DIALINE LOW CALCIUM PERITONEAL DIALYSIS SOLUTION WITH 1.5 % DEXTROSE

DIALINE

®

LOW CALCIUM PERITONEAL DIALYSIS SOLUTIONS

(2.5% mEq/L Calcium)

Dialine

®

Low Calcium Peritoneal Dialysis Solution with 1.5% Dextrose.

Dialine

®

Low Calcium Peritoneal Dialysis Solution with 2.5% Dextrose.

Dialine

®

Low Calcium Peritoneal Dialysis Solution with 4.25% Dextrose.

For Peritoneal Dialysis

For intraperitoneal administration only

Description

DIALINE Low Calcium peritoneal dialysis solutions are sterile, nonpyrogenic solutions in plastic containers for intraperitoneal administration only. They contain no bacteriostatic

or antimicrobial agents or added buffers.

Composition, calculated osmolarity, pH and ionic concentrations are shown in Table 1.

Potassium is omitted from peritoneal dialysis solutions because dialysis may be performed to correct hyperkalemia. In situations in which there is a normal serum potassium

level or hypokalemia, the addition of potassium chloride (up to a concentration of 4 mEq/L) may be indicated to prevent severe hypokalemia.

Addition of potassium chloride should be made after careful evaluation of serum and total body potassium and only under the direction of a physician. Frequent

monitoring of serum electrolytes is indicated.

In some patients calcium carbonate is used as a phosphate binder. Because serum calcium levels have been observed to be elevated in these patients (Slatopolsky et al.

1986), the calcium concentration of DIALINE Low Calcium peritoneal dialysis solutions has been appropriately reduced to 2.5 mEq/L. Serum calcium levels should be

monitored and if low, the amount of oral calcium carbonate phosphate binder may be increased or peritoneal dialysis solutions containing higher calcium concentrations may

be used. If serum calcium levels rise, adjustments to the dosage of the calcium carbonate phosphate binder and/or vitamin D analogs should be considered by the physician.

Because average plasma magnesium levels in some chronic CAPD patients have been observed to be elevated (Nolph et al. 1981), the magnesium concentration of this

formulation has been reduced to 0.5 mEq/L. Average plasma magnesium levels have not been reported for chronic IPD and CCPD patients. Serum magnesium levels should

be monitored and if low, oral magnesium supplements, oral magnesium containing phosphate binders, or peritoneal dialysis solutions containing higher magnesium

concentrations may be used.

Because average serum bicarbonate levels in some chronic CAPD patients (Nolph et al. 1981), some chronic IPD patients (La Greca et al. 1980), and some chronic

CCPDpatients (Diaz-Buxo et al. 1983), have been observed to be somewhat lower than normal values, the bicarbonate precursor (lactate) concentration of DIALINE Low

Calcium peritoneal dialysis solutions has been raised to 40 mEq/L. Serum bicarbonate levels should be monitored.

Dialine Low Calcium PDS 28. 5. 2012, RH

Dialine Low Calcium PDS 28. 5. 2012, RH

The osmolarities shown in Table 1 are calculated values. Calculated osmolarity of DIALINE Low Calcium peritoneal dialysis solution with 1.5% dextrose is 344 mOsmol/L,

compared with measured values in normal human serum of 280 mOsmol/L.

The plastic container is fabricated from a specially formulated polyvinyl chloride. The amount of water that can permeate from inside the container into the overpouch is

insufficient to affect the solution significantly. Solutions in contact with the plastic container can leach out certain of its chemical components in very small amounts within the

expiration period, e.g., di-2-ethylhexyl phthalate (DEHP), up to 5 parts per million; however, the safety of the plastic has been confirmed in tests in animals according to USP

biological tests for plastic containers as well as by tissue culture toxicity studies.

Clinical Pharmacology

Peritoneal dialysis is a procedure for removing toxic substances and metabolites normally excreted by the kidneys, and for aiding in the regulation of fluid and electrolyte

balance.

The procedure is accomplished by instilling peritoneal dialysis fluid through a conduit into the peritoneal cavity. With the exception of lactate, present as a bicarbonate

precursor, electrolyte concentrations in the fluid have been formulated in an attempt to normalize plasma electrolyte concentrations resulting from osmosis and diffusion across

the peritoneal membrane (between the patient's plasma and the dialysis fluid). Toxic substances and metabolites, present in high concentrations in the blood, cross the

peritoneal membrane into the dialyzing fluid.

