Adverse reactions : תופעות לוואי

4.8   Undesirable effects

The safety and efficacy of Toctino in patients with severe chronic hand eczema (CHE) unresponsive to treatment with potent topical corticosteroids has been evaluated in two randomised, double blind, placebo-controlled clinical studies (see section 5.1).

The most frequent adverse drug reactions (ADRs) observed under alitretinoin therapy are headache (30 mg: 23.9%; 10 mg: 10.8%), erythema (30 mg: 5.5%; 10 mg: 1.7%), nausea (30 mg: 5.1%; 10 mg: 2.4%), flushing (30 mg: 5.9%, 10 mg: 1.6%), and laboratory changes consisting of increased levels of triglycerides (30 mg: 35.4%; 10 mg: 17.0%), increased cholesterol (30 mg: 27.8%; 10 mg: 16.7%), decreased levels of thyroid stimulating hormone (TSH, 30 mg: 8.4%, 10 mg: 6.0%) and decreased levels of free T4 (30 mg: 10.5%; 10 mg: 2.9%). These reversible ADRs are dose dependent and may therefore be alleviated by dose reduction.

Very          Common       Uncommo Rare             Very Rare                     Unknown common        (≥ 1/100 < n            (≥ 1/10,000 <
(≥ 1/10)      1/10)        (≥ 1/1000, 1/1000)       (<1/10000)
< 1/100)
Blood and                   Anaemia,
lymphatic                   increased system                      iron binding disorders                   capacity,
monocytes decreased;
thrombocyte s increased
Immune                                                                                          Anaphylactic system                                                                                          reactions, disorders                                                                                       hypersensitiv ity
Endocrine                   TSH
Disorders                   decreased,
free      T4 decreased
Psychiatri                                                 Depression,      Suicide, suicide c                                                          depression       attempt, suicidal disorders                                                  aggravated,      ideation, aggressive       psychotic tendencies,      disorder,
anxiety,
Very        Common         Uncommo Rare                      Very Rare    Unknown common      (≥ 1/100 < n              (≥ 1/10,000 <
(≥ 1/10)    1/10)          (≥ 1/1000, 1/1000)                (<1/10000) < 1/100) mood                   abnormal alterations            behaviour
Nervous       Headache    Dizziness                 Benign system                                              intracranial disorders                                           hypertension
Eye                       Conjunctivit Blurred                                          Decreased disorders                 is, dry eye, vision,                                          night vision eye irritation cataract
Ear and                   Tinnitus labyrinth disorders
Vascular                  Flushing,                        Vasculitis disorders                 hypertensio n
Respirato                                   Epistaxis ry,
thoracic and mediastin al disorders
Gastroint                 Nausea, dry Dyspepsia                                         Inflammatory estinal                   mouth,                                                        bowel disorders                 vomiting                                                      disease Hepatobili                Transaminas ary                       e increased1) disorders
Skin and                  Dry      skin,    Pruritus,      Nail subcutane                 dry       lips,   rash, skin     disorders, ous tissues               cheileitis,       exfoliation    photosensitiv disorders                 eczema1),         , asteatotic   ity reaction, dermatitis1) ,    eczema         hair texture erythema,                        changes alopecia
Musculo-                  Arthralgia1),     Exostosis,
skeletal                  myalgia1)         (hyperosto and                                         sis),
connective                                  ankylosing tissue                                      spondylitis disorders
General                   Fatigue                                                       Peripheral disorders                                                                               oedema and administr ation site conditions
Investigati Hypertrigl    Blood ons         yceridemia    creatinine
,      high   phosphokina density       se increased lipoprotein decreased,
Very          Common     Uncommo Rare             Very Rare                   Unknown common        (≥ 1/100 < n          (≥ 1/10,000 <
(≥ 1/10)      1/10)      (≥ 1/1000, 1/1000)       (<1/10000)
< 1/100) hyperchole sterolaemi a
1)
The overall incidence of adverse events was not higher than those observed in the corresponding placebo group.

The following adverse events have not been observed in clinical trials with alitretinoin, but have been observed with other retinoids: diabetes mellitus, colour blindness (colour vision deficiencies), and contact lens intolerance (see section 4.4).

Changes in bone mineralisation and extra-osseous calcifications have been associated with systemic retinoid treatment. In clinical studies with alitretinoin, degenerative changes of the spine and ligamentous calcifications were frequent findings in patients with chronic hand eczema before treatment (baseline), with minor progression in a small number of patients during treatment. These observations were consistent with age dependent degenerative changes. Assessments of bone density (DXA) did not indicate a dose dependent effect on bone mineralisation.

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/ Additionally, you should also report to GSK Israel (il.safety@gsk.com).