Is diltiazem (Cardizem) or chlorthalidone (Thalitone) more likely to cause a skin reaction?

From the Guidelines

Diltiazem is more likely to cause skin reactions compared to chlorthalidone. Diltiazem, a calcium channel blocker commonly used for hypertension and certain cardiac conditions, has a higher incidence of dermatologic adverse effects including rash, photosensitivity, flushing, and pruritus. These skin reactions typically occur in about 1-2% of patients taking diltiazem 1. Chlorthalidone, a thiazide-like diuretic used primarily for hypertension, has a lower overall incidence of skin reactions, though it can occasionally cause photosensitivity and rarely more serious reactions like Stevens-Johnson syndrome.

Key Points to Consider

• The difference in skin reaction profiles relates to their distinct mechanisms of action - diltiazem's effects on calcium channels can influence mast cell degranulation and inflammatory mediator release, while chlorthalidone's effects on electrolyte balance generally have less direct impact on skin physiology.
• If a patient has a history of dermatologic adverse reactions, chlorthalidone might be preferred over diltiazem, though individual patient factors and the specific indication for treatment should guide medication selection.
• It is essential to monitor patients for signs of skin reactions when prescribing either medication and to adjust treatment accordingly.
• The guidelines from the American College of Cardiology/American Heart Association task force on clinical practice guidelines support the use of chlorthalidone as a preferred agent for hypertension management due to its proven trial reduction of cardiovascular disease 1.

Clinical Implications

• When choosing between diltiazem and chlorthalidone, clinicians should consider the patient's history of dermatologic adverse reactions and weigh the benefits and risks of each medication.
• The selection of antihypertensive medication should be individualized, taking into account the patient's specific clinical profile and the potential for adverse effects.
• Regular monitoring and follow-up are crucial to ensure the safe and effective use of these medications.

From the FDA Drug Label

ADVERSE REACTIONS Serious adverse reactions have been rare in studies carried out to date, but it should be recognized that patients with impaired ventricular function and cardiac conduction abnormalities usually have been excluded In domestic placebo-controlled angina trials, the incidence of adverse reactions reported during diltiazem hydrochloride therapy was not greater than that reported during placebo therapy. The following represent occurrences observed in clinical studies of angina patients. In many cases, the relationship to diltiazem hydrochloride has not been established The most common occurrences from these studies, as well as their frequency of presentation, are edema (2.4%), headache (2.1%), nausea (1.9%), dizziness (1.5%), rash (1.3%), and asthenia (1. 2%) The following postmarketing events have been reported infrequently in patients receiving diltiazem hydrochloride tablets: acute generalized exanthematous pustulosis, allergic reactions, alopecia, angioedema (including facial or periorbital edema), asystole, erythema multiforme (including Stevens-Johnson syndrome, toxic epidermal necrolysis), extrapyramidal symptoms, gingival hyperplasia, hemolytic anemia, increased bleeding time, leukopenia, photosensitivity (including lichenoid keratosis and hyperpigmentation at sun-exposed skin areas), purpura, retinopathy, myopathy, and thrombocytopenia There have been observed cases of a generalized rash, some characterized as leukocytoclastic vasculitis. In addition, events such as myocardial infarction have been observed, which are not readily distinguishable from the natural history of the disease in these patients. A definitive cause and effect relationship between these events and diltiazem hydrochloride therapy cannot yet be established Exfoliative dermatitis (proven by rechallenge) has also been reported.

Diltiazem has been reported to cause skin reactions, including:

• Rash (1.3%)
• Acute generalized exanthematous pustulosis
• Allergic reactions
• Angioedema
• Erythema multiforme
• Photosensitivity
• Purpura
• Exfoliative dermatitis

However, there is no information in the provided drug labels about chlorthaldone. The FDA drug label does not answer the question.

From the Research

Comparison of Diltiazem and Chlorthalidone

• Diltiazem has been associated with various skin reactions, including cutaneous eruptions, erythema-multiforme-like reactions, and photodistributed hyperpigmentation 2, 3, 4.
• Chlorthalidone, on the other hand, has been studied for its efficacy and metabolic side effects in the treatment of mild hypertension, but there is no mention of skin reactions in the provided studies 5.
• A study on photosensitive drugs and their effects on the skin mentions that phototoxicity and photoallergy are two different pathogenic mechanisms involved in photosensitization, but it does not specifically compare diltiazem and chlorthalidone 6.
• Based on the available evidence, diltiazem appears to be more likely to cause skin reactions, including photodistributed hyperpigmentation, compared to chlorthalidone 2, 3, 4.

Skin Reactions Associated with Diltiazem

• Cutaneous eruptions, including exanthemas and severe adverse events, have been reported in patients taking diltiazem 2.
• Photodistributed hyperpigmentation, characterized by slate-gray and reticulated hyperpigmentation on sun-exposed areas, has been associated with long-term administration of diltiazem 3, 4.
• Discontinuation of diltiazem therapy has been shown to result in the gradual resolution of skin reactions, including photodistributed hyperpigmentation 3, 4.