Niflec

Sodium chloride, sodium bicarbonate, potassium chloride, anhydrous sodium sulfate.

Each pack (137.155 g) of Niflec contains sodium chloride 2.93 g, potassium chloride 1.48 g, sodium bicarbonate 3.37 g and anhydrous sodium sulfate 11.37 g. It also contains polyethylene glycol 4000 for isotonicity.
Electrolytic Concentration of the Dissolved Solution (dissolve 1 pack in water to make 2 L): Na⁺ 125 mEq/L, K⁺ 10 mEq/L, Cl^- 35 mEq/L, HCO₃^- 20 mEq/L, SO₄^2- 80 mEq/L.
Niflec occurs as white powder and has a slightly characteristic odor with a slight salty taste. When dissolved in water, Niflec is colorless and clear with a pH of about 8 and osmotic pressure ratio of about 1.

Pharmacology: Intestinal Lavage Effect: As a result of repeated oral administration of Niflec, it was shown that the intestinal content significantly decreased through watery stool excretion (in nonfasted, fasted rats and nonfasted rats which had undergone cecectomy) enabling the identification of a definite intestinal lavage effect. Likewise, in (16-hr fasted) dogs, repeated oral administration caused excretion liquid to become clear, also enabling the identification of a definite intestinal lavage effect.
Effects on Electrolyte Balance: Niflec does not practically alter serum Na⁺, Cl^- and blood pH in (16-hr fasted) dogs and (24-hr fasted) rats, hence do not significantly disturb serum electrolyte balance. Moreover, changes in urine volume and urinary electrolyte in (24-hr fasted) rats were found to be smaller than those in saline solution and balanced electrolyte solution (BES).
Pharmacokinetics: As a result of administering 1, 2, 3 and 5 L of the solution to healthy adult male volunteers, and 4 L to 6 healthy male volunteers, it was found that no major changes which could cause clinical problems to serum electrolyte, urine volume and electrolyte in the urine were identified in all dosing groups. It was also found that Niflec was discharged from the body with stool.
Clinical Results: At the Time of Application for Approval: Comparative clinical and general clinical studies in terms of its use as pre-treatment for colonoscopy and large bowel operation were carried out. Studies were targeted at a total of 1072 trial subjects at 120 trial sites throughout the country. The profile outcome given in Table 1 shows high levels of efficacy. (See Table 1.)

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At the Time of Filing an Application for Additional Use: Comparative clinical study between administration on the day prior to examination and administration on the day of examination in pre-treatment for colonoscopy was carried out. It was targeted at a total of 153 subjects at 21 trial sites throughout the country. The profile of the outcome given in Table 2 shows that the efficacy of administration on the day before examination is comparable to that of administration on the day of examination. (See Table 2.)

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Elimination of the intestinal contents during pre-treatment for colonoscopy and large bowel operation.

Dissolve 1 pack of Niflec in water to make about 2 L of solution. Orally administer 2-4 L of the dissolved solution at a rate of about 1 L/hr. Discontinue dosing when excretion liquid becomes clear. Refrain from dosing >4 L.
Pre-treatment for Colonoscopy: Administration on the Day of Examination: Refrain from having breakfast on the day of examination (water intake is acceptable) and start dosing from about 4 hrs ahead of the scheduled time of examination.
Administration on the Day Before Examination: Refrain from having any food after previous day's supper (water intake is acceptable) and start dosing after at least 1 hr has elapsed following supper. The previous day's breakfast and lunch must contain smaller amounts of residue and supper must consist of liquid food (contains no solid matter).
Pre-treatment for Large Bowel Operation: Fast after lunch on the day before operation (water intake is acceptable) and start dosing after at least 3 hrs have elapsed following lunch.
Administration: Method of Preparation: Dissolve 1 full bag of Niflec in water to make about 2 L and then administer to subjects (since the individual ingredients in the bag are not mixed homogeneously, be sure to dissolve 1 full bag at a time).
Preparation: No additional ingredients or flavoring should be added to Niflec solution (see Important Basic Precautions under Precautions).
Dosing Velocity: Transfer the dissolved solution (about 180 mL) to glasses to get 6 glassfuls (about 1 L/hr) as a guide.
In most cases, defecation starts more or less from the time about 1 L of the product is administered, and defecation occurs several times thereafter; continue administration (with 4 L as maximum) until the rectal effluent turns clear. Defecation may be produced several times even after the subjects are given 2 L. Discontinue administration and resume when nausea, vomiting and abdominal pain are absent and when defecation is present.
It should be noted that Niflec is not suited for pre-treatment for barium enema x-ray colonography.

