Consumer medicine information

Clofen

Baclofen

BRAND INFORMATION

Brand name

Clofen

Active ingredient

Baclofen

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Clofen.

What is in this leaflet

This leaflet answers some common questions about CLOFEN.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking CLOFEN against the benefits expected for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What CLOFEN is used for

CLOFEN belongs to a group of medicines called muscle relaxants.

This medicine is used to reduce stiffness and/or spasms in your muscles.

CLOFEN is used to control muscle spasms in conditions such as:

  • multiple sclerosis
  • spinal cord damage resulting from disease or physical injury

Because this medicine reduces spasms and the pain that goes with them, it helps to make you more mobile and better able to manage your daily activities.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

CLOFEN is only available with a doctor's prescription.

Before you take CLOFEN

When you must not take it

Do not take CLOFEN if you have an allergy to:

  • any medicine containing baclofen
  • any of the ingredients listed at the end of this leaflet

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you are pregnant or plan to become pregnant or are breastfeeding or wish to breastfeed. There is very little information on the use of this medicine in pregnancy or breastfeeding. Your doctor can discuss with you the risks and benefits involved.

If you have to take CLOFEN when you are pregnant, your baby may have convulsions and other symptoms related to sudden discontinuation of the medicine just after delivery.

Tell your doctor if you have or have had any of the following medical conditions:

  • a mental illness
  • Parkinson's disease
  • seizures (fits) from any cause
  • stiffness and restriction of movement in a group of muscles
  • stomach ulcers
  • stroke or other blood circulation disease
  • heart disease
  • kidney disease
  • liver disease
  • lung problems which make breathing difficult
  • diabetes
  • porphyria, a rare disturbance in the production of porphyrin, a pigment important for liver function and blood formation
  • history of alcoholism, drink alcohol to excess or you have a history of drug abuse or dependence. Some people treated with baclofen have had thoughts of harming or killing themselves or have tried to kill themselves. Most of these people also had depression, had been using alcohol excessively or were prone to having thoughts of killing themselves. If you have thoughts of harming or killing yourself at any time, speak to your doctor straightaway or go to the hospital. Also, ask a relative or close friend to tell you if they are worried about any changes in your behaviour and ask them to read this leaflet.
  • high blood pressure

Your doctor may want to take special precautions if you have any of the above conditions. These precautions may include additional tests during or prior to taking CLOFEN.

If you have not told your doctor about any of the above, tell them before you start taking CLOFEN.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and CLOFEN may interfere with each other. These include:

  • medicines that can make you sleepy, such as medicines used to help you sleep or calm you down (sleeping tablets or sedatives), pain relievers and medicines for hay fever or allergy, cough and cold, blocked nose
  • some medicines used to treat mood disorders, including tricyclic antidepressants, lithium and monoamine oxidase inhibitors (MAOIs)
  • medicines used to treat diabetes
  • medicines for high blood pressure
  • medicines used to treat Parkinson's disease, including selegiline, levodopa and carbidopa

You may need different amounts of your medicines, or you may need to take different medicines.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take CLOFEN

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the bottle, ask your doctor or pharmacist for help.

How much to take

Treatment is usually started in hospital with small doses of CLOFEN. The dose is then gradually increased to an amount that works best for you. For example, CLOFEN may be started at a dose of 15 mg per day, then increased slowly to anywhere from 30 to 75 mg a day. Sometimes, doses up to 100 mg a day may be needed.

If you are under the age of 16 or over 65 or you have kidney disease, your doctor may start you on a lower dose and increase it more gradually to prevent unwanted side effects.

How to take it

Swallow the tablets during meals with a little liquid.

CLOFEN is usually taken in at least 3 divided doses throughout the day. But your doctor may tell you to take it more or less often, depending on your situation.

How long to take it

Continue taking your medicine for as long as your doctor tells you.

Your doctor will check your progress to make sure the medicine is working for you and will discuss with you how long your treatment should continue.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much CLOFEN.

Do this even if there are no signs of discomfort or poisoning.

