Most of the adverse effects of isotretinoin are dose related. In the proper dosage, tolerability is generally acceptable in view of the severity of the disease. Every patient should be warned about the possible occurrence of adverse effects.
The most frequently observed symptoms are those associated with hypervitaminosis A, i.e. dryness of the mucosa, which on the lips can be relieved by the application of a fatty ointment, dryness of the nasal mucosa which can lead to epistaxis, dryness of the pharyngeal mucosa and hoarseness and dryness of the vaginal and/or anal mucosa.
Dryness of the eyes can cause conjunctivitis and reversible corneal opacities.
Conjunctivitis can be improved by a mild eye ointment. Intolerance to contact lenses may force the patient to wear glasses during treatment. Isolated cases of photophobia, dark adaptation disturbances (decreased night vision) and lenticular cataracts have been reported. Keratitis in association with isotretinoin treatment is a rare event and possibly related to the dry eye syndrome. Therefore patients, particularly those with dry eye syndrome, should be monitored for the development of keratitis.
Exanthema, pruritus, dermatitis facialis, sweating, pyogenic granuloma, paronychia, nail dystrophy and increased formation of granulation tissue may occur. Rare cases of persistent hair thinning have been reported. Reversible alopecia has been observed. Hirsutism, acne fulminans and hyperpigmentation (facial) have been reported rarely. Rarely, patients may experience photosensitivity reactions.
Bone changes and hyperostosis have occurred in children (including premature epiphyseal closure) and adults treated over long periods with high doses of isotretinoin generally for indications other than cystic acne. In one patient, spinal hyperostoses and calcification of the spinal ligaments with subsequent compression of the spinal cord were observed following long-term treatment over several years with another retinoid, etretinate. Isotretinoin is not intended for long-term therapeutic use, and the possibility of this adverse effect occurring if it is used improperly for long-term treatment should be borne in mind.
Minimal hyperostosis has been observed in cystic acne patients treated with a single course of isotretinoin. Due to the possible occurrence of these bone changes, a careful evaluation of the risk/benefit ratio should be carried out in every patient and isotretinoin administration should be restricted to severe cases.
There have been cases of allergic vasculitis including Wegener's granulomatosis, decreases in white and red blood cell counts including anaemia and neutropenia, increases and decreases in platelet count, elevated sedimentation rate.
Respiratory System Disorders:
Bronchospasm has been rarely reported; sometimes in patients with a pre-history of asthma.
Psychiatric and Central Nervous System Disorders:
Behavioural disorders, depression (see Precautions), headache, increased intracranial pressure (pseudotumor cerebri) and seizures.
Rare (may affect up to 1 in 1,000 people): Depression, depression aggravated, aggressive tendencies, anxiety, mood alterations.
Very rare (may affect up to 1 in 10,000 people): Suicide, suicide attempt, suicidal ideation, psychotic disorder, abnormal behaviour.
Transitory and reversible increases in transaminases as well as some cases of hepatitis related to isotretinoin have been observed. In many such cases the changes have been within the normal range and values have returned to baseline levels during treatment. In other cases, however, it has been necessary to reduce the dosage or discontinue treatment with isotretinoin.
Increases in serum triglyceride and cholesterol levels as well as a decrease of HDL have also been observed, particularly at high dosages and in predisposed patients (with a family history of lipid metabolism disorders, diabetes, obesity or alcoholism). These changes too are dose-related, and values return to normal on reduction of the dosage or withdrawal of the medicine.
Isolated cases of benign intracranial hypertension and visual disturbances, and occasionally nausea and headache have been observed. Pancreatitis and haematuria/proteinurea occur rarely.
Impaired hearing in certain frequencies and local or systemic infections due to Gram-positive microorganisms (Staphylococcus aureus
) have been reported.
Muscle and joint pain and, more rarely, overdosage, inflammatory bowel disease (eg. Colitis, ileitis haemorrhage), and hyperuricaemia have been reported.
Lymphadenopathy has occasionally been noted.
Sexual dysfunction including erectile dysfunction and decreased libido have also been reported.