Visicol

Sodium biphosphate and sodium phosphate are forms of phosphorus, which is a naturally occurring substance that is important in every cell in the body.

Sodium biphosphate and sodium phosphate is a combination medicine used in adults to treat constipation and to clean the bowel before a colonoscopy.

Sodium biphosphate and sodium phosphate may also be used for purposes not listed in this medication guide.

In rare cases, this medicine can cause kidney failure. This effect may be more likely if you have:

• kidney disease;

• congestive heart failure;

• severe constipation or stomach pain, inflammatory bowel disease;

• if you take certain medicines to treat high blood pressure or heart disease;

• if you take an NSAID (nonsteroidal anti-inflammatory drug);

• if you are older than 55; or

• if you are dehydrated.

You should not use oral sodium biphosphate and sodium phosphate if you are allergic to it, or if you have:

• kidney disease (or if you have ever had a biopsy showing a kidney problem caused by too much phosphate);

• a bowel obstruction;

• a perforated bowel;

• colitis or toxic megacolon; or

• a history of gastric bypass surgery or stomach stapling.

To make sure this medicine is safe for you, tell your doctor if you have:

• inflammatory bowel disease;

• trouble swallowing, gastroesophageal reflux disease (GERD);

• heart disease, heart rhythm disorder, recent heart attack or heart surgery;

• a seizure disorder;

• recent withdrawal from drug or alcohol addiction;

• an electrolyte imbalance (such as high or low levels of potassium, sodium, phosphorous, or magnesium in your blood);

• if you have ongoing vomiting or diarrhea, or if you are sweating more than usual;

• if you take certain medicines to treat depression, seizures, or kidney problems;

• if you are on a low-salt diet; or

• if you have used any laxative within the past 7 days.

FDA pregnancy category C. It is not known whether sodium biphosphate and sodium phosphate will harm an unborn baby. Tell your doctor if you are pregnant.

It is not known whether sodium biphosphate and sodium phosphate passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not give this medicine to anyone under 5 years old without medical advice.

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.

To keep from getting dehydrated, drink a full glass (8 ounces) of water or other clear liquid each time you use this medicine. This includes water, flavored water, lemonade (no pulp), ginger ale, or apple juice, but nothing colored red or purple. Follow your doctor's instructions about the type and amount of liquids to drink for 24 hours after taking sodium biphosphate and sodium phosphate.

If you take the tablet form of this medicine, you will most likely start taking it the evening before your colonoscopy, and finish taking it on the day of your colonoscopy.

Measure the oral liquid and mix it with a full glass (8 ounces) of cool water. Stir and drink this mixture right away. Then drink another full glass of cool water.

Do not use more than 1 dose in any 24-hour period. If you do not get any results within 30 minutes after using this medicine, call your doctor before using another dose.

Using too much of this medicine can cause rare but life-threatening side effects on your kidneys and heart.

Do not use sodium biphosphate and sodium phosphate for longer than 1 week unless your doctor has told you to.

Call your doctor if you are sick with vomiting or diarrhea, or if you are sweating more than usual. You may need blood tests to check your electrolyte levels.

Store at room temperature away from moisture and heat. Throw away any leftover medicine after your treatment ends.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

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

Stop using this medicine and call your doctor at once if you have:

• headache, dizziness, vomiting, little or no urinating;

• fever, sudden or severe stomach pain, severe diarrhea, rectal bleeding or bright red bowel movements;

• fast, slow, or uneven heart rate;

• seizure (black-out or convulsions); or

• no bowel movement after use.

Common side effects may include:

• bloating, nausea, or mild stomach discomfort.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• Confusion
• convulsions (seizures)
• decrease in amount of urine or in frequency of urination
• fast, slow, or irregular heartbeat
• headache or dizziness
• increased thirst
• muscle cramps
• numbness, tingling, pain, or weakness in hands or feet
• numbness or tingling around lips
• shortness of breath or troubled breathing
• swelling of feet or lower legs
• tremor
• unexplained anxiety
• unusual tiredness or weakness
• weakness or heaviness of legs
• weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• nausea or vomiting
• stomach pain

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Use Visicol as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take this medicine as your doctor has told you. Follow all instructions you have been given closely. This includes when to take Visicol (sodium phosphates tablets), foods and drinks to avoid before the exam, and when to stop eating and drinking before the exam. Talk with your doctor if you have any questions.
• Drink clear liquids before, during, and after taking this medicine. Do not drink any liquids that are purple or red.
• Drink lots of noncaffeine liquids before, during, and after using Visicol unless you are told to drink less liquid by your doctor.
• Do not take other drugs within 1 hour of this medicine.

