Aldara warnings and precautions
If you notice severe skin irritation or flu-like symptoms (diarrhea, fatigue, fever, headache, or muscle pain), check with your doctor. It may be necessary for you to reduce the number of times a day that you use the medicine or to stop using the medicine for a short time until your skin is less irritated or your flu-like symptoms disappear. Avoid having genital, oral, or anal sex while the medicine is on your skin. Make sure you wash the cream off your skin before you engage in any sexual activity. Also, the medicine contains oils that can weaken latex (rubber) condoms, diaphragms, or cervical caps causing them not to work properly to prevent pregnancy. Do not use any other skin product on the same skin area on which you use this medicine, unless directed otherwise by your doctor. Do not share your medicine with others, even if you think that they have the same condition you have. If you are pregnant, check with your health care provider.
Warnings
The diagnosis of sBCC should be confirmed prior to treatment, since safety and effectiveness of Aldara Cream have not been established for other types of basal cell carcinomas, including nodular, morpheaform (fibrosing or sclerosing) types and is not recommended for treatment of BCC subtypes other than the superficial variant (i.e., sBCC). Patients with sBCC treated with Aldara Cream are recommended to have regular follow-up of the treatment site. See table of Estimated Clinical Clearance Rates for Superficial Basal Cell Carcinoma in the CLINICAL STUDIES section.
Aldara Cream has not been evaluated for the treatment of urethral, intra-vaginal, cervical, rectal, or intra-anal human papilloma viral disease and is not recommended for these conditions.
PRECAUTIONS
General
The safety and efficacy of Aldara Cream in immunosuppressed patients have not been established.
Aldara Cream administration is not recommended until the skin is completely healed from any previous drug or surgical treatment.
Aldara Cream has the potential to exacerbate inflammatory conditions of the skin including chronic graft versus host disease.
Aldara Cream should be used with caution in patients with pre-existing autoimmune conditions.
Intense local inflammatory reactions including skin weeping or erosion can occur after only a few applications of Aldara Cream. Local inflammatory reactions may be accompanied, or even preceded, by flu-like systemic signs and symptoms including malaise, fever, nausea, myalgias and rigors. An interruption of dosing should be considered.
Exposure to sunlight (including sunlamps) should be avoided or minimized during use of Aldara Cream because of concern for heightened sunburn susceptibility. Patients should be warned to use protective clothing (hat) when using Aldara Cream. Patients with sunburn should be advised not to use Aldara Cream until fully recovered. Patients who may have considerable sun exposure, e.g., due to their occupation, and those patients with inherent sensitivity to sunlight should exercise caution when using Aldara Cream. Phototoxicity has not been adequately assessed for Aldara Cream. The enhancement of ultraviolet carcinogenicity is not necessarily dependent on phototoxic mechanisms. Despite the absence of observed phototoxicity in humans (see ADVERSE REACTIONS ), Aldara Cream shortened the time to skin tumor formation in an animal photoco-carcinogenicity study (see Carcinogenesis, Mutagenesis, Impairment of Fertility). Therefore, it is prudent for patients to minimize or avoid natural or artificial sunlight exposure.
Actinic Keratosis
Safety and efficacy have not been established for Aldara Cream in the treatment of actinic keratosis with repeated use, i.e. more than one treatment course, in the same 25 cm2 area. The safety of Aldara Cream applied to areas of skin greater than 25 cm2 (e.g. 5 cm X 5 cm) for the treatment of actinic keratosis has not been established (see CLINICAL PHARMACOLOGY; Pharmacokinetics section regarding systemic absorption).
Superficial Basal Cell Carcinoma
The safety and efficacy of treating superficial basal cell carcinoma (sBCC) lesions on the face, head and anogenital area have not been established.
The efficacy and safety of Aldara Cream have not been established for patients with Basal Cell Nevus Syndrome or Xeroderma Pigmentosum.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Note: The Maximum Recommended Human Dose (MRHD) was set at 2 packets per treatment of Aldara Cream (25 mg imiquimod) for the animal multiple of human exposure ratios presented in this label. If higher doses than 2 packets of Aldara Cream are used clinically, then the animal multiple of human exposure would be reduced for that dose. A non-proportional increase in systemic exposure with increased dose of Aldara Cream was noted in the clinical pharmacokinetic study conducted in actinic keratosis subjects (see Pharmacokinetics). The AUC after topical application of 6 packets of Aldara Cream was 8 fold greater than the AUC after topical application of 2 packets of Aldara Cream in actinic keratosis subjects. Therefore, if a dose of 6 packets per treatment of Aldara Cream was topically administered to an individual, then the animal multiple of human exposure would be either 1/3 of the value provided in the label (based on body surface area comparisons) or 1/8 of the value provided in the label (based on AUC comparisons). The animal multiples of human exposure calculations were based on weekly dose comparisons for the carcinogenicity studies described in this label.
