Active ingredients: Hyoscine N-butylbromide, Paracetamol
Buscopan compositum 10 mg + 500 mg coated tablets
Buscopan Compositum package inserts are available for pack sizes:- Buscopan compositum 10 mg + 500 mg coated tablets
- Buscopan compositum 10 mg + 800 mg suppositories
Why is Buscopan Compositum used? What is it for?
Buscopan compositum contains two active substances: hyoscine N-butylbromide (medicine used in cases of motility disorders of the stomach and intestines, or of the urinary and biliary tract) and paracetamol (a medicine used to decrease pain).
Buscopan compositum is indicated in adults and children over 10 years of age in cases of:
- pain and spasms in the stomach and intestines
- pain due to obstacles in the flow of the urinary tract and biliary tract (where bile flows, a substance involved in some digestive processes)
- menstrual cramps.
Talk to your doctor if you don't feel better or if you feel worse after 3 days.
Contraindications When Buscopan Compositum should not be used
Do not take Buscopan compositum
- If you are allergic to hyoscine N-butylbromide or paracetamol or NSAIDs (Non Steroidal Anti-Inflammatory Drugs, medicines for pain and inflammation) or any of the other ingredients of this medicine (listed in section 6)
- if you suffer from acute angle glaucoma (severe form of glaucoma, which is a disease of the eye caused by an increase in the pressure of the fluid contained within the eye)
- if you suffer from prostatic hypertrophy (enlarged prostate)
- if you suffer from urinary retention (inability of the urinary bladder to empty completely)
- if you suffer from pyloric stenosis (narrowing of the pylorus, the terminal portion of the stomach) or stenosis of other parts of the gastrointestinal tract (narrowing of other areas of the stomach and intestines)
- if you suffer from bowel disease associated with bowel movement disorders such as paralytic ileus (intestinal obstruction), ulcerative colitis (chronic inflammatory bowel disease) and megacolon (dilation of the colon)
- if you suffer from reflux esophagitis (a disorder caused by frequent regurgitation of stomach contents into the gullet, the tube that carries food to the stomach)
- if you are elderly or if your physical condition is weak and you suffer from bowel atony (lack of bowel movements causing intestinal obstruction)
- if you suffer from myasthenia gravis (muscle weakness)
- in case of less than 10 years of age
- if your body does not produce an enzyme called glucose-6-phosphate dehydrogenase (a disease known as favism, which destroys certain blood cells, the red blood cells)
- if you have severe haemolytic anemia (disease due to the breakdown of red blood cells)
- if you suffer from severe hepatocellular insufficiency (abnormal liver function associated with the destruction of liver cells)
- in case of rare hereditary conditions which may be incompatible with an excipient of the product (see "Warnings and precautions").
Precautions for use What you need to know before taking Buscopan Compositum
Talk to your doctor or pharmacist before taking this medicine.
Contact your doctor immediately if you experience severe pain in the belly area that does not go away or gets worse or is accompanied by symptoms such as fever, nausea, vomiting, changes in bowel movements, swelling of the belly, decrease in blood pressure, fainting or blood in the stool.
To avoid taking an overdose of paracetamol, one of the active substances of Buscopan compositum, you must ensure that you do not take other medicines containing paracetamol at the same time, as if paracetamol is taken in high doses, serious side effects may occur, see section " If you take more Buscopan compositum than you should ".
Do not exceed the recommended doses (see section 3 "How to take Buscopan compositum"), as liver damage may occur (see section "If you take more Buscopan compositum than you should").
Buscopan compositum should be used with caution:
- if your body produces too little glucose-6-phosphate dehydrogenase (a disease known as favism, which destroys red blood cells)
- if you have liver disease such as hepatitis (inflammation of the liver), Gilbert's syndrome (a disease characterized by an "excessive increase in bilirubin in the blood, mild or moderate hepatocellular insufficiency (alteration of liver function associated with the destruction of liver cells )
- if you regularly use large quantities of alcohol
- if your kidneys are not working well
- if you are prone to narrow-angle glaucoma (severe form of glaucoma, which is a disease of the eye caused by an increase in the pressure of the fluid contained within the eye)
- if you are prone to intestinal or urinary tract obstructions
- if you are predisposed to tachycardia (increased heart rate)
- if you have high blood pressure
- if you suffer from congestive heart failure (heart disease)
- if you are prone to hyperthyroidism (exaggerated functional activity of the thyroid gland, with the presence of a high amount of thyroid hormones in the circulation)
- if you suffer from chronic obstructive diseases of the airways.
Buscopan compositum should only be used under medical supervision:
- if you have kidney failure (severe kidney disease)
- if you suffer from liver failure (severe liver disease)
In these conditions, if necessary, your doctor will decrease your dose or extend the interval between individual administrations.
If you need to take Buscopan compositum for a long time, you will also need to have the necessary tests to check your blood values and the function of your kidneys and liver, as determined by your doctor.