The main symptoms of overdose are: drowsiness, breathing difficulties, consciousness disorders and being unconscious (coma).

Other symptoms may include: feeling confused, hallucinations, agitation, convulsions, blurred vision, unusual muscle slackness, sudden contraction of the muscles, poor or absent reflexes, high or low blood pressure, slow, fast or irregular heartbeat, low body temperature, nausea, vomiting, diarrhoea, or excessive salivation, trouble breathing during sleep (sleep apnoea), pain in your muscles, fever and dark urine (rhabdomyolysis).

If you have kidney disease and have accidently taken more tablets than your doctor has prescribed, you may experience some neurological symptoms of overdose such as drowsiness, feeling confused or hallucinations.

While you are taking CLOFEN

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking CLOFEN.

Tell any other doctors, dentists and pharmacists who treat you that you are taking CLOFEN.

If you become pregnant while taking CLOFEN, tell your doctor immediately. Your doctor can discuss with you the risks of taking it while you are pregnant.

Be sure to keep all of your doctor's appointments so that your progress can be checked. To help prevent unwanted side effects from happening, your doctor may want to do some tests from time to time during the course of your treatment.

If your muscle spasms come back, tell your doctor. Your doctor may be able to change the dose of CLOFEN to make it work better for you.

Things you must not do

Do not stop taking CLOFEN suddenly. This medicine is not habit-forming but stopping it suddenly may bring on severe spasms and other unwanted symptoms, such as nervousness, feeling confused, hallucinations, abnormal thinking or behaviour, convulsions, uncontrollable twitching, jerking or writhing movements, fast heartbeat, high body temperature, pain in muscles, fever and dark urine. The excessive stiffness (spasms) in your muscles may also get worse.

If CLOFEN must be stopped, your doctor will reduce the dose gradually over a period of 1 to 2 weeks so that these unwanted effects are avoided.

Do not take CLOFEN to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if their symptoms seem to be similar to yours.

Things to be careful of

Be careful driving, operating machinery or doing other jobs that require you to be alert while you are taking CLOFEN until you know how it affects you. This medicine may cause sleepiness and decreased alertness in some people, especially at the start of treatment.

Be careful when drinking alcohol while taking CLOFEN. The combination may make you feel more sleepy and less alert than usual.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking CLOFEN.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of these side effects.

Side effects occur mainly at the start of treatment or if the dose is too high or increased too quickly. They can often be relieved by lowering the dose.

If you are over 65 years of age, you should be especially careful while taking this medicine. Report any side effects promptly to your doctor. As people grow older, they are more likely to get side effects from medicines.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • daytime sleepiness or drowsiness
  • tiredness, lack of energy
  • dizziness, light-headedness
  • spinning sensation (vertigo)
  • mental confusion
  • headache
  • difficulty sleeping, nightmares
  • nausea (feeling sick), vomiting, retching
  • constipation, diarrhoea, stomach pain
  • loss of appetite
  • stuffy or blocked nose
  • dry mouth
  • change in sense of taste
  • misuse, abuse and dependence
  • suicide or suicide attempts
  • numbness or tingling in hands and feet
  • muscle weakness, spasms or pain
  • problems with coordination and balance
  • difficulty in speaking
  • swelling of ankles due to fluid build-up
  • blurred vision or double
  • ringing in the ears
  • frequent urination or bed-wetting
  • excessive sweating
  • weight gain
  • impotence or inability to ejaculate
  • increased blood sugar
  • low body temperature

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • signs of an allergic reaction such as rash, itching or hives on the skin; swelling of the face, lips, tongue or other parts of the body; shortness of breath or wheezing
  • slow or difficulty breathing
  • irregular heart beat (fast or slow)
  • chest pain
  • uncontrollable muscle spasms affecting the eyes, head, neck or body
  • fainting or seizures (fits)
  • depression or other severe mood or mental changes
  • hallucinations (hearing or seeing things that are not there)
  • being unable to urinate or pain upon urinating; blood in the urine
  • symptoms following sudden discontinuation of the medicine (drug withdrawal syndrome).
    Refer to "Things you must not do" above

The above side effects could be serious. You may need medical attention.

