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Wednesday, 16 May 2012

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets

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BOXED WARNING

There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long-term dialysis. While some cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteriodal anti-inflammatory drugs [NSAIDs]). See WARNINGS.

It is important to use the dose and dosing regimen as recommended (pm/am split dose). SeeDOSAGE and ADMINISTRATION.

DESCRIPTION

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablet is a purgative used to clean the colon prior to colonoscopy. Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets are manufactured with a highly soluble tablet binder and does not contain microcrystalline cellulose (MCC). Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets are white to off-white modified oval shaped, biconvex, bisect on one side and plain on the other debossed “N” on the left side of bisect and “03” on the right side of the bisect. Each Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablet contains 1.102 grams of monobasic sodium phosphate, USP and 0.398 grams of dibasic sodium phosphate, USP for a total of 1.5 grams of sodium phosphate per tablet. Inert ingredients include polyethylene glycol 8000; and magnesium stearate. Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablet is gluten-free.

The structural and molecular formulae and molecular weights of the active ingredients are shown below:

Monobasic sodium phosphate, USP

Molecular Formula: NaH2PO4• H2O

Molecular Weight: 137.99

Dibasic sodium phosphate, USP

Molecular Formula: Na2HPO4

Molecular Weight: 141.96

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets are for oral administration only.

CLINICAL PHARMACOLOGY

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, a dosing regimen containing 48 grams of sodium phosphate (32 tablets), induces diarrhea, which effectively cleanses the entire colon. Each administration has a purgative effect for approximately 1 to 3 hours. The primary mode of action is thought to be through the osmotic effect of sodium, causing large amounts of water to be drawn into the colon, promoting evacuation.

Pharmacokinetics

Pharmacokinetic studies with Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets have not been conducted. However, the following pharmacokinetic study was conducted with Visicol tablets which contain the same active ingredients (sodium phosphate) as Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. In addition, Visicol is administered at a dose that is 25% greater than the Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets dose.

An open-label pharmacokinetic study of Visicol in healthy volunteers was performed to determine the concentration-time profile of serum inorganic phosphorus levels after Visicol administration. All subjects received the approved Visicol dosing regimen (60 grams of sodium phosphate with a total liquid volume of 3.6 quarts) for colon cleansing. A 30 gram dose (20 tablets given as 3 tablets every 15 minutes with 8 ounces of clear liquids) was given beginning at 6 PM in the evening. The 30 gram dose (20 tablets given as 3 tablets every 15 minutes with 8 ounces of clear liquids) was repeated the following morning beginning at 6 AM.

Twenty-three healthy subjects (mean age 57 years old; 57% male and 43% female; and 65% Hispanic, 30% Caucasian, and 4% African-American) participated in this pharmacokinetic study. The serum phosphorus level rose from a mean (± standard deviation) baseline of 4.0 (± 0.7) mg/dL to 7.7 (± 1.6 mg/dL), at a median of 3 hours after the administration of the first 30 gram dose of sodium phosphate tablets (see Figure 1). The serum phosphorus level rose to a mean of 8.4 (± 1.9) mg/dL, at a median of 4 hours after the administration of the second 30 gram dose of sodium phosphate tablets. The serum phosphorus level remained above baseline for a median of 24 hours after the administration of the initial dose of sodium phosphate tablets (range 16 to 48 hours).

Figure 1. Mean (± standard deviation) serum phosphorus concentrations

The upper (4.5 mg/dL) and lower (2.6 mg/dL) reference limits for serum phosphate are represented by solid bars.

Special Populations

Renal Insufficiency: The effect of renal dysfunction on the pharmacokinetics of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets has not been studied. Since the inorganic form of phosphate in the circulating plasma is excreted almost entirely by the kidneys, patients with renal disease may have difficulty excreting a large phosphate load. Thus, Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets should be used with caution in patients with impaired renal function (see WARNINGS).

Hepatic Insufficiency:

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets have not been investigated in patients with hepatic failure.

Geriatric:

In a single pharmacokinetic study of sodium phosphate tablets, which included 6 elderly volunteers, plasma half-life increased two-fold in subjects >70 years of age compared to subjects <50 years of age (3 subjects and 5 subjects, respectively).

Gender:

No difference in serum phosphate AUC values were observed in the single pharmacokinetic study conducted with sodium phosphate tablets in 13 male and 10 female healthy volunteers.

CLINICAL STUDIES

The colon-cleansing efficacy and safety of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets was evaluated in 2 randomized, investigator-blinded, actively-controlled, multi center, U.S. trials in patients scheduled to have an elective colonoscopy. The trials consisted of a dose ranging and a confirmatory phase 3 study.

In the phase 3 trial, patients were randomized into one of the following three sodium phosphate treatment groups: 1) Visicol containing 60 grams of sodium phosphate given in split doses (30 grams in the evening before the colonoscopy and 30 grams on the next day) with at least 3.6 quarts of clear liquids; 2) Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets containing 60 grams of sodium phosphate given in split doses (30 grams in the evening before the colonoscopy and 30 grams on the next day) with 2.5 quarts of clear liquids; and 3) Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets containing 48 grams of sodium phosphate (30 grams in the evening before the colonoscopy and 18 grams on the next day) with 2 quarts of clear liquids. Patients were instructed to eat a light breakfast before noon on the day prior to the colonoscopy and then were told to drink only clear liquids after noon on the day prior to the colonoscopy.

The primary efficacy endpoint was the overall colon cleansing response rate in the 4-point Colonic Contents Scale. Response was defined as a rating of “excellent” or “good” on the 4-point scale as determined by the blinded colonoscopist. This phase 3 study was planned to assess the non-inferiority of the two Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets groups compared to the Visicol group.

The efficacy analysis included 704 adult patients who had an elective colonoscopy. Patients ranged in age from 21 to 89 years old (mean age 56 years old) with 55% female and 45% male patients. Race was distributed as follows: 87% Caucasian, 10% African American, and 3% other race. The Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets 60 gram and 48 gram treatment groups demonstrated non-inferiority compared to Visicol. See Table 1 for the results.

Table 1: Phase 3 study- Overall Colon Content Cleansing Response Rates1
Treatment arm(grams of sodiumphosphate)	No. of tablets taken at 6 PM on the day prior to colonoscopy	No. of tablets taken the next day2	Excellent	Good	Fair	Inadequate	Overall response rate (excellent or good)
Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablet 32 tabs (48 g) n=236	20	12	76%	19%	3%	2%	95%
Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablet 40 tabs (60 g) n=233	20	20	73%	24%	2%	1%	97%
Visicol40tabs (60 g) n=235	20	20	51%	43%	6%	0%	94%

1Colon-cleansing efficacy was based on response rate to treatment. A patient was considered to be a responder if overall colon cleansing was rated as “excellent” or “good” on a 4-point scale based on the amount of retained “colonic contents”. Excellent was defined as >90% of mucosa seen, mostly liquid stool, minimal suctioning need for adequate visualization. Good was defined as >90% of mucosa seen, mostly liquid stool, significant suctioning needed for adequate visualization. Fair was defined as >90% of mucosa seen, mixture of liquid and semisolid stool, could be suctioned and/or washed. Inadequate was defined as <90% of mucosa seen, mixture of semisolid and/or solid stool which could not be suctioned or washed.

2On the day of the colonoscopy, study medication was taken 3 to 5 hours before the start of the colonoscopy.

Electrolyte Changes

In the Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets clinical studies, expected serum electrolyte changes (including phosphate, calcium, potassium, and sodium levels) have been observed in patients taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. In the overwhelming majority of patients, electrolyte abnormalities were not associated with any adverse events.

In the Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets phase 3 study, 96%, 96%, and 93% of patients who took 60 grams of Visicol, 60 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, and 48 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, respectively, developed hyperphosphatemia (defined as phosphate level > 5.1 mg/dL) on the day of the colonoscopy. In this study, patients who took 60 grams of Visicol, 60 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, and 48 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets had baseline mean phosphate levels of 3.5, 3.5, and 3.6 mg/dL and subsequently developed mean phosphate levels of 7.6, 7.9, and 7.1 mg/dL, respectively, on the day of the colonoscopy.

In the Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets phase 3 study, 20%, 22%, and 18% of patients who took 60 grams of Visicol, 60 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, and 48 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, respectively, developed hypokalemia (defined as a potassium level <3.4 mEq/L) on the day of the colonoscopy. In this study, patients who took 60 grams of Visicol, 60 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, and 48 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets all had baseline potassium levels of about 4.3 mEq/L and then developed a mean potassium level of 3.7 mEq/L on the day of the colonoscopy.

In the Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets phase 3 trial, several patients on all three sodium phosphate regimens developed hypocalcemia and hypernatremia that did not require treatment.

INDICATIONS AND USAGE

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older.

CONTRAINDICATIONS

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets are contraindicated in patients with biopsy-proven acute phosphate nephropathy.

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets are contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients.

WARNINGS

Administration of sodium phosphate products prior to colonoscopy for colon cleansing 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 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets be advised to adequately hydrate before, during, and after the use of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

Considerable caution should be advised before Monobasic Sodium Phosphate and Dibasic Sodium Phosphate 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, gastric retention, ileus, acute bowel obstruction, pseudo-obstruction of the bowel, severe chronic constipation, bowel perforation, acute colitis, toxic megacolon, 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, 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 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets with caution in patients with impaired renal function, patients with a history of acute phosphate nephropathy, 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 their electrolytes corrected before treatment with Monobasic Sodium Phosphate and Dibasic Sodium Phosphate 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. Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets 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. Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets 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.

