Largactil (Chlorpromazine) is a type of medicine called a phenothiazine antipsychotic. It is used in the treatment of various psychiatric illnesses and is also used in the management of nausea and vomiting associated with terminal illness.

What is it used for?

  • Psychotic illness such as schizophrenia.
  • Mania and hypomania.
  • Short-term treatment of severe anxiety.
  • Short-term treatment of severely agitated or excited behaviour and violent or dangerously impulsive behaviour.
  • Childhood autism.
  • Childhood schizophrenia.
  • Nausea and vomiting in terminal illness (when other medicines are ineffective).
  • Persistant hiccups.

How does it work?

  • Chlorpromazine is a type of medicine called a phenothiazine antipsychotic.
It is used in the treatment of various psychiatric illnesses and is also used in the management of nausea and vomiting associated with terminal illness.
  • When used in psychiatric illness, chlorpromazine is sometimes described as a neuroleptic or a 'major tranquilliser', though this last term is fairly misleading, as this type of medicine is not just a tranquilliser and any tranquillising effect is not as important as the main way it works in psychiatric illness.
  • Chlorpromazine works by blocking a variety of receptors in the brain, particularly dopamine receptors. Dopamine is a natural compound called a neurotransmitter and is involved in transmitting messages between brain cells. Dopamine is a neurotransmitter known to be involved in regulating mood and behaviour, amongst other things.
  • Psychotic illness, in particular schizophrenia, is considered to be caused by overactivity of dopamine in the brain. Chlorpromazine blocks the receptors that dopamine acts on and this prevents the overactivity of dopamine in the brain. This helps to control psychotic illness.
  • Chlorpromazine improves disturbed thoughts, feelings and behaviour in various mental conditions, including schizophrenia, mania, and behavioural disorders that involve aggression or severe agitation or excitement. It produces a calming effect and controls aggression, delusions and hallucinations.
  • Chlorpromazine is used used in the long-term management of psychotic conditions such as schizophrenia. It is also used in the short-term to manage severe anxiety and severely agitated, violent or dangerous behaviour.
  • Chlorpromazine also affects dopamine receptors in an area of the brain that controls nausea and vomiting. Vomiting is controlled by an area of the brain called the vomiting centre. The vomiting centre is responsible for causing feelings of sickness (nausea) and for the vomiting reflex. It is activated when it receives nerve messages from another area of the brain called the chemoreceptor trigger zone (CTZ) and when it receives nerve messages from the gut.
  • Chlorpromazine controls nausea and vomiting by blocking dopamine receptors found in the CTZ. This stops the CTZ from sending the messages to the vomiting centre that would otherwise cause nausea and vomiting. Chlorpromazine is sometimes used to provide relief from nausea and vomiting in terminal illness, when other available medicines have been unsuccessful.
  • Chlorpromazine is also effective in treating persistant hiccups, though how it works in this case is unclear.
  • How do I take it?

    • Chlorpromazine tablets and oral solution can be taken either with or without food.
    • The dose of this medicine that is prescribed and how often it needs to be taken depends on the condition being treated. It is important to follow the instructions given by your doctor. These will be printed on the dispensing label that your pharmacist has put on the medicine.
    • If you forget to take a dose take it as soon as you remember, unless it is nearly time for your next dose. In this case just leave out the forgotten dose and take the next dose as usual. Don't take a double dose to make up for a missed dose.
    • If you have been taking high doses of this medicine for a long time, for example to treat schizophrenia, you should not suddenly stop taking it unless your doctor tells you to, even if you feel better and think you don't need it any more. This is because the medicine controls the symptoms of the illness but doesn't actually cure it. This means that if you suddenly stop treatment your symptoms could come back. Stopping the medicine suddenly may also rarely cause withdrawal symptoms such as nausea, vomiting, difficulty sleeping or tremor. When long-term treatment with this medicine is stopped, it should be done gradually, following the instructions given by your doctor.

    Warning!

