Pharmaceutical excipients. Adverse effects associated with 'inactive' ingredients in drug products (Part II).
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Antioxidants↗
Biomedical subjects
M L Bennett
Publications and source records attributed to M L Bennett.
Oral griseofulvin remains the treatment of choice for tinea capitis in children.
Tinea capitis is one of the most common infections of children. The standard treatment is griseofulvin. Itraconazole and terbinafine have in large part replaced griseofulvin in the treatment of onychomycosis and, in addition to fluconazole and ketoconazole, are evolving treatments for tinea capitis. The purpose of this review is to compare the efficacy, safety, and cost of oral antifungal agents for tinea capitis. Small, open-label studies of itraconazole, terbinafine, and fluconazole have reported encouraging results, suggesting that these drugs may be effective alternatives to griseofulvin; however, in large controlled studies griseofulvin continues to exhibit greater or equal efficacy. Ketoconazole appears to be the least efficacious. All five drugs appear relatively safe, however, only griseofulvin has a long track record of safety, is Food and Drug Administration (FDA) approved for the treatment of tinea capitis in children, and has the least known drug interactions. Fluconazole is FDA approved for use in children more than 6 months of age, yet not for the treatment of tinea capitis. Oral griseofulvin and terbinafine tablets are the least expensive of the antifungal agents; griseofulvin suspension is, however, more expensive than fluconazole suspension. For the combined reasons of efficacy, safety, and cost, and a long track record of use, we feel oral griseofulvin is still the present treatment of choice for tinea capitis. Newer antifungals are currently under investigation, and their role in treating tinea capitis in children is still being defined.
Administration, Oral↗
Pharmaceutical excipients. Adverse effects associated with inactive ingredients in drug products (Part I).
Excipient reactions have resulted from the use of clearly toxic substances (e.g. diethyleneglycol), the use of certain excipients in a susceptible group (e.g. very low birthweight neonates, patients with large surface area burns, patients with a history of asthma or contact dermatitis), the alteration of an excipient mixture resulting in altered bioavailability (e.g. phenytoin), and the deliberate or inadvertent extradural administration of preserved medications intended for intravenous use. Inadvertent excipient overdose has also occurred when unusually large doses of a drug containing a preservative were used [chlorbutol in morphine, ethanol in glyceryl trinitrate (nitroglycerin)]. Most excipient problems are preventable with knowledge of the currently available formulation. Government drug regulatory agencies have largely prevented introduction of a new toxic excipient; however, the new use of previously approved (but not adequately studied) excipients continues to result in unfortunate tragedies (e.g. the E-ferol incident). Populations at risk should be monitored carefully. Very low birthweight infants (less than 100g) have a well-demonstrated intolerance to many excipients, particularly during the first 2 weeks of life. Research should be directed toward development of non-preserved medications and safer diluents for this population. Drugs and excipients which have previously been demonstrated to be safer in other populations (e.g. doxapram) should be meticulously studied in this age group before widespread use is recommended. Asthmatic patients comprise another population that are frequently sensitive to excipient toxicity. In some cases, as in sulphiting agents, which are ubiquitous in foods as well as in medications, total avoidance may not be possible and prophylactic therapy may be beneficial. Inactive ingredients are clearly not consistently inert in their biological activity and therefore should not be listed as such. A more useful and concise term is excipient. It is highly recommended that all pharmaceutical manufacturers list all their excipients and make this available to practitioners and drug information centres. Alternatively or additionally, the package insert should list these excipients in accordance with good manufacturing procedures. This disclosure will help to determine the relative frequency and magnitude of problems (bioequivalence, toxicity, etc.) that excipients may have in the population, as well as enabling susceptible patients to avoid inadvertent exposure.
Excipients↗