Baclofen

Increased sedation may occur when baclofen is taken concomitantly with other drugs causing CNS depression including other muscle relaxants (such as tizanidine), with synthetic opiates or with alcohol.

The risk of respiratory depression is also increased. In addition, hypotension has been reported with concomitant use of morphine and intrathecal baclofen. Careful monitoring of respiratory and cardiovascular functions is essential, especially in patients with cardiopulmonary disease and respiratory muscles weakness.

Pre-treatment with baclofen may prolong the duration of fentanyl induced anaesthesia.

The combined use of morphine and intrathecal baclofen has been responsible for hypotension in one patient; the potential for this combination to cause dyspnoea or other CNS symptoms cannot be excluded.

No studies have been performed in patients with hepatic impairment receiving baclofen therapy. The liver does not play a significant role in the metabolism of baclofen after oral administration of baclofen. However, baclofen has the potential of elevating liver enzymes. Baclofen should be prescribed with caution in patients with hepatic impairment.

No studies have been performed in patients with hepatic impairment receiving baclofen intrathecal therapy. No dosage adjustment is recommended as the liver does not play any significant role in the metabolism of baclofen after intrathecal administration. Therefore, hepatic impairment is not expected to impact the drug systemic exposure.

In patients with impaired renal function or undergoing chronic haemodialysis, a particularly low dosage of baclofen should be selected i.e. approximately 5 mg daily.

Baclofen should be administered to end stage renal failure patients only if the expected benefit outweighs the potential risk. These patients should be closely monitored for prompt diagnosis of early signs and/or symptoms of toxicity (e.g. somnolence, lethargy).

No studies have been performed in patients with renal impairment receiving baclofen intrathecal therapy. Because baclofen is primarily excreted unchanged by the kidneys it should be given with special care and caution in patients with impaired renal function.

During concomitant treatment with tricyclic antidepressants, the effect of baclofen may be potentiated, resulting in pronounced muscular hypotonia.

Since concomitant treatment with baclofen and anti-hypertensives is likely to increase the fall in blood pressure, the dosage of anti-hypertensive medication should be adjusted accordingly.

Concomitant use of intrathecal baclofen and general anaesthetics (e.g. fentanyl, propofol) may increase the risk of cardiac disturbances and seizures. Thus, caution should be exercised when anaesthetics are administered to patients receiving intrathecal baclofen.

In patients with Parkinson’s disease receiving treatment with baclofen and levodopa (alone or in combination with DDC inhibitor, carbidopa), there have been reports of mental confusion, hallucinations, nausea and agitation. Worsening of the symptoms of Parkinsonism has also been reported. Hence, caution should be exercised during concomitant administration of baclofen and levodopa/carbidopa.

Concomitant use of oral baclofen and lithium resulted in aggravated hyperkinetic symptoms. Thus, caution should be exercised when baclofen is used concomitantly with lithium.

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 patients.

Porphyria, history of alcoholism, hypertension, 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 appropriate supervision and adequate anticonvulsive therapy are maintained.

Oral administration

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.

Intrathecal administration

There are limited data on the use of intrathecal baclofen in pregnant women.

Reproductive toxicity has been observed at high oral doses of baclofen. After intrathecal administration small amounts of baclofen can be detected in maternal plasma. Animal data show that baclofen can cross the placental barrier. Therefore, baclofen should not be used during pregnancy unless the expected benefit outweighs the potential risk to the foetus.

After oral administration at therapeutic doses, baclofen passes into the breast milk, but in quantities so small that no undesirable effects on the infant are to be expected.

After intrathecal administration small amounts of baclofen can be detected in maternal plasma. Therefore, no baclofen is expected to be found in the milk of the mother receiving baclofen intrathecal therapy and no special recommendations are given.

Foetal/neonatal adverse reactions

Drug withdrawal syndrome including postnatal convulsions in neonates has also been reported after intra-uterine exposure to oral baclofen.

Women of child bearing potential

Preconceptual counselling before programmable baclofen pump placement and in women with intrathecal baclofen pumps already implanted is recommended to ensure proper preparation and management throughout pregnancy and the peripartum period.

Fertility

Animal studies have shown that intrathecal baclofen is unlikely to have an adverse effect on fertility under clinically-relevant conditions.

Oral administration

Baclofen may be associated with adverse effects such as dizziness, sedation, somnolence and visual impairment which may impair the patient’s reaction. Patients experiencing these adverse reactions should be advised to refrain from driving or operating machinery.

Intrathecal administration

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.

Oral administration

Adverse 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.

Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients. 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.

Certain patients have shown increased spasticity as a paradoxical reaction to the medication.

An undesirable degree of muscular hypotonia – making it more difficult for patients to walk or fend for themselves – may occur and can usually be relieved by re-adjusting the dosage (i.e. by reducing the doses given during the day and possibly increasing the evening dose).

Adverse reactions are ranked under the heading of frequency, the most frequent first, using the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000) and Not known (frequency cannot be estimated from the available data).

Tabulated summary of adverse drug reactions:

^* Drug withdrawal syndrome including postnatal convulsions in neonates has also been reported after intra-uterine exposure to oral baclofen.

^* Cases of central sleep apnoea syndrome have been observed with baclofen at high doses (≥100 mg) in patients who are alcohol dependent.

Intrathecal administration

Some of the adverse reactions listed below have been reported in patients with spasticity of spinal origin but could also occur in patients with spasticity of cerebral origin. Adverse reactions that are more frequent in either population are indicated below.

Adverse drug reactions are listed according to system organ classes in MedDRA. Within each system organ class, the adverse drug reactions are ranked under headings of frequency, the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category using the following convention (CIOMS III) is also provided for each adverse drug reaction: 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), and Not known (cannot be estimated from available data).

Adverse drug reactions:

Adverse events associated with the delivery system

Adverse events associated with the delivery system (inflammatory mass at the tip of the catheter, catheter dislocation with possible complications, pocket infection, meningitis, overdose due to wrong manipulation of the device) have been reported. Device malfunction resulting in altered drug delivery leading to withdrawal symptoms including death has been reported.