ANHYDROUS CITRIC ACID: 34 Adverse Event Reports & Safety Profile

CLENPIQ (sodium picosulfate, magnesium oxide, and anhydrous citric acid) oral solution is a stimulant and osmotic laxative that is provided as a cranberry-flavored, colorless to slightly yellow, clear solution with possible presence of visible particles. CLENPIQ is supplied as two bottles in each carton. Each bottle of CLENPIQ contains 10 mg sodium picosulfate, USP; 3.5 g magnesium oxide, USP; and 12 g anhydrous citric acid, USP. The product also contains the following inactive ingredients: acesulfame potassium, cranberry flavor, disodium edetate, malic acid, sodium benzoate, sodium hydroxide, sodium metabisulfite, sucralose, and water. The cranberry flavor contains glyceryl triacetate (triacetin), maltodextrin, and sodium octenyl succinated starch. The following is a description of the three active ingredients contained in CLENPIQ: Sodium picosulfate is a stimulant laxative.

Sodium Picosulfate

Chemical name: 4,4´-(2-pyridylmethylene) diphenyl bis(hydrogen sulfate) disodium salt, monohydrate Chemical formula: C 18 H 13 NNa 2 O 8 S 2 ∙H 2 O Molecular weight:

499.4 Structural formula: Sodium picosulfate Magnesium citrate, which is formed in solution by the combination of magnesium oxide and anhydrous citric acid, is an osmotic laxative.

Chemical Structure Magnesium Oxide

Chemical name: Magnesium oxide Chemical formula: Mg O Molecular weight:

40.3 Structural formula: Mg O Anhydrous Citric Acid Chemical name: 2-hydroxypropane-1,2,3-tricarboxylic acid Chemical formula: C 6 H 8 O 7 Molecular weight:

192.1 Structural formula: Anhydrous citric acid Chemical Structure

INDICATIONS AND USAGE Sodium Citrate and Citric Acid Oral Solution USP is an effective alkalinizing agent. It is useful in those conditions where long-term maintenance of an alkaline urine is desirable, and is of value in the alleviation of chronic metabolic acidosis, such as results from chronic renal insufficiency or the syndrome of renal tubular acidosis, especially when the administration of potassium salts is undesirable or contraindicated. This product is also useful for buffering and neutralizing gastric hydrochloric acid quickly and effectively.

Sodium

Citrate and Citric Acid Oral Solution USP is concentrated, and when administered after meals and before bedtime, allows one to maintain an alkaline urinary pH around the clock, usually without the necessity of a 2 A.M. dose. This product alkalinizes the urine without producing a systemic alkalosis in the recommended dosage. This product is highly palatable, pleasant tasting, and tolerable, even when administered for long periods.

AND ADMINISTRATION Administration: CLENPIQ is ready to drink. It does not need to be diluted prior to administration. One bottle of CLENPIQ is equivalent to one dose. ( 2.1 ) Two doses of CLENPIQ are required for a complete preparation for colonoscopy as a Split-Dose regimen. ( 2.1 ) Consume five or more 8-ounce cups of clear liquids after the first dose and four or more 8-ounce cups of clear liquids after the second dose. ( 2.2 ) Consume a variety of clear liquids after each dose of CLENPIQ. Ensure inclusion of balanced electrolyte solution along with other clear liquids. ( 2.1 , 5.1 , 5.5 ) Administer oral medications at least 1 hour before starting CLENPIQ. ( 2.1 , 7.2 ) If taking tetracycline or fluoroquinolone antibiotics, iron, digoxin, chlorpromazine, or penicillamine, take these medications at least 2 hours before and not less than 6 hours after administration of CLENPIQ. ( 2.1 , 7.3 ) For complete information on preparation before colonoscopy and administration of the dosage regimen, see full prescribing information. ( 2.1 , 2.2 ) Split-Dose Dosage Regimen ( 2.2 ) First dose: administer during evening before the colonoscopy Second dose: administer the next day, during the morning prior to the colonoscopy.