PRECAUTIONS

General

Patients should be instructed to drink 8 ounces of clear liquids with each 4-tablet dose of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. Patients should take a total of 2 quarts of clear liquids with Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. Inadequate fluid intake, as with any effective purgative, may lead to excessive fluid loss, hypovolemia, and dehydration. Dehydration from purgation may be exacerbated by inadequate oral fluid intake, vomiting, and/or use of diuretics.

Patients should be instructed not to administer additional laxative or purgative agents, particularly additional sodium phosphate-based purgative or enema products.

Prolongation of the QT interval has been observed in some patients who were dosed with sodium phosphate colon preparations. QT prolongation with sodium phosphate tablets has been associated with electrolyte imbalances, such as hypokalemia and hypocalcemia. Monobasic Sodium Phosphate and Dibasic Sodium Phosphate 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.

Administration of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets may induce colonic mucosal aphthous ulcerations, since this endoscopic finding was observed with other sodium phosphate cathartic preparations. In the Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets clinical program, aphthous ulcers were observed in 3% of patients who took the 48 gram Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets dosing regimen. This colonoscopic finding should be considered in patients with known or suspected inflammatory bowel disease.

Because published data suggest that sodium phosphate absorption may be enhanced in patients experiencing an acute exacerbation of chronic inflammatory bowel disease, Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets should be used with caution in such patients.

Drug Interactions

Medications administered in close proximity to Monobasic Sodium Phosphate and Dibasic Sodium Phosphate 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 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. Studies to evaluate the effect of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets on fertility or its mutagenic potential have not been performed.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Animal reproduction studies have not been conducted with Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. It is not known whether Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets can cause fetal harm when administered to a pregnant woman, or can affect reproduction capacity. Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets should be given to a pregnant woman only if clearly needed.

Pediatric Use

The safety and efficacy of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets have not been demonstrated in patients less than 18 years of age.

Geriatric Use

In controlled colon preparation trials of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, 228 (24%) of 931 patients were 65 years of age or older. In addition, 49 (5%) of the 931 patients were 75 years of age or older.

Of the 228 geriatric patients in the trials, 134 patients (59%) received at least 48 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. Of the 49 patients 75 years old or older in the trials, 27 (55%) patients received at least 48 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. No overall differences in safety or effectiveness were observed between geriatric patients and younger patients. However, the mean phosphate levels in geriatric patients were greater than the phosphate levels in younger patients after Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets administration. The mean colonoscopy-day phosphate levels in patients 18-64, 65-74, and ≥75 years old who received 48 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets in the phase 3 study were 7.0, 7.3, and 8.0 mg/dL, respectively. In addition, in all three sodium phosphate treatment groups, the mean phosphate levels in patients 18-64, 65-74, and ≥ 75 years old in the phase 3 study were 7.4, 7.9, and 8.0 mg/dL, respectively, after sodium phosphate administration. Greater sensitivity of some older individuals cannot be ruled out; therefore, Monobasic Sodium Phosphate and Dibasic Sodium Phosphate 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). It is recommended that patients receiving Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets be advised to adequately hydrate before, during, and after the use of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

ADVERSE REACTIONS

Abdominal bloating, abdominal pain, nausea, and vomiting were the most common adverse events reported with the use of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. Dizziness and headache were reported less frequently. Since diarrhea was considered as a part of the efficacy of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, diarrhea was not defined as an adverse event in the clinical studies. Table 2 shows the most common adverse events associated with the use of 48 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, 60 grams of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, and 60 grams of Visicol in the colon preparation trials (n=931).

Table 2: Frequency of Adverse Events of Any Severity Occurring in Greater than 3% of Patients in the Monobasic Sodium Phosphate and Dibasic Sodium Phosphate TabletsTrials
	Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets 32 tabs (48 g)N=272	Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets 40 tabs (60 g)N=265	Visicol40 tabs (60 g)N=268
Bloating	31%	39%	41%
Nausea	26%	37%	30%
Abdominal pan	23%	24%	25%
Vomiting	4%	10%	9%

Postmarketing Experience

In addition to adverse events reported from clinical trials, the following adverse events have been identified during post-approval use of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to either their seriousness, frequency of reporting or causal connection to Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, or a combination of these factors.

General:

Hypersensitivity reactions including anaphylaxis, rash, pruritus, urticaria, throat tightness, bronchospasm, dyspnea, pharyngeal edema, dysphagia, paresthesia and swelling of the lips and tongue, and facial swelling.

Cardiovascular: Arrhythmias

Nervous System: Seizures

Renal:

Renal impairment, increased blood urea nitrogen (BUN), increased creatinine, acute renal failure, acute phosphate nephropathy, nephrocalcinosis, and renal tubular necrosis.

DRUG ABUSE AND DEPENDENCE

Laxatives and purgatives (including Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets) have the potential for abuse by bulimia nervosa patients who frequently have binge eating and vomiting.

OVERDOSAGE

There have been no reported cases of overdosage with Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. Purposeful or accidental ingestion of more than the recommended dosage of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets might be expected to lead to severe electrolyte disturbances, including hyperphosphatemia, hypocalcemia, hypernatremia, or hypokalemia, as well as dehydration and hypovolemia, with attendant signs and symptoms of these disturbances. Certain severe electrolyte disturbances resulting from overdose may lead to cardiac arrhythmias, seizure, renal failure, and death. The patient who has taken an overdosage should be monitored carefully, and treated symptomatically for complications until stable.

DOSAGE AND ADMINISTRATION

The recommended dose of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets for colon cleansing for adult patients is 32 tablets (48 grams of sodium phosphate) taken orally with a total of 2 quarts of clear liquids in the following manner:

The evening before the colonoscopy procedure:

Take 4 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets with 8 ounces of clear liquids every 15 minutes for a total of 20 tablets.

On the day of the colonoscopy procedure:

Starting 3-5 hours before the procedure, take 4 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets with 8 ounces of clear liquids every 15 minutes for a total of 12 tablets.

Patients should be advised of the importance of taking the recommended fluid regimen. It is recommended that patients receiving Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets be advised to adequately hydrate before, during, and after the use of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

Patients should not use Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets for colon cleansing within seven days of previous administration. No additional enema or laxative is required, and patients should be advised NOT to take additional agents, particularly those containing sodium phosphate.

HOW SUPPLIED

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets are supplied in child-resistant bottles containing 100 tablets. Each tablet contains 1.102 g monobasic sodium phosphate, USP and 0.398 g dibasic sodium phosphate, USP for a total of 1.5 g of sodium phosphate per tablet. Each bottle contains two silica desiccant packets, which should not be ingested.

NDC 40032-030-24 (100 tablets)

Storage and Handling

Store at 25°C (77°F); excursions permitted to 15°-30° C (59°-86°F) [See USP Controlled Room Temperature]. Discard any unused portion.

Manufactured by:

Novel Laboratories, Inc.

Somerset, NJ 08873

Medguide

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets

Read the Medication Guide that comes with Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets before you take it and each time you take it. This Medication Guide does not take the place of talking with your doctor about your medical condition or your treatment. If you have any questions about Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, ask your doctor or pharmacist.

What is the most important information I should know about Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets can cause serious side effects, including:

Serious kidney problems. Rare, but serious kidney problems can happen in people who take medicines made with sodium phosphate, including Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, to clean your colon before a colonoscopy. These kidney problems can sometimes lead to kidney failure or the need for dialysis for a long time. These problems often happen within a few days, but sometimes may happen several months after taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

Conditions that can make you more at risk for having serious kidney problems with Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets include if you:

• lose too much body fluid (dehydration)

• have slow moving bowels

• have bowels blocked with stool (constipation)

• have severe stomach pain or bloating

• have any disease that causes bowel irritation (colitis)

• have kidney disease

• have heart failure

• take water pills or non-steroidal anti-inflammatory drugs (NSAIDS).

Your age may also affect your risk for having kidney problems with Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

Before you start taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, tell your doctor if you:

• have kidney problems

• take any medicines for blood pressure, heart disease, or kidney disease.

Severe fluid loss. People who take medicines that contain sodium phosphate can have severe loss of body fluid, with severe changes in body salts in the blood, and abnormal heart rhythms. These problems can lead to death.

Tell your doctor if you have any of these symptoms of loss of too much body fluid (dehydration) while taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets:

• vomiting

• dizziness

• urinating less often than normal

• headache

See "What are the possible side effects of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?" for more information about side effects.

What is Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets is a prescription medicine used in adults 18 years and older, to clean your colon before a colonoscopy. Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets cleans your colon by causing you to have diarrhea. Cleaning your colon helps your doctor see the inside of your colon more clearly during the colonoscopy.

It is not known if Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets is safe and works in children under age 18.

Who should not take Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

Do not take Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets if:

• you have had a kidney biopsy that shows you have kidney problems because of too much phosphate

• you are allergic to sodium phosphate salts or any of the ingredients in Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

See the end of this Medication Guide for a list of ingredients in Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

What should I tell my doctor before taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

Before taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, tell your doctor about all your medical conditions, including if you have:

• any of the medical conditions listed in the section "What is the most important information I should know about Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?"

• irritation of the bowel (colitis). Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets can cause symptoms of irritable bowel disease to flare-up.

• damage to your bowels

• problems with abnormal heart beat

• had a recent heart attack or have other heart problems

• symptoms of too much body fluid loss (dehydration) including vomiting, dizziness, urinating less often than normal, or headache

• had stomach surgery

• a history of seizures

• if you drink alcohol

• are on a low salt diet

• are pregnant. It is not known if Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets will harm your unborn baby.

