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2. QUALITATIVE AND QUANTITATIVE COMPOSITION
For a full list of excipients, see section 6.1.
4.5 Interaction with other medicinal products and other forms of interaction
Concurrent administration of isotretinoin with topical keratolytic or exfoliative anti-acne agents should be avoided as local irritation may increase (see section 4.4).
4.6 Pregnancy and lactation
Lactation:
Isotretinoin is highly lipophilic, therefore the passage of isotretinoin into human milk is very likely. Due to the potential for adverse effects in the mother and exposed child exposed via mothers¡¯ milk, the use of isotretinoin is contraindicated in nursing mothers.
4.7 Effects on ability to drive and use machines
Drowsiness, dizziness and visual disturbances have been reported very rarely. Patients should be warned that if they experience these effects, they should not drive, operate machinery or take part in any other activities where the symptoms could put either themselves or others at risk.
4.8 Undesirable effects
Some of the side effects associated with the use of isotretinoin are dose-related. The side effects are generally reversible after altering the dose or discontinuation of treatment, however some may persist after treatment has stopped. The following symptoms are the most commonly reported undesirable effects with isotretinoin: dryness of the skin, dryness of the mucosae e.g. of the lips, (cheilitis), the nasal mucosa, (epistaxis), and the eyes, (conjunctivitis)., dryness of the skin. Some of the side effects associated with the use of isotretinoin are dose-related. The side effects are generally reversible after altering the dose or discontinuation of treatment, however some may persist after treatment has stopped.
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Infections:
Very Rare (¡Ü 1/10 000)
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Gram positive (mucocutaneous) bacterial infection
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Blood and lymphatic system disorders:
Very common (¡Ý 1/10)
Common (¡Ý 1/100, < 1/10)
Very Rare (¡Ü 1/10 000)
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Anaemia, red blood cell sedimentation rate increased,
thrombocytopenia, thrombocytosis
Neutropenia
Lymphadenopathy
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Immune system disorders:
Rare (¡Ý 1/10 000,< 1/1000)
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Allergic skin reaction, anaphylactic reactions, hypersensitivity
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Metabolism and nutrition disorders:
Very Rare (¡Ü 1/10 000)
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Diabetes mellitus, hyperuricaemia
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Psychiatric disorders:
Rare (¡Ý 1/10 000,< 1/1000)
Very Rare (¡Ü 1/10 000)
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Depression, depression aggravated, aggressive tendencies, anxiety, mood alterations.
Abnormal behaviour, psychotic disorder, suicidal ideation suicide attempt, suicide
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Nervous system disorders:
Common (¡Ý 1/100, < 1/10)
Very Rare (¡Ü 1/10 000)
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Headache
Benign intracranial hypertension, convulsions, drowsiness, dizziness
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Eye disorders:
Very common (¡Ý 1/10)
Very Rare (¡Ü 1/10 000)
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Blepharitis, conjunctivitis, dry eye, eye irritation
blurred Blurred vision, cataract, colour blindness (colour vision deficiencies), contact lens intolerance, corneal opacity, decreased night vision, keratitis, papilloedema (as sign of benign intracranial hypertension), photophobia, visual disturbances.
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Ear and labyrinth disorders:
Very Rare (¡Ü 1/10 000)
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Hearing impaired
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Vascular disorders:
Very Rare (¡Ü 1/10 000)
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Vasculitis (for example Wegener¡¯s granulomatosis, allergic vasculitis)
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Respiratory, thoracic and mediastinal disorders:
Common (¡Ý 1/100, < 1/10)
Very Rare (¡Ü 1/10 000)
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Epistaxis, nasal dryness, nasopharyngitis
Bronchospasm (particularly in patients with asthma), hoarseness
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Gastrointestinal disorders:
Very Rare (¡Ü 1/10 000)
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Colitis, ileitis, dry throat, gastrointestinal haemorrhage, haemorrhagic diarrhoea and inflammatory bowel disease, nausea, pancreatitis (see section 4.4)
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Hepatobiliary disorders:
Very common (¡Ý 1/10)
Very Rare (¡Ü 1/10 000)
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Transaminase increased (see section 4.4)
Hepatitis
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Skin and subcutaneous tissues disorders:
Very common (¡Ý 1/10)
Rare (¡Ý 1/10 000,< 1/1000)
Very Rare (¡Ü 1/10 000)
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Cheilitis, dermatitis, dry skin, localised exfoliation, pruritus, rash erythematous, skin fragility (risk of frictional trauma)
Alopecia
Acne fulminans, acne aggravated (acne flare), erythema (facial), exanthema, hair disorders, hirsutism, nail dystrophy, paronychia, photosensitivity reaction, pyogenic granuloma, skin hyperpigmentation, sweating increased
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Musculo-skeletal and connective tissue disorders:
Very common (¡Ý 1/10)
Very Rare (¡Ü 1/10 000) Arthralgia, Myalgia
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Arthralgia, myalgia, back pain (particularly adolescent patients)
arthritisArthritis, calcinosis (calcification of ligaments and tendons), epiphyses premature fusion, exostosis, (hyperostosis), reduced bone density, tendonitis
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Renal and urinary disorders:
Very Rare (¡Ü 1/10 000)
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Glomerulonephritis
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General disorders and administration site conditions:
Very Rare (¡Ü 1/10 000)
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Granulation tissue (increased formation of), malaise
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Investigations:
Very common (¡Ý 1/10)
Common (¡Ý 1/100, < 1/10)
Very Rare (¡Ü 1/10 000)
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Blood triglycerides increased, high density lipoprotein decreased
Blood cholesterol increased, blood glucose increased, haematuria, proteinuria
Blood creatine phosphokinase increased
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The incidence of the adverse events was calculated from pooled clinical trial data involving 824 patients and from post-marketing data.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Retinoid for treatment of acne. anti-acne preparations for systemic use
ATC code: D10B A01
5.3 Preclinical safety data
Mutagenicity
Isotretinoin has not been shown to be mutagenic nor carcinogenic in in vitro or in vivo animal tests. respectively.
6.1 List of excipients
Capsule filling:
Beeswax, yellow;
Soya-bean oil, refined;
Soya-bean oil, hydrogenated,;
Soya-bean oil, partially hydrogenated.
Capsule shell:
Gelatin;
Glycerol;
Karion 83 containing sorbitol, mannitol, hydrogenated hydrolysed starch;
Titanium dioxide E171;
Canthaxanthin pigment E161, containing gelatin, arachis oil (peanut oil), canthaxanthin, ascorbyl palmitate, ¦Á-tocopherol and silica.
Printing ink:
Shellac, refined;
Black iron oxide E172.;
Titanium dioxide E171 (5 mg capsule only)
10. DATE OF REVISION OF THE TEXT
October 2006 November 2005
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