2.1 Important Administration Instructions Correct fluid and electrolyte abnormalities before administration of CLENPIQ <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span> . CLENPIQ is ready to drink. It is a clear solution with possible presence of visible particles and it does not need to be diluted prior to administration. One bottle of CLENPIQ is equivalent to one dose. Two doses of CLENPIQ are required for a complete preparation for colonoscopy as a Split-Dose regimen.

The

Split-Dose method consists of two separate doses: the first dose during the evening before the colonoscopy and the second dose the next day, during the morning prior to the colonoscopy [see Dosage and Administration (2.2) ] . Consume five or more 8-ounce cups of clear liquids after the first dose and four or more 8-ounce cups of clear liquids after the second dose [see Dosage and Administration (2.2) ] . Consume a variety of clear liquids. Clear liquids should include balanced electrolyte solution [see Warnings and Precautions (5.1 , 5.5) ] . Additional clear liquids, other than water, include black coffee or tea, plain jello, clear broth or bouillon, clear juices without pulp, ginger ale and other sodas, and frozen juice bars. Do not drink anything colored red or purple. Consume only clear liquids (no solid food) on the day before colonoscopy and until after the colonoscopy. Do not eat solid food or dairy and do not drink anything colored red or purple. Do not drink alcohol. Stop consumption of all liquids at least 2 hours before the colonoscopy. Do not take other laxatives while taking CLENPIQ. Administer oral medications at least one hour before starting each dose of CLENPIQ. If taking tetracycline or fluoroquinolone antibiotics, iron, digoxin, chlorpromazine, or penicillamine, take these medications at least 2 hours before and not less than 6 hours after administration of CLENPIQ.

2.2 Split-Dose Dosage Regimen The recommended dosage in adults and pediatric patients 9 years of age and older is shown below. Instruct patients to take two separate doses in conjunction with liquids, as follows: Dose 1 – On the day before colonoscopy: Instruct patients to consume only clear liquids (no solid food or dairy) on the day before the colonoscopy up until 2 hours before the time of the colonoscopy. Take the first dose (1 bottle) of CLENPIQ during the evening before the colonoscopy (e.g., 5:00 PM to 9:00 PM). Consume at least five 8-ounce cups (cup provided) of clear liquids after the CLENPIQ dose over the next 5 hours. If severe bloating, distention, or abdominal pain occurs, following the first dose, delay the second dose until the symptoms resolve.

Dose

2 – Next morning on the day of colonoscopy (start approximately 5 hours prior to colonoscopy): Continue to consume only clear liquids (no solid food or dairy). Take the second dose (the second bottle) of CLENPIQ. Consume four or more 8-ounce cups (cup provided) of clear liquids after the CLENPIQ dose and up to 2 hours before the colonoscopy.

CLENPIQ is contraindicated in the following conditions: Patients with severe renal impairment (creatinine clearance less than 30 mL/minute), which may result in accumulation of magnesium [see Warnings and Precautions (5.3) ]. Gastrointestinal obstruction or ileus [see Warnings and Precautions (5.6) ]. Bowel perforation [see Warnings and Precautions (5.6) ]. Toxic colitis or toxic megacolon. Gastric retention. Hypersensitivity to any of the ingredients in CLENPIQ [see Adverse Reactions (6.2) ]. Severe renal impairment (creatinine clearance less than 30 mL/minute) ( 4 , 5.3 , 8.6 ) Gastrointestinal (GI) obstruction or ileus ( 4 ) Bowel perforation ( 4 ) Toxic colitis or toxic megacolon ( 4 ) Gastric retention ( 4 ) Hypersensitivity to any of the ingredients in CLENPIQ ( 4 )

REACTIONS The following serious or otherwise important adverse reactions for bowel preparations are described elsewhere in the labeling: Serious Fluid and Electrolyte Abnormalities [see Warnings and Precautions (5.1) ] Seizures [see Warnings and Precautions (5.2) ] Use in Patients with Renal Impairment [see Warnings and Precautions (5.3) ]

