Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
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%). These adverse reactions mainly occurred within the first weeks of therapy and mostly resolved on continued treatment.


Tabulated list of adverse reactions
Within the following table, 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).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Adverse reactions with roflumilast in clinical COPD studies and post-marketing experience 
Frequency              Common               Uncommon                  Rare 
System
Organ Class
Immune system disorders                           Hypersensitivity          Angioedema Endocrine disorders                                                         Gynaecomastia Metabolism and nutrition     Weight decreased disorders                    Decreased appetite
Psychiatric disorders        Insomnia             Anxiety                   Suicidal ideation and behaviour*
Depression
Nervousness
Panic attack
Nervous system disorders     Headache             Tremor                    Dysgeusia Vertigo
Dizziness
Cardiac disorders                                 Palpitations
Respiratory, thoracic and                                                   Respiratory tract mediastinal disorders                                                       infections (excluding Pneumonia)
Frequency              Common                Uncommon                   Rare 
System
Organ Class
Gastrointestinal disorders   Diarrhoea             Gastritis                  Haematochezia Nausea                Vomiting                   Constipation
Abdominal pain        Gastro-esophageal reflux disease
Dyspepsia
Hepatobiliary disorders                                                       Gamma-GT increased Aspartate aminotransferase (AST) increased
Skin and subcutaneous                              Rash                       Urticaria tissue disorders
Musculoskeletal and                                Muscle spasms and          Blood creatine connective tissue                                  weakness                   phosphokinase (CPK) disorders                                          Myalgia                    increased Back pain
General disorders and                              Malaise administration site                                Asthenia conditions                                         Fatigue

Description of selected adverse reactions
* In clinical studies and post-marketing experience, rare instances of suicidal ideation and behaviour, including suicide, were reported. Patients and caregivers should be instructed to notify the prescriber of any suicidal ideation (see also section 4.4).

Other special populations
Elderly
A higher incidence of sleep disorders (mainly insomnia) in patients ≥75 years or older was observed in Study RO-2455-404-RD for patients treated with roflumilast when compared to those treated with placebo (3.9% vs 2.3%). The incidence observed was also higher in patients less than 75 years old, treated with roflumilast when compared to those treated with placebo (3.1% vs 2.0%).

Body weight <60kg

A higher incidence of sleep disorders (mainly insomnia) in patients with a baseline body weight <60 kg was observed in Study RO-2455-404-RD for patients treated with roflumilast when compared to those treated with placebo (6.0% vs 1.7%). The incidence was 2.5% vs 2.2% in patients with a baseline body weight ≥60 kg, treated with roflumilast when compared to those treated with placebo.

Concomitant treatment with long acting muscarinic antagonists (LAMA)

A higher incidence of weight decrease, decreased appetite, headache and depression was observed during Study RO-2455-404-RD in patients receiving concomitant roflumilast and long-acting muscarinic antagonists (LAMA) plus concomitant inhaled corticosteroids (ICS) and long acting B2 agonists (LABA) compared to those treated only with concomitant roflumilast, ICS and LABA.
Difference of incidence between roflumilast and placebo was quantitatively greater with concomitant LAMA for weight decreased (7.2% vs 4.2%), decreased appetite (3.7% vs 2.0%), headache (2.4% vs 1.1%) and depression (1.4% vs -0.3%).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form
 https://sideeffects.health.gov.il/