Drugs Details

Drugs Info of Calcium Disodium Versenate
Drugs Details
  • Drugs Type  : Multum
  • Date : 22nd Jan 2015 12:28 am
  • Brand Name : Calcium Disodium Versenate
  • Generic Name : edetate calcium disodium (Pronunciation: ED e tate KAL see um dye SOE dee um)
Descriptions

Calcium Disodium Versenate (edetate calcium disodium injection, USP) is a sterile, injectable, chelating agent in concentrated solution for intravenous infusion or intramuscular injection. Each 5 ml ampul contains 1000 mg of edetate calcium disodium (equivalent to 200 mg/ml) in water for injection. Chemically, this product is called [[N,N' -1,2-ethanediyl-bis[N-(carboxymethyl)-glycinato]](4-)- N,N',O,O',ON,ON']-,disodium,hydrate, (OC-6-21)-Calciate(2-).

Structural Formula:

 

Calcium Disodium Versenate
  (edetate calcium disodium) Structural Formula Illustration

C10H12CaN2Na2O8• x H2O
Molecular weight 374.27 (anhydrous)

What are the possible side effects of edetate calcium disodium (Calcium Disodium Versenate)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have any of these serious side effects:

  • urinating less than usual or not at all;
  • drowsiness, confusion, mood changes, increased thirst, loss of appetite, nausea and vomiting;
  • swelling, weight gain, feeling short of breath;
  • feeling like you might pass out; or
  • fast, slow, or uneven heart rate.

Less...

Read All Potential Side Effects and See Pictures of Calcium Disodium Versenate »

This monograph has been modified to include the generic and brand name in many instances.

Indications

Edetate calcium disodium is indicated for the reduction of blood levels and depot stores of lead in lead poisoning (acute and chronic) and lead encephalopathy, in both pediatric populations and adults.

Chelation therapy should not replace effective measures to eliminate or reduce further exposure to lead.

Dosage Administration

When a source for the lead intoxication has been identified, the patient should be removed from the source, if possible. The recommended dose of Calcium Disodium Versenate for asymptomatic adults and pediatric patients whose blood lead level is < 70 mcg/dl but > 20 mcg/dl (World Health Organization recommended upper allowable level) is 1000 mg/m2/day whether given intravenously or intramuscularly. (See Surface Area Nomogram.)

SURFACE AREA NOMOGRAM

Surface Area Nomogram - illustration

For adults with lead nephropathy, the following dosing regimen has been suggested: 500 mg/m2 every 24 hours for 5 days for patients with serum creatinine levels of 2-3 mg/dl, every 48 hours for 3 doses for patients with creatinine levels of 3-4 mg/dl, and once weekly for patients with creatinine levels above 4 mg/dl. These regimens may be repeated at one month intervals.12

Calcium Disodium Versenate (edetate calcium disodium injection) , used alone, may aggravate symptoms in patients with very high blood lead levels. When the blood lead level is > 70 mcg/dl or clinical symptoms consistent with lead poisoning are present, it is recommended that Calcium Disodium Versenate (edetate calcium disodium injection) be used in conjunction with BAL (dimercaprol). Please consult published protocols and specialized references for dosage recommendations of combination therapy.14-18

Therapy of lead poisoning in adults and pediatric patients with Calcium Disodium Versenate (edetate calcium disodium injection) is continued over a period of five days. Therapy is then interrupted for 2 to 4 days to allow redistribution of the lead and to prevent severe depletion of zinc and other essential metals. Two courses of treatment are usually employed; however, it depends on severity of the lead toxicity and the tolerance of the drug.

Calcium Disodium Versenate (edetate calcium disodium injection) is equally effective whether administered intravenously or intramuscularly. The intramuscular route is used for all patients with overt lead encephalopathy and this route is preferred by some for young pediatric patients.

