Active ingredients: Domperidone
RAXAR 10 mg orodispersible tablets
Why is Raxar used? What is it for?
This medicine contains domperidone, a dopamine antagonist. It is a medicine that acts on gastric motility.
This medicine is used in adults and adolescents (12 years of age or older and weighing 35 kg or more) to treat nausea (feeling sick) and vomiting (feeling sick).
Contraindications When Raxar should not be used
Do not take RAXAR 10 mg, orodispersible tablets in the following cases:
- Known allergy to domperidone or to any of the other ingredients of this medicine (see composition).
- Prolactinoma (pituitary gland disease)
- Gastric or intestinal bleeding, intestinal obstruction or gastrointestinal perforation.
- Moderate or severe hepatic impairment
- If the ECG (electrocardiogram) detects a heart disorder called "prolongation of the" corrected QT interval "
- If you have or have had a disorder where your heart is unable to pump blood around your body as it should (a condition called heart failure).
- If you have a disorder that causes you to have a low level of potassium or magnesium or a high level of potassium in your blood.
- If you are taking certain medicines (see "Other medicines and RAXAR")
IF IN ANY DOUBT, CONSULT YOUR DOCTOR OR PHARMACIST.
Precautions for use What you need to know before taking Raxar
Take special care with RAXAR 10 mg, orodispersible tablet:
- If you have been told by your doctor that you have "intolerance to some sugars, contact your doctor before taking this medicinal product;
- Tell your doctor if you have liver problems (hepatic impairment or failure) (see "Do not take RAXAR").
- If you are taking oral ketoconazole (to treat infections caused by microscopic fungi) or oral erythromycin (an antibiotic), do not take this medicine without first checking with your doctor (see "Other medicines and RAXAR").
- If you suffer from kidney problems (renal impairment or failure). Ask your doctor for advice in case of prolonged treatment as you may need to take a lower dose of this drug or take this drug less often and your doctor may want to visit you regularly.
- Domperidone may be associated with an increased risk of heart rhythm disturbance and cardiac arrest. This risk may be more likely in patients over 60 years of age or taking doses greater than 30 mg per day. The risk also increases when domperidone is given together with other drugs. Tell your doctor or pharmacist if you are taking medicines to treat infections (fungal infections or bacterial infections) and / or if you have heart problems or AIDS / HIV (see section Other medicines and RAXAR).
Domperidone should be used at the lowest effective dose in adults and children.
- The use of domperidone and other QTc interval prolonging medications requires caution in patients who have existing cardiac conduction interval prolongation, particularly QTc, patients with significant electrolyte abnormalities or underlying heart disease such as congestive heart failure.
- Rarely it can cause severe hypersensitivity reactions and bronchospasm. While taking domperidone, contact your doctor if you notice heart rhythm disturbances such as palpitations, breathing difficulties, fainting. In this case, the domperidone treatment should be stopped.
Interactions Which drugs or foods may change the effect of Raxar
Do not take RAXAR if you are taking medicines to treat:
- fungal infections, for example azole antifungals, especially oral ketoconazole, fluconazole, or voriconazole
- bacterial infections, especially erythromycin, clarithromycin, telithromycin, moxifloxacin, pentamidine (these drugs are antibiotics)
- heart problems or high blood pressure (e.g. amiodarone, dronedarone, quinidine, disopyramide, dofetilide, sotalol, diltiazem, verapamil)
- psychosis (e.g. haloperidol, pimozide, sertindole)
- depression (e.g. citalopram, escitalopram)
- gastrointestinal disorders (e.g. cisapride, dolasetron, prucalopride)
- allergy (e.g. mechitazine, mizolastine)
- malaria (especially halofantrine)
- AIDS / HIV (protease inhibitors)
- tumors (e.g. toremifene, vandetanib, vincamine)
Tell your doctor or pharmacist if you are taking any medications to treat infections, heart conditions or AIDS / HIV.
It is important to ask your doctor or pharmacist if RAXAR is safe for you while taking other medicines, including non-prescription medicines.
