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    Pyridoxine/Vitamin B6 Supplements

    DEA CLASS

    OTC, Rx

    DESCRIPTION

    Water-soluble B vitamin (Vitamin B6); naturally found in foods like cereal grains, legumes, vegetables, liver, meat, and eggs
    Used to treat and prevent vitamin B6 deficiency; also used to prevent or treat toxicity from isoniazid, cycloserine, or hydralazine
    Many other uses, including as a first-line supplement for nausea/vomiting of pregnancy

    COMMON BRAND NAMES

    Neuro-K-500

    HOW SUPPLIED

    Pyridoxine (Vitamin B6) Intramuscular Inj Sol: 1mL, 100mg
    Pyridoxine (Vitamin B6) Intravenous Inj Sol: 1mL, 100mg

    DOSAGE & INDICATIONS

    For nutritional supplementation.
    The recommended dietary allowance (RDA) of pyridoxine for nutritional supplementation in healthy individuals.
    Oral dosage
    Adult and Adolescent pregnant females

    1.9 mg/day PO.

    Adult and Adolescent lactating females

    2 mg/day PO.

    Adult females 51 years and older

    1.5 mg/day PO.

    Adult males 51 years and older

    1.7 mg/day PO.

    Adults 19 to 50 years

    1.3 mg/day PO.

    Adolescent females 14 years and older

    1.2 mg/day PO  is the recommended dietary allowance (RDA).

    Adolescent males 14 years and older

    1.3 mg/day PO is the recommended dietary allowance (RDA).

    Children and Adolescents 9 to 13 years

    1 mg/day PO is the recommended dietary allowance (RDA)..

    Children 4 to 8 years

    0.6 mg/day PO is the recommended dietary allowance (RDA)..

    Children 1 to 3 years

    0.5 mg/day PO is the recommended dietary allowance (RDA).

    Infants older than 6 months

    0.3 mg/day PO is the Adequate Intake (AI). Alternatively, weight-based dosing is approximately 0.033 mg/kg/day.

    Neonates and Infants 6 months and younger

    0.1 mg/day PO is the Adequate Intake (AI). Alternatively, weight-based dosing is approximately 0.014 mg/kg/day.

    Premature neonates

    150 to 210 mcg/kg/day PO. The daily requirement is directly related to protein intake.

    In patients receiving total parenteral nutrition (TPN).
    Intravenous dosage
    Adults

    Specific recommendations are not available; however, 10 mL/day of the IV adult parenteral multivitamin preparation, which contains 6 mg of pyridoxine, is recommended to be added to the TPN for nutritional supplementation in patients weighing more than 40 kg.

    Children† and Adolescents† weighing more than 40 kg

    Specific recommendations are not available; however, 10 mL/day of the IV adult parenteral multivitamin preparation, which contains 6 mg of pyridoxine, is recommended to be added to the TPN for nutritional supplementation in patients weighing more than 40 kg.

    Neonates†, Infants†, Children†, and Adolescents† weighing 2.5 to 40 kg

    1 mg/day IV admixed with TPN.

    Neonates† less than 2.5 kg

    0.4 mg/kg/day IV admixed with TPN. Max: 1 mg/day.

    For the treatment of vitamin B6 deficiency states, including neuritis, that are not drug-induced.
    Oral dosage
    Adults without neuritis

    2.5 to 10 mg/day PO. After the deficiency has been corrected, 2 to 5 mg/day may be given for several weeks.

    Adults with neuritis

    100 to 200 mg/day PO for 3 weeks, then 25 to 100 mg/day PO thereafter.

    Children without neuritis

    5 to 25 mg/day PO for 3 weeks, then 1.5 to 2.5 mg/day PO supplemented in a multivitamin product. A pyridoxal phosphate concentration less than 20 nmol/L indicates a vitamin B6 deficiency.

    Children with neuritis

    10 to 50 mg/day for 3 weeks, then 1 to 2 mg/day PO supplemented in a multivitamin product. A pyridoxal phosphate concentration less than 20 nmol/L indicates a vitamin B6 deficiency.

    For the treatment of sideroblastic anemia.
    Oral dosage
    Adults

    200—600 mg/day PO. Following an adequate response, 30—50 mg/day PO may be used.

    For the treatment of seizures due to acute mushroom poisoning.
    Intravenous dosage
    Adults

    25 mg/kg IV administered over 15 to 30 minutes. May be repeated as necessary to a total dose of 15 to 20 g/day.

    Infants†, Children†, and Adolescents†

    25 mg/kg IV administered over 15 to 30 minutes. Max initial dose: 5 grams. Repeat dose as necessary up to 300 mg/kg/day. Max: 15 to 20 grams/day.

    For the treatment of cycloserine toxicity related to pyridoxine deficiency.
    Oral dosage
    Adults

    200 to 300 mg PO once daily.

    For the treatment of hydralazine toxicity related to pyridoxine deficiency.
    Oral dosage
    Adults

    100 to 300 mg/day PO.

    Adolescents

    100 to 300 mg/day PO.

    Children

    10 to 50 mg/day PO.

    For cycloserine toxicity prophylaxis.
    Oral dosage
    Adults

    100 to 300 mg PO once daily.

