PATIENT INFORMATION LEAFLET PROCYCLIDINE HYDROCHLORIDE 5 mg/ml Solution for Injection

• K • If you have any further questions, ask your doctor or pharmacist. • This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours. • If an please tell your doctor or pharmacist.

1. What is PROCYCLIDINE Injection and what is it used for? 2. Before you are given PROCYCLIDINE Injection 3. How you will be given PROCYCLIDINE Injection 4. Possible side effects 5. Storing PROCYCLIDINE Injection 6. Further information 1. What is PROCYCLIDINE Injection and what Are you taking any of the following drugs? is it used for? • T ranquillisers (e.g. ) • T ricyclic and related antidepressants What is PROCYCLIDINE Injection? (e.g. ) PROCYCLIDINE Injection belongs to a group of • Monoamine oxidase inhibitors, otherwise known medicines called . Anticholinergics as MAOIs (used for depressive illness) block the effects of a substance called • (used for and viral in your body. infections) What is PROCYCLIDINE Injection used for? • Antihistamines (used to treat allergies) PROCYCLIDINE Injection is used to treat and relieve • K etoconazole (used as antifungals) the symptoms of Parkinson’s disease such as stiff • T acrine, , and neuroleptics (medicines used to treat mental writing and walking, overproduction of saliva and health problems including Alzheimer’s disease dribbling, sweating, uncontrolled eye movements and dementia) and depression. • (used for ) Some tranquillisers have side-effects like the • and disopyramide (used for arrhythmias symptoms of Parkinson’s disease and they can also – too fast, too slow or irregular heart beat) cause restlessness and abnormal head and body • Nef opam (used for moderate pain) movements. PROCYCLIDINE Injection is also • Me toclopramide, and domperidone sometimes used to control these side effects. (used for gastro-intestinal disorders) • Le vodopa (used for parkinsonism) 2. Before you are given PROCYCLIDINE • Nitrat e tablets that dissolve in the mouth Injection (used for angina attacks) Do not use PROCYCLIDINE Injection: If any of the above applies to you talk to your doctor Your doctor may decide that you should not be given or pharmacist. PROCYCLIDINE Injection if any of the points listed Pregnancy and breast feeding below applies to you: If you are pregnant, trying to become pregnant or • Ha ve you ever had an allergy (rash, itching, and breastfeeding, PROCYCLIDINE Injection will only be shortness of breath) to procyclidine or lactic acid? Special precautions to be taken: treatment outweighs the risk to the developing baby Your doctor may decide to take special precautions or new born baby. when giving you PROCYCLIDINE Injection if any of Driving and using machines the points listed below applies to you: PROCYCLIDINE Injection can cause blurred vision • Do you experience uncontrolled movements of the and at higher doses, dizziness, confusion and face and tongue (tardive dyskinesis)? hallucinations may occur. If you are affected in this • Do you suffer from glaucoma (eye disease caused way, do NOT drive or operate machinery while you by too much pressure within the eye)? are receiving PROCYCLIDINE 5 mg/ml Solution for • If you are a man, do you suffer from an enlarged Injection. prostate gland? • Do you often suffer from stomach cramps, 3. How you will be given PROCYCLIDINE abdominal pains or constipation? Injection • Do you suffer from kidney or liver disease? Important: If any of the above applies to you talk to your doctor PROCYCLIDINE Injection will be given to you as an or pharmacist. injection into a vein (intravenously) or muscle Taking other medicines (intramuscularly). Your doctor will decide on a dose Always tell your doctor if you are taking any other of PROCYCLIDINE Injection which is right for you. medicines because taking some medicines together Adults: can be harmful. Remember that the doctor at the Intravenous injection: hospital may not have been informed if you have • The usual starting dose is 2.5mg, three times a recently begun a course of treatment for another day, intravenously. Your doctor may then increase illness. this by 2.5mg to 5mg daily, every two or three days, until the desired effect is seen. This is known as the maintenance dose.