Dextrose in the dialyzing fluid is used to produce a solution hyperosmolar to the plasma, creating an osmotic gradient which facilitates fluid removal from the patient's plasma

into the peritoneal cavity. After a period of time (dwell time), the fluid is drained by gravity from the cavity.

Indications and Usage

DIALINE Low Calcium peritoneal dialysis solutions are indicated for use in chronic renal failure patients being maintained on peritoneal dialysis.

Contraindications

None known.

Warnings

Peritoneal dialysis should be done with great care, if at all, in patients with a number of abdominal conditions including disruption of the peritoneal membrane or diaphragm by

surgery or trauma, extensive adhesions, bowel distention, undiagnosed abdominal disease, abdominal wall infection, hernias or burns, fecal fistula or colostomy, tense ascites,

obesity, and large polycystic kidneys (Vaamonde and Perez 1977). Other conditions include recent aortic graft replacement and severe pulmonary disease. When assessing

peritoneal dialysis as the mode of therapy in such extreme situations, the benefits to the patient must be weighed against the possible complications.

An accurate fluid balance record must be kept and the weight of the patient carefully monitored to avoid over or under hydration with severe consequences including

congestive heart failure, volume depletion, and shock.

Excessive use of DIALINE peritoneal dialysis solution with 4.25% Dextrose during a peritoneal dialysis treatment can result in significant removal of water from the

patient.

Stable patients undergoing maintenance peritoneal dialysis should have routine periodic evaluation of blood chemistries and hematologic factors, as well as other indicators of

patient status.

Dialine Low Calcium PDS 28. 5. 2012, RH

In some patients calcium carbonate is used as a phosphate binder. Because serum calcium levels have been observed to be elevated in these patients (Slatopolsky et al.

1986), the calcium concentration of DIALINE Low Calcium peritoneal dialysis solutions have been appropriately reduced to 2.5 mEq/L. Serum calcium levels should be

monitored and if low, the amount of oral calcium carbonate phosphate binder may be increased or peritoneal dialysis solutions containing higher calcium concentrations may

be used. If serum calcium levels rise, adjustments to the dosage of the calcium carbonate phosphate binder and/or vitamin D analogs should be considered by the physician.

Because average plasma magnesium levels in some chronic CAPD patients have been observed to be elevated (Nolph et al. 1981), the magnesium concentration of this

formulation has been reduced to 0.5 mEq/L. Average plasma magnesium levels have not been reported for chronic IPD and CCPD patients. Serum magnesium levels should

be monitored and if low, oral magnesium supplements, oral magnesium containing phosphate binders, or peritoneal dialysis solutions containing higher magnesium

concentrations may be used.

Because average serum bicarbonate levels in some chronic CAPD patients (Nolph et al. 1981), some chronic IPD patients (La Greca et al. 1980), and some chronic CCPD

patients (Diaz-Buxo et al. 1983), have been observed to be somewhat lower than normal values, the bicarbonate precursor (lactate) concentration of DIALINE Low Calcium

peritoneal dialysis solutions has been raised to 40 mEq/L. Serum bicarbonate levels should be monitored.

Not for use in the treatment of lactic acidosis.

Potassium is omitted from DIALINE Low Calcium peritoneal dialysis solutions because dialysis may be performed to correct hyperkalemia. Addition of potassium chloride

should be made after careful evaluation of serum and total body potassium, and only under the direction of a physician.

The use of 5 liters of dialysis solutions is not indicated in a single exchange.

Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique. Mix thoroughly. Do not store.

Refer to manufacturer's directions accompanying drugs to obtain full information on additives.

If the resealable rubber plug on the medication port is missing or partially removed, do not use product if medication is to be added.

After removing overpouch, check for minute leaks by squeezing container firmly. If leaks are found, discard the solution because the sterility may be impaired.

Freezing of solution may occur at temperatures below 0

C (32

F). Allow to thaw naturally in ambient conditions and thoroughly mix contents by shaking.

Precautions

Aseptic technique must be used throughout the procedure and at its termination in order to reduce the possibility of infection. If peritonitis occurs, the choice and dosage of

antibiotics should be based upon the results of identification and sensitivity studies of the isolated organism(s) when possible. Prior to identification of the involved organism(s),

broad-spectrum antibiotics may be indicated.

Significant losses of protein, amino acids and water soluble vitamins may occur during peritoneal dialysis. Replacement therapy should be provided as necessary.

