Inovelon

/ Megapharm

Treatment with Inovelon should be initiated by a physician specialised in paediatrics or neurology with experience in the treatment of epilepsy. Inovelon is for oral use. It should be taken twice daily with water in the morning and in the evening, in two equally divided doses. As a food effect was observed, it will preferable to administer Inovelon with food. If the patient has difficulty with swallowing, tablets can be crushed and administered in half a glass of water.
Use in children four years of age or older and less than 30 kg Patients <30 kg not receiving valproate: Treatment should be initiated at a daily dose of 200 mg. According to clinical response and tolerability, the dose may be increased by 200 mg/day increments, as frequently as every two days, up to a maximum recommended dose of 1000 mg/day. Doses of up to 3600 mg/day have been studied in a limited number of patients.
Patients <30 kg also receiving valproate medication: As valproate significantly decreases clearance of Inovelon, a lower maximum dose of Inovelon is recommended for patients <30 kg being co-administered valproate. Treatment should be initiated at a daily dose of 200 mg. According to clinical response and tolerability, after a minimum of 2 days the dose may be increased by 200 mg/day, to the maximum recommended dose of 600 mg/day.
Use in adults and children four years of age or older of 30 kg or over: Treatment should be initiated at a daily dose of 400 mg. According to clinical response and tolerability, the dose may be increased by 400 mg/day increments, as frequently as every two days, up to a maximum recommended dose:
Weight range 30.0 – 50.0 kg 50.1 – 70.0 kg 70.1 kg Maximum recommended dose (mg/day) 1800 2400 3200 Doses of up to 4000 mg/day (in the 30-50 kg range) or 4800 mg/day (over 50 kg) have been studied in a limited number of patients.
Elderly: There is limited information on the use of Inovelon in the elderly. Since, the pharmacokinetics of rufinamide are not altered in the elderly, dosage adjustment is not required in patients over 65 years of age.
Patients with renal impairment: A study in patients with severe renal impairment indicated that no dose adjustments ar required for these patients.
Patients with hepatic impairment: Use in patients with hepatic impairment has not been studied. Caution and careful dose titration is recommended when treating patients with mild to moderate hepatic impairment. Therefore, use in patients with severe hepatic impairment is not recommended.
For full details see prescribing information.

Adjunctive therapy in the treatments of seizures associated with Lennox-Gastaut syndrome, in patients 4 years of age and older.

Hypersensitivity to the active substance, triazole derivatives or to any excipients. Pregnancy and lactation.

Status epilepticus cases have been observed during clinical development studies, under rufinamide whereas no such cases have been observed under placebo. These events led to rufinamide discontinuation in 20 % of the cases. If patients develop new seizure types and/or experience an increased frequency of status epilepticus that is different from the patient’s baseline condition, then the benefit risk ratio of the therapy should be reassessed. Antiepileptic medicinal products, including Inovelon, should be withdrawn gradually to reduce the possibility of seizures on withdrawal. In clinical studies discontinuation was achieved by reducing the dose by approximately 25% every two days. There are insufficient data on the withdrawal of concomitant antiepileptic medicinal products once seizure control has been achieved with the addition of Inovelon. Rufinamide treatment has been associated with dizziness, somnolence, ataxia and gait disturbances, which could increase the occurrence of accidental falls in this population. Patients and carers should exercise caution until they are familiar with the potential effects of this medicinal product. Serious antiepileptic drug hypersensitivity syndrome has occurred in association with rufinamide therapy. Signs and symptoms of this disorder were diverse; however, patients typically, although not exclusively, presented with fever and rash associated with other organ system involvement. Other associated manifestations included lymphadenopathy, liver function tests abnormalities, and haematuria. Because the disorder is variable in its expression, other organ system signs and symptoms not noted here may occur. This syndrome occurred in close temporal association to the initiation of rufinamide therapy and in the paediatric population. If this reaction is suspected, rufinamide should be discontinued and alternative treatment started. All patients who develop a rash while taking rufinamide must be closely monitored. In a thorough QT study, rufinamide produced a decrease in QTc interval proportional to concentration. Although the underlying mechanism and safety relevance of this finding is not known, clinicians should use clinical judgment when assessing whether to prescribe rufinamide to patients at risk from further shortening their QTc duration (eg. Congenital Short QT Syndrome or patients with a family history of such a syndrome). Women of childbearing potential must use contraceptive measures during treatment with Inovelon. Physicians should try to ensure that appropriate contraception is used, and should use clinical judgement when assessing whether oral contraceptives, or the doses of the oral contraceptive components, are adequate based on the individual patients clinical situation. Inovelon contains lactose, therefore patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Pregnancy and lactation: Women of childbearing age must use contraceptive measures during treatment. It is recommended to use an additional contraceptive in addition to hormonal contraceptive, since treatment might reduce the efficiency of hormonal contraceptives.
Effects on ability to drive and use machines: Inovelon may cause dizziness, somnolence and blurred vision. Depending on the individual sensitivity, Inovelon may have a mild to severe influence on the ability to drive or use machines. Patients must be advised to exercise caution during activities requiring a high degree of alertness, e.g., driving or operating machinery.
For full details see prescribing information.

