India Product

Aclotol Fast Gel

Aclotol Fast Gel

Why you have been prescribed this medicine?

You have been prescribed this medicine if you have any of the following:
Kusapin is indicated for the treatment of partial seizures with or without secondarily generalised tonic-clonic seizures. Kusapin is indicated for use as monotherapy or adjunctive therapy in adults and in children of 6 years of age and above.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:
Therapeutic indications.
Kusapin is indicated for the treatment of partial seizures with or without secondarily generalised tonic-clonic seizures. Kusapin is indicated for use as monotherapy or adjunctive therapy in adults and in children of 6 years of age and above.

Posology and method of administration

It is used orally, regardless of meal. Kusapin can be used as monotherapy and in combination with other antiepileptic medicines. In both cases, treatment begins with a clinically effective dose divided into two doses. The dose may be increased according to the treatment efficacy. In case of replacement of other antiepileptic medicine by Kusapin at the beginning of Kusapin use the dose of replaced medicine should be gradually lowered. In case of Kusapin usage in combination therapy it may be necessary to decrease the dose of concomitant antiepileptic agents and/or a slower increase of Kusapin dose.


Below recommendations are for patients with normal hepatic function. This group of patients does not need in monitoring of concentrations of active substance in plasma during the therapy with Kusapin. There are break-lines on tablets; therefore, they can be broken into two parts for easier swallowing.

Adults:
Monotherapy:
Initial dose of this medicine is 600 mg/day (8–10 mg/kg of body weight per day) divided into 2 doses. If necessary it may be necessary a gradual dose increase. The dose is increased not more than by 600 mg/day at 1 week interval up to reaching of the desired therapeutical effect. Therapeutical effect is observed within the dosage range of 600–2400 mg/day. In steady-state conditions while ensuring of adequate control of patient's state there is an experience of rapid dose increase up to 2400 mg/day within 48 hours.

Combination therapy:
If it is administered in combination therapy the initial dose is 600 mg/day (8–10 mg/kg of body weight per day) divided into 2 doses. If necessary it is possible a gradual dose increase. The dose is increased not more than by 600 mg/day, at 1 week intervals, to achieve the desired therapeutic effect. Therapeutical effect is observed within the dosage range of 600–2400 mg/day.
Most patients poorly tolerated 2400 mg/day dose without lowering the dose of other antiepileptic agents, which were concomitantly used, that was associated with the occurrence of CNS adverse reactions. Kusapin use in daily dose more than 2400 mg has not been studied.
Children:
It is used in children over 6 years old. Recommended initial dose for children is 8–10 mg/kg of body weight divided into 2 intakes both in monotherapy and in Kusapin use in combination therapy. If necessary, to achieve the desired therapeutic effect, it is possible a gradual dose increase: at an interval of about 1 week – the dose is increased by 10 mg/kg of body weight per day to maximum daily dose of 46 mg/kg of body weight per day. In Kusapin use in combination therapy in pediatrics children above 6 years old, an average dose of this medicine is 30 mg/kg of body weight per day.
There is no data concerning this medicine administered in children with kidney dysfunction. Patients with liver dysfunction of mild to moderate degree do not need dosage adjustment. There is no data concerning this medicine administration in patients with severe liver dysfunction, therefore it is not recommended to use Kusapin in this group of patients.
Recommended dose for patients with kidney dysfunction (creatinine clearance <30 ml/min) is 300 mg/day with its slow increase (at an interval of not less than 1 week) up to reaching of the desired therapeutical effect.

When you should consult your doctor?

You should consult your doctor if you experience any of the following:
In this section undesirable effects are defined as follows:
The most commonly reported adverse reactions are somnolence, headache, dizziness, diplopia, nausea, vomiting and fatigue occurring in more than 10% of patients.
The undesirable effect profile by body system is based on AEs from clinical trials assessed as related to Kusapin. In addition, clinically meaningful reports on adverse experiences from named patient programs and postmarketing experience were taken into account.