Acutely ill individuals may be dehydrated from vomiting. Since edetate calcium disodium is excreted almost exclusively in the urine, it is very important to establish urine flow with intravenous fluid administration before the first dose of the chelating agent is given; however, excessive fluid must be avoided in patients with encephalopathy. Once urine flow is established, further intravenous fluid is restricted to basal water and electrolyte requirements. Administration of Calcium Disodium Versenate (edetate calcium disodium injection) should be stopped whenever there is cessation of urine flow in order to avoid unduly high tissue levels of the drug. Edetate calcium disodium must be used in reduced doses in patients with pre-existing mild renal disease.

Intravenous Administration

Add the total daily dose of Calcium Disodium Versenate (edetate calcium disodium injection) (1000 mg/m2/day) to 250-500 ml of 5% dextrose or 0.9% sodium chloride injection. The total daily dose should be infused over a period of 8-12 hours. Calcium Disodium Versenate (edetate calcium disodium injection) injection is incompatible with 10% dextrose, 10% invert sugar in 0.9% sodium chloride, lactate molar sodium lactate injections, and with injectable amphotericin B and hydralazine hydrochloride.

Intramuscular Administration

The total daily dosage (1000 mg/m2/day) should be divided into equal doses spaced 8-12 hours apart. Lidocaine or procaine should be added to the Calcium Disodium Versenate (edetate calcium disodium injection) injection to minimize pain at the injection site. The final lidocaine or procaine concentration of 5 mg/ml (0.5%) can be obtained as follows: 0.25 ml of 10% lidocaine solution per 5 ml (entire content of ampul) concentrated Calcium Disodium Versenate (edetate calcium disodium injection) ; 1 ml of 1% lidocaine or procaine solution per ml of concentrated Calcium Disodium Versenate (edetate calcium disodium injection) . When used alone, regardless of method of administration, Calcium Disodium Versenate (edetate calcium disodium injection) should not be given at doses larger than those recommended.

Diagnostic Test

Several methods have been described for lead mobilization tests using edetate calcium disodium to assess body stores.7,9,12,13,18

These procedures have advantages and disadvantages that should be reviewed in current references. Edetate calcium disodium mobilization tests should not be performed in symptomatic patients and in patients with blood lead levels above 55 mcg/dl for whom appropriate therapy is indicated. Parenteral drugs should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

How Supplied

Calcium Disodium Versenate (edetate calcium disodium injection) injection, 5 ml ampul containing 200 mg of edetate calcium disodium per ml (1 g per ampul), in boxes containing 6 ampuls (NDC 0089-0510-06).

Store at controlled room temperature 15°-30°C (59°-86°F).

REFERENCES

7. Drug Evaluations, 6th Edition, American Medical Association, Saunders, Philadelphia, 1986, pp. 1637-1639.

9. Finberg L, Rajagopal V. Diagnosis and treatment of lead poisoning in children. J Family Med 1985 April: 3-12.

12. American Hospital Formulary Service, Drug Information, 1988, pp. 1695-1698.

13. Markowitz ME, Rosen JF. Assessment of lead stores in children: Validation of an 8-hour CaNa2EDTA (Calcium Disodium Versenate (edetate calcium disodium injection) ) provocative test. J Pediatrics 1984; 104:337-341.

14. Piomelli S, Rosen JF, Chisolm JJ, et al. Management of childhood lead poisoning. J Pediatrics 1984; 105:523-532.

15. Sachs HK, Blanksma LA, Murray EF, et al. Ambulatory treatment of lead poisoning: Report of 1,155 cases. Pediatrics 1970; 46:389.

16. Chisolm JJ. The use of chelating agents in the treatment of acute and chronic lead intoxication in childhood. J Pediatrics 1968; 73:1.

17. Coffin R, Phillips JL, Staples WI, et al. Treatment of lead encephalopathy in children. J Pediatrics 1966; 69:198-206.

18. Chisolm JJ. Increased lead absorption and acute lead poisoning. Current Pediatric Therapy 12, Gillis and Kagan, editors, WB Saunders, Philadelphia, 1986, pp. 667-671.