Cardiac

Arrhythmias [see Warnings and Precautions (5.4) ] Syncope [see Warnings and Precautions (5.5) ]

Colonic Mucosal

Ulceration, Ischemic Colitis and Ulcerative Colitis [see Warnings and Precautions (5.6) ] Use in Patients with Significant Gastrointestinal Disease [see Warnings and Precautions (5.7) ] Aspiration [see Warnings and Precautions (5.8) ] Most common adverse reactions are: Adults (≥2%): nausea, headache, hypermagnesemia, abdominal pain and dehydration or dizziness. ( 6.1 )

Pediatrics

9 to 16 years (>5%): nausea, vomiting, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ferring Pharmaceuticals Inc. at 1-888-FERRING (1-888-337-7464) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in practice.

Adults Clinical

Study of CLENPIQ - Study 1 Table 1 displays the most common adverse reactions in a randomized, multicenter, assessor-blinded, non-inferiority trial of CLENPIQ for colon cleansing in adults (Study 1). CLENPIQ was compared to another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product, both administered according to the Split-Dose dosage regimen [see Clinical Studies (14) ] .

Table

1: Common Adverse Reactions Observed in at Least 2% of Patients Undergoing Colon Cleansing in Study 1 Adverse Reaction Split-Dose Regimen CLENPIQ (N=448) % Sodium picosulfate, magnesium oxide, and anhydrous citric acid Powder for reconstitution (N=453) % Nausea 3 3 Headache 3 3 Hypermagnesemia Magnesium levels returned to normal within one week after colonoscopy in all patients in the CLENPIQ group. 2 5 Abdominal pain Abdominal pain included reports of abdominal pain, abdominal pain upper, and abdominal pain lower. 2 2 Dehydration or dizziness 2 2 Clinical Study of Another Sodium Picosulfate, Magnesium Oxide and Anhydrous Citric Acid Product - Study 2 In a randomized, multicenter, investigator-blinded, active-controlled clinical trial for colon cleansing in adults, another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product was compared with a regimen of two liters (2 L) of polyethylene glycol plus electrolytes solution (PEG + E) and two 5-mg bisacodyl tablets (Study 2). In this study the protocol specified that abdominal bloating, distention, pain/cramping, and watery diarrhea, which are known to occur in response to bowel preparation, were documented as adverse events only if they required medical intervention (such as a change in study drug or led to discontinuation, therapeutic or diagnostic procedures, met the criteria for serious adverse event) or showed clinically significant worsening during the study that was not in the frame of the usual clinical course, as determined by the investigator. The most common adverse reactions in Study 2 are shown in Table 2.

Table

2: Common Adverse Reactions abdominal bloating, distention, pain/cramping, and watery diarrhea not requiring an intervention were not collected Observed in at Least 1% of Patients Undergoing Colon Cleansing in Study 2 Adverse Reaction Split-Dose Regimen Sodium picosulfate, magnesium oxide, and anhydrous citric acid (N=305) % 2 L PEG + E 2 L PEG + E = two liters polyethylene glycol plus electrolytes solution with 2 × 5-mg bisacodyl tablets (N=298) % Nausea 3 4 Headache 2 2 Vomiting 1 3 Electrolyte Abnormalities In Study 1, rates of abnormal electrolyte shifts were generally similar between CLENPIQ and another sodium picosulfate, magnesium oxide, and anhydrous citric acid product (Table 3). In general, these shifts were transient and not clinically significant.

In Study

2, sodium picosulfate, magnesium oxide, and anhydrous citric acid was in general associated with numerically higher rates of abnormal electrolyte shifts on the day of colonoscopy compared to the control regimen (Table 3). These shifts were transient in nature and numerically similar between treatment arms at the Day 28 visit.

