Leitlinien & Arzneimittelsicherheit

HOS-217291 · has-adverse-reaction-information · PDF-Seite 11

Summary of the safety profile Zonisamide has been administered to over 1,200 patients in clinical studies, more than 400 of whom received zonisamide for at least 1 year. In addition there has been extensive post-marketing experience with zonisamide in Japan since 1989 and in the USA since 2000. It should be noted that zonisamide is a benzisoxazole derivative, which contains a sulfonamide group. Serious immune based adverse reactions that are associated with medicinal products containing a sulfonamide group include rash, allergic reaction and major haematological disturbances including aplastic anaemia, which very rarely can be fatal (see section 4.4). The most common adverse reactions in controlled adjunctive-therapy studies were somnolence, dizziness and anorexia. The most common adverse reactions in a randomised, controlled monotherapy trial comparing zonisamide with carbamazepine prolonged release were decreased bicarbonate, decreased appetite, and decreased weight. The incidence of markedly abnormally low serum bicarbonate (a decrease to less than 17 mEq/l and by more than 5 mEq/l) was 3.8%. The incidence of 11 marked decreases in weight of 20% or more was 0.7%. Tabulated list of adverse reactions Adverse reactions associated with zonisamide obtained from clinical studies and post-marketing surveillance are tabulated below. The frequencies are arranged according to the following scheme: 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 Table 4. Adverse reactions associated with zonisamide obtained from adjunctive use clinical studies and post-marketing surveillance System Organ Very Common Uncommon Very Rare Class (MedDRA Common terminology) Infections and Pneumonia infestation Urinary tract infection Blood and Ecchymosis Agranulocytosis lymphatic system Aplastic anaemia disorders Leucocytosis

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217287 · has-contraindication-information · PDF-Seite 5

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to sulfonamides.

HOS-217286 · has-indication-information · PDF-Seite 2

Zonisamide Viatris is indicated as: • monotherapy in the treatment of partial seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy (see section 5.1); • adjunctive therapy in the treatment of partial seizures, with or without secondary generalisation, in adults, adolescents, and children aged 6 years and above.

HOS-217289 · has-interaction-information · PDF-Seite 9

Effect of zonisamide on cytochrome P450 enzymes In vitro studies using human liver microsomes show no or little (< 25%) inhibition of cytochrome P450 isozymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 or 3A4 at zonisamide levels approximately two-fold or greater than clinically relevant unbound serum concentrations. Therefore, zonisamide is not expected to affect the pharmacokinetics of other medicinal products via cytochrome P450-mediated mechanisms, as demonstrated for carbamazepine, phenytoin, ethinylestradiol and desipramine in vivo. Potential for zonisamide to affect other medicinal products Anti-epileptic medicinal products In epileptic patients, steady-state dosing with zonisamide resulted in no clinically relevant pharmacokinetic effects on carbamazepine, lamotrigine, phenytoin, or sodium valproate. Oral contraceptives In clinical studies in healthy subjects, steady-state dosing with zonisamide did not affect serum concentrations of ethinylestradiol or norethisterone in a combined oral contraceptive. Carbonic anhydrase inhibitors Zonisamide should be used with caution in adult patients treated concomitantly with carbonic anhydrase inhibitors such as topiramate and acetazolamide, as there are insufficient data to rule out a 9 possible pharmacodynamic interaction (see section 4.4). Zonisamide should not be used as co-medication in paediatric patients with other carbonic anhydrase inhibitors such as topiramate and acetazolamide (see section 4.4: Paediatric population). P-gp substrate An in vitro study shows that zonisamide is a weak inhibitor of P-gp (MDR1) with an IC50 of 267 µmol/l and there is the theoretical potential for zonisamide to affect the pharmacokinetics of substances which are P-gp substrates. Caution is advised when starting or stopping zonisamide treatment or changing the zonisamide dose in patients who are also receiving medicinal products which are P-gp substrates (e.g. digoxin, quinidine). Potential medicinal product interactions affecting zonisamide In clinical studies co-administration of lamotrigine had no apparent effect on zonisamide pharmacokinetics. The combination of zonisamide with other medicinal products that may lead to urolithiasis may enhance the risk of developing kidney stones; therefore the concomitant administration of such medicinal products should be avoided. Zonisamide is metabolised partly by CYP3A4 (reductive cleavage), and also by N-acetyl-transferas

