Adverse reactions excipients

Table 4 Excipients Reported to Cause Adverse Reactions in Children...

Weiner M, Bernstein IL. Adverse Reactions to Drug Formulation Agents. A Handbook of Excipients. New York Marcel Dekker, 1989. 

Even for established excipients, regulators will look carefully at their presence in new drug formulations because they are not necessarily inert materials and some have well-established activity and/or toxicity. Clinically relevant adverse reactions are known for well-known excipients and the subject is covered elsewhere in the published literature (2,20,75-81). Findings tend to be uncommon compared to the overall prevalence of adverse drug reactions and often involve hypersensitivity reactions that are not likely to be predicted by conventional toxicity studies. 

Over the years there have been many failures with LNIT, due to the absence of standardization and the presence of local adverse reactions, particularly evident with the use of aqueous extracts. These inconvenients are synthesized in little stability (some molecules adhere to the inside surface of the container), autodigestion (presence of proteolytic enzymes in the extracts), and it is impossible to add propellants that enable their vaporization. It has become possible to overcome these problems after the realization of lyophilized allergenic preparations incorporated into an inert excipient in powder (lactose) and included in a rigid gelatine capsule [10, 26],... 

HNIG may interfere with immunisations, either recent or those scheduled in the next few weeks. Before administration of HNIG, patient history should be checked for adverse reactions to other blood products and excipients. Any side-effects should be reported immediately to your doctor. Side-effects include chills, fever, malaise and rarely anaphylaxis. 

Reference is an excellent resource on the safety and adverse reaction to several excipients. Sensitization reactions have been reported for the parabens, thi-merosal, and propyl gallate. Sorbitol is metabolized... 

Anonymous. Excipients-review of adverse reactions. WHO Newsletter 1998 11/12 5. 

Albumin occurs naturally in the body, comprising about 60% of all the plasma proteins. As an excipient, albumin is used primarily in parenteral formulations and is generally regarded as an essentially nontoxic and nonirritant material. Adverse reactions to albumin infusion rarely occur but include nausea, vomiting, increased salivation, chills, and febrile reactions. Urticaria and skin rash have been reported. Allergic reactions. 

Reports of adverse reactions to benzyl alcohol used as an excipient include toxicity following intravenous administra-... 

Benzyl benzoate is widely used as a 25% v/v topical application in the treatment of scabies and as an excipient in intramuscular injections and oral products. Adverse reactions to benzyl benzoate include skin irritation and hypersensitivity reactions. Oral ingestion may cause harmful stimulation of the CNS and convulsions. 

Although less toxic than phenol, chlorocresol may be irritant to the skin, eyes, and mucous membranes and has been reported to cause some adverse reactions when used as an excipient. " ... 

A number of adverse reactions to mannitol have been reported, primarily following the therapeutic use of 20% w/v aqueous intravenous infusions.The quantity of mannitol used as an excipient is considerably less than that used therapeutically and is consequently associated with a lower incidence of adverse reactions. However, allergic, hypersensitive-type reactions may occur when mannitol is used as an excipient. 

Almost all toxicological data for menthol relate to its use as a therapeutic agent rather than as an excipient. Inhalation or ingestion of large quantities can result in serious adverse reactions such as ataxia and CNS depression. Although menthol is essentially nonirritant there have been some reports of hypersensitivity following topical application. " In a Polish study approximately 1% of individuals were determined as being sensitive to menthol. ... 

Nitrous oxide is most commonly used therapeutically as an anesthetic and analgesic. Reports of adverse reactions to nitrous oxide therefore generally concern its therapeutic use, where relatively large quantities of the gas may be inhaled, rather than its use as an excipient. 

D Arcy PF. Adverse reactions to excipients in pharmaceutical formulations. In Florence AT, Salole EG, eds. Formulation Factors in Adverse Reactions. London Wright, 1990 1-22. 

Section 14, Safety, describes briefly the types of formulations in which the excipient has been used and presents relevant data concerning possible hazards and adverse reactions that have been reported. Relevant animal toxicity data are also... 

The Handbook of Pharmaceutical Excipients is a reference work containing a compilation of information on the uses and properties of pharmaceutical excipients, and the reader is assumed to possess the necessary knowledge to interpret the information that the Handbook contains. The Handbook of Pharmaceutical Excipients has no official status and there is no intent, implied or otherwise, that any of the information presented should constitute standards for the substances. The inclusion of an excipient, or a description of its use in a particular application, is not intended as an endorsement of that excipient or application. Similarly, reports of incompatibilities or adverse reactions to an excipient, in a particular application, may not necessarily prevent its use in other applications. Formulators should perform suitable experimental studies to satisfy themselves and regulatory bodies that a formulation is efficacious and safe to use. 

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