Tell your doctor about all the medicines you take, including prescription and non prescription medicines, vitamins, and herbal supplements. Any medicine that you take close to the time that you take Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets may not work as well. Especially tell your doctor if you take:

• water pills (diuretics)

• medicines for blood pressure or heart problems.

• medicines for kidney damage

• medicines for pain, such as aspirin or a non-steroidal anti-inflammatory drug (NSAID)

• a medicine for seizures

• a laxative for constipation in the last 7 days. You should not take another medicine that contains sodium phosphate while you take Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

Ask your doctor if you are not sure if your medicine is listed above.

Know the medicines you take. Keep a list of your medicines to show your doctor or pharmacist when you get a new prescription.

How should I take Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

• Take Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets exactly as prescribed by your doctor.

• It is important for you to drink clear liquids before, during, and after taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. This may help prevent kidney damage. Examples of clear liquids are water, flavored water, lemonade (no pulp), ginger ale, or apple juice. Do not drink any liquids colored purple or red.

You must read, understand, and follow these instructions to take Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets the right way:

On the evening before your colonoscopy, you will take a total of 20 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, as follows:

Take 4 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets with 8 ounces of clear liquids.

Wait 15 minutes.

Take 4 more Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets with 8 ounces of clear liquids.

Repeat steps 2 and 3 above, three more times. Make sure you wait 15 minutes after each time.

On the day of your colonoscopy you will take a total of 12 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, starting about 3 to 5 hours before your colonoscopy, as follows:

Take 4 Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets with 8 ounces of clear liquids.

Wait 15 minutes.

Take 4 more Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets with 8 ounces of clear liquids.

Repeat steps 2 and 3 one more time.
Tell your doctor if you have any of these symptoms while taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets:

vomiting, dizziness, or if you urinate less often than normal. These may be signs that you have lost too much fluid while taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

trouble drinking clear fluids

severe stomach cramping, bloating, nausea, or headache
If you take too much Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, call your doctor or get medical help right away.

What should I avoid while taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

You should not take other laxatives or enemas made with sodium phosphate, while taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

You should not use Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets if you have already used it in the last 7 days.
What are the possible side effects of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets can cause serious side effects, including:

See "What is the most important information I should know about Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?"

Seizures or fainting (black-outs). People who take a medicine that contains sodium phosphate, such as Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, can have seizures or faint (become unconscious) even if they have not had seizures before. Tell your doctor right away if you have a seizure or faint while taking Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets.

abnormal heart beat (arrhythmias)

changes in your blood levels of calcium, phosphate, potassium, sodium
The most common side effects of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets are:

bloating

stomach area (abdominal) pain

nausea

vomiting
These are not all the possible side effects of Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. For more information, ask your doctor or pharmacist.

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

How do I store Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

Store Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets at room temperature, between 59° F to 86° F(15° C to 30° C).

Throw away any Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets that is not needed.

Keep Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets and all medicines out of the reach of children.

General information about Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets for a condition for which it was not prescribed. Do not give Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets. If you would like more information about Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets, talk with your doctor or pharmacist. You can ask your doctor or pharmacist for information that is written for healthcare professionals. For more information, call 1-908-603-6000 or go to www.fda.gov.

What are the ingredients in Monobasic Sodium Phosphate and Dibasic Sodium Phosphate Tablets?

Active ingredients: sodium phosphate monobasic and sodium phosphate dibasic anhydrous

Inactive ingredients: polyethylene glycol 8000 and magnesium stearate

Novel Laboratories, Inc.

Somerset, NJ 08873, USA

NIN-030-00

Rev: 05/2011

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

MONOBASIC SODIUM PHOSPHATE AND DIBASIC SODIUM PHOSPHATE
monobasic sodium phosphate and dibasic sodium phosphate tablet

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	NDC Product Code (Source)	40032-030
Route of Administration	ORAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE (SODIUM CATION)	SODIUM PHOSPHATE, MONOBASIC, MONOHYDRATE	1.105 g
SODIUM PHOSPHATE, DIBASIC ANHYDROUS (SODIUM CATION)	SODIUM PHOSPHATE, DIBASIC ANHYDROUS	0.398 g

Inactive Ingredients
Ingredient Name	Strength
MAGNESIUM STEARATE
POLYETHYLENE GLYCOL 8000

Product Characteristics
Color	WHITE (white to off-white)	Score	2 pieces
Shape	OVAL (Modified)	Size	18mm
Flavor		Imprint Code	N;03
Contains

Tuesday, 15 May 2012

Metoclopramide Hydrochloride

Class: Prokinetic Agents
VA Class: AU300
Molecular Formula: C₁₄H₂₂ClN₃O₂₂O
CAS Number: 54143-57-6
Brands: Reglan

Tardive Dyskinesia

May result in tardive dyskinesia.⁵ ²⁶⁷ Risk increases with increasing duration of therapy and total cumulative dose.⁵ ²⁶⁷ (See Tardive Dyskinesia under Cautions.)

Discontinue metoclopramide in patients who develop signs or symptoms of tardive dyskinesia.⁵ ²⁶⁷ There is no known treatment for tardive dyskinesia; however, symptoms may lessen or resolve in some patients after discontinuance.⁵ ²⁶⁷

Avoid use for >12 weeks in all but rare cases where therapeutic benefit is thought to outweigh risk of developing tardive dyskinesia.⁵ ²⁶⁷

REMS:

FDA approved a REMS for metoclopramide to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of metoclopramide and consists of the following: medication guide. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antiemetic; stimulant of upper GI motility (prokinetic agent);¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ²⁶³ ²⁶⁷ potent dopamine-receptor antagonist.² ⁴ ⁵ ⁷ ¹⁹ ²⁸ ³⁴ ⁵² ²⁶⁷

Uses for Metoclopramide Hydrochloride

Diabetic Gastric Stasis

Symptomatic treatment of acute and recurrent diabetic gastric stasis (gastroparesis).⁵ ⁷ ³² ⁴⁴ ⁷⁶ ⁷⁷ ⁷⁸ ⁷⁹ ⁸⁰ ⁸³ ⁸⁴ ⁸⁸ ⁸⁹ ²⁶⁷ Successful therapy often requires long-term, intermittent use, since diabetic gastric stasis is a chronic, recurrent disease.⁵ ⁹

Postsurgical Gastric Stasis

Has been used for the symptomatic treatment of acute and chronic postsurgical gastric stasis† following vagotomy and gastric resection or vagotomy and pyloroplasty.³¹ ³⁷ ⁴⁴ ⁴⁹ ⁸⁴ ¹¹³ ¹¹⁴ ¹¹⁵ ¹⁴⁸ ¹⁴⁹ ¹⁵⁰

Prevention of Postoperative Nausea and Vomiting

Prevention of postoperative nausea and vomiting when nasogastric suction is considered undesirable.⁴ ¹²⁵ ²⁶⁷

Prevention of Cancer Chemotherapy-induced Emesis

Used parenterally in high doses for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy including cisplatin alone or in combination with other antineoplastic agents.⁹⁷ ⁹⁸ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ ²⁶³ ²⁶⁷

Prevention of nausea and vomiting associated with other antineoplastic agents (e.g., cyclophosphamide, dacarbazine, doxorubicin, methotrexate) and with cancer chemotherapy regimens that do not include cisplatin.¹⁰³ ¹⁴⁴ ¹⁴⁵ ¹⁴⁶ ¹⁴⁷ ²¹⁸ ²⁶³ ²⁶⁷

ASCO does not consider metoclopramide an appropriate first-line antiemetic for any group of patients receiving chemotherapy of high emetic risk and states that this drug should be reserved for patients unable to tolerate or refractory to first-line agents (i.e., a type 3 serotonin [5-HT₃] receptor antagonist [e.g., dolasetron, granisetron, ondansetron, palonosetron] with dexamethasone and aprepitant).²⁶³

ASCO states that the combination of a 5-HT₃ receptor antagonist, dexamethasone, and aprepitant is preferred in patients receiving combination chemotherapy with an anthracycline and cyclophosphamide; ASCO recommends combined therapy with a 5-HT₃ receptor antagonist and dexamethasone for other chemotherapy regimens of moderate emetic risk (i.e., 31–90% incidence of emesis without antiemetics) and dexamethasone alone for chemotherapy regimens of low emetic risk (i.e., 11–30% incidence).²⁶³

In patients experiencing nausea and vomiting despite recommended prophylaxis regimens, ASCO recommends that clinicians consider adding a benzodiazepine (e.g., alprazolam, lorazepam), butyrophenone, or phenothiazine to the regimen or substituting high-dose IV metoclopramide for the 5-HT₃ receptor antagonist in the regimen.²⁶³

Antiemetics can be prescribed on an as-needed basis for chemotherapy regimens with minimal emetic risk (<10% incidence of emesis without antiemetics).²⁶³

Metoclopramide has been used orally† for the prevention of chemotherapy-induced nausea and vomiting. ¹⁷⁷ ²¹⁸ ²²¹ ²²⁴ ²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ ²⁷⁵ Some experts state that patients receiving oral chemotherapy requiring only as-needed (“prn”) antiemetic therapy or receiving an IV chemotherapy regimen with low emetic risk may receive oral† metoclopramide.²⁷⁵

