Active ingredients: Rupatadine
Pafinur 10 mg tablets
Pafinur package inserts are available for pack sizes:- Pafinur 10 mg tablets
- Pafinur 1mg / ml Oral solution
Indications Why is Pafinur used? What is it for?
Rupatadine is an antihistamine.
Pafinur relieves the symptoms of allergic rhinitis such as sneezing, runny nose, itchy eyes and nose.
Pafinur is also used to relieve symptoms associated with chronic idiopathic urticaria (an allergic skin rash) such as itching and wheals (localized redness and swelling of the skin).
Contraindications When Pafinur should not be used
Do not use Pafinur
- If you are allergic (hypersensitive) to rupatadine or any of the other ingredients of Pafinur.
Precautions for use What you need to know before taking Pafinur
In case of renal or hepatic insufficiency, consult your doctor. The use of Pafinur 10 mg tablets is currently not recommended in patients with impaired renal or hepatic function.
If you have low levels of potassium in your blood and / or have a certain abnormal heartbeat rhythm (known prolongation of the QTc interval on the ECG) which can occur in some forms of heart disease, ask your doctor for advice.
This drug is not indicated for children under 12 years of age.
If you are over 65, consult your doctor or pharmacist.
Interactions Which drugs or foods may change the effect of Pafinur
Taking Pafinur with other medicines
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those that do not require a prescription.
Do not take medicines containing ketoconazole or erythromycin if you are using Pafinur.
If you are taking central nervous system depressant medicines or statin medicines, ask your doctor for advice before taking Pafinur.
Taking Pafinur with food and drink
Pafinur should not be given with grapefruit juice, as this drink may increase the level of Pafinur in the body. Pafinur, at the recommended dose (10 mg), does not increase alcohol-induced sleepiness.
Warnings It is important to know that:
Pregnancy and breastfeeding
Do not use Pafinur if you are pregnant or breastfeeding, unless clearly indicated by your doctor.
Ask your doctor or pharmacist for advice before using any medicine.
Driving and using machines
At recommended doses, Pafinur is not expected to affect the ability to drive or use machines. However, when starting treatment with Pafinur, you should use caution and monitor how the treatment affects you before driving or using machines.
Important information about some of the ingredients
This medicinal product contains lactose.
If your doctor has told you that you are intolerant to some sugars, ask him for advice before using this medicine.
Dose, Method and Time of Administration How to use Pafinur: Posology
Always take Pafinur exactly as your doctor has told you. If you are not sure you should consult your doctor or pharmacist.
Pafinur is indicated for adolescents (over 12 years of age) and adults. The usual dose is one tablet (10 mg of rupatadine) once a day on a full or empty stomach. Swallow the tablet with a sufficient amount of liquid (e.g. water).
The duration of treatment with Pafinur will be indicated by the attending physician.
Overdose What to do if you have taken too much Pafinur
If you take more Pafinur than you should
Contact your doctor or pharmacist immediately if you have accidentally taken too much of the medicine.
If you forget to take Pafinur
Take the dose as soon as possible and continue with the usual dosage. Do not take a double dose to make up for the single doses you have forgotten to take.
Side Effects What are the side effects of Pafinur
Like all medicines, Pafinur can cause side effects, although not everybody gets them.
Common side effects (may affect up to 1 in 10 people) are sleepiness, headache, dizziness, dry mouth, feeling weak and tired. Uncommon side effects (may affect up to 1 in 100 people) are increased appetite, irritability, attention disturbance, nasal bleeding, dry nose, sore throat, cough, dry throat, rhinitis, nausea, abdominal pain, diarrhea, indigestion, vomiting, constipation, rash, back pain, joint pain, muscle aches, thirst, general feeling of discomfort, fever, abnormal liver function tests and weight gain.
Rare side effects (may affect up to 1 in 1,000 people) are palpitations and increased heart rate.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep out of the reach and sight of children.
Do not use Pafinur after the expiry date which is stated on the blisters and carton. The expiry date refers to the last day of the month.
Keep the container in the outer packaging in order to protect it from light.
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
What Pafinur contains
- The active ingredient in Pafinur is rupatadine. Each tablet contains 10 mg of rupatadine (as fumarate).
- The other ingredients are: pregelatinised maize starch, microcrystalline cellulose, red iron oxide (E-172), yellow iron oxide (E-172), lactose monohydrate and magnesium stearate.
What Pafinur looks like and contents of the pack
Pafinur is presented as round, light salmon colored tablets, packaged in blisters containing 3, 7, 10, 15, 20, 30, 50 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
PAFINUR
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains:
10 mg of rupatadine (as fumarate).
Excipients: lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablet.
Round, light salmon colored tablets.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Symptomatic treatment of allergic rhinitis and chronic idiopathic urticaria in adults and adolescents (over 12 years of age).
04.2 Posology and method of administration
Adults and adolescents (over 12 years of age)
The recommended dose is 10 mg (one tablet) once a day, with or without food.
Senior citizens
Rupatadine should be used with caution in the elderly (see section 4.4).
Children
The use of rupatadine 10 mg tablets is not recommended in children below 12 years of age due to a lack of data on safety and efficacy.
Patients with renal or hepatic insufficiency
There is no clinical experience in patients with impaired renal or hepatic function, currently it is not recommended to administer 10 mg rupatadine to these patients.
04.3 Contraindications
Hypersensitivity to rupatadine or to any of the excipients.
04.4 Special warnings and appropriate precautions for use
Administration of rupatadine with grapefruit juice is not recommended (see section 4.5).
The cardiac safety of rupatadine was evaluated in a thorough QT / QTc study.
Rupatadine at up to ten times the therapeutic dose had no effect on the ECG and therefore did not raise any cardiac safety concerns.
However, rupatadine should be used with caution in patients with recognized prolongation of the QT interval, in patients with uncorrected hypokalaemia, in patients with ongoing proarrhythmic conditions, such as clinically significant bradycardia, acute myocardial ischaemia.
Rupatadine 10 mg tablets should be used with caution in the elderly (patients 65 years of age or older). Although no overall differences in drug efficacy or safety were observed during clinical trials, increased sensitivity of some elderly subjects cannot be ruled out due to the small number of elderly patients studied (see section 5.2).
For use in children under 12 years of age and in patients with impaired renal or hepatic function, see section 4.2.
Due to the presence of lactose monohydrate in rupatadine 10 mg tablets, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose / galactose malabsorption syndrome should not use this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Interaction with ketoconazole or erythromycin: concomitant administration of 20 mg rupatadine and ketoconazole or erythromycin increases the systemic exposure to rupatadine by 10-fold and 2-3-fold, respectively. These changes were not associated with an effect on the QT interval or with an increase in adverse reactions compared to when the drugs were administered separately.
However, the use of rupatadine in combination with these drugs and with other inhibitors of the CYP3A4 isoenzyme is not recommended.
Interaction with grapefruit juice: Concomitant administration of grapefruit juice increased the systemic exposure of rupatadine 3.5-fold. Therefore, concomitant administration of rupatadine with grapefruit juice is not recommended.
Interaction with alcohol: after the administration of alcohol, a dose of 10 mg of rupatadine produced marginal effects in some psychomotor tests, although these effects were not significantly different from those caused by alcohol alone. A dose of 20 mg increases the alterations caused by the "alcohol intake.
Interaction with CNS depressant substances: as for other antihistamines, interactions with substances having a depressive action on the central nervous system cannot be excluded.
Interaction with statins: Asymptomatic increases in CPK were not commonly reported in clinical trials with rupatadine. The risk of interactions with statins, some of which are also metabolised by cytochrome P450 (CYP3A4), is unknown. For this reason, rupatadine should be used with caution when administered concomitantly with statins.
04.6 Pregnancy and lactation
Data on a limited number of exposed pregnancies indicate no adverse effects of rupatadine on pregnancy or on the health of the fetus / newborn. No other relevant epidemiological data are available to date. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal / fetal development, parturition or postnatal development (see section 5.3).
Caution should be exercised when prescribing the medicine to pregnant women.
Rupatadine is excreted in the milk of animals. It is not known whether rupatadine is excreted in human milk. Due to the lack of data in men, caution should be exercised when prescribing the medicine to breastfeeding women.
04.7 Effects on ability to drive and use machines
10 mg rupatadine has not been shown to impair the ability to drive or use machines. Nevertheless, caution should be exercised before driving or operating machinery until the patient's subjective reaction to rupatadine is established.
04.8 Undesirable effects
Rupatadine 10 mg was administered to over 2025 patients in clinical trials, 120 of whom received rupatadine for at least 1 year.
The most common adverse reactions in controlled clinical trials were somnolence (9.5%), headache (6.9%) and fatigue (3.2%).
Most adverse reactions observed in clinical trials were mild to moderate in intensity and generally did not require discontinuation of therapy.
The frequencies are summarized according to the following scheme
04.9 Overdose
No cases of overdose have been reported. In a clinical safety study, rupatadine at a daily dose of 100 mg for a duration of 6 days was well tolerated. The most common adverse reaction was somnolence. Should "accidental ingestion of very high doses occur, symptomatic treatment associated with necessary supportive measures should be instituted."
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: other antihistamines for systemic use, ATC code: R06A X28.
Rupatadine is a second generation antihistamine, long-acting histamine antagonist with selective peripheral H1 receptor antagonist activity. Some of the metabolites (desloratadine and its hydroxylated metabolites) retain antihistamine activity and may partially contribute to the overall efficacy of the drug.
Studies in vitro performed with rupatadine at high concentrations have shown an inhibition of mast cell degranulation induced by immunological and non-immunological stimuli and inhibition of the release of cytokines, in particular of TNFα in human mast cells and monocytes. The clinical importance of these observations is still to be confirmed.
Clinical studies in volunteers (n = 375) and patients (n = 2650) with allergic rhinitis and chronic idiopathic urticaria showed no significant effect on the electrocardiogram when rupatadine was administered at doses between 2 and 100 mg.
In a placebo-controlled clinical trial in patients with Chronic Idiopathic Urticaria, rupatadine was effective in reducing the mean itch score from baseline over the 4-week treatment period (changes from baseline: rupatadine 57 , 5%, placebo 44.9%) and in reducing the mean number of wheals (54.3% versus 39.7%).
05.2 Pharmacokinetic properties
Absorption and bioavailability
Rupatadine is rapidly absorbed after oral administration, with a tmax of approximately 0.75 hours after dosing. The mean Cmax was 2.6 ng / ml after administration of a single oral dose of 10 mg and 4.6. ng / ml after a single 20 mg oral dose. The pharmacokinetics of rupatadine were linear over the dose range of 10 to 40 mg. After a dose of 10 mg once daily for 7 days, the mean C was 3.8 ng / mL. Plasma concentration decreased bi-exponentially with a mean elimination half-life of 5.9 hours. The plasma protein binding rate of rupatadine was 98.5-99%.
Since rupatadine has never been administered intravenously to humans, no data on its absolute bioavailability are available.
Effects of food intake
Food intake increased the systemic exposure (AUC) to rupatadine by approximately 23%. Exposure to one of its active metabolites and to the major inactive metabolite was virtually the same (approximately 5% and 3% reduction, respectively). The time taken to reach the maximum plasma concentration (tmax) of rupatadine was delayed 1 hour. Maximum plasma concentration (Cmax) was not affected by food intake. These differences have no clinical significance.
Metabolism and elimination
In a human excretion study (40 mg of 14C-rupatadine), 34.6% of the administered radioactivity was recovered in the urine and 60.9% in the faeces withdrawn within 7 days. Rupatadine is subjected to significant pre-systemic metabolism when administered orally. The amount of unchanged active substance found in urine and faeces was negligible. This means that rupatadine is almost completely metabolised. Education in vitro on metabolism in human liver microsomes indicate that rupatadine is primarily metabolised by cytochrome P450 (CYP 3A4).
Specific groups of patients
In a study in healthy volunteers comparing results in young adults and elderly patients, the AUC and Cmax values for rupatadine were higher in the elderly than in young adults. Presumably, this is due to a decrease. of hepatic first pass metabolism in the elderly. Such differences were not observed in the metabolites tested. The mean elimination half-life of rupatadine in elderly and young volunteers was 8.7 hours and 5.9 hours, respectively. Since these results for rupatadine and its metabolites were not clinically significant, it was concluded that no adjustment is necessary for the use of a 10 mg dose in the elderly.
05.3 Preclinical safety data
Non-clinical studies revealed no particular risk for humans based on conventional studies of pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.
A dose greater than 100 times the clinically recommended dose (10 mg) of rupatadine did not lengthen the QTc or QRS interval or cause arrhythmia in various animal species such as rats, guinea pigs and dogs. Rupatadine is one of its main ones. active metabolites in human subjects, 3-hydroxydesloratadine, did not affect the potential for cardiac action in isolated canine Purkinje fibers at concentrations at least 2000-fold higher than the C achieved after administration of a 10 mg dose in human subjects. In a study evaluating the effect on the cloned human HERG channel, rupatadine inhibited the channel at a concentration 1685 times the Cmax obtained after administration of 10 mg of rupatadine. Desloratadine, the metabolite with the highest activity, had no effect at a 10 micromolar concentration. Tissue distribution studies with radiolabelled rupatadine in rats showed that rupatadine does not accumulate in cardiac tissue.
Fertility studies in rats demonstrated a significant reduction in male and female fertility at a dose of 120 mg / kg / day, resulting in a Cmax of rupatadine 268 times higher than that obtained after administration of the therapeutic dose in humans (10 mg / day ). Fetal toxicity (developmental delay, incomplete ossification, minor skeletal changes) was detected in rats only at maternal toxic doses (25 and 120 mg / kg / day).
In rabbits, no developmental toxicity was shown for doses up to 100 mg / kg.
Dose levels at which no adverse developmental effects were observed (NOAELs) were identified at 5 mg / kg / day in rats and 100 mg / kg / day in rabbits, producing 45 and 116-fold higher Cmax, respectively, than that measured in men at therapeutic doses (10 mg / day).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
• Pregelatinised maize starch.
• Microcrystalline cellulose.
• Red iron oxide (E-172).
• Yellow iron oxide (E-172).
• Lactose monohydrate.
• Magnesium stearate.
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years.
06.4 Special precautions for storage
Keep the container in the outer packaging to keep it away from light.
06.5 Nature of the immediate packaging and contents of the package
PVC / PVDC / aluminum blisters.
Packs of 3, 7, 10, 15, 20, 30, 50 and 100 tablets. Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions.
Unused product and waste derived from this medicine must be disposed of in accordance with local legal requirements.
07.0 MARKETING AUTHORIZATION HOLDER
Biohorm S.A. - Av. Camí Reial, 51-57 - 08184 Palau-solità i Plegamans (Spain)
Dealer for sale
Rottapharm S.p.A. - Galleria Unione, 5 - 20122 Milan
08.0 MARKETING AUTHORIZATION NUMBER
PAFINUR 10 mg tablets 15 tablets - A.I.C. n. 037888017 / M
PAFINUR 10 mg tablets 20 tablets - A.I.C. n. 037888029 / M
PAFINUR 10 mg tablets 3 tablets - A.I.C. n. 037888031 / M
PAFINUR 10 mg tablets 7 tablets - A.I.C. n. 037888043 / M
PAFINUR 10 mg tablets 10 tablets - A.I.C. n. 037888056 / M
PAFINUR 10 mg tablets 30 tablets - A.I.C. n. 037888068 / M
PAFINUR 10 mg tablets 50 tablets - A.I.C. n. 037888070 / M
PAFINUR 10 mg tablets 100 tablets - A.I.C. n. 037888082 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization / Date of renewal of the authorization
10.0 DATE OF REVISION OF THE TEXT
May 2008
