Summary of Product Characteristics (SPC)
1. NAME OF THE MEDICINAL PRODUCT
Ospolot 200 mg, film-coated tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Ospolot 200 mg
1 film-coated tablet contains 200 mg sulthiame.
Excipient(s) with known effect: one tablet contains 50.0 mg lactose monohydrate
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Film-coated tablet
Ospolot 200 mg
White, round, slightly domed film-coated tablet with a dividing groove on one side and
marked “200” on the other side. The tablet can be divided into equal doses.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of epilepsy in adults and in treatment of the so called focal benign epilepsy of
children, when other medication was not adequate.
Note:
Treatment with Ospolot® should only be conducted by a paediatric neurologist with
sufficient experience in treating epilepsy.
Efficacy and safety of Ospolot® in the above-mentioned indication have not been
investigated in controlled studies. Prior to starting treatment with sulthiame, a thorough
differential diagnostic procedure regarding other types of childhood epilepsies is indicated.
Rolandic epilepsies demonstrate a high percentage of spontaneous remissions – even
without drug treatment – and usually show a favourable course of disease and a good
prognosis.
4.2 Posology and method of administration
Posology
The dosage must be established and monitored by the doctor on an individual basis. The
maintenance dose is about 5 to 10 mg/kg body weight/day. It should be built up step-wise
(tapered in) over a one-week period. Ospolot 200 mg film-coated tablets have a dividing
groove.
Due to the short half-life of sulthiame, the daily dose should as far as possible be spread
over three single doses. If the daily dose is spread over the day in this way, constant
plasma levels are to be expected after five to six days. Therapeutic plasma concentrations
of sulthiame have not yet been determined.
Method of administration
The film-coated tablets should be swallowed whole (unchewed) with plenty of liquid
(approx. one glass of water), as far as possible spread over 3 single doses.
A change from another medication or from combination treatment should be done
gradually. Ospolot® should not be discontinued abruptly. A paediatric neurologist
experienced in treating epilepsy should decide on dose adjustment, the duration of
treatment and discontinuation on an individual basis.
If therapy is not successful, treatment with sulthiame should be discontinued after about
one to two months.
It is recommendable to monitor the blood count, liver enzymes and renal function
parameters before treatment with Ospolot®, then at weekly intervals in the first month of
treatment, and thereafter at monthly intervals. After six months of treatment, two to four
checks per year are sufficient.
4.3 Contraindications
Ospolot may not be used in cases of
- known hypersensitivity to sulthiame, other sulphonamides or to any of the excipients
listed in section 6.1.
Sulthiame should not be used in patients with
- known acute porphyria
- hyperthyroidism or arterial hypertension.
4.4 Special warnings and precautions for use
Sulthiame should not be administered, or only administered with special caution and
adequate monitoring
- in patients with impaired renal function
- in patients with a history of psychiatric disorders
- during pregnancy and lactation (see also section 4.6)
The patients, their caregivers, and families should be instructed to consult the attending
doctor immediately if fever, sore throat, allergic skin reactions with lymph node swelling
and/or flu-like symptoms occur during treatment with Ospolot. Progressive
thrombocytopenias or leukopenias that are accompanied by clinical symptoms, such as
fever or sore throat, require interruption of treatment. In cases of severe allergic reactions,
Ospolot must be discontinued immediately. Treatment should also be interrupted if a
lasting increase in creatinine occurs. The blood count, liver enzymes and urine should be
checked regularly (see also section 4.2).
Patients with rare hereditary problems of galactose intolerance, lactase deficiency or
glucose-galactose malabsorption should not take Ospolot®.
Suicidal ideation and suicidal behaviour
Suicidal ideation and behaviour have been reported in patients treated with antiepileptic
agents in several indications. A meta-analysis of randomised placebo controlled trials of
anti-epileptic drugs has also shown a small increased risk of suicidal ideation and
behaviour. The mechanism of this risk is not known and the available data do not exclude
the possibility of an increased risk for sulthiame.
Therefore patients treated with any antiepileptic drug (AED) for any indication should be
monitored for the emergence or worsening of depression, suicidal thoughts or behaviour,
and / or any unusual changes in mood or behaviour and appropriate treatment should be
considered. Patients (and caregivers of patients) should be advised to seek medical
advice should signs of suicidal ideation or behaviour emerge.
