Pirenzepindihydrochlorid 1/3 PAR
AT/H/PSUR/0001/002
Annex I : CSP Gastrozepin
In PAR: Proposed CSP with assessor comments, if any
In Draft FAR:Proposed CSP with assessor comments
In FAR:Agreed CSP
Proposed CSP
4.2 POSOLOGY AND METHOD OF ADMINISTRATION
Tablets:
Unless otherwise prescribed, 50 to 150 mg per day in divided doses.In general, 50 mg twice daily, morning and evening, is recommended. Occasionally it may benecessary for the first 2 or 3 days of treatment to administer an additional dose at midday.The tablets should be taken approximately 1/2 hour before meals with a little liquid.In spite of a rapid subjective improvement, the patient should in no case reduce or break offthe treatment prescribed by the physician.
Therapy should always be continued with oral pirenzepine dihydrochloride for a period of 4 to 6 weeks.
Ampoules:
Unless otherwise prescribed, one ampoule should be injected intramuscularly orintravenously every 12 hours.
For the prophylaxis and treatment of stress ulcers, administration of one ampoule 3 timesdaily (every 8 hours) is recommended.
Parenteral pirenzepine dihydrochloride therapy should be continued until symptoms disappear, usuallyfor 2-3 days, when Pirenzepine can be administered orally.
Note:Intravenous administration should be by slow injection (more than 3 minutes), or preferably
by drip infusion.Intravenous infusion: pirenzepine dihydrochloride solution may be combined with isotonic salinesolution, Ringer solution, 5% laevulose, 5% glucose solution.
Paediatric population
The safety and efficacy of pirenzepine dihydrochloride in paediatricpopulations aged below 18 years has not been established.
4.3 CONTRAINDICATIONS
Pirenzepine dihydrochloride should not be used in cases of known hypersensitivity to any of thecomponents of the drug and in patients with paralytic ileus.
In case of rare hereditary conditions that may be incompatible with an excipient of theproduct (please refer to “Special warnings and precautions for use”) the use of this product iscontraindicated.
4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE
Pirenzepine should be used with caution in patients with:
- glaucoma
- prostatic hypertrophy
- tachycardia
Intravenous injection should always be slow:
1. because of the risk of thrombophlebitis in view of the content of 39,2% propyleneglycol
2. in patients with unstable circulation because of high initial pirenzepine plasmaconcentrations; blood pressure must be constantly monitored.
Tablets:
Pirenzepine dihydrochloride tablets 25 mg contain 833,64 mg lactose per maximum recommendeddaily dose. Patients with rare hereditary conditions of galactose intolerance e.g.galactosaemia, the Lapp lactase deficiency or glucose-galactose malabsorption should nottake this medicine.
Pirenzepine dihydrochloride tablets 50 mg contain 438.78 mg lactose per maximum recommendeddaily dose.
Patients with rare hereditary conditions of galactose intolerance e.g.galactosaemia should not take this medicine.
Ampoules:
This medicinal product contains less than 1 mmol sodium (23 mg) per single recommendeddose, i.e. essentially “sodium-free”.
4.5 INTERACTION WITH OTHER MEDICINAL PRODUCTS AND OTHERFORMS OFINTERACTIONS
Concurrent treatment with pirenzepine dihydrochloride and H2-receptor blockers leads to a morepronounced reduction in gastric acid secretion.The action of anti-inflammatory agents is not impaired when these are used togetherwith pirenzepine dihydrochloride. On the other hand, gastro-intestinal tolerance of these products isimproved.
4.6 FERTILITY, PREGNANCY AND LACTATION
There is limited data from the use of pirenzepine in pregnant women.Animal studies do not indicate direct or indirect harmful effects with respect to fertility andreproductive toxicity.
There is evidence that pirenzepine is excreted into breast milk, even though in small amounts.
As a result anticholinergic effects may occur in breast fed infants.
No studies on the effect in human fertility have been conducted.
As a precautionary measure, it is preferable to avoid the use of pirenzepine dihydrochloride duringpregnancy and lactation.
4.7 EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
No studies on the effects on the ability to drive and use machines have been performed.However, patients should be advised that they may experience undesirable effects such asaccommodation disorders during treatment with pirenzepine dihydrochloride. Therefore, caution shouldbe recommended when driving a car or operating machinery. If patients experienceaccommodation disorders they should avoid potentially hazardous tasks such as driving oroperating machinery.
4.8 UNDESIRABLE EFFECTS
Adverse reactions have been ranked under headings of frequency using the followingconvention:
very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100);rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from theavailable data).
System Organ Class: Frequency
MedDRA Term
Immune system disorders:
Anaphylactic reactions Not known
Hypersensitivity Not known
Nervous system disorders:
Headache Common
Eye disorders:
Accommodation disorders Common
Cardiac disorders:
Tachycardia Not known
Gastrointestinal disorders:
Dry mouth Very common
Constipation Common
Diarrhoea Common
Skin and subcutaneous disorders:
Rash Common
Renal and urinary disorders:
Urinary retention Uncommon
4.9 OVERDOSE
Symptoms
If large doses of pirenzepine are ingested the following anticholinergic effects may develop:warm, dry, flushed skin; dry mouth; mydriasis; delirium; tachycardia; ileus; urinaryretention; jerky myoclonicmovements; choreo-athetosis.
Therapy
Haemodialysis, haemoperfusion, peritoneal dialysis and repeated doses ofcharcoal are not effective in removing anticholinergic agents.In case of severe intoxication (e.g. hyperthermia, severe delirium or tachycardia) a smalldose of physostigmine intravenously can be given.
In case of an acute glaucoma episode treatment with miotic drops should be initiated andspecialist advice sought immediately