Manufactured for: 3M Pharmaceuticals, Northridge, CA 91324. By Hospira, Inc. Lake Forest, IL 60045. July 2004. FDA Rev date: 4/12/2002

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

The following adverse effects have been associated with the use of edetate calcium disodium:

Body as a Whole: pain at intramuscular injection site, fever, chills, malaise, fatigue, myalgia, arthralgia.

Cardiovascular: hypotension, cardiac rhythm irregularities.

Renal: acute necrosis of proximal tubules (which may result in fatal nephrosis), infrequent changes in distal tubules and glomeruli.

Urinary: glycosuria, proteinuria, microscopic hematuria and large epithelial cells in urinary sediment.

Nervous System: tremors, headache, numbness, tingling.

Gastrointestinal: cheilosis, nausea, vomiting, anorexia, excessive thirst.

Hepatic: mild increases in SGOT and SGPT are common, and return to normal within 48 hours after cessation of therapy.

Immunogenic: histamine-like reactions (sneezing, nasal congestion, lacrimation), rash.

Hematopoietic: transient bone marrow depression, anemia.

Metabolic: zinc deficiency, hypercalcemia.

Read the Calcium Disodium Versenate (edetate calcium disodium injection) Side Effects Center for a complete guide to possible side effects

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Interactions

There is no known drug interference with standard clinical laboratory tests. Steroids enhance the renal toxicity of edetate calcium disodium in animals.7 Edetate calcium disodium interferes with the action of zinc insulin preparations by chelating the zinc.7

REFERENCES

7. Drug Evaluations, 6th Edition, American Medical Association, Saunders, Philadelphia, 1986, pp. 1637-1639.

This monograph has been modified to include the generic and brand name in many instances.

Warnings

See Boxed Warning.

Precautions

General Precautions

Edetate calcium disodium may produce the same renal damage as lead poisoning, such as proteinuria and microscopic hematuria. Treatment-induced nephrotoxicity is dose-dependent and may be reduced by assuring adequate diuresis before therapy begins. Urine flow must be monitored throughout therapy which must be stopped if anuria or severe oliguria develop. The proximal tubule hydropic degeneration usually recovers upon cessation of therapy. Edetate calcium disodium must be used in reduced doses in patients with pre-existing mild renal disease.

Patients should be monitored for cardiac rhythm irregularities and other ECG changes during intravenous therapy.

Laboratory tests

Urinalysis and urine sediment, renal and hepatic function and serum electrolyte< levels should be checked before each course of therapy and then be monitored daily during therapy in severe cases, and in less serious cases after the second and fifth day of therapy. Therapy must be discontinued at the first sign of renal toxicity. The presence of large renal epithelial cells or increasing number of red blood cells in urinary sediment or greater proteinuria call for immediate stopping of edetate calcium disodium administration. Alkaline phosphatase values are frequently depressed (possibly due to decreased serum zinc levels), but return to normal within 48 hours after cessation of therapy. Elevated erythrocyte protoporphyrin levels ( > 35 mcg/dl of whole blood) indicate the need to perform a venous blood lead determination. If the whole blood lead concentration is between 25-55 mcg/dl a mobilization test can be considered.7,8 (See Diagnostic Test.) An elevation of urinary coproporphyrin (adults: > 250 mcg/day; pediatric patients under 80 lbs: > 75 mcg/day) and elevation of urinary delta aminolevulinic acid (ALA) (adults: > 4 mg/day; pediatric patients: > 3 mg/m2/day) are associated with blood lead levels > 40 mcg/dl. Urinary coproporphyrin may be falsely negative in terminal patients and in severely iron-depleted pediatric patients who are not regenerating heme.9 In growing pediatric patients long bone x-rays showing lead lines and abdominal x-rays showing radio-opaque material in the abdomen may be of help in estimating the level of exposure to lead.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long term animal studies have not been conducted with edetate calcium disodium to evaluate its carcinogenic potential, mutagenic potential or its effect on fertility.