Information for the Healthcare Professional PROCYCLIDINE HYDROCHLORIDE 5 mg/ml Solution for Injection 1. NAME OF THE MEDICINAL PRODUCT 4.4. Special Warnings and Special Precautions For Use Kemadrin 5mg/ml Solution for injection Procyclidine Hydrochloride 5mg/ml, Solution for Injection assessed when prescribing in Procyclidine patients with existing angle-closure (narrow angle) glaucoma or those considered to be 2. QUALITATIVE AND QUANTITATIVE COMPOSITION predisposed to glaucoma. Cautious prescribing is also indicated in Procyclidine Hydrochloride BP 5mg per ml (10mg in each 2ml patients predisposed to obstructive disease of the gastro-intestinal ampoule) tract and those with urinary symptoms associated with prostatic 3. PHARMACEUTICAL FORM hypertrophy. Solution for injection In a proportion of patients undergoing neuroleptic treatment, 4. CLINICAL PARTICULARS tardive dysknesias will occur. While agents do not cause this syndrome, when given in combination with neuroleptics 4.1. Therapeutic Indications they may exacerbate the symptoms of or reduce Procyclidine is indicated for the treatment and symptomatic relief the threshold at which these symptoms appear in predisposed of all forms of Parkinson’s disease e.g. idiopathic (paralysis patients. In such individuals subsequent adjustment of neuroleptic agitans), postencephalitic and arteriosclerotic disease. therapy or reduction in anticholinergic treatment should be Procyclidine is also used to control troublesome extra-pyramidal considered. symptoms induced by neuroleptic drugs including Pseudo- Patients with mental disorders occasionally experience a Parkinsonism, acute dystonic reactions and . precipitation of a psychotic episode when procyclidine is 4.2. Posology and Method of Administration administered for the treatment of the extrapyramidal The variation in optimum dosage from one patient to another side effects of neuroleptics. should be taken into consideration by the physician. Elderly patients, especially those on high doses of anticholinergics Dosage in adults:- may be more susceptible to the adverse events associated with Parkinson’s disease:- Treatment is usually started at 2.5mg three times per day, patient may be particularly vulnerable to Central Nervous System increasing by 2.5 to 5mg daily at intervals of two or three days disturbances such as confusion, impairment of cognitive function until the optimum clinical response is achieved. and memory, disorientation and hallucinations. These effects are usually reversible on reduction or discontinuation of anticholinergic The usual maintenance dose to achieve optimal response is therapy. 15 to 30mg procyclidine per day.

Addition of a fourth dose before retiring has been seen to be of procyclidine hydrochloride in patients with impaired renal or hepatic function. However, since procyclidine is metabolised in have been well tolerated, and at the discretion of the attending the liver and excreted via the urine care should be exercised when physician dosing to this level may be appropriate. administering procyclidine to patients with impairment of renal or In general younger patients or those with postencephalitic hepatic function. parkinsonism may require higher doses for a therapeutic response Procyclidine should not be withdrawn abruptly as rebound than older patients and those with arteriosclerotic parkinsonism. Parkinsonian symptoms may occur. Procyclidine may be combined with levodopa or amantadine in Abuse patients who are inadequately controlled on a single agent. Procyclidine, along with other anticholinergic drugs, has the Neuroleptic-induced :- potential to be abused. Although the cases of abuse are rare, physicians should exercise caution in prescribing to Procyclidine Treatment is usually initiated at 2.5mg procyclidine three times patients with symptoms that may not be genuine. per day increasing by 2.5 mg daily until symptoms are relieved. 4.5 Interaction with other medicinal products and other forms The effective maintenance dose is usually 10 to 30 mg procyclidine of interaction per day. After a period of 3 to 4 months of therapy, Procyclidine Monoamine oxidase inhibitors or drugs with anticholinergic should be withdrawn and the patient observed to see whether the properties, such as amantadine, memantine, antihistamines, neuroleptic-induced extra-pyramidal symptoms recur. phenothiazines, tricyclic and related antidepressants, clozapine, If this is the case Procyclidine should be reintroduced to avoid disopyramide and may increase the anticholinergic action debilitating extra-pyramidal symptoms. Cessation of treatment of procyclidine. periodically is to be recommended even in patients who appear The use of drugs with properties, such as tacrine, to require the drug for longer periods. may reduce the therapeutic response to Procyclidine. Furthermore, Procyclidine Injection may be given intramuscularly in doses of drugs with anticholinergic properties may antagonise the effect of 5 to 10mg, repeated after 20 minutes if necessary, up to a daily parasympathomimetic agents. maximum of 20mg procylidine. The concomitant use of procyclidine with some neuroleptics for In acute torsion and paroxysmal dyskinesias, doses of the treatment of extrapyramidal symptoms has been associated 5 to 10mg procyclidine intravenously are frequently effective within with a reduction in neuroleptic plasma concentrations. However 5 to 10 minutes. Occasionally, patients may need more than 10 mg procyclidine, and may require up to half an hour to obtain relief. reduction in clinical effect. Dosage in children:- Drugs with anticholinergic properties may decrease salivation The use of in Procyclidine this age group is not recommended. causing dry mouth and, in theory, may reduce the absorption and therefore the therapeutic effect of sublingual or buccal nitrate Dosage in Elderly:- tablets. Elderly patients may be more susceptible than younger adults to the anticholinergic effects of Procyclidine and a reduced dosage may be required (See Special Warnings and Special Precautions of levodopa by increasing gastric emptying time, resulting in for Use). enhanced gastric degradation. Administration:- The effect of anticholinergics such as procyclidine may antagonise Pharmacokinetic studies have indicated that the mean plasma the gastrointestinal effects of cisapride, domperidone and . administration orally or intravenously, if more convenient. Procyclidine may potentiate the vagolytic effects of quinidine. Oral administration may be better tolerated if associated with a Anticholinergics may reduce the absorption of ketoconazole. meal. Exposure to high environmental temperature and humidity in 4.3. Contra-Indications association with a /anticholinergic drug regimen Procyclidine is contra-indicated in individuals with known has rarely resulted in hyperpyrexia. hypersensitivity to any component of the preparation, untreated urinary retention, closed angle glaucoma and gastro-intestinal plasma levels of procyclidine. If anticholinergic effects are seen, obstruction. the dose of procyclidine should be reduced.

