Reactine Allergy & sinus 5mg/120mg

No clinically significant drug interactions have been found with cetirizine hydrochloride and theophylline, pseudoephedrine hydrochloride, cimetidine, erythromycin and ketoconazole. Epidemiologic data suggests that there also would not be interaction with other macrolide antibiotics or imidazole antifungals. In clinical trials, cetirizine hydrochloride has been safely administered with beta-agonists, non-steroidal anti-inflammatory drugs, oral contraceptives, narcotic analgesics, corticosteroids, H₂-antagonists, cephalosporins, penicillins, thyroid hormones and thiazide diuretics.

Based on: (a) its relatively low level of metabolic elimination, (b) no effect on corrected QT intervals at plasma concentrations three times the maximal therapeutic levels, and (c) no apparent interactions with ketoconazole or erythromycin, cetirizine hydrochloride is unlikely to have clinically significant interactions with other macrolides such as clarithromycin or other imidazole antifungals such as itraconazole in patients with normal renal and hepatic function. Although no data with these other drugs are available at the present time, there is no epidemiological evidence (the safety database comprised 6490 patients evaluated in U.S. and Canadian studies) of interactions between macrolide antibiotics and/or imidazole antifungals taken orally, and cetirizine hydrochloride/hydroxyzine. The epidemiologic data do not suggest an increase of adverse events, cardiac or non-cardiac, in patients treated with cetirizine hydrochloride and concomitant macrolide or imidazole antifungal medication.

Monoamine oxidase (MAO) inhibitors potentiate effects of sympathomimetic drugs such as pseudoephedrine hydrochloride. When sympathomimetic drugs are given to patients receiving MAO inhibitors, hypertensive crises may result. Pseudoephedrine hydrochloride should therefore be avoided in patients receiving drugs with MAO inhibiting activity. Pseudoephedrine hydrochloride may reduce the antihypertensive effects of methyldopa, mecamylamine, guanethidine, reserpine, and veratrum alkaloids. Beta adrenergic blocking agents may also interact with sympathomimetics. Increased ectopic pacemaker activity can occur when pseudoephedrine hydrochloride is used concomitantly with digitalis. Therefore, use of REACTINE ALLERGY & SINUS should be avoided in patients on digitalis. The antibacterial agent, furazolidone, is known to cause a dose-related inhibition of MAO. Although there are no reports of a hypertensive crisis caused by the concurrent administration of pseudoephedrine hydrochloride and furazolidone, they should not be taken together. Care should be taken in the administration of REACTINE ALLERGY & SINUS concomitantly with other sympathomimetic amines because combined effects on the cardiovascular system may be harmful to the patient (see Contraindications). Antacids increase the rate of pseudoephedrine absorption; kaolin decreases it.

Interaction studies with cetirizine hydrochloride and alcohol or diazepam indicate that cetirizine hydrochloride does not increase alcohol-induced or diazepam-induced impairment of motor and mental performance.

The recommended dose of REACTINE ALLERGY & SINUS (cetirizine hydrochloride/pseudoephedrine hydrochloride) is one tablet every 12 hours. REACTINE ALLERGY & SINUS may be given with or without food.

In patients with moderate hepatic and/or renal impairment, a dose of one tablet once daily is recommended.

nausea, pharnyngitis, appetite increased, dyspepsia, abdominal pain, diarrhea, flatulence, constipation, vomiting, stomatitis ulcerative, tongue disorder, tooth caries aggravated, stomatitis, tongue discoloration, tongue edema, gastritis, hemorrhage rectum, hemorrhoids, melena, hepatic function abnormal.

Occasional instances of transient, reversible hepatic transaminase elevations have occurred during cetirizine hydrochloride therapy, without evidence of jaundice, hepatitis or other clinical findings.

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

In controlled clinical trials, adverse reactions reported in more than 1% of the patients receiving the combination cetirizine/pseudoephedrine, were not different from those reported for cetirizine or pseudoephedrine alone. They included: dry mouth, headache, insomnia, somnolence, asthenia, tachycardia, nervousness, dizziness, vertigo, and nausea. Sympathomimetic drugs have also been associated with certain untoward reactions, including fear, anxiety, tenseness, restlessness, tremor, weakness, pallor, respiratory difficulty, dysuria, hallucinations, convulsions, CNS depression, arrhythmias and cardiovascular collapse with hypotension.