Warnings It is important to know that:
Pregnancy
As a precautionary measure it is preferable to avoid the use of RAXAR 10 mg during the first trimester of pregnancy. If necessary, consider using domperidone during the second and third trimester of pregnancy. If the medicine is prescribed during pregnancy, make sure you follow your doctor's instructions carefully.
If you become pregnant during treatment, tell your doctor who will decide whether or not to continue the treatment.
Breastfeeding
Small amounts of domperidone have been detected in breast milk. Domperidone can cause side effects on the heart of the breastfed baby. Domperidone should only be used during breastfeeding if your doctor deems it strictly necessary. Ask your doctor for advice before taking this drug.
Driving and using machines:
The medicine has no or negligible influence on the ability to drive or use machines.
Important information about some of the ingredients of RAXAR 10 mg, orodispersible tablets: glucose, sulfur dioxide (E220).
Dose, Method and Time of Administration How to use Raxar: Posology
Follow these instructions strictly, unless your doctor has given you different instructions.
Duration of treatment:
Symptoms usually resolve within 3-4 days of taking this medicine. Do not take RAXAR for more than 7 days without consulting your doctor.
Adults and adolescents 12 years of age and older and weighing 35 kg or more: The usual dose is one tablet taken three times a day, preferably before meals.
Do not take more than three tablets a day.
The orodispersible tablet is not suitable for children weighing less than 35 kg.
Children should be treated with the oral suspension.
Method of administration
Oral use.
The orodispersible tablet dissolves rapidly with saliva in the mouth and can be taken without water.
Let the tablet dissolve in your mouth without chewing it.
The tablets can also be dissolved in half a glass of water by shaking them immediately before administration.
The tablets should be taken before meals. If the tablet is taken after meals, its absorption into the body may be slowed down.
Hepatic impairment:
Contraindicated in case of moderate or severe hepatic impairment. In case of mild hepatic impairment, no dose modification is required.
Renal impairment
In case of renal impairment, it may be necessary to reduce the frequency and dose of administration. Cardiovascular effect Due to cardiovascular effects, Domperidone should be used in minimal effective dose. For patients who have pre-existing cardiac conduction interval prolongation, significant disturbances or underlying heart disease, caution should be exercised.
Overdose What to do if you have taken too much Raxar
If you have taken too much RAXAR, contact your doctor, pharmacist or the nearest poison center immediately, particularly if a child has taken too much. In the event of an overdose, symptomatic treatment can be adopted. Echocardiography monitoring may be done, given the possibility of a heart problem called QT prolongation.
If you forget to take RAXAR 10 mg orodispersible tablets:
Take the medicine as soon as you remember. If it is almost time for your next dose, wait until your next dose and then continue as normal. Do not take a double dose to make up for a forgotten dose.
Side Effects What are the side effects of Raxar
Like all medicines RAXAR 10 mg, orodispersible tablets can cause side effects, although not everybody gets them.
Very common: Affects more than 1 in 10 patients
Common: Affects 1 to 10 out of 100 patients
Uncommon: Affects 1 to 10 users in 1,000
Rare: Affects 1 to 10 out of 10,000 patients
Very rare: Affects less than 1 in 10,000 patients
Not known: frequency cannot be estimated from the available data
Very rare:
- Immune system disorders: Allergic reactions (e.g. rash, itching, shortness of breath, wheezing and / or swollen face) have been reported. If this happens, stop the treatment immediately and consult your doctor or pharmacist immediately.
- Nervous system disorders: Convulsions, sleepiness, headache, abnormal muscle movements or tremors (shaking) may occur. The onset of abnormal muscle movements is of greater importance when it occurs in newborns and infants.
- Psychiatric disorders: agitation, nervousness
- Investigations: liver function test abnormal
- Diarrhea.
Rare:
- Increased levels of prolactin (hormone that induces milk flow), galactorrhea (secretion of milk outside of breastfeeding periods), gynaecomastia (abnormal breast development in men), amenorrhea (irregular or absent menstruation), gastrointestinal disturbances including very rare and transient manifestations of muscle cramps.
