Talc

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)

3. DOSAGE FORMS AND STRENGTHS White or off-white to light gray sterile powder provided in the following strengths: Powder, for intrapleural use: STERITALC, 2 grams in a 50 mL single-dose vial Powder, for intrapleural use: STERITALC, 4 grams in a 50 mL single-dose vial Powder, for intrapleural use: STERITALC, 3 grams in a 10 mL single-dose vial, for use with Novatech SA’s NOVATECH® TALCAIR™ _______ DOSAGE FORMS AND STRENGTHS_ ______ Powder: 2 grams, in a 50 mL single-dose vial (3) Powder: 4 grams, in a 50 mL single-dose vial (3) Powder: 3 grams, in a 10 mL single-dose vial (3)

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)

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 [see DESCRIPTION (11)]. _ ______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)

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.

8. USE IN SPECIFIC POPULATIONS

8.1 Pregnancy Risk Summary STERITALC is contraindicated for use in pregnant women because it contains lead, which can cause fetal harm and potential loss of pregnancy [see Warnings and Precautions (5.3)] . There are no human data on the use of STERITALC in pregnant women. In an animal reproduction study, oral administration of talc in pregnant rabbits during organogenesis revealed no evidence of teratogenicity at dose up to approximately 5 times the human dose [see Data] . Data Animal Data In an embryo-fetal developmental toxicity study in rabbits, talc was administered to rabbits by oral gavage daily during the period of organogenesis at doses up to 900 mg/kg (approximately 5 times the human dose on a mg/m2 basis). No significant dose-related toxicity was reported except at maternally toxic doses. In multiple animal studies, intrapleurally administered talc was not absorbed systemically.

8.2 Lactation Risk Summary There is no information regarding the presence of talc in human milk, the effects on the breastfed infants, or the effects on milk production. STERITALC contains lead, which is known to have adverse effects on health and development in neonates, infants and children [see Warnings and Precautions (5.3)] . Because of the potential for serious adverse reactions in breast-fed infants from lead content in STERITALC, advise lactating women not to breastfeed during treatment with STERITALC and for 5 months after the final dose.

8.3 Females and Males of Reproductive Potential Contraception STERITALC contains lead, which can cause fetal harm when administered to a pregnant woman [see Warnings and Precautions (5.3) and Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment and for 5 months following the final dose of STERITALC. Infertility STERITALC contains lead, which may impair fertility in males of reproductive potential [see Warnings and Precautions (5.3)].

8.4 Pediatric Use Safety and effectiveness have not been established in pediatric patients. Lead is present in STERITALC as an impurity [see Warnings and Precautions (5.3)]. ————USE IN SPECIFIC POPULATIONS ————– Females and Males of Reproductive Potential: Advise females of reproductive potential to use effective contraception. (8.3) Lactation: Advise women not to breastfeed. (8.2)