In an oral (gavage) rat carcinogenicity study, imiquimod was administered to Wistar rats on a 2X/week (up to 6 mg/kg/day) or daily (3 mg/kg/day) dosing schedule for 24 months. No treatment related tumors were noted in the oral rat carcinogenicity study up to the highest doses tested in this study of 6 mg/kg administered 2X/week in female rats (87X MRHD based on weekly AUC comparisons), 4 mg/kg administered 2X/week in male rats (75X MRHD based on weekly AUC comparisons) or 3 mg/kg administered 7X/week to male and female rats (153X MRHD based on weekly AUC comparisons).
In a dermal mouse carcinogenicity study, imiquimod cream (up to 5 mg/kg/application imiquimod or 0.3% imiquimod cream) was applied to the backs of mice 3X/week for 24 months. A statistically significant increase in the incidence of liver adenomas and carcinomas was noted in high dose male mice compared to control male mice (251X MRHD based on weekly AUC comparisons). An increased number of skin papillomas was observed in vehicle cream control group animals at the treated site only. The quantitative composition of the vehicle cream used in the dermal mouse carcinogenicity study is the same as the vehicle cream used for Aldara Cream, minus the active moiety (imiquimod).
In a 52-week dermal photoco-carcinogenicity study, the median time to onset of skin tumor formation was decreased in hairless mice following chronic topical dosing (3X/week; 40 weeks of treatment followed by 12 weeks of observation) with concurrent exposure to UV radiation (5 days per week) with the Aldara Cream vehicle alone. No additional effect on tumor development beyond the vehicle effect was noted with the addition of the active ingredient, imiquimod, to the vehicle cream.
Imiquimod revealed no evidence of mutagenic or clastogenic potential based on the results of five in vitro genotoxicity tests (Ames assay, mouse lymphoma L5178Y assay, Chinese hamster ovary cell chromosome aberration assay, human lymphocyte chromosome aberration assay and SHE cell transformation assay) and three in vivo genotoxicity tests (rat and hamster bone marrow cytogenetics assay and a mouse dominant lethal test).
Daily oral administration of imiquimod to rats, throughout mating, gestation, parturition and lactation, demonstrated no effects on growth, fertility or reproduction, at doses up to 87X MRHD based on AUC comparisons.
Pregnancy
Pregnancy Category C:
Systemic embryofetal development studies were conducted in rats and rabbits. Oral doses of 1, 5 and 20 mg/kg/day imiquimod were administered during the period of organogenesis (gestational days 6-15) to pregnant female rats. In the presence of maternal toxicity, fetal effects noted at 20 mg/kg/day [8X MRHD based on body surface area (BSA) comparisons] included increased resorptions, decreased fetal body weights, delays in skeletal ossification, bent limb bones, and two fetuses in one litter (2 of 1567 fetuses) demonstrated exencephaly, protruding tongues and low-set ears. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 5 mg/kg/day (55X MRHD based on AUC comparisons).
Intravenous doses of 0.5, 1 and 2 mg/kg/day imiquimod were administered during the period of organogenesis (gestational days 6 18) to pregnant female rabbits. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 2 mg/kg/day (1.5X MRHD based on AUC comparisons), the highest dose evaluated in this study, or 1 mg/kg/day (407X MRHD based on AUC comparisons).
A combined fertility and peri- and post-natal development study was conducted in rats. Oral doses of 1, 1.5, 3 and 6 mg/kg/day imiquimod were administered to male rats from 70 days prior to mating through the mating period and to female rats from 14 days prior to mating through parturition and lactation. No effects on growth, fertility, reproduction or post-natal development were noted at doses up to 6 mg/kg/day (87X MRHD based on AUC comparisons), the highest dose evaluated in this study. In the absence of maternal toxicity, bent limb bones were noted in the F1 fetuses at a dose of 6 mg/kg/day (87X MRHD based on AUC comparisons). This fetal effect was also noted in the oral rat embryofetal development study conducted with imiquimod. No treatment related effects on teratogenicity were noted at 3 mg/kg/day (41X MRHD based on AUC comparisons).
There are no adequate and well-controlled studies in pregnant women. Aldara Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether topically applied imiquimod is excreted in breast milk.
Pediatric Use
Safety and efficacy in patients with external genital/perianal warts below the age of 12 years have not been established.
AK and sBCC are not conditions generally seen within the pediatric population. The safety and efficacy of Aldara Cream for AK or sBCC in patients less than 18 years of age have not been established.