Hypersensitivity reactions, including skin reactions and angioedema, may occur.

eye abnormality, vision abnormal, eye pain, conjunctivitis, xerophthalmia, glaucoma, ocular hemorrhage.

taste perversion, taste loss, parosmia.

lymphadenopathy.

thyroid disorder.

weight increase, back pain, malaise, pain, chest pain, fever, asthenia, edema generalized, edema periorbital, edema peripheral, rigors, edema legs, face edema, hot flushes, abdomen enlarged, allergic reaction, nasal polyps.

In post-marketing experience the following additional rare, but potential severe adverse events have been reported: hemolytic anemia, thrombocytopenia, orofacial dyskinesia, severe hypotension, anaphylaxis, hepatitis, glomerulonephritis, stillbirth, and cholestasis. In addition, isolated cases of the following adverse drug reactions have been reported: convulsions, syncope, aggression, and hypersensitivity.

Pseudoephedrine hydrochloride may cause mild CNS stimulation in hypertensive patients. As with other sympathomimetic amines, CNS stimulation, muscular weakness, tightness in the chest and syncope may also be encountered. Nervousness, excitability, restlessness, dizziness, weakness, or insomnia may occur. Headache, nausea, drowsiness, tachycardia, palpitation, pressor activity, and cardiac arrhythmias have been reported. Sympathomimetic drugs have also been associated with other untoward effects such as fear, anxiety, confusion, tenseness, tremor, hallucinations, seizures, dry mouth, difficulty in micturition, vomiting, pallor, respiratory difficulty, dysuria, fixed drug eruption, and cardiovascular collapse.

dysmenorrhea, menstrual disorder, breast pain female, intermenstrual bleeding, leukorrhea, menorrhagia, pregnancy unintended, vaginitis, testes disorder.

depression, emotional lability, concentration impaired, anxiety, depersonalization, paroniria, thinking abnormal, agitation, amnesia, libido decreased, euphoria.

fatigue, dizziness, insomnia, nervousness, paresthesia, confusion, hyperkinesia, hypertonia, migraine, tremor, vertigo, cramps legs, ataxia, dysphonia, coordination abnormal, hyperesthesia, hypoesthesia, myelitis, paralysis, ptosis, speech disorder, twitching, visual field defect.

polyuria, urinary tract infection, cystitis, dysuria, hematuria, urine abnormal.

myalgia, arthralgia, bone disorder, arthrosis, tendon disorder, arthritis, muscle weakness.

earache, tinnitus, deafness, ototoxicity.

epistaxis, rhinitis, coughing, respiratory disorder bronchospasm, dyspnea, upper respiratory tract infection, hyperventilation, sinusitis, sputum increased, bronchitis, pneumonia.

pruritus, rash, skin disorder, skin dry, urticaria, acne, dermatitis, rash erythematous, sweating increased, alopecia, angioedema, furunculosis, bullous eruption, eczema, hyperkeratosis, hypertrichosis, photosensitivity reaction, photosensitivity toxic reaction, rash maculopapular, seborrhea, purpura.

anorexia, urinary retention, flushing, saliva increased.

healing impaired, herpes simplex infection, infection fungal, infection viral.

The following events were observed infrequently (equal to or less than 2%), in 3982 patients who received cetirizine hydrochloride in worldwide trials, including an open study of 6 months duration; a causal relationship with cetirizine hydrochloride administration has not been established.

thirst, edema, dehydration, diabetes mellitus.

palpitation, tachycardia, hypertension, arrhythmia, cardiac failure.

REACTINE ALLERGY & SINUS Extended Release Tablets (cetirizine hydrochloride 5 mg/pseudoephedrine hydrochloride 120 mg) are indicated for the relief of symptoms associated with seasonal allergic rhinitis and perennial allergic rhinitis. Symptoms treated effectively include: sneezing, rhinorrhea, post nasal discharge, tearing and redness of the eyes and nasal congestion.

