Actidose

Actidose® WITH SORBITOL

Actidose®-AQUA

ACTIVATED CHARCOAL SUSPENSION

Actidose® with Sorbitol: Actidose® with Sorbitol, ready-to-use activated charcoal suspension with sorbitol, contains 25 gm or 50 gm of activated charcoal, and 48 gm or 96 gm of sorbitol, respectively, in an aqueous suspension with a unique preservative system. Each milliliter contains 208 mg (0.208 gm) of activated charcoal and 400 mg (0.400 gm) of sorbitol. Sorbitol reduces the gritty sensation associated with activated charcoal, imparts a sweet taste which enhances patient compliance, and usually produces a cathartic effect.

Actidose®-Aqua: Actidose®-Aqua, ready-to-use activated charcoal suspension, contains 15 gm, 25 gm or 50 gm of activated charcoal in an aqueous suspension with a unique preservative system. Each milliliter contains 208 mg (0.208 gm) of activated charcoal.

If patient has been given ipecac syrup, DO NOT give Actidose® WITH SORBITOL or Actidose®-AQUA until after last vomiting episode. Do not use in persons who are not fully conscious. Do not use this product unless directed by a health professional, if turpentine, corrosives, such as alkalies (lye) and strong acids, or petroleum distillates, such as kerosene, gasoline, paint thinner, cleaning fluid or furniture polish, have been ingested. This product is not recommended for use in children weighing less than 32 kg, or during multiple dose activated charcoal therapy since excessive catharsis and significant fluid and electrolyte abnormalities may occur.

Keep this and all drugs out of the reach of children.

Do not use Actidose® with Sorbitol or Actidose®-Aqua in any person known to have a rare autosomal recessive genetic intolerance to fructose. Do not use Actidose® with Sorbitol in patients who are dehydrated. Actidose® with Sorbitol may cause excessive diarrhea.

Activated Charcoal:

Activated charcoal is produced by pyrolysis of organic material, such as wood, and an activation process which cleanses and fragments the charcoal by exposure to an oxidizing gas compound of steam, oxygen, and acids at high temperatures resulting in increased surface area through the creation of numerous external and internal pores. These pores serve as reservoirs to adsorb substances admixed with activated charcoal, making it a useful adsorbent for specified toxins.

Activated charcoal is pharmacologically inert and is not absorbed in the gastrointestinal tract. Activated charcoal will adsorb a variety of organic and inorganic substances, but is especially effective in adsorbing compounds within a molecular weight range of 100 to 1,000 Daltons (AMU’s).1 Several other physiologic and physicochemical factors influence the adsorptive capacity of activated charcoal including: pH, charcoal: drug ratio, gastric contents, and adsorption kinetics.2

Much of the published scientific literature which studied the adsorptive capacity of activated charcoal was conducted using in vitro models. A considerable amount of the research may be invalid since the effects of physiologic pH were not taken into consideration or held constant. Using research models which simulate the gastric environment, some toxins were not adsorbed by activated charcoal. This data was inappropriately extended to imply that activated charcoal did not adsorb a toxin and therefore had no efficacy in the management of that type of poisoning incident. However, the research failed to consider that the increased pH of the small intestine provides a receptive environment for the adsorption of the toxin by activated charcoal. Activated charcoal will effectively adsorb acidic, alkaline and neutral substances (not to suggest use of activated charcoal in poisonings caused by corrosive agents2). The extent of adsorption will be dependent upon the relative solubility of the drug at a specified pH.

The optimal dosage ratio of activated charcoal to toxin is described as 10:1.3,4,17,18 Numerous factors contribute to and interfere with adsorptive capacity, therefore, the 10:1 ratio may not be valid in the clinical setting. Furthermore, a primary application of activated charcoal is in adult patients who have intentionally ingested a toxin for drug abuse or suicidal purposes. These patients may not freely provide information about the substance or amount ingested, or have a decreased level of consciousness. Under these conditions it is difficult to determine the ingestion history, making it impractical to use the 10:1 ratio. The 10:1 ratio is also impractical when large amounts of toxin have been ingested (i.e., an overdose of 50 gm of aspirin would then require 500 gm [1.1 lbs.] of activated charcoal).

Gastric contents may also compete with ingested toxins and compromise the adsorption of the toxins by activated charcoal.2 If activated charcoal is to be administered to a patient known to have ingested a large meal in close proximity to the time of treatment, a larger dose of activated charcoal may be appropriate.

Under appropriate physiologic conditions activated charcoal adsorbs toxins instantaneously. This adsorptive process is reversible and an equilibrium between free and bound toxin will exist. According to the law of mass action the amount of free drug decreases as the dose of activated charcoal increases. Therefore, large doses of activated charcoal can favor the equilibrium toward greater toxin adsorption and efficacy. There is limited evidence that desorption of a toxin from activated charcoal may occur.19 Therefore, there is a potential for toxin readsorption and enhanced toxicity. The current standard of care is to administer a cathartic with single doses of activated charcoal to hasten the elimination of the toxin/activated charcoal complex from the gastrointestinal tract.5 Cathartics should be used with extreme care during multiple dose activated charcoal therapy and it is not recommended to use a cathartic with each dose of activated charcoal.5

Sorbitol:

Sorbitol is a hexahydric sugar alcohol which primarily serves as an osmotic cathartic in Actidose® with Sorbitol.6 A secondary advantage of using sorbitol is as a palatability enhancer to decrease the innate gritty texture of activated charcoal and to provide a sweet vehicle to increase patient compliance. Sorbitol is poorly absorbed during its transit through the gastrointestinal tract. Absorbed sorbitol is metabolized by the liver and slowly converted to fructose. Insulin is not necessary for intracellular transport of sorbitol, therefore customary cathartic doses can be safely used by patients with diabetes mellitus.