Oral† metoclopramide has been effective when given in combination with dexamethasone for the prevention of delayed emesis in patients receiving chemotherapy.²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶ For prevention of delayed emesis in patients receiving cisplatin or other chemotherapy of high emetic risk, ASCO recommends the combination of dexamethasone and aprepitant.²⁶³

Intubation of the Small Intestine

Used parenterally to facilitate small intestine intubation when the tube (e.g., endoscope, biopsy tube) does not pass through the pylorus during 10 minutes of conventional maneuvers.¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁹ ¹⁷⁶ ²⁶⁷

Radiographic Examination of the Upper GI Tract

Used parenterally to stimulate gastric emptying and intestinal transit of barium when delayed emptying interferes with radiographic examination of the stomach and/or small intestine.⁴ ⁴³ ¹¹⁰ ¹⁸⁴ ²⁶⁷

Gastroesophageal Reflux

Short-term (≤12 weeks) relief of symptomatic, documented gastroesophageal reflux in adults who are unresponsive to conventional therapy (e.g., changes in lifestyle, habits, diet, weight reduction) alone.⁵ ⁹ ³⁰ ³⁹ ⁴⁰ ⁴¹ ⁴² ¹¹¹ ¹¹² ¹¹⁶ ¹¹⁷ ¹²⁵ ¹²⁹ ¹⁸⁵ ¹⁸⁶ ¹⁸⁷ ¹⁸⁸ ¹⁸⁹ ¹⁹⁰

Regular use for this purpose has declined; proton-pump inhibitors provide greater control of acid reflux.²⁵⁸ ²⁷³ ²⁷⁴ Some experts recommend against use of metoclopramide for this purpose based on the drug’s adverse effect profile and lack of high-quality supporting data.²⁷³ ²⁷⁴

Metoclopramide Hydrochloride Dosage and Administration

Administration

Administer orally, by direct IV injection or IV infusion, or IM.⁵ ²⁶³ ²⁶⁷

Metoclopramide therapy should not exceed 12 weeks’ duration.⁵ ²⁶⁷ ²⁶⁸ ²⁶⁹

Oral Administration

Metoclopramide oral solution and tablets are recommended for use in adults only.⁵ ²⁶⁸ ²⁶⁹

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Dilution

For direct IV injection, use without further dilution.²⁶⁷

If dose is >10 mg, dilute in 50 mL of a compatible IV solution.²⁶⁷

For IV infusion, manufacturer recommends dilution in 50 mL of 5% dextrose, 0.9% sodium chloride, 5% dextrose and 0.45% sodium chloride, Ringer’s, or lactated Ringer’s injection.²⁶⁷

Manufacturer states that 0.9% sodium chloride injection is preferred because metoclopramide hydrochloride is most stable in this solution.²⁶⁷

Rate of Administration

Direct IV injection: Administer each 10 mg slowly over 1–2 minutes.²⁶⁷ Rapid IV injection may cause transient but intense feelings of anxiety and restlessness, followed by drowsiness.²⁶⁷

IV infusion: Administer slowly over ≥15 minutes.²⁶⁷

IM Administration

Inject without further dilution.²⁶⁷

Dosage

Available as metoclopramide hydrochloride; dosage expressed in terms of metoclopramide.⁵ ²⁶⁷

Pediatric Patients

Intubation of the Small Intestine

IV

Children <6 years of age: Usually, one 0.1-mg/kg dose given by direct IV injection.²⁶⁷

Children 6–14 years of age: Usually, one 2.5- to 5-mg dose given by direct IV injection.²⁶⁷

Children >14 years of age: Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Adults

Diabetic Gastric Stasis

Oral

10 mg 4 times daily, given 30 minutes before meals and at bedtime.⁵ Continue for 2–8 weeks, depending on response and likelihood of continued well-being if drug is discontinued.⁵ Reinstitute at earliest symptom recurrence.⁵

IV

If symptoms are severe or oral use is not feasible, 10 mg 4 times daily, given by direct IV injection 30 minutes before meals and at bedtime.⁵ ²⁶⁷ Continued use for up to 10 days may be required until symptoms subside enough to allow oral administration;⁵ ²⁶⁷ however, thoroughly assess the risks and benefits prior to continuing therapy.²⁶⁷

IM

If symptoms are severe or oral use is not feasible, 10 mg 4 times daily, given 30 minutes before meals and at bedtime.⁵ ²⁶⁷ Continued use for up to 10 days may be required until symptoms subside enough to allow oral administration;⁵ ²⁶⁷ however, thoroughly assess the risks and benefits prior to continuing therapy.²⁶⁷

Prevention of Postoperative Nausea and Vomiting

IM

Manufacturer states that usual dose is 10 mg administered near the end of the surgical procedure; 20 mg also may be used.²⁶⁷

Prevention of Cancer Chemotherapy-induced Emesis

Oral†

Some experts state that patients receiving IV chemotherapy regimens with low emetic risk may receive 10–40 mg of metoclopramide before the chemotherapy dose and then every 4 or 6 hours as needed.²⁷⁵

Some experts state that patients receiving oral chemotherapy requiring only as-needed (“prn”) antiemetic therapy may receive 10–40 mg of metoclopramide before the chemotherapy dose and then every 4 or 6 hours as needed.²⁷⁵

When given in combination with dexamethasone in clinical trials for the prevention of delayed emesis (i.e., vomiting occurring ≥24 hours after chemotherapy), 20–40 mg (or 0.5 mg/kg) of metoclopramide has been given 2–4 times daily for 3 or 4 days.²⁶³ ²⁶⁴ ²⁶⁵ ²⁶⁶

IV

Manufacturer states that metoclopramide usually is given by IV infusion 30 minutes before administration of chemotherapy, and then repeated every 2 hours for 2 additional doses followed by every 3 hours for 3 additional doses.²⁶⁷ Manufacturer states that initial 2 doses should be 2 mg/kg if highly emetogenic chemotherapy used;²⁶⁷ for less emetogenic drugs or regimens, initial 1-mg/kg dose may be sufficient.²⁶⁷ However, combinations of other antiemetic agents generally are preferred as first-line regimens in patients receiving chemotherapy of moderate or high emetic risk (see Prevention of Cancer Chemotherapy-induced Emesis under Uses). ²⁶³ ²⁷⁵

Intubation of the Small Intestine

IV

Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Radiographic Examination of the Upper GI Tract

IV

Usually, one 10-mg dose given by direct IV injection.²⁶⁷

Gastroesophageal Reflux

Oral

Usually, 10–15 mg up to 4 times daily (30 minutes before each meal and at bedtime) for 4–12 weeks, depending on symptoms and response.⁵ Patients sensitive to therapeutic and/or adverse effects of metoclopramide may require initial dose of 5 mg.⁵

For intermittent symptoms or symptoms at specific times of the day, one 20-mg dose before the provoking situation may be preferred to daily administration of multiple doses.⁵

In patients with esophageal erosion and ulceration, 15 mg 4 times daily for 12 weeks has provided healing; monitor endoscopically because of the poor correlation between symptoms and healing.⁵

Prescribing Limits

Adults

Avoid use of metoclopramide for >12 weeks in all but rare cases where therapeutic benefit is thought to outweigh risk of developing tardive dyskinesia.⁵ ²⁶⁷ (See Boxed Warning and see Tardive Dyskinesia under Cautions.)

Gastroesophageal Reflux

Oral

Safety and efficacy beyond 12 weeks not established; use beyond 12 weeks not recommended.⁵

Special Populations

Hepatic Impairment

Dosage modification does not appear to be necessary.⁵ ²⁶⁷

Renal Impairment

Modify dosage according to degree of renal impairment.⁵ ⁵⁴ ⁵⁸ ⁵⁹ ¹³⁵ ¹⁴² ²⁶⁷

In patients with Cl_cr <40 mL/minute, manufacturers recommend an initial dosage of approximately 50% of the usual dosage.⁵ ²⁶⁷ Subsequently, increase or decrease dosage according to response and tolerance.⁵ ²⁶⁷

Geriatric Patients

Select dosage with caution, usually initiating therapy at the low end of the dosage range.⁵ ²⁶⁷

Administer lowest effective dosage.⁵ ²⁶⁷ In geriatric patients with gastroesophageal reflux, initial 5-mg dose may be required due to possible sensitivity to therapeutic and/or adverse effects of metoclopramide.⁵

Cautions for Metoclopramide Hydrochloride

Contraindications

Mechanical obstruction or perforation or other situations in which stimulation of GI motility might be dangerous.⁵ ²⁶⁷

GI hemorrhage⁵ ²⁶⁷ (however, has been used to empty the stomach of blood prior to endoscopy in patients with acute upper GI hemorrhage).⁴ ¹²⁵

Pheochromocytoma (due to potential for hypertensive crisis).⁵ ²⁶⁷

History of seizure disorders.⁴ ⁵ ²⁶⁷

Concomitant therapy with drugs likely to cause extrapyramidal reactions (e.g., phenothiazines, butyrophenones).⁴ ⁵ ²⁶⁷

Known intolerance to metoclopramide.⁵ ²⁶⁷

Known hypersensitivity to metoclopramide or any ingredient in the formulation.⁵ ²⁶⁷

Warnings/Precautions

Warnings

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements involving the tongue, face, mouth, or jaw, and sometimes the trunk and/or extremities, may occur; movements may be choreoathetotic in appearance.⁵ ⁹³ ⁹⁴ ¹³⁰ ¹⁵⁷ ¹⁵⁸ ¹⁵⁹ ²⁶⁷ ²⁷⁰ ²⁷¹ ²⁷² (See Boxed Warning.)

