NDC 44523-415 Potassium Citrate

Potassium Citrate

NDC Product Code 44523-415

NDC CODE: 44523-415

Proprietary Name: Potassium Citrate What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Potassium Citrate What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to make the urine less acidic. This effect helps the kidneys get rid of uric acid, thereby helping to prevent gout and kidney stones. This medication can also prevent and treat certain metabolic problems (acidosis) caused by kidney disease. Citric acid and citrate salts (which contain potassium and sodium) belong to a class of drugs known as urinary alkalinizers. If you have a condition that requires you to limit your intake of potassium and sodium, your doctor may direct you to take a product that is lower in potassium and sodium.

Product Characteristics

Color(s):
YELLOW (C48330 - TAN TO YELLOWISH)
Shape: RECTANGLE (C48347)
Size(s):
20 MM
Imprint(s):
M15
Score: 1

NDC Code Structure

  • 44523 - Biocomp Pharma, Inc.

NDC 44523-415-01

Package Description: 100 TABLET in 1 BOTTLE

NDC Product Information

Potassium Citrate with NDC 44523-415 is a a human prescription drug product labeled by Biocomp Pharma, Inc.. The generic name of Potassium Citrate is potassium citrate. The product's dosage form is tablet and is administered via oral form.

Labeler Name: Biocomp Pharma, Inc.

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Potassium Citrate Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • POTASSIUM CITRATE 15 meq/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • CARNAUBA WAX (UNII: R12CBM0EIZ)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.
  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Acidifying Activity - [MoA] (Mechanism of Action)
  • Calculi Dissolution Agent - [EPC] (Established Pharmacologic Class)
  • Anti-coagulant - [EPC] (Established Pharmacologic Class)
  • Decreased Coagulation Factor Activity - [PE] (Physiologic Effect)
  • Calcium Chelating Activity - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Biocomp Pharma, Inc.
Labeler Code: 44523
FDA Application Number: NDA019071 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA AUTHORIZED GENERIC - A product marketed as a “generic” drug under an approved New Drug Application (NDA), rather than an Abbreviated New Drug Application (ANDA),. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 12-23-2013 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

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Potassium Citrate Product Label Images

Potassium Citrate Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1.1  Renal Tubular Acidosis (Rta) With Calcium Stones

Potassium Citrate is indicated
for the management of renal tubular acidosis [see Clinical
Studies (14.1)].

1.2  Hypocitraturic Calcium Oxalate Nephrolithiasis Of Any Etiology

Potassium Citrate is indicated
for the management of Hypocitraturic calcium oxalate nephrolithiasis [see Clinical Studies (14.2)].

1.3  Uric Acid Lithiasis With Or Without Calcium Stones

Potassium Citrate is indicated
for the management of Uric acid lithiasis with or without calcium
stones [see Clinical Studies (14.3)].

2.1  Dosing Instructions

Treatment with extended release Potassium
Citrate should be added to a regimen that limits salt intake (avoidance
of foods with high salt content and of added salt at the table) and
encourages high fluid intake (urine volume should be at least two
liters per day). The objective of treatment with Potassium Citrate
is to provide Potassium Citrate in sufficient dosage to restore normal
urinary citrate (greater than 320 mg/day and as close to the normal
mean of 640 mg/day as possible), and to increase urinary pH to a level
of 6.0 or 7.0.Monitor
serum electrolytes (sodium, potassium, chloride and carbon dioxide),
serum creatinine and complete blood counts every four months and more
frequently in patients with cardiac disease, renal disease or acidosis.
Perform electrocardiograms periodically. Treatment should be discontinued
if there is hyperkalemia, a significant rise in serum creatinine or
a significant fall in blood hemocrit or hemoglobin.

2.2  Severe Hypocitraturia

In patients with severe hypocitraturia (urinary
citrate < 150 mg/day), therapy should be initiated at a dosage
of 60 mEq/day (30 mEq two times/day or 20 mEq three times/day with
meals or within 30 minutes after meals or bedtime snack). Twenty-four
hour urinary citrate and/or urinary pH measurements should be used
to determine the adequacy of the initial dosage and to evaluate the
effectiveness of any dosage change. In addition, urinary citrate and/or
pH should be measured every four months. Doses of Potassium Citrate
greater than 100 mEq/day have not been studied and should be avoided.