Geriatric Use
Of the 215 patients in the 2X/week clinical studies evaluating the treatment of AK lesions with Aldara Cream, 127 patients (59%) were 65 years and older, while 60 patients (28%) were 75 years and older. Of the 185 patients in the 5X/week treatment groups of clinical studies evaluating the treatment of sBCC with Aldara Cream, 65 patients (35%) were 65 years and older, while 25 patients (14%) were 75 years and older. No overall differences in safety or effectiveness were observed between these patients and younger patients. No other clinical experience has identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Warnings and precautions at aldara.com
Warnings
The diagnosis of sBCC should be confirmed prior to treatment, since safety and effectiveness of Aldara Cream have not been established for other types of basal cell carcinomas, including nodular, morpheaform (fibrosing or sclerosing) types and is not recommended for treatment of BCC subtypes other than the superficial variant (i.e., sBCC). Patients with sBCC treated with Aldara Cream are recommended to have regular follow-up of the treatment site. See table of Estimated Clinical Clearance Rates for Superficial Basal Cell Carcinoma in the CLINICAL STUDIES section.
Aldara Cream has not been evaluated for the treatment of urethral, intra-vaginal, cervical, rectal, or intra-anal human papilloma viral disease and is not recommended for these conditions.
PRECAUTIONS
General
The safety and efficacy of Aldara Cream in immunosuppressed patients have not been established.
Aldara Cream administration is not recommended until the skin is completely healed from any previous drug or surgical treatment.
Aldara Cream has the potential to exacerbate inflammatory conditions of the skin including chronic graft versus host disease.
Aldara Cream should be used with caution in patients with pre-existing autoimmune conditions.
Intense local inflammatory reactions including skin weeping or erosion can occur after only a few applications of Aldara Cream. Local inflammatory reactions may be accompanied, or even preceded, by flu-like systemic signs and symptoms including malaise, fever, nausea, myalgias and rigors. An interruption of dosing should be considered.
Exposure to sunlight (including sunlamps) should be avoided or minimized during use of Aldara Cream because of concern for heightened sunburn susceptibility. Patients should be warned to use protective clothing (hat) when using Aldara Cream. Patients with sunburn should be advised not to use Aldara Cream until fully recovered. Patients who may have considerable sun exposure, e.g., due to their occupation, and those patients with inherent sensitivity to sunlight should exercise caution when using Aldara Cream. Phototoxicity has not been adequately assessed for Aldara Cream. The enhancement of ultraviolet carcinogenicity is not necessarily dependent on phototoxic mechanisms. Despite the absence of observed phototoxicity in humans (see ADVERSE REACTIONS ), Aldara Cream shortened the time to skin tumor formation in an animal photoco-carcinogenicity study (see Carcinogenesis, Mutagenesis, Impairment of Fertility). Therefore, it is prudent for patients to minimize or avoid natural or artificial sunlight exposure.
Actinic Keratosis
Safety and efficacy have not been established for Aldara Cream in the treatment of actinic keratosis with repeated use, i.e. more than one treatment course, in the same 25 cm2 area. The safety of Aldara Cream applied to areas of skin greater than 25 cm2 (e.g. 5 cm X 5 cm) for the treatment of actinic keratosis has not been established (see CLINICAL PHARMACOLOGY; Pharmacokinetics section regarding systemic absorption).
Superficial Basal Cell Carcinoma
The safety and efficacy of treating superficial basal cell carcinoma (sBCC) lesions on the face, head and anogenital area have not been established.
The efficacy and safety of Aldara Cream have not been established for patients with Basal Cell Nevus Syndrome or Xeroderma Pigmentosum.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Note: The Maximum Recommended Human Dose (MRHD) was set at 2 packets per treatment of Aldara Cream (25 mg imiquimod) for the animal multiple of human exposure ratios presented in this label. If higher doses than 2 packets of Aldara Cream are used clinically, then the animal multiple of human exposure would be reduced for that dose. A non-proportional increase in systemic exposure with increased dose of Aldara Cream was noted in the clinical pharmacokinetic study conducted in actinic keratosis subjects (see Pharmacokinetics). The AUC after topical application of 6 packets of Aldara Cream was 8 fold greater than the AUC after topical application of 2 packets of Aldara Cream in actinic keratosis subjects. Therefore, if a dose of 6 packets per treatment of Aldara Cream was topically administered to an individual, then the animal multiple of human exposure would be either 1/3 of the value provided in the label (based on body surface area comparisons) or 1/8 of the value provided in the label (based on AUC comparisons). The animal multiples of human exposure calculations were based on weekly dose comparisons for the carcinogenicity studies described in this label.
In an oral (gavage) rat carcinogenicity study, imiquimod was administered to Wistar rats on a 2X/week (up to 6 mg/kg/day) or daily (3 mg/kg/day) dosing schedule for 24 months. No treatment related tumors were noted in the oral rat carcinogenicity study up to the highest doses tested in this study of 6 mg/kg administered 2X/week in female rats (87X MRHD based on weekly AUC comparisons), 4 mg/kg administered 2X/week in male rats (75X MRHD based on weekly AUC comparisons) or 3 mg/kg administered 7X/week to male and female rats (153X MRHD based on weekly AUC comparisons).
