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

Roflumilast is a selective phosphodiesterase-4 (PDE4) inhibitor. By inhibiting the PDE4 enzyme, it leads to increased intracellular cyclic adenosine monophosphate (cAMP) levels. This elevation of cAMP is believed to be responsible for its anti-inflammatory and immunomodulatory effects in the pulmonary system.

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.

No well-documented or proven hazardous drug interactions have been established with Roflumilast. However, isolated case reports suggest possible interactions with ethanol and a combination of pyrimethamine with dapsone, as well as potentiation effects when betahistine is used with salbutamol. As betahistine is a histamine analogue, concurrent use with H1 antihistamines may lead to mutual reduction of therapeutic effects.

Roflumilast is contraindicated in patients with hypersensitivity to the drug or any of its excipients. It is also contraindicated in patients with moderate to severe hepatic impairment.

In clinical COPD trials, about 16% of patients experienced adverse reactions compared to 5% with placebo. The most common effects include diarrhea, weight loss, nausea, abdominal pain, and headache. Most reactions are mild to moderate and occur mainly in the initial weeks of therapy, often resolving with continued use. Other reported adverse reactions include hypersensitivity, insomnia, anxiety, depression, suicidal ideation, tremor, dizziness, palpitations, respiratory infections, gastritis, vomiting, dyspepsia, rash, muscle cramps, fatigue, and increased liver enzymes.

There is limited human data on use during pregnancy. Animal studies have shown reproductive toxicity. Roflumilast is not recommended during pregnancy or in women not using contraception. It crosses the placenta in animal studies.

Animal data show excretion in milk, and risk to breastfed infants cannot be excluded. Therefore, Roflumilast should not be used during breastfeeding.

All patients should be informed about the potential risks of Roflumilast and the necessary precautions for safe use.

Rescue medicinal products: Roflumilast is an anti-inflammatory agent and should not be used for the relief of acute bronchospasm.

Weight decrease: In 1-year clinical studies, weight loss occurred more frequently in patients treated with Roflumilast compared to placebo. After discontinuation, most patients regained weight within 3 months. Body weight should be monitored regularly, especially in underweight patients. In case of unexplained or clinically significant weight loss, treatment should be stopped and further evaluation is required.

Special clinical conditions: Due to limited experience, Roflumilast should not be initiated or should be discontinued in patients with severe immunological diseases (e.g., HIV infection, multiple sclerosis, systemic lupus erythematosus, progressive multifocal leukoencephalopathy), severe acute infections, or malignancies (except basal cell carcinoma). It should also be avoided in patients receiving long-term immunosuppressive therapy such as methotrexate, azathioprine, infliximab, etanercept, or long-term oral corticosteroids (except short-term use). Data are limited in latent infections such as tuberculosis, viral hepatitis, herpes infections, and herpes zoster. It is not recommended in patients with severe congestive heart failure (NYHA class III–IV).

Psychiatric disorders: Roflumilast is associated with an increased risk of psychiatric symptoms including insomnia, anxiety, nervousness, and depression. Rare cases of suicidal thoughts and behavior, including completed suicide, have been reported, usually within the first weeks of treatment. Careful assessment of risks and benefits is required in patients with a history of psychiatric illness or when used with other drugs that may cause psychiatric effects. It is not recommended in patients with a history of depression associated with suicidal ideation or behavior. Patients and caregivers should report any mood or behavioral changes immediately. Treatment should be discontinued if new or worsening psychiatric symptoms or suicidal behavior occurs.

Persistent intolerability: Gastrointestinal side effects such as diarrhea, nausea, abdominal pain, and headache usually occur in the first weeks and may resolve with continued therapy. If intolerance persists, treatment should be reassessed. Higher exposure may occur in certain groups such as black, non-smoking females or patients taking CYP1A2 inhibitors (e.g., fluvoxamine) or dual CYP3A4/1A2 inhibitors (e.g., enoxacin, cimetidine).

Theophylline: No clinical evidence supports combined use with theophylline for maintenance therapy; therefore, concurrent use is not recommended.

Lactose: Roflumilast tablets contain lactose. Patients with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should avoid this medicine.

Overdose may cause headache, gastrointestinal disturbances, dizziness, palpitations, hypotension, and other systemic symptoms. Treatment is supportive. Hemodialysis is unlikely to be effective due to high protein binding.

Antihistamines, anti-allergy & desensitizing agents

Store below 30°C. Protect from light and moisture. Keep out of reach of children.