Active ingredients: Paracetamol, Codeine
TACHIDOL 500 mg / 30 mg effervescent granules
TACHIDOL 500 mg / 30 mg effervescent tablets
TACHIDOL 500mg / 30mg film-coated tablets
Why is Tachidol used? What is it for?
The combination of paracetamol and codeine is indicated for the symptomatic treatment of moderate to severe pain unresponsive to treatment with non-opioid analgesics used alone.
Codeine can be used in children over 12 years of age, in the short-term treatment of acute moderate pain that is not relieved by other pain relievers such as acetaminophen or ibuprofen alone. This product contains codeine. Codeine belongs to a group of drugs called opioid analgesics that work to relieve pain. It can be used alone or in combination with other pain relievers such as acetaminophen.
Contraindications When Tachidol should not be used
Hypersensitivity to the active substances or to any of the excipients. Patients with severe haemolytic anemia. Severe hepatocellular insufficiency and active liver disease. Respiratory failure.
To relieve pain in children and adolescents (0-18 years of age) after removal of the tonsils or adenoids due to obstructive sleep apnea syndrome. If it is known that it rapidly metabolizes codeine into morphine.
If you are breast-feeding. Pregnancy (see "Special Warnings"). Tachidol granules and Tachidol effervescent tablets contain a source of phenylalanine. It can be harmful to those with phenylketonuria.
Precautions for use What you need to know before taking Tachidol
Codeine is transformed into morphine in the liver by an enzyme. Morphine is the substance that relieves pain. Some people have a variation of this enzyme and this can affect people in different ways. In some people, morphine isn't made or produced in very small quantities, and it won't be enough to relieve pain. Other people produce a high amount of morphine and are highly likely to have serious side effects. If you notice any of the following side effects, you should stop treatment and seek medical attention immediately: slow or shallow breathing, confusion, drowsiness, reduced pupils, nausea or vomiting, constipation, lack of appetite.
Administer with caution in subjects with renal (creatinine clearance ≤ 30 ml / min) or hepatic insufficiency. In such cases it is advisable to space the doses by at least 8 hours.
In case of allergic reactions the administration should be discontinued.
Use with caution in case of chronic alcoholism, excessive alcohol intake (3 or more alcoholic drinks per day), anorexia, bulimia or cachexia, chronic malnutrition (low reserves of hepatic glutathione), dehydration, hypovolemia.
Use with caution in subjects with glucose-6-phosphate dehydrogenase deficiency.
During treatment with paracetamol, before taking any other drug, check that it does not contain the same active ingredient, as serious adverse reactions can occur if paracetamol is taken in high doses.
Also, before combining any other drug, contact your doctor. See also "Interactions".
It is advisable, due to the presence of codeine, not to take alcoholic beverages; codeine can cause increased intracranial hypertension.
In patients who have had their gallbladder (gallbladder) removed, codeine may induce acute biliary or pancreatic abdominal pain, usually associated with abnormal laboratory tests, indicative of spasm of the sphincter of Oddi.
In the presence of cough that produces phlegm, codeine can prevent expectoration. Do not combine with other depressant drugs such as sedatives, tranquilizers and antihistamines.
Children and adolescents
Use in children and adolescents after surgery. Codeine should not be used to relieve pain in children and adolescents after removal of the tonsils or adenoids due to Obstructive Sleep Apnea Syndrome. Use in children with respiratory problems. Codeine is not recommended for children with respiratory problems, as the symptoms of morphine toxicity may be worse in these children.
Interactions Which drugs or foods can modify the effect of Tachidol
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those without a prescription. Paracetamol can increase the chance of side effects if given at the same time as other drugs.
Do not administer during chronic treatment with drugs that can determine the induction of hepatic monooxygenases, nor expose yourself to substances that can have the same effect. Doses should be reduced during therapy with oral anticoagulants.
