Baclofen Bioindustria L.I.M.

Package leaflet: Information for the user

BACLOFENE Bioindustria L.I.M. 10 mg/20 ml injectable solution for intrathecal use, 10 mg/5 ml injectable solution for intrathecal use, 0.05 mg/1 ml injectable solution for intrathecal use

Baclofen
Equivalent medicine
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet:

1. What BACLOFENE Bioindustria L.I.M. is and what it is used for
2. What you need to know before you are given BACLOFENE Bioindustria L.I.M.
3. How BACLOFENE Bioindustria L.I.M. will be administered to you
4. Possible side effects
5. How to store BACLOFENE Bioindustria L.I.M.
6. Contents of the pack and other information

1. What BACLOFENE Bioindustria L.I.M. is and what it is used for

BACLOFENE Bioindustria L.I.M. contains the active substance baclofen, which belongs to a class of medicines known as "centrally acting muscle relaxants". Baclofen works by relaxing muscles.

Adults
This medicine is indicated for the treatment of severe and chronic conditions characterised by increased muscle tone and muscle contractions, in cases of:

• severe muscular disorders (severe chronic spasticity) associated with multiple sclerosis, spinal cord injuries, or other spinal cord diseases, when treatments with oral medications used to reduce muscle contractions (antispastics, including baclofen) are not effective or cannot be used due to unacceptable side effects;
• brain disorders (cerebral spasticity), such as in cerebral palsy, head injuries, or cerebral infarctions;
• tetanus, an infectious disease affecting muscles and nerves, to reduce tendon reflexes (hyperreflexia), involuntary muscle contractions (clonus), and painful contractions of the jaw muscles (trismus).

Children and adolescents (from 4 to 18 years of age)
BACLOFENE Bioindustria L.I.M. is indicated in children aged between 4 and 18 years with severe and chronic disorders of the nervous system (chronic cerebral or spinal spasticity) characterised by increased muscle tone and muscle contractions, associated with brain damage or diseases, spinal cord trauma or diseases, and multiple sclerosis, when treatments with oral medications used to reduce muscle contractions (antispastics, including baclofen) are not effective or cannot be used due to unacceptable side effects at therapeutic doses of orally administered medicines.

2. What you need to know before you are given BACLOFENE Bioindustria L.I.M.

BACLOFENE Bioindustria L.I.M. must not be administered to you

• if you/your child are allergic to baclofen or to any of the other ingredients of this medicine (listed in section 6);
• by intravenous, intramuscular, subcutaneous or epidural route;
• if you/your child suffer from drug-resistant epilepsy;
• during pregnancy, unless under strict medical supervision (see section "Pregnancy, breastfeeding and fertility").

Warnings and precautions
Before you are given this medicine, you must gradually discontinue, under medical supervision, the use of medicines taken by mouth used to reduce muscle contractions (antispasmodics), to avoid the possibility of overdose or drug interactions.
Contact your doctor or nurse before you are given BACLOFENE Bioindustria L.I.M. if you/your child:

• have an ongoing infection,
• have heart problems,
• have lung problems (respiratory failure),
• have weak muscles of the lungs,
• have abnormalities in the distribution of the fluid surrounding the central nervous system (cerebrospinal fluid),
• suffer from mood disorders (e.g. psychosis, schizophrenia),
• suffer from confusional states,
• have Parkinson's disease,
• have epilepsy,
• suffer from a disorder of the autonomic nervous system called autonomic dysreflexia, which may manifest, for example, as elevated blood pressure accompanied by slow heart rate, sweating, headache,
• have severe problems with blood vessels in the brain associated with reduced oxygen supply to the brain or suffer from severe respiratory problems (cerebrovascular or respiratory insufficiency), as these conditions may worsen,
• have or have had a stomach or first part of the intestine ulcer (peptic ulcer),
• suffer from a long-term condition characterized by excessive increase in muscle tone of the sphincters, known as sphincter hypertonia,
• suffer from kidney problems (renal insufficiency).