Tell your doctor if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people.

After taking CLOFEN

Storage

Keep your tablets in the bottle until it is time to take them. If you take the tablets out of the bottle they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store CLOFEN or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Keep Clofen where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking this medicine, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

CLOFEN tablets are available in 2 strengths:

  • CLOFEN 10 - round, white, scored tablet, marked "BN" over 00"10" on one side and "G" on the other.
  • CLOFEN 25 - round, white, scored tablet, marked "BN" over "25" on one side and "G" on the other.

Each bottle contains 100 tablets.

Ingredients

The active ingredient in CLOFEN is baclofen.

  • Each CLOFEN 10 contains 10 mg of baclofen
  • Each CLOFEN 25 contains 25 mg of baclofen

The tablets also contain the following inactive ingredients:

  • lactose monohydrate
  • microcrystalline cellulose
  • calcium hydrogen phosphate
  • sodium starch glycollate
  • colloidal anhydrous silica
  • magnesium stearate

The tablets are gluten free.

Manufacturer

Alphapharm Pty Ltd
Level 1, 30 The Bond
30 - 34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian registration numbers:

CLOFEN 10 - AUST R 42146

CLOFEN 25 - AUST R 42147

- This leaflet was prepared in March 2020.

clofen_cmi\Mar20/00

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Clofen

Active ingredient

Baclofen

Schedule

S4

 

1 Name of Medicine

Baclofen.

2 Qualitative and Quantitative Composition

Each Clofen 10 and Clofen 25 tablet contains baclofen 10 mg and baclofen 25 mg, as the active ingredient, respectively.

Excipients with known effect.

Sugars as lactose.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Clofen 10.

10 mg tablet: white, flat bevelled edged, marked "BN" breakline "10" on one side and "G" on the other.

Clofen 25.

25 mg tablet: white, flat bevelled edged, marked "BN" breakline "25" on one side and "G" on the other.

4 Clinical Particulars

4.1 Therapeutic Indications

Suppression of voluntary muscle spasm in:
multiple sclerosis;
spinal lesions of traumatic, infectious, degenerative, neoplastic and unknown origin, causing: skeletal hypertonus and spastic and dyssynergic bladder dysfunction.
Baclofen is not recommended in Parkinson's disease or spasticity arising from strokes, cerebral palsy or rheumatoid disorders.

4.2 Dose and Method of Administration

Treatment with baclofen should always be started in hospital using small doses which are then gradually increased in a stepwise manner. The lowest dose compatible with an optimal response is recommended. The optimum daily dosage should be individually adapted to each patient's requirements, so that clonus, flexor and extensor spasms, and spasticity are reduced, at the same time retaining enough muscle tone to permit active movements and avoiding adverse effects as far as possible.
In order to prevent excessive weakness and falling, baclofen should be used with caution when spasticity is needed to sustain upright posture and balance in locomotion or whenever spasticity is used to maintain function. It may be important to maintain some degree of muscle tone and allow occasional spasms to help support circulatory function.
Abrupt discontinuation of treatment should be avoided (see Section 4.4 Special Warnings and Precautions for Use).
Clofen should be taken during meals with a little liquid.
In adults, Clofen should be given in at least three divided doses daily.

Dosage regimen.

As a rule, treatment should be started with a dose of 5 mg three times daily, subsequently increased at three day intervals by 5 mg three times daily (i.e. the dosage regimen is 5 mg three times a day for three days, then 10 mg three times a day for three days, etc.) until the optimum response has been attained. In certain patients reacting sensitively to drugs, it may be advisable to begin with a lower daily dose (5 mg or 10 mg), increased by smaller steps at longer intervals (see Section 4.4 Special Warnings and Precautions for Use). The optimum dosage generally ranges from 30 to 75 mg daily, although occasionally in hospitalised patients daily doses up to 100 mg may be necessary.
If no benefit is apparent within 6 to 8 weeks of achieving the maximum dosage, a decision whether or not to continue treatment with baclofen should be made.
Discontinuation of the treatment should always be gradual by successively reducing the dosage over a period of approximately 1 to 2 weeks, except in overdose related emergencies, or where serious adverse effects have occurred (see Section 4.4 Special Warnings and Precautions for Use).