Patients being treated with rifampicin, cimetidine or other antiepileptic drugs such as glutethimide, phenobarbital, carbamazepine should use paracetamol with extreme caution and only under strict medical supervision.
Patients being treated with phenytoin should avoid high and / or chronic doses of paracetamol.
The administration of paracetamol can interfere with the determination of uricaemia (by the phosphotungstic acid method) and with that of blood glucose (by the glucose-oxidase-peroxidase method).
The effects of opium alkaloids can be enhanced by other depressant drugs such as sedatives, tranquilizers, antihistamines.
TACHIDOL is contraindicated in combination with:
- Morphine agonists and antagonists (buprenorphine, nalbuphine, pentazocine) As a function of the reduced analgesic effect due to the competitive blocking of receptors, with the risk of onset of rejection syndrome.
- Alcohol: Alcohol increases the sedative effect of morphine analgesics. Reduced alertness can make it dangerous to drive and use machines.
- Naltrexone There is a risk of reduced analgesic effect. The dosage of morphine derivatives should be increased if necessary.
The use of TACHIDOL should be evaluated in association with:
- Other morphine agonist analgesics (alfentanil, dextromoramide, dextropropoxyphene, fentanyl, dihydrocodeine, hydromorphone, morphine, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol), morphine-like antitussive drugs, morphine dextrine-like drugs (suppressor metorphine), morphine dextrine suppressors cough (codeine, etymorphine), benzodiazepines, barbiturates, methadone Increased risk of respiratory depression which can be fatal in case of overdose.
- Other sedative drugs: morphine derivatives (analgesics, cough suppressants and replacement treatments), neuroleptics, barbiturates, benzodiazepines, anxiolytics other than benzodiazepines (meprobramate), hypnotics, sedative antidepressants (amitriptyline, doxepine, mirtazapine, mianserin), trimipramerine sedative H1 antihistamines, centrally acting antihypertensive drugs, baclofen and thalidomide. Increased central depressive action. The altered state of alertness can make it dangerous to drive or use machines
Warnings It is important to know that:
High or prolonged doses of the product can cause a high-risk liver disease and even serious changes in the kidney and blood (paracetamol) or cause addiction (codeine).
In the elderly, the prolonged use of opium alkaloids can aggravate a pre-existing pathology (cerebral, bladder, etc.).
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy: During pregnancy, the medicinal product should only be used after a careful risk / benefit assessment and under direct medical supervision. As the product crosses the placental barrier, it may induce depressant effects on the central nervous system of the fetus.
Breastfeeding: Do not take codeine while breastfeeding. Codeine and morphine pass into breast milk. The drug passes into breast milk and there have been rare cases of adverse reactions in infants.
Effects on ability to drive and use machines
The product may cause drowsiness and it is therefore advisable to refrain from driving vehicles or using machines.
Important information about some of the ingredients of Tachidol
Tachidol effervescent granules contains:
- maltitol: if you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicine;
- 12.3 mmol (282 mg) of sodium per sachet: to be taken into consideration in people with reduced kidney function or who follow a low sodium diet;
- aspartame, a source of phenylalanine, can be harmful to those with phenylketonuria (see "Contraindications").
Tachidol effervescent tablets contain:
- sorbitol: if you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicine;
- 15.2 mmol (349 mg) of sodium per effervescent tablet: to be taken into consideration in people with reduced kidney function or who follow a low sodium diet;
- aspartame, a source of phenylalanine, can be harmful to those suffering from phenylketonuria (see "Contraindications");
Tachidol film-coated tablets contain:
- lactose: patients with rare hereditary galactose disease, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Dosage and method of use How to use Tachidol: Dosage
The drug should not be taken for more than 3 days. If the pain does not improve after 3 days, speak to your doctor for advice.
Tachidol should not be taken by children under the age of 12 due to the risk of severe breathing problems.