    Infants†, Children†, and Adolescents†

    1 to 2 mg/kg/dose (Max: 100 mg/dose) PO once daily.

    For hydralazine toxicity prophylaxis.
    Oral dosage
    Adults

    100 mg PO once daily.

    Adolescents†

    25 to 100 mg/day PO.

    Children†

    1 to 2 mg/kg/day PO.

    For oral contraceptive toxicity prophylaxis.
    Oral dosage
    Adult females

    25—30 mg/day PO.

    For the treatment of isoniazid toxicity (other than seizures) related to pyridoxine deficiency.
    Oral dosage†
    Adults

    100 mg PO once daily for patients with peripheral neuropathy.

    Infants, Children, and Adolescents

    1 to 2 mg/kg/dose (Max: 100 mg/dose) PO once daily for patients with peripheral neuropathy.

    Intravenous or Intramuscular dosage
    Adults

    100 mg IV or IM once daily for 3 weeks, followed by 30 mg IV or IM once daily.

    For the treatment of acute penicillamine toxicity.
    Oral dosage
    Adults

    25 to 100 mg PO once daily for 3 weeks followed by 2 to 2.5 mg PO once daily.

    Adolescents†

    100 to 300 mg/day PO.

    Children†

    10 to 50 mg/day PO.

    For penicillamine toxicity prophylaxis.
    Oral dosage
    Adults

    10 to 50 mg/day PO.

    Adolescents†

    25 to 100 mg/day PO.

    Children†

    1 to 2 mg/kg/day PO.

    For isoniazid toxicity prophylaxis.
    For isoniazid toxicity prophylaxis during treatment of active tuberculosis infection.
    Oral dosage
    Adults

    25 to 50 mg PO once daily for patients at risk of neuropathy (e.g., persons with HIV, diabetes, alcoholism, nutritional deficiency, chronic renal failure, advanced age). 

    Infants, Children, and Adolescents

    1 to 2 mg/kg/dose (Max: 50 mg/dose) PO once daily for patients at risk of neuropathy (e.g., persons with HIV, diabetes, alcoholism, nutritional deficiency, chronic renal failure, or breast-feeding children).  

    Neonates†

    1 to 2 mg/kg/dose PO once daily for patients at risk of neuropathy (e.g., persons with HIV, nutritional deficiency, or breast-feeding children).[53484] [65675]

    For isoniazid toxicity prophylaxis during daily treatment for latent tuberculosis infection (LTBI).
    Oral dosage
    Adults

    25 to 50 mg PO once daily for patients at risk of neuropathy (e.g., persons with HIV, diabetes, alcoholism, nutritional deficiency, chronic renal failure, advanced age). 

    Infants, Children, and Adolescents

    1 to 2 mg/kg/dose (Max: 50 mg/dose) PO once daily for patients at risk of neuropathy (e.g., persons with HIV, diabetes, alcoholism, nutritional deficiency, chronic renal failure, or breast-feeding children).  

    For isoniazid toxicity prophylaxis during weekly treatment of latent tuberculosis infection (LTBI).
    Oral dosage
    Adults

    50 mg PO once weekly for patients at risk of neuropathy (e.g., persons with HIV, diabetes, alcoholism, nutritional deficiency, chronic renal failure, advanced age). 

    Children and Adolescents 2 to 17 years

    50 mg PO once weekly for patients at risk of neuropathy (e.g., persons with HIV, diabetes, alcoholism, nutritional deficiency, chronic renal failure, or breast-feeding children).[34362] [44180] [65621] [65734]

    For the treatment of selected metabolic disorders including primary cystathioninuria, primary homocystinuria, or xanthurenic aciduria.
    Oral dosage
    Adults

    100—500 mg/day PO, or more, adjusted to clinical response.

    Children

    Listings in pediatric references vary. Typical doses range from 200—1000 mg/day PO, adjusted to clinical response.

    For the treatment of premenstrual syndrome (PMS).
    Oral dosage
    Adults

    Most studies have shown some benefit of pyridoxine in PMS, but some studies fail to meet methodologic standards for research of this condition. Doses have ranged from 80—500 mg/day PO.

    For the treatment of drug-induced seizures secondary to acute isoniazid overdose.
    Intravenous dosage
    Adults

    A dose of pyridoxine equal to the amount of isoniazid ingested is usually given (i.e., mg-for-mg). In general, 1 to 4 grams IV bolus followed by IM dosing every 30 minutes until the entire dose has been given.

    Infants†, Children†, and Adolescents†

    For acute ingestion of a known amount, a dose of pyridoxine IV equal to the amount of isoniazid ingested is recommended (i.e., if 2 grams of isoniazid is ingested, administer 2 grams of pyridoxine). Max: 70 mg/kg/dose up to 5 grams. For acute ingestion of an unknown amount, give 70 mg/kg/dose IV. Max: 5 grams/dose. Administer dose at a rate of 500 mg/minute until seizures stop or the maximum initial dose has been administered. If the entire initial dose is not administered, give the remaining initial dose over the next 4 to 6 hours to maintain pyridoxine availability while isoniazid is being eliminated. May repeat dose every 5 to 30 minutes as needed if seizures do not resolve or consciousness is not regained. If asymptomatic patients present within 2 hours of acute ingestion, patients should be treated prophylactically with the initial ingestion dose (e.g., 70 mg/kg/dose or 5 grams) and monitored for 6 hours.