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217290 · has-pregnancy-information · PDF-Seite 10

Women of childbearing potential Women of childbearing potential must use effective contraception during treatment with zonisamide, and for one month after discontinuation. Zonisamide must not be used in women of childbearing potential not using effective contraception unless clearly necessary and only if the potential benefit is considered to justify the risk to the foetus. Specialist medical advice should be given to women treated with zonisamide who are of childbearing potential. The woman should be fully informed of and understand the possible effects of Zonisamide Viatris on the foetus and these risks should be discussed with the patient in relation to the benefits before starting treatment. Pregnancy testing in women of childbearing potential should be considered prior to initiating treatment with zonisamide. Women planning a pregnancy should meet with their specialists to reassess treatment with zonisamide and to consider other therapeutic options prior to conception and before contraception is discontinued. 10 As with all antiepileptic medicines, sudden discontinuation of zonisamide should be avoided as this may lead to breakthrough seizures that could have serious consequences for the woman and the unborn child. The risk of birth defect is increased by factor 2 to 3 in the offspring of mothers treated with an antiepileptic medicinal product. The most frequently reported are cleft lip, cardiovascular malformations and neural tube defect. Multiple antiepileptic medicinal product therapy may be associated with a higher risk of congenital malformations than monotherapy. Pregnancy There are limited data from the use of zonisamide in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). In humans the potential risk of major congenital malformations and neurodevelopmental disorders is unknown. Data from a registry study suggest an increase in the proportion of babies born at a low birth weight (LBW), pre-term or small for gestational age (SGA). These increases are from about 5% to 8% for LBW, from about 8% to 10% for pre-term birth and from about 7% to 12% for SGA, all compared with mothers treated with lamotrigine monotherapy. Zonisamide must not be used during pregnancy unless clearly necessary and only if the potential benefit is considered to justify the risk to the foetus. If zonisamide is prescribed during pregnancy, patients should be fully informed of the

Auszug; vollständigen Abschnitt im Original lesen.

HOS-217288 · has-warning-information · PDF-Seite 5

Unexplained rash Serious rashes occur in association with zonisamide therapy, including cases of Stevens-Johnson syndrome. Consideration must be given to discontinuing zonisamide in patients who develop an otherwise unexplained rash. All patients who develop a rash while taking zonisamide must be closely supervised, with additional levels of caution applied to those patients receiving concomitant antiepileptic agents that may independently induce skin rashes. Withdrawal seizures In accordance with current clinical practice, discontinuation of zonisamide in patients with epilepsy must be accomplished by gradual dose reduction, to reduce the possibility of seizures on withdrawal. There are insufficient data for the withdrawal of concomitant antiepileptic medicines once seizure control with zonisamide has been achieved in the add-on situation, in order to reach monotherapy with zonisamide. Therefore, withdrawal of concomitant anti-epileptic medicinal products must be undertaken with caution. Sulfonamide reactions Zonisamide is a benzisoxazole derivative, which contains a sulfonamide group. Serious immune based adverse reactions that are associated with medicinal products containing a sulfonamide group include rash, allergic reaction and major haematological disturbances, including aplastic anaemia, which very rarely can be fatal. Cases of agranulocytosis, thrombocytopenia, leucopenia, aplastic anaemia, pancytopenia and leucocytosis have been reported. There is inadequate information to assess the relationship, if any, between dose and duration of treatment and these events. Acute myopia and secondary angle closure glaucoma A syndrome consisting of acute myopia associated with secondary angle closure glaucoma has been reported in adult and paediatric patients receiving zonisamide. Symptoms include acute onset of 5 decreased visual acuity and/or ocular pain. Ophthalmologic findings can include myopia, anterior chamber shallowing, and ocular hyperaemia (redness) and increased intraocular pressure. This syndrome may be associated with supraciliary effusion resulting in anterior displacement of the lens and iris, with secondary angle closure glaucoma. Symptoms may occur within hours to weeks of initiating therapy. Treatment includes discontinuation of zonisamide, as rapidly as possible in the judgment of the treating physician, and appropriate measures to reduce intraocular pressure. Elevated intraocular

Auszug; vollständigen Abschnitt im Original lesen.