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.

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.

Signs of overdose have been observed in patients with renal impairment taking baclofen at doses of more than 5 mg per day. Baclofen should be used with caution in patients with renal insufficiency and should only be administered to patients with end-stage renal failure (CKD stage 5, GFR <15 ml/min) only if the expected benefit outweighs the potential risk. Neurological signs and symptoms of overdose including clinical manifestations of toxic encephalopathy (e.g. confusion, disorientation, somnolence and depressed level of consciousness) have been observed in patients with renal impairment taking oral baclofen at doses of more than 5mg per day. Patients with impaired renal function should be closely monitored for prompt diagnosis of early symptoms of toxicity.

Cases of baclofen toxicity have been reported in patients with acute renal failure.

Particular caution is required when combining baclofen with drugs or medicinal products that can significantly affect renal function. Renal function should be closely monitored and baclofen daily dosage adjusted accordingly to prevent baclofen toxicity.

Besides discontinuing treatment, unscheduled haemodialysis might be considered as a treatment alternative in patients with severe baclofen toxicity. Haemodialysis effectively removes baclofen from the body, alleviates clinical symptoms of overdose and shortens the recovery time in these patients.

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.

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

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.

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.

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

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.

Suicide and suicide-related events have been reported in patients treated with baclofen. In most cases, the patients had additional risk factors associated with an increased risk of suicide including alcohol use disorder, depression and/or a history of previous suicide attempts. Close supervision of patients with additional risk factors for suicide should accompany drug therapy. 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.

Baclofen may also exacerbate epileptic manifestations but can be employed provided appropriate supervision and adequate anticonvulsive therapy are maintained.

There are no adequate and well-controlled studies in pregnant women. Oral baclofen increases the incidence of omphaloceles (ventral hernias) in the foetuses of rats at high doses. No teratogenic effects have been noted in mice or rabbits.

A 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.

During pregnancy, especially in the first 3 months, oral 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 intrathecal should not be used during pregnancy unless the potential benefit is judged to outweigh the potential risk to the foetus.

Baclofen crosses the placental barrier.

Intrathecal administration

In mothers taking oral 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. It is not known whether detectable levels of drug are present in the breast milk of nursing mothers receiving baclofen intrathecal.

Oral administration

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.

One case of suspected withdrawal reaction (generalised convulsions) has been reported in a week-old infant whose mother had taken oral baclofen 80 mg daily throughout her pregnancy. The convulsions, which were refractory to standard anticonvulsant treatment, ceased within 30 minutes of giving baclofen to the infant.

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.