Your doctor will keep you/your child under close medical supervision during treatment with BACLOFENE Bioindustria L.I.M., particularly monitoring lung, blood vessel and heart function.
You/your child must contact your doctor or nurse immediately if, during treatment with BACLOFENE Bioindustria L.I.M., you experience any of the following symptoms, as they may indicate problems at the injection site or with drug delivery:

• increased muscle tone and contractions (spasticity),
• poor response to increasing doses of BACLOFENE Bioindustria L.I.M.,
• pain at the intrathecal injection site,
• itching,
• tingling,
• low blood pressure,
• state of hyperactivity with rapid, uncontrolled spasms,
• increased body temperature,
• altered mental status and muscle rigidity, increased body temperature, increased heart rate, elevated blood pressure (neuroleptic malignant syndrome),
• breakdown of muscle tissue (rhabdomyolysis),
• epileptic seizures,
• convulsions,
• altered blood coagulation,
• multi-organ failure,
• elevated blood pressure accompanied by slow heart rate, sweating, headache (symptoms of autonomic dysreflexia),
• severe infection (sepsis).

Contact your doctor immediately if, during treatment with BACLOFENE Bioindustria L.I.M., you experience any of the following symptoms:

• back, shoulder, neck or buttock pain (symptoms of a specific type of spinal deformity known as scoliosis),
• if at any time you develop thoughts of self-harm or suicide, speak to your doctor immediately or go to hospital. In addition, ask a relative or close friend to inform you if they notice any changes in your behaviour, and encourage them to read this leaflet.

Children and adolescents
In children with increased muscle tone and contractions (spasticity) due to head trauma, your doctor will not administer long-term intrathecal BACLOFENE Bioindustria L.I.M. therapy until spasticity symptoms have stabilized (at least one year after the trauma).
BACLOFENE Bioindustria L.I.M. must not be used in children under 4 years of age.
Elderly
If you are over 65 years of age, this medicine must be administered with great caution.
Other medicines and BACLOFENE Bioindustria L.I.M.
Inform your doctor or nurse if you/your child are taking, have recently taken, or might take any other medicines.
Inform your doctor if you/your child are taking or will take:

• medicines used for Parkinson’s disease (levodopa, DOPA decarboxylase inhibitors),
• medicines used to relieve pain during surgery (general anaesthetics) such as fentanyl and propofol,
• morphine, a medicine used to relieve severe pain,
• medicines acting on the central nervous system, for example: pain relievers (analgesics), neuroleptics (psychotropic drugs), medicines for epilepsy, insomnia and mood disorders (barbiturates, benzodiazepines, anxiolytics), opioid medicines (which may increase the risk of breathing problems in you/your child),
• medicines for depression belonging to the tricyclic class (tricyclic antidepressants),
• medicines used to control high blood pressure (antihypertensives).

BACLOFENE Bioindustria L.I.M. and alcohol
Avoid alcohol consumption during treatment with this medicine, as it may enhance the effect of the medicine.
Pregnancy, breastfeeding and fertility
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or nurse before this medicine is administered to you.
Pregnancy
There are no adequate studies in pregnant women. Small amounts of baclofen may reach maternal blood. Animal studies have shown that baclofen crosses the placenta; therefore, if you are pregnant, the medicine will only be prescribed when clearly necessary and under strict medical supervision.
Breastfeeding
After intrathecal administration, small amounts of baclofen have been detected in blood; it is not expected that baclofen would pass into breast milk, and therefore no adverse effects in the breastfed infant are anticipated.
Fertility
There are no special recommendations for women of childbearing age.
Driving and using machines
Exercise particular caution if you/your child need to drive vehicles (including bicycles) or operate machinery.
During treatment with BACLOFENE Bioindustria L.I.M., you/your child may experience symptoms that reduce alertness and thus may affect the ability to drive or operate machinery, such as:

drowsiness,
sedation,
movement difficulties (ataxia),
hallucinations,
double vision (diplopia),
withdrawal symptoms (see section "If you/your child stop treatment with BACLOFENE Bioindustria L.I.M.").