Very common: Dizziness, headache, nausea, vomiting, sleepiness, fatigue.
Common: Problems associated with nerves including: Difficulty walking, abnormal movement, convulsions/seizures, unusual eye movements, blurred vision, trembling.
Problems associated with stomach including: Pain, constipation, indigestion, loose stools (diarrhea), loss or change in appetite, weight loss.
Infections: Ear infection, flu, nasal congestion, chest infections.
In addition, patients have experienced: Anxiety, insomnia, nose bleeds, acne, rash, back pain, infrequent periods, bruising, head injury.
For full details see prescribing information.

Potential for other medicinal products to affect Inovelon: Other anti-epileptic medicinal products Rufinamide concentrations may be decreased by co-administration with carbamazepine, phenobarbital, phenytoin, vigabatrin or primidone. For patients on Inovelon treatment who have administration of valproate initiated, significant increases in rufinamide plasma concentrations may occur. The most pronounced increases were observed in patients of low body weight (<30 kg). Therefore, consideration should be given to a dose reduction of Inovelon in patients <30 kg who are initiated on valproate therapy . The addition or withdrawal of these drugs or adjusting of the dose of these drugs during Inovelon therapy may require an adjustment in dosage of Inovelon. No significant changes in rufinamide concentration are observed following co-administration with lamotrigine, topiramate or benzodiazepines.
Potential for Inovelon to affect other medicinal products: Other anti-epileptic medicinal products The pharmacokinetic interactions between rufinamide and other anti-epileptic drugs have been evaluated in patients with epilepsy using population pharmacokinetic modelling. Rufinamide appears not to have clinically relevant effect on carbamazepine, lamotrigine, phenobarbital, topiramate or valproate steady state concentrations. Since rufinamide may decrease phenytoin clearance and increase average steady state plasma concentrations of co-administered phenytoin, consideration should be given to reducing the dose of phenytoin. Oral contraceptives Co-administration of rufinamide 800 mg b.i.d. and a combined oral contraceptive (ethinyloestradiol 35 μg and norethindrone 1 mg) for 14 days resulted in a mean decrease in the ethinyl estradiol AUC0-24 of 22% and in norethindrone AUC0-24 of 14%. Studies with other oral or implant contraceptives have not been conducted. Women of child-bearing potential using hormonal contraceptives are advised to use an additional safe and effective contraceptive method.
For full details see prescribing information.

Risk related to epilepsy and antiepileptic medicinal products in general: It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to three times greater than the rate of approximately 3% in the general population. In the treated population, an increase in malformations has been noted with polytherapy; however, the extent to which the treatment and/or the illness is responsible has not been elucidated. Moreover, effective anti-epileptic therapy must not be interrupted, since the aggravation of
the illness is detrimental to both the mother and the foetus.
Risk related to rufinamide: Studies in animals revealed no teratogenic effect but foetotoxicity in presence of maternal toxicity. The potential risk for humans is unknown. For rufinamide, no clinical data on exposed pregnancies are available. Taking these data into consideration, rufinamide should not be used during pregnancy unless clearly necessary and in women of childbearing age not using contraceptive measures. Women of childbearing potential must use contraceptive measures during treatment with Inovelon. Physicians should try to ensure that appropriate contraception is used, and should use clinical judgement when assessing whether oral contraceptives, or the doses of the oral contraceptive components, are adequate based on the individual patients clinical situation. If women treated with rufinamide plan to become pregnant, the indication of this product should be carefully weighed. During pregnancy, an effective antiepileptic rufinamide treatment must not be interrupted, since the aggravation of the illness is detrimental to both the mother and the foetus. It is not known if rufinamide is excreted in human breast milk. Due to the potential harmful effects for the breast fed infant, the lactation should be avoided during maternal treatment with rufinamide.

After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. There is no specific antidote for Inovelon. Treatment should be supportive and may include haemodialysis.