If you often use pain relieving medicines (analgesics), especially in high doses, you may get a headache. In this case, you do not have to increase the dose of the analgesic to cure it.
If after taking Buscopan compositum you experience allergic reactions (seen very rarely, see section "Possible side effects"), stop taking Buscopan compositum at the first signs of an allergic reaction and contact your doctor immediately.
Do not take Buscopan compositum for more than 3 days unless otherwise prescribed by your doctor. If the pain does not go away or gets worse, if you get new symptoms, or if you have redness or swelling, see your doctor as these could be symptoms of a serious condition. Also, consult your doctor before taking any other medicines. See also section "Other medicines and Buscopan compositum".
Children
Buscopan compositum should not be used in children below 10 years of age.
Interactions Which drugs or foods may modify the effect of Buscopan Compositum
Other medicines and Buscopan Compositum
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. In particular, use this medicine with caution and only under strict medical supervision in the following situations:
- if you regularly take medicines or substances that work the liver out of work, for example: rifampicin (an antibiotic), cimetidine (a medicine used in stomach ulcers), antiepileptics (medicines used to treat epilepsy such as glutethimide , phenobarbital, carbamazepine) This also applies to all those substances that can be harmful to the liver
- if you are taking chloramphenicol (to treat infections), as Buscopan compositum may delay the elimination of chloramphenicol from your body by creating a harmful effect on your body
- if you have to take Buscopan compositum for a long time and are taking anticoagulants at the same time (medicines to thin the blood, for example warfarin and coumarin derivatives)
- if you are taking zidovudine (AZT or retrovir, a medicine to treat HIV) because you may have a reduction in the number of some blood cells, white blood cells
- if you are taking probenecid (medicine used to treat for example gout) because a reduction in the dose of paracetamol may be needed
- if you are taking cholestyramine (to lower cholesterol) as it decreases the absorption of paracetamol
- if you are taking antidepressant medicines (especially tri- and tetracyclic antidepressants), antihistamines (medicines used for allergies or for stomach acid), antipsychotics (medicines used for mental disorders), quinidine (heart medicine), amantadine ( medicine for central nervous system diseases resulting in loss of movement control, such as Parkinson's disease), disopyramide (heart medicine) and other medicines such as tiotropium, ipratropium (used for respiratory diseases), similar substances all "atropine (substance that acts on the nervous system), because their effect can be increased by Buscopan compositum
- if you are taking medicines for vomiting and nausea, such as metoclopramide, as both their effect and that of Buscopan compositum may decrease
- if you are taking medicines called beta-adrenergics, because Buscopan compositum can increase the tachycardia (increase in the number of heart beats) induced by these medicines.
Medicines that slow down stomach emptying (such as propantheline, a medicine for stomach ulcer) can reduce the rate of absorption of paracetamol, delaying its effect; on the other hand, medicines that increase the rate of stomach emptying (such as metoclopramide, a medicine against vomiting and nausea) lead to an increase in the rate of absorption of paracetamol.
Laboratory tests
Paracetamol, one of the active substances in Buscopan compositum, can alter the results of some laboratory tests, such as the determination of uric acid (amount of uric acid in the blood) and blood glucose (blood sugar). blood, tell your doctor or laboratory staff that you are taking Buscopan compositum.
Buscopan compositum with alcohol
If you regularly consume large amounts of alcohol, you should use Buscopan compositum with extreme caution, otherwise your liver could be damaged.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.
Pregnancy
There are no adequate data on the use of Buscopan compositum during pregnancy. The available data from the use of hyoscine bromide and paracetamol alone indicated insufficient evidence of undesirable effects during pregnancy in women.
During pregnancy, the data obtained in the case of excessive doses of paracetamol did not show an increased risk of malformations or harmful effects.
During pregnancy, paracetamol should not be taken for prolonged periods, in high doses, or in combination with other medicines as the safety of using the medicine in these cases has not been established. Therefore, Buscopan compositum is not recommended during pregnancy. and can only be taken after consulting your doctor.
Feeding time
The safety of drug use during breastfeeding has not yet been established. Paracetamol passes into breast milk. However, at normal doses it is not expected to cause unwanted effects in the newborn. The decision to continue or discontinue breastfeeding or to continue or discontinue therapy with Buscopan compositum should only be made after consultation with your physician.
Fertility
No studies on the effects on human fertility have been conducted.
This medicinal product contains 4.32 mg of sodium per tablet. To be taken into consideration in patients on a controlled sodium diet
Driving and using machines
No studies on the ability to drive and use machines have been performed. However, visual disturbances and drowsiness may occur, take this into consideration if you drive or drive vehicles or perform jobs that require attention and vigilance.
Dose, Method and Time of Administration How to use Buscopan Compositum: Posology
Always take this medicine exactly as described in this leaflet or as directed by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
The following dosage is recommended for adults and children aged 10 years and over, unless otherwise prescribed:
The recommended dose is 1-2 tablets 3 times a day. Do not exceed 6 tablets per day. The tablets should not be chewed, but swallowed whole with a sufficient amount of water.