    Intramuscular dosage
    Adults

    A dose of pyridoxine equal to the amount of isoniazid ingested is usually given (i.e., mg-for-mg). In general, an initial IV bolus followed by 1 gram IM every 30 minutes until the entire dose has been given.

    Oral dosage
    Infants†, Children†, and Adolescents†

    If adequate amounts of IV pyridoxine are unavailable, the same dose of pyridoxine tablets may be crushed and administered as a slurry via nasogastric tube. For acute ingestion of a known amount, a dose of pyridoxine equal to the amount of isoniazid ingested is recommended (i.e., if 2 grams of isoniazid is ingested, administer 2 grams of pyridoxine). Max: 70 mg/kg/dose up to 5 grams. For acute ingestion of an unknown amount, give 70 mg/kg/dose. Max: 5 grams/dose. Administer dose until seizures stop or the maximum initial dose has been administered. If the entire initial dose is not administered, give the remaining initial dose over the next 4 to 6 hours to maintain pyridoxine availability while isoniazid is being eliminated. May repeat dose every 5 to 30 minutes as needed if seizures do not resolve or consciousness is not regained. If asymptomatic patients present within 2 hours of acute ingestion, patients should be treated prophylactically with the initial ingestion dose (e.g., 70 mg/kg/dose or 5 grams) and monitored for 6 hours.

    For ethionamide toxicity prophylaxis.
    Oral dosage
    Adults

    100 mg PO once daily.

    Infants, Children, and Adolescents

    1 to 2 mg/kg/dose (Max: 100 mg/dose) PO once daily.

    For the treatment of primary hyperoxaluria† in combination with oral orthophosphate therapy.
    Oral dosage
    Adults and Children

    In one trial, the initial dose of pyridoxine ranged 1.8—7 mg/kg/day (mean 3.4 mg/kg/day) PO with a final dose of 1—7 mg/kg/day (mean 2.9 mg/kg/day) was given in combination with oral orthophosphate therapy. Five patients or 25 patients progressed to end-stage renal disease which occurred from 7—23 years after treatment began. No patient had neuropathy or other signs of pyridoxine toxicity.

    For the treatment of pregnancy-induced nausea/vomiting†.
    Oral dosage
    Adult pregnant females

    10 mg to 25 mg PO (taken either alone or in combination with doxylamine 12.5 mg PO), 3 or 4 times per day. Pyridoxine is a first-line pharmacologic agent in the ACOG treatment algorithm for nausea and vomiting due to pregnancy. In clinical trials, pyridoxine decreased the number of vomiting episodes and reduced nausea severity as compared with data from women who received placebo. Treatment was for 3 days in 1 study and for 5 days in the other; reassess women for continued need of pyridoxine.[24394] [56206]

    Adolescent pregnant females

    10 mg to 25 mg PO (taken either alone or in combination with doxylamine 12.5 mg PO), 3 or 4 times per day. Pyridoxine is a first-line pharmacologic agent in the ACOG treatment algorithm for nausea and vomiting due to pregnancy. In clinical trials, pyridoxine decreased the number of vomiting episodes and reduced nausea severity as compared with data from women who received placebo. Treatment was for 3 days in 1 study and for 5 days in the other; reassess women for continued need of pyridoxine.[24394] [56206]

    For the treatment of pyridoxine-dependent seizures†.
    Intravenous dosage
    Neonates, Infants, and Children

    50 to 100 mg IV as a single dose for diagnostic purposes. If EEG and/or clinical improvement is not observed within 10 minutes, administer 100 mg IV sequentially every 5 to 10 minutes until improvement is seen. Recommended max: 500 mg total dose, however larger doses have been reported. Monitor neurologic, respiratory, and cardiovascular status carefully; resuscitative equipment should be readily available. If the patient responds to pyridoxine, it is recommended to begin a daily oral maintenance dose and discontinue other anticonvulsant medications.

    Oral dosage (Diagnosis)
    Neonates, Infants, Children

    50 to 100 mg PO as a single dose; response should occur within 12 hours. Alternatively, 15 to 30 mg/kg/day PO has been used with a less dramatic clinical response occurring within 3 to 7 days of implementation. While some experts use a maximum dose similar to single dose therapy (50 mg), doses as high as 1000 mg/kg/day have been described. Monitor neurologic, respiratory, and cardiovascular status carefully during administration of large doses; resuscitative equipment should be readily available. Definitive diagnosis is made when therapy discontinuation results in a reemergence of seizure activity within several days to 6 weeks, which then again responds to pyridoxine monotherapy. Although dosing is provided for the oral formulation, most experts recommend IV pyridoxine for diagnosis. If the patient responds to a diagnostic dose of pyridoxine, it is recommended to begin a daily oral maintenance dose and discontinue other anticonvulsant medications.

