TALC: 933 Adverse Event Reports & Safety Profile

11. DESCRIPTION STERITALC (talc) is a sclerosing agent for intrapleural administration. The molecular formula for talc is Mg3Si4O10(OH)2. The molecular weight is 379.3 g/mole. The chemical name of talc is hydrated magnesium silicate. The talc powder contains ≥ 95% of hydrated magnesium silicate; associated minerals include chlorites (hydrated aluminum and magnesium silicates), magnesite (magnesium carbonate), calcite (calcium carbonate), and dolomite (calcium and magnesium carbonate). The talc elementary sheet is composed of a layer of magnesium-oxygen/hydroxyl octahedra, sandwiched between two layers of silicon-oxygen tetrahedra. Talc is insoluble in water. STERITALC is tested for asbestos and asbestiform fibers consistent with USP standards for talc-containing products. STERITALC is supplied as 2 grams, 3 grams, and 4 grams white or off-white to light gray, sterile powder. STERITALC contains particle size-controlled talc, graded to decrease the proportion of smaller particles.

1.INDICATIONS AND USAGE 1.INDICATIONS AND USAGE

1.1 Malignant Pleural Effusion STERITALC is indicated to decrease the recurrence of malignant pleural effusions in symptomatic patients following maximal drainage of the pleural effusion.

1.2 Pneumothorax STERITALC is indicated in adults to decrease the recurrence of pneumothorax. ___________ INDICATIONS AND USAGE__ __________ STERITALC® is a sclerosing agent indicated: To decrease the recurrence of malignant pleural effusions in symptomatic patients following maximal drainage of the pleural effusion. (1.1) In adults to decrease the recurrence of pneumothorax. (1.2)

2. DOSAGE AND ADMINISTRATION

2.1 Important Use Information STERITALC is for pleurodesis only - Do NOT administer STERITALC intravenously. Administer STERITALC after adequate drainage of the pleural effusion or air.

2.2 Recommended Dose for Malignant Pleural Effusion The recommended dose for malignant pleural effusion is 2 to 5 grams administered intrapleurally. According to the physician’s discretion, and in consideration of diagnosis and patient’s condition, different dosages may be applied, but a total dosage of 10 grams should not be exceeded.

2.3 Recommended Dose for Pneumothorax The recommended dose for pneumothorax is 2 grams administered intrapleurally. According to physician’s discretion and in consideration of diagnosis and patient’s condition, different dosages may be applied, but a cumulative dosage of 10 grams should not be exceeded.

2.4 Preparation Slurry for Tube Thoracostomy STERITALC 2 grams and 4 grams dosage forms Do not prepare the slurry in advance. Use the slurry immediately after preparation. Prepare the talc suspension using aseptic technique in an appropriate laminar flow hood as follows: Step 1 : Fully bend or remove the flap into the direction of the arrow. The top can now be punctured to mix the slurry.

Step

2 : Using a 16 gauge needle attached to a 60-mL Luer Lok syringe, draw up 50 mL of 0.9 % Sodium Chloride injection, USP. Vent the talc bottle using a needle. Slowly inject the 50 mL of 0.9% Sodium Chloride Injection, USP into the glass vial.

Step

3: Swirl the glass vial to disperse the talc powder.

Step

4 : Divide the contents of the glass vial equally into two 60-mL Luer Lok syringes, each attached with a 16 gauge needle, by withdrawing 25 mL of the suspension into each syringe with continuous swirling.

Add

0.9% Sodium Chloride Injection, USP to a total volume of 50 mL in each syringe.

Draw

10 mL of air into each syringe to the 60 mL mark to serve as a headspace for mixing prior to administration. For STERITALC 2 grams, each syringe should contain 1 gram of Sterile Talc Powder in 50 mL of 0.9% Sodium Chloride Injection, USP with an air headspace of 10 mL. For STERITALC 4 grams, each syringe should contain 2 grams of Sterile Talc Powder in 50 mL of 0.9% Sodium Chloride Injection, USP with an air headspace of 10 mL.

Step

5: Label the syringes with the talc concentration, the expiration date and time, the identity of the patient intended to receive the material, and the following statements: “SHAKE SYRINGE WELL to resuspend before administration” “FOR PLEURODESIS ONLY – not for intravenous administration” Step 6: If not used immediately, store prepared suspension in refrigerator. Discard the prepared suspension if not used within 12 hours. Insufflation/Poudrage STERITALC 2 grams and 4 grams dosage forms Use an FDA-approved or cleared device for STERITALC insufflation/poudrage.

Step

1: Fully remove the top from the vial.

Step

2 : Fill the content into the applicator for insufflation/poudrage.

Step

3 : Follow the selected device manufacturer's instructions for insufflation/poudrage. STERITALC 3 grams dosage form STERITALC 3 grams is designed to be used for the administration of talc in combination with a compatible FDA approved or FDA cleared device intended for manual insufflation of medical grade talc into the pleural cavity during pleurodesis such as Novatech SA’s NOVATECH® TALCAIR™.

Step

1 : Remove the aluminum tear-off cap from the vial.

Step

2: Remove the stopper from the vial.

Step

3 : Close the vial with the vial coupling.

Step

4 : Firmly press the vial coupling onto the vial until you feel and hear the lid "click" onto the vial top. To do this, place the vial on a firm and level base.

Step

5 : Connect the insufflation bulb to the vial coupling using the Luer lock connector.

Step

6 : Ensure that all components are firmly connected with each other.

2.5 Administration Slurry for Tube Thoracostomy STERITALC 2 grams and 4 grams dosage forms Prior to administration, continuously agitate the syringes to evenly redisperse the talc and avoid settlement. Immediately prior to administration, vent the 10 mL air headspace from each syringe. Administer the talc suspension through the chest tube according to standard procedures.