Reported in about 20% of patients receiving the drug for ≥12 weeks.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ Avoid use of metoclopramide for >12 weeks in all but rare cases where therapeutic benefit is thought to outweigh risk of developing tardive dyskinesia.⁵ ²⁶⁷ ²⁷²

Although risk of developing tardive dyskinesia may be increased in geriatric patients, women, and patients with diabetes mellitus, it is not possible to predict which patients will develop metoclopramide-induced tardive dyskinesia.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ ²⁷² Risk of occurrence and irreversibility increases with increasing duration of therapy and total cumulative dose.⁵ ²⁶⁷ ²⁷¹ ²⁷²

Discontinue metoclopramide in patients who develop signs or symptoms of tardive dyskinesia.⁵ ²⁶⁷ ²⁷⁰ ²⁷¹ There is no known effective treatment for tardive dyskinesia; however, tardive dyskinesia may remit, either partially or completely, in some patients within several weeks to months after discontinuance.⁵ ²⁶⁷ ²⁷¹

Metoclopramide may suppress or partially suppress signs of tardive dyskinesia, thereby masking the underlying disease process; effect of this suppression on the long-term course of tardive dyskinesia is unknown.⁵ ²⁶⁷ Do not use metoclopramide for symptomatic control of tardive dyskinesia.⁵ ²⁶⁷

Extrapyramidal Symptoms

Potential for extrapyramidal reactions,⁴ ⁵ ⁹⁰ ⁹¹ ¹²⁵ ¹⁶⁹ ²⁰⁵ ²⁰⁶ ²⁰⁷ ²⁶⁷ especially in pediatric patients and adults <30 years of age or when high doses (e.g., IV doses for prophylaxis of cancer chemotherapy-induced nausea and vomiting) are administered.⁵ ⁹¹ ¹⁶⁹ ²⁶⁷

Commonly manifested as acute dystonic reactions or akathisia; stridor and dyspnea (possibly due to laryngospasm) reported rarely.⁵ ²⁶⁷

Generally occur within 24–48 hours after starting therapy⁵ ²⁰⁵ ²⁰⁶ ²⁰⁷ ²⁶⁷ and usually subside within 24 hours following drug discontinuance.⁴ ⁹⁰ ²⁰⁵

Most patients respond rapidly to treatment with diazepam⁴ or an agent with central anticholinergic activity (e.g., diphenhydramine hydrochloride 20–50 mg orally, IM, or IV;⁵ ²⁶⁷ ²⁷⁵ ²⁷⁶ benztropine 1–2 mg IM⁵ ²⁶⁷ ).⁴ ⁵ ¹⁷⁰ ²⁰⁶ ²⁰⁷ ²⁶⁷

Parkinsonian Symptoms

Parkinsonian symptoms (e.g., tremor, rigidity, bradykinesia, akinesia) occur rarely; may be associated with usual¹⁶⁰ or excessive metoclopramide doses⁶² or decreased renal function.⁹ ⁵⁴

Possible exacerbation of parkinsonian symptoms;⁵ ⁹ ⁵⁴ ⁶² ¹⁶⁰ ²⁶⁷ use with caution, if at all, in patients with parkinsonian syndrome.⁵ ²⁶⁷

More common during first 6 months of therapy but occur occasionally after longer periods.⁵ ²⁶⁷

Symptoms generally subside within 2–3 months following drug discontinuance.⁵ ²⁶⁷

Neuroleptic Malignant Syndrome (NMS)

NMS (characterized by hyperthermia, varying levels of consciousness, muscular rigidity, and autonomic dysfunction) reported rarely.⁵ ²⁰⁸ ²⁶⁷

Important to determine whether untreated or inadequately treated extrapyramidal reactions and serious medical illness (e.g., pneumonia, systemic infection) may coexist.⁵ ²⁶⁷ Also consider the possibility of central anticholinergic toxicity, heat stroke, malignant hyperthermia, drug fever, and primary CNS pathology.⁵ ²⁶⁷

Immediately discontinue metoclopramide and other drugs not considered essential, provide intensive symptomatic treatment, monitor patient, and treat any concomitant serious medical condition for which specific therapies are available.⁵ ²⁶⁷ Dantrolene and bromocriptine have been used in the treatment of NMS, but their efficacy has not been established and there currently is no specific drug therapy.⁵ ²⁶⁷

Depression

Mild to severe depression (including suicidal ideation and suicide) has occurred in patients with or without prior history of depression.⁵ ²¹⁰ ²¹¹ ²¹⁵ ²⁶⁷

Use with extreme caution and only when anticipated benefits outweigh possible risks in patients with a history of mental depression, especially those with suicidal tendencies.⁵ ²⁶⁷

Sensitivity Reactions

Procainamide Cross-sensitivity

Theoretical potential for patients who are allergic to procainamide to exhibit cross-sensitivity to metoclopramide (since the drugs are structurally similar).¹¹ ¹²

General Precautions

GI Anastomosis or Closure

When deciding whether to use metoclopramide or NG suction to prevent postoperative nausea and vomiting, consider the possibility that metoclopramide theoretically could produce increased pressure on suture lines following GI anastomosis or closure.²⁶⁷

Fluid and Electrolyte Effects

Possible transient increases in plasma aldosterone concentrations and sodium retention; closely monitor patients (e.g., those with CHF or cirrhosis) at risk of developing fluid retention and volume overload or hypokalemia.³ ⁵ ⁶⁹ ²⁶⁷

Discontinue metoclopramide if fluid retention or volume overload occurs at any time during therapy.⁵ ²⁶⁷

Hypertension

Possible increase in circulating catecholamines in hypertensive patients; use with caution in these patients.⁵ ²⁶⁷

CNS Depression

Drowsiness may occur, particularly at higher dosages.⁵ ²⁶⁷ Performance of activities requiring mental alertness and physical coordination (operating machinery, driving a motor vehicle) may be impaired.⁵ ²⁶⁷

Withdrawal Effects

Adverse reactions, particularly CNS reactions, may occur following discontinuance of drug.⁵ Some patients may experience withdrawal symptoms including dizziness, nervousness, and/or headaches following discontinuance.⁵

Patients with Cytochrome-b₅ Reductase Deficiency

Patients with cytochrome-b₅ reductase deficiency have an increased risk of methemoglobinemia and/or sulfhemoglobinemia when metoclopramide is administered.⁵ ²⁶⁷

Patients with Glucose-6-phosphate Dehydrogenase Deficiency

Methylene blue is not recommended for treatment of metoclopramide-induced methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.⁵ ²⁶⁷

Specific Populations

Pregnancy

Category B.⁵ ²⁶⁷

Lactation

Distributed into milk.⁵ ¹³⁹ ¹⁴⁰ ²⁶⁷ Use caution in nursing women.⁵ ²⁶⁷

Pediatric Use

Manufacturers currently recommend use in children only to facilitate intubation of the small intestine;²⁶⁷ however, has been effective for the management of gastric stasis†¹⁷⁸ ¹⁸⁰ ¹⁸¹ and gastroesophageal reflux†¹⁷⁹ ¹⁸² in infants and children.

Use with caution; incidence of extrapyramidal reactions is increased in children.⁵ ⁹¹ ¹²⁵ ¹⁵⁶ ²⁶⁷

Use with caution in neonates.⁵ ²⁶⁷ Neonatal susceptibility to methemoglobinemia is increased due to prolonged clearance (may cause excessive serum concentrations) in combination with decreased neonatal levels of cytochrome-b₅ reductase.⁵ ²⁶⁷

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients repond differently than younger adults.⁵ ²⁶⁷

Possible increased risk of tardive dyskinesia.⁵ ²⁶⁷

Risk of adverse parkinsonian effects increases with increasing dosage; administer lowest effective dosage in geriatric patients.⁵ ²⁶⁷ If parkinsonian symptoms develop, generally should discontinue metoclopramide before initiating specific antiparkinsonian therapy.⁵ ²⁶⁷

Confusion and oversedation may occur.⁵ ²⁶⁷

Substantially eliminated by kidneys; risk of adverse reactions may be greater in patients with impaired renal function.⁵ ²⁶⁷ (See Renal Impairment under Dosage and Administration.)

Select dosage with caution because of age-related decreases in renal function and concomitant disease and drug therapy.⁵ ²⁶⁷ (See Geriatric Patients under Dosage and Administration).

Hepatic Impairment

Possible increased risk of fluid retention and hypokalemia in patients with cirrhosis.³ ⁵ ⁶⁹ ²⁶⁷ (See Fluid and Electrolyte Effects under Cautions.)