Frequency estimate*:- very common: 1/10; common: 1/100 - < 1/10; uncommon: 1/1,000 - < 1 /100; rare: 1/10,000 - < 1/1,000; very rare: < 1/10,000; unknown: cannot be estimated from the available data.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
(Better in tabulated form)
Blood and lymphatic system disorder
Uncommon- leucopenia
Very rare- thrombocytopenia
Unknown- bone marrow depression, aplastic anemia, agranulocytosis, pancytopenia, neutropenia

Immune system disorders
Very rare- hypersensitivity (including multi-organ hypersensitivity) characterised by features such as rash, fever. Other organs or systems may be affected such as blood and lymphatic system (e.g. eosinophilia, thrombocytopenia, leucopenia, lymphadenopathy and splenomegaly), liver (e.g. abnormal liver function tests, hepatitis), muscles and joints (e.g. joint swelling, myalgia and arthralgia), nervous system (e.g. hepatic encephalopathy), kidney (e.g. proteinuria, nephritis interstitial, renal failure), lungs (e.g. dyspnea, pulmonary oedema, asthma, bronchospasms, interstitial lung disease), angioedema.

Unknown- anaphylactic reactions

Metabolism and nutrition disorders
Common- hyponatraemia
Very rare- hyponatraemia associated with signs and symptoms such as seizures, confusion, depressed level of consciousness, encephalopathy (see also Nervous system disorders for further undesirable effects), vision disorders (e.g. blurred vision), vomiting, nausea† . Unknown- hypothyroidism

Psychiatric disorders
Common- confusional state, depression, apathy, agitation (e.g. nervousness), affect lability

Nervous system disorders
Very common- somnolence, headache, dizziness
Common- ataxia, tremor, nystagmus, disturbance in attention, amnesia

Eye disorders
Very common- diplopia
Common- vision blurred, visual disturbance

Ear and labyrinth disorders
Common- vertigo

Cardiac disorders
Very rare- arrhythmia, atrioventricular block.

Vascular disorders Unknown- hypertension

Gastrointestinal disorders
Very common- nausea, vomiting
Common- diarrhoea, constipation, abdominal pain
Very rare- pancreatitis and/or lipase and/or amylase increase
Hepato-biliary disorders
Very rare- hepatitis

Skin and subcutaneous tissue disorders
Common- rash, alopecia, acne
Uncommon- urticaria
Very rare- angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme

Musculoskeletal, connective tissue and bone disorders
Very rare- systemic lupus erythematosus

General disorders and administration site conditions
Very common- fatigue
Common- asthenia

Investigations
Uncommon- hepatic enzymes increased, blood alkaline phosphatase increased
Unknown- decrease in T4 (with unclear clinical significance)
* according to CIOMS III frequency classification
†Very rarely clinically significant hyponatraemia (sodium <125 mmol/l) can develop during Kusapin use. It generally occurred during the first 3 months of treatment with Kusapin, although there were patients who first developed a serum sodium <125 mmol/l more than 1 year after initiation of therapy (see section 4.4).

Когда Вы должны проконсультироваться с вашим врачем ?

Если приближается время для принятия следующей дозы , проигнорируйте пропущенную дозу и примите следующую дозу как вам назначено.
В противном случае , примите дозу сразу , как только Вы вспомнили о ней и далее принимайте как обычно.

Things you MUST NOT DO while on this medicine?

Contraindications.
Hypersensitivity to the active substance or to any of the excipients.

What to do if you accidentally take too much (overdose) of the medicine?

Overdose
There are single reports of this medicine overdose; maximum dose, specified in these reports, was 24 g.
Symptoms:
somnolence, dizziness, nausea, vomiting, hyperkinesia, hyponatremia, ataxia, nystagmus.
Treatment:
There is no specific antidote. Symptomatic and supporting treatment is used. In case of recent use (within the last 2 hours) it is recommended a gastric lavage and activated charcoal use to reduce absorption.