Table

3: Shifts from Normal Baseline to Outside the Normal Range Post-Baseline Laboratory Parameter (direction of change)

Visit

Split-Dose Regimen Study 1 Split-Dose Regimen Study 2 CLENPIQ Sodium picosulfate, magnesium oxide, and anhydrous citric acid Powder for reconstitution Sodium picosulfate, magnesium oxide, and anhydrous citric acid 2 L PEG+E with 2 × 5 mg bisacodyl tablets n/N (%) n/N (%) N/A: not applicable. Potassium (low) Day of Colonoscopy 34/422 (8.1) 10/423 (2.4) 19/260 (7.3) 11/268 (4.1) 24-48 hours 13/417 (3.1) 3/423 (0.7) 3/302 (1.0) 2/294 (0.7)

Day

7 7/420 (1.7) 6/425 (1.4) 11/285 (3.9) 8/279 (2.9)

Day

28 3/421 (0.7) 7/423 (1.7) 11/284 (3.9) 8/278 (2.9) Sodium (low) Day of Colonoscopy 4/426 (0.9) 23/443 (5.2) 11/298 (3.7) 3/295 (1.0) 24-48 hours 6/423 (1.4) 9/441 (2.0) 1/303 (0.3) 1/295 (0.3)

Day

7 6/423 (1.4) 9/440 (2.0) 2/300 (0.7) 1/292 (0.3)

Day

28 8/427 (1.9) 9/439 (2.1) 2/299 (0.7) 3/291 (1.0) Chloride (low) Day of Colonoscopy 23/437 (5.3) 16/444 (3.6) 11/301 (3.7) 1/298 (0.3) 24-48 hours 3/434 (0.7) 3/442 (0.7) 1/303 (0.3) 0/295 (0.0)

Day

7 3/434 (0.7) 2/441 (0.5) 1/303 (0.3) 3/295 (1.0)

Day

28 4/438 (0.9) 1/440 (0.2) 2/302 (0.7) 3/294 (1.0) Magnesium (high) Day of Colonoscopy 112/431 (26.0) 143/440 (32.5) 34/294 (11.6) 0/294 (0.0) 24-48 hours 23/427 (5.4) 21/440 (4.8) 0/303 (0.0) 0/295 (0.0)

Day

7 11/428 (2.6) 9/440 (2.0) 0/297 (0.0) 1/291 (0.3)

Day

28 10/432 (2.3) 12/438 (2.7) 1/296 (0.3) 2/290 (0.7) Calcium (low) Day of Colonoscopy 8/436 (1.8) 1/446 (0.2) 2/292 (0.7) 1/286 (0.3) 24-48 hours 1/434 (0.2) 0/444 (0.0) 0/303 (0.0) 0/295 (0.0)

Day

7 0/434 (0.0) 0/444 (0.0) 0/293 (0.0) 1/283 (0.4)

Day

28 0/439 (0.0) 2/442 (0.5) 0/292 (0.0) 1/282 (0.4) Bicarbonate (low) Day of Colonoscopy 6/431 (1.4) 35/438 (8.0) N/A Bicarbonate was not analyzed in Study 2. N/A 24-48 hours 40/430 (9.3) 43/434 (9.9) N/A N/A Day 7 37/430 (8.6) 40/438 (9.1) N/A N/A Day 28 33/433 (7.6) 43/436 (9.9) N/A N/A Creatinine (high) Day of Colonoscopy 6/427 (1.4) 1/432 (0.2) 5/260 (1.9) 13/268 (4.9) 24-48 hours 6/425 (1.4) 5/431 (1.2) 1/303 (0.3) 0/295 (0.0)

Day

7 5/426 (1.2) 4/431 (0.9) 10/264 (0.4) 13/267 (4.8)

Day

28 4/429 (0.9) 6/429 (1.4) 11/264 (4.2) 14/265(5.3) Pediatrics In the pediatric patients aged 9 to 16 years who received another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid, the most common adverse reactions (> 5%) were nausea, vomiting, and abdominal pain [see Clinical Studies (14) ] . Electrolytes abnormalities were observed in pediatric patients similar to those seen in adults. Three patients had abnormally low glucose levels (40 to 47 mg/dL). Two patients received sodium picosulfate, magnesium oxide, and anhydrous citric acid and one received the comparator (PEG). The abnormal values occurred at the colonoscopy visit for one patient (sodium picosulfate, magnesium oxide, and anhydrous citric acid) and at the 5-day follow up visit for the other two patients (sodium picosulfate, magnesium oxide, and anhydrous citric acid and PEG). All three patients were asymptomatic.