Important information about certain excipients
BACLOFENE Bioindustria L.I.M. 10 mg/20 ml contains up to 73.9 mg (3.08 mmol) of sodium (the main component of table salt) per 20 millilitres.
This corresponds to 3.7% of the maximum daily dietary intake recommended for an adult.
BACLOFENE Bioindustria L.I.M. 10 mg/5 ml and BACLOFENE Bioindustria L.I.M. 0.05 mg/1 ml contain less than 23 mg (1 mmol) of sodium per dose, i.e. essentially "sodium-free".
If your doctor needs to dilute BACLOFENE Bioindustria L.I.M. intrathecal 0.05 mg/1 ml or BACLOFENE Bioindustria L.I.M. intrathecal 10 mg/5 ml with a common sodium solution, the amount of sodium administered will be higher.

3. How BACLOFENE Bioindustria L.I.M. will be administered to you

The administration of BACLOFENE Bioindustria L.I.M. will be performed only by properly trained medical personnel in a suitably equipped environment, with devices available for resuscitation.
BACLOFENE Bioindustria L.I.M. is used with a dedicated infusion device that can be programmed. This device will be implanted under your skin, usually in the abdominal area, and is equipped with reservoirs for drug release that can be refilled.

• To determine the most suitable dose of BACLOFENE Bioindustria L.I.M., you/your child will undergo: first, a single test dose to verify that you/your child responds to the treatment (selection phase)
• followed by a careful dose escalation (individualized titration phase)
• leading to maintenance therapy.

During the selection phase, the physician will inject a single dose of BACLOFENE Bioindustria L.I.M. to evaluate your/your child’s response.
To determine the initial total daily dose of BACLOFENE Bioindustria L.I.M. to be used, the physician will then double the dose administered during the selection phase and deliver it over a 24-hour period.
If the effect of the dose used during the selection phase lasts longer than 12 hours, the physician will administer to you/your child a dose equal to that used in the selection phase, but slowly over 24 hours.
After the first 24 hours, the physician will gradually increase the dose with small daily adjustments until reaching the most appropriate maintenance dose for you/your child.
To maintain an optimal response during maintenance therapy, the physician may further increase the dose over time.
If you/your child use BACLOFENE Bioindustria L.I.M. for prolonged periods, it is possible that BACLOFENE Bioindustria L.I.M. may no longer be effective. The physician will evaluate how to manage this situation.
If you/your child experience adverse effects, the physician may reduce the dose of BACLOFENE Bioindustria L.I.M.

Use in adults
The dose used in the selection phase is generally 25 or 50 micrograms, which may be increased by 25 micrograms at 24-hour intervals until a clinical response lasting between 4 and 8 hours is observed.
The maximum selection dose should not exceed 100 micrograms per day.
The maintenance dose of BACLOFENE Bioindustria L.I.M. may range from 10 to 1,200 micrograms per day; most patients respond well to doses between 300 and 800 micrograms per day.

Use in children and adolescents (aged 4 to 18 years)
The dose used in the selection phase is generally 25 or 50 micrograms per day, depending on age and body weight.
The dose may be increased by 25 micrograms per day every 24 hours.
The maximum selection dose should not exceed 100 micrograms per day. The maintenance dose ranges between 25 and 200 micrograms per day.

Use in children under 4 years of age
BACLOFENE Bioindustria L.I.M. will not be administered to children under 4 years of age.

Use in patients with kidney or liver problems
The physician will exercise particular caution before prescribing BACLOFENE Bioindustria L.I.M. and will monitor you/your child closely.