Dialine Low Calcium PDS 28. 5. 2012, RH

Pregnancy: Teratogenic Effects

Pregnancy Category C. Animal reproduction studies have not been conducted with DIALINE Low Calcium peritoneal dialysis solutions. It is also not known whether DIALINE

Low Calcium peritoneal dialysis solutions can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. DIALINE Low Calcium peritoneal

dialysis solutions should be given to a pregnant woman only if clearly needed.

Do not administer unless solution is clear and seal is intact.

Adverse Reactions

Adverse reactions to peritoneal dialysis include mechanical and solution related problems as well as the results of contamination of equipment or improper technique in

catheter placement. Abdominal pain, bleeding, peritonitis, subcutaneous infection around a chronic peritoneal catheter, catheter blockage, difficulty in fluid removal, and ileus

are among the complications of the procedure. Solution related adverse reactions may include electrolyte and fluid imbalances, hypovolemia, hypervolemia, hypertension,

hypotension, disequilibrium syndrome, and muscle cramping.

When prescribing the solution to be used for an individual patient,

consideration should be given to the potential interaction between the dialysis treatment and therapy directed at other existing illnesses. For example, rapid potassium removal

may create arrhythmias in cardiac patients using digitalis or similar drugs; digitalis toxicity may be masked by elevated potassium or magnesium, or by hypocalcemia.

Correction of electrolytes by dialysis may precipitate signs and symptoms of digitalis excess. Conversely, toxicity may occur at suboptimal dosages of digitalis if potassium is

low or calcium high. Azotemic diabetics require careful monitoring of insulin requirements during and following dialysis with dextrose containing solutions.

Dosage and Administration

DIALINE Low Calcium peritoneal dialysis solutions are intended for intraperitoneal administration only.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. whenever solution and container permit.

The mode of therapy (Intermittent Peritoneal Dialysis [IPD], Continuous Ambulatory Peritoneal Dialysis [CAPD], or Continuous Cyclic Peritoneal Dialysis [CCPD]), frequency of

treatment, formulation, exchange volume, duration of dwell, and length of dialysis should be selected by the physician responsible for and supervising the treatment of the

individual patient.

To avoid the risk of severe dehydration and hypovolemia and to minimize the loss of protein, it is advisable to select the peritoneal dialysis solution with the lowest level of

osmolarity consistent with the fluid removal requirements for that exchange.

Heating the dialysis solution to 37

C (98.6

F) may decrease discomfort and heat loss and result in increased clearances of urea when compared to solutions at room

temperature (Gross and McDonald 1967).

The addition of heparin to the dialysis solution may be indicated to aid in prevention of catheter blockage in patients with peritonitis, or when the solution drainage contains

fibrinous or proteinaceous material (Ribot et al. 1966). 1000 to 2000 USP units of heparin per liter of solution has been recommended for adults (Furman et al. 1978). For

children, 50 units of heparin per 100 mL of dialysis fluid has been recommended (Irwin et al. 1981).

Additives may be incompatible. Complete information is not available. Those additives known to be incompatible should not be used. Consult with pharmacist, if available. If, in

the informed judgment of the physician, it is deemed advisable to introduce additives, use aseptic technique. Mix thoroughly when additives have been introduced. Do not store

solutions containing additives.

Dialine Low Calcium PDS 28. 5. 2012, RH

Intermittent Peritoneal Dialysis (IPD)

For maintenance dialysis of chronic renal failure patients.

The cycle of instillation, dwell and removal of dialysis fluid is repeated sequentially over a period of hours (8 to 36 hours) as many times per week as indicated by the condition

of the patient. For chronic renal failure patients, maintenance dialysis is often accomplished by periodic dialysis (3 to 5 times weekly) for shorter time periods (8 to 14 hours per

session) (Mattocks and El Bassiouni 1971).

Continuous Ambulatory Peritoneal Dialysis (CAPD) and Continuous Cyclic Peritoneal Dialysis (CCPD).

For maintenance dialysis of chronic renal failure patients.

In CAPD, typically 1.5 to 3.0 liters of dialysis solution (depending upon patient size) are instilled into the peritoneal cavity of adults and the peritoneal access device is then

clamped (Kim et al. 1984; Twardowski and Janicka 1981; Twardowski and Burrows1984). For children, 30 to 50 mL/kg body weight with a maximum of 2 liters has been

recommended (Potter et al. 1981; Irwin et al. 1981). The solution remains in the cavity for dwell times of 4 to 8 hours during the day and 8 to 12 hours overnight. At the

conclusion of each dwell period, the access device is opened, the solution drained and fresh solution instilled. The procedure is repeated 3 to 5 times per day, 6 to 7 days per

week. Solution exchange volumes and frequency of exchanges should be individualized for adequate biochemical and fluid volume control (Moncrief et al. 1982; Twardowski et

al. 1983). The majority of exchanges will utilize 1.5% or 2.5% dextrose containing peritoneal dialysis solutions, with 3.5% or 4.25% dextrose containing solutions being used

when extra fluid removal is required. Patient weight is used as the indicator of the need for fluid removal (Popovich et al. 1978).