Discontinue if fluid retention or volume overload occurs at any time during therapy.⁵ ²⁶⁷

Renal Impairment

Clearance may be reduced.⁵ ⁵⁴ ⁵⁹ ¹⁴² ¹⁹² ²⁶⁷ Possible increased risk of adverse effects.⁵ ²⁶⁷ Use with caution; reduce dosage during prolonged therapy in patients with renal impairment.⁵ ⁵⁴ ⁵⁸ ⁵⁹ ⁶⁹ ¹³⁵ ¹⁴² ²⁶⁷ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Restlessness, drowsiness, fatigue, lassitude, nausea, bowel disturbances (principally diarrhea).⁴ ⁵ ⁹⁰ ¹²⁵ ²⁶⁷

Interactions for Metoclopramide Hydrochloride

Orally Administered Drugs

Possible decreased absorption of certain drugs that disintegrate, dissolve, and/or are absorbed mainly in the stomach.⁴ ⁵ ¹¹⁹ ¹²⁵ ²⁶⁷ Clinical importance not determined.^c

Possible enhanced rate and extent of absorption of drugs mainly absorbed in the small intestine.⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷ Clinical importance not determined.^c

Specific Drugs

Drug	Interaction	Comments
Acetaminophen	Possible enhanced rate and extent of acetaminophen absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Clinical importance not determined^c
Anesthetic agents	Acute hypotension reported with concomitant IV metoclopramide and hypotensive anesthetic agents (with or without ganglionic blocking agents) during neurosurgical procedures¹⁶² ¹⁶³	Clinical importance not known¹²⁵ ¹⁶² ¹⁶³
Anticholinergic agents (e.g., atropine)	Antagonism of GI motility effects of metoclopramide ⁵ ²⁶⁷
Aspirin	Possible enhanced rate and extent of aspirin absorption⁴ ¹²⁰ ¹²⁵	Clinical importance not determined^c
Butyrophenones	Potential for extrapyramidal reactions⁴ ⁵ ²⁶⁷ and worsening of symptoms in patients with parkinsonian syndrome¹³⁰ ¹⁵⁸ ¹⁶⁰	Concomitant use contraindicated⁴ ⁵ ²⁶⁷
Cholinergic agents	Potentiation of GI motility effects of metoclopramide⁵
CNS depressants (alcohol, opiates or other analgesics, barbiturates or other sedatives, anesthetics)	Increased CNS depressant effects;⁵ ²⁶⁷ possible enhanced rate and extent of alcohol absorption⁴ ⁵ ¹²⁵ ²⁶⁷	Use caution to avoid excessive sedation;^c clinical importance of enhanced alcohol absorption not determined^c
Cyclosporine	Possible enhanced rate and extent of cyclosporine absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Clinical importance not determined^c
Diazepam	Possible enhanced rate and extent of diazepam absorption⁴ ¹²⁰ ¹²⁵	Clinical importance not determined^c
Digoxin	Possible decreased digoxin absorption; Lanoxin tablets apparently not affected because of small drug-particle size and rapid absorption⁴ ⁵ ¹¹⁹ ¹²⁵ ²⁶⁷
Insulin	Possible alteration of glycemic control secondary to metoclopramide-related changes in the delivery of food to and the rate of absorption in the intestine⁵ ²⁶⁷	Adjustment of insulin dose or timing may be necessary⁵ ²⁶⁷
Levodopa	Possible enhanced rate and extent of levodopa absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Clinical importance not determined^c
Lithium	Possible enhanced rate and extent of lithium absorption⁴ ¹²⁰ ¹²⁵	Clinical importance not determined^c
MAO inhibitors	Possible hypertensive reaction due to metoclopramide-induced release of catcholamines⁵ ²⁶⁷	Use with caution, if at all⁵ ²⁶⁷
Opiate analgesics	Antagonism of GI motility effects of metoclopramide⁵ ¹⁵ ³³ ²⁶⁷
Phenothiazines	Potential for extrapyramidal reactions⁴ ⁵ ²⁶⁷ and worsening of symptoms in patients with parkinsonian syndrome¹³⁰ ¹⁵⁸ ¹⁶⁰	Concomitant use contraindicated⁴ ⁵ ²⁶⁷
Tetracycline	Possible enhanced rate and extent of tetracycline absorption⁴ ⁵ ¹²⁰ ¹²⁵ ²⁶⁷	Clinical importance not determined^c

Metoclopramide Hydrochloride Pharmacokinetics

Absorption

Bioavailability

Following oral administration, rapidly and almost completely absorbed;⁴ ⁵ ⁷ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶ ¹³³ ¹³⁴ ¹³⁵ ²⁶⁷ limited data indicate that 30–100% of an oral dose reaches systemic circulation as unchanged metoclopramide.⁵ ⁵⁴ ⁵⁶ ¹³³ ¹³⁴ ¹³⁵ ²⁶⁷ Peak plasma concentration usually attained at 1–2 hours.⁵ ⁵⁵ ²⁶⁷

Following IM administration, absolute bioavailability is 74–96%.⁷

Onset

Following oral administration, 30–60 minutes for effects on GI tract.⁵ ⁷ ²⁶⁷

Following IM administration, 10–15 minutes for effects on GI tract.⁵ ⁷ ²⁶⁷

Following IV administration, 1–3 minutes for effects on GI tract.⁵ ⁷ ²⁶⁷

Duration

1–2 hours.⁵ ²⁶⁷

Special Populations

In patients with gastric stasis, absorption may be delayed or diminished.¹⁴

In infants, metoclopramide may accumulate in plasma after multiple doses; mean peak plasma concentration was 2-fold higher after 10th dose compared with that after first dose in infants (3.5 weeks–5.4 months of age) with gastroesophageal reflux receiving metoclopramide oral solution.⁵ ²⁶⁷

Distribution

Extent

In mice, distributed into most body tissues and fluids; high concentrations in GI mucosa, liver, biliary tract, and salivary glands, with lower concentrations in brain, heart, thymus, adrenals, adipose tissue, and bone marrow.⁴ ⁷

Crosses the placenta¹³⁸

Distributed into milk in humans;⁵ ¹³⁹ ¹⁴⁰ ²⁶⁷ milk concentrations are higher than plasma concentrations 2 hours after oral administration.¹³⁹ ¹⁴⁰

Plasma Protein Binding

13–30% (principally albumin).⁵ ⁷ ²⁶⁷

Elimination

Metabolism

Minimally metabolized; not known whether major metabolite found in urine is active.⁵ ⁵³ ²⁶⁷

Elimination Route

Excreted in urine (85%) as unchanged drug and metabolites⁵ ⁷ ⁵³ ⁵⁴ ¹³³ ²⁶⁷ and also in feces (about 5%).⁷ ⁵³

Minimally removed by hemodialysis⁵ ¹²⁹ ¹⁹²

Saturday, 12 May 2012

Tusana-D

Generic Name: chlorpheniramine, hydrocodone, and phenylephrine (KLOR fe NEER a meen, HYE droe KOE done, FEN il EFF rin)

Brand Names: B-Tuss, Coughtuss, Cytuss HC, De-Chlor HC, DroTuss-CP, Ed-TLC, Ed-Tuss HC, Endal-HD Plus, H-C Tussive, Histussin-HC, Hydro-PC II, Hydro-PC II Plus, Hydron CP, Liquicough HC, Maxi-Tuss HCX, Mintuss MS, Neo HC, Poly-Tussin, Poly-Tussin HD, Relacon-HC, Relacon-HC NR, Relasin-HC, Rindal HD Plus, Rindal-HD, Triant-HC, Tusana-D, Z-Cof HC

What is Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Chlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Hydrocodone is a narcotic cough medicine.

Phenylephrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of chlorpheniramine, hydrocodone, and phenylephrine is used to treat runny or stuffy nose, sinus congestion, and cough caused by the common cold or flu.

Chlorpheniramine, hydrocodone, and phenylephrine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Do not take this medication if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. Serious, life threatening side effects can occur if you use chlorpheniramine, hydrocodone, and phenylephrine before the MAO inhibitor has cleared from your body. Chlorpheniramine, hydrocodone, and phenylephrine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine, hydrocodone, and phenylephrine. Before using this medication, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by chlorpheniramine, hydrocodone, and phenylephrine. Hydrocodone may be habit-forming and should be used only by the person it was prescribed for. Never share hydrocodone with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

What should I discuss with my healthcare provider before taking Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

To make sure you can safely take this medication, tell your doctor if you have any of these other conditions:

asthma, COPD, sleep apnea, or other breathing disorder;

liver or kidney disease;

heart disease or high blood pressure;

diabetes;

a thyroid disorder;

curvature of the spine;

a history of head injury or brain tumor;

epilepsy or other seizure disorder;

low blood pressure;

glaucoma;

gallbladder disease;

Addison's disease or other adrenal gland disorders;

enlarged prostate, urination problems;

mental illness; or

a history of drug or alcohol addiction.

Hydrocodone may be habit-forming and should be used only by the person it was prescribed for. Never share hydrocodone with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it. FDA pregnancy category C. It is not known whether chlorpheniramine, hydrocodone, and phenylephrine will harm an unborn baby. Hydrocodone may cause addiction or withdrawal symptoms in a newborn if the mother takes the medication during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant while using chlorpheniramine, hydrocodone, and phenylephrine. It is not known whether chlorpheniramine, hydrocodone, and phenylephrine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

You may take this medication with or without food.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

Store at room temperature away from moisture and heat. Keep track of the amount of medicine used from each new bottle. Hydrocodone is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of hydrocodone can be fatal.

Overdose symptoms may include extreme drowsiness, feeling restless or nervous, vomiting, stomach pain, warmth or tingly feeling, seizure (convulsions), pinpoint pupils, confusion, cold and clammy skin, weak pulse, shallow breathing, fainting, or breathing that stops.

What should I avoid while taking Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Chlorpheniramine, hydrocodone, and phenylephrine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine, hydrocodone, and phenylephrine.

Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine) side effects

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. Stop using this medication and call your doctor at once if you have a serious side effect such as:

severe dizziness, anxiety, restless feeling, or nervousness;

fast, pounding, or uneven heartbeats;

shallow breathing, slow heartbeat;

confusion, hallucinations, unusual thoughts or behavior;

feeling like you might pass out;

urinating less than usual or not at all;

easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms;

dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, chest pain, shortness of breath, seizure); or

upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

nausea, vomiting, upset stomach, constipation;

dry mouth;

blurred vision;

dizziness, drowsiness;

problems with memory or concentration;

sleep problems (insomnia);

ringing in your ears;

warmth, tingling, or redness under your skin; or

skin rash or itching.

