Talc (Intrapleural-Local)


VA CLASSIFICATION
Primary: IP100

Commonly used brand name(s): Sclerosol.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Sclerosing agent, intrapleural—

Indications

Accepted

Pleural effusions, malignant, recurrence (prophylaxis)—Talc intrapleural aerosol is indicated to prevent recurrence of malignant pleural effusions in symptomatic patients. It is administered during thoracoscopy or open thoracotomy. {01}

Note: Talc has no antineoplastic activity and is not recommended for treating malignant pleural effusions associated with potentially curable malignancies (e.g., malignant effusions secondary to a potentially curable lymphoma), for which systemic therapy would be more appropriate. {01}



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    A naturally occurring substance. {01}

Note: Talc contains ³ 95% hydrated magnesium silicate, with small quantities of other naturally occurring minerals including chlorite (hydrated aluminum and magnesium silicate), dolomite (calcium and magnesium carbonate), calcite (calcium carbonate), and quartz. The grade of talc used in the intrapleural aerosol formulation is asbestos-free and brucite-free, and the granule size is controlled and uniform. Also, the talc and container have been sterilized. {01}

Molecular weight—
    Magnesium silicate, hydrous: 379.3 {01}

Solubility
    Practically insoluble in water and in dilute solutions of acids or alkali hydroxides. {01}

Mechanism of action/Effect:

Talc is believed to act in the pleural cavity by inducing an inflammatory reaction that results in sclerosis and in pleurodesis (adherence of the visceral to the parietal pleura), which obliterates the pleural space and prevents reaccumulation of pleural fluid. {01}

Absorption:

The extent of systemic absorption after application to the pleura has not been studied adequately, but may be affected by the integrity of the visceral pleura. Therefore, systemic exposure could be increased if the medication is administered immediately following lung resection or biopsy. {01}


Precautions to Consider

Carcinogenicity

Studies performed to date have used non-standard designs, which prevents firm conclusions regarding any potential carcinogenicity of talc. Also, the composition of the talc used in these studies (including asbestos content) was not characterized. {01}

Tumorigenicity

No increase in tumor development was found in studies in mice observed for at least 6 months after being given single 20-mg intraperitoneal doses or in studies in rats observed for at least 84 weeks after being given four 25-mg intraperitoneal doses at one-week intervals. The composition of the talc used in these studies (including any asbestos content) was not characterized. {01}

Mutagenicity

Genotoxicity studies, performed in cultured rat pleural mesothelial cells with asbestos-free talc, did not reveal enhancement of unscheduled DNA synthesis or sister chromatid exchanges. {01}

Pregnancy/Reproduction

Pregnancy—
Adequate and well-controlled studies in humans have not been done. Risk-benefit should be considered. {01}

Studies in rabbits given oral doses of 900 mg per kg of body weight (approximately five-fold higher than the human dose on a mg per square meter of body surface area basis) found no evidence of teratogenicity. {01}

FDA Pregnancy Category B. {01}

Pediatrics

Safety and efficacy in pediatric patients have not been established. {01}


Geriatrics


Evaluation of the relationship of age to the effects of talc in geriatric patients has not been done. The mean and median ages of patients in clinical trials with intrapleural talc ranged between 50 and 62 years. {01}

Surgical

The possibility should be considered that talc-induced sclerosis may complicate or preclude performance of future surgical or diagnostic procedures involving the treated hemithorax (e.g., ipsilateral lung resective surgery, including pneumonectomy for transplantation purposes). {01}


Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Diagnostic procedures involving the treated hemithorax    (the possibility should be considered that talc-induced sclerosis may interfere with future diagnostic procedures {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to talc{01}