Effervescent granules in sachets:
ADULTS: 1 - 2 sachets up to 3 times a day. Tachidol effervescent granules (sachets) should be dissolved in half a glass of water and taken at intervals of at least 4 hours.
Effervescent tablets:
ADULTS: 1 - 2 effervescent tablets as needed, up to 3 times a day.
Tachidol effervescent tablets should be taken at intervals of at least 4 hours. The effervescent tablets must be dissolved in a glass of water.
Film-coated tablets:
ADULTS: 1-2 tablets as needed, up to 3 times a day. Tachidol tablets should be taken at intervals of at least 4 hours.
Overdose What to do if you have taken too much Tachidol
There is a risk of intoxication, especially in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition and in patients receiving enzyme inducers. In these cases, overdose can be fatal.
Acute intoxication is manifested by nausea, vomiting, anorexia, pallor, abdominal pain, malaise, sweating (paracetamol), respiratory depression, cyanosis, somnolence, pruritus, ataxia, miosis, convulsions, urticaria (codeine), metabolic acidosis, increased transaminases , lactic dehydrogenase and bilirubin and decrease in the prothrombin value.
IN THE EVENT OF ACCIDENTAL SWALLOWING / TAKING AN EXCESSIVE DOSE OF TACHIDOL, NOTIFY YOUR DOCTOR IMMEDIATELY OR SEEK THE NEAREST HOSPITAL.
If you have any questions about the use of Tachidol, ask your doctor or pharmacist.
Side Effects What are the side effects of Tachidol
Like all medicines, Tachidol can cause side effects, although not everybody gets them.
Skin reactions of various types and severities have been reported with the use of paracetamol including cases of erythema multiforme, Stevens Johnson syndrome and epidermal necrolysis.
Hypersensitivity reactions such as angioedema, larynx edema, anaphylactic shock have been reported. In addition, the following undesirable effects have been reported: thrombocytopenia, leukopenia, anemia, agranulocytosis, liver function abnormalities and hepatitis, kidney disorders (acute renal failure, interstitial nephritis, haematuria, anuria), gastrointestinal reactions and dizziness.
In rare cases, somnolence and respiratory depression may occur. In case of overdose, paracetamol can cause hepatic cytolysis which can evolve towards massive and irreversible necrosis.
At therapeutic doses, codeine-related undesirable effects are comparable to those of other opioids, although they are rarer and more modest.
It is possible the occurrence of:
- constipation, nausea, vomiting - sedation, euphoria, dysphoria
- miosis, urinary retention
- hypersensitivity reactions (itching, hives and rash)
- drowsiness and dizziness
- bronchospasm, respiratory depression
- acute biliary or pancreatic abdominal pain syndrome, suggesting spasm of the sphincter of Oddi, which occurs particularly in patients who have had their gallbladder removed
At higher than therapeutic dosages there is a risk of addiction and withdrawal syndrome following a "sudden interruption of administration which can be observed in both patients and infants born to codeine-dependent mothers."
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
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. Undesirable effects can also be reported directly through 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 the safety of this medicine.
Expiry and Retention
Expiry: see the expiry date printed on the package.
Warning: do not use the medicine after the expiry date shown on the package.
The expiry date indicated refers to the product in intact packaging, correctly stored.
Effervescent granules in sachets: store below 25oC.
Effervescent tablets: Store in the original package to protect the medicine from moisture. Store at a temperature below 30oC. Use the product within 3 months of first opening the tube, excess product must be discarded.
Syrup: does not require any particular storage temperature. Film-coated tablets: do not require any special storage conditions; The half tablet can be stored for 24 hours in the original package to protect the medicine from light.
KEEP THE MEDICINAL PRODUCT OUT OF THE REACH AND SIGHT OF CHILDREN.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
COMPOSITION:
Tachidol 500 mg / 30 mg effervescent granules
Each sachet contains: active ingredients: paracetamol 500 mg and codeine phosphate 30 mg. Excipients: maltitol, mannitol, sodium bicarbonate, citric acid, lemon flavor, aspartame, povidone, docusate sodium.