    • This medicine may cause drowsiness. If affected do not drive or operate machinery. You should avoid drinking alcohol while taking this medicine because it can make drowsiness worse.
    • This medicine can occasionally cause your blood pressure to drop when you move from a lying down or sitting position to sitting or standing, especially when you first start taking the medicine, or if you are elderly. This may make you feel dizzy or unsteady. To avoid this try getting up slowly. If you do feel dizzy, sit or lie down until the symptoms pass.
    • High doses of this medicine may make your skin more sensitive to sunlight than it usually is, so you should avoid exposing your skin to direct sunlight or sunlamps until you know how your skin reacts. If you can't avoid sunlight you should use a sunscreen lotion or make sure your skin is protected with clothing.
    • Chlorpromazine can cause rare but serious contact skin sensitisation in people who regularly handle the medicine. For this reason chlorpromazine tablets should not be broken or crushed and you should avoid any unnecessary contact of the tablets with the skin.
    • It is recommended that you have regular eye examinations if you are taking this medicine for long periods of time, as it can sometimes cause eye problems. Consult your doctor if you experience any disturbances in your vision while taking this medicine.
    • Antipsychotic medicines are associated with an increased risk of getting a blood clot in a vein (deep vein thrombosis) or in the lungs (pulmonary embolism). For this reason, you should consult a doctor immediately if you get any of the following symptoms, which could suggest you have a blood clot: stabbing pains and/or unusual redness or swelling in one leg, pain on breathing or coughing, coughing up blood or sudden breathlessness.
    • Antipsychotic medicines can sometimes affect the ability of the body to control its core body temperature. This is more likely to be a problem in elderly people and can result in heat stroke in hot temperatures and hypothermia in cold temperatures. It is important to avoid situations that can result in you overheating or getting dehydrated. Ask your doctor or pharmacist for more advice.
    • This medicine may rarely cause a decrease in the normal amounts of blood cells in the blood. For this reason you should consult your doctor immediately if you experience any of the following symptoms: unexplained bruising or bleeding, purple spots, sore throat, mouth ulcers, high temperature (fever), feeling tired or general illness. Your doctor may want to take a blood test to check your blood cells.
    • Consult your doctor immediately if you experience abnormal body movements, particularly of the face, lips, jaw and tongue, while taking this medicine. These symptoms may be indicative of a rare side effect known as tardive dyskinesia, and your doctor may ask you to stop taking this medicine, or decrease your dose.
    • Consult your doctor immediately if you experience the following symptoms while taking this medicine: high fever, sweating, muscle stiffness, faster breathing and drowsiness or sleepiness. These symptoms may be due to a rare side effect known as the neuroleptic malignant syndrome, and your treatment may need to be stopped.

    Use with caution in

    • Elderly people.
    • Decreased kidney function.
    • Decreased liver function.
    • Elderly people with dementia. (Antipsychotic medicines have been shown to increase the risk of stroke in this group of patients. Chlorpromazine is not licensed or recommended for treating behavioural disturbances in elderly people with dementia).
    • Severe disease affecting the airways or lungs.
    • Heart disease, such as heart failure, recent heart attack, very slow heart rate (bradycardia) or irregular heart beats (arrhythmias).
    • People with a personal or family history of a type of abnormal heart rhythm, seen on a heart monitoring trace (ECG) as a 'prolonged QT interval'.
    • People with low levels of potassium or magnesium in their blood (hypokalaemia or hypomagnesaemia).
    • People with low fluid volume in their body, eg due to diuretic therapy, kidney dialysis, diarrhoea, vomiting, dehydration.
    • People with risk factors for having a stroke, for example a history of stroke or mini-stroke (TIA), smoking, diabetes, high blood pressure, or a type of irregular heartbeat called atrial fibrillation.
    • People with a personal or family history of blood clots (venous thromboembolism), for example in a vein of the leg (deep vein thrombosis) or in the lungs (pulmonary embolism).
    • People with other risk factors for getting a blood clot, for example smoking, being overweight, taking the contraceptive pill, being over 40, recent major surgery or being immobile for prolonged periods.
    • Diabetes. People with diabetes should monitor their blood sugar levels more closely whilst taking this medicine. This medicine may increase the blood sugar levels in the body.
    • Epilepsy.
    • People with conditions that increase the risk of epilepsy or convulsions, eg brain damage or withdrawal from alcohol.
    • Parkinson's disease.
    • Abnormal muscle weakness (myasthenia gravis).
    • People with a history of closed angle glaucoma.
    • Men with an enlarged prostate gland (prostatic hypertrophy).
    • Underactive thyroid gland (hypothyroidism).
    • Tumour of the adrenal gland (phaeochromocytoma).
    • People who are allergic to other phenothiazine medicines, such as prochlorperazine or trifluoperazine.

