Rofumil Tablet

Rofumil is indicated for maintenance treatment of severe chronic obstructive pulmonary disease (COPD) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add on to bronchodilator treatment.

Roflumilast is a phosphodiesterase-4 (PDE-4) inhibitor which, due to its selective inhibition of the PDE4 isoenzyme, has potential antiinflammatory and antimodulatory effects in the pulmonary system. It is thought that the increased levels of intracellular cyclic AMP are responsible for the therapeutic actions of Roflumilast.

Adult dose: The recommended dose is one tablet of 500 micrograms Roflumilast once daily. Roflumilast may need to be taken for several weeks to achieve its effect. Roflumilast has been studied in clinical trials for up to one year.

Elderly (65 years and older): No dose adjustment is necessary.

Renal impairment: No dose adjustment is necessary. Hepatic impairment: The clinical data with Roflumilast in patients with mild hepatic impairment classified as Child-Pugh A are insufficient to recommend a dose adjustment and therefore Roflumilast should be used with caution in these patients. Patients with moderate or severe hepatic impairment classified as Child-Pugh B or C must not take Roflumilast.

Pediatric population: There is no relevant use of Roflumilast in the paediatric population (under 18 years). The tablet should be swallowed with water and taken at the same time every day. The tablet can be taken with or without food.

There are no proven cases of hazardous interactions. There is a case report of an interaction with ethanol and a compound containing pyrimethamine with dapsone and another of potentiation of betahistine with salbutamol. Betahistine is a histamine analogue, concurrent administration of H1 antagonists may cause a mutual attenuation of effect of the active agents.

Hypersensitivity to Roflumilast or to any of the excipients. Moderate or severe hepatic impairment.

In clinical COPD studies, approximately 16% of patients experienced adverse reactions with Rofumil (compared to 5% in placebo). The most commonly reported adverse reactions were diarrhoea (5.9%), weight decreased (3.4%), nausea (2.9%), abdominal pain (1.9%) and headache (1.7%). The majority of these adverse reactions were mild or moderate. These adverse reactions mainly occurred within the first weeks of therapy and mostly resolved on continued treatment. In the following data, adverse reactions are ranked under the MedDRA frequency classification: Very common (1/10); common (1/100 to <1/10); uncommon (1/1,000 to <1/100); rare (1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). Immune system disorders: Uncommon: Hypersensitivity;Endocrine disorders: Rare: Gynaecomastia; Metabolism and nutrition disorders: Common: Weight decreased, Decreased appetite; Psychiatric disorders: Common: Insomnia, Uncommon: Anxiety, Rare: Suicidal ideation and behavior, Depression, Nervousness; Nervous system disorders: Common: Headache, Uncommon: Tremor, Vertigo, Dizziness, Rare: Dysgeusia; Cardiac disorders: Uncommon: Palpitations; Respiratory, thoracic and mediastinal disorders: Rare: Respiratory tract infections (excluding Pneumonia); Gastrointestinal disorders: Common: Diarrhoea, Nausea, Abdominal pain, Uncommon: Gastritis, Vomiting, Gastro-esophageal reflux disease, Dyspepsia, Rare: Haematochezia, Constipation; Hepatobiliary disorders: Rare: Gamma- GT increased, Aspartate aminotransferase (AST) increased; Skin and subcutaneous tissue disorders: Uncommon: Rash, Rare: Urticaria; Musculoskeletal and connective tissue disorders: Uncommon: Muscle spasms and weakness, Myalgia, Back pain, Rare: Blood creatine phosphokinase (CPK) increased; General disorders and administration site conditions: Uncommon: Malaise, Asthenia, Fatigue.

Pregnancy: There are limited amount of data from the use of Roflumilast in pregnant women. Studies in animals have shown reproductive toxicity. Roflumilast is not recommended during pregnancy and in women of childbearing potential not using contraception. Roflumilast has been demonstrated to cross the placenta in pregnant rats.

Lactation: Available pharmacokinetic data in animals have shown excretion of Roflumilast or its metabolites in milk. A risk to the suckling child cannot be excluded. Roflumilast should not be used during breastfeeding.

All patients should be informed about the risks of Rofumil and the precautions for safe use.

Rescue medicinal products: Rofumil is an anti-inflammatory substance; it is not indicated as rescue medicinal product for the relief of acute bronchospasms.

Weight decrease: In 1-year studies, a decrease of body weight occurred more frequently in patients treated with Rofumil compared to placebo-treated patients. After discontinuation of Rofumil, 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 Rofumil should be stopped and body weight should be further followed-up. Special clinical conditions: Due to lack of relevant experience, treatment with Rofumil should not be initiated or existing treatment with Rofumil 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: Rofumil 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 with Rofumil 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. Rofumil 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 with Rofumil.

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, Rofumil 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, nonsmoking females or in patients concomitantly treated with the CYP1A2 inhibitor such as fluvoxamine or the dual CYP3A4/1A2 inhibitors such as 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.

Lactose: Rofumil tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

In Phase I studies, 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 Rofumil is highly protein bound, haemodialysis is not likely to be an efficient method of its removal. It is not known whether Rofumil is dialysable by peritoneal dialysis.

Antihistamines anti-allergies & hypo-sensitisation

Store below 30° C, keep away from light, moisture. Keep out of the reach of children.