Pregnancy

Category B: One reproduction study was performed in rats at doses up to 13 times the human dose and revealed no evidence of impaired fertility or harm to the fetus due to Calcium Disodium Versenate (edetate calcium disodium injection) .10 Another reproduction study performed in rats at doses up to about 25 to 40 times the human dose revealed evidence of fetal malformations due to Calcium Disodium Versenate, which were prevented by simultaneous supplementation of dietary zinc.11 There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Labor and Delivery

Calcium Disodium Versenate (edetate calcium disodium injection) has no recognized use during labor and delivery, and its effects during these processes are unknown.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Calcium Disodium Versenate is administered to a nursing woman.

Pediatric Use

Since lead poisoning occurs in pediatric populations and adults but is frequently more severe in pediatric patients, Calcium Disodium Versenate (edetate calcium disodium injection) is used in patients of all ages. The intramuscular route is preferred by some for young pediatric patients. In cases where the intravenous route is necessary, avoid rapid infusion. (See WARNINGS.) Urine flow must be monitored throughout therapy; Calcium Disodium Versenate (edetate calcium disodium injection) therapy must be stopped if anuria or severe oliguria develops. (See General Precautions.) At no time should the recommended daily dosage be exceeded. (See DOSAGE AND ADMINISTRATION.)

REFERENCES

7. Drug Evaluations, 6th Edition, American Medical Association, Saunders, Philadelphia, 1986, pp. 1637-1639.

8. Centers for Disease Control: Preventing lead poisoning in young children. Atlanta, GA, Department of Health and Human Services, 1985 Jan.

9. Finberg L, Rajagopal V. Diagnosis and treatment of lead poisoning in children. J Family Med 1985 April: 3-12.

10. Schardein JL, Sakowski R, Petrere J, et al. Teratogenesis studies with EDTA and its salts in rats. Toxicol Appl Pharmacol 1981; 61:423-428.

11. Swenerton H, Hurley LS. Teratogenic effects of a chelating agent and their prevention by zinc. Science 1971; 173:62-64.

This monograph has been modified to include the generic and brand name in many instances.

OverDose

Symptoms

Inadvertent administration of 5 times the recommended dose, infused intravenously over a 24 hour period, to an asymptomatic 16 month old patient with a blood lead content of 56 mcg/dl did not cause any ill effects. Edetate calcium disodium can aggravate the symptoms of severe lead poisoning, therefore, most toxic effects (cerebral edema, renal tubular necrosis) appear to be associated with lead poisoning.

Because of cerebral edema, a therapeutic dose may be lethal to an adult or a pediatric patient with lead encephalopathy. Higher dosage of edetate calcium disodium may produce a more severe zinc deficiency.

Treatment

Cerebral edema should be treated with repeated doses of mannitol. Steroids enhance the renal toxicity of edetate calcium disodium in animals and, therefore, are no longer recommended.7Zinc levels must be monitored. Good urinary output must be maintained because diuresis will enhance drug elimination. It is not known if edetate calcium disodium is dialyzable.

ContrainDications

Edetate calcium disodium should not be given during periods of anuria, nor to patients with active renal disease or hepatitis.

REFERENCES

7. Drug Evaluations, 6th Edition, American Medical Association, Saunders, Philadelphia, 1986, pp. 1637-1639.

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

The pharmacologic effects of edetate calcium disodium are due to the formation of chelates with divalent and trivalent metals. A stable chelate will form with any metal that has the ability to displace calcium from the molecule, a feature shared by lead, zinc, cadmium, manganese, iron and mercury. The amounts of manganese and iron mobilized are not significant. Copper1 is not mobilized and mercury is unavailable for chelation because it is too tightly bound to body ligands or it is stored in inaccessible body compartments. The excretion of calcium by the body is not increased following intravenous administration of edetate calcium disodium, but the excretion of zinc is considerably increased.1

Edetate calcium disodium is poorly absorbed from the gastrointestinal tract. In blood, all the drug is found in the plasma. Edetate calcium disodium does not appear to penetrate cells; it is distributed primarily in the extracellular fluid with only about 5% of the plasma concentration found in spinal fluid.

