUTION, RENTHYROID, SYNTHROID, THYQUIDITY, THYROID, TIROSINT, TIROSINT-SOL, UNITHROID |
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 |
Phenytoin/Aluminum-Magnesium Hydroxide; Oral Calcium 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) |
DILANTIN, DILANTIN-125, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED |
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 Cephalosporins/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Absorption of oral cefuroxime may be reduced in patients receiving concomitant treatment with acid reducing agents.(1,2) CLINICAL EFFECTS: Antibiotic efficacy against organisms with a high minimum inhibitory concentration (MIC) to cefuroxime could be decreased. PREDISPOSING FACTORS: Taking cefuroxime on an empty stomach magnifies this effect. PATIENT MANAGEMENT: Separate the administration of cefuroxime by at least 1-2 hours after administration of antacids. Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. Since concurrent use of H2 antagonists and proton pump inhibitors (PPIs) in patients taking cefuroxime should be avoided, these would not be alternatives to antacids in these patients. DISCUSSION: In a study performed prior to the introduction of PPIs, administration of ranitidine 300 mg and sodium bicarbonate followed by cefuroxime taken on a empty stomach lowered both Cmax and AUC of cefuroxime by approximately 40 per cent compared with administration of cefuroxime alone on an empty stomach. Postprandial administration of cefuroxime in subjects taking ranitidine was similar to that of subjects taking cefuroxime on an empty stomach.(2) |
CEFUROXIME |
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 |
Riociguat/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of interaction is not clear. Increased gastric pH is thought to decrease riociguat solubility and absorption.(1) CLINICAL EFFECTS: Simultaneous administration of riociguat with an antacid may result in decreased levels and effectiveness of riociguat.(1-2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Separate the administration of antacids and riociguat by at least 1 hour.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: Administration of 10 mL of an aluminum hydroxide-magnesium hydroxide containing antacid decreased the area-under-curve (AUC)and maximum concentration (Cmax)of riociguat by 34% and 56% respectively.(1) |
ADEMPAS |
Nadolol/Green Tea SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Nadolol is a substrate of OATP1A2, an influx transporter found in intestinal epithelium. Green tea catechins inhibit several drug transporters, including OATP1A2, leading to decreased absorption of nadolol. P-glycoprotein may also be involved, however no studies have confirmed its role. CLINICAL EFFECTS: Concomitant use of nadolol with green tea or green tea catechins may decrease the effectiveness of nadolol.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Advise patients maintained on nadolol to avoid green tea and green tea supplements. DISCUSSION: In a randomized crossover study in 10 healthy subjects, concurrent use of nadolol (30 mg daily) and green tea (700 mL/day), decreased the maximum concentration (Cmax) and area-under-curve (AUC) of nadolol by 85.3% and 85%, respectively. Pharmacodynamic parameters assessed included pulse rate, systolic blood pressure, and diastolic blood pressure. Although all parameters were affected slightly, nadolol's systolic blood pressure lowering effect was significantly suppressed (p = 0.042).(1) |
NADOLOL |
Ledipasvir; Velpatasvir/Antacids; H2 Antagonists SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of ledipasvir and velpatasvir is pH dependent. Higher gastric pH leads to lower solubility which may reduce ledipasvir and velpatasvir's absorption.(1-3) CLINICAL EFFECTS: Administration of antacids and H2 antagonists may reduce the bioavailability of ledipasvir and velpatasvir, leading to decreased systemic levels and effectiveness.(1-3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: In order to assure systemic absorption and maximal effectiveness from use of this Hepatitis C treatment, counsel patient to separate products containing ledipasvir or velpatasvir from antacid administration by 4 hours.(1-3) H2 antagonists may be administered simultaneously or 12 hours apart from products containing ledipasvir or velpatasvir at a dose that does not exceed doses comparable to famotidine 40 mg twice daily (or a total daily dose comparable to famotidine 80 mg).(1-3) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: In an interaction study, famotidine 40 mg, given with or 12 hours after a ledipasvir-sofosbuvir dose did not have significant effects on ledipasvir-sofosbuvir exposure.(1) In an interaction study, famotidine 40 mg, given with or 12 hours prior to a velpatasvir-sofosbuvir dose did not have a significant effect on velpatasvir-sofosbuvir exposure.(2) In an interaction study, famotidine (dosage not stated) did not have a significant effect on the pharmacokinetic of sofosbuvir, velpatasvir, or voxilaprevir.(3) |
EPCLUSA, HARVONI, LEDIPASVIR-SOFOSBUVIR, SOFOSBUVIR-VELPATASVIR, VOSEVI |
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 |
Bictegravir/Calcium & Iron Containing Supplements 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) |
BIKTARVY |
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 |