Duration of treatment
Do not take Buscopan compositum for more than 3 days unless otherwise prescribed by your doctor.
Talk to your doctor if you are taking other medicines containing paracetamol at the same time, as your dose may need to be adjusted (see section "Warnings and precautions").
Use in children
Buscopan compositum should not be used in children below 10 years of age.
Overdose What to do if you have taken an overdose of Buscopan Compositum
If you take more Buscopan compositum than you should
If you take an overdose of Buscopan compositum tell your doctor immediately or go to the nearest hospital. Elderly people, young children, those suffering from liver problems, those who regularly consume alcohol or those who are undernourished are more at risk of intoxication, even with a fatal outcome, when taking an excessive dose of paracetamol.
Symptoms in case of overdose
Hyoscine N-Butylbromide
Effects such as urinary retention (difficulty of the urinary bladder to empty completely), dry mouth, redness of the skin, tachycardia, decreased motility of the stomach and intestines and transient visual disturbances have been observed in case of overdose.
Paracetamol
Symptoms usually occur during the first 24 hours and include paleness, nausea, vomiting, anorexia (lack of appetite) and pain in the belly area (abdominal pain). You may experience temporary improvement in these symptoms, but mild abdominal pain may persist, which may still be a sign of liver damage. There may be an increase in transaminases in the blood (substances found in the liver), jaundice (manifested by yellowing of the skin or whites of the eyes), blood clotting disorders (disorders that change the fluidity of the blood), hypoglycaemia (low amounts blood sugar) and transition to liver coma (severe liver damage associated with brain disorders, i.e. affecting the brain).
If you take an overdose of acetaminophen, there is a risk of severe liver damage, which can lead to coma and death. Liver damage should be assessed by your doctor who will order the necessary tests to evaluate the function of your liver.
If you take too much paracetamol, it can also develop kidney damage, heart and pancreas problems (gland involved in the digestion and transformation of some nutrients).
Chronic intoxication
In cases of chronic intoxication, haemolytic anemia (disease due to the destruction of some blood cells, red blood cells), cyanosis (a state in which the skin turns blue), weakness, dizziness, paraesthesia (a condition that occurs mostly with tingling legs or arms), tremors, insomnia, headache (headache), memory loss, central nervous system disorders, delirium (confused state) and convulsions (involuntary twitching of one or more muscles).
If you have taken too much of this medicine contact your doctor immediately or go to the nearest hospital. Your doctor will prescribe the appropriate therapy.
If you forget to take Buscopan compositum
Do not take a double dose to make up for a forgotten dose.
If you stop taking Buscopan compositum
If you suddenly stop taking pain relieving medicines (analgesics), after using them for a long time in high doses, you may experience symptoms such as headache, tiredness, nervousness, which usually pass within a few days. Before starting to take painkillers again, consult your doctor and wait for these symptoms to pass. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Buscopan Compositum
Like all medicines, this medicine can cause side effects, although not everybody gets them. The possible side effects are listed below according to the following frequency:
Uncommon (may affect up to 1 in 100 patients)
- skin reactions (redness of the skin)
- abnormal sweating
- itch
- nausea
- dry mouth
Rare (may affect up to 1 in 1,000 patients)
- shock (decrease in blood pressure with severe reduction in heart function)
- tachycardia (increased heart rate)
- erythema (skin irritation)
Very rare (may affect up to 1 in 10,000 patients)
- Stevens-Johnson syndrome and epidermal necrolysis (severe skin diseases characterized by erythema, bullous lesions with areas of peeling of the skin)
- generalized exentematic pustulosis (characterized by the appearance of numerous small pustules, burning sensation, widespread itching and high fever)
Frequency not known (frequency cannot be estimated from the available data)
- pancytopenia (reduction in the number of all types of cells in the blood)
- agranulocytosis (reduction in the number of blood granulocytes, a type of white blood cell)
- thrombocytopenia (reduction in the number of platelets in the blood)
- leukopenia (reduction in the number of white blood cells)
- anemia (reduction of hemoglobin in the blood, a substance that carries oxygen in the blood)
- increase in blood transaminases (substances in the liver which increase may indicate liver damage)
- allergic reactions, including severe ones (anaphylactic shock, anaphylactic reactions, skin reaction from medicine, hypersensitivity), edema of the larynx (swelling of the larynx, the throat organ that produces the voice), angioedema (allergic reaction with symptoms such as swelling of the face, tongue or throat, difficulty swallowing, itching, difficulty breathing)
- skin reactions of various types and severities including cases of erythema multiforme (a condition characterized by the appearance of red spots on the skin with a "bull's eye" appearance associated with itching)
- inflammation of the skin (hives, rash, rash)
- difficulty in breathing
- spasms of the bronchial muscles (especially in asthma or allergy sufferers)
- urinary retention (inability of the urinary bladder to empty completely)
- kidney disorders: acute renal failure (rapid reduction in kidney function), interstitial nephritis (inflammation of the kidneys), haematuria (presence of blood in the urine), anuria (cessation or reduction of urine production)
- difficulty urinating
- sweating
- mydriasis (pupil dilation)
- visual disturbances (disturbances of accommodation ie difficulty in focusing images, increase in ocular tone ie increase in the pressure of the internal fluid of the eye)
- constipation
- reactions to the stomach and intestines
- liver disorders (such as hepatitis or liver function disorders)
- drowsiness
- dizziness
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety. of this medicine.