If you/your child receive more BACLOFENE Bioindustria L.I.M. than you should
In case of accidental administration of an excessive dose of BACLOFENE Bioindustria L.I.M., contact your physician immediately or go to the nearest hospital.
It is important that you/your child and caregivers are able to recognize symptoms related to an overdose of BACLOFENE Bioindustria L.I.M. The medical staff will inform you how to identify its signs and symptoms.
If an excessive dose of BACLOFENE Bioindustria L.I.M. has been administered to you/your child, the following may occur:
excessive reduction in muscle tone (hypotonia), drowsiness, feeling of emptiness in the head, dizziness, seizures, loss of consciousness, decreased body temperature (hypothermia), increased saliva production (hypersalivation), nausea and vomiting, and at excessive doses, breathing problems (respiratory depression), absence of breathing (apnea), coma, rapid heartbeat (tachycardia), ringing/buzzing/whistling in the ears (tinnitus). The physician will determine the appropriate treatment.
If you experience these effects, contact your physician immediately or go to the nearest hospital.

If you/your child forget to use BACLOFENE Bioindustria L.I.M.
This medicine will be administered to you by a physician; therefore, it is unlikely that a dose will be missed.

If you/your child stop using BACLOFENE Bioindustria L.I.M.
Except in emergency situations due to overdose or the occurrence of particularly severe adverse effects, intrathecal BACLOFENE Bioindustria L.I.M. treatment must always be discontinued gradually, with progressive dose reduction.
Intrathecal BACLOFENE Bioindustria L.I.M. must not be stopped abruptly.
Sudden discontinuation of intrathecal BACLOFENE Bioindustria L.I.M. treatment may cause:

• increased muscle tone and contraction (spasticity)
• itching
• tingling
• decreased blood pressure
• hyperactive state with rapid, uncontrolled spasms
• increased body temperature, potentially fatal
• altered mental status and muscle rigidity, increased body temperature, increased blood pressure (neuroleptic malignant syndrome), rapid heartbeat (tachycardia)
• destruction of muscle tissue (rhabdomyolysis)
• epileptic seizures
• convulsions
• elevated blood pressure accompanied by slowed heartbeat, sweating, headache (autonomic dysreflexia symptoms)
• severe infection (sepsis)
• coagulation disorders
• prolonged and painful erection of the penis (priapism)
• multi-organ failure
• death. In most cases, symptoms due to discontinuation appeared from a few hours to a few days after stopping treatment with BACLOFENE Bioindustria L.I.M.

Treatment discontinuation with BACLOFENE Bioindustria L.I.M. could be caused by catheter malfunction, low pump reservoir volume, battery depletion, or malfunction of the delivery device.
It is very important to schedule regular physician visits for battery recharge and to check the proper functioning of the pump. It is equally important that you/your child and caregivers are able to recognize symptoms related to interruption of therapy with BACLOFENE Bioindustria L.I.M.

If you have any doubts about the use of this medicine, consult your physician or nurse.

4. Possible side effects

Like all medicines, this medicine may cause side effects, although not everybody gets them.
The following side effects may occur:
Very common (may affect more than 1 in 10 people):

• drowsiness,
• feeling of instability,
• decreased muscle tone (hypotonia).

Common (may affect up to 1 in 10 people):