    Oral dosage (Maintenance)
    Neonates, Infants, Children

    If the patient responds to a diagnostic dose of pyridoxine, it is recommended to begin a daily oral maintenance dose and discontinue other anticonvulsant medications. An initial maintenance dose of 5 mg/kg/day PO once daily or divided twice daily, titrated as needed to suppress seizure activity has been recommended. Maintenance dosing is not firmly established; some experts recommend doses up to 20 mg/kg/day with a maximum dose of 500 mg. Typically, the final dose maintains efficacy throughout childhood, without weight-adjustment for growth. Dosing requirements may transiently increase with illness.

    For linezolid toxicity prophylaxis†.
    Oral dosage
    Adults

    100 mg PO once daily.

    Infants, Children, and Adolescents

    1 to 2 mg/kg/dose (Max: 100 mg/dose) PO once daily.

    †Indicates off-label use

    MAXIMUM DOSAGE

    NOTE: The Tolerable Upper Intake Level (UL) is defined as the highest daily intake of a nutrient that is likely to pose no risk (e.g., sensory neuropathy) in otherwise healthy individuals. The ULs are not intended to apply to individuals with specific vitamin-deficiency conditions; maximum doses for these conditions are based on indication and patient response.

    Adults

    100 mg/day PO.

    Geriatric

    100 mg/day PO.

    Adolescents

    14 years and older: 80 mg/day PO is the tolerable upper intake level (UL). For isoniazid-induced seizures, initial dose should not exceed 70 mg/kg/dose or 5 grams/dose, whichever is less. For mushroom ingestion, do not exceed a total dose of 20 grams.
    13 years: 60 mg/day PO is the tolerable upper intake level (UL). For isoniazid-induced seizures, initial dose should not exceed 70 mg/kg/dose or 5 grams/dose, whichever is less. For mushroom ingestion, do not exceed a total dose of 20 grams.

    Children

    9 to 12 years: 60 mg/day PO is the tolerable upper intake level (UL). For isoniazid-induced seizures, initial dose should not exceed 70 mg/kg/dose or 5 grams/dose, whichever is less. For mushroom ingestion, do not exceed a total dose of 20 grams.
    4 to 8 years: 40 mg/day PO is the tolerable upper intake level (UL). For isoniazid-induced seizures, initial dose should not exceed 70 mg/kg/dose or 5 grams/dose, whichever is less. For mushroom ingestion, do not exceed a total dose of 20 grams.
    1 to 3 years: 30 mg/day PO is the tolerable upper intake level (UL). For pyridoxine-dependent seizures, a maximum diagnostic dose of 500 mg IV has been recommended; however, higher doses have been used. Dose is dependent on patient response. For isoniazid-induced seizures, initial dose should not exceed 70 mg/kg/dose or 5 grams/dose, whichever is less. For mushroom ingestion, do not exceed a total dose of 20 grams.

    Infants

    Tolerable upper intake level (UL) is not determinable. For pyridoxine-dependent seizures, a maximum diagnostic dose of 500 mg IV has been recommended; however, higher doses have been used. Dose is dependent on patient response. For isoniazid-induced seizures, initial dose should not exceed 70 mg/kg/dose or 5 grams/dose, whichever is less. For mushroom ingestion, do not exceed a total dose of 20 grams.

    Neonates

    Tolerable upper intake level (UL) is not determinable. For pyridoxine-dependent seizures, a maximum diagnostic dose of 500 mg IV has been recommended; however, higher doses have been used. Dose is dependent on patient response. For isoniazid-induced seizures, initial dose should not exceed 70 mg/kg/dose or 5 grams/dose, whichever is less. For mushroom ingestion, do not exceed a total dose of 20 grams.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed with oral therapy. However, limit intravenous pyridoxine use as aluminum accumulation may result (see Contraindications).

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Extended-release tablets or capsules: Administer whole do not crush, break, or chew. Alternatively, in patients unable to swallow the capsule, the contents of the capsule may be mixed with a small amount of jelly or jam prior to administration.

    Injectable Administration

    Pyridoxine is administered intramuscularly or intravenously. Parenteral therapy is usually reserved for patients for which oral pyridoxine is not feasible.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The parenteral solution should be protected from light to prevent decomposition.

    Intravenous Administration

    Administer as a direct IV injection or as an intermittent IV infusion in a standard IV solution. May also be admixed in compatible total parenteral nutrition (TPN) solutions.

    Intramuscular Administration

    Inject into a large muscle. Rotate sites of injection.

    STORAGE

    Generic:
    - Avoid excessive heat (above 104 degrees F)
    - Store at room temperature (between 59 to 86 degrees F)
    Neuro-K-500 :
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a dry place

    CONTRAINDICATIONS / PRECAUTIONS

    Premature neonates, renal impairment

    Parenteral pyridoxine solutions contain varying concentrations of aluminum. Patients with renal impairment, especially as seen in premature neonates, are at risk of aluminum accumulation which may result in toxicity. Limit intravenous pyridoxine therapy and consider the cumulative aluminum content among all therapies under administration in patients with renal impairment. It is noted that 4—5 mcg/kg/day of IV aluminum leads to accumulation at concentrations associated with CNS and bone toxicity; further, aluminum tissue loading is possible at lesser, but undefined, daily administration rates. Aluminum concentration in parenteral solutions can be obtained by direct manufacturer inquiry.