2.3  Mild To Moderate Hypocitraturia

In patients with mild to moderate hypocitraturia
(urinary citrate > 150 mg/day) therapy should be initiated at 30 mEq/day
(15 mEq two times/day or 10 mEq three times/day within 30 minutes
after meals or bedtime snack). Twenty-four hour urinary citrate and/or
urinary pH measurements should be used to determine the adequacy of
the initial dosage and to evaluate the effectiveness of any dosage
change. Doses of Potassium Citrate greater than 100 mEq/day have not
been studied and should be avoided.

3  Dosage Forms And Strengths

  • 15 mEq tablets are uncoated, tan to yellowish in color,
  • Modified rectangle shaped, with M15 debossed on one side and blank
  • On the other

4  Contraindications

  • Potassium Citrate is contraindicated:In patients with hyperkalemia (or who have conditions pre-disposing
  • Them to hyperkalemia), as a further rise in serum potassium concentration
  • May produce cardiac arrest. Such conditions include: chronic renal
  • Failure, uncontrolled diabetes mellitus, acute dehydration, strenuous
  • Physical exercise in unconditioned individuals, adrenal insufficiency,
  • Extensive tissue breakdown or the administration of a potassium-sparing
  • Agent (such as triamterene, spironolactone or amiloride).In patients in whom there is cause for arrest or delay in
  • Tablet passage through the gastrointestinal tract, such as those suffering
  • From delayed gastric emptying, esophageal compression, intestinal
  • Obstruction or stricture, or those taking anticholinergic medication.In patients with peptic ulcer disease because of its ulcerogenic
  • Potential.In patients with active urinary tract infection (with either
  • Urea-splitting or other organisms, in association with either calcium
  • Or struvite stones). The ability of Potassium Citrate to increase
  • Urinary citrate may be attenuated by bacterial enzymatic degradation
  • Of citrate. Moreover, the rise in urinary pH resulting from Potassium
  • Citrate therapy might promote further bacterial growth.In patients with renal insufficiency (glomerular filtration
  • Rate of less than 0.7 ml/kg/min), because of the danger of soft tissue
  • Calcification and increased risk for the development of hyperkalemia.

5.1  Hyperkalemia

In patients with impaired mechanisms for
excreting potassium, Potassium Citrate administration can produce
hyperkalemia and cardiac arrest. Potentially fatal hyperkalemia can
develop rapidly and be asymptomatic. The use of Potassium Citrate
in patients with chronic renal failure, or any other condition which
impairs potassium excretion such as severe myocardial damage or heart
failure, should be avoided. Closely monitor for signs of hyperkalemia
with periodic blood tests and ECGs.

5.2  Gastrointestinal Lesions

Because of reports of upper gastrointestinal
mucosal lesions following administration of potassium chloride (wax-matrix),
an endoscopic examination of the upper gastrointestinal mucosa was
performed in 30 normal volunteers after they had taken glycopyrrolate
2 mg p.o. t.i.d., Potassium Citrate 95 mEq/day, wax-matrix potassium
chloride 96 mEq/day or wax-matrix placebo, in thrice daily schedule
in the fasting state for one week. Potassium Citrate and the wax-matrix
formulation of potassium chloride were indistinguishable but both
were significantly more irritating than the wax-matrix placebo. In
a subsequent, similar study, lesions were less severe when glycopyrrolate
was omitted.Solid
dosage forms of potassium chlorides have produced stenotic and/or
ulcerative lesions of the small bowel and deaths. These lesions are
caused by a high local concentration of potassium ions in the region
of the dissolving tablets, which injured the bowel. In addition, perhaps
because wax-matrix preparations are not enteric-coated and release
some of their potassium content in the stomach, there have been reports
of upper gastrointestinal bleeding associated with these products.
The frequency of gastrointestinal lesions with wax-matrix potassium
chloride products is estimated at one per 100,000 patient-years. Experience
with Potassium Citrate is limited, but a similar frequency of gastrointestinal
lesions should be anticipated.If there is severe vomiting, abdominal pain
or gastrointestinal bleeding, Potassium Citrate should be discontinued
immediately and the possibility of bowel perforation or obstruction
investigated.

6.1  Postmarketing Experience

Some patients may develop minor gastrointestinal
complaints during Potassium Citrate therapy, such as abdominal discomfort,
vomiting, diarrhea, loose bowel movements or nausea. These symptoms
are due to the irritation of the gastrointestinal tract, and may be
alleviated by taking the dose with meals or snacks, or by reducing
the dosage. Patients may find intact matrices in their feces.