• mood disorder (depression),
• feeling of worry or fear (anxiety),
• agitation,
• seizures,
• confusion,
• sedation,
• dizziness/sensation of emptiness in the head,
• headache,
• disturbance in sensation of arms, legs or other body parts (paraesthesia),
• speech disorders in which words are spoken slowly and imperfectly (dysarthria),
• tendency to continuous sleep (lethargy),
• decreased coordination,
• sleep disorders (insomnia),
• disorientation,
• seizures and headache (cephalalgia), especially in patients with muscle disorders (spasticity) of cerebral rather than spinal origin,
• difficulty of the eyes to focus on objects (accommodation disorder), blurred vision, double vision (diplopia),
• reduced blood pressure (hypotension),
• breathing problems (respiratory depression),
• lung inflammation (pneumonia),
• difficulty breathing (dyspnoea),
• nausea,
• vomiting,
• constipation (stipsis),
• especially in patients with motor disorders (spasticity) of cerebral rather than spinal origin,
• dry mouth (xerostomia),
• diarrhoea,
• decreased appetite,
• increased salivation,
• skin irritation (urticaria),
• itching,
• swelling of the face and/or legs and feet (facial and/or peripheral oedema),
• excessive increase in muscle tone (hypertonia),
• involuntary loss of urine (urinary incontinence),
• inability of the bladder to empty (urinary retention), especially in patients with motor disorders (spasticity) of cerebral rather than spinal origin,
• bladder disorders,
• sexual disorders (sexual dysfunction),
• reduced muscle strength (asthenia),
• fever (pyrexia),
• pain,
• chills.

Uncommon (may affect up to 1 in 100 people):

• lack of water in the body (dehydration),
• suicidal thoughts,
• suicide attempt,
• hallucinations,
• paranoia,
• euphoric state,
• disorders of muscle coordination (ataxia),
• memory impairment,
• rapid, oscillating and involuntary eye movements (nystagmus),
• reduced heart rate (bradycardia),
• high blood pressure (hypertension),
• formation of blood clots in a deep vein (deep vein thrombosis),
• skin redness,
• reduced skin colour (pallor),
• intestinal obstruction,
• difficulty swallowing (dysphagia),
• reduced sense of taste (hypogeusia),
• hair loss (alopecia),
• excessive sweating (hyperhidrosis),
• reduced body temperature (hypothermia).

Rare (may affect up to 1 in 1,000 people):

• life-threatening withdrawal symptoms due to failure of drug release (see section “If you stop treatment with Baclofene Bioindustria L.I.M.”).

Frequency not known (frequency cannot be estimated from the available data):

• mood disorders (dysphoria),
• reduced number of breaths (bradypnoea),
• increased lateral curvature of the spine (scoliosis),
• inability to achieve or maintain an erection (erectile dysfunction),
• allergic reaction (hypersensitivity).

The following side effects associated with the device delivering the medicine may also occur:

• inflammation at the site where the catheter is inserted,
• catheter displacement with possible complications,
• infection of the subcutaneous pocket,
• infection of the central nervous system (meningitis),
• overdose due to incorrect handling of the device,
• death.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the following website:
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store BACLOFENE Bioindustria L.I.M.

Medical personnel are aware of the storage conditions for this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging.
The expiry date refers to the last day of that month.
Do not freeze the vials.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What BACLOFENE Bioindustria L.I.M. 10 mg/20 ml injectable solution for intrathecal use contains

• The active substance is baclofen: 1 vial containing 20 ml of solution has 10 mg of baclofen.
• The other components are: sodium chloride, water for injections.

What BACLOFENE Bioindustria L.I.M. 10 mg/5 ml injectable solution for intrathecal use contains

• The active substance is baclofen: 1 vial containing 5 ml of solution has 10 mg of baclofen.
• The other components are: sodium chloride, water for injections.

What BACLOFENE Bioindustria L.I.M. 0.05 mg/1 ml injectable solution for intrathecal use contains

• The active substance is baclofen: 1 vial containing 1 ml of solution has 0.05 mg of baclofen.
• The other components are: sodium chloride, water for injections.