    Pregnancy

    Appropriate maternal pyridoxine (vitamin B6) intake is encouraged during pregnancy, and the requirement for pyridoxine appears to be increased during pregnancy. Pyridoxine (up to 40 mg/day) in combination with doxylamine is FDA-approved for the treatment of pregnancy-induced nausea and vomiting. Pyridoxine is a first-line pharmacologic agent in the ACOG treatment algorithm for nausea and vomiting due to pregnancy and may be used with or without doxylamine. A meta-analysis of 16 cohort and 11 case-control studies published between 1963 and 1991 reported no increased risk for malformations from first trimester exposures to doxylamine succinate and pyridoxine hydrochloride, with or without dicyclomine hydrochloride. A second meta-analysis of 12 cohort and 5 case-control studies published between 1963 and 1985 reported no statistically significant relationships between fetal abnormalities and the first trimester use of the combination doxylamine succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride.

    Breast-feeding

    Pyridoxine is considered compatible with breast-feeding. Pyridoxine is excreted in human milk. Appropriate maternal intake of pyridoxine (vitamin B6) is important during lactation, and no problems have been identified with maternal supplementation to achieve adequate intake goals during breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known

    Moderate

    ataxia / Delayed / Incidence not known
    hyperesthesia / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    metabolic acidosis / Delayed / Incidence not known

    Mild

    vomiting / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    nausea / Early / Incidence not known