Expiry and Retention
Store below 25 ° C.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Buscopan compositum contains
- The active ingredients are: hyoscine N-butylbromide and paracetamol. Each tablet contains 10 mg of hyoscine N-butylbromide and 500 mg of paracetamol.
- The other ingredients are: tablet core: microcrystalline cellulose, carmellose sodium, corn starch, ethylcellulose, colloidal silica, magnesium stearate; tablet coating: hypromellose, polyacrylates, titanium dioxide, macrogol 6000, talc, silicone-antifoam agent.
Description of the appearance of Buscopan compositum and contents of the pack
Buscopan compositum 10 mg + 500 mg coated tablets available in a pack of 30 tablets contained in 3 blisters of 10 tablets each.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
BUSCOPAN COMPOSITUM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Buscopan compositum 10 mg + 500 mg coated tablets
One coated tablet contains:
Active ingredients: hyoscine N-butylbromide 10 mg, paracetamol 500 mg.
Buscopan compositum 10 mg + 800 mg suppositories
One suppository contains:
Active ingredients: hyoscine N-butylbromide 10 mg, paracetamol 800 mg.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Coated tablets.
Suppositories.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Paroxysmal pains in affections of the gastrointestinal tract, spastic pains, dyskinesias of the urinary and biliary tract, dysmenorrhea.
04.2 Posology and method of administration
The following dosage is recommended for adults, unless otherwise prescribed:
Coated tablets
1-2 tablets 3 times a day. Do not exceed 6 tablets per day. The tablets should not be chewed, but swallowed whole with a sufficient amount of water.
Suppositories
1 suppository 3-4 times a day.
Do not exceed 4 suppositories per day.
Duration of treatment
Buscopan compositum should not be taken for more than three days unless prescribed by a doctor (see section 4.4).
Pediatric population
Buscopan compositum is not recommended for use in children below 10 years of age.
Co-administration of other paracetamol-containing drugs may require dose adjustment, see section 4.4.
04.3 Contraindications
Buscopan compositum should not be used in case of
- Hypersensitivity to the active substances, to non-steroidal anti-inflammatory drugs or to any of the excipients.
- Acute angle glaucoma.
- Prostatic hypertrophy or other causes of urinary retention.
- Pyloric stenosis and other conditions stenosing the gastrointestinal canal, paralytic ileus, ulcerative colitis, megacolon.
- Reflux esophagitis.
- Intestinal atony of the elderly and debilitated subjects.
- Myasthenia gravis.
- Pediatric age.
- Paracetamol-based products are contraindicated in patients with manifest insufficiency of glucose-6-phosphate dehydrogenase and in those suffering from severe haemolytic anemia.
- Severe hepatocellular insufficiency (Child - Pugh C).
The use of Buscopan compositum is contraindicated in case of rare hereditary conditions which may be incompatible with an excipient of the product (see section 4.4).
Buscopan compositum 10 mg + 800 mg suppositories should not be used in patients with a history of soy or peanut allergy.
04.4 Special warnings and appropriate precautions for use
Buscopan compositum should not be taken for more than 3 days unless directed by your doctor. Instruct the patient to seek medical attention if pain persists or worsens, if new symptoms occur, or if redness or swelling develops as these could be symptoms of a serious condition.
If severe abdominal pain of unknown origin persists, worsens or is accompanied by symptoms such as fever, nausea, vomiting, abnormal bowel movements, distended abdomen, drop in blood pressure, fainting or blood in stool, seek immediate medical attention.
To prevent overdose, it must be ensured that any other drugs taken at the same time do not contain paracetamol, one of the active ingredients of Buscopan compositum.
Liver damage may occur if the recommended dosage for paracetamol is exceeded (see section 4.9).
Buscopan compositum should be used with caution in case of:
• glucose-6-phosphate dehydrogenase insufficiency
• liver dysfunction (eg due to chronic alcohol abuse, hepatitis)
• impaired renal function
• Gilbert's syndrome
• hepatocellular insufficiency (Child - Pugh A / B)
Administer with caution in subjects with renal or hepatic insufficiency.
In such conditions Buscopan compositum should only be administered under medical supervision, if necessary, by reducing the dose or by extending the interval between individual administrations.
