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  • Daliresp
    / Rafa


    Active Ingredient
    Roflumilast 500 mcg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    30 X 500 mcg

    partial basket chart 51024 4607

    Film Coated Tablets

    90 X 500 mcg

    partial basket chart

    Related information


    Dosage

    The recommended dose is one tablet of 500 micrograms should be swallowed once daily same time every day with or without food.
    Elderly (65 years and older): No dose adjustment is necessary.
    Renal impairment: No dose adjustment is necessary.
    Hepatic impairment: The clinical data in patients with mild hepatic impairment classified as Child-Pugh A are insufficient to recommend a dose adjustment and therefore this drug should be used with caution in these patients. Patients with moderate or severe hepatic impairment classified as Child-Pugh B or C should not take.


    Indications

    Maintenance treatment of severe chronic obstructive pulmonary disease (COPD) (FEV1 post-bronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment.


    Contra-Indications

    Hypersensitivity to roflumilast or to any of the excipients.
    Moderate or severe hepatic impairment (Child-Pugh B or C).


    Special Precautions

    All patients should be informed about the risks and the precautions for safe use.
    Rescue medicinal products: Roflumilast is an anti-inflammatory substance indicated for maintenance treatment of severe COPD associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment. It is not indicated as rescue medicinal product for the relief of acute bronchospasms.
    Weight decrease: In 1-year studies (M2-124, M2-125), a decrease of body weight occurred more frequently in patients treated with Daliresp compared to placebo-treated patients. After discontinuation, the majority of patients had regained body weight after 3 months.
    Body weight of underweight patients should be checked at each visit. Patients should be advised to check their body weight on a regular basis. In the event of an unexplained and clinically concerning weight decrease, the intake of this drug should be stopped and body weight should be further followed-up.
    Special clinical conditions: Due to lack of relevant experience, treatment should not be initiated or existing treatment should be stopped in patients with severe immunological diseases (e.g. HIV infection, multiple sclerosis, lupus erythematosus, progressive multifocal leukoencephalopathy), severe acute infectious diseases, cancers (except basal cell carcinoma), or patients being treated with immunosuppressive medicinal products (i.e.: methotrexate, azathioprine, infliximab, etanercept, or oral corticosteroids to be taken long-term; except short-term systemic corticosteroids). Experience in patients with latent infections such as tuberculosis, viral hepatitis, herpes viral infection and herpes zoster is limited.
    Patients with congestive heart failure (NYHA grades 3 and 4) have not been studied and therefore treatment of these patients is not recommended.
    Psychiatric disorders: This drug is associated with an increased risk of psychiatric disorders such as insomnia, anxiety, nervousness and depression. Rare instances of suicidal ideation and behaviour, including completed suicide, have been observed in patients with or without history of depression, usually within the first weeks of treatment. The risks and benefits of starting or continuing treatment should be carefully assessed if patients report previous or existing psychiatric symptoms or if concomitant treatment with other medicinal products likely to cause psychiatric events is intended. It is not recommended in patients with a history of depression associated with suicidal ideation or behaviour. Patients and caregivers should be instructed to notify the prescriber of any changes in behaviour or mood and of any suicidal ideation. If patients suffered from new or worsening psychiatric symptoms, or suicidal ideation or suicidal attempt is identified, it is recommended to discontinue treatment.
    Persistent intolerability: While adverse reactions like diarrhoea, nausea, abdominal pain and headache mainly occur within the first weeks of therapy and mostly resolve on continued treatment, treatment should be reassessed in case of persistent intolerability. This might be the case in special populations that may have higher exposure, such as in black, non-smoking females or in patients concomitantly treated with the CYP1A2 inhibitor fluvoxamine or the dual CYP3A4/1A2 inhibitors enoxacin and cimetidine.
    Theophylline: There are no clinical data to support the concomitant treatment with theophylline for maintenance therapy. Therefore, the concomitant treatment with theophylline is not recommended.
    See prescribing information for full details.          


    Side Effects

    Insomnia, headache, weight decreased, decreased appetite, diarrhea, nausea, abdominal pain.
    See prescribing information for full details.


    Drug interactions

    Interaction studies have only been performed in adults. A major step in roflumilast metabolism is the N-oxidation of roflumilast to roflumilast N-oxide by CYP3A4 and CYP1A2. Both roflumilast and roflumilast N-oxide have intrinsic phosphodiesterase 4 (PDE4) inhibitory activity. Therefore, following administration of roflumilast, the total PDE4 inhibition is considered to be the combined effect of both roflumilast and roflumilast N-oxide. Clinical interaction studies with CYP 3A4 inhibitors erythromycin and ketoconazole showed increases of 9% of the total PDE4 inhibitory activity (i.e. total exposure to roflumilast and roflumilast N-oxide). Interaction studies with CYP1A2 inhibitor fluvoxamine, and the dual CYP3A4/1A2 inhibitors enoxacin and cimetidine resulted in increases of the total PDE4 inhibitory activity of 59%, 25% and 47%, respectively. A combination of Daliresp with these active substances might lead to an increase of exposure and persistent intolerability. In this case, Daliresp treatment should be reassessed.
    Administration of the cytochrome P450 enzyme inducer rifampicin resulted in a reduction in total PDE4 inhibitory activity by about 60%. Therefore, the use of strong cytochrome P450 inducers (e.g. phenobarbital, carbamazepine, phenytoin) may reduce the therapeutic efficacy of roflumilast.
    Co-administration with theophylline resulted in an increase of 8% of the total PDE4 inhibitory activity.
    In an interaction study with an oral contraceptive containing gestodene and ethinyl oestradiol, the total PDE4 inhibitory activity was increased by 17%.
    No interactions were observed with inhaled salbutamol, formoterol, budesonide and oral montelukast, digoxin, warfarin, sildenafil and midazolam.
    Co-administration with an antacid (combination of aluminium hydroxide and magnesium hydroxide) did not alter the absorption or pharmacokinetics of roflumilast or it’s N-oxide.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: The drug is not recommended during pregnancy and in women of childbearing potential not using contraception.
    Lactation: The drug should not be used during lactation.
    See prescribing information for full details. 


    Overdose

    The following symptoms were observed at an increased rate after single oral doses of 2,500 micrograms and one single dose of 5,000 micrograms (ten times the recommended dose): headache, gastrointestinal disorders, dizziness, palpitations, light-headedness, clamminess and arterial hypotension.
    In case of overdose, it is recommended that the appropriate supportive medical care is provided. Since roflumilast is highly protein bound, haemodialysis is not likely to be an efficient method of its removal. It is not known whether roflumilast is dialysable by peritoneal dialysis.
    See prescribing information for full details. 

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