Since RAXAR 10 mg, orodispersible tablet contains sulfur dioxide (E220) there is a risk, in rare cases, of severe allergic reactions and breathing problems.
Not known (frequency cannot be estimated from the available data):
- Cardiac disorders: heart rhythm disturbances, sudden death
Cardiovascular system disorders have been reported: heart rhythm disturbances (rapid or irregular heart rhythm); in the presence of such complaints, you should stop treatment immediately. Domperidone may be associated with an increased risk of heart rhythm disturbances and cardiac arrest. This risk may be more likely in patients over 60 years of age or taking doses greater than 30 mg per day. Domperidone should be used at the lowest effective dosage in adults and children.
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 the safety of this medicine.
Expiry and Retention
Keep out of the sight and reach of children.
Do not use after the expiry date stated on the package after EXP. The expiry date refers to the last day of that month.
Do not store above 30 ° C. Keep the blister tightly closed to protect from moisture.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
What does RAXAR 10, orodispersible tablets contain:
The active ingredient is domperidone
One orodispersible tablet contains 10 mg of domperidone.
The other ingredients are:
Microcrystalline cellulose, crospovidone, lemon flavor *, magnesium stearate, sodium saccharin, sodium lauryl sulfate, anhydrous hydrophobic colloidal silica. * lemon flavor: maltodextrin (source of glucose), gum arabic, butylated hydroxyanisole, sulfur dioxide (E220), alpha-pinene, beta-pinene, myrcene, limonene, gamma-terpinene, neral and geranial.
What RAXAR 10 mg, orodispersible tablet looks like and contents of the pack:
RAXAR 10 mg, orodispersible tablets are white to off-white, round and biconvex orodispersible tablets.
It is available in packs containing 10, 20, 30, 40, 60 and 100 tablets. Not all pack sizes may be marketed.
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
RAXAR 10 MG GOLD DISPERSIBLE TABLETS
▼ Medicinal product subject to additional monitoring. This will allow the rapid identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for information on how to report adverse reactions.
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One orodispersible tablet contains 10 mg of domperidone.
Excipients: glucose, sulfur dioxide (E 220).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Orodispersible tablet.
White or almost white, round, biconvex tablet.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
RAXAR is indicated to relieve the symptoms of nausea and vomiting.
04.2 Posology and method of administration
It is preferable that children are treated with the oral suspension.
RAXAR should be used at the lowest effective dose for the shortest duration necessary to control nausea and vomiting.
It is recommended that oral RAXAR be taken before meals. If taken after meals, the absorption of the drug is rather delayed.
Patients should try to take each dose at the correct time. If a dose is missed, it should be missed and the usual dosing schedule should be resumed. A double dose should not be taken to make up for a forgotten dose.
As a rule, the maximum treatment duration should not exceed one week.
Adults and adolescents (12 years of age or older and 35 kg or more weight)
One 10 mg tablet up to three times a day for a maximum dose of 30 mg per day.
The orodispersible tablet dissolves rapidly in the mouth with the help of saliva and can be taken with or without water. If taken without water, the tablet should be placed on the tongue and dissolved in the mouth before swallowing. If appropriate, it can be drunk later. a glass of water.
The orodispersible tablet can also be dissolved by shaking it in half a glass of water immediately before administration.
Hepatic impairment
RAXAR is contraindicated in moderate and severe hepatic insufficiency (see section 4.3). However, no dosage adjustment is necessary in case of mild hepatic impairment (see section 5.2).
Renal impairment
Since the half-life of domperidone is prolonged in severe renal insufficiency, for repeated dosing, the frequency of administration of RAXAR should be reduced to once or twice daily depending on the severity of the renal impairment, and the severity of renal impairment may need to be reduced. Such patients on prolonged therapy should be followed up regularly (see sections 4.4 and 5.2).