Description of the appearance of BACLOFENE Bioindustria L.I.M. and contents of the pack
BACLOFENE Bioindustria L.I.M. 10 mg/20 ml: 1 vial of 10 mg/20 ml
BACLOFENE Bioindustria L.I.M. 10 mg/5 ml: 5 vials of 10 mg/5 ml
BACLOFENE Bioindustria L.I.M. 0.05 mg/1 ml: 10 vials of 0.05 mg/1 ml

Marketing Authorization Holder and Manufacturer
Bioindustria Laboratorio Italiano Medicinali S.p.A.
(Bioindustria L.I.M. S.p.A.)
Via De Ambrosiis, 2
15067 Novi Ligure (AL)
Italy

Package leaflet: information for the physician

BACLOFENE Bioindustria L.I.M. 10 mg/20 ml injectable solution for intrathecal use, 10 mg/5 ml injectable solution for intrathecal use, 0.05 mg/1 ml injectable solution for intrathecal use

Baclofen
Generic medicinal product
The following information is intended exclusively for physicians or healthcare professionals
Dosage and method of administration: Baclofene Bioindustria L.I.M. intrathecal is intended for single bolus administration with test doses (via spinal or lumbar catheter) and for chronic use with an implantable pump suitable for continuous administration of Baclofene Bioindustria L.I.M. intrathecal into the intrathecal space. Before initiating chronic infusion with Baclofene Bioindustria L.I.M. intrathecal, patients must demonstrate a response to intrathecal baclofen bolus during the screening phase. The initial test dose is usually 25 micrograms or 50 micrograms, which may be increased by 25 micrograms at 24-hour intervals until a clinical response lasting between 4 and 8 hours is observed; the dose must be administered fully over no less than one minute. For this purpose, low-dose vials (0.05 mg/1 ml) are particularly suitable. The first dose must be administered in a setting equipped for resuscitation. Patients who do not respond to a test dose of 100 micrograms must not receive further drug quantities and must not be included in a chronic intrathecal infusion treatment.

Paediatric population: For patients aged 4 to < 18 years, the initial test dose via lumbar puncture should be 25–50 micrograms/day, based on the child's age and weight. Patients who do not respond may receive dose increments of 25 micrograms/day every 24 hours. In paediatric patients, the maximum screening dose must not exceed 100 micrograms/day.

Dose titration: Intrathecal infusion must be performed using a suitable delivery device. To determine the initial total daily dose of Baclofene Bioindustria L.I.M. intrathecal to be used in the device, double the dose that produced a positive effect during the screening phase and administer it over a 24-hour period. If the efficacy of the bolus dose lasted more than 12 hours, the initial daily dose should equal the bolus dose administered slowly over 24 hours. During the first 24 hours, the dosage must not be increased. After the first 24 hours, dosage should be adjusted slowly, with small daily changes, to achieve the desired effect, increasing the dose by 10 to 30% to avoid overdose. In patients with cerebral-origin spasticity: after the first 24 hours, the dose may be gradually adjusted on a daily basis to achieve the desired effect. To avoid overdose, dose increases should not exceed 5–15%.

With programmable pumps, dosage should be increased only once every 24 hours. For non-programmable pumps with a 76 cm catheter delivering 1 ml per day, it is preferable to wait 48 hours before assessing response. If the daily dose has been significantly increased without observing any clinical effect, the function of the pump or catheter should be checked. Experience with doses exceeding 1000 micrograms per day is limited. Resuscitation equipment must always be readily available in case of sudden life-threatening events or severe adverse reactions.

Maintenance therapy: The lowest dose producing an effective response should be used. To maintain optimal response during chronic therapy, many patients require a gradual increase in dose over time; this may be due to reduced responsiveness to therapy or progressive worsening of the disease. To adequately maintain symptom control, the daily dose may be gradually increased by 10 to 30%; the increase can be achieved by adjusting the pump release rate and/or the concentration of Baclofene Bioindustria L.I.M. intrathecal in the reservoir. The daily dose may also be reduced by 10 to 20% if the patient experiences side effects. The need to increase the dose may suggest catheter obstruction, catheter displacement, or pump malfunction. The maintenance dose for continuous intrathecal baclofen infusion may range from 10 micrograms/day to 1200 micrograms/day; most patients respond well to doses between 300–800 micrograms/day. In long-term treatments, approximately 5% of patients become refractory to dose increases, due to tolerance or drug delivery issues. This tolerance may be managed by gradually reducing the dose of Baclofene Bioindustria L.I.M. intrathecal over a period of 2 to 4 weeks and switching to alternative methods for treating spasticity (e.g. pure intrathecal morphine sulphate). After several days, response to Baclofene Bioindustria L.I.M. intrathecal may be restored, and treatment should restart with the initial infusion dose, followed by a titration phase to avoid overdose. When switching between Baclofene Bioindustria L.I.M. intrathecal and morphine, caution is required.