The half life of edetate calcium disodium is 20 to 60 minutes. It is excreted primarily by the kidney, with about 50% excreted in one hour and over 95% within 24 hours.2 Almost none of the compound is metabolized.

The primary source of lead chelated by Calcium Disodium Versenate (edetate calcium disodium injection) is from bone; subsequently, soft-tissue lead is redistributed to bone when chelation is stopped.3,4 There is also some reduction in kidney lead levels following chelation therapy.

It has been shown in animals that following a single dose of Calcium Disodium Versenate urinary lead output increases, blood lead concentration decreases, but brain lead is significantly increased due to internal redistribution of lead.5 (See WARNINGS.) These data are in agreement with the recent results of others in experimental animals showing that after a five day course of treatment there is no net reduction in brain lead.6

REFERENCES

1. Thomas DJ, Chisolm JJ. Lead, zinc and copper decorporation during calcium disodium ethylenediamine tetraacetate treatment of lead-poisoned children. J Pharmacol Exp Therapeu 1986; 239:829-835.

2. The Pharmacological Basis of Therapeutics, 7th edition, Goodman and Gilman, editors. MacMillan Publishing Company, New York, 1985, pp. 1619-1622.

3. Hammond PB, Aronson AL, Olson WC. The mechanism of mobilization of lead by ethylenediaminetetraacetate. J Pharmacol Exp Therapeu 1967; 157:196-206.

4. Van deVyver FL, D'Haese r WJ, et al. Bone lead in dialysis patients. Kidney Intl 1988;PC, Visse 33:601-607.

5. Cory-Slecta DA, Weiss B, Cox C. Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy. J Pharmacol Exp Therapeu 1987; 243:804-813.

6. Chisolm JJ. Mobilization of lead by calcium disodium edetate. Am J Dis Child 1987; 141:1256-1257.

This monograph has been modified to include the generic and brand name in many instances.

Patient Information

Patients should be instructed to immediately inform their physician if urine output stops for a period of 12 hours.

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

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Consumer Overview Side Effect

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Consumer Overview Missed Dose

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Patient Detailed Side Effect

Brand Names: Calcium Disodium Versenate

Generic Name: edetate calcium disodium (Pronunciation: ED e tate KAL see um dye SOE dee um)

  • What is edetate calcium disodium (Calcium Disodium Versenate)?
  • What are the possible side effects of edetate calcium disodium (Calcium Disodium Versenate)?
  • What is the most important information I should know about edetate calcium disodium (Calcium Disodium Versenate)?
  • What should I discuss with my health care provider before receiving edetate calcium disodium (Calcium Disodium Versenate)?
  • How is edetate calcium disodium given (Calcium Disodium Versenate)?
  • What happens if I miss a dose (Calcium Disodium Versenate)?
  • What happens if I overdose (Calcium Disodium Versenate)?
  • What should I avoid after receiving edetate calcium disodium (Calcium Disodium Versenate)?
  • What other drugs will affect edetate calcium disodium (Calcium Disodium Versenate)?
  • Where can I get more information?

What is edetate calcium disodium (Calcium Disodium Versenate)?

Edetate calcium disodium is a chelating (KEE-late-ing) agent. A chelating agent is capable of removing a heavy metal, such as lead or mercury, from the blood.

Edetate calcium disodium is used to treat lead poisoning.

Edetate calcium disodium may also be used for other purposes not listed in this medication guide.