Special populations.

Renal impairment.

In patients with impaired renal function or undergoing chronic haemodialysis, low doses (i.e. approximately 5 mg daily) should be used. These patients should be closely monitored for prompt diagnosis of early signs and/or symptoms of toxicity (e.g. somnolence, lethargy) (see Section 4.4 Special Warnings and Precautions for Use; Section 4.9 Overdose). Signs and symptoms of overdosage have been reported with doses above 5 mg daily in this setting (see Section 4.9 Overdose).
Clofen should only be administered to end stage renal failure patients when benefit outweighs risk.

Hepatic impairment.

No studies have been performed in patients with hepatic impairment under baclofen therapy. Baclofen should be prescribed with caution in patients with hepatic impairment (see Section 4.4 Special Warnings and Precautions for Use).

Elderly patients (aged 65 years or above).

Since unwanted effects are more likely to occur in elderly patients (due to increased risk of renal function impairment and CNS toxicity), a very cautious dosage schedule should be adopted and the patient kept under appropriate surveillance.
Toxicity due to baclofen may be mistaken for uraemic encephalopathy.

Paediatric patients.

Baclofen should be given with extreme caution to children under 16 years of age, as only limited data are available. Clofen tablets are not suitable for use in children with a body weight below 33 kg.

Monitoring advice.

Since in rare instances elevated AST, alkaline phosphatase or glucose levels in the serum have been recorded, appropriate laboratory tests should be performed periodically in patients with liver diseases or diabetes mellitus, in order to ensure that no drug induced changes in these underlying diseases have occurred.
Careful monitoring of respiratory and cardiovascular function is essential especially in patients with cardiopulmonary disease and respiratory muscle weakness.

4.3 Contraindications

Known hypersensitivity to baclofen or any of the components of the formulation.

4.4 Special Warnings and Precautions for Use

Psychiatric and nervous system disorders.

Patients suffering not only from spasticity but also from psychotic disorders, schizophrenia, depressive or manic disorders or confusional states should be treated cautiously with baclofen and kept under careful surveillance, because exacerbations of these conditions may occur.
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.
Cases of misuse, abuse and dependence have been reported with baclofen. Caution should be exercised in patients with a history of substance abuse and the patient should be monitored for symptoms of baclofen misuse, abuse or dependence e.g. dose escalation, drug-seeking behaviour, development of tolerance.

Epilepsy or other potential convulsive conditions.

Caution is needed in patients with epilepsy or other convulsive conditions, cortical or subcortical brain damage or significant EEG abnormalities, since ingestion of baclofen may cause deterioration of seizure control and EEG changes, and may precipitate convulsions. In patients with epilepsy and muscle spasticity, baclofen can be used under appropriate supervision, provided adequate anticonvulsive therapy is continued.
Lowering of the convulsion threshold may occur and seizures have been reported occasionally after cessation of baclofen or with overdosage.

Encephalopathy.

Cases of encephalopathy have been reported in patients treated with baclofen (see Section 4.8 Adverse Effects (Undesirable Effects); Section 4.9 Overdose). Symptoms included somnolence, depressed level of consciousness, confusion, myoclonus and coma which are usually reversible after treatment discontinuation. If any signs or symptoms of encephalopathy are observed, baclofen should be discontinued.

Other concomitant conditions.

Baclofen should be used with caution in patients with:
peptic ulcers or with a history of peptic ulcers;
cerebrovascular diseases or respiratory or hepatic insufficiency;
porphyria;
a history of alcoholism;
diabetes mellitus (baclofen may increase blood glucose concentrations);
hypertension (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Since unwanted effects are more likely to occur, a cautious dosage schedule should be adopted in elderly and patients with spasticity. Baclofen is not recommended in Parkinson's disease or spasticity arising from strokes, cerebral palsy or rheumatoid disorders.