In a dermal mouse carcinogenicity study, imiquimod cream (up to 5 mg/kg/application imiquimod or 0.3% imiquimod cream) was applied to the backs of mice 3X/week for 24 months. A statistically significant increase in the incidence of liver adenomas and carcinomas was noted in high dose male mice compared to control male mice (251X MRHD based on weekly AUC comparisons). An increased number of skin papillomas was observed in vehicle cream control group animals at the treated site only. The quantitative composition of the vehicle cream used in the dermal mouse carcinogenicity study is the same as the vehicle cream used for Aldara Cream, minus the active moiety (imiquimod).
In a 52-week dermal photoco-carcinogenicity study, the median time to onset of skin tumor formation was decreased in hairless mice following chronic topical dosing (3X/week; 40 weeks of treatment followed by 12 weeks of observation) with concurrent exposure to UV radiation (5 days per week) with the Aldara Cream vehicle alone. No additional effect on tumor development beyond the vehicle effect was noted with the addition of the active ingredient, imiquimod, to the vehicle cream.
Imiquimod revealed no evidence of mutagenic or clastogenic potential based on the results of five in vitro genotoxicity tests (Ames assay, mouse lymphoma L5178Y assay, Chinese hamster ovary cell chromosome aberration assay, human lymphocyte chromosome aberration assay and SHE cell transformation assay) and three in vivo genotoxicity tests (rat and hamster bone marrow cytogenetics assay and a mouse dominant lethal test).
Daily oral administration of imiquimod to rats, throughout mating, gestation, parturition and lactation, demonstrated no effects on growth, fertility or reproduction, at doses up to 87X MRHD based on AUC comparisons.
Pregnancy
Pregnancy Category C:
Systemic embryofetal development studies were conducted in rats and rabbits. Oral doses of 1, 5 and 20 mg/kg/day imiquimod were administered during the period of organogenesis (gestational days 6-15) to pregnant female rats. In the presence of maternal toxicity, fetal effects noted at 20 mg/kg/day [8X MRHD based on body surface area (BSA) comparisons] included increased resorptions, decreased fetal body weights, delays in skeletal ossification, bent limb bones, and two fetuses in one litter (2 of 1567 fetuses) demonstrated exencephaly, protruding tongues and low-set ears. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 5 mg/kg/day (55X MRHD based on AUC comparisons).
Intravenous doses of 0.5, 1 and 2 mg/kg/day imiquimod were administered during the period of organogenesis (gestational days 6 18) to pregnant female rabbits. No treatment related effects on embryofetal toxicity or teratogenicity were noted at 2 mg/kg/day (1.5X MRHD based on AUC comparisons), the highest dose evaluated in this study, or 1 mg/kg/day (407X MRHD based on AUC comparisons).
A combined fertility and peri- and post-natal development study was conducted in rats. Oral doses of 1, 1.5, 3 and 6 mg/kg/day imiquimod were administered to male rats from 70 days prior to mating through the mating period and to female rats from 14 days prior to mating through parturition and lactation. No effects on growth, fertility, reproduction or post-natal development were noted at doses up to 6 mg/kg/day (87X MRHD based on AUC comparisons), the highest dose evaluated in this study. In the absence of maternal toxicity, bent limb bones were noted in the F1 fetuses at a dose of 6 mg/kg/day (87X MRHD based on AUC comparisons). This fetal effect was also noted in the oral rat embryofetal development study conducted with imiquimod. No treatment related effects on teratogenicity were noted at 3 mg/kg/day (41X MRHD based on AUC comparisons).
There are no adequate and well-controlled studies in pregnant women. Aldara Cream should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether topically applied imiquimod is excreted in breast milk.
Pediatric Use
Safety and efficacy in patients with external genital/perianal warts below the age of 12 years have not been established.
AK and sBCC are not conditions generally seen within the pediatric population. The safety and efficacy of Aldara Cream for AK or sBCC in patients less than 18 years of age have not been established.
Geriatric Use
Of the 215 patients in the 2X/week clinical studies evaluating the treatment of AK lesions with Aldara Cream, 127 patients (59%) were 65 years and older, while 60 patients (28%) were 75 years and older. Of the 185 patients in the 5X/week treatment groups of clinical studies evaluating the treatment of sBCC with Aldara Cream, 65 patients (35%) were 65 years and older, while 25 patients (14%) were 75 years and older. No overall differences in safety or effectiveness were observed between these patients and younger patients. No other clinical experience has identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Warnings and precautions at aldara.com
Labels: aldara, aldara warnings precautions
Posted by Buy Tramadol online @ Info Aldara warnings and precautions
|
0 Comments