Procyclidine 5 mg/ml Solution for injection PIL - UK

approved for print/date Item number: BBBA7086 Colours Non Printing Colours 1. Black 1. Profile Originator: G. Worth Dimensions: 148 x 520 Origination Date: 06/12/2019 Min Body Text Size: 6.25 pt 2. 2. Text area Revision Date: Supplier: IL/Rotexmedica 3. 3. Revised By: GmbH 4. 4. 5. 5. Proof Round Technical Date sent: 06/12/2019 6. 6. 3 Approval Date received: 11/12/2019 [email protected]

GTIN 13 (if no barcode on artwork): n/a

* Please note that only Artwork Studio is permitted to make changes to the above artwork. Version 4 No changes are permitted by any 3rd party other than added notes and mark ups for required changes. 19.11.2019 • The usual total daily maintenance dose is 15 Uncommon (less than 1 in 100, but more than to 30mg, however, in certain cases your doctor 1 in 1000 patients): may decide to prescribe more (up to a maximum • Dizziness of 60mg). • Feeling confused • Although the dose is usually taken three times • Hearing unexpected noises or seeing unexpected a day, your doctor may give you a fourth dose sights (hallucinations) before bedtime. • Nausea (feeling sick) or vomiting (being sick) • If PROCYCLIDINE Injection is being used to control • the side-effects of another drug, then the usual • Nervousness maximum daily dose is 30mg. • Skin rash • Your doctor may decide to stop PROCYCLIDINE • Reduced concentration or memory Injection after 3 or 4 months to see if the • Anxiety side-effects return. • Agitation (feeling irritable) • Given intravenously, a 5mg to 10mg dose of Please also note that if you are taking tranquillisers, PROCYCLIDINE may relieve abnormal head unusual body movements, particularly of your and body movements within 5 to 10 minutes. hands, arms and legs may occur. If you are receiving Occasionally, a higher dose is needed and may PROCYCLIDINE Injection to control these side take up to half an hour to bring relief. effects, it has been reported, on rare occasions, that Intramuscular injection: • PROCYCLIDINE Injection may be given is happening, tell your doctor who may decide to intramuscularly in doses of 5 to 10mg; change your tranquilliser dosage. this may be repeated after 20 minutes, If any of the side effects gets serious, or if you up to a daily maximum of 20mg. notice any side effects not listed in this leaflet, Elderly: please tell your doctor or pharmacist. Your doctor may decide to use a lower dose than Reporting of side effects the above. If you get any side effects, talk to your doctor or Children: pharmacist. This includes any possible side effects PROCYCLIDINE Injection is not usually recommended for use in children. However, effects directly via the Yellow Card Scheme in certain cases your doctor may decide that (Website: www.mhra.gov.uk/yellowcard). PROCYCLIDINE Injection is required. By reporting side effects, you can help provide more information on the safety of this medicine. Treatment with PROCYCLIDINE Injection should not be stopped suddenly. 5. Storing PROCYCLIDINE Injection If you think you have been given too much Keep out of the sight and reach of children. PROCYCLIDINE Injection or if someone else takes Do not use PROCYCLIDINE Injection after the expiry your medicine by mistake, tell a doctor or nurse date on the carton. The expiry date refers to the last immediately. day of that month. If you think you have been given more PROCYCLIDINE Injection should be stored PROCYCLIDINE Injection than you should: below 25 ºC. As this medicine will be given to you whilst you are in hospital, it is unlikely that you will be given too 6. Further information little or too much, however, tell your doctor or nurse if you have any concerns. What PROCYCLIDINE Injection contains: The active substance is PROCYCLIDINE Symptoms of overdose: Agitation, restlessness, HYDROCHLORIDE 5 mg in each 1 ml of