Warfarin/Milk Thistle SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Milk thistle may inhibit the metabolism of warfarin through CYP2C9.(1) CLINICAL EFFECTS: Concurrent use of warfarin and milk thistle may result in elevated INR values and increased risk of bleeding. PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Advise patients against using milk thistle products with warfarin and to report the initiation or discontinuation of any alternative therapy agents. If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit,fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black,tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: A review of in vivo and in vitro drug interaction studies with milk thistle suggests there is the possibility of significant CYP2C9 inhibition by milk thistle. In one case study, an individual stable on a warfarin dose of 36.5 mg per week for 8 months began taking a supplement containing 200 mg of milk thistle. At a 4-week follow up, the patient's INR had increased from 2.64 to 4.12. The patient was instructed to stop the supplement, hold one dose of warfarin, and then continue his previous dose. At a 1-week follow-up, his INR was slightly sub-therapeutic at 2.37, but repeat INRs were therapeutic at 3.24 and 2.98 at 4 and 8 weeks.(2) A study was conducted to investigate the effects of milk thistle on the pharmacokinetics of losartan (a CYP2C9 substrate) and its active metabolite E-3147, and its relationship with CYP2C9 genotypes. The AUC of losartan increased significantly following a 14-day milk thistle treatment in subjects with CYP2C9*1/*1 genotype. The results showed that milk thistle inhibits the metabolism of losartan to E-3147, with the magnitude of the interaction differing in individuals with different CYP2C9 genotypes.(3) |
JANTOVEN, WARFARIN SODIUM |
Infigratinib; Selpercatinib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The solubility of infigratinib and selpercatinib is pH dependent. Antacid-induced changes in gastric pH may decrease the absorption of infigratinib and selpercatinib.(1,2) CLINICAL EFFECTS: Simultaneous administration of antacids may result in decreased levels and effectiveness of infigratinib and selpercatinib.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of antacids, proton pump inhibitors (PPIs), and H2 antagonists, in patients receiving treatment with infigratinib or selpercatinib. If coadministration with antacids cannot be avoided, take infigratinib or selpercatinib at least 2 hours before or 2 hours after the antacid.(1,2) If the antacid is replaced with a H2 antagonist, take infigratinib or selpercatinib 2 hours before or 10 hours after the H2 antagonist.(1,2) If the antacid is replaced with a PPI, take selpercatinib with food.(2) DISCUSSION: Infigratinib is practically insoluble at pH 6.8.(1) Selpercatinib solubility is pH dependent.(2) Antacids may decrease the solubility and absorption of infigratinib and selpercatinib and decrease their effectiveness. |
RETEVMO |
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 |
Sotorasib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of sotorasib is pH dependent. Higher gastric pH leads to lower solubility which may reduce sotorasib absorption.(1) CLINICAL EFFECTS: Coadministration of antacids may reduce the bioavailability of sotorasib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of sotorasib with proton pump inhibitors, H2 antagonists, and antacids should be avoided. If coadministration with an acid-reducing agent is unavoidable, take sotorasib 4 hours before or 10 hours after a locally acting antacid.(1) DISCUSSION: The solubility of sotorasib in the aqueous media decreases over the range pH 1.2 to 6.8 from 1.3 mg/mL to 0.03 mg/mL. In an interaction study, coadministration of repeat doses of omeprazole with a single dose of sotorasib decreased sotorasib maximum concentration (Cmax) by 65% and area-under-curve (AUC) by 57% under fed conditions, and decreased sotorasib Cmax by 57% and AUC by 42% under fasted conditions. Coadministration of a single dose of famotidine given 10 hours prior to and 2 hours after a single dose of sotorasib under fed conditions decreased sotorasib Cmax by 35% and AUC by 38%.(1) |
LUMAKRAS |
Pafolacianine/Folic Acid SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Folate, folic acid, and folate-containing supplements may reduce binding of pafolacianine to folate receptors expressed on ovarian cancer cells. CLINICAL EFFECTS: Folate, folic acid, and folate-containing supplements could reduce the detection of malignant lesions with pafolacianine. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid administration of folate, folic acid, or folate-containing supplements within 48 hours before administration of pafolacianine. DISCUSSION: Folate, folic acid, and folate-containing supplements may reduce binding of pafolacianine to folate receptors expressed on cancer cells, which could result in reduced detection of malignant lesions with pafolacianine. |
CYTALUX |