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.

What other drugs will affect Tusana-D (chlorpheniramine, hydrocodone, and phenylephrine)?

Before using this medication, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by chlorpheniramine, hydrocodone, and phenylephrine.

Tell your doctor about all other medications you use, especially:

blood pressure medication;

cimetidine (Tagamet);

rifampin (Rifadin, Rifater, Rifamate, Rimactane);

zidovudine (Retrovir, AZT);

an antidepressant;

a diuretic (water pill);

medication to treat irritable bowel syndrome;

bladder or urinary medications such as oxybutynin (Ditropan, Oxytrol) or tolterodine (Detrol);

aspirin or salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others);

seizure medication such as phenytoin (Dilantin) or phenobarbital (Luminal, Solfoton);

a beta-blocker such as atenolol (Tenormin), carteolol (Cartrol), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal), sotalol (Betapace), timolol (Blocadren), and others; or

medicines to treat psychiatric disorders, such as chlorpromazine (Thorazine), haloperidol (Haldol), mesoridazine (Serentil), pimozide (Orap), or thioridazine (Mellaril).

This list is not complete and other drugs may interact with chlorpheniramine, hydrocodone, and phenylephrine. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Tusana-D resources

Tusana-D Side Effects (in more detail)
Tusana-D Use in Pregnancy & Breastfeeding
Tusana-D Drug Interactions
Tusana-D Support Group
0 Reviews for Tusana-D - Add your own review/rating

Chlorpheniramine/Hydrocodone/Phenylephrine Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Tusana-D with other medications

Cough and Nasal Congestion

Where can I get more information?

Your pharmacist can provide more information about chlorpheniramine, hydrocodone, and phenylephrine.

See also: Tusana-D side effects (in more detail)

Thursday, 10 May 2012

Questran Powder for Oral Suspension 4g

1. Name Of The Medicinal Product

Questran Powder for Oral Suspension 4g

2. Qualitative And Quantitative Composition

Each sachet contains 4g anhydrous colestyramine (a basic anion-exchange resin).

3. Pharmaceutical Form

Powder for Oral Suspension.

4. Clinical Particulars

4.1 Therapeutic Indications

Questran is used for:

1.	Primary prevention of coronary heart disease in men between 35 and 59 years of age and with primary hypercholesterolaemia who have not responded to diet and other appropriate measures.
2.	Reduction of plasma cholesterol in hypercholesterolaemia, particularly in those patients who have been diagnosed as Fredrickson's Type II (high plasma cholesterol with normal or slightly elevated triglycerides).
3.	Relief of pruritus associated with partial biliary obstruction and primary biliary cirrhosis.
4.	Relief of diarrhoea associated with ileal resection, Crohn's disease, vagotomy and diabetic vagal neuropathy.
5.	Management of radiation-induced diarrhoea.

4.2 Posology And Method Of Administration

Adults:

As a precautionary measure, where concurrent drug therapy exists then such drugs should be administered at least one hour before or 4-6 hours after Questran.

Questran should not be taken in its dry form.

Questran should be administered mixed with water or a suitable liquid, such as fruit juice, and stirred to a uniform consistency.

Questran may also be mixed with skimmed milk, thin soups, pulpy fruits with high moisture content, e.g. apple sauce, etc..

1. For primary prevention of coronary heart disease and to reduce cholesterol: After initial introduction over a three to four week period, 3 to 6 Questran sachets per day, administered either as a single daily dose or in divided doses up to four times daily, according to dosage requirements and patient acceptability. Dosage may be modified according to response and can be increased to 9 sachets per day if necessary.

Occasional slight gastro-intestinal upsets, e.g. constipation, may occur when starting Questran. These usually pass with continued usage of Questran and are minimised by starting therapy gradually.

Final dose required	Week 1	Week 2	Week 3	Week 4
	Sachets per day
3	1	2	3	3
4	1	2	3	4
6	1	2	3	6

2. To relieve pruritus: One or two sachets daily are usually sufficient.

3. To relieve diarrhoea: As for reduction of cholesterol but it may be possible to reduce this dosage. In all patients presenting with diarrhoea induced by bile acid malabsorption, if a response is not seen within 3 days, then alternative therapy should be initiated.

Children 6 - 12 years:

The initial dose is determined by the following formula:

Subsequent dosage adjustment may be necessary where clinically indicated.

Children under 6 years: The dose has not been established in infants and children under 6 years.

Elderly:

No dosage adjustment is necessary.

4.3 Contraindications

Questran is contra-indicated in patients who have shown hypersensitivity to any of the product ingredients.

In patients with complete biliary obstruction, since Questran cannot be effective where bile is not secreted into the intestine.

4.4 Special Warnings And Precautions For Use

Reduction of serum folate concentrations has been reported in children with familial hypercholesterolaemia. Supplementation with folic acid should be considered in these cases.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Questran may delay or reduce the absorption of certain drugs (such as digitalis, tetracycline, chlorothiazide, warfarin and thyroxine). The response to concomitant medication should be closely monitored and appropriate adjustments made if necessary.

Questran may interfere with the pharmacokinetics of drugs that undergo enterohepatic recirculation.

Patients should take other drugs at least one hour before or 4-6 hours after Questran to minimise possible interference with their absorption.

4.6 Pregnancy And Lactation

The safety of colestyramine in pregnancy and lactation has not been established and the possibility of interference with absorption of fat soluble vitamins should be considered.

4.7 Effects On Ability To Drive And Use Machines

None.

4.8 Undesirable Effects

Since Questran may interfere with the absorption of fat soluble vitamins, the diet may require supplementation with Vitamins A, D and K during prolonged high dose administration.

Chronic use of Questran may be associated with increased bleeding tendency due to hyperprothrombinaemia associated with Vitamin K deficiency. This will usually respond promptly to parenteral Vitamin K administration; recurrences can be prevented by oral administration of Vitamin K.

Hyperchloraemic acidosis has occasionally been reported following the prolonged use of anion exchange resins.

Gastro-intestinal side effects are those most frequently reported. The principal complaint is constipation which may be controlled with the usual remedies, and frequently disappears on continued usage of Questran. Large doses of Questran can cause diarrhoea.

Taste disturbance and skin irritation have been reported rarely but causal relationship to colestyramine remains undetermined. Rare reports of intestinal obstruction have been received.

4.9 Overdose

One case of medication error experienced heartburn and nausea after taking colestyramine 27g t.i.d. for a week. The potential problem in overdosage would be obstruction of the gastrointestinal tract.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Colestyramine resin absorbs and combines with the bile acids in the intestine to form an insoluble complex which is excreted in the faeces. This results in a continuous, though partial, removal of bile acids from the enterohepatic circulation by preventing their reabsorption. The increased faecal loss of bile acids leads to an increased oxidation of cholesterol to bile acids and a decrease in serum cholesterol levels and low density lipoprotein serum levels. Colestyramine is hydrophilic but it is not soluble in water, nor is it hydrolysed by digestive enzymes.

In patients with partial biliary obstruction, the reduction of serum bile acid levels reduces excess bile acids deposited in the dermal tissue with resultant decrease in pruritus.

5.2 Pharmacokinetic Properties

Colestyramine is not absorbed from the digestive tract.

5.3 Preclinical Safety Data

No further significant information.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Acacia

Citric acid anhydrous

Orange juice flavour

Polysorbate 80

Propylene glycol

Alginate

Sucrose

6.2 Incompatibilities

None known.

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

Do not store above 30°C. .

6.5 Nature And Contents Of Container

Original packs containing 50 or 60 laminate sachets composed of paper, polyethylene and aluminium.

6.6 Special Precautions For Disposal And Other Handling

No special instructions.

7. Marketing Authorisation Holder

Bristol-Myers Squibb Holdings Limited

t/a Bristol-Myers Pharmaceuticals

Uxbridge Business Park

Sanderson Road

Uxbridge

Middlesex UB8 1DH

8. Marketing Authorisation Number(S)

PL 0125/5009R

9. Date Of First Authorisation/Renewal Of The Authorisation

22 January 1987/23 April 1997

10. Date Of Revision Of The Text

8^th September 2010

Friday, 4 May 2012

Idamycin

Generic Name: idarubicin (EYE da ROO bi sin)

Brand Names: Idamycin PFS

What is Idamycin (idarubicin)?

Idarubicin is a cancer (antineoplastic) medication. Idarubicin interferes with the growth of cancer cells and slows their growth and spread in the body.

Idarubicin is used to treat a type of blood cancer (acute myeloid leukemia -AML) in adults .

Idarubicin may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Idamycin (idarubicin)?

Idarubicin should only be administered under the supervision of a qualified healthcare provider experienced in the use of cancer chemotherapeutic agents.

Serious side effects have been reported with the use of idarubicin including: allergic reactions (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives); severe heart damage with prolonged use; decreased bone marrow function and blood problems (extreme fatigue; easy bruising or bleeding; black, bloody or tarry stools; fever or chills; or signs of infection); severe nausea, vomiting, diarrhea, and loss of appetite; and others.Talk to your doctor about the possible side effects from treatment with idarubicin.

What should I discuss with my healthcare provider before using Idamycin (idarubicin)?