    DRUG INTERACTIONS

    Abacavir; Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Alendronate: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
    Alendronate; Cholecalciferol: (Moderate) Separate administration of alendronate and calcium-containing supplements by at least 30 minutes. Calcium will interfere with the absorption of alendronate.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Altretamine: (Major) Data from a randomized trial of altretamine and cisplatin plus or minus pyridoxine, vitamin B6 in ovarian cancer indicated that pyridoxine significantly reduced drug-induced neurotoxicity; however, it adversely affected response duration suggesting that pyridoxine should not be administered with altretamine and/or cisplatin.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Atenolol: (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
    Atenolol; Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended. (Minor) Calcium antacids (e.g., calcium carbonate) and supplements (e.g., other oral calcium salts) have been reported to reduce the mean peak concentrations by 51% and the AUC of atenolol by 32%. In another study, antacids reduced the AUC of atenolol by 33%. Separate doses of atenolol and calcium-containing antacids or supplements by at least 2 hours to minimize this potential interaction,. However, most clinicians consider the interaction of atenolol with antacids to be of minor clinical significance, since clinical efficacy (heart rate and blood pressure parameters) appear to be unchanged under usual intermittent clinical use.
    Azilsartan; Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Baloxavir Marboxil: (Major) Do not administer baloxavir with products that contain calcium. Polyvalent cations, such as calcium, can chelate with baloxavir, reducing its absorption.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) In a limited case report, the administration of pyridoxine, vitamin B6 (200 mg once daily x 4 weeks) resulted in reduced serum phenobarbital concentrations in 5 patients with epilepsy; the reductions approached 50%. The evidence for the interaction is limited, and there is no data to suggest that lower supplemental doses would result in alterations in the pharmacokinetics of phenobarbital. The clinical significance of this potential interaction is questionable. If a patient is using large doses of pyridoxine, then the clinician should be alert to possible alterations.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Bendroflumethiazide; Nadolol: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Administer bictegravir with food at the same time as oral calcium supplements. Routine administration of bictegravir under fasting conditions simultaneously with, or 2 hours after, calcium supplements is not recommended. Calcium is a polyvalent cation that can bind bictegravir in the GI tract. Taking these drugs simultaneously without food results in reduced bioavailability of bictegravir. In drug interaction studies, simultaneous administration of bictegravir with another calcium supplement under fasted conditions decreased the mean AUC of bictegravir by approximately 33%.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Cabotegravir: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
    Cabotegravir; Rilpivirine: (Moderate) Administer oral calcium at least two hours before or four hours after taking oral cabotegravir. Calcium is a polyvalent cation that can bind cabotegravir in the GI tract. Taking these drugs simultaneously may result in reduced oral bioavailability of cabotegravir.
    Calcipotriene: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
    Calcipotriene; Betamethasone: (Minor) There is evidence that calcipotriene can be absorbed in amounts that are sufficient to produce systemic effects, including elevated serum calcium; hypercalcemia has been observed in normal prescription use. Use calcipotriene cautiously with other agents that can produce hypercalcemia (e.g., calcium salts or supplements including calcium carbonate).
    Calcitonin: (Moderate) Calcitonin is given to hypercalcemic patients to reduce serum calcium concentrations. For the treatment of hypercalcemia, calcium supplements should be avoided. Calcium salts, including calcium carbonate, can elevate serum calcium concentrations and antagonize the effects of the calcitonin for this condition. For the treatment of osteoporosis adequate intake of calcium salts are necessary in conjunction with calcitonin. An increase in serum calcium concentrations helps to reduce bone resorption and loss of bone mass, and offsets the effect of calcitonin in lowering serum calcium levels.
    Calcium Carbonate; Risedronate: (Moderate) Separate administration of oral risedronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral risedronate.
    Calcium Phosphate, Supersaturated: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Carbidopa; Levodopa: (Contraindicated) Pyridoxine, vitamin B6, in doses as low as 10 mg/day, can accelerate the rate of aromatic amino acid decarboxylation, thus increasing the peripheral conversion of levodopa to dopamine. This action diminishes levodopa's therapeutic effects by decreasing the amount of levodopa that is available to cross into the CNS. Patients receiving levodopa single-agent therapy should avoid vitamin B6 supplements.
    Carbidopa; Levodopa; Entacapone: (Contraindicated) Pyridoxine, vitamin B6, in doses as low as 10 mg/day, can accelerate the rate of aromatic amino acid decarboxylation, thus increasing the peripheral conversion of levodopa to dopamine. This action diminishes levodopa's therapeutic effects by decreasing the amount of levodopa that is available to cross into the CNS. Patients receiving levodopa single-agent therapy should avoid vitamin B6 supplements.
    Cardiac glycosides: (Moderate) Monitor serum calcium regularly in patients receiving digoxin. Calcium salts augment the actions of digoxin. In addition, when calcium is administered via rapid intravenous injection, the risk of serious arrhythmias in digitalized patients is increased.
    Chlorothiazide: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Chlorthalidone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Chlorthalidone; Clonidine: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Ciprofloxacin: (Moderate) Administer oral ciprofloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Ciprofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
    Colesevelam: (Moderate) It is not known if colesevelam can reduce the absorption of oral vitamin supplements including fat soluble vitamins A, D, E, and K. To minimize potential interactions, administer vitamins at least 4 hours before colesevelam.
    Conjugated Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Cycloserine: (Moderate) Cycloserine can either interfere with the actions of pyridoxine, vitamin B6 or increase its clearance, which may result in a secondary niacin deficiency. It may be necessary to administer pyridoxine to patients receiving prolonged therapy with cycloserine to prevent the development of anemia or peripheral neuritis.
    Delafloxacin: (Major) Administer oral delafloxacin at least 2 hours before or 6 hours after oral products that contain calcium. Delafloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with fluoroquinolone bioavailability include antacids and multivitamins that contain calcium.
    Desogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Dichlorphenamide: (Moderate) Use dichlorphenamide and pyridoxine, vitamin B6 together with caution. Metabolic acidosis is associated with the use of dichlorphenamide and has been reported with the rapid infusion of large pyridoxine doses. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy.
    Dienogest; Estradiol valerate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Diethylstilbestrol, DES: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Dolutegravir: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Dolutegravir; Lamivudine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Dolutegravir; Rilpivirine: (Moderate) Administer dolutegravir 2 hours before or 6 hours after taking supplements containing calcium if given under fasting conditions. When taken with food, dolutegravir and supplements containing calcium can be taken at the same time. Simultaneous administration under fasted conditions may result in reduced bioavailability of dolutegravir.
    Drospirenone; Estetrol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Drospirenone; Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Drospirenone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Edetate Calcium Disodium, Calcium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
    Edetate Disodium, Disodium EDTA: (Major) Because edetate disodium chelates and lowers serum calcium, oral or parenteral calcium salts should not be administered concomitantly.
    Elagolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Eltrombopag: (Major) Eltrombopag chelates polyvalent cations (e.g., calcium, aluminum, and magnesium) in food, mineral supplements, and antacids. In a clinical study, systemic exposure to eltrombopag was decreased by 70% when it was administered with a polyvalent cation-containing antacid. Administer eltrombopag at least 2 hours before or 4 hours after any oral products containing polyvalent cations, such as aluminum salts, (like aluminum hydroxide), calcium salts, (including calcium carbonate), and magnesium salts.
    Elvitegravir: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Separate administration of elvitegravir and calcium by at least 2 hours. Due to the formation of ionic complexes in the gastrointestinal tract, simultaneous administration results in lower elvitegravir plasma concentrations.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Esterified Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Esterified Estrogens; Methyltestosterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol; Levonorgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol; Norgestimate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estradiol; Progesterone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estramustine: (Major) Administration of estramustine with calcium impairs the oral absorption of estramustine significantly, due to formation of a calcium-phosphate complex. Calcium-containing drugs must not be taken simultaneously with estramustine. Patients should be instructed to take estramustine with water at least 1 hour before or 2 hours after calcium supplements.