Tachidol 500 mg / 30 mg effervescent tablets
Each effervescent tablet contains: active ingredients: paracetamol 500 mg and codeine phosphate 30 mg. Excipients: anhydrous citric acid, sodium bicarbonate, anhydrous sodium carbonate, sorbitol, aspartame, orange flavor, lemon flavor, docusate sodium, simethicone emulsion.
Tachidol 500 mg / 30 mg film-coated tablets
Each tablet contains: active ingredients: paracetamol 500 mg and codeine phosphate 30 mg. Excipients: croscarmellose sodium, stearic acid, povidone, precipitated silica, sodium lauryl sulfate, lactose monohydrate, hypromellose, titanium dioxide (E171), Macrogol 4000.
PHARMACEUTICAL FORM AND CONTENT
EFFERVESCENT GRANULATE FOR ORAL USE: pack of 10 bipartite sachets
EFFERVESCENT TABLETS: pack of two tubes, each of which contains 8 divisible effervescent tablets.
TABLETS COATED WITH FILM: packs of 10, 12, 16, 20 and 24 tablets in blister packs.
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
TACHIDOL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each sachet contains: paracetamol 500 mg and codeine phosphate 30 mg.
Each effervescent tablet contains: paracetamol 500 mg and codeine phosphate 30 mg.
Each tablet contains: paracetamol 500 mg and codeine phosphate 30 mg.
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Effervescent granules
White granulate.
Effervescent tablets
White to off-white, round tablet with dividing line on one side only.
The tablet can be divided into equal halves.
Film-coated tablets
White to off-white, elongated tablets with a dividing line on one side only.
The tablet can be divided into equal halves.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
The combination paracetamol and codeine is indicated for the symptomatic treatment of moderate to severe pain unresponsive to treatment with non-opioid analgesics used alone.
Codeine is indicated in patients over 12 years of age for the treatment of acute moderate pain that is not adequately controlled by other analgesics such as acetaminophen or ibuprofen (alone).
04.2 Posology and method of administration
The drug should not be taken for more than 3 days. If the pain does not improve after 3 days, speak to your doctor for advice.
Tachidol should not be taken by children under the age of 12 due to the risk of severe breathing problems.
Sachets
adults and children over 12 years: 1-2 sachets as needed, up to 3 times a day.
Tachidol effervescent granules should be dissolved in half a glass of water and taken at intervals of at least 4 hours.
Effervescent tablets
adults and children over 12 years: 1 - 2 effervescent tablets as needed, up to 3 times a day.
Tachidol effervescent tablets should be taken at intervals of at least 4 hours.
The effervescent tablets must be dissolved in a glass of water.
Film-coated tablets
adults and children over 12 years: 1-2 tablets as needed, up to 3 times a day.
Tachidol tablets should be taken at intervals of at least 4 hours.
Pediatric population
Children under the age of 12
Codeine should not be used in children below 12 years of age due to the risk of opioid toxicity due to the variable and unpredictable metabolism of codeine to morphine (see sections 4.3 and 4.4).
04.3 Contraindications
Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.
Patients with severe haemolytic anemia.
Severe hepatocellular insufficiency and active liver disease.
Respiratory failure.
Subjects with phenylketonuria (see section 4.4).
In all pediatric patients (0-18 years of age) undergoing tonsillectomy and / or adenoidectomy for obstructive sleep apnea syndrome due to an increased risk of developing serious and life-threatening adverse reactions (see paragraph 4.4).
Pregnancy (see section 4.6)
In women during breastfeeding (see section 4.6).
In patients known to be CYP2D6 ultra-rapid metabolisers.
04.4 Special warnings and appropriate precautions for use
High or prolonged doses of the product can cause a high risk liver disease and alterations, even serious ones, to the kidney and blood (paracetamol) or addiction (codeine).