Blood counts and renal and hepatic function should be monitored after prolonged use.
The extensive use of analgesics, especially at high doses, can induce headache which should not be treated with increased doses of the drug.
Severe acute hypersensitivity reactions (e.g. anaphylactic shock) are observed very rarely. Treatment should be discontinued at the first signs of a hypersensitivity reaction following administration of Buscopan compositum.
Abrupt discontinuation of analgesics after prolonged use in high doses may cause withdrawal symptoms (e.g. headache, fatigue, nervousness), which usually resolve within a few days. Resumption of analgesics should be subject to medical advice and remission of withdrawal symptoms.
Due to the potential risk of anticholinergic complications, it should be used with caution in patients predisposed to narrow-angle glaucoma, in patients prone to intestinal or urinary tract obstructions and in those prone to tachyarrhythmia with disorders of the autonomic central nervous system, in tachyarrhythmias, in arterial hypertension, congestive heart failure and hyperthyroidism. All antimuscarinics reduce the volume of bronchial secretions; therefore they must be used with caution in subjects with chronic obstructive inflammatory diseases of the respiratory system.
During treatment with paracetamol before taking any other drug, check that it does not contain the same active ingredient, as if paracetamol is taken in high doses, serious adverse reactions may occur, see section 4.2.
Instruct the patient to contact the physician before associating any other medication. See also section 4.5.
Buscopan compositum 10 mg + 500 mg tablets contain 4.32 mg of sodium per tablet. To be taken into consideration in patients on a controlled sodium diet.
04.5 Interactions with other medicinal products and other forms of interaction
Use with extreme caution and under strict control during chronic treatment with drugs that can determine the induction of hepatic monooxygenases or in case of exposure to substances that can have this effect (for example rifampicin, cimetidine, antiepileptics such as glutethimide, phenobarbital, carbamazepine) The same situation occurs with potentially hepatotoxic substances and with alcohol abuse.
Concomitant administration of chloramphenicol can induce a prolongation of the half-life of chloramphenicol, with the risk of elevating its toxicity.
Since the clinical relevance of the interactions of paracetamol with warfarin and coumarin derivatives has not yet been established, long-term use of Buscopan compositum in patients on oral anticoagulant therapy should only take place under medical supervision.
Concomitant use of paracetamol and zidovudine (AZT or retrovir) increases the tendency to shrink leukocytes (neutropenia). Therefore Buscopan compositum should only be taken together with zidovudine under medical supervision.
Intake of probenecid inhibits the binding of paracetamol to glucuronic acid, thereby reducing the clearance of paracetamol by approximately a factor of 2. The dose of paracetamol should therefore be reduced during co-administration with probenecid.
Cholestyramine reduces the absorption of paracetamol.
The administration of paracetamol can interfere with the determination of uric acid (by the method of phosphotungstic acid) and with that of blood glucose (by the method of glucose-oxidase-peroxidase).
The anticholinergic effect of medicinal products such as tri- and tetracyclic antidepressants, antihistamines, antipsychotics, quinidine, amantadine, disopyramide and other anticholinergics (eg tiotropium, ipratropium, atropine-like substances) can be enhanced by Buscopan compositum.
Concomitant treatment with dopamine antagonists, such as metoclopramide, may result in a reduced effect of both drugs on the gastrointestinal tract.
Β-adrenergic drug-induced tachycardia can be potentiated by Buscopan compositum.
The tachycardic effects of beta-adrenergic agents can be intensified by Buscopan compositum.
Additionally for oral use:
Drugs that slow down gastric emptying (eg. Propantheline) can reduce the absorption rate of paracetamol, delaying its therapeutic effect; on the contrary, drugs that increase gastric emptying speed (eg metoclopramide) lead to an increase in the rate of gastric emptying. absorption of paracetamol.
04.6 Pregnancy and lactation
Pregnancy
There are no adequate data on the use of Buscopan compositum during pregnancy.
Long experience with the two substances alone has indicated "insufficient evidence of adverse effects during pregnancy in women.
After the use of hyoscine N-butylbromide, pre-clinical studies in rats and rabbits showed neither embryotoxic nor teratogenic effects.
Potential data on paracetamol overdose during pregnancy did not show an increased risk of malformations. Reproduction studies to investigate oral use have shown no signs suggesting malformations of fetotoxicity. Under normal conditions of use, paracetamol can be taken during pregnancy after careful consideration of the risk-benefit ratio.
During pregnancy, paracetamol should not be taken for prolonged periods, in high doses, or in combination with other medicines as safety has not been confirmed in such cases. Therefore, Buscopan compositum is not recommended during pregnancy.
Feeding time
The safety of hyoscine N-butylbromide during breastfeeding has not yet been established.
Paracetamol is excreted in breast milk. However, it is expected that at therapeutic doses it will not cause undesirable effects in the newborn.
