Severe but reversible spasticity of the muscles resulting from multiple sclerosis.

Can be used in patients with spinal spasticity of infectious, degenerative, traumatic or neoplastic origin.

Treatment should be initiated with small doses of Bastix, then gradually increased. It is recommended that the lowest effective dose be used. The optimum dosage must be individually adapted to the patient’s requirements so that clonus, flexor and extensor spasms and spasticity are reduced, while avoiding adverse effects as far as possible.

In order to prevent excessive weakness and falling, Bastix must be used with caution when spasticity is needed to maintain upright posture and balance in locomotion or other functions. It may be important to maintain a certain degree of muscle tone and allow occasional spasms to help support circulatory function and, possibly, prevent deep vein thrombosis.

Close monitoring is required at the start of treatment so that potential adverse effects such as general muscle weakness, abrupt loss of muscle tone (risk of falling!), fatigue or confusion can be rapidly detected, and the dosage adjusted as necessary.

If baclofen is to be withdrawn after prolonged administration (longer than 2-3 months), the dose should be reduced gradually over the course of about 3 weeks except in overdose-related emergencies, or where serious adverse effects have occurred, since abrupt withdrawal may occasionally be associated with anxiety and confusional states, hallucinations, cerebral seizures, dyskinesia, tachycardia or hyperthermia. Withdrawal should also be gradual on account of the risk of a transient rebound effect involving increased spasm frequency and/or severity.

Treatment with Bastix should be re-evaluated if it has not proved successful within 6-8 weeks of the patient’s reaching the maximum recommended dose.

Adults

Treatment should be started with a dosage of 5 mg three times daily, given in 3 divided doses, then gradually increased. Depending on the response, each of the divided doses should subsequently be cautiously increased by 5 mg every three days. 30-80 mg per day is considered the standard daily dose, but 100 to 120 mg/day may be given in isolated cases (patients under medical supervision in hospitals).

Children (0 to < 18 years)

Experience with Bastix tablets is limited in children and adolescents. The minimum age for treatment is 12 months.

Treatment usually starts with very low amounts, e.g. 0.3 mg/kg/day, given in 4 divided doses. The dosage should be cautiously raised, at intervals of about 1-2 weeks, until it becomes sufficient for the individual patient’s requirements. The daily dosage for maintenance therapy is 0.75-2 mg/kg. However, in patients over 10 years of age, a maximum daily dose of 2.5 mg/kg may be given.

The dose should not exceed 40 mg/day in children under 8 years of age, but a maximum dose of 60 mg/day may be given in children over 8 years of age.

Elderly patients (aged 65 years or above) and patients with spasticity of cerebral origin

The dosage should be increased particularly slowly in elderly and weak patients suffering from organic brain disorders, cardiovascular disease, respiratory failure, or hepatic or renal impairment, and also in patients with spasticity of cerebral origin.

Patients with kidney problems

Bastix should be used with caution in patients with renal impairment. Plasma concentrations

of baclofen are elevated in patients undergoing chronic haemodialysis, and a particularly low dose of Bastix (about 5 mg/day) should therefore be selected. Signs and symptoms of overdosage have been reported with doses of over 5 mg per day in this clinical situation.

Bastix should not be used in patients with end-stage renal failure unless the expected benefit outweighs the potential risk of further treatment. Such patients must be closely monitored for early signs and symptoms of overdosage (e.g. drowsiness, lethargy).

Method of administration

Bastix tablets should be taken at mealtimes with a small amount of liquid.

·         Be careful when drinking alcohol - it may affect you more than usual.

·         Your doctor may want to give you a checkup from time to time while you are taking Bastix Tablets.

·         If you are going to have an operation of any kind, make sure that the doctor knows that you are taking Bastix Tablets

Some medicines can interfere with your treatment. Tell your doctor or pharmacist if you are taking any of the following:

·         Other medicines to relax muscles e.g. tizanidine

·         Medicines to treat mood disorders such as lithium or tricyclic antidepressants such as

amitriptyline

·         Medicines for high blood pressure e.g. diltiazem

·         Other drugs which also affect the kidney, e.g. ibuprofen

·         Medicines for Parkinson’s disease e.g. levodopa or carbidopa

·         Medicines which slow down the nervous system, e.g. anti-histamines such as promethazine, sedatives such as temazepam, opiates for pain relief such as morphine and anti-convulsants (antiepileptic medicines such as carbamazepine).