Side/Adverse Effects

Note: Intravenously administered talc is known to cause pulmonary hypertension and pulmonary lung parenchymal disease, but these complications have not been reported with intrapleural administration. Also, talc inhalation has been associated with the development of pulmonary complications such as silicosis, asbestosis-like diseases, chronic bronchitis, bronchogenic carcinoma, and pleural plaques. {01}
In addition to the adverse effects listed below, acute pneumonitis and acute respiratory distress syndrome (ARDS) have been reported rarely, after intrapleural talc administration. However, a causal relationship has not been established. Talc was not applied thoracoscopically or via insufflation in any of the reported cases. Most cases of ARDS occurred after administration of 10 grams of talc via intrapleural chest tube instillation. {01}
In addition to the adverse effects listed below, cardiovascular complications including asystolic arrest, hypotension, hypovolemia, myocardial infarction, and tachycardia have been reported, rarely, and have been attributed to the surgical procedure and/or anesthesia used at the time of talc delivery rather than to the medication itself. Other adverse effects associated with the delivery procedure or other procedures performed at the time of talc administration (e.g., biopsy) include infection at the site of thoracostomy or thoracoscopy, fever, localized bleeding, and subcutaneous emphysema. {01}
One study comparing the long-term effects of treating idiopathic spontaneous pneumothorax with talc poudrage or only drainage via an intercostal tube found no significant differences between the groups in lung function as assessed 22 to 35 years later by standard pulmonary function tests. Also, none of the patients had developed mesothelioma. However, two patients treated with talc had extensive pleural thickening with calcification, and the mean total lung capacities were lower in the talc group (89% of predicted capacity) than in the drainage only group (96% of predicted capacity). {01}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Pain{01}

Note: In clinical trials, more than half of the cases of pain occurred in patients who received diagnostic biopsies at the time of talc administration. {01}


Incidence rare
    
Dyspnea{01} (shortness of breath)
    
empyema{01} (fever; shortness of breath or troubled breathing)
    
hemoptysis{01} (coughing or spitting up blood)
    
pulmonary complications, including bronchopleural fistula{01} and pulmonary emboli{01} (shortness of breath or troubled breathing)

Note: In clinical trials, more than half of the cases of empyema occurred in patients who received diagnostic biopsies at the time of talc administration. {01}






Overdose
For more information on the management of overdose, contact a Poison Control Center (see Poison Control Center Listing ).

No cases of overdose have been reported, but the possibility of an increased risk of pulmonary complications should be considered if an excessive quantity is administered. {01}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Talc (Intrapleural-Local) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to talc

Proper use of this medication

» Proper dosing


Side/adverse effects
Signs of potential side effects, especially pain, dyspnea, empyema, hemoptysis, and other pulmonary complications


General Dosing Information
Talc is administered during thoracoscopy or open thoracotomy. The delivery tube (provided in the package) is affixed to the canister, then inserted through the pleural trocar. Care must be taken not to place the distal end of the delivery tube directly against the chest wall or adjacent to the parenchyma of the lung. {01}

Talc is administered after the effusion has been adequately drained. Successful treatment depends on even distribution of talc over the pleural surface, the completeness of pleural fluid drainage, and full re-expansion of the lung, all of which promote symphysis of the pleural surfaces. {01}


Intrapleural Dosage Forms

TALC INTRAPLEURAL AEROSOL (POWDER)

Usual adult dose
Prevention of recurrence of malignant pleural effusions
Intrapleural, via delivery tube inserted through the pleural trocar, 4 to 8 grams (one or two canisters). {01}

Note: To ensure that the talc is distributed equally and extensively over all visceral and parietal pleural surfaces, the total dose should be administered in several short bursts, given with the delivery tube pointing in different directions. Also, the canister should be kept in an upright position during administration. {01}
The spray valve delivers talc at a rate of approximately 0.4 grams per second, but the medication is not delivered as a metered dose. Delivery depends on the extent and duration of manual compression of the actuator button. {01}
The duration of chest drainage after talc administration depends on the clinical situation. {01}



Usual pediatric dose
Safety and efficacy have not been established. {01}

Size(s) usually available:
U.S.—


4 grams per single-use canister (Rx) [Sclerosol (pressurized canister, packaged together with two delivery tubes 15 and 25 cm in length) (dichlorodifluoromethane [CFC-12] 26 grams per canister [inert propellant])]

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), protected against direct sunlight and from freezing. Must not be exposed to temperatures higher than 49 °C (120 °F). {01}

Preparation of dosage form:
Talc intrapleural aerosol is prepared for administration by shaking the canister well, removing the protective cap, and securely attaching the actuator button with the selected delivery tube (either 15 or 25 cm in length) to the valve stem. {01}

Auxiliary labeling:
   • Shake well.


Caution:
Contents are under pressure. The container must not be punctured or incinerated. {01}

The propellant, CFC-12, harms public health and the environment by destroying ozone in the upper atmosphere. {01}



Revised: 08/06/1998



References
  1. Sclerosol package insert (Bryan—U.S.), undated, Rec. 2/15/98.
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