solution. confusion, sleeplessness lasting up to 24 hours or more, hallucinations, euphoria, anxiousness, The solution for injection also contains lactic acid aggressiveness, dilation of pupils and increased and water for injections. heart beat. Contents of the pack: Tell your doctor or healthcare professional if you PROCYCLIDINE Injection is supplied in cartons of have any of these side effects so that he/she can give appropriate treatment. If you have already left of procyclidine hydrochloride. the medical premises, contact your nearest hospital, Marketing authorisation holder: doctor or pharmacist. Accord Healthcare Limited If you have any further questions on the use of this Sage House, 319 Pinner Road product, ask your doctor or pharmacist. North Harrow, Middlesex, HA1 4HF, United Kingdom Manufacturer: 4. Possible side effects Panpharma GmbH Like all medicines PROCYCLIDINE Injection can Bunsenstrasse 4, Trittau, Schleswig-Holstein, cause side effects, although not everybody gets 22946, Germany. them. This leaflet was last approved in December 2019. Common (more than 1 in 100 patients): For information in large print, • A dry mouth on tape, on CD or in Braille, • Blurred vision phone 01271 385257. • Constipation • BBBA7086

4.6. Pregnancy and Lactation 5. PHARMACOLOGICAL PROPERTIES Pregnancy:- 5.1. Pharmacodynamic Properties The safety of using Procyclidine during pregnancy has not been Procyclidine is a synthetic anticholinergic agent which blocks the established. excitatory effects of acetylcholine at the muscarinic receptor. However, extensive clinical use has not given any evidence that Idiopathic Parkinson’s disease is thought to result from it in any way compromises the normal course of pregnancy. degeneration of neurones in the substantia nigra whose axons Nevertheless, as with all drugs, use should be considered only project and inhibit cells in the corpus striatum. Blockade by neuroleptic drugs of the released by these terminals outweighs any possible risk to the developing foetus. produces a similar clinical picture. The cell bodies in the corpus Lactation:- striatum also receive cholinergic innervation which is excitatory. No information is available on the passage of procyclidine into Relief of the Parkinsonian syndrome can be achieved, either by human breast milk following administration of Procyclidine. potentiation of the system or blockade of the 4.7. Effects on Ability to Drive and Use Machines cholinergic input by anticholinergics. It is by a central action of Adverse events of a neurological character such as blurred vision, this latter type by which procyclidine exerts its effect. dizziness, confusion and disorientation have been reported with Procyclidine is particularly effective in the alleviation of rigidity. procyclidine. Therefore, if affected, patients should be advised not to drive or operate machinery. and drooling, sweating, oculogyric crises and depressed mood are 4.8 Undesirable effects For this preparation there is no modern clinical documentation 5.2. Pharmacokinetic Properties which can be used as support for determining the frequency of Procyclidine is adequately absorbed from the gastro-intestinal tract adverse reactions. with a bioavailability of 75% and disappears rapidly from the The main undesirable effects are those to be expected from any tissues. The relatively low clearance of 68 ml/min represents a anticholinergic agent these are generally reversible on reducing the dosage. The mean plasma elimination half-life after both oral and With high doses of procyclidine dizziness, mental confusion, intravenous administration is approximately 12 hours. impaired cognition and memory, disorientation, anxiety, agitation No detailed information is available on the metabolic fate of and hallucinations may occur. procyclidine but very little of the parent compound is excreted in