Domperidone should be used at the lowest effective dose due to cardiovascular effects. For patients who have existing cardiac conduction interval prolongation, significant disturbances or underlying cardiac disease, caution should be used (see section 4.4).
04.3 Contraindications
This medicine is contraindicated in the following situations:
• Known hypersensitivity to domperidone or to any of the excipients.
• Prolactin-releasing pituitary tumors (prolactinomas).
• In patients with moderate or severe hepatic impairment (see section 5.2).
• In patients with known prolongation of cardiac conduction intervals, particularly the QTc interval, in patients with significant electrolyte disturbances and pre-existing heart disease, eg congestive heart failure (see section 4.4).
• Concomitant administration of all drugs that prolong the QT interval (see section 4.5).
• Concomitant administration of potent CYP3A4 inhibitors (regardless of their effects on QT interval prolongation) (see section 4.5).
This medicinal product should not be used in cases where stimulation of gastric motility could be harmful: gastrointestinal bleeding, mechanical obstruction or intestinal perforation.
04.4 Special warnings and appropriate precautions for use
Renal impairment
The elimination half-life of domperidone is prolonged in severe renal insufficiency. In case of repeated administration, the dosing frequency of domperidone should be reduced to once or twice daily depending on the severity of the impairment. the dosage.
Taking with potent CYP3 inhibitors A4
Co-administration with oral ketoconazole, erythromycin or other potent inhibitors of CYP3 A4 which prolong the QTc interval should be avoided (see section 4.5 Interactions with other medicinal products and other forms of interaction).
Patients with rare hereditary problems of galactose intolerance, eg. galactosemia or glucose-galactose malabsorption should not take this medicine.
Cardiovascular effects
Domperidone has been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, very rare cases of QT interval prolongation e have been found twists of the point in patients taking domperidone. Such cases included patients with confounding risk factors, electrolyte disturbances and concomitant treatment that may have been contributing factors (see section 4.8).
Epidemiological studies have shown that domperidone was associated with an increased risk of severe ventricular arrhythmias or sudden cardiac death (see section 4.8). An increased risk has been observed in patients over 60 years of age, in patients taking daily doses greater than 30 mg and in patients taking concomitant QT-prolonging drugs or CYP3A4 inhibitors.
Domperidone should be used at the lowest effective dose in adults and children.
Domperidone is contraindicated in patients with known existing prolongation of cardiac conduction intervals, particularly the QTc interval, in patients with significant electrolyte disturbances (hypocalcaemia, hypercalcaemia, hypomagnesaemia), or bradycardia, or in patients with pre-existing heart disease such as insufficiency congestive heart rate due to the increased risk of ventricular arrhythmia (see section 4.3).
Electrolyte disturbances (hypocalcemia, hypercalcemia, hypomagnesaemia) or bradycardia are known to be conditions that increase proarrhythmic risk.
Domperidone treatment should be discontinued in the presence of signs or symptoms associated with cardiac arrhythmia and patients should consult their physician.
Patients should be advised to promptly report any cardiac symptoms.
04.5 Interactions with other medicinal products and other forms of interaction
Domperidone is predominantly metabolised by CYP3A4.
Data from in vitro studies suggest that concomitant use of drugs that significantly inhibit CYP3 A4 may lead to increased plasma levels of domperidone.
Increased risk of QT interval prolongation occurring due to pharmacodynamic and / or pharmacokinetic interactions.
Concomitant intake of the following substances is contraindicated
Medicines that prolong the QTc interval
• class IA anti-arrhythmics (eg disopyramide, hydroquinidine, quinidine)
• class III anti-arrhythmics (eg amiodarone, dofetilide, dronedarone, ibutilide, sotalol)
• some antipsychotics (eg haloperidol, pimozide, sertindole)
• some antidepressants (eg citalopram, escitalopram)
• some antibiotics (for example erythromycin, levofloxacin, moxifloxacin, spiramycin)
• some antifungal agents (eg pentamidine)
• some antimalarial agents (in particular halofantrine, lumefantrine)
• some gastrointestinal medications (eg cisapride, dolasetron, prucalopride)
• some antihistamines (eg mechitazine, mizolastine)
• some drugs used in the treatment of cancers (for example toremifene, vandetanib, vincamine)
• some other medicines (eg bepridil, diphemanil, methadone) (see section 4.3).