    Estrogens: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Estropipate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethinyl Estradiol; Norgestrel: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ethotoin: (Major) Oral absorption of phenytoin can be reduced by calcium salts. Calcium salts can form complexes that are nonabsorbable. Separating the administration of phenytoin and calcium salts by at least 2 hours to help avoid this interaction. A similar interaction may occur with ethotoin.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Etidronate: (Moderate) Separate administration of oral etidronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral etidronate.
    Etonogestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Fosphenytoin: (Minor) In a limited case report, the administration of pyridoxine, vitamin B6 (range of 80 to 400 mg PO) once daily for 2-4 weeks, resulted in approximate 35% (range 17 to 70%) reductions in serum phenytoin concentrations. The authors postulated that pyridoxine increased the metabolism of phenytoin anticonvulsants. The evidence for the interaction is limited, and there is no data to suggest that lower supplemental doses would result in alterations in the pharmacokinetics of phenytoin or fosphenytoin. The clinical significance of this potential interaction is questionable. If a patient is using large doses of pyridoxine, then the clinician should be alert to possible alterations.
    Gallium: (Moderate) Concurrent administration products containing calcium salts may antagonize the effects of gallium nitrate.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Ibandronate: (Moderate) Separate administration of oral ibandronate and calcium-containing supplements by at least 1 hour. Calcium will interfere with the absorption of oral ibandronate.
    Ibritumomab Tiuxetan: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Levodopa: (Contraindicated) Pyridoxine, vitamin B6, in doses as low as 10 mg/day, can accelerate the rate of aromatic amino acid decarboxylation, thus increasing the peripheral conversion of levodopa to dopamine. This action diminishes levodopa's therapeutic effects by decreasing the amount of levodopa that is available to cross into the CNS. Patients receiving levodopa single-agent therapy should avoid vitamin B6 supplements.
    Levofloxacin: (Moderate) Administer oral products that contain calcium at least 2 hours before or 2 hours after orally administered levofloxacin. Levofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Chelation of divalent cations with levofloxacin is less than with other quinolones. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
    Levonorgestrel; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Mestranol; Norethindrone: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Methyclothiazide: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Metolazone: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Moxifloxacin: (Major) Administer oral moxifloxacin at least 4 hours before or 8 hours after oral products that contain calcium. Moxifloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and calcium may result in resistance to neuromuscular blockade. Calcium antagonizes the potentiating effect of magnesium on neuromuscular blockade. Also, calcium triggers acetylcholine release, and therefore, may both reduce the sensitivity to neuromuscular blockers and decrease the duration of neuromuscular blockade.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Norethindrone; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Norfloxacin: (Major) Administer oral products that contain calcium at least 2 hours before or 2 hours after norfloxacin. Norfloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
    Norgestimate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Ofloxacin: (Moderate) Administer oral products that contain calcium at least 2 hours before or 2 hours after ofloxacin. Ofloxacin absorption may be reduced as quinolone antibiotics can chelate with divalent or trivalent cations. Examples of compounds that may interfere with quinolone bioavailability include antacids and multivitamins that contain calcium.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Penicillamine: (Moderate) Pyridoxine, vitamin B6 excretion can be increased during the administration of penicillamine, possibly causing anemia or peripheral neuritis. Pyridoxine dosages may need to be increased during concomitant administration of penicillamine.
    Phenobarbital: (Minor) In a limited case report, the administration of pyridoxine, vitamin B6 (200 mg once daily x 4 weeks) resulted in reduced serum phenobarbital concentrations in 5 patients with epilepsy; the reductions approached 50%. The evidence for the interaction is limited, and there is no data to suggest that lower supplemental doses would result in alterations in the pharmacokinetics of phenobarbital. The clinical significance of this potential interaction is questionable. If a patient is using large doses of pyridoxine, then the clinician should be alert to possible alterations.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) In a limited case report, the administration of pyridoxine, vitamin B6 (200 mg once daily x 4 weeks) resulted in reduced serum phenobarbital concentrations in 5 patients with epilepsy; the reductions approached 50%. The evidence for the interaction is limited, and there is no data to suggest that lower supplemental doses would result in alterations in the pharmacokinetics of phenobarbital. The clinical significance of this potential interaction is questionable. If a patient is using large doses of pyridoxine, then the clinician should be alert to possible alterations.
    Phenytoin: (Minor) Limited data suggests that large doses (greater than 80 mg per day) of pyridoxine, vitamin B6 may result in reduced serum phenytoin concentrations. Regular doses, such as in multivitamins, probably will have little effect. Monitor for reduced serum phenytoin concentrations or changes in seizure control if large doses of pyridoxine, vitamin B6 are coadminsitered.
    Phosphorated Carbohydrate Solution: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Phosphorus: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Potassium Phosphate: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Potassium Phosphate; Sodium Phosphate: (Moderate) The oral absorption of phosphorus is reduced by ingestion of pharmacologic doses of calcium carbonate or other phosphate-lowering calcium salts (e.g., calcium acetate). There is, however, no significant interference with phosphorus absorption by oral dietary calcium at intakes within the typical adult range. If the patient requires multiple calcium supplements or a calcium-containing antacid, it may be wise to separate the administration of phosphorus salts from calcium-containing products. In some instances the administration of calcium salts or calcium carbonate is used therapeutically (e.g., uremia) to decrease serum phosphorus levels, so the administration of phosphorus supplements would dynamically counteract the intended use of calcium in these settings, assuming hypophosphatemia is not present. Appropriate calcium-phosphorus ratios in vivo are important for proper calcium homeostasis in tissues and bone; if the serum ionized calcium concentration is elevated, the concomitant use of calcium salts and phosphorus salts may increase the risk of calcium deposition in soft tissue.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Relugolix; Estradiol; Norethindrone acetate: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Risedronate: (Moderate) Separate administration of oral risedronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral risedronate.
    Segesterone Acetate; Ethinyl Estradiol: (Minor) Estrogens can increase calcium absorption. Use caution in patients predisposed to hypercalcemia or nephrolithiasis.
    Sodium Fluoride: (Moderate) Absorption of sodium fluoride may be reduced by concomitant use of antacids that contain magnesium, aluminum, or calcium. An interval of at least 2 hours is advisable between administration of sodium fluoride and antacids.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: (Moderate) The concomitant use of oral sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous preparations in conjunction with antacids containing calcium (e.g., calcium carbonate, calcium salts) may bind the phosphate in the stomach and reduce its absorption. If the patient requires multiple mineral supplements or concurrent use of antacids, it is prudent to separate the administration of sodium phosphate salts from calcium containing products by at least one hour.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Tetracyclines: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
    Thiazide diuretics: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Thyroid hormones: (Moderate) Thyroid hormones should be administered at least 4 hours before or after the ingestion of oral calcium supplements. Calcium salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral calcium supplements.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Trientine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of trientine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and trientine each inhibit oral absorption of the other, 2 hours should elapse between administration of trientine and iron doses.
    Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) The simultaneous administration of thiazide diuretics and calcium salts or calcium carbonate may lead to hypercalcemia. Thiazides cause a decrease in renal tubular excretion of calcium as well as increase in distal tubular reabsorption. Moderate increases in serum calcium have been seen during the treatment with thiazides; if calcium salts are used concomitantly, careful monitoring of serum calcium in recommended.
    Vitamin A: (Minor) Doses in excess of 1,500 to 2,000 mcg per day of Vitamin A may lead to bone loss and will counteract the effects of supplementation with calcium salts.
    Vitamin D analogs: (Moderate) Dose adjustment of vitamin D analogs may be necessary during coadministration with calcium salts. Additionally, serum calcium concentrations should be monitored frequently. Monitor more frequently in patients with a history of hypercalcemia. Hypercalcemia may be exacerbated by coadministration of vitamin D analogs and high doses of calcium-containing salts.