Is it safe in pregnancy and breast-feeding?

Tell your doctor immediately if you become pregnant while taking this medication.
For safety of any drug during pregnancy or breastfeeding – please consult your doctor.

Storage Conditions:

Store below 30°C. Keep out of reach of children.

Drug Description

Each film-coated tablet contains:
Oxcarbazepine……300 mg
For excipients, see section 6.1

Indications and dosage.

Therapeutic indications.
Kusapin is indicated for the treatment of partial seizures with or without secondarily generalised tonic-clonic seizures. Kusapin is indicated for use as monotherapy or adjunctive therapy in adults and in children of 6 years of age and above.

Posology and method of administration

It is used orally, regardless of meal. Kusapin can be used as monotherapy and in combination with other antiepileptic medicines. In both cases, treatment begins with a clinically effective dose divided into two doses. The dose may be increased according to the treatment efficacy. In case of replacement of other antiepileptic medicine by Kusapin at the beginning of Kusapin use the dose of replaced medicine should be gradually lowered. In case of Kusapin usage in combination therapy it may be necessary to decrease the dose of concomitant antiepileptic agents and/or a slower increase of Kusapin dose.


Below recommendations are for patients with normal hepatic function. This group of patients does not need in monitoring of concentrations of active substance in plasma during the therapy with Kusapin. There are break-lines on tablets; therefore, they can be broken into two parts for easier swallowing.

Adults:
Monotherapy:
Initial dose of this medicine is 600 mg/day (8–10 mg/kg of body weight per day) divided into 2 doses. If necessary it may be necessary a gradual dose increase. The dose is increased not more than by 600 mg/day at 1 week interval up to reaching of the desired therapeutical effect. Therapeutical effect is observed within the dosage range of 600–2400 mg/day. In steady-state conditions while ensuring of adequate control of patient's state there is an experience of rapid dose increase up to 2400 mg/day within 48 hours.

Combination therapy:
If it is administered in combination therapy the initial dose is 600 mg/day (8–10 mg/kg of body weight per day) divided into 2 doses. If necessary it is possible a gradual dose increase. The dose is increased not more than by 600 mg/day, at 1 week intervals, to achieve the desired therapeutic effect. Therapeutical effect is observed within the dosage range of 600–2400 mg/day.
Most patients poorly tolerated 2400 mg/day dose without lowering the dose of other antiepileptic agents, which were concomitantly used, that was associated with the occurrence of CNS adverse reactions. Kusapin use in daily dose more than 2400 mg has not been studied.
Children:
It is used in children over 6 years old. Recommended initial dose for children is 8–10 mg/kg of body weight divided into 2 intakes both in monotherapy and in Kusapin use in combination therapy. If necessary, to achieve the desired therapeutic effect, it is possible a gradual dose increase: at an interval of about 1 week – the dose is increased by 10 mg/kg of body weight per day to maximum daily dose of 46 mg/kg of body weight per day. In Kusapin use in combination therapy in pediatrics children above 6 years old, an average dose of this medicine is 30 mg/kg of body weight per day.
There is no data concerning this medicine administered in children with kidney dysfunction. Patients with liver dysfunction of mild to moderate degree do not need dosage adjustment. There is no data concerning this medicine administration in patients with severe liver dysfunction, therefore it is not recommended to use Kusapin in this group of patients.
Recommended dose for patients with kidney dysfunction (creatinine clearance <30 ml/min) is 300 mg/day with its slow increase (at an interval of not less than 1 week) up to reaching of the desired therapeutical effect.

Side effects and drug interactions.

Undesirable effects
The most commonly reported adverse reactions are somnolence, headache, dizziness, diplopia, nausea, vomiting and fatigue occurring in more than 10% of patients.
The undesirable effect profile by body system is based on AEs from clinical trials assessed as related to Kusapin. In addition, clinically meaningful reports on adverse experiences from named patient programs and postmarketing experience were taken into account.