REACTINE ALLERGY & SINUS Extended Release Tablets are indicated for the relief of symptoms associated with seasonal allergic rhinitis and perennial allergic rhinitis. Symptoms treated effectively include: sneezing, rhinorrhea, post nasal discharge, tearing and redness of the eyes and nasal congestion. Refer to Warnings and Precautions for additional information regarding pediatric patients.

In elderly patients, sympathomimetics are more likely to cause adverse reactions such as confusion, hallucination, convulsions, and/or CNS depression.

Cetirizine hydrochloride was well tolerated by patients aged 65 and over. Clearance of cetirizine hydrochloride is reduced in proportion to creatinine clearance. In patients whose creatinine clearance is reduced (i.e., those with moderate renal impairment), a starting dose of 5 mg/day (one REACTINE ALLERGY & SINUS tablet) is recommended.

Pseudoephedrine is incompletely metabolized (less than 1%) in the liver by N-demethylation to an inactive metabolite. The drug and its metabolite are excreted in urine; 55-96% of a dose is excreted unchanged. Therefore, pseudoephedrine may accumulate in patients with renal insufficiency.

Occasional instances of liver function test (transaminase) elevations have occurred during cetirizine hydrochloride therapy. This incidence was 1.6% in the short-term trials and 4.4% in the 6 month trials. These liver enzyme elevations, mainly ALT, were generally reversible. There was no evidence of jaundice or hepatitis, and the clinical significance is presently unknown. Consequently, cetirizine hydrochloride should be used with caution in patients with pre-existing liver disease. In patients with moderate hepatic impairment, a starting dose of 5 mg is recommended.

The effect of hepatic impairment on pseudoephedrine hydrochloride pharmacokinetics is unknown.

Studies using objective measurements have shown no effect of cetirizine hydrochloride on cognitive function, motor performance or sleep latency in healthy volunteers. However, in clinical trials the appearance of some CNS effects, particularly somnolence, have been observed. If drowsiness occurs, do not drive or operate machinery.

Sympathomimetics should be used with caution in patients with stenosing peptic ulcer, pyloroduodenal obstruction, prostatic hypertrophy, or bladder neck obstruction, cardiovascular disease, arrhythmia, tachycardia, hypertension, hyperthyroidism, increased intraocular pressure, renal or hepatic insufficiency or diabetes mellitus. Sympathomimetics should be used with caution in patients receiving decongestants, appetite suppressants, psychostimulants (such as amphetamines), tricyclic antidepressants, and digitalis. Sympathomimetics may cause central nervous system (CNS) stimulation and convulsions or cardiovascular collapse with accompanying hypotension.

REACTINE ALLERGY & SINUS contains a fixed dose of pseudoephedrine hydrochloride 120 mg in an extended release formulation. This dose of pseudoephedrine hydrochloride is not recommended for pediatric patients under 12 years of age. The safety and effectiveness of REACTINE ALLERGY & SINUS in pediatric patients under the age of 12 years has not been established.

There are no adequate and well-controlled studies in pregnant women. Until such data become available, REACTINE ALLERGY & SINUS (cetirizine hydrochloride/pseudoephedrine hydrochloride) should not be used during pregnancy, unless advised otherwise by a physician.

Cetirizine has been reported to be excreted in human breast milk. For pseudoephedrine hydrochloride administered alone, about 0.5% of the dose has been reported to be excreted in human breast milk. Because cetirizine and pseudoephedrine are excreted in milk, use of REACTINE ALLERGY & SINUS in nursing mothers is not recommended.

Hepatic Insufficiency/Renal Insufficiency: In patients with mild to moderate hepatic and renal impairment, total body clearance of cetirizine hydrochloride is reduced and AUC and half-life increased by about 2 to 3 fold. Clearance is reduced in proportion to the decline in creatinine clearance. Plasma levels are unaffected by hemodialysis. The plasma elimination half-life in dialysis patients is approximately 20 hours and the plasma AUC is increased by about threefold.

Plasma protein binding of cetirizine hydrochloride is 93% in the concentration range observed in clinical studies.

The bioavailability of cetirizine hydrochloride and pseudoephedrine hydrochloride from REACTINE ALLERGY & SINUS Extended Release Tablets is not significantly different from that achieved with separate administration of cetirizine hydrochloride 5 mg tablets and pseudoephedrine hydrochloride 120 mg extended release caplets. Co-administration of cetirizine hydrochloride and pseudoephedrine hydrochloride does not significantly affect the bioavailability of either component.