Changes in muscle tone.

Baclofen should be used with caution in patients who use spasticity to maintain an upright posture and balance in moving. If an undesirable degree of muscular hypotonia occurs, making it more difficult for patients to walk or fend for themselves, this can usually be relieved by adjusting the dosage (i.e. by reducing the doses given during the day and possibly increasing the evening dose).
During treatment with baclofen, neurogenic disturbances affecting emptying of the bladder may improve, whereas in patients with pre-existing sphincter hypertonia, acute retention of urine may occur. The drug should, therefore, be used with caution in such cases.

Abrupt discontinuation.

Anxiety and confusional states, delirium, hallucinations, psychotic, manic or paranoid states, convulsions (status epilepticus), dyskinesia, tachycardia, hyperthermia and, as a rebound phenomenon, temporary aggravation of spasticity and hypertonia, have been reported upon the abrupt withdrawal of baclofen, especially after long-term medication.
Drug withdrawal reactions including postnatal convulsions in neonates have been reported after intrauterine exposure to oral baclofen (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Except in overdose-related emergencies or where serious adverse effects have occurred, treatment should, therefore, always be gradually withdrawn by successive dosage reduction over a period of approximately 1 to 2 weeks.
If withdrawal symptoms occur, restarting baclofen therapy and withdrawing over a longer period may help to resolve withdrawal problems.

Posture and balance.

Baclofen should be used with caution when spasticity is needed to sustain upright posture and balance in locomotion (see Section 4.2 Dose and Method of Administration).

Use in hepatic impairment.

Because baclofen is partially metabolised in the liver, patients with impaired hepatic function should be periodically monitored with laboratory tests (see Section 4.2 Dose and Method of Administration, Monitoring advice).

Use in renal impairment.

Since baclofen is largely eliminated by the kidneys, a dosage reduction is advised to avoid drug accumulation. Baclofen should be used with caution in patients with renal insufficiency and should only be administered to end stage renal failure patients only if the expected benefit outweighs the potential risk (see Section 4.2 Dose and Method of Administration, Renal impairment).
Neurological signs and symptoms of overdose including clinical manifestations of toxic encephalopathy (e.g. confusion, somnolence, hallucination) have been observed in patients with renal impairment taking baclofen at doses at and above 5 mg daily. Patients with renal impairment should be closely monitored for prompt diagnosis of early signs and symptoms of toxicity (see Section 4.9 Overdose).
Particular caution is required when combining baclofen to drugs or medicinal products that can significantly impact renal function. Renal function shall 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.

Use in the elderly.

See Section 4.2 Dose and Method of Administration.

Paediatric use.

Baclofen should be given with extreme caution to children under 16 years, as only limited data are available. Clofen tablets are not suitable for use in children with a bodyweight below 33 kg (see Section 4.2 Dose and Method of Administration).

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Levodopa/dopa decarboxylase (DDC) inhibitor (carbidopa).

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, headaches, 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.

Drugs causing central nervous system (CNS) depression.

Increased sedation may occur where baclofen is taken concomitantly with other drugs causing CNS depression including other muscle relaxants (such as tizanidine), with synthetic opiates or with alcohol (see Section 4.4 Special Warnings and Precautions for Use). 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 muscle weakness.

Antidepressants.

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

Lithium.

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

Antihypertensives and other drugs known to lower blood pressure.

Since concomitant treatment with drugs that lower blood pressure is likely to increase the fall in blood pressure, the dosage of concomitant medications should be adjusted accordingly.

Agents reducing renal function.

Drugs or medical products that can significantly impact renal function may reduce baclofen excretion leading to toxic effects (see Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment).

Others.

The concurrent use of baclofen with monoamine oxidase (MAO) inhibitors may result in increased CNS-depressant and hypotensive effects. Caution is recommended and dosage of one or both agents may require reduction.
Since baclofen may increase blood glucose concentrations, dosage adjustments of insulin and/or oral hypoglycaemic agents may be necessary during and after concurrent therapy.
Studies in rats indicate that the agonistic effects of baclofen on gastric acid secretion are potentiated by diazepam.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no data available on the effect of baclofen on fertility in humans.
(Category B3)

Risk summary.