As a hyperosmotic cathartic sorbitol produces a hygroscopic action resulting in increased water in the large intestine and increased intraluminal pressure which stimulates catharsis. Studies have been conducted in healthy adult human volunteers using therapeutic amounts of activated charcoal and sorbitol.8,9 Catharsis of activated charcoal occurred in an average of 1.0 - 1.5 hours and persisted for 8 - 12 hours. Fourteen poisoned patients are reported in one series representing a wide range of toxins and dosages of sorbitol resulting in the onset of catharsis in an average of 7.7 hours.10 The onset of action may be expected to be longer in patients who have ingested toxins which decrease bowel motility, such as pharmacological agents and plants with anticholinergic properties, and drugs like narcotics.20

Sorbitol does not compromise the adsorptive capacity of activated charcoal.11, 12

Activated charcoal with sorbitol has produced severe hypernatremic dehydration when used in excessive amounts in pediatric patients.25, 27

Aspiration of activated charcoal has been reported to produce airway obstruction and a limited number of fatalities have occurred. 28,29,30,31 Bronchiolitis obliterans resulting in death has developed several weeks after the aspiration of activated charcoal.32

Gastrointestinal obstruction associated with the use of multiple dose activated charcoal therapy has been reported.33 An overdose of carbamazepine was responsible for the antiperistaltic effects which led to bowel obstruction.

NDC 0574-0121-76

Actidose®-AQUA

ACTIVATED CHARCOAL SUSPENSION

50 grams Activated Charcoal

STORE ON SIDE

SHAKE WELL BEFORE USING

CONTENTS: 240 mL (8 fl oz)

Emergency Phone Number:

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dark stools.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Applies to charcoal: compounding powder, oral capsule, oral delayed release tablet, oral granule for reconstitution, oral powder for reconstitution, oral suspension, oral tablet

Gastrointestinal

Gastrointestinal side effects have frequently included nausea and vomiting (13% to 30%) and constipation. Bowel obstruction, ileus, chalk like taste, perforation of the gastrointestinal tract and subsequent charcoal peritoneum, and black colored stools have also been reported.[Ref]

A young woman developed a surgically acute abdomen following orogastric lavage and charcoal administration. Laparotomy revealed charcoal throughout the peritoneum. Complications included peritonitis, adhesions, abscess formation, persistent peritoneal charcoal deposits, oophorectomy, and small bowel resection.

A case report has described charcoal bezoar and small bowel obstruction following administration of 30 to 60 g of activated charcoal via nasogastric tube every 4 to 6 hours for 5 days.

In a study of 275 patients, 18 years old or younger, 20.4% (56/275) experienced vomiting within < 1 to 120 minutes (mean of 10 minutes) following enteral administration of 1 g/kg (no more than 50 g) of activated charcoal for acute poison ingestion. The following risk factors for vomiting were identified: nausea, a vomiting occurrence prior to charcoal ingestion, presence of signs or symptoms of poisoning (exclusive of nausea &/or vomiting), age greater than 12 years, administration by nasogastric or orogastric tube, and ingestion of emetogenic drug or chemical.

Bowel obstruction and ileus have occurred with multiple-dose administration.

Although charcoal is tasteless, it adheres to the surfaces of the mouth and tongue, producing a chalk like taste that can be unpalatable.[Ref]

Metabolic

Metabolic side effects have included hypernatremia, hypermagnesemia. electrolyte abnormalities, dehydration, and shock.[Ref]

Metabolic side effects occur primarily when sorbitol is combined with charcoal. Multiple-dose activated charcoal has been associated with hypernatremia and hypermagnesemia.[Ref]

Respiratory

Respiratory side effects have included bronchiolitis obliterans, empyema, and Adult Respiratory Distress Syndrome.[Ref]

Bronchiolitis obliterans and empyema have occurred due to charcoal aspiration following emesis.

Accidental administration of charcoal directly into the lungs has resulted in Adult Respiratory Distress Syndrome.[Ref]

Ocular

Ocular side effects have included corneal abrasions.[Ref]

Corneal abrasions may occur if charcoal comes in contact with eyes.[Ref]

Hematologic

Exacerbation of variegate porphyria may lead to increases in skin lesions, and urine and plasma porphyrins.[Ref]

Hematologic side effects have included exacerbation of variegate porphyria.[Ref]

Some side effects of charcoal may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For gastrointestinal decontamination, time since ingestion is a critical criterion in the decision to use charcoal for decontamination purposes. Typically, the recommended cutoff point for administration of charcoal for gastrointestinal decontamination is 1 to 2 hours post- ingestion. However, in cases where the ingested agent has anticholinergic activity (e.g., tricyclic antidepressants) or can slow the rate of gastric emptying by another mechanism (e.g., pentazocine, meperidine) then use of charcoal beyond 2 hours may still be beneficial.