In the elderly, the prolonged use of opium alkaloids can aggravate a pre-existing pathology (cerebral, bladder, etc.).
Administer with caution in subjects with renal (creatinine clearance ≤ 30ml / min) or hepatic insufficiency. In such cases it is advisable to space the doses by at least 8 hours.
Use with caution in case of chronic alcoholism, excessive alcohol intake (3 or more alcoholic drinks per day), anorexia, bulimia or cachexia, chronic malnutrition (low reserves of hepatic glutathione), dehydration, hypovolemia.
During treatment with paracetamol, before taking any other drug, check that it does not contain the same active ingredient, as serious adverse reactions can occur if paracetamol is taken in high doses.
In case of allergic reactions the administration should be discontinued. It is advisable, due to the presence of codeine, not to take alcoholic beverages; codeine can cause increased intracranial hypertension.
In patients who have had the gallbladder removed, codeine can induce acute biliary or pancreatic abdominal pain, usually associated with abnormal laboratory tests, indicative of sphincter of Oddi spasm.
In the presence of a cough that produces phlegm, codeine can prevent expectoration.
Use with caution in subjects with glucose-6-phosphate dehydrogenase deficiency.
Instruct the patient to contact the physician before combining Tachidol with any other drug (see also section 4.5.).
Tachidol effervescent granules contains:
• maltitol: patients with rare hereditary problems of fructose intolerance should not take this medicine;
• 12.3 mmol (282 mg) of sodium per sachet: to be taken into consideration in people with reduced kidney function or who follow a low sodium diet;
• aspartame, a source of phenylalanine. It can be harmful to those with phenylketonuria (see section 4.3).
Tachidol effervescent tablets contain:
• sorbitol, patients with rare hereditary problems of fructose intolerance should not take this medicine.
• 15.2 mmol (349 mg) of sodium per effervescent tablet: to be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
• aspartame, a source of phenylalanine. It can be harmful to those with phenylketonuria (see section 4.3).
Tachidol film-coated tablets contain:
• lactose: patients with rare hereditary galactose disease, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
Ultra-rapid metabolisers and morphine intoxication-CYP2D6 metabolism
Codeine is metabolised by the hepatic enzyme CYP2D6 to morphine, its active metabolite.
If a patient has a deficiency or is completely lacking in this enzyme, a sufficient analgesic effect will not be obtained. Estimates indicate that up to 7% of the Caucasian population may have this deficiency. However, if the patient is a large or ultrafast metaboliser there is an increased risk of developing side effects of opioid toxicity even at commonly prescribed doses.
These patients convert codeine to morphine rapidly resulting in an increase in the expected serum morphine levels.
General symptoms of opioid toxicity include confusion, sleepiness, shallow breathing, miotic pupil, nausea, vomiting, constipation, and lack of appetite. In severe cases this can include symptoms of respiratory and circulatory depression, which can be life-threatening and very rarely fatal.
Prevalence estimates of ultrafast metabolisers in different populations are summarized below:
Post-operative use in children
There have been reports in the literature where codeine, given to children after tonsillectomy and / or adenoidectomy for obstructive sleep apnea, has induced rare, but life-threatening, adverse events including death (see see also section 4.3). All children received doses of codeine that were within the appropriate dose range; however, there was evidence that these children were ultra-rapid or strong metabolisers in their ability to metabolize codeine to morphine.
Children with impaired respiratory function
Codeine is not recommended for use in children in whom respiratory function may be impaired, including neuromuscular disorders, severe heart or respiratory conditions, upper respiratory or lung infections, multiple trauma, or extensive surgical procedures. These factors can worsen. symptoms of morphine toxicity.
04.5 Interactions with other medicinal products and other forms of interaction
Paracetamol can increase the chance of side effects if given at the same time as other drugs.
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).
During therapy with oral anticoagulants it is advisable to reduce the doses.