Anyone considering prescribing sulthiame or any other AED must balance this risk with
the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are
prescribed are themselves associated with morbidity and mortality and an increased risk
of suicidal thoughts and behaviour. Should suicidal thoughts and behaviour emerge during
treatment, the prescriber needs to consider whether the emergence of these symptoms in
any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of
suicidal thoughts and behaviour and should be advised of the need to be alert for the
emergence or worsening of the signs and symptoms of depression, any unusual changes
in mood or behaviour, or the emergence of suicidal thoughts, behaviour, or thoughts about
self-harm. Behaviours of concern should be reported immediately to the treating doctor.
Effect on Laboratory Tests
Sulthiame may interfere with the estimation of barbiturates in laboratory tests on blood.
4.5 Interaction with other medicinal products and other forms of interaction
Prior to starting treatment with Ospolot®, the patient should be asked about other
medicines, including OTC products, he/she is using.
Primidone
The concomitant use of sulthiame and primidone may lead to severe side-effects,
especially in children, including dizziness, unstable gait, drowsiness and psychotic
reactions.
Carbamzepine
There are indications that sulthiame serum levels may decrease if carbamazepine is taken
concomitantly.
Phenytoin
If sulthiame is combined with phenytoin, the plasma levels of phenytoin can be markedly
elevated. This combination requires especially strict monitoring and frequent controls of
phenytoin plasma levels, particularly in the case of impaired renal function.
Phenobarbitone: Sulthiame may also induce a rise in the serum level of phenobarbitone.
Lamotrigine
In combination with lamotrigine, an elevation of lamotrigine levels in the blood has also
been observed in individual cases. Therefore, lamotrigine levels should be checked more
frequently at the beginning of such a treatment.
Carboanhydrase-Inhibitors
Concomitant use of sulthiame and other carbonic anhydrase inhibitors (e.g. topiramate,
acetazolamide) may increase the risk of undesirable effects due to carbonic anhydrase
inhibition (see also section 4.8).
Alcohol
During treatment with sulthiame, the patient should abstain from alcohol, since
sulphonamides have an effect similar to that of disulfiram, and sulthiame, as a
sulphonamide derivative, can theoretically have a similar effect. These symptoms include
a very unpleasant, although generally self-limiting systemic reaction caused by
vasodilatation, with pulsating headache, respiratory depression, nausea, vomiting,
tachycardia, hypotension, amblyopia, confusion, shock reactions, arrhythmias, loss of
consciousness and seizures. The degree and duration of these symptoms can vary to a
great extent.
4.6 Fertility, pregnancy and lactation
No systematically gained experience on administration of sulthiame in humans during
pregnancy and lactation is available, in animal studies, embryotoxic effects have been
revealed (see also section 5.3). Therefore Ospolot® may not be used during pregnancy
and lactation.
4.7 Effects on ability to drive and use machines
Even when used as directed, these medicinal products can affect reactions to such an
extent - especially at the start of treatment - that the ability to drive a vehicle or use
machines may be impaired. This applies to a greater extent in combination with alcohol.
4.8 Undesirable effects
The following frequency categories are used for the evaluation of undesirable effects:
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 (frequency cannot be estimated from the available data)
Metabolism and nutrition disorders
Very common: anorexia
Common: weight loss
Psychiatric disorders
Uncommon: hallucinations, anxiety, lack of drive, psychic changes, depression,
behavioural anomaly (e.g. aggressiveness, irritability, mood swings)
Nervous system disorders
Common: ataxia, paraesthesias in the extremities and in the face (dose
dependent), dizziness (giddiness),
Uncommon: headache, myasthenic phenomena, grand-mal status, increased
seizure activity, drooling, insomnia
Not known: polyneuritis
Eye disorders
Common: double vision
Not known: significant deterioration of vision
Cardiac disorders
Common: stenocardia, tachycardia
Respiratory, thoracic and mediastinal disorders
Very common: hyperpnoea, dyspnoea
Common: tachypnoea, , singultus
Gastrointestinal disorders
Very common: gastric complaints (in about 10% of patients)
Uncommon: abdominal pain, nausea
Hepatobiliary disorders
Not known: hepatotoxic reactions, increase of liver enzymes
Skin and subcutaneous disorders
Uncommon: Stevens-Johnson syndrome,
Not Known: Rash, Lyell's syndrome
Musculoskeletal and connective tissue disorders
Uncommon: joint pain
Renal and urinary disorders
Not known: acute renal failure
Blood and lymphatic system disorders
Uncommon: leucopenia
In one case, administration of Ospolot® led to progressive weakness of the limbs,
hypersalivation, slurred speech, increasing drowsiness up to coma. The symptoms abated
within hours of Ospolot® being discontinued.