In CCPD, the patient receives 3 or 4 dialysis exchanges during the night which range from 2-1/2 to 3 hours dwell duration. Typically 1.5 to 2.0 liters of dialysis solution

(depending upon patient's size) are delivered each cycle by an automatic peritoneal dialysis cycler machine. After the last outflow during the night, an additional exchange is

infused by the cycler machine into the peritoneum. The equipment is then disconnected from the patient, and the dialysate remains in the peritoneum for 14 to 15 hours during

the day until the next nocturnal cycle (Diaz-Buxo et al. 1981). Combinations of 1.5% or 2.5% dextrose containing peritoneal dialysis solutions are usually used for the nighttime

exchanges, while 3.5% or 4.25% dextrose containing solution is used when extra fluid removal is required such as during the daytime exchange. Patient weight is used as the

indicator of the need for fluid removal (Popovich et al. 1978) so therapy should be individualized according to the patient's need for ultrafiltration.

It is recommended that adult patients being placed on peritoneal dialysis or, in the case of pediatric patients, the selected caretaker, (as well as the patient, when suitable),

should be appropriately trained in a program which is under the supervision of a physician.

How Supplied

DIALINE Low Calcium peritoneal dialysis solutions in plastic containers are available in nominal size containers with fill volumes as indicated in Table 1.

All DIALINE Low Low Calcium peritoneal dialysis solutions have overfills which are declared on container labelling.

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended the product be stored at room temperature (25

C, 77

F); brief

exposure up to 40

C does not adversely affect the product.

Dialine Low Calcium PDS 28. 5. 2012, RH

Directions for use

Use aseptic technique.

For complete system preparation, see directions accompanying ancillary equipment.

Warming the DIALINE Low Calcium peritoneal dialysis solution if desired should be done in the overpouch using dry heat only. For patient comfort, the solution should be at

body temperature (37

C; 98.6

F). The solution container should be comfortably warm to the touch. Exceeding 45

C (113

F) solution temperature may be detrimental to the

solution; do not overheat. If the warming method itself exceeds 45

C (113

F), frequently check the solution container and remove it from the heat source when the container

becomes warm to the touch.

To Open

Do not remove units from overwrap until ready for use. Use all units promptly when pouch is opened. The overwrap is a moisture barrier. The inner bag maintains the sterility of

the product.

Tear overpouch down side at slit and remove solution container. Check for minute leaks by squeezing inner bag firmly, if leaks are found, discard solution as sterility may be

impaired. If supplemental medication is desired follow directions below before preparing for administration.

To Add Medication

Additive may be incompatible.

If the resealable rubber plug on the medication port is missing or partially removed, do not use product if medication is to be added.

Prepare medication site.

Using a syringe with a 1 inch long 19 to 25 gauge needle, puncture resealable medication port and inject.

Position container with ports up and evacuate the medication port by squeezing and tapping it.

Mix solution and medication thoroughly.

Preparation for Administration

1. Place container on table or suspend from support (depending on technique).

2. Remove protector from outlet port of container. If a continuous fluid flow is noted, discard container.

3. Attach appropriate solution transfer set to container. Refer to complete directions in hardware manual or directions accompanying transfer set.

4. To establish fluid flow from the DIALINE LOW CALCIUM solution container, grasp the tubing over the frangible seal with one hand and the outlet port connector with the

other hand. See figure 1. Break the frangible seal by bending 90

in one direction, then 180

in the opposite direction. Move the broken end of the frangible seal back into

the tubing approximately 3 mm (1/8 inch) by regrasping a short distance behind thefrangible seal and again bending the frangible seal 90

in one direction, then 180

in the

opposite direction. See Figure 2.

5. If container has not been suspended, suspend at this time.

6. Check for flow of solution through the solution transfer set and frangible closure tubing area. If solution flow is not visualized or air bubbles are seen in the frangible closure

or connector area, gently squeeze the solution container to start solution flow and/or dislodge air bubbles.

Discard unused portion.

