Sclerosol

SCLEROSOL- talc aerosol, powder
Bryan Corporation

Prescribing Information

For Intrapleural Administration Only

Shake Well Immediately Before Using

DESCRIPTION

Sclerosol® Intrapleural Aerosol (sterile talc powder 4 g) is a sclerosing agent for intrapleural administration supplied as a single-use, pressurized spray canister with two delivery tubes of 15 cm and 25 cm in length. Each canister contains 4.0 g of talc, either white or off-white to light grey, asbestos-free, and brucite-free grade of talc of controlled granulometry. The composition of the talc is ≥ 95% talc as hydrated magnesium silicate. The empirical formula is Mg3 Si4 O10 (OH)2 with molecular weight of 379.3. Associated naturally occurring minerals include chlorite (hydrated aluminum and magnesium silicate), dolomite (calcium and magnesium carbonite), calcite (calcium carbonate) and quartz. Talc is practically insoluble in water, and in dilute solutions of acids and alkali hydroxides. The canister and delivery tubes have been sterilized by gamma irradiation. The aerosol propellant contained in Sclerosol® Intrapleural Aerosol is dichlorodifluoromethane (CFC-12) with 26 g present per canister. The canister delivers 0.4 g of talc per second through the valve and the product contains no other excipients.

CLINICAL PHARMACOLOGY

Mechanism of Action:

The therapeutic action of talc instilled into the pleural cavity is believed to result from induction of an inflammatory reaction. This reaction promotes adherence of the visceral to the parietal pleura, obliterating the pleural space and preventing reaccumulation of pleural fluid. The extent of talc systemically absorbed after intrapleural administration has not been adequately studied. Systemic exposure could be affected by the integrity of the visceral pleura, and therefore could be increased if talc is administered immediately following lung resection or biopsy.

CLINICAL STUDIES

The data demonstrating safety and efficacy of talc in the treatment of malignant pleural effusions are derived from the published medical literature. The following four trials were prospective, randomized studies of talc vs. a concurrent control, and provide sufficient detail for evaluation, including a clear, readily determined definition of response (no fluid reaccumulation by chest roentgenogram at one month or greater) and information allowing an analysis of all patients randomized. Talc was statistically significantly superior to the control arms in evaluable patients across the studies.

REFERENCE TREATMENT TUMOR RESPONSE RATE INEVALUABLE PTSp value: Fisher’s Exact* RESPONSE RATE INALL PATIENTSp value: Fisher’s Exact* MINIMUMDURATION OF RESPONSE

*p values are two-sided

Sorenson et al.Eur J Respir Dis.1984; 65:131 Talc slurryvsChest tube drainage Variety 100% (9/9)vs58% (7/12)p=0.022 64% (9/14)vs41% (7/17)p=0.285 3 months
Fentiman et al .Eur J Cancer ClinOncol 1986;22:1079 Talc poudragevsTetracycline solution Breast 92% (11/12)vs48% (10/21)p=0.022 61% (11/18)vs43% (10/23)p=0.345 12 months
Fentiman et al .Cancer 1983;52:737 Talc poudragevsMustine solution Breast 90% (18/20)vs53% (9/17)p=0.023 78% (18/23)vs39% (9/23)p=0.016 6 months
Hamed et al .Br. J. Surg1989; 76:1266 Talc poudragevsBleomycin solution Breast 100% (10/10 procedures)vs33% (5/15 procedures)p=0.001 (unclear; results reported as procedures, not patients) ≥1 months

In other studies, greater than 1000 patients with malignant pleural effusions have been reported (with varying degrees of detail and durations of response) to have had successful pleurodesis with talc.

INDICATIONS AND USAGE

Sclerosol® Intrapleural Aerosol, administered by aerosol during thoracoscopy or open thoracotomy, is indicated to prevent recurrence of malignant pleural effusions in symptomatic patients.

CONTRAINDICATIONS

None known.

WARNINGS

None.

PRECAUTIONS

General:

1) Future procedures. The possibility of future diagnostic and therapeutic procedures involving the hemithorax to be treated must be considered prior to administering Sclerosol® Intrapleural Aerosol. Sclerosis of the pleural space may preclude subsequent diagnostic procedures of the pleura on the treated side. Talc sclerosis may complicate or preclude future ipsilateral lung resective surgery, including pneumonectomy for transplantation purposes.

2) Use in potentially curable disease. Talc has no known antineoplastic activity and should not be used for potentially curable malignancies where systemic therapy would be more appropriate, e.g., a malignant effusion secondary to a potentially curable lymphoma.

3) Potential pulmonary complications. Acute pneumonitis or acute respiratory distress syndrome (ARDS) have rarely been reported in association with intrapleural talc administration. Whether these were causally related to talc is unclear. In none of the reported cases was talc applied thoracoscopically or by insufflation. Three of four case reports of ARDS have occurred after treatment with 10 g of talc administered via intrapleural chest tube instillation. One patient died one month post treatment and two patients recovered without further sequelae.

Intravenous administration of talc is a well-recognized cause of pulmonary hypertension and pulmonary lung parenchymal disease, but these complications have not been reported after intrapleural administration. Pulmonary diseases, e.g., silicosis or asbestosis-like diseases, chronic bronchitis, bronchogenic carcinoma, and pleural plaques have been reported in association with inhaled talc.

4) Contents under pressure. The contents of the Sclerosol® Intrapleural Aerosol (sterile talc powder) canister are under pressure. The canister must not be punctured and should not be used or stored near heat or open flame.

Drug Interactions: It is not known whether the effectiveness of a second sclerosing agent after prior talc pleurodesis would be diminished by the absorptive properties of talc.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Studies on the carcinogenicity of talc have been performed using non-standard designs, which prevent firm conclusions on its carcinogenicity. With single intraperitoneal administration to mice at 20 mg and observation for at least 6 months, or 4 weekly doses administered intraperitoneally at 25 mg/dose to rats with observation for at least 84 weeks, tumor incidence was not increased. In these studies, the talc and its asbestos content were not characterized. Genotoxicity was assessed in cultures of rat pleural mesothelial cells (RPMC), as unscheduled DNA syntheses (UDS) and sister chromatid exchanges (SCEs). None of the talc samples (which were asbestos free) enhanced UDS or SCEs in treated cultures. No information is available on impairment of fertility in animals by talc.

Pregnancy: Pregnancy category B. An oral administration study has been performed in the rabbit at 900 mg/kg, approximately 5-fold higher than the human dose on mg/m2 basis, and has revealed no evidence of teratogenicity due to talc. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should not be used during pregnancy unless it is clearly needed.

Pediatric Use: The safety and efficacy of Sclerosol Intrapleural Aerosol® (sterile talc powder) in pediatric patients have not been established.

Geriatric Use: The mean and median ages of patients treated with talc in the clinical studies table were 50-62 years. No analyses to specifically evaluate the safety and efficacy in the geriatric population have been reported.

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