Gastrointestinal tract obstruction. (Intestinal perforation may occur.) Intestinal perforation. (Peritonitis of other serious complications may occur.) Toxic megacolon. (Peritonitis or intestinal bleeding may occur, following perforation triggered by the symptom.)

Since shock, anaphylactoid symptoms may occur after taking Niflec, patients should be provided explanation of measures to be taken when adverse reactions arise.

Careful Administration: Niflec should be administered with caution in the following patients: Patients with angina pectoris or patients with history of myocardial infarction. (As Niflec can cause chilliness in the body, chest pain may rarely occur.) Patients with impaired renal function. (Vomiting may rarely occur.)
Important Basic Precautions: Since Mallory-Weiss syndrome, intestinal perforation and ischaemic colitis may rarely occur, the following points should be kept in mind:
Since Mallory-Weiss syndrome can occur due to increased gastric internal pressure, vomiting and nausea, administration in a short period of time should be avoided (dosing should be given at a rate of 1 L/hr as a guide). Furthermore, careful administration is required since intestinal stricture or retention of Niflec or the intestinal contents may cause nausea or vomiting which can trigger the onset of the syndrome.
Careful administration is required since intestinal perforation and ischaemic colitis can be caused by the increased intestinal internal pressure, intestinal stricture or retention of intestinal contents eg, in case of constipation. Administration should be done after making sure that there was defecation on the previous day. Further, administration in a short period of time, which may give rise to increased intestinal internal pressure, should be avoided (dosing should be given at a rate of 1 L/hr as a guide). In addition, in the absence of defecation after dosing about 1 L, dosing should be resumed only in the absence of nausea, vomiting and abdominal pain. Close monitoring should be exercised until defecation is present. Particular caution should be exercised in patients having prior intestinal diverticulum, since it has been reported that intestinal perforation may be triggered by increased intestinal internal pressure in these patients.
When any other ingredient or flavor is added to the dissolved solution of Niflec, the osmotic pressure or concentration of electrolyte may change and inflammable gas may be produced due to enterobacterium; therefore, addition of such substances should be avoided.
In case patients are allowed to take Niflec at home, the following points should be kept in mind: Taking countermeasures may occasionally be difficult in case of adverse reactions. Patients should be advised to avoid taking the drug when there is nobody else nearby.
Particularly, patients should be guided to take the initial 2 or 3 glassfuls of Niflec slowly and to pay attention to any signs of anaphylactoid symptoms.
Patients should be advised of Niflec's adverse reactions eg, digestive symptoms (nausea, vomiting, abdominal pain, etc), shock, anaphylactoid symptoms, etc. When such symptoms appear, they should discontinue medication and consult their physician without delay. Moreover, similar symptoms may arise even after medication. When such symptoms arise, the patients should also consult their physician without delay.
Administration to Patients Receiving Insulin or Oral Hypoglycemic Agents: In patients whose blood glucose is being controlled by insulin or an oral hypoglycemic agent, administration of Niflec on the day preceding examination should be avoided. Patients should be given Niflec on the day of examination under close observation. Dosing of insulin or an oral hypoglycemic agent should be started after dietary intake on the day of examination (because dietary restriction may cause hypoglycemia).
Effect on the Absorption of Drugs: Caution should be exercised as to dosing time since intestinal lavage by Niflec may disturb the absorption of an orally administered drug. Moreover, in patients on any drug which can cause clinically serious problems once the drug's absorption is inhibited, administration should be exercised while closely monitoring the patient's condition in the hospital.
Use in pregnancy & lactation: Niflec should be administered to women who are or may be pregnant only when the benefit of the treatment in judged to outweigh its possible risks. Safety during pregnancy has not yet been established.
Use in children: Safety of Niflec in children has not been established. (Fewer previous uses.)
Use in the elderly: In general, physiological function in the elderly is decreasing; therefore, one should slow down the dosing velocity while closely observing elderly patients.

