TOLAK SIDE EFFECTS
The following serious adverse reactions are discussed in more detail in other sections of the labeling:
- Application Site Adverse Reactions
- Hypersensitivity Reactions
- Ophthalmic Adverse Reactions
- Embryofetal toxicity
- Toxicity in Patients with Dihydropyrimidine Dehydrogenase Deficiency
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described below reflect exposure to Tolak Cream in 397 subjects with actinic keratosis in vehicle-controlled trials. The population ranged in age from 33 to 94 years, was 80% male, and almost all were Caucasian. Most subjects were treated with Tolak Cream once daily for 4 weeks. Throughout the 4-week treatment and the 4-week post-treatment periods, the trials specifically monitored for adverse reactions related to tolerability, including erythema, scaling/dryness, edema, crusting, erosions, stinging/burning, and pruritus.
The number and percentage of subjects with each of these monitored adverse reactions at one or more post-baseline visit(s) during the clinical trials are shown in Table 1.
Table 1: Incidence of Application Site Adverse Reactions Occurring with 4 Weeks of Tolak Cream Treatment in Clinical Trials 1 and 2
N=397 n (%)
N=120 n (%)
|Mild, Moderate or Severe||Severe Only||Mild, Moderate or Severe||Severe Only|
|Erythema||394 (99%)||174 (44%)||102 (85%)||0 (0%)|
|Scaling/ Dryness||377 (95%)||94 (24%)||99 (83%)||0 (0%)|
|Crusting||346 (87%)||87 (22%)||46 (38%)||0 (0%)|
|Pruritus||337 (85%)||65 (16%)||46 (38%)||1 (1%)|
|Stinging/ Burning||346 (87%)||101 (25%)||42 (35%)||0 (0%)|
|Edema||275 (69%)||30 (8%)||11 (9%)||0 (0%)|
|Erosions||271 (68%)||44 (11%)||14 (12%)||0 (0%)|
In these clinical trials, the intensity of the adverse reactions in subjects using Tolak Cream generally increased over the 4-week treatment period, usually reaching maximal levels at 4 weeks of treatment and then diminishing to baseline levels within 4 weeks after cessation of treatment.
In Trials 1 and 2, 11% of Tolak Cream-treated and 3% of vehicle-treated subjects discontinued treatment because of adverse reactions. Of these subjects, the majority had adverse reactions at the application site. Eye swelling, leading to discontinuation, occurred in one subject with Tolak Cream use.
The following adverse reactions have been identified during post-approval use of topical fluorouracil. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Blood and Lymphatic System Disorders : leukocytosis, pancytopenia, thrombocytopenia, eosinophilia, neutrophil toxic granulation
Eyedisorders : corneal disorder, conjunctival disorder, eye irritation, conjunctivitis, lacrimation
Gastrointestinal disorders : stomatitis
General Disorders and Administration Site Conditions :medicinal taste
Infections and Infestations : herpes simplex
Neoplasms : chronic lymphocytic leukemia, non-melanoma skin cancer
Nervous system disorders : insomnia, irritability
Psychiatric disorders : emotional distress
Skin and subcutaneous tissue disorders : blistering, allergic contact dermatitis, photosensitivity, pain, scarring, skin irritation, rash, ulceration, hyperpigmentation, alopecia, bullous pemphigoid, ichthyosis, suppuration, swelling, soreness, telangiectasia, tenderness, urticaria.
SRC: NLM .