There are no adequate and well-controlled studies in pregnant women. Animal data showed that baclofen crosses the placental barrier. Therefore, baclofen should not be used during pregnancy unless the expected benefit outweighs the potential risk to the fetus.
Drug withdrawal reactions including postnatal convulsions in neonates following intra-uterine exposure to oral baclofen, have been reported. In one suspected case of postnatal baclofen withdrawal, the convulsions were refractory to various anticonvulsants, but responsive to the administration of baclofen to the affected neonate (see Section 4.4 Special Warnings and Precautions for Use, Abrupt discontinuation).
 Studies in lactating women are limited to one (1) patient. In this particular case, available evidence suggests that baclofen is found in quantities so small that adverse effects in the infant would have been unlikely.

4.7 Effects on Ability to Drive and Use Machines

Baclofen may be associated with adverse effects such as dizziness, sedation, somnolence and visual disturbance (see Section 4.8 Adverse Effects (Undesirable Effects)) which may impair the patient's reaction. Patients experiencing these adverse reactions should be advised to refrain from driving or using machines.
The patient's ability to react may be adversely affected by sedation and decreased alertness caused by baclofen. Patients should, therefore, exercise due caution when driving a vehicle or operating machinery.

4.8 Adverse Effects (Undesirable Effects)

Adverse effects mainly occur at the start of treatment (e.g. sedation, somnolence), if the dosage is increased too quickly, if large doses are used, or if the patient is elderly. They are often transitory and can be attenuated or eliminated by reducing the dosage. They may necessitate withdrawal of the medication.
In patients with a history of psychiatric illness, cortical or organic brain disorders, or with cerebrovascular disorders (such as stroke), as well as in elderly patients, adverse reactions may be more serious.
It is often difficult to distinguish whether some of these are drug effects or manifestations of the diseases under treatment. Psychiatric manifestations can occur in acute or chronic toxicity due to baclofen.
Lowering of the convulsion threshold and convulsions may occur, particularly in epileptic patients (see Section 4.4 Special Warnings and Precautions for Use).
Certain patients have shown increased muscle spasticity as a paradoxical reaction to the medication.
Within each system organ class, adverse reactions are ranked under heading of frequency, the most frequent first, using the following convention: Very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1000); very rare < 1/10,000), not known (cannot be estimated from the available data).

Immune system disorders.

Not known: hypersensitivity.

Psychiatric disorders.

Common: confusional state, hallucination, depression, insomnia, euphoric mood, nightmare.

Musculoskeletal and connective tissue disorders.

Common: muscle weakness, myalgia.

Respiratory, thoracic and mediastinal disorders.

Common: respiratory depression.

Cardiac disorders.

Rare: arrhythmias, palpitations, chest pain.
Not known: bradycardia.

Vascular disorders.

Common: hypotension.
Rare: dyspnoea, ankle oedema.

Gastrointestinal disorders.

Very common: nausea (particularly at the start of treatment).
Common: gastrointestinal disorder, constipation, diarrhoea, retching, vomiting, dry mouth.
Rare: colicky abdominal pain, anorexia.

Hepatobiliary disorders.

Rare: hepatic function abnormal.

Nervous system disorders.

Very common: sedation, somnolence.
Common: dizziness, personality changes, vertigo, headache, ataxia, tremor, nystagmus, tinnitus.
Rare: paresthesia, dysarthria, dysgeusia, syncope, dyskinesia, coma, taste disturbances.
Not known: Cases of misuse, abuse and dependence have been reported with baclofen. Suicide and suicide-related events have been reported in patients treated with baclofen (see Section 4.4 Special Warnings and Precautions for Use, Psychiatric and nervous system disorders), encephalopathy.

Eye disorders.

Common: accommodation disorders, visual impairment.

Skin and subcutaneous tissue disorders.

Common: hyperhidrosis, rash, pruritus.
Not known: urticaria, alopecia.