Monooxygenase inducing drugs
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) .
Phenytoin
Concomitant administration of phenytoin may result in decreased efficacy of paracetamol and an increased risk of hepatotoxicity. Patients being treated with phenytoin should avoid high and / or chronic doses of paracetamol. Patients should be monitored for evidence of hepatotoxicity.
Probenecid
Probenecid causes an at least two-fold reduction in paracetamol clearance through inhibition of its conjugation with glucuronic acid. A dose reduction of paracetamol should be considered when administered concomitantly with probenecid.
Salicylamide
Salicylamide can prolong the elimination half-life (t1 / 2) of paracetamol.
Contraindicated associations
• morphine agonists and antagonists (buprenorphine, nalbuphine, pentazocine)
in function of the reduced analgesic effect due to the competitive block of the receptors, with risk of onset of rejection syndrome
• alcohol
alcohol increases the sedative effect of morphine analgesics. Reduced alertness can make it dangerous to drive and use machines
• Naltrexone
There is a risk of reduced analgesic effect. The dosage of morphine derivatives should be increased if necessary.
Associations to be evaluated
• Other morphine agonist analgesics (alfentanil, dextromoramide, dextropropoxyphene, fentanyl, dihydrocodeine, hydromorphone, morphine, oxycodone, pethidine, phenoperidine, remifentanil, sufentanil, tramadol), morphine-like antitussive drugs, morphine dextrin-methorphin cough (codeine, etymorphine), benzodiazepines, barbiturates, methadone
Increased risk of respiratory depression which can be fatal in case of overdose.
• Other sedative drugs: morphine derivatives (analgesics, cough suppressants and replacement treatments), neuroleptics, barbiturates, benzodiazepines, anxiolytics other than benzodiazepines (meprobamate), hypnotics, sedative antidepressants (amitriptyline, doxepine, mirtazapine, mianserin, trimipramerine) ), sedative H1 antihistamines, centrally acting antihypertensive drugs, baclofen and thalidomide. Increased central depressive action. The altered state of alertness can make it dangerous to drive or use machines.
04.6 Pregnancy and lactation
Clinical experience with the use of paracetamol during pregnancy and lactation is limited.
Pregnancy
Epidemiological data on the use of therapeutic doses of oral paracetamol indicate that no undesirable effects occur in pregnant women or on the health of the fetus or newborns. Reproductive studies with paracetamol have shown no malformation or foetotoxic effects. Paracetamol must, however, , to be used during pregnancy only after a "careful evaluation of the risk / benefit ratio.
In pregnant patients, the recommended posology and duration of treatment should be strictly observed.
As regards the presence of codeine, if the drug is taken at the end of pregnancy, its morphine mimetic characteristics must be taken into consideration (theoretical risk of respiratory depression in newborns in case of high doses taken before birth, risk of withdrawal syndrome in case of chronic administration at the end of pregnancy).
In clinical practice, although an increased risk of cardiac malformations has been demonstrated in some sample cases, most epidemiological studies exclude the risk of malformations.
Studies in animals have shown a teratogenic effect.
Feeding time
Codeine should not be used during breastfeeding (see section 4.3).
Codeine passes into breast milk.
At normal therapeutic doses, codeine and its active metabolite may be present in breast milk at very low doses and are unlikely to adversely affect the infant. However, if the patient is an ultra-rapid metaboliser of CYP2D6, higher levels of the active metabolite, morphine, may be present in breast milk and in very rare cases, may cause symptoms of opioid toxicity in the newborn, which can be fatal.
A case of morphine intoxication was reported in a breastfed infant whose mother was an ultra-rapid metabolizer treated with codeine at therapeutic doses.
04.7 Effects on ability to drive and use machines
The product may cause drowsiness and it is therefore advisable to refrain from driving vehicles or using machines.