7.1  Potential Effects Of Potassium Citrate On Other Drugs

Potassium-sparing Diuretics: Concomitant administration of Potassium Citrate and a potassium-sparing
diuretic (such as triamterene, spironolactone or amiloride) should
be avoided since the simultaneous administration of these agents can
produce severe hyperkalemia.

7.2  Potential Effects Of Other Drugs On Potassium Citrate

Drugs that slow gastrointestinal
transit time: These agents (such as anticholinergics) can
be expected to increase the gastrointestinal irritation produced by
potassium salts.

Pregnancy Category C

Animal reproduction studies have not been
conducted. It is also not known whether Potassium Citrate can cause
fetal harm when administered to a pregnant woman or can affect reproduction
capacity. Potassium Citrate should be given to a pregnant woman only
if clearly needed.

8.3  Nursing Mothers

The normal potassium ion content of human milk is about 13
mEq/L. It is not known if Potassium Citrate has an effect on this
content. Potassium Citrate should be given to a woman who is breast
feeding only if clearly needed.

8.4  Pediatric Use

Safety and effectiveness in children have not been established.

10  Overdosage

Treatment of Overdosage: The administration of potassium
salts to persons without predisposing conditions for hyperkalemia
rarely causes serious hyperkalemia at recommended dosages. It is important
to recognize that hyperkalemia is usually asymptomatic and may be
manifested only by an increased serum potassium concentration and
characteristic electrocardiographic changes (peaking of T-wave, loss
of P-wave, depression of S-T segment and prolongation of the QT interval).
Late manifestations include muscle paralysis and cardiovascular collapse
from cardiac arrest.Treatment measures for hyperkalemia include the following: 1. Patients
should be closely monitored for arrhythmias and electrolyte changes.
2. Elimination of medications containing potassium and of agents with
potassium-sparing properties such as potassium-sparing diuretics,
ARBs, ACE inhibitors, NSAIDs, certain nutritional supplements and
many others. 3. Elimination of foods containing high levels of potassium
such as almonds, apricots, bananas, beans (lima, pinto, white), cantaloupe,
carrot juice (canned), figs, grapefruit juice, halibut, milk, oat
bran, potato (with skin), salmon, spinach, tuna and many others. 4.
Intravenous calcium gluconate if the patient is at no risk or low
risk of developing digitalis toxicity. 5. Intravenous administration
of 300-500 mL/hr of 10% dextrose solution containing 10-20 units of
crystalline insulin per 1,000 mL. 6. Correction of acidosis, if present,
with intravenous sodium bicarbonate. 7. Hemodialysis or peritoneal
dialysis. 8. Exchange resins may be used. However, this measure alone
is not sufficient for the acute treatment of hyperkalemia.Lowering potassium levels too
rapidly in patients taking digitalis can produce digitalis toxicity.

11  Description

Potassium Citrate is a citrate salt of potassium.
Its empirical formula is K3C6H507 • H20, and it has the following chemical structure:Potassium Citrate yellowish
to tan, oral wax-matrix tablets, contain 15 mEq (1620 mg) potassium
citrate each. Inactive ingredients include carnauba wax and magnesium
stearate.