Sulthiame is a carbonic anhydrase inhibitor. Therefore, undesirable effects of carbonic
anhydrase inhibition, such as renal stone formation, metabolic acidosis, haemodilution
and changes in serum electrolyte values, cannot be excluded during administration of
sulthiame (see also section 4.5).
Disturbances in calcium and Vitamin D metabolism have been occasionally reported in
association with long-term anticonvulsant therapy.
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 events should be reported to the Ministry of Health according to
the National Regulation by using an online form
http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMed
ic@moh.gov.il
4.9 Overdose
Symptoms of intoxication
Headache, vomiting, hypotension, dizziness, ataxia, impaired consciousness, metabolic
acidosis, crystals in the urine. Sulthiame has a low toxicity. Overdoses of 4 to 5 g
sulthiame have been survived. The intake of about 20 g sulthiame by adults with the
intention of committing suicide was fatal in one case. In another case, a restitutio ad
integrum was achieved.
Treatment of intoxications
A specific antidote is not known. The standard measures (gastric lavage and active
charcoal) for minimising absorption and for maintaining vital functions should be taken.
Sodium bicarbonate can be infused to treat acidosis. Alkalising diuretic therapy is
recommended for preventing renal damage and crystalluria.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antiepileptics
ATC code: N03AX03
Sulthiame belongs to the group of carbonic anhydrase inhibitors and displays an
anticonvulsant effect in the electroconvulsion test (rat and mouse) and in the convulsion
test with pentamethylene tetrazole (mouse).
5.2 Pharmacokinetic properties
Sulthiame pharmacokinetics were not systematically investigated in different age
categories in children and adolescents.
Absorption
After oral administration, sulthiame is rapidly and completely absorbed, predominantly
from the upper section of the small intestine. Peak plasma concentrations are measured
after 1 - 5 hours.
Distribution
About 29% of the active substance is bound to plasma proteins.
Elimination
80 to 90% is eliminated with the urine and 10 to 20% with the faeces after biliary
secretion. Within 24 hours, 32% of the administered dose is excreted unchanged via the
kidneys.
5.3 Preclinical safety data
Acute toxicity
See section 4.9.
Chronic toxicity
Long-term investigations on various animal species (rat, dog) have revealed no evidence
of dose-dependent toxic changes. With high doses, renal damage has been observed due
to crystallisation of the substance.
Carcinogenic and mutagenic potential
In three different in vivo and in vitro experimental models, no mutagenic potential of
sulthiame has been revealed. Long-term carcinogenicity studies have not been
conducted.
Reproductive toxicity
Reproductive toxic properties of sulthiame are not sufficiently investigated. In an
embryotoxicity study on rats, embryotoxic effects have been revealed at the lowest
investigated dose (30 mg/kg/day). Studies on fertility disorders and effects on peri- and
postnatal development of the off-spring are lacking.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize Starch, Lactose monohydrate, Talc, colloidal anhydrous Silica, Gelatin,
Magnesium stearate, Hypromellose, Macrogol 4000, Titanium dioxide.
One tablet contains 50.0 mg lactose monohydrate.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
The medicinal product should not be used after the expiry date (see folding box).
6.4 Special precautions for storage
Keep the container tightly closed.
Store below 25˚c
Use this medicine within 12 weeks after first opening
6.5 Nature and contents of container
Folding boxes containing 200 film-coated tablets in brown glass bottles with a child-proof
polyethylene stopper.
Folding boxes containing 200 film-coated tablets in polyethylene containers with a child-
proof polypropylene screw cap.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements.
7. MANUFACTURER
DESITIN ARZNEIMITTEL GMBH
Weg beim Jäger 214
22335 Hamburg, Germany
8. LICENSE HOLDER
Megapharm Ltd. Hod Hasharon P.O.Box 519 4510501
9. MARKETING AUTHORISATION NUMBER
066-04-28222-00
The format of this leaflet was determined by the ministry of health and its content was
checked and approved January 2016
OSP SPC 012016 P.1