Potent CYP3A4 inhibitors (regardless of their QT-prolonging effects), for example:
• protease inhibitors
• systemic azole antifungals
• some macrolides (erythromycin, clarithromycin and telithromycin) (see section 4.3).
Concomitant use of the following substances is not recommended
Moderate inhibitors of CYP3A4, eg diltiazem, verapamil and some macrolides. (see section 4.3)
The concomitant intake of the following substances requires caution in use
Caution should be exercised in the case of drugs that induce bradycardia and hypocalcaemia, as well as with the following macrolides involved in the prolongation of the QT interval: azithromycin and roxithromycin (clarithromycin is contraindicated as it is a potent inhibitor of CYP3A4).
The above list of substances is indicative and not exhaustive.
04.6 Pregnancy and lactation
Pregnancy :
There are limited data on the use of domperidone in pregnant women; no risks to the embryo, fetus or neonate have been identified following exposure to domperidone during pregnancy.
Studies in one animal species have shown reproductive toxicity associated with maternal toxicity after administration of very high doses (see section 5.3).
As a precautionary measure it is preferable to avoid the use of domperidone during the first trimester of pregnancy. If necessary, the use of domperidone during the second and third trimester of pregnancy can be considered.
Breastfeeding
Domperidone is excreted in human milk and breastfed infants receive less than 0.1% of the dose adjusted for maternal weight. The occurrence of adverse effects, particularly cardiac effects, cannot be excluded after exposure via breast milk. In this case, a decision must be made whether to discontinue breastfeeding or to discontinue / discontinue domperidone therapy by evaluating the benefits. of breastfeeding for the infant and the benefits of therapy for the mother. Caution should be exercised in case of risk factors that prolong the QTc interval in breastfed infants.
04.7 Effects on ability to drive and use machines
The medicine has no or negligible influence on the ability to drive or use machines.
04.8 Undesirable effects
Adverse drug reactions are listed below by frequency using the following convention: very common (≥1 / 10); common (≥1 / 100,
1 Domperidone can cause increased prolactin levels as the pituitary is located outside the blood brain barrier.
In rare cases, this hyperprolactinaemia can cause neuro-endocrine side effects such as galactorrhea, gynaecomastia and amenorrhea.
2 Extrapyramidal side effects are very rare in infants and young children and exceptional in adults.
These effects disappear spontaneously and completely upon discontinuation of treatment.
3 Other central nervous system related effects such as convulsion, agitation and somnolence are very rare and have mainly been reported in infants and children.
Due to the presence of sulfur dioxide (E220) there is a risk that hypersensitivity reactions and bronchospasm may occur in rare cases.
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
Symptoms
Cases of overdose have mainly been reported in infants and children. Symptoms of overdose may include agitation, changes in consciousness, seizures, disorientation, somnolence and extrapyramidal manifestations.
Treatment
There is no specific antidote for domperidone. In the event of an overdose, standard symptomatic treatment should be given immediately. ECG monitoring should be performed due to the possibility of QT interval prolongation.
Gastric lavage and the use of activated charcoal can be useful.
Anticholinergic and antiparkinsonian drugs may be useful in controlling extrapyramidal reactions.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: prokinetics.
ATC code: A03F A 03.
Domperidone is a dopamine antagonist with antiemetic properties, which does not readily cross the blood brain barrier.
In patients treated with domperidone, especially in adults, extrapyramidal side effects are very rare, but domperidone promotes the release of prolactin from the pituitary. The antiemetic effect of domperidone may result from the combination of peripheral (gastrokinetic) effects and antagonism. of dopaminergic receptors in the "chemoreceptor trigger zone", located outside the blood brain barrier in the postrema area. Animal studies, according to the low concentrations found in the brain, indicate a predominantly peripheral effect of domperidone on dopaminergic receptors.
