Leone

Leone is a third-generation non-sedative antihistamine indicated for the relief of symptoms associated with seasonal and perennial allergic rhinitis and uncomplicated skin manifestations of chronic idiopathic urticaria. It was developed from the second-generation antihistamine cetirizine. Leone is the R-enantiomer of the cetirizine racemate. Leone is an inverse agonist that decreases activity at histamine H1 receptors. This in turn prevents the release of other allergy chemicals and increased blood supply to the area, and provides relief from the typical symptoms of hay fever. It does not prevent the actual release of histamine from mast cells. Leone was approved by the United States Food and Drug Administration on May 25, 2007 and is marketed under the brand Leone® by sanofi-aventis U.S. LLC.

Seasonal Allergic Rhinitis

Leone dihydrochloride is indicated for the relief of symptoms associated with seasonal allergic rhinitis in adults and children 2 years of age and older.

Perennial Allergic Rhinitis

Leone dihydrochloride is indicated for the relief of symptoms associated with perennial allergic rhinitis in adults and children 6 months of age and older.

Chronic Idiopathic Urticaria

Leone dihydrochloride is indicated for the treatment of the uncomplicated skin manifestations of chronic idiopathic urticaria in adults and children 6 years of age and older.

Leone is an antihistamine that reduces the effects of natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Leone is used to treat symptoms of year-round (perennial) allergies in adults and children who are at least 6 months old. It is also used to treat symptoms of seasonal allergies in adults and children who are at least 2 years old.

Leone is also used to treat itching and swelling caused by chronic urticaria (hives) in adults and children who are at least 6 months old.

Leone may also be used for purposes not listed in this medication guide.

Leone is available as 2.5 mg/5 mL (0.5 mg/mL) oral solution and as 5 mg breakable (scored) tablets, allowing for the administration of 2.5 mg, if needed. Leone can be taken without regard to food consumption.

Adults And Children 12 Years Of Age and Older

The recommended dose of Leone is 5 mg (1 tablet or 2 teaspoons [10 mL] oral solution) once daily in the evening. Some patients may be adequately controlled by 2.5 mg (½ tablet or 1 teaspoon [5 mL] oral solution) once daily in the evening.

Children 6 To 11 Years Of Age

The recommended dose of Leone is 2.5 mg (½ tablet or 1 teaspoon [5 mL] oral solution) once daily in the evening. The 2.5 mg dose should not be exceeded because the systemic exposure with 5 mg is approximately twice that of adults.

Children 6 Months To 5 Years Of Age

The recommended initial dose of Leone is 1.25 mg (½ teaspoon oral solution) [2.5mL] once daily in the evening. The 1.25 mg once daily dose should not be exceeded based on comparable exposure to adults receiving 5 mg.

Dose Adjustment For Renal And Hepatic Impairment

In adults and children 12 years of age and older with:

• Mild renal impairment (creatinine clearance [CLCR] = 50-80 mL/min): a dose of 2.5 mg once daily is recommended;
• Moderate renal impairment (CLCR = 30-50 mL/min): a dose of 2.5 mg once every other day is recommended;
• Severe renal impairment (CLCR = 10-30 mL/min): a dose of 2.5 mg twice weekly (administered once every 3-4 days) is recommended;
• End-stage renal disease patients (CLCR < 10 mL/min) and patients undergoing hemodialysis should not receive Leone.

No dose adjustment is needed in patients with solely hepatic impairment. In patients with both hepatic impairment and renal impairment, adjustment of the dose is recommended.

How supplied

Dosage Forms And Strengths

Leone oral solution is a clear, colorless liquid containing 0.5 mg of Leone dihydrochloride per mL.

Leone tablets are white, film-coated, oval-shaped, scored, imprinted (with the letter Y in red color on both halves of the scored tablet) and contain 5 mg Leone dihydrochloride.

Storage And Handling

Leone tablets are white, film-coated, oval-shaped, scored, imprinted (with the letter Y in red color on both halves of the scored tablet) and contain 5 mg Leone dihydrochloride. They are supplied in unit of use HDPE bottles.

90 Tablets (NDC 50474-920-90)

Leone oral solution is a clear, colorless liquid containing 0.5 mg of Leone dihydrochloride per mL.

Oral Solution in 5 oz polypropylene bottles (

Storage

Store at 20 to 25°C (68 to 77°F); excursions permitted to 15 to 30°C (59 to 86°F).