04.8 Undesirable effects
Skin reactions of various types and severities have been reported with the use of paracetamol, including cases of erythema multiforme, Stevens-Johnson syndrome and epidermal necrolysis.
At therapeutic doses, codeine-related undesirable effects are comparable to those of other opioids, although they are rarer and more modest.
The following are the side effects of TACHIDOL organized according to the MedDRA system organ class.
The following frequency scales were used: very common (≥1 / 10); common (≥1 / 100,
Side effects related to paracetamol
Undesirable effects related to codeine
* particularly in patients who have undergone cholecystectomy
Very rare cases of severe skin reactions have been reported.
In case of overdose, paracetamol can cause hepatic cytolysis which can evolve towards massive and irreversible necrosis.
At higher than therapeutic dosages there is a risk of addiction and withdrawal syndrome following a "sudden interruption of dosing which can be observed in both patients and infants born to codeine-dependent mothers."
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
Paracetamol
There is a risk of intoxication, especially in patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition and in patients receiving enzyme inducers. In these cases, overdose can be fatal.
Acute intoxication is manifested by nausea, vomiting, anorexia, pallor, abdominal pain, malaise, sweating: these symptoms usually appear within the first 24 hours.
Paracetamol, taken in high doses far exceeding those commonly recommended, can cause hepatic cytolysis which can evolve towards complete and irreversible necrosis, which involves hepatocellular insufficiency, metabolic acidosis and encephalopathy, which can lead to coma and death.
At the same time, increased levels of hepatic transaminases (AST, ALT), lactic dehydrogenase and bilirubin are observed, together with a decrease in the prothrombin value, which may occur 12 to 48 hours after administration. Clinical symptoms of liver damage usually manifest themselves after a day or two, and peak after 3-4 days.
Emergency measures:
• Immediate hospitalization
• Before starting treatment, take a blood sample to determine plasma paracetamol levels as soon as possible, but not earlier than 4 hours after the overdose
• Rapid elimination of paracetamol by gastric lavage
• Treatment following an overdose includes administering the antidote N-acetylcysteine (NAC) intravenously or orally, if possible within 8 hours of ingestion. N-acetylcysteine may, however, give some of protection even after 16 hours.
The dosage is 150 mg / kg / i.v. in glucose solution in 15 minutes, then 50 mg / kg in the following 4 hours and 100 mg / kg in the following 16 hours, ie a total of 300 mg / kg in 20 hours.
• Symptomatic treatment
Liver tests should be performed at the start of treatment, which will be repeated every 24 hours. In most cases, liver transaminases return to normal within one to two weeks with full recovery of liver function. In very severe cases, however, liver transplantation may be required.
Codeine
Signs in adults:
the symptoms are represented by acute depression of the respiratory centers (cyanosis, reduced respiratory function), drowsiness, rash, itching, vomiting, ataxia, pulmonary edema (rare).
Signs in children (toxic dose: 2 mg / kg as a single dose):
reduced respiratory function, respiratory arrest, miosis, convulsions, histamine release signals: facial redness and swelling, hives, collapse, urinary retention.
Emergency measures:
• Assisted ventilation
• Administration of naloxone.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Analgesic-antipyretic
ATC code: N02BE51
Codeine is a weak centrally acting analgesic. Codeine exerts its effect through the mc opioid receptors, although codeine has a low affinity for these receptors, and its analgesic effect is due to its conversion into morphine. Codeine, particularly in combination with other pain relievers such as acetaminophen, has been shown to be effective in acute nociceptive pain.
The paracetamol-codeine association possesses a higher antalgic activity than that of its components taken individually, with a much longer lasting effect. Their action is synergistic as paracetamol acts on the central and peripheral biochemical mechanisms of pain, while codeine interacts with opioid receptors.