Do not use idarubicin without first talking to your doctor if you have

kidney disease;

liver disease;

heart disease;

poor bone marrow function;

received radiation therapy that encompassed the heart; or

previously received treatment with doxorubicin (Adriamycin, Rubex), doxorubicin liposomal (Doxil), daunorubicin (Cerubidine), daunorubicin liposomal (Daunoxome), idarubicin (Idamycin), or mitoxantrone (Novantrone).

The use of idarubicin may be dangerous if you have any of the conditions listed above.

Idarubicin is in the FDA pregnancy category D. This means that idarubicin is known to be harmful to an unborn baby. Do not use idarubicin without first talking to your doctor if you are pregnant or could become pregnant during treatment. Discuss with your doctor the appropriate use of birth control during treatment with idarubicin if necessary. Because of the potential for serious side effects in a nursing infant, breast-feeding should be avoided during treatment with idarubicin. The safety and effectiveness of idarubicin in children has not been established.

How should I use Idamycin (idarubicin)?

Idarubicin should only be administered under the supervision of a qualified healthcare provider experienced in the use of cancer chemotherapeutic agents.

Your doctor will determine the correct amount and frequency of treatment with idarubicin depending upon the type of cancer being treated and other factors. Talk to your doctor if you have any questions or concerns regarding the treatment schedule.

Your doctor will probably want you to have regularly scheduled blood tests and other medical evaluations during treatment with idarubicin to monitor progress and side effects.

Skin accidentally exposed to idarubicin should be rinsed thoroughly with soap and warm water.

Your healthcare provider will store idarubicin as directed by the manufacturer. If you are storing idarubicin at home, follow the directions provided by your healthcare provider.

What happens if I miss a dose?

Contact your doctor if you miss a dose of idarubicin.

What happens if I overdose?

If for any reason an overdose of idarubicin is suspected, seek emergency medical attention or contact your healthcare provider immediately.

Symptoms of a idarubicin overdose tend to be similar to side effects caused by the medication, although often more severe.

What should I avoid while using Idamycin (idarubicin)?

Skin accidentally exposed to idarubicin should be rinsed thoroughly with soap and warm water.

Do not receive "live" vaccines during treatment with idarubicin. Administration of a live vaccine may be dangerous during treatment with idarubicin.

Idamycin (idarubicin) side effects

If you experience any of the following serious side effects from idarubicin, contact your doctor immediately:

an allergic reaction (including difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives);

decreased bone marrow function and blood problems (extreme fatigue; easy bruising or bleeding; black, bloody or tarry stools; or fever, chills, or signs of infection);

congestive heart failure (difficulty breathing, fluid retention, chest pain);

irregular heartbeats;

tissue or vein reactions near the site of administration;

liver damage (abdominal pain, yellowing of the skin or eyes);

severe nausea, vomiting, diarrhea, and loss of appetite;

inflamation and sores inside the mouth, throat, or intestines;

fever, chills, or other signs of infection;

numbness, tingling, or difficult movement of a body part;

seizures; or

increased levels of uric acid in the body (joint pain and stiffness).

Other, less serious side effects may be more likely to occur. Continue taking idarubicin and talk to your doctor if you experience:

facial flushing during administration;

eye irritation or tearing;

darkening of the nail beds and skin folds;

temporary hair loss; or

red colored urine for 1 or 2 days following a dose.

Some breast cancer patients developed a second cancer (leukemia) after treatment with idarubicin. Idarubicin may cause premature menopause.

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.

What other drugs will affect Idamycin (idarubicin)?

Do not use idarubicin without first talking to your doctor if you have had previous treatment with doxorubicin (Adriamycin, Rubex), doxorubicin liposomal (Doxil), daunorubicin (Cerubidine), daunorubicin liposomal (Daunoxome), idarubicin (Idamycin), or mitoxantrone (Novantrone). Because there is a maximum amount of these medications that should be administered to an individual, you may not be able to use idarubicin.

Before using idarubicin, tell your doctor if you are taking any of the following medicines.

paclitaxel (Taxol);

cimetidine (Tagamet, Tagamet HB, others);

progesterone (Prometrium);

verapamil (Calan, Calan SR, Covera-HS, Isoptin, Isoptin SR, Verelan, Verelan PM, others)

cyclosporine (Gengraf, Neoral, Sandimmune);

cyclophosphamide (Cytoxan, Cytoxan Lyophilized, Neosar);

phenobarbital;

phenytoin (Dilantin); or

streptozocin (Zanosar).

You may not be able to take idarubicin, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medicines listed above.

Do not receive "live" vaccines during treatment with idarubicin. Administration of a live vaccine may be dangerous during treatment with idarubicin.

Drugs other than those listed here may also interact with idarubicin. Talk to your doctor and pharmacist before taking any other prescription or over-the-counter medicines, including vitamins, minerals, and herbal products, during treatment with idarubicin.

More Idamycin resources

Idamycin Side Effects (in more detail)
Idamycin Use in Pregnancy & Breastfeeding
Idamycin Drug Interactions
Idamycin Support Group
0 Reviews for Idamycin - Add your own review/rating

Idamycin Prescribing Information (FDA)

Idamycin PFS Prescribing Information (FDA)

Idamycin PFS MedFacts Consumer Leaflet (Wolters Kluwer)

Idamycin PFS Monograph (AHFS DI)

Idamycin PFS Advanced Consumer (Micromedex) - Includes Dosage Information

Idarubicin Prescribing Information (FDA)

Idarubicin Professional Patient Advice (Wolters Kluwer)

Compare Idamycin with other medications

Leukemia
Leukocytoclastic Vasculitis
Solid Tumors

Where can I get more information?

Your pharmacist can provide more information about idarubicin.

See also: Idamycin side effects (in more detail)

Wednesday, 2 May 2012

Excedrin Tension Headache Express Gels

Generic Name: acetaminophen and caffeine (a SEET a MIN oh fen and KAF een)

Brand Names: Excedrin Quick Tab Peppermint, Excedrin Quick Tab Spearmint, Excedrin Tension Headache, Excedrin Tension Headache Caplet, Excedrin Tension Headache Express Gels, Excedrin Tension Headache Geltab, Valorin Extra

What is Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Acetaminophen is a pain reliever and a fever reducer.

Caffeine is used in this product to increase the pain relieving effects of acetaminophen.

The combination of acetaminophen and caffeine is used to treat pain from conditions such as headache, muscle aches, menstrual cramps, arthritis, backache, toothaches, colds and fevers.

Acetaminophen and caffeine may also be used for purposes not listed in this medication guide.

What is the most important information I should know about Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen. Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death. Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen.

What should I discuss with my healthcare provider before taking Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Do not take this medication if you are allergic to acetaminophen (Tylenol) or caffeine. Do not take this medication without a doctor's advice if you have ever had alcoholic liver disease (cirrhosis) or if you drink more than 3 alcoholic beverages per day. You may not be able to take medicine that contains acetaminophen.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have kidney or liver disease, or a history of alcoholism.

It is not known whether this medicine will harm an unborn baby. Do not take acetaminophen and caffeine without medical advice if you are pregnant. Acetaminophen and caffeine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Use this medication exactly as directed on the label, or as prescribed by your doctor.

Do not take more of this medication than is recommended. An overdose of acetaminophen can damage your liver or cause death.

One acetaminophen and caffeine pill contains 500 mg of acetaminophen. Know the amount of acetaminophen in the specific product you are taking.

The orally disintegrating tablet (Excedrin QuickTabs) should be placed directly on the tongue. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing. Swallow several times as the tablet dissolves. If desired, you may drink liquid to help swallow the dissolved tablet.

Call your doctor if your symptoms do not improve, especially if you still have a fever after 3 days of using this medication, or pain after 10 days of use. Stop taking acetaminophen and caffeine and call your doctor at any time if your symptoms get worse.

Acetaminophen may cause false urine glucose test results. Talk to your doctor if you have diabetes and you notice changes in glucose test results while taking acetaminophen and caffeine.

Store at room temperature away from heat and moisture.

What happens if I miss a dose?

Since acetaminophen and caffeine is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

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

Overdose symptoms may include loss of appetite, confusion, nausea, vomiting, diarrhea, sweating, fast or uneven heart rate, seizure (convulsions), pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

What should I avoid while taking Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

Ask a doctor or pharmacist before using any other cold, allergy, pain, or sleep medication. Acetaminophen (sometimes abbreviated as APAP) is contained in many combination medicines. Taking certain products together can cause you to get too much acetaminophen which can lead to a fatal overdose. Check the label to see if a medicine contains acetaminophen or APAP. Avoid drinking alcohol. It may increase your risk of liver damage while taking acetaminophen. Avoid coffee, tea, cola, energy drinks or other sources of caffeine while taking this medication. They can add to the side effects of the caffeine in the medication.

Excedrin Tension Headache Express Gels (acetaminophen and caffeine) side effects

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. Stop using acetaminophen and caffeine and call your doctor at once if you have a serious side effect such as:

low fever with nausea, stomach pain, and loss of appetite;

dark urine, clay-colored stools; or

jaundice (yellowing of the skin or eyes).

Less serious side effects may include:

sleep problems (insomnia); or

feeling nervous, irritable, or jittery.

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.

What other drugs will affect Excedrin Tension Headache Express Gels (acetaminophen and caffeine)?

There may be other drugs that can interact with acetaminophen and caffeine. Tell your doctor about all medications you use. This includes prescription, over the counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Excedrin Tension Headache Express Gels resources

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Where can I get more information?

Your pharmacist can provide more information about acetaminophen and caffeine.

See also: Excedrin Tension Headache Expresss side effects (in more detail)