What do I do if I miss a dose?

• If you are using Visicol before an exam, take a missed dose as soon as you think about it.

Administration of sodium phosphate products prior to colonoscopy has resulted in fatalities due to significant fluid shifts, severe electrolyte abnormalities, and cardiac arrhythmias. These fatalities have been observed in patients with renal insufficiency, in patients with bowel perforation, and in patients who misused or overdosed sodium phosphate products. It is recommended that patients receiving Visicol be advised to adequately hydrate before, during, and after the use of Visicol.

Considerable caution should be advised before Visicol Tablets are used in patients with the following illnesses: severe renal insufficiency (creatinine clearance less than 30 mL/minute), congestive heart failure, ascites, unstable angina, acute bowel obstruction, bowel perforation, toxic megacolon, gastric retention, ileus, pseudo-obstruction of the bowel, severe chronic constipation, acute colitis, gastric bypass or stapling surgery or hypomotility syndrome.

Consider performing baseline and post-colonoscopy labs (phosphate, calcium, potassium, sodium, creatinine, and BUN) in patients who may be at increased risk for serious adverse events, including those with history of renal insufficiency, history of ─ or at greater risk of ─ acute phosphate nephropathy, known or suspected electrolyte disorders (such as dehydration), seizures, arrhythmias, cardiomyopathy, prolonged QT, recent history of a MI and those with known or suspected hyperphosphatemia, hypocalcemia, hypokalemia, and hypernatremia. Also if patients develop vomiting and/or signs of dehydration then measure post-colonoscopy labs (phosphate, calcium, potassium, sodium, creatinine, and BUN).

Renal Disease, Acute Phosphate Nephropathy, and Electrolyte Disorders
There have been rare, but serious reports of renal failure, acute phosphate nephropathy, and nephrocalcinosis in patients who received oral sodium phosphate products (including oral sodium phosphate solutions and tablets) for colon cleansing prior to colonoscopy. These cases often resulted in permanent impairment of renal function and several patients required long-term dialysis. The time to onset is typically within days; however, in some cases, the diagnosis of these events has been delayed up to several months after the ingestion of these products. Patients at increased risk of acute phosphate nephropathy may include patients with the following: hypovolemia, baseline kidney disease, increased age, and patients using medicines that affect renal perfusion or function [such as diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers, and possibly nonsteroidal anti-inflammatory drugs (NSAIDs).

Use Visicol with caution in patients with impaired renal function, known or suspected electrolyte disturbances (such as dehydration), or people taking concomitant medications that may affect electrolyte levels (such as diuretics). Patients with electrolyte abnormalities such as hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia should have them corrected before treatment with Visicol Tablets.

Seizures
There have been rare reports of generalized tonic-clonic seizures and/or loss of consciousness associated with use of sodium phosphate products in patients with no prior history of seizures. The seizure cases were associated with electrolyte abnormalities (e.g., hyponatremia, hypokalemia, hypocalcemia, and hypomagnesemia) and low serum osmolality. The neurologic abnormalities resolved with correction of fluid and electrolyte abnormalities. Visicol should be used with caution in patients with a history of seizures and in patients at higher risk of seizure [patients using concomitant medications that lower the seizure threshold (such as tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, or patients with known or suspected hyponatremia].

Cardiac Arrhythmias
There have been rare, but serious reports of arrhythmias associated with the use of sodium phosphate products. Visicol should be used with caution in patients with higher risk of arrhythmias (patients with a history of cardiomyopathy, patients with prolonged QT, patients with a history of uncontrolled arrhythmias, and patients with a recent history of a myocardial infarction). Pre-dose and post-colonoscopy ECGs should be considered in patients with high risk of serious, cardiac arrhythmias.

General

Patients should be instructed to drink 8 ounces of clear liquids with each 3-tablet (or each 2-tablet) dose of Visicol. Patients should take a total of 3.6 quarts of clear liquids with Visicol. Inadequate fluid intake, as with any effective purgative, may lead to excessive fluid loss and hypovolemia. Dehydration from purgation may be exacerbated by inadequate oral fluid intake, vomiting, and/or the use of diuretics. Patients should not take additional laxatives or purgatives, particularly additional sodium phosphate-based products.