The decision to continue or discontinue breastfeeding or to continue or discontinue Buscopan compositum therapy must be made considering the benefits of breastfeeding for the baby and the benefits of Buscopan compositum therapy for the mother.
Fertility
No studies on the effects on fertility in humans have been conducted (see section 5.3).
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed.
However, anticholinergics can induce disturbances in visual accommodation and drowsiness, this must be taken into account by those who drive vehicles or machinery or carry out work for which integrity of the degree of vigilance is required.
04.8 Undesirable effects
Adverse reactions are listed below by system organ class and frequency, according to the following categories:
Very common: ≥ 1/10
Common: ≥ 1/100
Uncommon: ≥ 1 / 1,000
Rare: ≥ 1 / 10,000
Very rare:
Not known: frequency cannot be estimated from the available data.
Disorders of the blood and lymphatic system:
Not known: pancytopenia, agranulocytosis, thrombocytopenia, leukopenia.
Immune system disorders, skin and subcutaneous tissue disorders:
Uncommon: skin reactions, abnormal sweating, pruritus, nausea.
Rare: erythema, decrease in blood pressure including shock.
Not known: anaphylactic shock, anaphylactic reactions, skin drug reaction, dyspnoea, hypersensitivity, angioedema, urticaria, skin rash, exanthema.
Very rare cases of severe skin reactions (such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and generalized exanthematous pustulosis (AGEP)) have been reported with the use of paracetamol.
Cardiac pathologies:
Rare: tachycardia.
Respiratory, thoracic and mediastinal disorders:
Not known: bronchial muscle spasms (especially in patients with a history of bronchial asthma or allergy).
Gastrointestinal disorders:
Uncommon: dry mouth.
Hepatobiliary disorders:
Not known: increased transaminases.
Renal and urinary disorders:
Not known: urinary retention.
Cases of erythema multiforme have been reported with the use of paracetamol.
Hypersensitivity reactions such as angioedema, larynx edema have been reported. In addition, the following undesirable effects have been reported: anemia, liver function abnormalities and hepatitis, kidney changes (acute renal failure, interstitial nephritis, haematuria, anuria), gastrointestinal reactions and dizziness.
Somnolence, mydriasis, accommodation disturbances, increased eye tone, constipation and difficulty in urination have also been reported.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Due to paracetamol overdose, elderly people, young children, patients with liver disorders, chronic alcohol consumption or chronic malnutrition, such as patients treated with enzyme-induced medicinal products, are at increased risk of intoxication, even with a fatal outcome.
Symptoms
Hyoscine N-Butylbromide
Anticholinergic effects have been observed in case of overdose.
Paracetamol
In cases of chronic intoxication, hemolytic anemia, cyanosis, weakness, dizziness, paraesthesia, tremors, insomnia, headache, memory loss, irritation of the central nervous system, delirium and convulsions may occur.
Symptoms usually occur during the first 24 hours and include paleness, nausea, vomiting, anorexia and abdominal pain. Patients may then experience temporary subjective improvement but mild abdominal pain possibly indicative of liver damage may persist; there may be a considerable increase in transaminases, jaundice, bleeding disorders, hypoglycemia and transition to hepatic coma.
A single dose of paracetamol of approximately 6 g or more in adults or 140 mg / kg in children can cause hepatocellular necrosis. This can lead to irreversible complete necrosis and subsequently hepatocellular failure, metabolic acidosis and encephalopathy, which in turn can progress to coma and death. Concurrent elevations of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin and an increase in prothrombin time, which occurs 12 to 48 hours after ingestion, have been observed. Clinical symptoms of liver injury are usually evident after 2 days and they reach a maximum after 4 - 6 days.
Acute renal failure with acute tubular necrosis can develop even in the absence of severe liver damage. Other non-hepatic symptoms have also been reported such as myocardial abnormalities and pancreatitis to be verified after an overdose with paracetamol.
Therapy
Hyoscine N-Butylbromide
If required, parasympathomimetic medicinal products should be administered. In cases of glaucoma an ophthalmological examination must be carried out urgently. Cardiovascular complications must be treated according to the usual therapeutic principles. In case of respiratory paralysis: intubation and artificial respiration must be considered. Catheterization may be required for urinary retention. In addition, appropriate supportive measures should be used as needed.
Paracetamol
Where paracetamol intoxication is suspected, intravenous administration of SH group donors such as N-acetylcysteine within the first 10 hours of ingestion is indicated. Although N-acetylcysteine is most effective if administered within this period, it may still offer some degrees of protection if given 48 hours after ingestion, in which case it should be taken longer. The plasma concentration of paracetamol can be lowered by dialysis. Quantitative analyzes of the plasma concentration of paracetamol are recommended.
Further measures will depend on the severity, nature and course of the clinical symptoms of acetaminophen intoxication and must follow standard intensive care protocols.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antispasmodics in combination with analgesics.
ATC code: A03DB04.
