Benzalkonium chloride adverse effects

Many of these reactions are related to the quantity of excipient found in a dosage form. Benzyl alcohol benzalkonium chloride, propylene glycol, lactose, and polysorbates are all associated with dose-related toxic reactions [52-54], Large-volume parenterals containing 1.5% benzyl alcohol as a preservative have caused metabolic acidosis, cardiovascular collapse, and death in low birth weight premature neonates and infants. The cumulative dose of benzyl alcohol ranged from 99 to 234 mg/kg per day in these patients [55,56], Dose-related adverse effects to excipients are of particular concern in the preterm, low birth weight infant because... 

HaUen H, Graf P. Benzalkonium chloride in nasal decon-gestive sprays has a long-lasting adverse effect on the nasal mucosa of healthy volunteers. Clin Exp Allergy 1995 25(5) 401-5. 

Benzalkonium chloride is usually nonirritating, nonsensitizing, and is well tolerated in the dilutions normally employed on the skin and mucous membranes. However, benzalkonium chloride has been associated with adverse effects when used in some pharmaceutical formulations. ... 

Local irritation of the throat, esophagus, stomach, and intestine can occur following contact with strong solutions (>0.1% w/v). The fatal oral dose of benzalkonium chloride in humans is estimated to be 1-3 g. Adverse effects following oral ingestion include vomiting, collapse, and coma. Toxic doses lead to paralysis of the respiratory muscles, dyspnea, and cyanosis. 

At pH 7, tragacanth has been reported to considerably reduce the efficacy of the antimicrobial preservatives benzalkonium chloride, chlorobutanol, and methylparaben, and to a lesser extent that of phenol and phenylmercuric acetate. However, at pH < 5 tragacanth was reported to have no adverse effects on the preservative efficacy of benzoic acid, chlorobutanol, or methylparaben. ... 

Many excipients have been associated with adverse reactions in those ingesting drugs and vitamin/mineral formulations containing these compoundsJ78 79 Antioxidants (e.g., sodium sulfite, sodium and potassium bisulfites, and metabisulfites), bacterial preservatives (e.g., benzyl alcohol and benzalkonium chloride), artificial sweeteners (e.g., aspartame and saccharine), coloring agents (e.g., FD C yellow 5, blue 2, and red 40), and propylene glycol. A few examples of the toxic effects of these follow. 

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