Prolongation of the QT interval has been observed in some patients who were dosed with Visicol Tablets. QT prolongation with Visicol Tablets has been associated with electrolyte imbalances, such as hypokalemia and hypocalcemia. Visicol Tablets should be used with caution in patients who are taking medications known to prolong the QT interval, since serious complications may occur. Pre-dose and post-colonoscopy ECGs should be considered in patients with known prolonged QT. In these studies, prolongation of the QT interval was also observed in some patients treated with PEG-salt solution.

Patients with a history of swallowing difficulties or anatomic narrowing of the esophagus, such as a stricture, may have difficulty swallowing Visicol Tablets. Undigested or partially digested Visicol Tablets may be seen in the stool or during colonoscopy. In addition, undigested tablets from other medications may be seen in the stool or during colonoscopy.

Administration of Visicol Tablets may induce colonic mucosal aphthous ulcerations, since this endoscopic finding observed with other sodium phosphate cathartic preparations. This colonoscopic finding should be considered in patients with known or suspect inflammatory bowel disease (IBD).

Because published data suggest that sodium phosphate absorption may be enhanced in patients experiencing an acute exacerbation of IBD, Visicol Tablets should be used with caution in IBD patients.

Since Visicol Tablets were not studied in patients who recently had cardiac surgery (including coronary artery bypass graft surgery) Visicol should be used with caution in these patients.

Drug Interactions

Medications administered in close proximity to Visicol Tablets may not be absorbed from the gastrointestinal tract due to the rapid intestinal peristalsis and watery diarrhea induced by the purgative agent.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Visicol. Studies to evaluate the effect of Visicol on fertility or its mutagenic potential have not been performed.

Pregnancy

Category C. Reproduction studies have not been conducted with Visicol. It is also not known whether Visicol can cause fetal harm when administered to a pregnant woman, or can affect reproduction capacity. Visicol Tablets should be given to a pregnant woman only if clearly needed.

Pediatric Use

Safety and efficacy of Visicol Tablets have not been demonstrated in patients less than 18 years of age.

Geriatric Use

Of the 980 subjects/patients in the Visicol studies, 284 (29%) subjects/patients were 65 years of age or older. Of the 548 subjects/patients who received Visicol in these studies, 146 (27%) were 65 years of age or older and 42 (8%) subjects/patients were 75 years of age or older.

In two phase 3 Visicol trials (Study A and Study B), no overall differences in safety or effectiveness were observed between geriatric patients and younger patients. Greater sensitivity of some older individuals cannot be ruled out; therefore, Visicol Tablets should be used with caution in geriatric patients.

Sodium phosphate is known to be substantially excreted by the kidney, and the risk of adverse reactions with sodium phosphate may be greater in patients with impaired renal function. Since geriatric patients are more likely to have impaired renal function, consider performing baseline and post-colonoscopy labs (phosphate, calcium, potassium, sodium, creatinine, and BUN) in these patients (see WARNINGS).

Applies to sodium biphosphate / sodium phosphate: oral liquid, oral solution, oral tablet

Other dosage forms:

• rectal enema

Along with its needed effects, sodium biphosphate / sodium phosphate may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking sodium biphosphate / sodium phosphate:

• Abdominal or stomach pain
• bloating
• nausea
• vomiting

• Agitation
• bloody or cloudy urine
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• coma
• confusion
• cough
• decreased urine output
• depression
• difficult or labored breathing
• difficult or painful urination
• difficulty with swallowing
• dizziness
• fainting
• fast, slow, or irregular heartbeat
• headache
• hostility
• irritability
• lethargy
• muscle twitching
• noisy breathing
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• redness of the skin
• seizures
• skin rash, hives or welts, or itching
• stupor
• swelling of the face, ankles, or hands
• tightness in the chest
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur while taking sodium biphosphate / sodium phosphate:

• Abdominal or stomach cramps
• blurred vision
• chest pain or discomfort
• decreased frequency of urine
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• dry mouth
• increase in heart rate
• increased thirst
• lightheadedness
• loss of appetite
• lower back or side pain
• muscle cramps in the hands, arms, feet, legs, or face
• muscle pain
• pounding or rapid pulse
• rapid breathing
• restlessness
• sunken eyes
• sweating
• tremor
• weakness
• weight gain
• wrinkled skin