Psychiatric Uncommon Agitation, anxiety, is known to be metabolised in the liver, principally by cytochrome disorders (>1/1000 and nervousness, P450 and then conjugated with glucuronic acid. This conjugate <1/100) confusion, has been detected in the urine. disorientation, hallucinations. 5.3. Pre-clinical Safety Data Fertility:- Rare (<1/1000) Psychotic disorder A three generation study in rats dosed at 40 mg/kg/day via the diet before and during pregnancy showed only that the number Nervous system Uncommon Dizziness, memory of viable pups was slightly decreased from the second mating. disorders (>1/1000 and impairment impaired No other parameters were affected. <1/100) cognition Teratogenicity:- Eye disorders Common (> 1/100) Blurred vision No teratogenic effects were seen in rats dosed subcutaneously with 10, 30 or 100 mg/kg/day on days 8 to 16 of pregnancy. Gastrointestinal Common (> 1/100) Dry mouth, Maternal bodyweight gain was reduced at doses of 30 or disorders constipation 100 mg/kg/day, and a 10% reduction in foetal weight was Uncommon (>1/1000 and Nausea, vomiting, seen at 100 mg/kg/day <1/100) gingivitis Mutagenicity:- Skin and Uncommon Rash No data is available regarding the mutagenic potential of subcutaneous (>1/1000 and procyclidine hydrochloride. tissue disorders <1/100) Carcinogenicity:- Renal and Common (> 1/100) Urinary retention There is no data on the carcinogenic potential of procyclidine urinary disorders hydrochloride. 6. PHARMACEUTICAL PARTICULARS Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the 6.1. List of Excipients medicinal product is important. It allows continued monitoring of Lactic acid 10μg

professionals are asked to report any suspected adverse Water for Injections to 2ml reactions via the Yellow Card Scheme (Website: www.mhra.gov.uk/ 6.2. Incompatibilities yellowcard). None known. 4.9 Overdose 6.3. Shelf Life Symptoms & Signs: 5 years. Reports of overdosage are relatively rare and no fatalities are 6.4. Special Precautions for Storage known. Symptoms of overdosage are agitation, restlessness Store below 25°C and confusion with severe sleeplessness lasting up to 24 hours or more. Visual and auditory hallucinations have been reported. 6.5. Nature and Contents of Container Most subjects are euphoric but the occasional patient may be 2ml Neutral glass ampoules anxious and aggressive. The pupils are widely dilated and 6.6. Instructions for Use, Handling and Disposal unreactive to light. No special instructions In recorded cases, the disorientation has lasted 1 to 4 days 7. Marketing authorisation holder and ended in a recuperative sleep. Tachycardia has also been Accord Healthcare Limited reported in association with cases of Procyclidine overdose. Sage House, 319 Pinner Road Treatment: North Harrow, Middlesex, HA1 4HF, United Kingdom If procyclidine has been ingested within the previous hour or two 8. MARKETING AUTHORISATION NUMBER (or possibly longer in view of its likely effects on gastric motility) PL 20075/0706 then gastric lavage is probably indicated. Other active measures such as the use of cholinergic agents or haemodialysis are 9. DATE OF FIRST AUTHORISATION/ extremely unlikely to be of clinical value although if convulsions RENEWAL OF AUTHORISATION occur they should be controlled by injections of diazepam. 24 April 2003 10. DATE OF REVISION OF THE TEXT 28/03/2018

BBBA7086

Procyclidine 5 mg/ml Solution for injection PIL - UK approved for print/date Item number: BBBA7086 Colours Non Printing Colours 1. Black 1. Profile Originator: G. Worth Dimensions: 148 x 520 Origination Date: 06/12/2019 Min Body Text Size: 6.25pt 2. 2. Text area Revision Date: Supplier: IL/Rotexmedica 3. 3. Revised By: GmbH 4. 4. 5. 5. Proof Round Technical Date sent: 06/12/2019 6. 6. 3 Approval Date received: 11/12/2019 [email protected]

GTIN 13 (if no barcode on artwork): n/a

* Please note that only Artwork Studio is permitted to make changes to the above artwork. Version 4 No changes are permitted by any 3rd party other than added notes and mark ups for required changes. 19.11.2019