12.1  Mechanism Of Action

When Potassium Citrate is given orally, the metabolism of
absorbed citrate produces an alkaline load. The induced alkaline load
in turn increases urinary pH and raises urinary citrate by augmenting
citrate clearance without measurably altering ultrafilterable serum
citrate. Thus, Potassium Citrate therapy appears to increase urinary
citrate principally by modifying the renal handling of citrate, rather
than by increasing the filtered load of citrate. The increased filtered
load of citrate may play some role, however, as in small comparisons
of oral citrate and oral bicarbonate, citrate had a greater effect
on urinary citrate.In addition to raising urinary pH and citrate, Potassium Citrate
increases urinary potassium by approximately the amount contained
in the medication. In some patients, Potassium Citrate causes a transient
reduction in urinary calcium. The changes induced by Potassium Citrate
produce urine that is less conducive to the crystallization of stone-forming
salts (calcium oxalate, calcium phosphate and uric acid). Increased
citrate in the urine, by complexing with calcium, decreases calcium
ion activity and thus the saturation of calcium oxalate. Citrate also
inhibits the spontaneous nucleation of calcium oxalate and calcium
phosphate (brushite).The increase in urinary pH also decreases calcium ion activity by
increasing calcium complexation to dissociated anions. The rise in
urinary pH also increases the ionization of uric acid to the more
soluble urate ion.Potassium Citrate therapy does not alter the urinary saturation of
calcium phosphate, since the effect of increased citrate complexation
of calcium is opposed by the rise in pH-dependent dissociation of
phosphate. Calcium phosphate stones are more stable in alkaline urine.In the setting of normal renal
function, the rise in urinary citrate following a single dose begins
by the first hour and lasts for 12 hours. With multiple doses the
rise in citrate excretion reaches its peak by the third day and averts
the normally wide circadian fluctuation in urinary citrate, thus maintaining
urinary citrate at a higher, more constant level throughout the day.
When the treatment is withdrawn, urinary citrate begins to decline
toward the pre-treatment level on the first day.The rise in citrate excretion is directly
dependent on the Potassium Citrate dosage. Following long-term treatment,
Potassium Citrate at a dosage of 60 mEq/day raises urinary citrate
by approximately 400 mg/day and increases urinary pH by approximately
0.7 units.In patients
with severe renal tubular acidosis or chronic diarrheal syndrome where
urinary citrate may be very low (<100 mg/day), Potassium Citrate
may be relatively ineffective in raising urinary citrate. A higher
dose of Potassium Citrate may therefore be required to produce a satisfactory
citraturic response. In patients with renal tubular acidosis in whom
urinary pH may be high, Potassium Citrate produces a relatively small
rise in urinary pH.

14  Clinical Studies

The pivotal Potassium Citrate trials were non-randomized
and non-placebo controlled where dietary management may have changed
coincidentally with pharmacological treatment. Therefore, the results
as presented in the following sections may overstate the effectiveness
of the product.

14.1  Renal Tubular Acidosis (Rta) With Calcium Stones

The effect of oral Potassium
Citrate therapy in a non-randomized, non-placebo controlled clinical
study of five men and four women with calcium oxalate/calcium phosphate
nephrolithiasis and documented incomplete distal renal tubular acidosis
was examined. The main inclusion criterion was a history of stone
passage or surgical removal of stones during the 3 years prior to
initiation of Potassium Citrate therapy. All patients began alkali
treatment with 60-80 mEq Potassium Citrate daily in 3 or 4 divided
doses. Throughout treatment, patients were instructed to stay on a
sodium restricted diet (100 mEq/day) and to reduce oxalate intake
(limited intake of nuts, dark roughage, chocolate and tea). A moderate
calcium restriction (400-800 mg/day) was imposed on patients with
hypercalciuria.X-rays
of the urinary tract, available in all patients, were reviewed to
determine presence of pre-existing stones, appearance of new stones,
or change in the number of stones.Potassium Citrate therapy was associated
with inhibition of new stone formation in patients with distal tubular
acidosis. Three of the nine patients continued to pass stones during
the on-treatment phase. While it is likely that these patients passed
pre-existing stones during therapy, the most conservative assumption
is that the passed stones were newly formed. Using this assumption,
the stone-passage remission rate was 67%. All patients had a reduced
stone formation rate. Over the first 2 years of treatment, the on-treatment
stone formation rate was reduced from 13±27 to 1±2 per year.

14.2  Hypocitraturic Calcium Oxalate Nephrolithiasis Of Any Etiology

Eighty-nine patients with hypocitraturic
calcium nephrolithiasis or uric acid lithiasis with or without calcium
nephrolithiasis participated in this non-randomized, non-placebo controlled
clinical study. Four groups of patients were treated with Potassium
Citrate: Group 1 was comprised of 19 patients, 10 with renal tubular
acidosis and 9 with chronic diarrheal syndrome, Group 2 was comprised
of 37 patients, 5 with uric acid stones alone, 6 with uric acid lithiasis
and calcium stones, 3 with type 1 absorptive hypercalciuria, 9 with
type 2 absorptive hypercalciuria and 14 with hypocitraturia. Group
3 was comprised of 15 patients with history of relapse on other therapy
and Group 4 was comprised of 18 patients, 9 with type 1 absorptive
hypercalciuria and calcium stones, 1 with type 2 absorptive hypercalciuria
and calcium stones, 2 with hyperuricosuric calcium oxalate nephrolithiasis,
4 with uric acid lithiasis accompanied by calcium stones and 2 with
hypocitraturia and hyperuricemia accompanied by calcium stones. The
dose of Potassium Citrate ranged from 30 to 100 mEq per day, and usually
was 20 mEq administered orally 3 times daily. Patients were followed
in an outpatient setting every 4 months during treatment and were
studied over a period from 1 to 4.33 years. A three-year retrospective
pre-study history for stone passage or removal was obtained and corroborated
by medical records. Concomitant therapy (with thiazide or allopurinol)
was allowed if patients had hypercalciuria, hyperuricosuria or hyperuricemia.
Group 2 was treated with Potassium Citrate alone.In all groups, treatment that included Potassium
Citrate was associated with a sustained increase in urinary citrate
excretion from subnormal values to normal values (400 to 700 mg/day),
and a sustained increase in urinary pH from 5.6-6.0 to approximately
6.5. The stone formation rate was reduced in all groups as shown in Table 1.Table 1. Effect of Potassium Citrate With Calcium Oxalate
Nephrolithiasis. Stones Formed Per Year* Remission defined as “the percentage of patients remaining free
of newly formed stones during treatment”.GroupBaselineOn TreatmentRemission*Any DecreaseI (n=19)12 ± 300.9 ± 1.358%95%II (n=37)1.2 ± 20.4 ± 1.589%97%III (n=15)4.2 ± 70.7 ± 267%100%IV (n=18)3.4 ± 80.5 ± 294%100%Total (n=89)4.3 ±150.6 ± 280%98%

