Akineton Tablets & Injection

AKINETON is indicated for the management of:

• Parkinsonism
• Drug-induced extrapyramidal symptoms

Posology
Treatment with AKINETON is normally initiated with small incremental doses, depending on the therapeutic effect and side effects.
Parkinsonism:
Tablets: Gradually increase from 1 mg (u00bd a tablet) twice daily up to the individually adjusted optimal dose which generally ranges between 1 mg (u00bd a tablet) to 4 mg (2 tablets) three to four times daily. The total daily dose should be spread evenly throughout the day.
Ampoules: In severe cases 10 to 20 mg (2 to 4 mL) intramuscularly or slowly intravenously administered, over the duration of the day.
Drug-induced extrapyramidal symptoms:
Tablets: Adults: Take orally, concomitant with the neuroleptic medicines, 1 mg (u00bd a tablet) to 4 mg (2 tablets) one to four times daily, increased as required, to maximum of 18 mg (9 tablets) daily. Children aged between 3 to 15 years: Take 1 mg (u00bd a tablet) to 2 mg (1 tablet) three times daily. The total daily dose should be spread evenly throughout the day.
Ampoules: Adults: The parental dose for adults is 2.5 to 5 mg (0.5 to 1 ml) given intramuscularly or slowly intravenously. Children: The suggested dose for children up to 1 year of age is 1 mg, up to 6 years 2 mg, and up to 10 years 3 mg, given slowly intravenously.
Dependent on individual reactivity, extrapyramidal symptoms may disappear already in the course of injection. In this case the injection should be stopped immediately. If required, injection of a dose appropriate to the childu2019s age can be repeated after 30 minutes.

AKINETON is contraindicated in:

• patients with a hypersensitivity to biperiden or to any of the excipients in AKINETON (See section 6.1);
• Narrow angle glaucoma;
• Mechanical stenosis or obstruction (ileus) in the gastro-intestinal tract;
• Megacolon;
• Patients with cerebral impairment crisis (See section 4.4);
• Pregnancy and lactation (See section 4.6);
• Myasthenia gravis.

u2022 Patients with central nervous system impairment may have an increased risk of side effects of AKINETON.
u2022 Feeling of unrest, confusion, or conditions similar to psychoses, are symptoms of overdosage which in patients with low tolerance, such as patients with cerebral arteriosclerosis, may occur even with doses falling into the therapeutic range; similar symptoms occur if AKINETON is given together with antidepressants or neuroleptics (See section 4.8).
u2022 In patients with prostatic enlargement, AKINETON may cause urinary retention.
u2022 AKINETON should be used with caution in patients diagnosed with lower urinary tract symptoms (LUTS) or benign prostatic hypertrophy obstruction (BPH) due to the possible development of acute urinary retention, voiding difficulty, and other anticholinergic side effects.
u2022 AKINETON should be administered with caution in conditions which may be associated with tachycardia or in patients who show an increased tendency to convulsions.
u2022 The consumption of alcohol should be avoided under AKINETON therapy (See section 4.5).
u2022 Following parenteral administration, severe blood pressure decrease and severe bradycardia may occur especially if the injection is too rapid. (See section 4.2)
u2022 AKINETON should not be used in patients with myasthenia gravis.
u2022 Impaired memory, as well as lack of concentration and euphoria frequently occur in patients taking AKINETON (see section 4.8).
u2022 Tolerance, withdrawal and relapse are consistent with AKINETON dependence due to long-term use of anticholinergics.
u2022 They may cause dependency.
Excipients
AKINETON tablets contain lactose monohydrate 38 mg per tablet. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Withdrawal symptoms
Upon cessation of treatment or reduction of the dose, insomnia develops. Abrupt cessation can lead to the following withdrawal symptoms: nausea, sweating, and urinary urgency (See section 4.8).

