PRESCRIBING INFORMATION
Presentation
RESTOBAC 10 Tablet: Each tablet contains Baclofen BP 10 mg.

Indications
RESTOBAC is useful for the alleviation of signs and symptoms of spasticity. RESTOBAC is indicated for:
● Spasm
● Spasticity of skeletal muscles in multiple sclerosis
● Spastic conditions occuring in spinal cord diseases
● Tension type headache
● Muscle spasm of cerebral origin, especially infantile cerebral palsy
● Cerebrovascular accidents, neoplastic, degenerative brain diseases
● Syringomyelia, transverse myelitis, traumatic paraplegia, spastic spinal paralysis
● Flexor spasms and concomitant pain

Pharmacodynamic properties
Baclofen is an antispastic agent acting at the spinal level. A gamma-aminobutyric acid (GABA) derivative, Baclofen is chemically unrelated to other antispastic agents. Baclofen depresses monosynaptic and polysynaptic reflex transmission, probably by stimulating the GABAB-receptors, this stimulation in turn inhibiting the release of the excitatory amino acids glutamate and aspartate. Neuromuscular transmission is unaffected by Baclofen. The major benefits of Baclofen 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. Baclofen 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.

Pharmacokinetic properties
Absorption: Baclofen is rapidly and completely absorbed from the gastro-intestinal tract. 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 and the protein binding rate is approximately 30%. In cerebrospinal fluid active substance concentrations are approximately 8.5 times lower than in the plasma. Biotransformation: Baclofen is metabolized to only a minor extent. De-amination yields the main metabolite, ß-(p-chlorophenyl)-4-hydroxybutyric acid, which is pharmacologically inactive.
Elimination/Excretion: The plasma elimination half-life of Baclofen averages 3 to 4 hours. The serum protein binding rate is approximately 30% Baclofen is eliminated largely in unchanged form. Within 72 hours, about 75% of the dose is excreted via the kidneys with about 5% of this amount as metabolites.
Elderly: The pharmacokinetics of Baclofen in elderly patients is virtually the same as in young subjects. The peak plasma concentrations of Baclofen in elderly patients are slightly lower and occur later than in healthy young subjects but the AUCs are similar in the two groups.
Dosage and administration:
Should be individualized according to the patient's requirements. The determination of optimal dosage requires individual titration. Start therapy at a low dosage and increase gradually until optimum effect is achieved (usually between 40 to 80 mg daily). The following dosage titration schedule is suggested:

Adults
● 5 mg t.i.d. for 3 days
● 10 mg t.i.d. for 3 days
● 15 mg t.i.d. for 3 days
● 20 mg t.i.d. for 3 days
Thereafter additional increases may be necessary but the total daily dose should not exceed a maximum of 80 mg daily (20 mg q.i.d.).

Elderly
Elderly patients may be more susceptible to side effects, particularly in the early stages of introducing Baclofen. Small doses should therefore be used at the start of treatment, the dose being titrated gradually against the response, under careful supervision. There is no evidence that the eventual average maximum dose differs from that in younger patients.

Children
A dosage range of 0.75-2mg/kg body weight should be used. In children over 10 years of age, however a maximum daily dosage of 2.5mg/kg body weight may be given. Treatment is usually started with 2.5mg given 4 times daily. The dosage should be cautiously raised at about 3 day intervals, until it becomes sufficient for the child's individual requirements. The recommended daily dosages for maintenance therapy are as follows:
● Children aged: 12 months - 2 years : 10-20mg
● 2 years - 6 years : 20-30mg
● 6 years - 10 years : 30-60mg

Patients with impaired renal function
In patients with impaired renal function or undergoing chronic haemodialysis, a particularly low dosage of Baclofen should be selected i.e. approx. 5mg daily. Signs of overdose have been observed in patients with renal impairment taking oral Baclofen at doses of more than 5mg per day.

Patients with spastic states of cerebral origin
Unwanted effects are more likely to occur in these patients. It is therefore recommended that a very cautious dosage schedule be adopted and that patients be kept under appropriate surveillance.

Contraindications
This tablet is contraindicated in patients with hypersensitivity to Baclofen or any excipients of this tablet. Also is contraindicated in case of Peptic Ulcer.