Frequency estimate*:- very common: 1/10; common: 1/100 - < 1/10; uncommon: 1/1,000 - < 1 /100; rare: 1/10,000 - < 1/1,000; very rare: < 1/10,000; unknown: cannot be estimated from the available data.
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
(Better in tabulated form)
Blood and lymphatic system disorder
Uncommon- leucopenia
Very rare- thrombocytopenia
Unknown- bone marrow depression, aplastic anemia, agranulocytosis, pancytopenia, neutropenia

Immune system disorders
Very rare- hypersensitivity (including multi-organ hypersensitivity) characterised by features such as rash, fever. Other organs or systems may be affected such as blood and lymphatic system (e.g. eosinophilia, thrombocytopenia, leucopenia, lymphadenopathy and splenomegaly), liver (e.g. abnormal liver function tests, hepatitis), muscles and joints (e.g. joint swelling, myalgia and arthralgia), nervous system (e.g. hepatic encephalopathy), kidney (e.g. proteinuria, nephritis interstitial, renal failure), lungs (e.g. dyspnea, pulmonary oedema, asthma, bronchospasms, interstitial lung disease), angioedema.

Unknown- anaphylactic reactions

Metabolism and nutrition disorders
Common- hyponatraemia
Very rare- hyponatraemia associated with signs and symptoms such as seizures, confusion, depressed level of consciousness, encephalopathy (see also Nervous system disorders for further undesirable effects), vision disorders (e.g. blurred vision), vomiting, nausea† . Unknown- hypothyroidism

Psychiatric disorders
Common- confusional state, depression, apathy, agitation (e.g. nervousness), affect lability

Nervous system disorders
Very common- somnolence, headache, dizziness
Common- ataxia, tremor, nystagmus, disturbance in attention, amnesia

Eye disorders
Very common- diplopia
Common- vision blurred, visual disturbance

Ear and labyrinth disorders
Common- vertigo

Cardiac disorders
Very rare- arrhythmia, atrioventricular block.

Vascular disorders Unknown- hypertension

Gastrointestinal disorders
Very common- nausea, vomiting
Common- diarrhoea, constipation, abdominal pain
Very rare- pancreatitis and/or lipase and/or amylase increase
Hepato-biliary disorders
Very rare- hepatitis

Skin and subcutaneous tissue disorders
Common- rash, alopecia, acne
Uncommon- urticaria
Very rare- angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme

Musculoskeletal, connective tissue and bone disorders
Very rare- systemic lupus erythematosus

General disorders and administration site conditions
Very common- fatigue
Common- asthenia

Investigations
Uncommon- hepatic enzymes increased, blood alkaline phosphatase increased
Unknown- decrease in T4 (with unclear clinical significance)
* according to CIOMS III frequency classification
†Very rarely clinically significant hyponatraemia (sodium <125 mmol/l) can develop during Kusapin use. It generally occurred during the first 3 months of treatment with Kusapin, although there were patients who first developed a serum sodium <125 mmol/l more than 1 year after initiation of therapy (see section 4.4).

Interaction with other medicinal products and other forms of interaction.
Inhibitors of microsomal enzymes:
Oxcarbazepine and its active pharmacokinetic metabolite MND are inhibitors of cytochrome CYP2S19. Thus,
co-administration of high doses of Kusapin and agents, which metabolize CYP2S19 (phenobarbital, phenytoin), may lead to interaction. For some patients it may be necessary the dose lowering of agents-substrates of CYP2S19.

