Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
Undesirable effects are seen in most patients receiving acitretin. However, the toxic dose of Neotigason is close to the therapeutic dose and most patients experience some side- effects during the initial period whilst dosage is being adjusted. They are usually reversible with reduction of dosage or discontinuation of therapy.
The skin and mucous membranes are most commonly affected, and it is recommended that patients should be so advised before treatment is commenced. An initial worsening of psoriasis symptoms is sometimes seen at the beginning of the treatment period.

The most frequent undesirable effects observed are symptoms of hypervitaminosis A, e.g.
dryness of the lips, which can be alleviated by application of a fatty ointment.

Undesirable effects reported for acitretin in clinical trials or as post-marketing events are listed below by System Organ Class and frequency. The frequencies of adverse events are ranked according to the following:

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)

Infections and infestations
Frequency not known      Vulvo-vaginitis due to Candida albicans Immune system disorders
Frequency not known       Type I hypersensitivity
Nervous system disorders
Common                   Headache


Neotigason Capsules 10mg, 25mg, SPC, 02-2020, HH, Notification
Uncommon                 Dizziness
Rare                     Neuropathy peripheral
Very rare                Benign intracranial hypertension (see section 4.4) Eye disorders
Very common              Drying of and inflammation of mucous membranes (e.g.
conjunctivitis, xerophthalmia)*
Uncommon                 Vision blurred
Very rare                Night blindness (see section 4.4), ulcerative keratitis Ear and labyrinth disorders
Frequency not known      Hearing impaired, tinnitus
Vascular disorders
Frequency not known      Flushing, Capillary Leak Syndrome/ retinoic acid syndrome Respiratory, thoracic and mediastinal disorders
Very common              Drying of and inflammation of mucous membranes (e.g.epistaxis and rhinitis)

Frequency not known      Dysphonia
Gastrointestinal disorders
Very common              Dry mouth, thirst
Common                   Stomatitis, gastro-intestinal disorders (e.g. abdominal pain, diarrhoea, nausea, vomiting)

Uncommon                 Gingivitis
Frequency not known      Dysgeusia, rectal haemorrhage
Hepatobiliary disorders
Uncommon                 Hepatitis
Very rare                Jaundice
Skin and subcutaneous tissue disorders
Very common              Cheilitis, pruritus, alopecia, skin exfoliation (all over the body, particularly on the palms and soles)

Common                   Skin fragility, sticky skin, dermatitis, hair texture abnormal, brittle nails, paronychia, erythema

Uncommon                 Rhagades, dermatitis bullous, photosensitivity reaction Frequency not known      Pyogenic granuloma, madarosis, dryness of the skin may be 
Neotigason Capsules 10mg, 25mg, SPC, 02-2020, HH, Notification
associated with scaling, thinning, erythema (especially of the face), , hair thinning and frank alopecia**, granulomatous lesions, sweating, rhagades of the corner of the mouth,
angioedema, urticaria, exfoliative dermatitis
Musculoskeletal and connective tissue disorders
Common                   Arthralgia, myalgia
Very rare                Bone pain, exostosis (maintenance treatment may result in progression of existing spinal hyperostosis, in appearance of new hyperostotic lesions and in extraskeletal calcification, as has been observed in longterm systemic treatment withretinoids) (see section 4.4).
General disorders and administration site conditions
Common                   Peripheral oedema
Frequency not known      malaise, drowsiness
Investigations
Very common              Liver function test abnormal (transient, usually reversible elevation of transaminases and alkaline phosphatises) (see section 4.4)
Lipids abnormal (during treatment with high doses of acitretin, reversible elevation of serum triglycerides and serum cholesterol has occurred, especially in high-risk patients and during long-term treatment (see section 4.4).
An associated risk of atherogenesis cannot be ruled out if these conditions persist)

* Dryness of the conjunctivae may lead to mild-to-moderate conjunctivitis or xerophthalmia and result in intolerance of contact lenses; it may be alleviated by lubrication with artificial tears or topical antibiotics.

** Usually noted 4 to 8 weeks after starting therapy, and are reversible following discontinuation of Neotigason. Full recovery usually occurs within 6 months of stopping treatment in the majority of patients.

Paediatric population
There have been occasional reports of bone changes in children, including premature epiphyseal closure, skeletal hyperostosis and extraosseous calcification after long-term treatment with etretinate, these effects may be expected with acitretin. In children, growth parameters and bone development must be closely monitored.

Other special populations
Diabetics

Neotigason Capsules 10mg, 25mg, SPC, 02-2020, HH, Notification
Retinoids can either improve or worsen glucose tolerance (see section 4.4).
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: sideeffects.health.gov.il