Following a single dose of the REACTINE ALLERGY & SINUS Tablet, cetirizine hydrochloride was rapidly absorbed and produced a mean peak plasma concentration (Cmax) of 114 ng/mL at a time (Tmax) 2.2 hours postdose. Pseudoephedrine hydrochloride produced a mean peak plasma concentration of 309 ng/mL at 4.4 hours postdose.

When healthy volunteers were administered multiple doses of the REACTINE ALLERGY & SINUS Tablet to reach steady state concentrations (cetirizine hydrochloride 5 mg/pseudoephedrine hydrochloride 120 mg twice daily for seven days), a mean peak plasma concentration (Cmax) of 178 ng/mL was observed for cetirizine and 526 ng/mL for pseudoephedrine.

Food had no significant effect on the extent of cetirizine hydrochloride absorption (AUC), but Tmax was delayed by 1.8 hours and Cmax was decreased by 30%. Food had no significant effect on the pharmacokinetics of pseudoephedrine hydrochloride. REACTINE ALLERGY & SINUS Tablets may be given with or without food.

Cetirizine hydrochloride, an active human metabolite of hydroxyzine, is a histamine H₁ receptor antagonist anti-allergic compound; its principal effects are mediated via selective inhibition of peripheral H₁ receptors. Cetirizine hydrochloride is distinguished from other histamine H₁ receptor antagonists by the presence of a carboxylic acid function. This difference may be partly responsible for the selectivity of cetirizine hydrochloride seen in pharmacologic models and its distinctive pharmacokinetic properties in humans.

After administration of the REACTINE ALLERGY & SINUS Tablet, the mean elimination half-life of cetirizine was 7.9 hours and the mean elimination half-life of pseudoephedrine was 6.0 hours.

See Hepatic Insufficiency.

In adults, cetirizine hydrochloride is less extensively metabolized than other antihistamines and approximately 60% of an administered dose is excreted unchanged in 24 hours. The high bioavailability associated with generally low inter-subject variation in blood levels is attributable primarily to low first-pass metabolism. Only one metabolite has been identified in humans—the product of oxidative dealkylation of the terminal carboxymethyl group. The antihistaminic activity of this metabolite is negligible.

The antihistaminic activity of cetirizine hydrochloride has been well documented in a variety of animal and human models. In vivo animal models have shown negligible anticholinergic or antiserotonergic activity. In vitro receptor binding studies have detected no measurable affinity for other than H₁ receptors. Autoradiographic studies have shown negligible penetration into the brain. Systemically administered cetirizine does not significantly occupy cerebral H₁ receptors. Several studies involving objective and subjective tests in healthy volunteers have demonstrated that cetirizine hydrochloride at doses up to 10 mg did not significantly differ from placebo with respect to CNS impairment, daytime drowsiness, reaction times, mental alertness, task performance, objective CNS depression and various other tests of cognitive function.

Cetirizine hydrochloride does not exacerbate asthma and is effective in a variety of histamine mediated disorders. In adults, oral doses of 5-20 mg in humans strongly inhibit the skin wheal and flare response caused by the intradermal injection of histamine. The onset of activity occurs within 20 (50% of subjects) to 60 (95% of subjects) minutes and persists for at least 24 hours following a single dose. The effects of intradermal injection of various other mediators or histamine releasers as well as components of the allergic inflammatory response to cutaneous antigen challenge are also inhibited.

Pseudoephedrine hydrochloride is an orally active sympathomimetic amine and is recognized as an effective agent for the relief of nasal congestion due to allergic rhinitis. Pseudoephedrine acts directly on α-adrenergic receptors in the mucosa of the respiratory tract producing vasoconstriction which results in shrinkage of swollen nasal mucous membranes, reduction of tissue hyperemia, edema, and nasal congestion, and an increase in nasal airway patency. Drainage of sinus secretions is increased and obstructed eustachian ostia may be opened. Pseudoephedrine produces peripheral effects similar to those of ephedrine and has the potential for excitatory side effects.