Levoketoconazole/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of levoketoconazole is pH dependent. Higher gastric pH leads to lower solubility. Antacids increase gastric pH and may decrease the absorption of levoketoconazole.(1) CLINICAL EFFECTS: Coadministration of antacids may reduce the bioavailability of levoketoconazole, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of levoketoconazole with proton pump inhibitors and H2 antagonists should be avoided. If coadministration with an acid-reducing agent is unavoidable, take the antacid 2 hours before levoketoconazole.(1) DISCUSSION: Levoketoconazole is very slightly soluble in water but soluble below pH 2. Antacids raise gastric pH and may impair dissolution and absorption of levoketoconazole.(1) |
RECORLEV |
Sparsentan/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of sparsentan is pH dependent. Higher gastric pH leads to lower solubility. Antacids increase gastric pH and may decrease the absorption of sparsentan.(1) CLINICAL EFFECTS: Coadministration of antacids may reduce the bioavailability of sparsentan, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If coadministration with an acid-reducing agent is unavoidable, take an antacid 2 hours before or 2 hours after sparsentan. Coadministration of sparsentan with proton pump inhibitors and H2 antagonists should be avoided.(1) DISCUSSION: Sparsentan is practically insoluble in water but has intrinsic solubility of 1.48 mg/mL and 0.055 mg/mL below pH 1.2 and 6.8, respectively. Antacids raise gastric pH and may impair dissolution and absorption of sparsentan.(1) |
FILSPARI |
Migalastat/Caffeine-Containing Products SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The mechanism of this interaction is unknown. CLINICAL EFFECTS: Concurrent use of a caffeine-containing product may result in decreased levels and effectiveness of migalastat.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid coadministration of migalastat with caffeine-containing products. Do not administer caffeine-containing products within 2 hours before and 2 hours after taking migalastat.(1) DISCUSSION: Coadministration of migalastat with caffeine 190 mg decreased the migalastat maximum concentration (Cmax) by 60% and area-under-curve (AUC) by 55%.(1) |
GALAFOLD |
Nirogacestat/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of nirogacestat is pH dependent. Higher gastric pH leads to lower solubility which may reduce nirogacestat absorption.(1) CLINICAL EFFECTS: Coadministration of antacids may reduce the bioavailability of nirogacestat, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of nirogacestat with proton pump inhibitors, H2 antagonists, and antacids should be avoided. If coadministration with an acid-reducing agent is unavoidable, take nirogacestat 2 hours before or 2 hours after a locally acting antacid.(1) DISCUSSION: The solubility of nirogacestat is poor at a pH >= 6.(1) Concomitant use of proton pump inhibitors, H2 antagonists, or antacids are expected to reduce concentrations of nirogacestat.(1) |
OGSIVEO |
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 |
Cefpodoxime/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Absorption of oral cefpodoxime may be reduced in patients receiving concomitant treatment with acid reducing agents.(1-3) CLINICAL EFFECTS: Antibiotic efficacy against organisms with a high minimum inhibitory concentration (MIC) to cefpodoxime could be decreased. PREDISPOSING FACTORS: Taking cefpodoxime on an empty stomach magnifies this effect. PATIENT MANAGEMENT: Separate the administration of cefpodoxime by at least 1-2 hours after administration of antacids. Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. Since concurrent use of H2 antagonists and proton pump inhibitors (PPIs) in patients taking cefpodoxime should be avoided, these would not be alternatives to antacids in these patients. DISCUSSION: In a study of ten subjects, administration of cefpodoxime after single dose famotidine 40 mg decreased both maximum concentration (Cmax) and area-under-curve (AUC) by approximately 40% compared with administration of cefpodoxime on an empty stomach.(2) In a study of 17 subjects, administration of cefpodoxime after single dose ranitidine 150 mg decreased Cmax and AUC by approximately 40% compared with administration of cefpodoxime on an empty stomach.(3) |
CEFPODOXIME PROXETIL |
Mavorixafor/P-glycoprotein (P-gp) Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Mavorixafor is a substrate of the P-glycoprotein (P-gp) transporter. P-gp inhibitors may significantly increase the absorption of mavorixafor.(1) CLINICAL EFFECTS: Concurrent administration of mavorixafor with an inhibitor of P-glycoprotein may result in elevated levels of and effects from mavorixafor, including potentially life-threatening cardiac arrhythmias, torsades de pointes, and sudden death.(1) PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, and/or renal/hepatic dysfunction).(2) PATIENT MANAGEMENT: When used concomitantly with P-gp inhibitors, monitor more frequently for mavorixafor adverse effects and reduce the dose in 100 mg increments, if necessary, but not to a dose less than 200 mg.(1) The manufacturer of vimseltinib states concurrent use with P-gp substrates should be avoided. If concurrent use cannot be avoided, take vimseltinib at least 4 hours prior to mavorixafor.(4) When concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring EKG at baseline and regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. DISCUSSION: In a study with healthy subjects, itraconazole 200 mg daily (a strong CYP3A4 and P-gp inhibitor) increased the exposure to single-dose mavorixafor 200 mg similar to that from single-dose mavorixafor 400 mg alone. This suggests that itraconazole increased mavorixafor exposure by about 2-fold.(1) A study in healthy volunteers found that ritonavir 100 mg twice daily (a strong CYP3A4 inhibitor and P-gp inhibitor) increased the area-under-curve (AUC) and maximum concentration (Cmax) of single-dose mavorixafor 200 mg by 60% and 39%, respectively.(1) P-glycoprotein inhibitors linked to this monograph include: abrocitinib, Asian ginseng, asunaprevir, capmatinib, carvedilol, cyclosporine, danicopan, daridorexant, diosmin, elagolix, flibanserin, fostamatinib, ginkgo biloba, glecaprevir/pibrentasvir, ivacaftor, milk thistle, neratinib, pirtobrutinib, quercetin, rolapitant, sofosbuvir/velpatasvir/voxilaprevir, tepotinib, tezacaftor, velpatasvir, vilazodone, vimseltinib, and voclosporin.(1,4-6) |
