Do not get it in your eyes, nose, or mouth. Do not use on skin areas that have cuts or scrapes. If it does get on these areas, rinse it off right away. The dose of this medicine will be different for different patients.
Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so. The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing. Do not leave the ointment in the car in cold or hot weather. Only the lower, 0.
It will be prescribed initially by a skin specialist doctor. Tacrolimus is also available as a medicine which is taken by mouth, but this is prescribed for a completely different medical condition. There is a separate information leaflet available about this, called Tacrolimus to prevent organ rejection.
Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start using tacrolimus ointment it is important that your doctor knows:.
Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with tacrolimus ointment.
You will find a full list in the manufacturer's information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.
If you experience any other symptoms which you think may be due to the ointment, speak with your doctor or pharmacist for further advice. If you are having an operation or dental treatment, tell the person carrying out the treatment which medicines you are using.
Patients were also extremely satisfied with their improvement and at week 2, Separate analyses of the head and neck area showed overall results similar to the analyses of combined body regions: Patients reported a progressive improvement in quality of life throughout the study.
At the day 1 visit, the median DLQI was 6. Median percentage affected total body surface area BSA between visit at day 1 and month Table III. Clinical improvement in atopic dermatitis between day 1 and end of study. Skin burning patients, Of the 17 patients 2. Other adverse events leading to study discontinuation included herpes simplex 2 patients , folliculitis, pruritus, eczema, skin infection, manic depressive reaction, application-site reaction and hypertension all 1 patient, respectively.
Table IV. Incidence of most common a causally related adverse events during 0. Few serious adverse events occurred during the study 28 patients, 4. The most commonly reported serious adverse event was lack of drug effect 7, 1. Four patients 0. Tacrolimus ointment application was discontinued in all 4 patients.
Reports of infections, benign neoplasms and malignancies were examined carefully. The most commonly reported infections during this study were flu syndrome With regard to herpes simplex, except for 6 patients 0.
In addition, the prevalence of herpes simplex decreased throughout the study period in parallel with the decrease in severity and extent of disease as the skin barrier function improved Fig. Two malignancies were reported during the study, and in both patients the relationship to tacrolimus ointment was assessed as being unlikely.
Table V. Overall incidence of most common a infections and incidence of all benign neoplasms and malignancies, irrespective of causality, during 0. Prevalence of herpes simplex during the study. M: month. With respect to the 7 patients with benign skin neoplasms, 5 had neoplasms that were assessed by the physician as having an unlikely relationship to the study ointment each one patient: seborrhoeic wart, strange coloured mole, junctional nevus, molluscum pendulum, inflammatory sebaceous cyst.
Two patients had benign skin neoplasms that were possibly related to the study medication one patient with a wart and one patient with neck skin tags.
All 7 patients continued with tacrolimus ointment application and recovered prior to the end of the study. Twenty-seven patients had at least one laboratory value that occurred during the study that was considered to be clinically relevant by the investigator.
None of these clinically-relevant laboratory values affected the management of the patient or led to discontinuation of the patient from the study. This is the first European study to investigate the long-term efficacy and safety of 0.
The efficacy data showed clearly that the patients had substantial improvement in the signs and symptoms of AD. Large decreases in total affected BSA and EASI became apparent after 2 weeks of treatment and clinical improvement continued throughout the study. The positive results of the DLQI showed that patients had a greater feeling of well-being and felt that their lives were less impaired by their disease.
Treatment efficacy was maintained in the majority of patients who required only one to two treatment episodes during the study period, and the total amount of ointment applied decreased as the condition of the skin improved.
This is of particular importance as there is concern that patients who have large affected areas and open lesions may be at a risk of increasing their systemic exposure to tacrolimus. Rubins et al. As treatment with tacrolimus ointment normally helps to restore the skin barrier quickly, exposure to tacrolimus is reduced as the lesions heal.
In a month, open-label study in patients with moderate to severe AD, tacrolimus whole blood concentrations decreased from 0. Nonetheless, patients should be monitored carefully to identify any side-effects related to long-term treatment, and additional studies measuring whole blood concentrations of tacrolimus in patients applying tacrolimus ointment for prolonged periods of time will help clarify whether systemic accumulation can occur with long-term treatment.
Irritation at the site of ointment application is the most common adverse effect associated with tacrolimus ointment and has been reported in both short-term and long-term clinical studies Transient skin burning at the site of ointment application was the most common adverse event reported during our study, and in most patients, was mild to moderate in severity, decreased in prevalence after the first 2 weeks of treatment, and only a few patients required medical intervention.