14.3  Uric Acid Lithiasis With Or Without Calcium Stones

A long-term non-randomized, non-placebo
controlled clinical trial with eighteen adult patients with uric acid
lithiasis participated in the study. Six patients formed only uric
acid stones, and the remaining 12 patients formed mixed stones containing
both uric acid and calcium salts or formed both uric acid stones (without
calcium salts) and calcium stones (without uric acid) on separate
occasions.Eleven of
the 18 patients received Potassium Citrate alone. Six of the 7 other
patients also received allopurinol for hyperuricemia with gouty arthritis,
symptomatic hyperuricemia, or hyperuricosuria. One patient also received
hydrochlorothiazide because of unclassified hypercalciuria. The main
inclusion criterion was a history of stone passage or surgical removal
of stones during the 3 years prior to initiation of Potassium Citrate
therapy. All patients received potassium citrate at a dosage of 30-80
mEq/day in three-to-four divided doses and were followed every four
months for up to 5 years.While on Potassium Citrate treatment, urinary pH rose significantly
from a low value of 5.3 ± 0.3 to within normal limits (6.2 to 6.5).
Urinary citrate which was low before treatment rose to the high normal
range and only one stone was formed in the entire group of 18 patients.

15  References

1. Pak, C. (1987). Citrate and Renal Calculi. Mineral and Electrolyte Metabolism 13, 257-266.2. Pak, C. (1985). Long-Term
Treatment of Calcium Nephrolithiasis with Potassium Citrate. The Journal of Urology 134, 11-19.3. Preminger, G.M., K. Sakhaee, C. Skurla
and C.Y.C. Pak. (1985). Prevention of Recurrent Calcium Stone Formation
with Potassium Citrate Therapy in Patients with Distal Renal Tubular
Acidosis. The Journal of Urology 134, 20-23.4. Pak, C.Y.C., K. Sakhaee and
C. Fuller. (1986). Successful Management of Uric Acid Nephrolithiasis
with Potassium Citrate. Kidney International 30,
422-428.5. Hollander-Rodriguez,
J et al. (2006). Hyperkalemia, American Family Physician, Vol. 73/No. 2.6.
Greenberg, A et al. (1998). Hyperkalemia: treatment options. Semen Nephrol. Jan; 18 (1): 46-57.

16  How Supplied/Storage And Handling

Potassium Citrate 15 mEq tablets are uncoated, tan to yellowish in
color, modified rectangle shaped, with M15 debossed on one side and
blank on the other, supplied in bottles as:NDC 44523-415-01 Bottle of 100Storage: Store
in a tight container.

17.1  Administration Of Drug

Tell patients to take each dose without
crushing, chewing or sucking the tablet.Tell patients to take this medicine only
as directed. This is especially important if the patient is also taking
both diuretics and digitalis preparations.Tell patients to check with the doctor if
there is trouble swallowing tablets or if the tablet seems to stick
in the throat.Tell
patients to check with the doctor at once if tarry stools or other
evidence of gastrointestinal bleeding is noticed.Tell patients that their doctor will perform
regular blood tests and electrocardiograms to ensure safety.

Other

Manufactured for:BioComp Pharma®, Inc.San Antonio, TX 78230-1355  BCP-004 C01
Rev 004130

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