Always tell your doctor or pharmacist about all the medicines you are taking. This means medicines you have bought yourself as well as medicines on prescription from your doctor.

Ask your doctor or pharmacist for advice before taking any medicine.

You should not use Bastix during pregnancy unless your doctor advises you to do so. Tell your doctor if you are pregnant, or planning to become pregnant.

If you have to take Bastix during pregnancy, your unborn baby will also be exposed to Bastix. After birth your baby may develop withdrawal symptoms such as convulsions (symptoms of withdrawal are described in the section “If you stop taking Bastix”).

Only a very small amount of Bastix passes into breast milk. Your doctor will discuss with you whether you should breast-feed whilst taking Bastix.

Some people may feel drowsy and/or dizzy or have problems with their eyes while they are taking Bastix Tablets. If this happens, you should not drive or do anything that requires you to be alert (such as operate tools or machinery) until these effects have worn off.

Bastix Tablets are suitable for most people, but, like all medicines, they can sometimes cause side effects.

The side effects listed below have been reported:

More than 1 in 10 people have experienced:

Tiredness, sleepiness, nausea (feeling sick).

Up to 1 in 10 people have experienced:

Excessively weak limbs or feeling tired and exhausted, aching muscles

Headache, dizziness or light-headedness

Breathing difficulties

Sleeplessness

Mood changes, confusion, hallucinations or nightmares

Dry mouth

Problems with their eyes

Unsteadiness, trembling or other problems with muscle control

Low blood pressure (fainting)

Stomach problems including retching, vomiting, constipation and diarrhoea

Excessive sweating, rash

Increased need to pass urine or pain on passing urine.

Up to 1 in 1,000 people have experienced:

Numbness or tingling in hands or feet

Increased muscle spasm

Disturbed sense of taste

Slurred or slow speech

Stomachache

Liver problems

Difficulty in passing urine

Sexual problems in men, e.g. impotence

Convulsions (particularly in epileptics).

Very rarely (less than 1 in 10,000) people have experienced:

Hypothermia (low body temperature).

Other side-effects (how often they happen is not known)

Raised, itchy rash (urticaria – also known as nettle rash or hives).

Slow heartbeat.

Increase in blood sugar.

Trouble breathing during sleep (sleep apnoea syndrome)

Symptoms caused by stopping treatment suddenly (see ‘3. How to take Bastix Tablets’).

If any of the symptoms become troublesome, or if you notice anything else not mentioned here, please go and see your doctor. He/she may want to adjust the dose or give you a different medicine.

If you accidentally take too many Bastix Tablets, tell your doctor at once or contact your nearest hospital casualty department. Take your medicine with you.

Pharmacotherapeutic group: Antispastic with spinal site attack, ATC code: M03B X01

Bastix is an antispastic agent acting at the spinal level. A gamma-aminobutyric acid (GABA) derivative, Bastix is chemically unrelated to other antispastic agents.

Bastix depresses monosynaptic and polysynaptic reflex transmission, probably by stimulating the GABA_B-receptors, this stimulation in turn inhibiting the release of the excitatory amino acids glutamate and aspartate. Neuromuscular transmission is unaffected by Bastix.

The major benefits of Bastix stem from its ability to reduce painful flexor spasms and spontaneous clonus thereby facilitating the mobility of the patient, increasing his independence and helping rehabilitation.

Bastix also exerts an antinociceptive effect. General well being is often improved and sedation is less often a problem than with centrally acting drugs.

Baclofen stimulates gastric acid secretion.