    Not to be used in

    • People in unresponsive unconscious states (comatose states).
    • People with reduced awareness, slow reactions or drowsiness due to medicines or illness that reduce activity in the central nervous system.
    • Severe disease involving the heart and blood vessels (cardiovascular disease).
    • People with a history of a drop in the normal number of blood cells in the blood.
    • This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

    If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

    Pregnancy and breastfeeding

    Certain medicines should not be used during pregnancy or breastfeeding. However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby. Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

    • The safety of this medicine during pregnancy has not been established. It should not be used in pregnancy, particularly in the first and third trimesters, unless considered essential by your doctor. If the medicine is used during the third trimester it could cause side effects or withdrawal symptoms in the baby after birth and the baby may need extra monitoring because of this. Seek further medical advice from your doctor.
    • If you do get pregnant while taking this medicine it is important to consult your doctor straight away for advice. If you have been taking the medicine for long periods of time, for instance to treat schizophrenia, you should not suddenly stop taking it unless your doctor tells you to, as this could cause your symptoms to come back.
    • This medicine may pass into breast milk. As it could cause drowsiness and potentially other side effects in a nursing infant, it is recommended that women who need treatment with this medicine should not breastfeed. Seek further medical advice from your doctor.

    Label warnings

    • This medication may cause drowsiness. If affected do not drive or operate machinery. Avoid alcoholic drink.
    • Avoid exposure of skin to direct sunlight or sun lamps.

    Side effects

    Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

    • Drowsiness.
    • Abnormal movements of the hands, legs, face, neck and tongue, eg tremor, twitching, rigidity (extrapyramidal effects, dyskinesia or dystonia).
    • Anxiety, restlessness and agitation (akathisia).
    • A drop in blood pressure that occurs when moving from a lying down or sitting position to sitting or standing, which results in dizziness and lightheadedness (postural hypotension - see warning section above).
    • Dry mouth.
    • Blocked nose.
    • Difficulty sleeping (insomnia).
    • Nightmares.
    • High blood prolactin (milk producing hormone) level (hyperprolactinaemia). Sometimes this may lead to symptoms such as breast enlargement, production of milk, stopping of periods or problems getting an erection.
    • Weight gain.
    • Abnormal heart beats (arrhythmias).
    • Jaundice (tell your doctor straight away if you notice any yellowing of your eyes or skin while taking this medicine).
    • Skin rashes.
    • Increased sensitivity of the skin to UV light (photosensitivity - see warning section above).
    • Metallic grey/mauve discolouration of the skin and parts of the eyes.
    • Clouding of the lens or cornea in the eyes.
    • Increased blood glucose levels. Tell your doctor if you notice you feel unusually hungry or thirsty, or need to pass urine more often than usual. People with diabetes should monitor their blood sugar closely.
    • Decrease in the number of white blood cells in the blood (leucopenia - see warning section above).
    • Interference with the body's temperature regulation (this is more common in elderly people and may cause heat stroke in very hot weather or hypothermia in very cold weather).
    • Rhythmical involuntary movement of the tongue, face, mouth and jaw, which may sometimes be accompanied by involuntary movements of the arms and legs (tardive dyskinesia). See warning section above.
    • High temperature combined with falling levels of consciousness, paleness, sweating and a fast heart beat (neuroleptic malignant syndrome). Requires stopping the medicine and immediate medical treatment - see warning section above.
    • Convulsions.
    • Abnormal blood clot in the blood vessels.

    The side effects listed above may not include all of the side effects reported by the medicine's manufacturer.

    For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

    How can this medicine affect other medicines?

    It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while taking this one, to ensure that the combination is safe.

    There may be an increased risk of drowsiness and sedation if chlorpromazine is taken with any of the following, which can also cause drowsiness:

    • alcohol
    • barbiturates, eg amobarbital, phenobarbital
    • benzodiazepines, eg diazepam, temazepam
    • MAOI antidepressants, eg phenelzine
    • sedating antihistamines, eg chlorphenamine, hydroxyzine
    • sleeping tablets, eg zopiclone
    • strong opioid painkillers, eg morphine, codeine
    • tricyclic antidepressants, eg amitriptyline.