Step

1: Inject the slurry through the pleural drainage into the pleural cavity.

Step

2: Clamp the pleural drainage. Keep the negative pressure in the pleural cavity.

Step

3 : While the slurry remains in the pleural cavity, reposition the patient regularly to achieve even distribution of the slurry.

Step

4: Aspirate the slurry through the pleural drainage.

Insufflation/Poudrage

Perform intervention by means of a tube thoracoscopy. Follow the selected device manufacturer's instructions for insufflation/poudrage. STERITALC 2 grams and 4 grams dosage forms Step 1 : Introduce the cannula into the trocar.

Step

2: Distribute the talc evenly in the pleural cavity. To do this, carefully spray several times. After spraying a few times, change the cannula direction. After use, some talc may remain in the vial. Discard unused portion. STERITALC 3 grams dosage form Keep the product upright during use. Avoid contact between the cannula tip and tissue/body fluids. Otherwise the cannula may be blocked. In case of blockage: Shorten the cannula with a scalpel to be able to continue the intervention. Cut perpendicularly to the cannula and ensure that the cutting edge is straight and free of burs.

Step

1: Introduce the cannula into the trocar.

Step

2 : Distribute the talc evenly in the pleural cavity. To do this, press the insufflation bulb carefully and at regular intervals. After spraying a few times, change the cannula direction. After use, some talc may remain in the vial. Discard unused portion ________ DOSAGE AND ADMINISTRATION ________ Malignant Pleural Effusion: The recommended dose is 2 to 5 grams administered intrapleurally. (2.2) Pneumothorax: The recommended dose is 2 grams administered intrapleurally. Do not exceed a total cumulative dosage of 10 grams per procedure. (2.3) Prepare and administer as recommended. (2.5)

4.

Contraindications

Due to lead content, STERITALC® is contraindicated in pregnant women and can cause fetal harm and potential loss of pregnancy [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1)]. _____________ CONTRAINDICATIONS_ ____________ Pregnancy. (4, 5.3, 8.1)

6.

Adverse Reactions

The following clinically significant adverse reactions are described elsewhere in the labeling. Pneumonitis and Acute Respiratory Distress Syndrome (ARDS) [see Warnings and Precautions (5.1)]

Lead

Content [see Warnings and Precautions (5.3)]

Asbestos

Content [see Warnings and Precautions (5.4)] Common adverse reactions observed with intrapleural use of various talc products are fever and pain. Other adverse reactions include dyspnea, arrhythmia, empyema, pneumonitis and acute respiratory distress syndrome (ARDS). Procedure related adverse reactions such as bleeding, hemothorax, wound infections, atelectasis and pneumonia may occur. _____________ ADVERSE REACTIONS _____________ Common adverse reactions are fever and pain. (6) To report suspected adverse reactions contact Boston Medical Product Inc., at 508-898-9300 and FDA at 1-800-332-1088 or www.fda.gov/medwatch.

5. WARNINGS AND PRECAUTIONS

5.1 Pneumonitis and Acute Respiratory Distress Syndrome (ARDS)

Acute

Pneumonitis and ARDS, including fatal cases, have been reported with intrapleural use of various talc products. Systemic exposure of talc could be affected by the integrity of the visceral pleura and could be increased if talc is administered immediately after mechanical abrasion or biopsy of the pleura. The literature also suggests a possible correlation between talc particle size distribution and risk of toxicity. There are published reports of two large, prospective trials conducted to evaluate the safety of STERITALC administered intrapleurally. One trial evaluated 558 patients treated with STERITALC 4g by poudrage for MPE. The second trial evaluated 418 patients with recurrent primary spontaneous pneumothorax treated with STERITALC 2 g by poudrage. No cases of ARDS or talc-related lung injury were reported.

5.2 Interference with Future Procedures Sclerosis of the pleural space may preclude or complicate subsequent ipsilateral surgery and diagnostic procedures. Consider the possible effects of the use of STERITALC on future diagnostic and therapeutic procedures prior to administration.

5.3 Lead Content Lead is present in STERITALC as an impurity. The main target organ for lead toxicity is the nervous system, but effects of lead exposure also include increased blood pressure, anemia, decreased sperm production, and damage to the kidneys in children and adults. Minimal risk levels of lead have not been derived for humans because clear thresholds for effects have not been identified. Children are more sensitive to lead toxicity than adults, and no safe blood level has been determined in children. Cognitive and neurobehavioral deficits are observed in children exposed to lead. Exposure of a pregnant woman to lead may cause miscarriage, premature birth, lower birth weights and slow or impaired mental development in the child. Administration of STERITALC at the highest recommended dose of 10 grams may deliver up to 40 mcg of lead.

5.4 Asbestos Content Talc products may contain trace amounts of asbestos. Asbestos is a known human carcinogen. Exposure to asbestos may increase the risk of mesotheliomas and other cancers including lung, larynx, and ovarian cancer. STERITALC is tested for asbestos and asbestiform fibers <span class="opacity-50 text-xs">[see DESCRIPTION (11)]</span>. _ ______WARNINGS AND PRECAUTIONS _____________ Pneumonitis and Acute Respiratory Distress Syndrome (ARDS): Acute Pneumonitis and ARDS, have been reported with intrapleural use of various talc products. (5.1) Interference with Future Procedures: Sclerosis of the pleural space may preclude or complicate subsequent ipsilateral surgery and diagnostic procedures. (5.2)

Lead

Content: STERITALC® contains lead as an impurity. May cause lead toxicity, especially in children. (5.3)

Asbestos

Content: Talc products may contain trace amounts of asbestos. Exposure to asbestos may increase the risk of mesotheliomas and other cancers. (5.4, 11)