XOLREMDI |
Defactinib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of defactinib is pH dependent. Higher gastric pH leads to lower solubility which may reduce defactinib absorption.(1) CLINICAL EFFECTS: Coadministration with antacids may reduce the bioavailability of defactinib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of defactinib states that patients requiring acid-lowering therapy should separate defactinib from antacid administration by 2 hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: The impact of antacids on the pharmacokinetics of defactinib has not been investigated in clinical studies. In an interaction study, defactinib area-under-the-curve (AUC) decreased by 79% and maximum concentration (Cmax) decreased by 85% following concomitant use of multiple doses of omeprazole 40 mg daily. The AUC and Cmax of N-desmethyl amide (M4), a major active metabolite of defactinib, decreased by 83% and 88%, respectively.(1) |
AVMAPKI-FAKZYNJA, FAKZYNJA |
Taletrectinib/Antacids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The aqueous solubility of taletrectinib is pH dependent. Higher gastric pH leads to lower solubility which may reduce taletrectinib absorption.(1) CLINICAL EFFECTS: Coadministration with antacids may reduce the bioavailability of taletrectinib, leading to decreased systemic levels and effectiveness.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of taletrectinib states that patients requiring acid-lowering therapy should separate taletrectinib from antacid administration by 2 hours.(1) Some vitamin preparations may contain sufficient quantities of calcium and/or magnesium salts with antacid properties to interact as well. DISCUSSION: The impact of antacids on the pharmacokinetics of taletrectinib has not been investigated in clinical studies. In an interaction study, taletrectinib area-under-the-curve (AUC) decreased by 40% and maximum concentration (Cmax) decreased by 65% following concomitant use of omeprazole 40 mg daily.(1) |
IBTROZI |
The following contraindication information is available for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320):
Drug contraindication overview.
No enhanced Contraindications information available for this drug.
No enhanced Contraindications information available for this drug.
There are 2 contraindications.
Absolute contraindication.
Contraindication List |
---|
Biliary obstruction |
Leber's hereditary optic atrophy |
There are 2 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
Severe List |
---|
Biliary calculus |
Insomnia |
There are 7 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
Moderate List |
---|
Anxiety disorder |
Atrophic gastritis |
Diabetes mellitus |
Disease of liver |
Hypertension |
Hypokalemia |
No disease contraindications |
The following adverse reaction information is available for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320):
Adverse reaction overview.
No enhanced Common Adverse Effects information available for this drug.
No enhanced Common Adverse Effects information available for this drug.
There are 2 severe adverse reactions.
More Frequent | Less Frequent |
---|---|
None. | None. |
Rare/Very Rare |
---|
Hypoglycemic disorder Insulin autoimmune syndrome |
There are 0 less severe adverse reactions.
The following precautions are available for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320):
No enhanced Pediatric Use information available for this drug.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Contraindicated
None |
Severe Precaution
None |
Management or Monitoring Precaution
None |
Adequate and well-controlled studies have not been conducted in pregnant women. However, vitamin B12 requirements are increased in pregnant women. Parenteral preparations should be used during pregnancy only when the potential benefits justify the potential risks to the fetus.
Vitamin B12 is distributed into human milk. Vitamin B12 requirements are increased in lactating women. Hydroxocobalamin may be administered to lactating women with suspected or known cyanocobalamin poisoning. There is no data available to determine when breastfeeding may be restarted following administration of IV hydroxocobalamin.
No enhanced Geriatric Use information available for this drug.
The following prioritized warning is available for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for MEDCAPS DPO (pyridoxal phos/methyltetrahydrofolate/mecobalamin/herb 320)'s list of indications:
No ICD codes found for this drug.
No ICD codes found for this drug.
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