    There may be an increase in side effects such as dry mouth, constipation, confusion or heat stroke (in hot and humid conditions) if chlorpromazine is taken with other medicines that have anticholinergic effects, including the following:

    • anticholinergic medicines for Parkinson's symptoms, eg procyclidine
    • antihistamines, eg brompheniramine, chlorphenamine
    • other antipsychotic medicines
    • other antisickness medicines, eg promethazine, meclozine, cyclizine
    • antispasmodic medicines, eg hyoscine
    • MAOI antidepressants, eg phenelzine
    • medicines for urinary incontinence, eg oxybutynin, flavoxate, tolterodine, propiverine, trospium
    • muscle relaxants, eg baclofen
    • tricyclic antidepressants, eg amitriptyline.
    • Anticholinergic medicines such as procyclidine, which are sometimes used to treat the Parkinson-like side effects of chlorpromazine, may oppose the antipsychotic effect of this medicine.

    Chlorpromazine may enhance the blood pressure-lowering effects of medicines that lower blood pressure, including medicines used to treat high blood pressure (antihypertensives) and medicines that lower blood pressure as a side effect, eg benzodiazepines. If you are taking medicines that lower blood pressure you should tell your doctor if you feel dizzy or faint after starting treatment with this medicine, as your doses may need adjusting.

    Medicines that increase the risk of a type of abnormal heart rhythm, seen as a 'prolonged QT interval' on an ECG, should be avoided in combination with chlorpromazine. These medicines include the following:

    • antiarrhythmics (medicines to treat abnormal heart beats), eg amiodarone, procainamide, disopyramide, sotalol
    • the antihistamines astemizole, mizolastine or terfenadine
    • arsenic trioxide
    • atomoxetine
    • certain antidepressants, eg amitriptyline, imipramine, maprotiline
    • certain antimalarials, eg halofantrine, chloroquine, quinine, mefloquine, Riamet
    • certain antipsychotics, eg thioridazine, pimozide, sertindole , haloperidol
    • cisapride
    • dronedarone
    • droperidol
    • intravenous erythromycin or pentamidine
    • methadone
    • moxifloxacin
    • saquinavir.

    There may also be an increased risk of a prolonged QT interval if medicines that can alter the levels of salts such as potassium or magnesium in the blood, eg diuretics such as furosemide, are taken in combination with chlorpromazine.

    There may be an increased risk of a drop in the number of white blood cells in the blood if chlorpromazine is taken in combination with other medicines that can have this side effect, such as the following:

    • anti-cancer chemotherapy medicines
    • carbamazepine
    • co-trimoxazole
    • penicillamine
    • phenylbutazone
    • sulphonamides, eg sulfadiazine.

    Chlorpromazine may oppose the effect of anticonvulsant medicines used to treat epilepsy.

    Chlorpromazine may increase blood sugar levels and disturb the control of diabetes. People with diabetes may need an adjustment in the dose of their antidiabetic medication.

    Chlorpromazine may oppose the effects of dopamine agonists used to treat Parkinson's disease, eg levodopa, apomorphine, bromocriptine, cabergoline, pergolide, ropinirole, rotigotine.

    Chlorpromazine may oppose the effect of histamine (used to treat leukaemia) and is not recommended for people having this treatment.

    If chlorpromazine is used in combination with propranolol the breakdown of both medicines by the liver may decrease, resulting in increased levels of both medicines in the blood. This could increase the risk of side effects of both medicines.

    Cimetidine may enhance or reduce the effect of chlorpromazine.

    Phenobarbital may increase the breakdown of chlorpromazine by the liver and so could make it less effective.

    Lithium may lower the amount of chlorpromazine in the blood and could make it less effective. There may also be an increased risk of extrapyramidal side effects (abnormal body movements) with this combination.

    Antacids for indigestion may potentially reduce the absorption of this medicine from the gut and so could make it less effective. To avoid a possible interaction, you should avoid taking antacids within two to three hours of taking this medicine.

    References:

    http://www.sanofi.com.au/products/aus_pi_largactil.pdf

    http://www.netdoctor.co.uk/medicines/brain-and-nervous-system/a6987/chlorpromazine/

    http://www.mydr.com.au/medicines/cmis/largactil

    https://en.wikipedia.org/wiki/Chlorpromazine

    http://www.medicines.org.uk/emc/medicine/804/SPC/Largactil+Injection

    http://www.schizophrenia.on.ca/Schizophrenia-Psychosis/Medication-Resource-Centre/Typical-Antipsychotic-Medications/Largactil-(chlorpromazine)