Adverse reactions : תופעות לוואי

6      ADVERSE REACTIONS
The following serious adverse reactions are described elsewhere in the labeling: • Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.1)] • Suicidal Behavior and Ideation [see Warnings and Precautions (5.2)] • Serious Dermatologic Reactions [see Warnings and Precautions (5.3)] • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see Warnings and Precautions (5.4)]
• Hypersensitivity [see Warnings and Precautions (5.5)]
• Cardiac Effects [see Warnings and Precautions (5.6)]
• Angioedema [see Warnings and Precautions (5.7)]
• Hepatic Injury [see Warnings and Precautions (5.8)]
• Hematopoietic Complications [see Warnings and Precautions (5.9)]
• Effects on Vitamin D and Bone [see Warnings and Precautions (5.10)] • Exacerbation of Porphyria [see Warnings and Precautions (5.11)]
• Teratogenicity and Other Harm to the Newborn [see Warnings and Precautions (5.12)] • Hyperglycemia [see Warnings and Precautions (5.14)]

The following adverse reactions associated with the use of Epanutin were identified in clinical studies or postmarketing reports. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body as a Whole: Allergic reactions in the form of rash and rarely more serious forms and DRESS have been observed, as has angioedema [see Warnings and Precautions (5.3, 5.4, 5.7)]. Anaphylaxis has also been reported.
There have also been reports of coarsening of facial features, systemic lupus erythematosus, periarteritis nodosa, and immunoglobulin abnormalities.
Digestive System: Acute hepatic failure, toxic hepatitis, liver damage, nausea, vomiting, constipation, enlargement of the lips, and gingival hyperplasia.
Hematologic and Lymphatic System: Hematopoietic complications, some fatal, have occasionally been reported in association with administration of phenytoin. These have included thrombocytopenia, leukopenia, granulocytopenia, agranulocytosis, and pancytopenia with or without bone marrow suppression. While macrocytosis and megaloblastic anemia have occurred, these conditions usually respond to folic acid therapy.
Lymphadenopathy including benign lymph node hyperplasia, pseudolymphoma, lymphoma, and Hodgkin’s disease have been reported [see Warnings and Precautions (5.9)]. Pure red cell aplasia has also been reported.

Laboratory Test Abnormality: Phenytoin may decrease serum concentrations of thyroid hormone (T4 and T3), sometimes with an accompanying increase in thyroid-stimulating hormone (TSH), but usually in the absence of clinical hypothyroidism. Phenytoin may also produce lower than normal values for dexamethasone or metyrapone tests. Phenytoin may cause increased serum levels of glucose [see Warnings and Precautions (5.14)], alkaline phosphatase, and gamma glutamyl transpeptidase (GGT).
Nervous System: The most common adverse reactions encountered with phenytoin therapy are nervous system reactions and are usually dose-related. Reactions include nystagmus, ataxia, slurred speech, decreased coordination, somnolence, and mental confusion. Dizziness, vertigo, insomnia, transient nervousness, motor twitchings, paresthesias, and headaches have also been observed. There have also been rare reports of phenytoin-induced dyskinesias, including chorea, dystonia, tremor and asterixis, similar to those induced by phenothiazine and other neuroleptic drugs. Cerebellar atrophy has been reported, and appears more likely in settings of elevated phenytoin levels and/or long-term phenytoin use [see Warnings and Precautions (5.15)].
A predominantly sensory peripheral polyneuropathy has been observed in patients receiving long-term phenytoin therapy.
Skin and Appendages: Dermatological manifestations sometimes accompanied by fever have included scarlatiniform or morbilliform rashes. A morbilliform rash (measles-like) is the most common; other types of dermatitis are seen more rarely. Other more serious forms which may be fatal have included bullous, exfoliative or purpuric dermatitis, acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, and toxic epidermal necrolysis [see Warnings and Precautions (5.3)]. There have also been reports of hypertrichosis and urticaria.
Special Senses: Altered taste sensation including metallic taste.
Urogenital: Peyronie’s disease

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 event should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il