As there is concern that the prolonged application of tacrolimus ointment may cause systemic immunosuppression, we investigated infections and malignancies in detail. The nature and incidence of infections observed during the study were consistent with what has been reported previously in a cohort of patients with AD followed for this length of time Only one patient 0.
For determination of tacrolimus concentrations, whole blood samples were collected at day 1, week 1, week 2, month 1, month 3, and the last visit. The samples were assayed for tacrolimus concentration using a validated high-performance liquid chromatography method with repeated mass spectrometry. The limit of quantification was 0. Patients assessed the intensity of itch experienced during the previous 24 hours using a cm visual analog scale, with 0 cm indicating "no itch" and 10 cm indicating "worst itch imaginable.
Itch was included in the mEASI because it is considered a primary symptom of atopic dermatitis. The evaluable population comprised patients who received at least 1 application of tacrolimus and had at least 1 assessment after baseline. Data were summarized by descriptive statistics and frequency counts. The COSTART term "flu syndrome" was used to code investigator terms such as "cold," "common cold," "flu," "influenza," and "upper respiratory tract infection.
Adverse events were summarized by frequency counts. Cox regression analyses were used to assess any effect of cumulative ointment use on the time to first occurrence of selected adverse events. Of patients screened, were eligible for study entry. Two hundred patients were assigned to treatment for 6 months and for 12 months.
In total, patients Patient demographic and baseline characteristics are presented in Table 1. Comparison of the mean age of patients 31 years in the total study population with the mean duration of atopic dermatitis 25 years in the total study population indicates that most patients experienced onset of the disease during childhood. The long duration of the current episode with a mean of several years reflects a patient population with persistent disease.
The affected body surface area was extensive at baseline a median of approximately one third of total body surface area , and most patients had active disease on all body regions, including the head and neck.
The most common adverse events were related to local irritation; these were burning sensation, pruritus, and skin erythema Table 2. In practice, pruritus seemed related to burning; patients reported these events in the context of local discomfort. The incidence and intensity of these adverse events, particularly skin burning, decreased with time. For example, the incidence of skin burning at the application site was During months 10 to 12, only 2.
The higher incidence of events that occurred exclusively at a treated site compared with the incidence of those that occurred in a patient at both a treated and nontreated site Table 2 suggests that skin burning, pruritus, skin erythema, folliculitis, herpes simplex, alcohol intolerance, and maculopapular rash were specific for the area of application.
Folliculitis, maculopapular rash, and pustular rash are suspected to be related to the occlusive properties of the ointment. Because lack of drug effect and skin infection were not localized to the treated area Table 2 , these events probably represent a generalized flare-up of the disease.
Flu syndrome was reported most frequently during the winter months. There was otherwise no increase in the prevalence of any infection over time. In total, 6 patients 1. There were 5 serious adverse events for which a causal relation with the study drug was unknown or considered possible; all were associated with hospitalization.
These constituted 1 patient who experienced a severe flare-up of atopic dermatitis, 1 who experienced a Staphylococcus superinfection of the skin, 1 with eczema herpeticum the patient had a long history of relapses , 1 with varicella, and 1 with cellulitis.
All but cellulitus were present on the application site. Cox regression analyses were performed to assess the effect of cumulative ointment use on the time to first occurrence of skin infection, nonskin infection, adverse events of the digestive system, adverse events of the nervous system, and severe related adverse events that required medical intervention.
No significant increase in the risk of these types of adverse events was found with increased cumulative ointment use. Laboratory measurements showed mean eosinophil counts and lactate dehydrogenase concentrations greater than the reference range at baseline and all study visits, as expected for this study population.
One patient experienced an increase in transaminase levels that resolved before treatment discontinuation. Median whole blood concentrations of tacrolimus were minimal during the study: 0. All tacrolimus blood concentrations within the limit of quantification 0. Results of the Recall Antigen Test showed a patient population with depressed cell-mediated immunity at baseline, but no notable changes were observed with prolonged treatment. The proportion of patients with no positive reactions was also similar over time: 28 patients The greatest decrease in symptoms, as measured by the mEASI, was seen during the first week of treatment Figure 2.
The mEASI continued to decrease until month 3, and maximal improvement was maintained during the rest of the study. Decreases in affected body surface area showed the same trend over time Figure 2. The size of the treated area over time was nearly identical to the size of the affected area data not shown. Ointment use also decreased; median daily ointment use was 3.
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