Studies in humans have shown that oral domperidone increases lower esophageal sphincter pressure, improves anthroduodenal motility and accelerates gastric emptying. It has no effect on gastric secretion.
A thorough QT interval study was performed in accordance with ICH-E14 guidelines. This study included a placebo, an active comparator and a positive control and was conducted in healthy subjects with a domperidone dosage of up to 80 mg per day. in doses of 10 or 20 mg administered 4 times a day. This study identified a maximum difference in corrected QT interval (QTc) between domperidone and placebo in LS mean (Least Squares) in the change from baseline of 3.4 msec for 20 mg of domperidone administered 4 times daily on Day 4. The two-way confidence interval of 90% (1.0 to 5.9 msec) did not exceed 10 msec. No relevant effects on QTc interval were observed in this study. when domperidone was given at a dose of up to 80 mg / day (e.g. more than twice the maximum recommended dose).
However, two previous drug interaction studies have shown evidence of QTc interval prolongation when domperidone was given as monotherapy (10 mg 4 times a day).
The maximum time-matched mean difference in Fridericia corrected QT interval (QTcF) between domperidone and placebo was 5.4 msec (95% CI: -1.7 to 12.4) and 7.5 msec (95 CI), respectively. %: 0.6 to 14.4).
05.2 "Pharmacokinetic properties
Absorption
Domperidone is rapidly absorbed following oral administration, with peak plasma concentrations occurring approximately 1 hour after dosing. Domperidone Cmax and AUC values increased proportionally with doses ranging from 10 mg to 20 mg. A 2- or 3-fold accumulation of domperidone AUC was observed with repeated dosing four times daily (every 5 hours) of domperidone for 4 days.
Although the bioavailability of domperidone is increased in healthy subjects when taken after a meal, patients with gastrointestinal disorders should take the drug 15-30 minutes before a meal. Reduced gastric acidity impairs the absorption of domperidone. Oral bioavailability is reduced by previous concomitant administration of cimetidine and sodium bicarbonate.
The time to peak absorption is slightly delayed and the AUC is somewhat increased when the drug is taken orally after a meal.
Distribution
Oral domperidone does not show accumulation or metabolic self-induction phenomena; 90 minutes after administration, a peak plasma level of 21 ng / ml, after two weeks of oral administration at a daily dose of 30 mg, was found to be almost comparable to that of 18 ng / ml obtained after the first dose. Domperidone is 91-93% bound to plasma proteins.
Distribution studies in animals, performed with radiolabelled drug, showed "wide tissue distribution but low brain concentrations. Small amounts of the drug pass the placenta in rats."
Metabolism
Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and Ndealkylation. Metabolism Studies in vitro with diagnostic inhibitors indicate that CYP3A4 is the form of cytochrome P-450 most involved in the N-dealkylation of domperidone, while CYP3A4, CYP1A2 and CYP2E1 are involved in the aromatic hydroxylation of domperidone.
Excretion
Urinary and faecal excretion amount to 31% and 66% of the oral dose, respectively. The proportion of unchanged drug excreted is small (10% of faecal excretion and approximately 1% of urinary excretion).
The plasma half-life after a single oral dose is 7-9 hours in healthy volunteers but is prolonged in patients with severe renal insufficiency.
Hepatic impairment
In subjects with moderate hepatic impairment (Pugh score 7 to 9, Child-Pugh classification B), the AUC and C of domperidone are 2.9 and 1.5 times higher, respectively, than in healthy subjects.
The unbound fraction is increased by 25% and the terminal elimination half-life is prolonged from 15 to 23 hours. Subjects with mild hepatic impairment have a slightly lower systemic exposure than healthy subjects based on Cmax and AUC values, without no changes in protein binding or terminal half-life. Subjects with severe hepatic impairment have not been studied. Domperidone is contraindicated in patients with moderate or severe hepatic impairment (see section 4.3).