The hyoscine N-butylbromide contained in Buscopan compositum exerts a spasmolytic action on the smooth muscles of the gastrointestinal, biliary and genitourinary tracts. As a derivative of quaternary ammonium, hyoscine N-butylbromide does not penetrate the central nervous system. Therefore, anticholinergic undesirable effects in the central nervous system do not occur. The peripheral anticholinergic action results from ganglionic blockade within the visceral wall as well as from an antimuscarinic activity.
The paracetamol contained in Buscopan compositum exerts analgesic and antipyretic actions, together with a very weak anti-inflammatory effect. Its mechanism of action is not fully known. It strongly inhibits the synthesis of central prostaglandins but only weakly inhibits the synthesis of peripheral prostaglandins. It also inhibits the effect of endogenous pyrogenesis on the temperature regulation center in the hypothalamus.
05.2 "Pharmacokinetic properties
Hyoscine N-Butylbromide
Absorption
As a derivative of quaternary ammonium, hyoscine N-butylbromide is highly polar and therefore only partially absorbed following oral (8%) or rectal (3%) administration. Following oral administration of single doses of hyoscine N-butylbromide in the range of 20 to 400 mg, mean peak plasma concentrations were reported after approximately 2 hours and ranged from 0.11 ng / ml to 2, 04 ng / mL. In the same dose range, mean AUC0-tz values ranged from 0.37 to 10.7 ng h / mL. The absolute median bioavailability of different formulations, i.e. film-coated tablets, suppositories and oral solution, containing each 100 mg of hyoscine N-butylbromide were found to be less than 1%.
Distribution
After intravenous administration, the substance is rapidly cleared from the plasma during the first 10 minutes with a half-life of 2 - 3 minutes. The volume of distribution (Vss) is 128 L. Following oral and intravenous administration, N-butylbromide hyoscine is concentrated in the tissues of the gastrointestinal tract, liver and kidneys. Despite the short measurability of extremely low blood levels, hyoscine N-butylbromide remains available at the site of action due to its high affinity for tissues. Autoradiography confirms that hyoscine N-butylbromide does not cross the barrier. hematoencephalic. Hyoscine N-butylbromide is low in plasma protein binding.
Metabolism and elimination
The mean total clearance after intravenous administration is approximately 1.2 L / min, of which approximately half is performed in the kidney. The final elimination half-life is approximately 5 hours.
After oral administration of single doses in the range of 100 to 400 mg, terminal elimination half-lives were between 6.2 and 10.6 hours. The major metabolic pathway is ester-binding hydrolysis. Orally administered hyoscine N-butylbromide is excreted in faeces and urine. Studies in humans show that 2 to 5% of radioactive doses are eliminated by the kidney after oral administration and 0.7% to " 1.6% after rectal administration. Approximately 90% of the recovered radioactivity can be recovered in faeces after oral administration. Urinary excretion of hyoscine N-butylbromide is less than 0.1% of the dose. Mean apparent clearances after oral doses ranging from 100 to 400 mg range from 881 to 1,420 l / min, while the corresponding volumes of distribution for the same range range from 6.13 to 11.3 x 105l, possibly due to very low systemic availability.
Renally excreted metabolites bind poorly to muscarinic receptors and therefore are not thought to contribute to the hyoscine N-butylbromide effect.
Paracetamol
Absorption and distribution
Following oral administration, paracetamol is rapidly and almost completely absorbed from the small intestine with peak plasma concentrations occurring approximately 0.5 to 2 hours after ingestion. After rectal administration, the absorption of paracetamol is less and slower than with oral administration with an absolute bioavailability of approximately 30 to 40% and peak plasma concentrations at 1.5 - 3 hours.
The drug is rapidly and evenly distributed in the tissues and crosses the blood brain barrier. Absolute bioavailability after oral administration varies between 65% and 89% indicating a first pass effect of approximately 20 - 40%. Fasting accelerates absorption but does not affect bioavailability. Plasma protein binding is low (approximately 5 to 20%) at therapeutic doses.
Metabolism
Paracetamol is extensively metabolised in the liver mainly to inactive conjugates of glucuronic acid (about 60%) and sulfuric acid (about 35%). Above therapeutic doses, the second route rapidly becomes saturated. A small amount is metabolised by the cytochrome P450 isoenzyme (mainly CYP2E1), which leads to the formation of a toxic metabolite, N-acetyl-p-benzoquinoneimine (NAPQI), which is usually rapidly detoxified from glutathione and excreted as conjugates of the mercaptopurine and cysteine. Following high overdose, however, NAPQI levels increased.
Elimination
The glucuronide and sulfate conjugates are completely excreted via the urine within 24 hours. Less than 5% of the dose is excreted as an unchanged parent compound. Total clearance is approximately 350 ml / min.
The plasma half-life is 1.5 - 3 hours at therapeutic doses. In young children the half-life is prolonged and sulphate conjugation is the dominant metabolic pathway. The plasma half-life of paracetamol is also prolonged in the case of chronic liver disease and in patients with severe renal impairment.