05.2 Pharmacokinetic properties
Paracetamol and codeine have overlapping pharmacokinetic characteristics and are characterized by rapid intestinal absorption and total bioavailability, low affinity for plasma proteins and "equally rapid distribution into tissues. Paracetamol is metabolized in the liver and excretion," predominantly urinary, is completed within 24 hours. Codeine is also metabolised by the liver and excreted in the urine mainly in the form of glucuroconjugated inactive metabolites.
Codeine crosses the fetal-placental barrier and passes into breast milk.
Special patient groups
Slow and ultra-rapid metabolisers of the CYP2D6 enzyme
Codeine is metabolised primarily via glucuroconjugation, but through a minor metabolic pathway, such as O-demethylation, it is converted to morphine. This metabolic transformation is catalyzed by the CYP2D6 enzyme. About 7% of the Caucasian population has a deficiency of the CYP2D6 enzyme due to genetic variation. These subjects are called poor metabolisers and may not benefit from the expected therapeutic effect as they are unable to transform codeine into its active metabolite morphine.
Conversely, about 5.5% of the population in Western Europe is made up of ultra-rapid metabolisers. These subjects have one or more duplicates of the CYP2D6 gene and therefore may have higher concentrations of morphine in the blood resulting in an increased risk of adverse reactions (see also sections 4.4 and 4.6).
The existence of ultra-rapid metabolisers should be considered with particular attention in the case of patients with renal insufficiency in whom an increase in the concentration of the active metabolite morphine-6-glucuronide may occur.
The genetic variation related to the CYP2D6 enzyme can be ascertained by the genetic typing test.
05.3 Preclinical safety data
Acute and chronic toxicity studies did not show a negative potentiation between the two active ingredients, whose metabolic characteristics remain unchanged.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Effervescent granules: maltitol, mannitol, sodium bicarbonate, citric acid, lemon flavor, aspartame, povidone, docusate sodium.
Effervescent tablets: citric acid, sodium bicarbonate, sodium carbonate, sorbitol, aspartame, orange flavor, lemon flavor, docusate sodium, simethicone emulsion.
Film-coated tablets: croscarmellose sodium, stearic acid, povidone, precipitated silica, sodium lauryl sulfate, lactose monohydrate, hypromellose, titanium dioxide (E171), Macrogol 4000.
06.2 Incompatibility
There are no known chemical-physical incompatibilities towards other compounds.
06.3 Period of validity
Effervescent granules: 2 years.
Effervescent tablets and tablets: 3 years.
06.4 Special precautions for storage
Effervescent granules: store below 25oC.
Effervescent tablets: Store in the original package to protect from moisture. Store below 30oC.
Film-coated tablets: does not require any particular storage conditions.
The half tablet can be stored for 24 hours in the original package to protect the medicine from light.
06.5 Nature of the immediate packaging and contents of the package
Tachidol effervescent granules:
Box containing 10 bipartite heat-sealed paper-aluminum-polyethylene sachets.
Tachidol effervescent tablets:
Carton containing two polypropylene tubes closed with polyethylene cap each of which contains 8 divisible effervescent tablets.
Tachidol film-coated tablets:
opaque PVC / PVC / aluminum blister: packs of 10, 12, 16, 20 and 24 tablets.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Joint Chemical Companies Angelini Francesco - A.C.R.A.F. S.p.A.
Viale Amelia, 70 - 00181 ROME
08.0 MARKETING AUTHORIZATION NUMBER
Tachidol effervescent granules, 10 sachets: 031825021
TACHIDOL effervescent tablets, 16 tablets: 031825096
TACHIDOL film-coated tablets, 10 divisible tablets: 031825045
TACHIDOL film-coated tablets, 12 divisible tablets: 031825058
TACHIDOL film-coated tablets, 16 divisible tablets: 031825060
TACHIDOL film-coated tablets, 20 divisible tablets: 031825072
TACHIDOL film-coated tablets, 24 divisible tablets: 031825084
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
June 1997 / June 2007.
10.0 DATE OF REVISION OF THE TEXT
May 2015