    PREGNANCY AND LACTATION

    Pregnancy

    Appropriate maternal pyridoxine (vitamin B6) intake is encouraged during pregnancy, and the requirement for pyridoxine appears to be increased during pregnancy. Pyridoxine (up to 40 mg/day) in combination with doxylamine is FDA-approved for the treatment of pregnancy-induced nausea and vomiting. Pyridoxine is a first-line pharmacologic agent in the ACOG treatment algorithm for nausea and vomiting due to pregnancy and may be used with or without doxylamine. A meta-analysis of 16 cohort and 11 case-control studies published between 1963 and 1991 reported no increased risk for malformations from first trimester exposures to doxylamine succinate and pyridoxine hydrochloride, with or without dicyclomine hydrochloride. A second meta-analysis of 12 cohort and 5 case-control studies published between 1963 and 1985 reported no statistically significant relationships between fetal abnormalities and the first trimester use of the combination doxylamine succinate and pyridoxine hydrochloride with or without dicyclomine hydrochloride.

    Pyridoxine is considered compatible with breast-feeding. Pyridoxine is excreted in human milk. Appropriate maternal intake of pyridoxine (vitamin B6) is important during lactation, and no problems have been identified with maternal supplementation to achieve adequate intake goals during breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

    MECHANISM OF ACTION

    Mechanism of Action: Vitamin B6 is composed of pyridoxine, pyridoxal, and pyridoxamine, and food usually contains all three forms. Pyridoxine is converted in erythrocytes to its active moiety, pyridoxal phosphate (requiring riboflavin for the conversion), while pyridoxamine is converted into pyridoxamine phosphate. These active forms act as coenzymes for no fewer than 60 metabolic processes including the metabolism of fat, protein, and carbohydrate. Their role in protein metabolism includes decarboxylation of amino acids, conversion of tryptophan to niacin or serotonin, deamination, and transamination of amino acids. In carbohydrate metabolism, it is necessary for the conversion of glycogen to glucose-1-phosphate. Pyridoxine is essential for synthesis of gamma aminobutyric acid (GABA) in the CNS and synthesis of heme.

    PHARMACOKINETICS

    Pyridoxine is administered orally and by intramuscular or intravenous injection. Vitamin B6 is stored in the liver, with small amounts in the brain and muscles. The total body storage for adults is between 16 to 27 mg. Pyridoxal crosses the placenta, with fetal concentrations five times that of maternal plasma concentrations. Pyridoxal and pyridoxal phosphate are the primary forms of vitamin B6 in the blood. Pyridoxal phosphate is 100% protein-bound. The half-life of pyridoxine is 15 to 20 days. Conversion of pyridoxine to pyridoxal phosphate and pyridoxamine to pyridoxamine phosphate takes place in erythrocytes. Pyridoxine is also phosphorylated in the liver. Pyridoxal is oxidized in the liver to produce 4-pyridoxic acid, which is excreted in the urine.

    Oral Route

    Absorption of pyridoxine is rapid following oral administration. The extent of absorption is decreased following gastric resection or in patients with malabsorption syndromes.

    Intravenous Route

    After intravenous infusion of pyridoxine 100 mg over six hours in adult patients, pyridoxal phosphate (PLP) plasma and erythrocyte concentrations increased rapidly from 37 nmol/L to 2183 nmol/L in the plasma and undetectable to 5593 nmol/L in erythrocytes. Peak concentrations were achieved at the end of the infusion.