Paediatric population: In children aged 4 to < 18 years with cerebral or spinal origin spasticity, the initial maintenance dose for long-term continuous infusion of Baclofene Bioindustria L.I.M. intrathecal ranges between 25 and 200 micrograms/day (median dose: 100 micrograms/day). The maintenance dose should be adjusted based on individual clinical response, and thus the total daily dose tends to increase over time during therapy. Experience with doses exceeding 1000 micrograms/day is limited.

Special warnings and precautions for use
Reservoir refill: The refill interval for the reservoir must be carefully calculated to prevent complete emptying, which could lead to recurrence of severe spasticity or the onset of neuroleptic malignant syndrome, hyperthermia, and confusion. Refilling must be performed under maximum aseptic conditions to avoid microbial contamination and severe central nervous system infections.

Treatment interruption: The recommended treatment for interruption of Baclofene Bioindustria L.I.M. intrathecal is resumption of Baclofene Bioindustria L.I.M. intrathecal at a dose equal to or close to the one previously administered before interruption. However, if restoration of intrathecal delivery is delayed, treatment with GABA-agonist drugs such as oral baclofen, or oral, enteral, or intravenous benzodiazepines, may prevent potentially fatal sequelae. Oral baclofen alone should not be used to block the progression of withdrawal effects from intrathecal baclofen.

Treatment in case of overdose: Remove any residual Baclofene Bioindustria L.I.M. solution from the pump as quickly as possible. If the patient develops respiratory depression, intubate until complete elimination of the drug. If lumbar injection is not contraindicated, in the early stage of intoxication, withdrawal of 30 to 40 ml of cerebrospinal fluid may be considered to reduce baclofen concentrations. Support cardiovascular functions. In case of seizures, administer intravenous diazepam cautiously.

Incompatibilities: Vials of Baclofene Bioindustria L.I.M. for intrathecal administration must not be mixed with other infusion or injectable solutions. Dextrose has been shown to be chemically incompatible with baclofen.

Special precautions for disposal and handling: Each vial should be used only once. It is recommended to discard each vial even if partially used. Do not sterilize vials by heat.

Stability: Baclofene Bioindustria L.I.M. intrathecal is stable in the SynchroMed infusion system for 180 days. Parenteral vials must be carefully inspected before administration to ensure there is no particulate matter or discoloration of the solution.

Instructions for dilution: The specific concentration to be used depends on the total daily dose and the pump release rate. It is recommended to consult the manufacturer's manual of the delivery system for specific recommendations. For patients requiring concentrations other than 50 µg/ml, 500 µg/ml, or 2000 µg/ml, Baclofene Bioindustria L.I.M. intrathecal should be diluted under aseptic conditions with sodium chloride for injectable preparations (sterile and preservative-free).

Delivery systems: Various delivery systems have been used for long-term administration of intrathecal baclofen; among these is the Medtronic SynchroMed infusion system, an implantable delivery system with a refillable reservoir implanted subcutaneously, usually in the abdominal wall, after local or general anaesthesia. Specific details of this delivery system may be obtained directly from the manufacturer. Before using another infusion system, technical specifications, including chemical stability of baclofen in the reservoir, must be confirmed as compatible with intrathecal use of Baclofene Bioindustria L.I.M.

For further information, consult the Summary of Product Characteristics.