Manufactured for: UCB, Inc., Smyrna, GA 30080. Revised: June 2016

See also:
What is the most important information I should know about Leone?

You should not use this medication if you are allergic to Leone or cetirizine (Zyrtec).

Do not take Leone if you have end-stage kidney disease or if you are on dialysis. Any child younger than 12 years old with kidney disease should not take Leone.

Before taking Leone, tell your doctor if you have liver disease, kidney disease, or gallbladder problems.

It is very important not to give a child more than the prescribed dose of this medication. A child's body absorbs twice as much of the same dose size of Leone as an adult's body.

Call your doctor if your symptoms do not improve, if they get worse, or if you also have a fever.

Use Leone solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Leone solution by mouth with or without food. Take it in the evening unless your doctor tells you otherwise.
• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.
• If you miss a dose of Leone solution, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Leone solution.

Leone is used to treat symptoms of allergic conditions such as allergic fever (hay fever), year-round allergies like dust or pet allergies and chronic nettle rash.

See also:
What other drugs will affect Leone?

Drug interaction studies have been performed with racemic cetirizine.

Antipyrine, Azithromycin, Cimetidine, Erythromycin, Ketoconazole, Theophylline and Pseudoephedrine: Pharmacokinetic interaction studies performed with racemic cetirizine demonstrated that cetirizine did not interact with antipyrine, pseudoephedrine, erythromycin, azithromycin, ketoconazole and cimetidine. There was a small decrease (approximately 16%) in the clearance of cetirizine caused by theophylline 400 mg dose. It is possible that higher theophylline doses could have a greater effect.

Interactions with Other Medicaments:

The extent of absorption of Leone is not reduced with food, although the rate of absorption is decreased.

In sensitive patients the simultaneous administration of cetirizine or Leone and alcohol or other CNS depressants, may have effects on the central nervous system, although it has been shown that the racemate cetirizine does not potentiate the effect of alcohol.

See also:
What are the possible side effects of Leone?

Use of Leone has been associated with somnolence, fatigue, asthenia, and urinary retention.

Clinical Trials Experience

The safety data described below reflect exposure to Leone in 2708 patients with seasonal or perennial allergic rhinitis or chronic idiopathic urticaria in 14 controlled clinical trials of 1 week to 6 months duration.

The short-term (exposure up to 6 weeks) safety data for adults and adolescents are based upon eight clinical trials in which 1896 patients (825 males and 1071 females aged 12 years and older) were treated with Leone 2.5, 5, or 10 mg once daily in the evening.

The short-term safety data from pediatric patients are based upon two clinical trials in which 243 children with seasonal or perennial allergic rhinitis (162 males and 81 females 6 to 12 years of age) were treated with Leone 5 mg once daily for 4 to 6 weeks, one clinical trial in which 114 children (65 males and 49 females 1 to 5 years of age) with allergic rhinitis or chronic idiopathic urticaria were treated with Leone 1.25 mg twice daily for 2 weeks, and one clinical trial in which 45 children (28 males and 17 females 6 to 11 months of age) with symptoms of allergic rhinitis or chronic urticaria were treated with Leone 1.25 mg once daily for 2 weeks.

The long-term (exposure of 4 or 6 months) safety data in adults and adolescents are based upon two clinical trials in which 428 patients (190 males and 238 females) with allergic rhinitis were exposed to treatment with Leone 5 mg once daily. Long term safety data are also available from an 18-month trial in 255 Leone-treated subjects 12-24 months of age.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice.

Adults and Adolescents 12 years of Age and Older

In studies up to 6 weeks in duration, the mean age of the adult and adolescent patients was 32 years, 44% of the patients were men and 56% were women, and the large majority (more than 90%) was Caucasian.

In these trials 43% and 42% of the subjects in the Leone 2.5 mg and 5 mg groups, respectively, had at least one adverse event compared to 43% in the placebo group.

In placebo-controlled trials of 1-6 weeks in duration, the most common adverse reactions were somnolence, nasopharyngitis, fatigue, dry mouth, and pharyngitis, and most were mild to moderate in intensity. Somnolence with Leone showed dose ordering between tested doses of 2.5, 5 and 10 mg and was the most common adverse reaction leading to discontinuation (0.5%).

Table 1 lists adverse reactions that were reported in greater than or equal to 2% of subjects aged 12 years and older exposed to Leone 2.5 mg or 5 mg in eight placebo-controlled clinical trials and that were more common with Leone than placebo.