It was shown that oxcarbazepine and MND weakly or nearly interact with the following microsomal isoenzymes: CYP1A2, CYP2A6, CYP2D9, CYP2E1, CYP4A4 and CYP4C11.
Inducers of microsomal enzymes: Being inducers of CYP3A4 and CYP3A5, oxcarbazepine and MND reduce plasma
concentrations of agents, which are metabolized by these enzymes: immunosuppressive agents (cyclosporine, tacrolimus), dihydropyridine calcium antagonists, oral contraceptives and antiepileptic drugs (eg, carbamazepine). A new level of induction is achieved during 2–3 weeks after the therapy start or change of this medicine dose. Valproic acid and lamotrigine: In vitro MND is a weak inducer of UDP-glucuronyltransferase. Taking into account even weak induction capacity of oxcarbazepine and MND it may be necessary to increase doses of concomitant agents, which are metabolized by CYP3A4 system or UDP- glucuronyltransferase. In case of Kusapin medicine withdrawal it may be necessary these drugs dosage lowering and adjustment of the final dose during 2–3 weeks (induction reducing is possible).
Antiepileptic medicinal products
Potential interactions between Kusapin and other antiepileptic medicinal products were assessed in clinical studies. The effect of these interactions on mean AUCs and Cmin are summarised in the following table,
Summary of antiepileptic medicinal product interactions with Kusapin

Antiepileptic medicinal product

Influence of Kusapin on antiepileptic medicinal product

Influence of antiepileptic medicinal product on MHD

Co-administered

Concentration

Concentration

Carbamazepine

0 - 22 % decrease
(30 % increase of carbamazepine-epoxide)

40 % decrease

Clobazam

Not studied

No influence

Felbamate

Not studied

No influence

Lamotrigine

Slight decrease*

No influence

Phenobarbitone

14 - 15 % increase

30 - 31 % decrease

Phenytoin

0 - 40 % increase

29 - 35 % decrease

Valproic acid

No influence

0 – 18 % decrease

Results of previous studies have shown that oxcarbazepine may decrease lamotrigine concentration that is important for use in children; however, the potential of oxcarbazepine interaction is lower than interaction with enzyme inducers (carbamazepine, phenobarbital, phenytoin).
Phenytoin concentration in plasma is increased up to 40% in simultaneous administration of Kusapin in dose of 1200 mg/day and more. Therefore, during usage of Kusapin doses of more than1200 mg/day it may be necessary to decrease the dose of phenytoin. Increasing of phenobarbital concentration in serum is approximately 15% in concurrent use with Kusapin.
Co-administration of strong inducers of cytochrome P450 isoenzymes (ie, carbamazepine, phenytoin and phenobarbital) leads to decreasing of MND concentration in plasma (by 29-40%). In children aged 6 to 12 years old in concurrent administration of one of antiepileptic enzyme-inducing drugs, clearance of MND was increased by 35% compared with monotherapy.
Co-administration of Kusapin and lamotrigine was associated with increased risk of adverse reactions (nausea, drowsiness, dizziness and head ache). In concurrent administration of some antiepileptic medicinal products it is necessary for dosage adjustment and monitoring of plasma concentrations, especially in pediatrics, in patients simultaneously receiving this medicine with lamotrigine.
Kusapin auto-induction has not been studied yet.
Hormonal contraceptives:
It was found Kusapin interaction with ethinylestradiol and levonorgestrel. Their mean values of area under the curve "concentration-time" (AUC) were decreased by 48–52% and 35–52% correspondingly. There is no data concerning other oral or implanted contraceptives. Simultaneous use of Kusapin medicine and hormonal contraceptives may reduce the effectiveness of the latter.

Calcium channel blockers:
Concurrent use with verapamil may decrease serum concentrations of MND by 20% (decrease of serum concentrations of MND is clinically insignificant).

Cimetidine, erythromycin, dextropropoxyphene do not influence on pharmacokinetic parameters of MND. Viloxazine insignificantly influences on MND concentration in plasma (concentration of MND is increased by 10% after re-simultaneous use).
It was not observed any interaction with warfarin in administration of both occasional and repeated doses of Kusapin.
Kusapin may enhance sedative effect of ethanol.
In vitro studies confirmed a weak inductor ability of oxcarbazepine and MND in regard to isozymes of subsystems of CYP2B and CYP3A4 enzymes. Inductor influence of oxcarbazepine and MND on other CYP isozymes is unknown.