Bioavailability of a combination of hyoscine N-butylbromide and paracetamol
A study carried out in healthy patients to evaluate the bioavailability of hyoscine N-butylbromide and paracetamol in three different pharmaceutical forms of Buscopan compositum (tablets, suppositories, oral solution) showed that the bioavailability of the two associated substances was comparable with that obtained. in previous studies on the two individual components There was no significant effect on bioavailability due to combined administration.
05.3 Preclinical safety data
The acute oral toxicity of the paracetamol / hyoscine N-butylbromide combination (in the ratio 50/1) was the following: the LD50 in mice was 980 mg / kg, in rats it was about 3,000 mg / kg. Signs of toxicity were apathy, reduced motility, bristling coat, and weight loss. The animals died between 1.25 and 48 hours after administration. There was no difference in product sensitivity between the genres.
Acute paracetamol intoxication has been reported in humans. The lethal dose of paracetamol reported in humans is approximately 10 g (hepatotoxicity) (for more details see section 4.9).
The repeat-dose toxicity of the paracetamol / hyoscine N-butylbromide combination in the 50/1 ratio was investigated in a 13-week study in rats. At doses> 250/5 mg / kg / day of the combination, adverse effects included reduced weight gain, anemia, polydipsia, an increase in SGPT, SGOT and SAP, testicular atrophy with impaired spermiogenesis. All of these findings were reversible or showed a clear trend towards reversibility during the five-week recovery period.
In both single-dose and 13-week studies, the signs of toxicity and the toxic dose range were related to paracetamol, the active substance present in greater quantities in Buscopan compositum.
No enhancement of toxicity or new toxic effects of hyoscine N-butylbromide or paracetamol was observed in the combination.
Reproduction, mutagenicity and carcinogenicity studies have not been conducted with the combination.
However, studies conducted with the individual active substances may be a source of additional data for the evaluation of the toxic potential of Buscopan compositum.
In reproduction studies carried out with hyoscine N-butylbromide administered orally to rats and rabbits, no teratogenic potential, nor impaired fertility and the ability to generate was shown.
Paracetamol crosses the placenta. It was not teratogenic in either animals or humans. There are no reports of paracetamol-induced deterioration of fertility and peri / postnatal development in either laboratory animals or humans.
Doses> 250/5 mg / kg / day of the paracetamol / N-butylbromide hyoscine combination administered for 13 weeks to rats produced testicular atrophy and inhibition of spermatogenesis; the importance of this finding for humans is unknown.
Hyoscine N-butylbromide did not reveal mutagenic or clastogenic potential in the Ames test, the mammalian V79 cell gene mutation test (HPRT test) and a chromosomal aberration test in human peripheral lymphocytes as in the micronucleus test in human peripheral lymphocytes. rats There are no carcinogenicity studies of hyoscine N-butylbromide; however, no tumorigenic potential was found in two studies in which it was administered orally at doses up to 1000 mg / kg for 26 weeks in rats.
Overall investigations did not indicate any evidence of clinically relevant genotoxic risk for paracetamol when used at therapeutic, i.e. non-toxic, dosages.
The results of the genotoxicity and carcinogenicity studies conducted in rats and mice were heterogeneous. Based on data from the NTP assay conducted in rats and mice, the International Agency for Research on Cancer (IARC) classified paracetamol as non-genotoxic and non-carcinogenic.
Hyoscine N-butylbromide suppositories were well tolerated locally after rectal administration.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Coated tablets:
Nucleus:
microcrystalline cellulose,
carmellose sodium,
cornstarch,
ethylcellulose,
colloidal silica,
magnesium stearate.
Coating:
hypromellose,
polyacrylates,
titanium dioxide,
macrogol 6000,
talc,
silicone-antifoam agent.
Suppositories:
glyceride esters of saturated fatty acids,
soy lecithin.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
Coated tablets: 5 years.
Suppositories: 5 years.
06.4 Special precautions for storage
Tablets: Store below 25 ° C.
Suppositories: store below 30 ° C.
06.5 Nature of the immediate packaging and contents of the package
Buscopan compositum 10 mg + 500 mg coated tablets:
Carton containing 3 blisters of ALU / PVC of 10 coated tablets.
Buscopan compositum 10 mg + 800 mg suppositories:
Box containing 6 suppositories in PE / Al strips.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
BOEHRINGER INGELHEIM ITALIA S.p.A.
Via Lorenzini, 8
20139 Milan
08.0 MARKETING AUTHORIZATION NUMBER
Buscopan compositum 10 mg + 500 mg coated tablets AIC n. 029454016
Buscopan compositum 10 mg + 800 mg suppositories AIC n. 029454028
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
12.10.1998 / 03.11.2008
10.0 DATE OF REVISION OF THE TEXT
8 May 2015
