Pharmacy Times

generic times: product profiles

Author: Jim Middleton, BS, RPh

Sodium Sulfacetamide Topical Lotion 10%

The arts and sciences often cross in unexpected ways. Paul Fildes, the son of an illustrator for Charles Dickens, became known as the father of British microbiology while creating biological weapons during World War II. During these investigations, he formulated a theory with Donald Woods describing a proposed action for sulfonamide drugs. This premise was based on the structural similarity between sulfonamides and para-aminobenzoic acid (PABA) and the use of that similarity to interrupt essential functions in bacterial cell growth. The Woods-Fildes theory is still accepted today.

Sulfonamides have several dosage forms and many indications. Topical administration results in about 4% percutaneous absorption, and this amount creates effective antibiotic activity against Propionbacterium acnes while limiting potential systemic resistance.

The common skin disease known as acne vulgaris knows no age boundaries, but it is most fond of the adolescent dermis. Although not fatal, acne can often result in physical and emotional scarring. Even in the light of general concerns over bacterial resistance, topical sulfacetamide for acne generates over 5 million prescriptions annually. Among the therapies in current vogue is a 10% concentration of sulfacetamide in lotion form. Sodium sulfacetamide topical lotion is now available in a 10% concentration from Prasco Laboratories and is AB-rated to the brand product Klaron (Dermik Laboratories, a business of sanofi-aventis US LLC).

Pharmacology

In addition to the competitive antagonism to PABA as a major inhibitor to bacterial cell growth, the sulfur molecule itself serves as a direct keratolytic agent and inhibits the development of free fatty acids, part of the inflammatory process surrounding acne vulgaris.

Administration

The lotion should be shaken well before each use to evenly disperse the drug. The patient should apply a thin film to the areas affected by the acne eruptions once to twice a day. Hand washing is encouraged before and after each application.

Safety Profile

Adverse effects from topical sulfacetamide are infrequent, with studies reporting incidences of fewer than 2%. These generally involve localized irritation, erythema, stinging, and burning. Because it is a sulfonamide-based compound, the potential for severe reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, should be considered. Sodium metabisulfite is also part of the formulation, and this sulfite has been implicated in rare, but nevertheless potentially severe, allergic reactions. Allergies to sulfa drugs represent a contraindication to the use of topical sulfacetamide.

Outlook

The pathogenesis of acne vulgaris represents a collection of causative factors that promote the inflammatory effects of P acnes. Sulfacetamide, while it is becoming less effective against certain strains of staphylococcus, has not shown diminished activity against Propionbacterium in acne.

Trandolapril Oral Tablets

Recent studies continue to reinforce the value of using angiotensin-converting enzyme (ACE) inhibitors to reduce the primary end points of cardiovascular disease, myocardial infarction, and cardiac arrest. Trandolapril is one of many ACE inhibitors and has recently been made available in generic form. Trandolapril is available from Teva Pharmaceuticals in 1-, 2-, and 4-mg tablets.

Pharmacology

Inhibition of the enzyme that activates angiotensin results in a diminished level of physiologic aldosterone. This in turn reduces sodium and fluid retention. The inhibition also allows for a shift in balance between angiotensin II and bradykinin, with increases in bradykinin promoting the reduction in vascular tone that, in turn, further promotes sodium excretion and diuresis.

Additional beneficial actions of ACE inhibition include localized reduction of the inflammatory processes that create atherosclerosis within arterial walls. Although this action may not reverse existing plaque formation, an ACE inhibitor may help stabilize the lesion and prevent rupture and its associated complications. ACE inhibitors such as trandolapril may be used as monotherapy for treatment of hypertension, but they are often used in combination with other antihypertensive agents. In addition,

ACE inhibitors reduce the mortality and clinically significant risk of heart failure among patients following myocardial infarction. Hypertensive patients with comorbid diabetes may benefit from ACE-inhibitor therapy as a means to slow the progression rate of renal disease in the presence of proteinuria or existing nephropathy.

Ethnic background has an effect on response to ACE inhibitors. African Americans respond better to monotherapy with diuretics or calcium channel blocking drugs than to ACE inhibitors or β-blockers, and they are more prone to some serious side effects associated with ACE inhibition. The causative mechanism for this effect is unclear. When used among African Americans, trandolapril requires a higher dose to achieve the same therapeutic effect.

Dosage and Administration

The general starting dose among non-African American patients is 1 mg daily; African American patients generally require 2 mg daily.

Dosing changes should be made at 2-to 3-week intervals. At steady state, the general maintenance dose of trandolapril is 2 mg to 4 mg, taken once daily. Daily doses beyond 8 mg have not been studied for either safety or efficacy.

To minimize clinically hypotensive responses with combination therapy, diuretics should be discontinued 2 to 3 days prior to initiating trandolapril. If a diuretic is to be continued, the starting trandolapril dose should be 0.5 mg daily.

Safety Profile

Based on reports published in 2006, ACE inhibitors administered during the first trimester of pregnancy are associated with an increase in major congenital malformations in the developing fetus. Although ACE inhibitors have not been recategorized by the FDA to reflect this information, the current recommendation is to discontinue any ACE inhibitor as soon as possible if a patient becomes pregnant. Presently, ACE inhibitors are labeled as pregnancy category C for the first trimester and category D during the second and third.

The potential for neutropenia and agranulocytosis associated with captopril has not become manifest with trandolapril; leukocyte monitoring should still be considered in the presence of collagen vascular disease, however, especially with the existence of renal impairment.

ACE inhibitors are also associated with a rare hepatic syndrome, clinically manifesting as cholestatic jaundice and potentially evolving to necrosis. Potentially fatal angioedema may also occur with ACE inhibitors, requiring patient education for the appropriate response to any swelling of the face, larynx, or extremities.

Angioedema is a rare consequence of ACE-inhibitor treatment, with African Americans at 4.5 times the risk of developing the condition over the rest of the population. Angioedema can, however, appear without any other direct correlation to age, sex, dosage, or concurrent treatment.

In addition, patients with diabetes need to be instructed on the potential for changes in blood glucose levels while using an ACE inhibitor. There is also the potential for pancreatitis during this therapy.

Outlook

Affecting physiologic levels of angiotensin is demonstrating a wide variety of effects, including activity that has not been predicted by tracing the usual ACE-mediated pathways. Despite the potential for serious side effects, ACE inhibitors are also being increasingly examined for their effects on thrombosis and inflammation within the cardiovascular system.

Mr. Middleton is an instructor of pharmacology at Kellogg Community College in Battle Creek, Mich.