Dialine Low Calcium PDS 28. 5. 2012, RH

References

Diaz-Buxo, J.A. et al. 1981. Continuous cyclic peritoneal dialysis: a preliminary report. Int Soc Artif Organs 81:157-161.

Diaz-Buxo, J.A. et al. 1983. Observations on inadequate base buffer concentrations in peritoneal dialysis solutions. ASAIO Abstracts 43.

Furman, K.I. et al. 1978. Activity of intraperitoneal heparin during peritoneal dialysis. Clin Nephrol 9:15-18.

Gross, M. and McDonald, Jr., H.P. 1967. Effect of dialysate temperature and flow rate on peritoneal clearance. JAMA 202:363-365.

Irwin, M.A. et al. 1981. Continuous ambulatory peritoneal dialysis in pediatrics. AANNT J 8:11-13,44.

Kim, D. et al. 1984. Continuous ambulatory peritoneal dialysis with three-liter exchanges: a prospective study. Peritoneal Dial Bull 4:82-85.

La Greca, G. et al. 1980. Acid base balance on peritoneal dialysis. Clinical Nephrology 16(1):1-6.

Mattocks, A.M. and El-Bassiouni, E.A. 1971. Peritoneal dialysis: a review. J Pharm Sci 60:1767-1782.

Moncrief, J.W. et al. 1982. CAPD: Are three exchanges per day adequate? AANNT J 9:39-43

Nolph, K.D. et al. 1981. Considerations for dialysis solution modifications. In Peritoneal Dialysis, eds. Robert C. Atkins et al. Chapter 25. New York: Churchill Livingston.

Popovich, R.P. et al. 1978. Continuous ambulatory peritoneal dialysis. Ann Intern Med 8:449-456

Potter, D.E. et al. 1981. Continuous ambulatory dialysis (CAPD) in children. Trans Am Soc Artif Intern Organs 27:64-67.

Ribot, S. et al. 1966. Complications of peritoneal dialysis. Am J Med Sci 252:505-517.

Slatopolsky, E. et al. 1986. Calcium carbonate as a phosphate binder in patients with chronic renal failure undergoing dialysis. NEJM 3:315, 157-160.

Twardowski, Z.J. and Janicka, L. 1981. Three exchanges with a 2.5 liter volume for continuous ambulatory peritoneal dialysis. Kidney Int 20:281-284.

Twardowski, Z.J. et al. 1983. High volume, low frequency continuous ambulatory peritoneal dialysis. Kidney Int 23:64-70.

Twardowski, Z.J. and Burrows. L. 1984. Two year experience with high volume, low frequency continuous ambulatory peritoneal dialysis. Peritoneal Dial Bull 4:S67.

Vaamonde, C.A. and Perez, G.O. 1977. Peritoneal dialysis today. Kidney 10:31-36.

Dialine Low Calcium PDS 28. 5. 2012, RH

Table 1

COMPOSITION/100 mL

ION CONCENTRATION (mEq/L)

Dextrose

Hydrous,

Sodium

Chloride,

(NaCl)

Sodium

Lactate

NaO3)

Calcium

Chloride, USP

(CaCl

Magnesium

Chloride

(MgC

Osmolarity

(mOsmol/L

(calc.)

Sodium

Calcium

Magnesium

Chloride

Lactate

Dialine

Calcium

Peritoneal

Dialysis

Solution with

1.5% Dextrose

and 2.5 mEq./L

Calcium

1.5 g.

538 mg

448 mg

18.3 mg

5.08 mg

(4.0-

6.5)

Dialine

Calcium

Peritoneal

Dialysis

Solution with

2.5% Dextrose

and 2.5 mEq./L

Calcium

2.5 g.

538 mg

448 mg

18.3 mg

5.08 mg

(4.0-

6.5)

Dialine

Calcium

Peritoneal

Dialysis

Solution with

4.25% Dextrose

and 2.5 mEq./L

Calcium

4.25 g.

538 mg

448 mg

18.3 mg

5.08 mg

(4.0-

6.5)

Dialine Low Calcium PDS 28. 5. 2012, RH

Registration Numbers:

Dialine

Low Calcium Peritoneal Dialysis Solution with 1.5% Dextrose: 056 81 27028 00.

Dialine

Low Calcium Peritoneal Dialysis Solution with 2.5% Dextrose.: 057 34 27327 00.

Dialine

Low Calcium Peritoneal Dialysis Solution with 4.25% Dextrose: 056 82 27333 00.

Manufactured by

Teva Medical Ltd.

P.O. Box 2, Ashdod 77100, Israel