Renal impairment
In subjects with severe renal impairment (creatinine clearance 2) the elimination half-life of domperidone increased from 7.4 to 20.8 hours but plasma drug levels were lower than in healthy volunteers.
Since a very small amount of unchanged drug is excreted (approximately 1%) via the kidneys, it is unlikely that the dose of a single administration will need to be adjusted in patients with renal insufficiency.
However, in case of repeated administration, the dosing frequency should be reduced to once or twice daily depending on the severity of the disorder and the dosage may need to be reduced.
05.3 Preclinical safety data
Electrophysiological studies in vitro And in vivo indicate a moderate overall risk of QTc interval prolongation in humans for domperidone. In in vitro experiments on isolated cells transfected with hERG and on isolated myocytes from guinea pigs, exposure ratios ranged from 26 to 47 times, based on IC50 values that inhibit currents through IKr ion channels compared to free plasma concentrations in the " after administration of the maximum daily dose of 10 mg administered 3 times a day. The safety margins for prolongation of the duration of action potential in in vitro experiments on isolated cardiac tissues were 45 times higher than the free plasma concentrations in human "human at the maximum daily dose (10 mg administered 3 times a day). The safety margins in pro-arrhythmic models in vitro (isolated Langendorff perfused heart) were 9 to 45 times higher than the free plasma concentrations in humans at maximum daily dose (10 mg administered 3 times a day). In models in vivo the no-effect levels for prolonged corrected QT interval (QTc) in dogs and induction of arrhythmias in a rabbit model sensitized for torsades de pointes were more than 22-fold and 435-fold, respectively, above the free plasma concentrations in "man at the maximum daily dose (10 mg administered 3 times daily). In the model with anesthetized guinea pig following intravenous infusions, there was no effect on the corrected QT interval (QTc) at total plasma concentrations of 45.4 ng. / ml, which are 3 times higher than the total plasma levels in humans at the maximum daily dose (10 mg administered 3 times a day). The relevance of this latest study to humans following exposure to administered domperidone orally is uncertain.
In the presence of inhibition of metabolism by CYP3A4 the free plasma concentrations of domperidone can triple.
At a high maternal toxic dosage (more than 40 times the recommended human dose) teratogenic effects were seen in the rat. No teratogenicity was observed in mice and rabbits.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Microcrystalline cellulose, crospovidone, lemon flavor *, magnesium stearate, sodium saccharin, sodium lauryl sulfate, anhydrous hydrophobic colloidal silica.
* lemon flavor: maltodextrin (source of glucose), gum arabic, butylated hydroxyanisole, sulfur dioxide (E220), alpha-pinene, beta-pinene, myrcene, limonene, gamma-terpinene, neral and geranial.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Do not store above 30 ° C.
Keep the blister tightly closed to protect from moisture.
06.5 Nature of the immediate packaging and contents of the package
10, 20, 30, 40, 60 and 100 tablets in blisters (PVC / PVDC / Aluminum).
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
CRINOS S.p.A., Via Pavia 6, 20136 Milan
08.0 MARKETING AUTHORIZATION NUMBER
RAXAR 10 mg orodispersible tablets, 10 tablets in blister PVC / PVDC / Al AIC N. 039200011
RAXAR 10 mg orodispersible tablets, 20 tablets in PVC / PVDC / Al AIC blister No. 039200023
RAXAR 10 mg orodispersible tablets, 30 tablets in PVC / PVDC / Al AIC blister No. 039200035
RAXAR 10 mg orodispersible tablets, 40 tablets in PVC / PVDC / Al AIC blister No. 039200047
RAXAR 10 mg orodispersible tablets, 60 tablets in PVC / PVDC / Al AIC blister No. 039200050
RAXAR 10 mg orodispersible tablets, 100 tablets in PVC / PVDC / Al AIC blister No. 039200062
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
20 November 2009/7 November 2012
10.0 DATE OF REVISION OF THE TEXT
March 2015
