Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Intrathecal baclofen therapy is valuable but hazardous. Careful pre-operative assessment is mandatory.
The patient must be given adequate information regarding the risks of this mode of treatment, and be physically and psychologically able to cope with the pump. It is essential that the responsible physicians and all those involved in the care of the patient receive adequate instruction on the signs and symptoms of overdose, procedures to be followed in the event of an overdose and the proper home care of the pump and insertion site.

Inflammatory mass at the tip of the implanted catheter: cases of inflammatory mass at the tip of the implanted catheter that can result in serious neurological impairment, including paralysis, have been reported. Although they have been reported with baclofen, they have not been confirmed by contrast MRI or histopathology. The most frequent symptoms associated with inflammatory mass are: 1) decreased therapeutic response (worsening spasticity, return of spasticity when previously well controlled, withdrawal symptoms, poor response to escalating doses, or frequent or large dosage increases), 2) pain, 3) neurological deficit/dysfunction. Clinicians should monitor patients on intraspinal therapy carefully for any new neurological signs or symptoms. Clinicians should use their medical judgement regarding the most appropriate monitoring specific to their 'patients' medical needs to identify prodromal signs and symptoms for inflammatory mass especially if using pharmacy compounded drugs or admixtures that include opioids. In patients with new neurological signs or symptoms suggestive of an inflammatory mass, consider a neurosurgical consultation since many of the symptoms of inflammatory mass are not unlike the symptoms experienced by patients with severe spasticity from their disease. In some cases, performance of an imaging procedure may be appropriate to confirm or rule-out the diagnosis of an inflammatory mass.

Pump Implantation
Patients should be infection-free prior to pump implantation because the presence of infection may increase the risk of surgical complications. Moreover, a systemic infection may complicate attempts to adjust the dose. A local infection or catheter malplacement can also lead to drug delivery failure, which may result in sudden Baclofen Sintetica withdrawal and its related symptoms (see Section 4.4 – Special Precautions for Use “Treatment Withdrawal” section).

Reservoir refilling
Reservoir refilling must be performed by trained and qualified personnel in accordance with the instructions provided by the pump manufacturer. Refills should be timed to avoid excessive depletion of the reservoir, as this would result in the return of spasticity or potentially life-threatening symptoms of Baclofen Sintetica withdrawal (see Section 4.4 – Special Precautions for Use “Treatment Withdrawal” section).
When refilling the pump care should be taken to avoid discharging the contents of the catheter into the intrathecal space.
Strict asepsis is required to avoid microbial contamination and infection.
Extreme caution must be taken when filling a pump equipped with an injection port that allows direct access to the intrathecal catheter as a direct injection into the catheter through the access port could cause a life-threatening overdose.

Precautions in pediatric patients
For patients with spasticity due to head injury, it is recommended not to proceed to long-term Baclofen Sintetica therapy until the symptoms of spasticity are stable (i.e. at least one year after the injury).
Children should be of sufficient body mass to accommodate the implantable pump for chronic infusion.
Use of Baclofen Sintetica in the pediatric population should be only prescribed by medical specialists with the necessary knowledge and experience. There is very limited clinical data regarding the safety and efficacy of the use of Baclofen Sintetica in children under the age of four years.

Precautions in special patient populations
In patients with abnormal CSF flow the circulation of drug and hence antispastic activity may be inadequate.