6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of oral sodium picosulfate, magnesium oxide, and anhydrous citric acid products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity : rash, urticaria, and purpura Gastrointestinal: abdominal pain, diarrhea, fecal incontinence, proctalgia, vomiting, reversible aphthoid ileal ulcers, and ischemic colitis <span class="opacity-50 text-xs">[see Warnings and Precautions (5.5) ]</span> Neurologic: generalized tonic-clonic seizures with and without hyponatremia in epileptic patients, and syncope <span class="opacity-50 text-xs">[see Warnings and Precautions (5.2 , 5.5) ]</span> .

AND PRECAUTIONS Risk of fluid and electrolyte abnormalities, arrhythmia, seizures, and renal impairment : Encourage adequate hydration, assess concurrent medications, and consider laboratory assessments prior to and after use. ( 5.1 , 5.2 , 5.3 , 5.4 , 7.1 ) Use in patients with renal impairment or taking concomitant medications that affect renal function : Use caution, ensure adequate hydration, and consider testing. ( 4 , 5.3 , 7.1 ) Syncope : Resulted in serious outcomes including falls, head injuries, and fractures; encourage adequate hydration. ( 5.5 ) Mucosal ulcerations : Consider potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease. ( 5.6 ) Suspected GI obstruction or perforation : Rule out diagnosis before administration. ( 4 , 5.7 ) Patients at risk for aspiration : Observe during administration. ( 5.8 )

5.1 Serious Fluid and Electrolyte Abnormalities Advise patients to hydrate adequately before, during, and after the use of CLENPIQ. Use caution in patients with congestive heart failure when replacing fluids. If a patient develops significant vomiting or signs of dehydration including signs of orthostatic hypotension after taking CLENPIQ, consider performing post-colonoscopy lab tests (electrolytes, creatinine, and BUN) and treat accordingly.

Approximately

20% of patients in both arms (sodium picosulfate, magnesium oxide, and anhydrous citric acid, or 2 L of PEG + E plus two × 5-mg bisacodyl tablets) of clinical trials of another oral sodium picosulfate, magnesium oxide, and anhydrous citric acid product had orthostatic changes in blood pressure and/or heart rate on the day of colonoscopy and up to seven days post colonoscopy. In a single study of patients 9 to 16 years of age, approximately 20% of patients who received another oral product of sodium picosulfate, magnesium oxide, and anhydrous citric acid had orthostatic changes (changes in blood pressure and/or heart rate) compared with approximately 7% of those who received the comparator (PEG) [see Clinical Studies (14) ] . These changes occurred up to five days post colonoscopy. Fluid and electrolyte disturbances can lead to serious adverse reactions including cardiac arrhythmias, seizures, renal impairment, and syncope [see Warnings and Precautions (5.5) ] . Correct fluid and electrolyte abnormalities before treatment with CLENPIQ. Advise patients to consume a variety of clear liquids (e.g., balanced electrolyte solution), and not only water after each dose of CLENPIQ. In addition, use caution when prescribing CLENPIQ for patients who have conditions or who are using medications that increase the risk for fluid and electrolyte disturbances or that may increase the risk of seizure, arrhythmia, and renal impairment [see Drug Interactions (7.1) ] .

5.2 Seizures There have been reports of generalized tonic-clonic seizures and/or loss of consciousness with the use of bowel preparation 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. Use caution when prescribing CLENPIQ for patients with a history of seizures and in patients at risk of seizure, such as patients taking medications that lower the seizure threshold (e.g., tricyclic antidepressants), patients withdrawing from alcohol or benzodiazepines, patients with known or suspected hyponatremia <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> .