MAO inhibitors:
Oxcarbazepine interaction with inhibitors is theoretically possible due to structural interaction of oxcarbazepine and tricyclic antidepressants.
It was not observed clinically significant interactions with oxcarbazepine in patients who received antidepressant agents.
Lithium:
Concomitant use of lithium and oxcarbazepine may cause neurotoxicity.

Warnings and precautions

Pregnancy and lactation
Clinical data concerning oxcarbazepine influence during pregnancy period is insufficient to evaluate its teratogenic potential. Oxcarbazepine and monohydroxy derivative (MND) pass through placental barrier. During Kusapin use in toxic doses it was observed an increase of embryo mortality, development and growth retardation and disorder.
If women becomes pregnant or plans to become pregnant during this medicine administration or if the problem of initiating treatment with Kusapin arises during pregnancy, the therapy's expected benefits must be carefully weighed against possible risk for foetus. Minimum effective doses of this medicine should be used during pregnancy. Patient should be warned about possible embryo development disorders.
During pregnancy an effective antiepileptic treatment should not be interrupted, since the aggravation of the illness is detrimental to both the mother and the fetus.
Folic acid deficiency is known to occur in pregnancy. Antiepileptic agents can aggravate this deficiency, which is one of possible reason of increased incidences of embryo development disorders; therefore, folic acid supplementation is recommended.
Antiepileptic agents use during pregnancy can lead to increased bleeding risk in the offspring. To prevent this risk it is also recommended to administer vitamin K1 to the mother during the last weeks of pregnancy as well as to the neonate.
Oxcarbazepine and monohydroxy derivative (MND) pass through placental barrier. Therefore, if necessary use of Kusapin during lactation period should be stopped.
Effects on ability to drive and use machines.
It is recommended to avoid driving motor transport or operating other mechanisms during Kusapin use due to dizziness, somnolence or other CNS disturbances.

Overdosage and Contraindications

Overdose
There are single reports of this medicine overdose; maximum dose, specified in these reports, was 24 g.
Symptoms:
somnolence, dizziness, nausea, vomiting, hyperkinesia, hyponatremia, ataxia, nystagmus.
Treatment:
There is no specific antidote. Symptomatic and supporting treatment is used. In case of recent use (within the last 2 hours) it is recommended a gastric lavage and activated charcoal use to reduce absorption.

Contraindications.
Hypersensitivity to the active substance or to any of the excipients.

Clinical pharmacology.

PHARMACEUTICAL FORM
Film coated tablet.
Capsule shape, yellow colored, film coated tablet, having break line on both sides of the tablet.

PHARMACEUTICAL PARTICULARS
List of excipients
Microcrystalline cellulose, Crosspovidone, Polyvinyl Pyrollidone, Colloidal anhydrous silica, magnesium stearate, Opadry Yellow 04F82782, Isopropyl alcohol & purified water.

Incompatibilities
Not applicable.

Shelf life
2 years.

Special precautions for storage
Store below 30°C. Keep out of reach of children.
Nature and contents of container
tablets are packed in an Alu/PVC-PVDC clear blister pack and such 10 blisters are packed in a carton along with pack insert.

MARKETING AUTHORISATION HOLDER
Kusum Healthcare Private Limited
D-158 A, Okhla Industrial Area,
Phase I, New Delhi-110020,
India.
MARKETING AUTHORISATION NUMBER(S)
-------
MANUFACTURER NAME
Kusum Healthcare Private Limited
SP 289 (A), RIICO Industrial Area.
Chopanki, Bhiwadi.
Distt. Alwar - 301707
India
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
-------
DATE OF REVISION OF THE TEXT -------

CERTIFICATES

KEEP IN TOUCH

Kusum Healthcare Pvt Ltd

Regd. Office: D-158A, Okhla Industrial Area

Phase-1, New Delhi-110020, India

Tel: 011-41005147, 40514919

Fax: +91-11-40527575

Email: kusumhealth@kusumhealthcare.com

CIN: U65929DL1997PTC085780