Absorption: Bastix (baclofen) is rapidly and completely absorbed from the gastro-intestinal tract. No significant difference between the liquid and tablet formulations is observed in respect of T_max, C_max and bioavailability. Following oral administration of single doses (10-30mg) peak plasma concentrations are recorded after 0.5 to 1.5 hours and areas under the serum concentration curves are proportional to the dose.

Distribution: The volume of distribution of baclofen is 0.7 l/kg,. The protein binding rate is approximately 30% and is constant in the concentration range of 10 nanogram/mL to 300 microgram/mL.. In cerebrospinal fluid active substance concentrations are approximately 8.5 times lower than in the plasma.

Biotransformation: Baclofen is metabolised to only a minor extent. Deamination yields the main metabolite, β-(p-chlorophenyl)-4-hydroxybutyric acid, which is pharmacologically inactive.

Elimination/excretion: The plasma elimination half-life of baclofen averages 3 to 4 hours.

Baclofen is eliminated largely in unchanged form. Within 72 hours, approximately 75% of the dose is excreted via the kidneys with about 5% of this amount as metabolites.

Special populations

Elderly patients (aged 65 years or above)

The pharmacokinetics of baclofen in elderly patients are virtually the same as in patients below 65 years of age. Following a single oral dose, elderly patients have slower elimination but a similar systemic exposure of baclofen compared to adults below 65 years of age. Extrapolation of these results to multi-dose treatment suggests no significant pharmacokinetic difference between patients below 65 years of age and elderly patients.

Paediatric patients

Following oral administration of 2.5 mg Bastix tablet in children (aged 2 to12 years), Cmax of 62.8±28.7 nanogram/mL, and Tmax in the range of 0.95-2 h have been reported. Mean plasma clearance (Cl) of 315.9 mL/h/kg; volume of distribution (Vd) of 2.58 L/kg; and half-life (T_1⁄2) of 5.10 h have been reported.

Hepatic impairment

No pharmacokinetic data are available in patients with hepatic impairment after administration of Bastix. However, as the liver does not play a significant role in the disposition of baclofen, it is unlikely that baclofen pharmacokinetics would be altered to a clinically significant level in patients with hepatic impairment.

Renal impairment

No controlled clinical pharmacokinetic study is available in patients with renal impairment after administration of Bastix. Baclofen is predominantly eliminated unchanged in urine. Sparse plasma concentration data collected only in female patients under chronic hemodialysis or compensated renal failure indicate significantly decreased clearance and increased half-life of baclofen in these patients. Dosage adjustment of baclofen based on its systemic levels should be considered in renal impairment patients, and prompt hemodialysis is an effective means of reversing excess baclofen in systemic circulation.

Baclofen increases the incidence of omphaloceles (ventral hernias) in the foetuses of rats given approximately 13 times the maximum oral dose (on a mg/kg basis) recommended for human use. This was not seen in mice or rabbits.

An apparently dose related increase in the incidence of ovarian cysts, and a less marked increase in enlarged and/or haemorrhagic adrenals have been observed in female rats treated for 2 years. The clinical relevance of these findings is not known.

Experimental evidence to date suggests that baclofen does not possess either carcinogenic or mutagenic properties.

Microcrystalline Cellulose

Copovidone

Sodium Starch Glycolate A

Silica, Colloidal Anhydrous

Magnesium Stearate

Not applicable.

Keep this medicine out of the sight and reach of children.

Do not store above 30ºC. Keep in the original package.

Do not take the tablets after the expiry date which is printed on the outside of the pack.

If your doctor tells you to stop taking Bastix Tablets, please take any which are left back to your pharmacist to be destroyed. Only keep them if the doctor tells you to. Do not throw them away with your normal household water or waste. This

PVC/PE/PVDC (250 μm / 25 μm / 120 gsm) versus 25 μm Aluminum foil

Packs with 50 tablets.

No special requirements.

- To report any side effect(s)

• Saudi Arabia

NPC contact information Saudi Arabia:

The National Pharmacovigilance Centre (NPC):

·                     SFDA Call Center: 19999

·                     Fax: +966112057662

·                     E-mail: npc.drug@sfda.gov.sa

·                     Website ade.sfda.gov.s