5.3 Use in Patients with Renal Impairment CLENPIQ is contraindicated in patients with severe renal impairment (creatinine clearance less than 30 mL/min), accumulation of magnesium in plasma may occur. Use caution when prescribing CLENPIQ for patients with mild to moderate renal impairment or patients taking concomitant medications that may affect renal function (such as diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or non-steroidal anti-inflammatory drugs) <span class="opacity-50 text-xs">[see Drug Interactions (7.1) ]</span> . These patients may be at increased risk for renal injury. Advise these patients of the importance of adequate hydration before, during, and after the use of CLENPIQ. Consider performing baseline and post-colonoscopy laboratory tests (electrolytes, creatinine, and BUN) in these patients.

5.4 Cardiac Arrhythmias There have been rare reports of serious arrhythmias associated with the use of ionic osmotic laxative products for bowel preparation. Use caution when prescribing CLENPIQ for patients at increased risk of arrhythmias (e.g., patients with a history of prolonged QT, uncontrolled arrhythmias, recent myocardial infarction, unstable angina, congestive heart failure, or cardiomyopathy). Consider pre-dose and post-colonoscopy ECGs in patients at increased risk of serious cardiac arrhythmias.

5.5 Syncope Syncope has been reported with CLENPIQ in the postmarketing setting. Some cases were serious events that included falls with associated head injuries or fractures requiring hospitalization. In some cases, electrolyte abnormalities were also present (e.g., hyponatremia and hypokalemia). Cases have been reported after one or two CLENPIQ doses and many of these cases occurred within 12 hours of dosing. Patients should be aware of the risk of syncope during treatment and adequately hydrate before, during, and after the use of CLENPIQ. Advise patients to consume a variety of clear liquids (e.g., balanced electrolyte solution), not only water after each dose of CLENPIQ and to get up gradually from a lying or sitting position <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1) ]</span> .

5.6 Colonic Mucosal Ulceration, Ischemic Colitis, and Ulcerative Colitis Osmotic laxatives may produce colonic mucosal aphthous ulcerations and there have been reports of more serious cases of ischemic colitis requiring hospitalization. Concurrent use of additional stimulant laxatives with CLENPIQ may increase this risk. Consider the potential for mucosal ulcerations when interpreting colonoscopy findings in patients with known or suspected inflammatory bowel disease <span class="opacity-50 text-xs">[see Adverse Reactions (6.2) ]</span> .

5.7 Use in Patients with Significant Gastrointestinal Disease If gastrointestinal obstruction or perforation is suspected, perform appropriate diagnostic studies to rule out these conditions before administering CLENPIQ <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . Use with caution in patients with severe active ulcerative colitis.

5.8 Aspiration Patients with impaired gag reflex are at risk for regurgitation or aspiration during the administration of CLENPIQ. Observe these patients during the administration of CLENPIQ.

PRECAUTIONS Maintain Patency of the Urethral Catheter or Cystostomy Tube Care must be taken during therapy with Renacidin to maintain the patency of the urethral catheter or cystostomy tube. Calculus fragments and debris may obstruct the catheter. Catheter outflow blockage may be prevented by flushing the catheter with saline and repositioning of the catheter. Frequent monitoring of the system should be performed by a nurse, an aide or any person with sufficient skills to be able to detect any problems with the patency of the catheter. At the first sign of obstruction, Renacidin should be discontinued. Caution in Patients with Vesicoureteral Reflux Patients with an indwelling urethral catheter or a cystostomy tube may have undiagnosed vesicoureteral reflux. Appropriate evaluation prior to initiation of Renacidin is recommended. If reflux is demonstrated, the potential benefits of therapy should outweigh the risks, and all recommended safety monitoring precautions should be strictly implemented.