Niflec should be administered to women who are or may be pregnant only when the benefit of the treatment in judged to outweigh its possible risks. Safety during pregnancy has not yet been established.

Results Obtained up to the Time of Completion of Post-Marketing Surveillance for Re-Examination: Out of a total 11,866 patients, 298 patients (2.51%) presented adverse reactions. The primary reactions were 100 cases of vomiting (0.84%), 55 cases of feeling of enlarged abdomen (0.46%), 54 cases of retching (0.46%), 40 cases of feeling cold (0.34%), 37 cases of nausea (0.31%), etc. Anomaly of laboratory findings was seen in 157 patients (1.32%) or 224 cases. The primary ones were 28 cases of positive urine ketone bodies (0.24%), 22 cases of increased GOT (0.19%), 22 cases of increased GPT (0.19%) and 16 cases of increased LDH (0.13%).
Results of a Controlled Study Dedicated to the Addition of the Previous-Day Dosing Method: Out of a total 147 dosed patients, 130 patients (88.4%) (including anomaly of laboratory findings) presented adverse reactions. The primary ones were 92 cases of feeling of enlarged abdomen (62.6%), 52 cases of nausea (35.4%), 34 cases of abdominal pain (23.1%), 40 cases of feeling cold (27.2%), 20 cases of malaise (13.6%), 15 cases of dizziness (10.2%), 9 cases of vomiting (6.1%), 7 cases of headache (4.8%), 6 cases of sleep loss (appeared only in the previous-day dosing method) (4.1%), 6 cases of increased bilirubin value (4.1%), 4 cases of increased GOT (2.7%), 2 cases of increased GPT (1.4%), etc. It should be noted that in this study, all subjective and objective symptoms with which causal relationship of Niflec cannot be denied were included in the category of adverse reactions.
Clinically Significant Adverse Reactions: Shock, Anaphylactoid Symptoms: Since shock and anaphylactoid symptoms may occur, close monitoring should be carried out. When facial pallor, decreased blood pressure, vomiting, continuous nausea, feeling bad, vertigo, feeling cold, urticaria, dyspnea, face oedema and so forth arise, administration should be discontinued and adequate treatment should be given. In cases where patients are allowed to take Niflec at home, it is necessary to offer them guidance by referring to Important Basic Precautions under Precautions.
Intestinal Perforation: Since intestinal perforation may occur, close monitoring should be carried out. When anomaly is observed, administration should be discontinued and adequate treatment should be given. In cases where patients are allowed to take Niflec at home, it is necessary to offer them guidance by referring to Important Basic Precautions under Precautions.
Hyponatraemia: Since vomiting may cause hyponatraemia which can lead to disturbed consciousness, convulsion, etc, adequate treatment should be given (eg, correction of electrolyte) when such symptoms arise. In cases where patients are allowed to take the drug at home, it is necessary to offer them guidance by referring to Important Basic Precautions under Precautions.
Others: See Table 3.

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Store between 25-35°C.
Use Niflec immediately after dissolution. When unused, keep Niflec solution refrigerated and use within 48 hrs of dissolution.

Laxatives, Purgatives

V07A - ALL OTHER NON-THERAPEUTIC PRODUCTS ; Other products with non-therapeutic properties.

NDD