Renal and urinary disorders.

Common: pollakiuria, dysuria, enuresis.
Rare: urinary retention, nocturia, haematuria.

Reproductive system and breast disorders.

Rare: erectile dysfunction, inability to ejaculate.
Not known: sexual dysfunction.

General disorders and administration site conditions.

Common: fatigue.
Very rare: hypothermia.
Not known: drug withdrawal syndrome*, swelling face and peripheral oedema.

Investigations.

Common: cardiac output decreased.
Not known: blood glucose increase.

Miscellaneous.

Rare: nasal congestion, weight gain.
* Drug withdrawal syndrome including postnatal convulsions has also been reported after intra-uterine exposure to oral baclofen.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

Signs and symptoms.

Prominent features are signs of central nervous depression or encephalopathy: somnolence, depressed level of consciousness, respiratory depression due to absent respiratory movement, coma.
Also liable to occur are: confusion, hallucinations, agitation, abnormal electroencephalogram (burst suppression pattern and triphasic waves), accommodation disorders, impaired pupillary reflex; generalised muscular hypotonia, myoclonus, hyporeflexia or areflexia; convulsions; peripheral vasodilatation, hypotension or hypertension, bradycardia, tachycardia or cardiac arrhythmias; hypothermia; nausea, vomiting, diarrhoea, hypersalivation; increased hepatic enzymes, sleep apnoea, rhabdomyolysis, tinnitus.
A deterioration in the condition may occur if various substances or drugs acting on the central nervous system (e.g. alcohol, diazepam, tricyclic antidepressants) have been taken at the same time.
Adult patients have ingested up to 1,125 mg of baclofen and survived. Ingestion of 1,250 to 2,500 mg by one patient was fatal. Serious poisoning has occurred with doses of 150 and 300 mg in adults.

Treatment.

No specific antidote is known.
Supportive measures and symptomatic treatment should be given for complications, such as hypotension, hypertension, convulsions, gastrointestinal disturbances, and respiratory or cardiovascular depression.
Symptomatic treatment should include the following:
Elimination of the drug from the gastrointestinal tract, e.g. administration of activated charcoal; if necessary, saline laxatives.
Since the drug is excreted chiefly via the kidneys, generous quantities of fluid should be given, possibly together with a diuretic.
Measures in support of cardiovascular functions.
In the case of respiratory muscle weakness, administration of artificial respiration.
In the event of convulsions, diazepam should be administered cautiously intravenously, paying attention to increased muscle relaxation, and possible respiratory insufficiency, if the patient is not already being artificially ventilated.
Haemodialysis (sometimes unscheduled) may be useful in severe poisoning associated with renal failure (see Section 4.4 Special Warnings and Precautions for Use).
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Baclofen is an effective antispastic agent with a spinal site of action. Its mechanism of action and pharmacological properties are different from those of other antispastic agents.
Baclofen also has central sites of action given the adverse event profile and general CNS depressant properties.
Baclofen depresses monosynaptic and polysynaptic reflex transmission, probably by various actions, including stimulation of GABAβ-receptors. This stimulation in turn inhibits the release of excitatory amino acids (glutamate and aspartate) in guinea pig preparations. Neuromuscular transmission is not affected by baclofen.
Baclofen exerts an antinociceptive effect. The clinical significance of this awaits clarification. In neurological diseases associated with spasm of the skeletal muscles, the clinical effects of baclofen take the form of a beneficial action on reflex muscle contractions and of marked relief from painful spasm, automatism and clonus. Baclofen, where indicated, improves the patient's mobility, making for greater independence and facilitating passive and active physiotherapy. Baclofen stimulates gastric acid secretion.

Clinical trials.

See Section 4.4 Special Warnings and Precautions for Use, Use in renal impairment; Section 5.1 Pharmacodynamic Properties.

5.2 Pharmacokinetic Properties

Absorption.