Safety Monitoring

While on Therapy with Renacidin Patients should be monitored throughout the course of therapy with Renacidin. Serum creatinine, phosphate and magnesium should be obtained every several days. Urine specimens should be collected for culture and antibacterial sensitivity approximately every three days and at the first sign of fever. Therapy with Renacidin should be stopped if any culture exhibits growth and appropriate antibacterial therapy should be initiated. Therapy with Renacidin may be started again after a course of antibacterial therapy upon demonstration of sterile urine. Struvite calculi frequently contain bacteria within the stone and antibacterial therapy should therefore be continued throughout the course of dissolution therapy. An elevated serum creatinine concentration is also an indication to stop therapy with Renacidin.

Concomitant

Use with Medications Containing Magnesium Concomitant use of Renacidin and medications containing magnesium may contribute to hypermagnesemia in susceptible individuals, such as patients with vesicoureteral reflux.

Renacidin

Irrigation should be used with caution in patients taking concomitant medications containing magnesium. Carcinogenesis, Mutagenesis, Impairment of Fertility Long term studies to evaluate carcinogenic potential of Renacidin in animals have not been conducted. Mutagenicity studies have not been conducted.

Pregnancy

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

Nursing Mothers

Magnesium is known to be excreted into human milk. It is not known whether Renacidin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Renacidin is administered to a nursing woman.

INTERACTIONS Drugs that increase risks due to fluid and electrolyte changes. ( 7.1 )

7.1 Drugs That May Increase Risks of Fluid and Electrolyte Abnormalities Use caution when prescribing CLENPIQ for patients with conditions or who are taking other drugs, that increase the risk for fluid and electrolyte disturbances or may increase the risk of renal impairment, seizures, syncope, arrhythmias or QT prolongation in the setting of fluid and electrolyte abnormalities <span class="opacity-50 text-xs">[see Warnings and Precautions (5.1 , 5.2 , 5.3 , 5.4 , 5.5) ]</span> .

7.2 Potential for Reduced Drug Absorption CLENPIQ can reduce the absorption of other co-administered drugs <span class="opacity-50 text-xs">[see Dosage and Administration (2.1) ]</span> : Administer oral medications at least one hour before of the start of administration of CLENPIQ. Administer tetracycline and fluoroquinolone antibiotics <span class="opacity-50 text-xs">[see Drug Interactions (7.3) ]</span> , iron, digoxin, chlorpromazine, and penicillamine at least 2 hours before and not less than 6 hours after administration of CLENPIQ to avoid chelation with magnesium.

7.3 Antibiotics Prior or concomitant use of antibiotics with CLENPIQ may reduce efficacy of CLENPIQ as conversion of sodium picosulfate to its active metabolite BHPM is mediated by colonic bacteria.

Active Ingredients Allium Sativum 3X 6X 9X 12X 15X Arsenicum Album 6X 8X 10X 12X 15X 30X Benzoicum Acidum 6X 9X 12X 30X Berberis Vulgaris 3X 6X 9X 12X Betula Verrucosa Leaf 3X 6X 9X Calcarea Carbonica 8X 10X 12X 30X Carbolicum Acidum 4X 6X 9X 12X 30X Chelidonium Majus 3X 6X 9X Chlorinum 6X 9X 12X 15X 30X Citricum Acidum 6X 9X 12X 15X 30X Histaminum Hydrochloricum 6X 9X 12X 15X 30X Ichthyolum 6X 9X 12X 15X Juniperus Communis Stem 3X 6X 9X Lycopodium Clavatum 6X 7X 8X 9X 10X 12X 30X Mercurius Solubilis 9X 12X 15X 30X Natrum Bicarbonicum 6X 9X 12X 15X 30X Sodium Hypochlorite 6X 9X 12X 15X 30X Solidago Virgaurea 2X 3X 6X 9X Sulphur 6X 7X 8X 9X 10X 12X 15X

Inactive ingredients Maltodextrin, natural orange flavor, sodium saccharin.