Psychotic disorders, schizophrenia, confusional states or Parkinson's disease may be exacerbated by treatment with oral baclofen. Patients suffering from these conditions should therefore be treated cautiously and kept under close surveillance.
Close supervision of patients with additional risk factors for suicide should accompany therapy with Baclofen Sintetica. Patients (and caregivers of patients) should be alerted about the need to monitor for clinical worsening, suicidal behaviour or thoughts or unusual changes in behaviour and to seek medical advice immediately if these symptoms present (see section 4.8 – Psychiatric disorders).
Special attention should be given to patients known to suffer from epilepsy as seizures have occasionally been reported during overdose with, and withdrawal from, Baclofen Sintetica as well as in patients maintained on therapeutic doses.
Baclofen Sintetica should be used with caution in patients with a history of autonomic dysreflexia. The presence of nociceptive stimuli or abrupt withdrawal of Baclofen Sintetica may precipitate an autonomic dysreflexic episode.
Baclofen should be used with caution in patients with cerebrovascular or respiratory insufficiency.
An effect of Baclofen Sintetica on underlying, non-CNS related diseases is unlikely because its systemic availability is substantially lower than after oral administration. Caution should be exercised in patients with a history of peptic ulcers and based on observations after oral baclofen therapy, in those with pre-existing sphincter hypertonia.


Renal impairment
After oral baclofen dosing severe neurological outcomes have been reported in patients with renal impairment. Thus caution should be exercised while administering Baclofen Sintetica in patients with renal impairment.
In rare instances elevated SGOT, alkaline phosphatase and glucose levels in the serum have been recorded when using oral baclofen.

Treatment withdrawal (including associated with catheter or device malfunction) 
Abrupt discontinuation of Baclofen Sintetica, regardless of cause, manifested by increased spasticity, pruritus, paraesthesia and hypotension, has resulted in sequelae including a hyperactive state with rapid uncontrolled spasms, hyperthermia, tachycardia and symptoms consistent with neuroleptic malignant syndrome, e.g. altered mental status and muscle rigidity. In rare cases this has advanced to seizures/status epilepticus, rhabdomyolysis, coagulopathy, multiple organ failure and death. All patients receiving intrathecal baclofen therapy are potentially at risk for withdrawal.
Some clinical characteristics associated with intrathecal baclofen withdrawal may resemble autonomic dysreflexia, infection (sepsis), malignant hyperthermia, neuroleptic-malignant syndrome, or other conditions associated with a hypermetabolic state or widespread rhabdomyolysis.
Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the signs and symptoms of baclofen withdrawal particularly those seen early in the withdrawal syndrome (e.g. priapism).
In most cases, symptoms of withdrawal appeared within hours to a few days following interruption of baclofen therapy. Common reasons for abrupt interruption of intrathecal baclofen therapy included malfunction of the catheter (especially disconnection), low volume in the pump reservoir, end of pump battery life and device malfunction. Device malfunction resulting in altered drug delivery leading to withdrawal symptoms including death has been reported.

Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. The suggested treatment for intrathecal baclofen withdrawal is the restoration of intrathecal baclofen at or near the same dosage as before therapy was interrupted. However, if restoration of intrathecal delivery is delayed, treatment with GABA-ergic agonist drugs such as oral or enteral baclofen, or oral, enteral, or intravenous benzodiazepines may prevent potentially fatal sequelae. Oral or enteral baclofen alone should not be relied upon to halt the progression of intrathecal baclofen withdrawal.

Scoliosis
The onset of scoliosis or worsening of a pre-existing scoliosis has been reported in patients treated with Baclofen Sintetica. Signs of scoliosis should be monitored during treatment with Baclofen Sintetica.

Excipients:

Baclofen Sintetica 0.5 mg/ml and Baclofen Sintetica 2 mg/ml 20 ml ampoules contain 69.3 mg sodium per dose, equivalent to 3.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.


Baclofen Sintetica 2 mg/ml 5 ml ampoule contains 17.5 mg sodium per dose, that is to say essentially 'sodium-free'


This medicinal product may be diluted with sodium-containing solutions (see section 6.2); this should be considered in relation to the total sodium from all sources that will be administered to the patient.

Effects on Driving

4.7 Effects on ability to drive and use machines
Central nervous system (CNS) depressant effects such as somnolence and sedation have been reported in some patients receiving intrathecal baclofen, and patients should be advised to exercise due caution.
Other listed events include ataxia, hallucinations, vision blurred, diplopia and withdrawal symptoms.
Operating equipment or machinery may be hazardous.