What are the possible side effects of edetate calcium disodium (Calcium Disodium Versenate)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Tell your caregivers at once if you have any of these serious side effects:

  • urinating less than usual or not at all;
  • drowsiness, confusion, mood changes, increased thirst, loss of appetite, nausea and vomiting;
  • swelling, weight gain, feeling short of breath;
  • feeling like you might pass out; or
  • fast, slow, or uneven heart rate.

Less serious side effects include:

  • fever, chills, tired feeling, and muscle or joint pain;
  • numbness or tingly feeling;
  • tremors;
  • runny or stuffy nose, sneezing, water eyes;
  • mild skin rash;
  • headache; or
  • pain where the medicine was injected.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Calcium Disodium Versenate (edetate calcium disodium injection) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about edetate calcium disodium (Calcium Disodium Versenate)?

You should not receive this medication if you are unable to urinate, or if you have active hepatitis or kidney disease.

Edetate calcium disodium is given as an injection through a needle placed into a vein or muscle. You will receive this injection in a hospital or emergency setting.

When injected into a vein, edetate calcium disodium must be given slowly through an IV infusion and can take up to 12 hours to complete.

If possible before you receive this medication, tell your caregivers if you kidney disease.

In an emergency situation, it may not be possible before you are treated to tell your caregivers about any health conditions you have or if you are pregnant or breast-feeding. However, make sure any doctor caring for you afterward knows that you have received this medication.

Side Effects Centers
  • Calcium Disodium Versenate

Patient Detailed How Take

What should I discuss with my health care provider before receiving edetate calcium disodium (Calcium Disodium Versenate)?

You should not receive this medication if you are unable to urinate, or if you have active hepatitis or kidney disease.

If possible, before you receive edetate calcium disodium, tell your doctor if you are allergic to any drugs, or if you have kidney disease. You may need a dose adjustment or special tests to safely receive this medication.

FDA pregnancy category B. Edetate calcium disodium is not expected to be harmful to an unborn baby. However, tell your doctor if you are pregnant before receiving this medication.

It is not known whether edetate calcium disodium passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

In an emergency situation, it may not be possible before you are treated with edetate calcium disodium to tell your caregivers if you are pregnant or breast-feeding. However, make sure any doctor caring for your pregnancy or your baby knows that you have received this medication.

How is edetate calcium disodium given (Calcium Disodium Versenate)?

Edetate calcium disodium is given as an injection through a needle placed into a vein or muscle. You will receive this injection in a hospital or emergency setting.

When injected into a vein, edetate calcium disodium must be given slowly through an IV infusion and can take up to 12 hours to complete.

To be sure this medication is helping your condition and not causing harmful side effects, your blood and urine will need to be tested often. Your heart rate will be constantly monitored through electrocardiograph or ECG (sometimes called an EKG). This machine measures electrical activity of the heart. This will help your doctor determine how long to treat you with edetate calcium disodium.

Side Effects Centers
  • Calcium Disodium Versenate

Patient Detailed Avoid Taking

What happens if I miss a dose (Calcium Disodium Versenate)?

Since edetate calcium disodium is given by a healthcare provider, it is not likely that you will miss a dose.

What happens if I overdose (Calcium Disodium Versenate)?

Tell your caregivers right away if you think you have received too much of this medicine. An overdose of edetate calcium disodium is not expected to produce life-threatening symptoms.

What should I avoid after receiving edetate calcium disodium (Calcium Disodium Versenate)?

Follow your doctor's instructions about the amount of liquids you should drink while being treated with this medication. In some cases, drinking too much liquid can cause a harmful electrolyte imbalance.

What other drugs will affect edetate calcium disodium (Calcium Disodium Versenate)?

The following drugs can interact with edetate calcium disodium. Tell your doctor if you are using any of these:

  • insulin zinc (Iletin Lente); or
  • steroids such as prednisone, fluticasone (Advair), mometasone (Asmanex, Nasonex), dexamethasone (Decadron, Hexadrol) and others.

This list is not complete and there may be other drugs that can interact with edetate calcium disodium. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about edetate calcium disodium.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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