Table 1 : Adverse Reactions Reported in ≥ 2%* of Subjects Aged 12 Years and Older Exposed to Leone 2.5 mg or 5 mg Once Daily in Placebo-Controlled Clinical Trials 1-6 Weeks in Duration

Additional adverse reactions of medical significance observed at a higher incidence than in placebo in adults and adolescents aged 12 years and older exposed to Leone are syncope (0.2%) and weight increased (0.5%).

Pediatric Patients 6 To 12 Years Of Age

A total of 243 pediatric patients 6 to 12 years of age received Leone 5 mg once daily in two short-term placebo controlled double-blind trials. The mean age of the patients was 9.8 years, 79 (32%) were 6 to 8 years of age, and 50% were Caucasian. Table 2 lists adverse reactions that were reported in greater than or equal to 2% of subjects aged 6 to 12 years exposed to Leone 5 mg in placebo-controlled clinical trials and that were more common with Leone than placebo.

Table 2 : Adverse Reactions Reported in ≥ 2%* of Subjects Aged 6-12 Years Exposed to Leone 5 mg Once Daily in Placebo-Controlled Clinical Trials 4 and 6 Weeks in Duration

Pediatric Patients 1 To 5 Years Of Age

A total of 114 pediatric patients 1 to 5 years of age received Leone 1.25 mg twice daily in a two week placebo-controlled double-blind safety trial. The mean age of the patients was 3.8 years, 32% were 1 to 2 years of age, 71% were Caucasian and 18% were Black. Table 3 lists adverse reactions that were reported in greater than or equal to 2% of subjects aged 1 to 5 years exposed to Leone 1.25 mg twice daily in the placebo-controlled safety trial and that were more common with Leone than placebo.

Table 3 : Adverse Reactions Reported in ≥ 2%* of Subjects Aged 1-5 Years Exposed to Leone 1.25 mg Twice Daily in a 2-Week Placebo-Controlled Clinical Trial

Pediatric Patients 6 To 11 Months Of Age

A total of 45 pediatric patients 6 to 11 months of age received Leone 1.25 mg once daily in a two week placebo-controlled double-blind safety trial. The mean age of the patients was 9 months, 51% were Caucasian and 31% were Black. Adverse reactions that were reported in more than 1 subject (i.e. greater than or equal to 3% of subjects) aged 6 to 11 months exposed to Leone 1.25 mg once daily in the placebo-controlled safety trial and that were more common with Leone than placebo included diarrhea and constipation which were reported in 6 (13%) and 1 (4%) and 3 (7%) and 1 (4%) children in the Leone and placebo-treated groups, respectively.

Long-Term Clinical Trials Experience

In two controlled clinical trials, 428 patients (190 males and 238 females) aged 12 years and older were treated with Leone 5 mg once daily for 4 or 6 months. The patient characteristics and the safety profile were similar to that seen in the short-term studies. Ten (2.3%) patients treated with Leone discontinued because of somnolence, fatigue or asthenia compared to 2 ( < 1%) in the placebo group.

There are no long term clinical trials in children below 12 years of age with allergic rhinitis or chronic idiopathic urticaria.

Laboratory Test Abnormalities

Elevations of blood bilirubin and transaminases were reported in < 1% of patients in the clinical trials. The elevations were transient and did not lead to discontinuation in any patient.

Post-Marketing Experience

In addition to the adverse reactions reported during clinical trials and listed above, adverse reactions have also been identified during post-approval use of Leone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions of hypersensitivity and anaphylaxis, increased appetite, angioedema, fixed drug eruption, pruritus, rash and urticaria, convulsion, paraesthesia, dizziness, tremor, dysgeusia, vertigo, movement disorders (including dystonia and oculogyric crisis), aggression and agitation, hallucinations, depression, insomnia, suicidal ideation, visual disturbances, blurred vision, palpitations, tachycardia, dyspnea, nausea, vomiting, hepatitis, dysuria, urinary retention, myalgia, arthralgia, and edema have been reported.

Besides these reactions reported under treatment with Leone, other potentially severe adverse events have been reported from the post-marketing experience with cetirizine. Since Leone is the principal pharmacologically active component of cetirizine, one should take into account the fact that the following adverse events could also potentially occur under treatment with Leone: orofacial dyskinesia, severe hypotension, cholestasis, glomerulonephritis, still birth, tic, myoclonus, and extrapyramidal symptoms.