Precautions
Psychotic disorders, schizophrenia, depressive or manic disorders, confusional states or Parkinson's disease may be exacerbated by treatment with Baclofen. Patients suffering from these conditions should therefore be treated cautiously and kept under close surveillance. Baclofen may also exacerbate epileptic manifestations but can be employed provided that appropriate supervision and adequate anticonvulsive therapy are maintained. Baclofen should be used with extreme care in patients already receiving antihypertensive therapy, (see Interactions). Baclofen should be used with caution in patients suffering from cerebrovascular accidents or from respiratory, hepatic or renal impairment. Signs of overdose have been observed in patients with renal impairment taking oral Baclofen at doses of more than 5mg per day. Under treatment with Baclofen neurogenic disturbances affecting emptying of the bladder may show an improvement. In patients with pre-existing sphincter hypertonia, acute retention of urine may occur; the drug should be used with caution in such cases. Baclofen tablets contain wheat starch. Wheat starch may contain gluten, but only in trace amounts. Taking Baclofen tablets is therefore considered safe for people with coeliac disease. Abrupt withdrawal: Anxiety and confusional states, hallucinations, psychotic, manic or paranoid states, convulsions (status epilepticus), dyskinesia, tachycardia, hyperthermia and as rebound phenomenon temporary aggravation of spasticity have been reported with abrupt withdrawal of Baclofen, especially after long term medication. Treatment should always, (unless serious adverse effects occur), therefore be gradually discontinued by successively reducing the dosage over a period of about 1-2 weeks.

Drug interactions
Where Baclofen is taken concomitantly with other drugs acting on the CNS, with synthetic opioid or with alcohol, increased sedation may occur. The risk of respiratory depression is also increased. Careful monitoring of respiratory and cardiovascular functions is essential especially in patients with cardiopulmonary disease and respiratory muscle weakness. During concurrent treatment with TCA, the effect of Baclofen may be potentiated, resulting in pronounced muscular hypotonia. Since concomitant treatment with Baclofen and anti-hypertensives is likely to increase hypotension, the dosage of antihypertensive medication should be adjusted accordingly. Hypotension has been reported in one patient receiving morphine and intrathecal Baclofen. Drugs which may produce renal insufficiency e.g. ibuprofen may reduce Baclofen excretion leading to toxic effects. In patients with Parkinson's disease receiving treatment with Baclofen and Levodopa plus Carbidopa, there have been reports of mental confusion, hallucinations, nausea and agitation.

Use in pregnancy and lactation
Pregnancy category C. During pregnancy, especially in the first 3 months, Baclofen should only be employed if its use is of vital necessity. The benefits of the treatment for the mother must be carefully weighed against the possible risks for the child. Baclofen crosses the placental barrier. In mothers taking Baclofen in therapeutic doses, the active substance passes into the breast milk, but in quantities so small that no undesirable effects on the infant are to be expected.

Side effects
Unwanted effects occur mainly at the start of treatment (e.g. sedation, somnolence and nausea), if the dosage is raised too rapidly, if large doses are employed, or in elderly patients. They are often transitory and can be attenuated or eliminated by reducing the dosage; they are seldom severe enough to necessitate withdrawal of the medication. Should nausea persist following a reduction in dosage, it is recommended that Baclofen be ingested with food or a milk beverage. In patients with a history of psychiatric illness or with cerebrovascular disorders (e.g. stroke) as well as in elderly patients, adverse reactions may assume a more serious form. Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients. Unlikely to occur clinical events include mental/mood changes, seizures, vision changes, muscle stiffness, stomach pain, vomiting, trouble breathing, painful urination, change in urine amount. Very unlikely events are impotence, chest pain, black stools, fainting, and unsteadiness. If you notice other effects not listed above, contact your physician immediately.

Overdose
Prominent features are signs of central nervous depression: drowsiness, impairment of consciousness, respiratory depression, coma also liable to occur are: confusion, hallucinations, agitation, accommodation disorders, absent papillary reflex; generalized muscular hypotonia, myoclonia, hyporeflexia or areflexia; convulsions; peripheral vasodilatation, hypotension, bradycardia; hypothermia; nausea, vomiting, diarrhoea, hypersalivation; elevated LDH, AST and ALP values. Patients with renal impairment can develop signs of overdose even on low doses of oral Baclofen. Deterioration in the condition may occur if various substances or drugs acting on the central nervous system (e.g. alcohol, diazepam, TCA) have been taken at the same time.

Treatment of Overdose
No specific antidote is known. Supportive measures and symptomatic treatment should be given for complications such as hypotension, hypertension, convulsions, respiratory or cardiovascular depression. After ingestion of a potentially toxic amount, activated charcoal should be considered. In the early period after ingestion charcoal should be considered in adults who ingested more than 100mg Baclofen within 1 hour, and in children who have ingested more than 5mg/kg Baclofen within 1 hour. Gastric decontamination (e.g. gastric lavage) should be considered in individual cases, especially in the early period (60 minutes) after ingestion of a potentially life-threatening overdose.

Storage precaution
Store at a cool and dry place, protected from light and moisture.

Commercial pack
Each box contains 3 Alu-PVC blister packs of 10 tablets.