Baclofen is rapidly and completely absorbed from the gastrointestinal tract. Maximum concentrations of unchanged drug are achieved in plasma in 2 to 4 hours after an oral dose. The bioavailability of oral baclofen is 70-80%.
Following oral administration of a single dose of 40 mg baclofen, a peak serum concentration between 500 to 600 nanogram/mL was reached. The serum concentration remains above 200 nanogram/mL for 8 hours. The onset of action is highly variable and may range from hours to weeks.

Distribution.

The distribution volume of baclofen amounts to 0.7 L/kg. In cerebrospinal fluid, the active substance attains concentrations approximately 8.5 times lower than in the plasma.
Baclofen is bound to plasma proteins to the extent of approximately 30%.

Metabolism.

About 15% of the baclofen dose is metabolised in the liver. Deamination yields the main metabolite, β-(chlorophenyl)- γ-hydroxybutyric acid, which is pharmacologically inactive.

Excretion.

Approximately 70% of baclofen is eliminated in the urine in the unchanged form. The plasma elimination half-life of baclofen averages 3 to 4 hours. Within 72 hours, approximately 75% of the dose is excreted via the kidneys, approximately 5% of this quantity being in the form of metabolites. The remainder of the dose, including 5% as metabolites, is excreted in the faeces.

5.3 Preclinical Safety Data

Genotoxicity.

Baclofen did not induce mutations in bacterial or mammalian cells in vitro, lacked DNA damaging activity in the sister chromatid exchange assay, and had no clastogenic activity in the nuclear anomaly test.

Animal data.

In two teratogenic studies in pregnant rats, baclofen has been shown to increase the incidence of omphaloceles (ventral hernias) in fetuses at a dose of 20 mg/kg/day, which is maternotoxic. The relevance of this finding to humans is unknown. At the same dose there was also an increased incidence of incomplete sternebral ossification in the fetuses.
In mice, no teratogenic effects were observed at a dose of 81.5 mg/kg/day given via the diet or up to 40 mg/kg/day given by gavage.
At 40 mg/kg/day by gavage, a delay in fetal growth was associated with maternal anorexia. The lack of maternotoxicity seen in the dietary study suggests that the dose used was inadequate.
In pregnant rabbits, oral doses up to 10 mg/kg/day were manifested as a sedative effect. Skeletal examination of fetuses revealed a marked increase in the absence of ossification of the phalangeal nuclei of fore-limbs and hind-limbs.

Carcinogenicity.

A two year carcinogenicity study in rats found no evidence that baclofen had carcinogenic potential at oral doses up to 100 mg/kg/day. An apparently dose related increase in the incidence of ovarian cysts and of enlarged and/or haemorrhagic adrenals at the highest two doses (50 and 100 mg/kg/day) was observed in female rats. The clinical relevance of these findings is not known.
Ovarian cysts have been found by palpation in about 5% of the multiple sclerosis patients who were treated with oral baclofen for up to one year. In most cases these cysts disappeared spontaneously while patients continued to receive the drug. Ovarian cysts are known to occur spontaneously in a proportion of the normal female population.

6 Pharmaceutical Particulars

6.1 List of Excipients

The tablets also contain the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, calcium hydrogen phosphate, sodium starch glycollate, colloidal anhydrous silica, magnesium stearate.

6.2 Incompatibilities

See Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. The tablets should be kept out of reach of children.

6.5 Nature and Contents of Container

Container type: HDPE bottles with PP lidded child resistant caps.
Pack sizes: available in bottles of 100's.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian Register of Therapeutic Goods (ARTG).

AUST R 42146 - Clofen 10 baclofen 10 mg tablet bottle.
AUST R 42147 - Clofen 25 baclofen 25 mg tablet bottle.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Chemical name: (3RS)-4-amino-3- (4-chlorophenyl) butanoic acid.
Molecular formula: C10H12ClNO2.
Molecular weight: 213.7.
Baclofen is a derivative of gamma-aminobutyric acid (GABA). It is slightly soluble in water, very slightly soluble in ethanol (96%), practically insoluble in acetone and in ether. It dissolves in dilute mineral acids and in dilute alkali hydroxides.

CAS number.

1134-47-0.
Baclofen is a white or almost white powder.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes