Reactine 5 mg + 120 mg 6 prolonged release tablets

In ottemperanza all'articolo 118 “autorizzazione della pubblicità presso il pubblico” del decreto legislativo 24 aprile 2006, numero 219

INDICATIONS

REACTINE is indicated in the short-term symptomatic treatment of seasonal and/or perennial allergic rhinitis with nasal congestion and hypersecretion, nasal and/or ocular itching, sneezing and tearing.

ACTIVE INGREDIENTS

One tablet contains: • active ingredient: - cetirizine dihydrochloride 5 mg; - pseudoephedrine hydrochloride 120 mg. • excipient with known effects: lactose, sodium. For the full list of excipients, see section 6.1.

EXCIPIENTS

First layer excipients Hypromellose, microcrystalline cellulose, anhydrous colloidal silica, magnesium stearate. Second layer excipients Lactose, microcrystalline cellulose, crosscaramellose sodium, colloidal anhydrous silica, magnesium stearate. Coating excipients Opadry Y-1-7000 white (methocel E5, premium (hypromellose) (E 464), titanium dioxide (E 171), macrogol 400).

CONTRAINDICATIONS AND SIDE EFFECTS

REACTINE is contraindicated in the following cases: • hypersensitivity to the active ingredients, to any of the excipients listed in paragraph 6.1, to hydroxyzine or piperazine derivatives; • severe renal insufficiency (patients with creatinine clearance less than 10 ml/min); • severe hypertension; • severe coronary heart disease; • pheochromocytoma; • history of stroke; • high risk of developing hemorrhagic stroke; • serious arrhythmia; • uncontrolled hyperthyroidism; • patients who are being treated or who have been treated in the previous two weeks with monoamine oxidase inhibitors (see section 4.5); • patients who are being treated with dihydroergotamine; • increased intraocular pressure; • urinary retention; • children under 12 years old; • pregnancy and breastfeeding (see section 4.6).

DOSAGE

Dosage Adults and children aged 12 and over: one tablet 2 times a day, one in the morning and one in the evening, to be taken without chewing during or between meals. The duration of treatment should not exceed the period of acute symptoms and in any case should not be continued beyond 7 days. After 7 days of therapy, continue treatment with cetirizine alone. Special populations Elderly patients The dose should be halved in elderly patients. Patients with renal impairment The dose should be halved in patients with renal insufficiency. Patients with hepatic impairment The dose should be halved in patients with hepatic impairment. Pediatric population REACTINE is contraindicated in children under 12 years of age (see section 4.3). Method of administration Oral use. The tablets should be taken with a little water and should not be divided, chewed or crushed.

CONSERVATION

No special precautions for storage.

WARNINGS

REACTINE is intended for short-term treatments only. Reactine must be used under medical supervision in diabetic patients and in subjects with thyroid problems, prostatic hypertrophy, hepatic insufficiency or reduced renal function, positive history of bronchospasm, as well as in elderly subjects. This medicine should be used under medical supervision in patients with pre-existing cardiovascular problems, including those with a history of myocardial infarction, coronary artery disease, hypertension, tachycardia and arrhythmia. Caution must also be exercised in subjects treated with sympathomimetics (decongestants, anorectics, psychostimulants) such as amphetamines, antihypertensive medicines, tricyclic antidepressants and digitalis or following the intake of higher quantities of alcohol or other substances with a depressant action on the central nervous system (CNS). Although at therapeutic doses of cetirizine, no clinically significant interactions with alcohol have been demonstrated (for a blood alcohol level of 0.5 g/l), caution is recommended if alcohol is taken simultaneously. Caution should also be exercised in patients with risk factors that may increase the risk of haemorrhagic stroke (such as concomitant use of vasoconstrictors such as bromocriptine, pergolide, lisuride, cabergoline, ergotamine) or any other drug with decongestant activity (for example phenylpropanolamine, phenylephrine, ephedrine), used orally or nasally, due to the risk of vasoconstriction and increase in blood pressure (see paragraph 4.5). Increased ectopic pacemaker activity may occur when pseudoephedrine is used concomitantly with cardiac glycosides, such as digoxin or digitoxin; the use of the combination of cetirizine and pseudoephedrine should therefore be avoided in patients treated with cardiac glycosides (see section 4.5). Pseudoephedrine is associated with the risk of abuse. High doses may eventually induce toxicity. Prolonged use may induce habituation with an increased risk of overdose. Rapid discontinuation can induce depression. Use caution in patients with predisposing factors for urinary retention (e.g., spinal cord injury, prostatic hyperplasia), as cetirizine may increase the risk of urinary retention. Caution is recommended in patients at risk of hypercoagulation such as in inflammatory bowel disease, due to the vasoconstrictor effect of pseudoephedrine. Isolated cases of ischemic colitis have been reported in association with pseudoephedrine. The product should be discontinued in case of sudden abdominal pain, rectal bleeding or other symptoms of ischemic colitis. Caution is required in hypertensive patients receiving concomitant treatment with non-steroidal anti-inflammatory drugs (NSAIDs) as both pseudoephedrine and NSAIDs can increase blood pressure (see section 4.5). Severe skin reactions such as acute generalized exanthematous pustulosis (AGEP) may occur with medicines containing pseudoephedrine. This acute pustular eruption can occur within the first 2 days of treatment, with fever, and numerous small pustules, mostly non-follicular, resulting from a widespread edematous erythema and localized mainly on the skin folds, trunk and upper limbs. Patients should be carefully monitored. If signs and symptoms such as pyrexia, erythema or numerous small pustules are observed, the administration of Reactine should be stopped and appropriate measures taken if necessary. The medicine can act as a brain stimulant and give rise to episodes of insomnia, nervousness, hyperpyrexia, tremor and epileptic-type convulsions. During treatment with indirect sympathomimetic agents, acute postoperative hypertension may occur if they are used halogenated volatile anesthetics. Therefore, if surgery is planned, it is advisable to stop treatment 24 hours before anesthesia. Ischemic optic neuropathy Cases of ischemic optic neuropathy have been reported with pseudoephedrine. Pseudoephedrine should be discontinued if sudden loss of vision or reduction in visual acuity occurs, for example in the case of a scotoma. Allergy skin tests are inhibited by antihistamines therefore a washout period (3 days) is required before performing them. Athletes should be informed that treatment with pseudoephedrine could lead to a positive doping test result. If symptoms persist or worsen, or if new symptoms occur, discontinue use and consult a doctor. Pediatric population The combination of cetirizine and pseudoephedrine is contraindicated in children under 12 years of age (see sections 4.2 and 4.3) due to the presence of pseudoephedrine and because this combination has not been studied in this age group. Excipient with known effects The medicine contains lactose: patients suffering from rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicine. This medicinal product contains less than 1 mmol (23 mg) sodium per single dose and can therefore be considered essentially sodium-free.

INTERACTIONS

Due to the pharmacokinetic, pharmacodynamic and tolerability profile of cetirizine, no interactions are expected with this antihistamine. In reality, no significant pharmacodynamic or pharmacokinetic interactions were reported in drug-drug interaction studies carried out, in particular, with pseudoephedrine or theophylline (400 mg/day). The activity of sympathomimetic amines such as pseudoephedrine contained in this medicinal product is increased by the concomitant administration of monoamine oxidase inhibitors and β-blockers. Due to the long duration of action of monoamine oxidase inhibitors, the activity of sympathomimetic amines can be observed even 15 days after discontinuation of administration (see section 4.3). Sympathomimetic amines reduce the antihypertensive effects of β-blockers, methyldopa, guanethidine, and reserpine. Antacids increase the absorption of pseudoephedrine while it is reduced by the simultaneous intake of kaolin. Concomitant administration of linezolid and pseudoephedrine may cause an increase in blood pressure in normotensive patients. Caution is also required in patients taking: - sympathomimetic drugs such as decongestants (e.g. phenylpropanolamine, phenylephrine, ephedrine), anorectics, psychostimulants such as amphetamines (combined effects on the cardiovascular system), - antihypertensive drugs (reduction of antihypertensive effects), - bromocriptine, pergolide, lisuride, cabergoline, ergotamine (risk of vasoconstriction and increase in blood pressure (see section 4.4), - tricyclic antidepressants, - alcohol or other substances with depressant action on the central nervous system (CNS) (possible intensification of the depressant action on the CNS and deterioration of performance), - cardiac glycosides such as digoxin or digitoxin (risk of cardiac arrhythmia) (see section 4.4), - non-steroidal anti-inflammatories (NSAIDs) (both pseudoephedrine and NSAIDs can increase blood pressure) (see section 4.4). The degree of absorption of cetirizine is not reduced by food intake, although the percentage of absorption is decreased.

SIDE EFFECTS

Clinical studies have shown that cetirizine at a dose of 10 mg has minor side effects on the central nervous system, including drowsiness, fatigue, dizziness and headache. In some cases, paradoxical CNS stimulation has been reported. The following adverse reactions were reported by ≥ 1% of adult subjects in randomized, placebo-controlled trials with cetirizine alone: ​​drowsiness, nervousness, fatigue, dry mouth, dizziness, headache, nausea, pharyngitis, abdominal pain. Drowsiness was mild to moderate in the majority of cases, although statistically more common than with placebo. Further studies in which objective tests were carried out have shown that usual daily activities are not compromised at the recommended daily dose in healthy young volunteers. Although cetirizine is a selective H₁-peripheral and is relatively devoid of anticholinergic activity, cases of dysuria, accommodation disorder and dry mouth have been reported. Cases of abnormal liver function with elevations in liver enzymes accompanied by elevated bilirubin have been reported. This mainly resolves with discontinuation of treatment with cetirizine dihydrochloride. Isolated cases of stroke and ischemic colitis associated with the use of pseudoephedrine have been described in the literature. The following adverse reactions were reported by ≥ 1% of subjects in randomized, placebo-controlled trials with pseudoephedrine alone: ​​dry mouth, nausea, dizziness, insomnia, and nervousness. Clinical studies The safety of the combination of cetirizine and pseudoephedrine from clinical studies is based on data from 3 randomized double-blind placebo-controlled studies for the treatment of seasonal allergic rhinitis. Table 1 includes adverse reactions that occurred in patients in whom more than one event was reported, and the incidence was higher than placebo and in 1% or more of patients. Table 1: Side effects reported by > 1% of adult subjects treated with the combination of cetirizine and pseudoephedrine in 3 randomized placebo-controlled clinical trials.

System Organ Classification: Cetirizine 5 mg/Pseudoephedrine 120 mg Multi-dose (N =840) Placebo (N =831).

Preferred Term: % (frequency) % (frequency).

Systemic pathologies and conditions relating to the administration site.

Asthenia: 2.0 (Common) 0.7 (Uncommon).

Gastrointestinal disorders.

Dry mouth: 3.3 (Common) 0.4 (Uncommon).

Nervous system disorders.

Dizziness: 1.1 (Common) 0.1 (Uncommon).

Insomnia: 3.8 (Common) 0.5 (Uncommon).

Drowsiness: 2.5 (Common) 0.2 (Uncommon).

Side effects observed and reported during treatment with REACTINE are reported according to system organ class according to MedDRA. Frequencies are defined as follows: • Very common (≥ 1/10); • Common (≥ 1/100, < 1/10); • Uncommon (≥ 1/1,000, < 1/100); • Rare (≥ 1/10,000, <1/1,000); • Very rare (<1/10,000); • Not known (frequency cannot be estimated from the available data).

Table 2. Adverse reactions identified during post-marketing experience with cetirizine, pseudoephedrine or the combination of cetirizine and pseudoephedrine by frequency category estimated from spontaneous reporting *.

SOCFrequency: Adverse reaction.

Pathologies of the blood and lymphatic system:

Very rare: thrombocytopenia.

Immune system disorders:

Rare: Hypersensitivity (including anaphylactic shock).

Metabolism and nutrition disorders:

Not known: increased appetite.

Psychiatric disorders:

Common: nervousness.

Uncommon: anxiety.

Uncommon: agitation.

Rare: hallucinations.

Rare: psychotic disorder.

Rare: assault.

Rare: confusional state.

Rare: depression.

Rare: insomnia.

Very rare: tic.

Not known: euphoric behavior.

Very rare: visual hallucination.

Not known: suicidal behavior.

Nervous system disorders:

Common: dizziness.

Common: headache.

Common: drowsiness.

Uncommon: restlessness.

Uncommon: paraesthesia.

Rare: convulsion.

Very rare: dysgeusia.

Very rare: syncope.

Very rare: tremor.

Very rare: dystonia.

Very rare: dyskinesia.

Very rare: cerebrovascular accidents (stroke)†

Not known: amnesia.

Not known: memory impairment.

Eye disorders:

Very rare: accommodation disorder.

Very rare: blurred vision.

Very rare: oculogyric crisis.

Very rare: swelling of the eyes.

Not known: mydriasis.

Not known: eye pain.

Not known: vision impairment.

Not known: photophobia.

Not known: Ischemic optic neuropathy.

Ear and labyrinth disorders:

Not known: dizziness.

Cardiac disorders:

Uncommon: palpitations.

Rare: arrhythmia.

Rare: tachycardia.

Not known: myocardial infarction†

Vascular pathologies:

Rare: paleness.

Rare: hypertension.

Very rare: circulatory collapse.

Very rare: hypotension.

Respiratory, thoracic and mediastinal disorders:

Very rare: cough.

Uncommon: dyspnoea.

Gastrointestinal disorders:

Common: dry mouth.

Common: nausea.

Uncommon: diarrhoea.

Rare: vomiting.

Very rare: ischemic colitis; Abdominal discomfort.

Hepatobiliary disorders:

Rare: Abnormal liver function (transaminases increased, alkaline phosphatase increased, gamma GT increased, blood bilirubin increased).

Skin and subcutaneous tissue disorders:

Uncommon: pruritus.

Uncommon: skin rash.

Rare: dry skin.

Rare: hyperhidrosis.

Rare: urticaria.

Very rare: fixed drug eruption.

Very rare: angioedema.

Very rare: skin disease.

Very rare: acute generalized exanthematous pustulosis.

Pathologies of the musculoskeletal system and connective tissue.

Not known: arthralgia.

Renal and urinary disorders:

Very rare: enuresis.

Very rare: dysuria.

Not known: urinary retention.

Systemic disorders and conditions relating to the administration site:

Common: weakness.

Uncommon: asthenia.

Uncommon: malaise.

Rare: edema.

Not known: itching after withdrawal.

Metabolism and nutrition disorders:

Rare: weight gain.

Reproductive system and breast disorders:

Not known: erectile dysfunction.

* Patient exposure was estimated from the calculation of sales data from IMS MIDAS. ^†These adverse reactions have been reported very rarely in post-marketing safety studies. A recent post-authorisation safety study (PASS) provided no evidence of an increased risk of myocardial infarction or cerebrovascular accident associated with the use of vasoconstrictors, including pseudoephedrine, for nasal decongestion. Reporting of suspected adverse reactions Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.

OVERDOSE

Symptoms In case of overdose the following may be observed: tachycardia, arrhythmias, hypertension, depressant or stimulant effects on the CNS. (sedation, apnea, collapse, insomnia, hallucinations, tremors, convulsions). These effects can be fatal. Symptoms observed after overdose of cetirizine are mainly associated with CNS effects or effects that might suggest an anticholinergic effect. Adverse events reported after taking at least 5 times the 10 mg dose of cetirizine are: confusion, diarrhea, dizziness, fatigue, headache, malaise, mydriasis, itching, restlessness, sedation, drowsiness, stupor, tachycardia, tremor and urinary retention. In case of overdose of pseudoephedrine, nausea, vomiting, mydriasis, anxiety, agitation, palpitations and reflex bradycardia may occur. Other possible effects are dysrhythmia, hypertensive crisis, intracerebral hemorrhage, myocardial infarction, psychosis, rhabbomyolysis, hypokalemia, and ischemic infarction of the intestine. In the case of overdose in children, drowsiness has been reported. Keep out of reach of children. In case of overdose, seek medical help or contact a poison control center immediately. Treatment Treatment, which should preferably take place in a hospital environment, must be symptomatic. If vomiting does not occur spontaneously it must be induced. Gastric lavage is recommended. There are no known antidotes. It is important to avoid the use of sympathomimetics. Hypertension can be controlled with α-blockers, possible tachycardia with β-blockers, convulsions with iv diazepam (or with diazepam administered rectally in the case of children). There is no specific antidote for cetirizine. Should overdose occur, symptomatic or supportive treatment is recommended. Following recent ingestion, gastric lavage is recommended. Cetirizine is not effectively eliminated by dialysis.

PREGNANCY AND BREASTFEEDING

REACTINE is contraindicated during pregnancy and breastfeeding. Pregnancy Very little clinical data on pregnancies exposed to treatment are available for cetirizine. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development. Breastfeeding Both cetirizine and pseudoephedrine are excreted in breast milk, therefore REACTINE should not be taken during breastfeeding. Cetirizine is excreted in breast milk at concentrations representing 25% to 90% of those measured in plasma, depending on the sampling time after administration.

EFFECTS ON DRIVING ABILITY

Cetirizine at recommended doses does not influence cognitive and motor functions; no effect on these abilities has been demonstrated with pseudoephedrine. However, due to its potential sedative action, caution should be exercised when driving or operating machinery. Objective measurements of driving ability, sleep latency and assembly line performance demonstrated no clinically relevant effects at the 10 mg dose of cetirizine. Patients intending to drive, engage in potentially dangerous activities or operate machinery should not exceed the dose of 10 mg of cetirizine and consider their response to the medicine. Patients should not drive, engage in potentially hazardous activities, or operate machinery if they feel drowsy or dizzy. In sensitive patients, concomitant use with alcohol or other CNS depressants may cause further reductions in alertness and impaired performance.