The administration of AKINETON in combination with other anticholinergic psychotropic drugs, antihistamines, antiparkinsonian drugs and antispasmodics can potentiate the CNS and peripheral side effects. The concomitant intake of quinidine may potentiate the anticholinergic effect (especially AV conduction).
The concurrent administration of levodopa and AKINETON may potentiate dyskinesia. Generalised choreic movements have been reported in Parkinson's disease following concurrent administration of carbidopa/levodopa and AKINETON (biperiden).
Tardive dyskinesia induced by neuroleptics may be intensified by AKINETON. Parkinsonian symptoms in the presence of existing tardive dyskinesia are occasionally so serious as to mandate continued anticholinergic therapy.
The effect of metoclopramide and compounds with similar activity on the gastrointestinal tract is attenuated by anticholinergics such as AKINETON.
As with all other drugs acting on the central nervous system, the consumption of alcohol should be avoided under AKINETON therapy.

Pregnancy
The safety and efficacy of AKINETON in pregnant women has not been established.
Lactation
The safety and efficacy of AKINETON in lactating women has not been established.

AKINETON may impair the patientu2019s speed of reaction. Since adverse reactions such as tiredness, dizziness, drowsiness, delirium, hallucination, anxiety, agitation, euphoric mood, confusional state, accommodation disorders, mydriasis, photophobia, and narrow-angle glaucoma may occur in patients receiving AKINETON, patients should be advised not to drive a motor vehicle, climb dangerous heights or operate dangerous machinery or perform any tasks that requires coherent concentration especially if used with other medicines that affect the central nervous system or alcohol (See section 4.8). In these situations, impaired decision making could lead to accidents.

a. Summary of the safety profile:
No text
b. Tabulated list of adverse reactions:
Adverse events are listed below by system organ class and frequency. The following frequencies are used as the basis in the evaluation of side-effects: Very common (u22651/10); Common (u22651/100 to <1/10); Uncommon (u22651/1,000 to <1/100); Rare (u22651/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).
System Organ Class Frequency grouping
Infections and infestations Not known: parotis
Immune system disorders Very rare: hypersensitivity
Psychiatric disorders Rare: delirium*, hallucination*, insomnia*, excitement*, agitation*, fear*, depersonalisation, derealisation and confusional state* Very rare: anxiety, euphoric mood
Nervous system disorders Rare: dizziness, fatigue, memory impairment, impaired cognitive function Very rare: headache, tardive dyskinesia, ataxia and speech disorder, convulsions
Eye disorders Very rare: accommodation disorders, blurred vision, mydriasis, photophobia, and narrow-angle glaucoma
Ear and labyrinth disorders Not known: vertigo
Cardiac disorders Rare: tachycardia Very Rare: bradycardia
Vascular disorders Not known: hypotension
Gastrointestinal disorders Rare: dry mouth, nausea, gastric disorder Very Rare: constipation, obstipation, abdominal discomfort
Skin and subcutaneous tissue disorders Very rare: hypohidrosis, allergic rash
Musculoskeletal and connective tissue disorders Rare: Muscle twitching
Renal and urinary disorders Very Rare: urinary retention
General disorders and administrative site conditions Not known: fever, hot skin

c. Description of selected adverse reactions
Psychiatric disorders Restlessness, or conditions similar to psychotic disorder, are symptoms of overdosage which in patients with low tolerance, such as patients with cerebral arteriosclerosis, may occur even with doses falling into the therapeutic range; similar symptoms occur if AKINETON is given together with antidepressants or neuroleptics in high doses (See section 4.4).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who- umc.org) found on SAHPRA website.

Symptoms
The picture of intoxication is essentially the same as that of atropine intoxication with peripheral anticholinergic symptoms (such as wide, sluggish pupils, dilated pupils, slowing of movements, reddening of face, dryness of mucous membranes, flushing, rise in heart rate, atony of bowels and bladder, increased temperature, especially in children) and disorders of the central nervous system (such as excitation, confusion, clouding of consciousness, agitation, delirium, mental fog and/or hallucinations). In case of massive intoxication there is a risk of circulatory failure and central respiratory paralysis.
Treatment
Acetylcholinesterase inhibitors may be used as antidotes, especially physostigmine, which passes the blood brain barrier, and also influences the centrally induced symptoms.