For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only

GENERIC NAME

Fexofenadine Hydrochloride

BRAND NAME

FEXIGRA Oral Suspension

QUALITATIVE AND QUANTITATIVE COMPOSITION

FEXIGRA Oral Suspension

Each 5 mL (one teaspoonful) contains:

Fexofenadine Hydrochloride IP………….. 30 mg

In a flavoured syrup base

Colour: Titanium Dioxide IP

DOSAGE FORM AND STRENGTH

Each 5 mL of suspension contains fexofenadine hydrochloride 30 mg

CLINICAL PARTICULARS

Therapeutic Indications

Fexofenadine hydrochloride oral suspension is indicated for relief of symptoms associated with allergic rhinitis in children 2 to 11 years of age, and uncomplicated skin manifestations of chronic idiopathic urticaria in children 6 months to 11 years of age.

Posology and Method of Administration

Shake well before using.

Use only with enclosed dosing cup.

Allergic Rhinitis

Children (2 to 11 years of age)

Recommended dose is 30 mg twice daily. A dose of 30 mg (5 mL in case of FEXIGRA Oral Suspension) once daily is recommended as the starting dose for paediatric patients with decreased renal function.

Adults and Children (aged 12 years and over)

Recommended dose is 120 mg once daily or 180 mg once daily. A dose of 60 mg once daily is recommended as the starting dose in patients with decreased renal function.

Chronic Idiopathic Urticaria

Children (6 months to 11 years of age)

Recommended dose is 30 mg (5 mL) twice daily for patients 2 to 11 years of age, and 15 mg (2.5 mL) twice daily for patients 6 months to less than 2 years of age.

For paediatric patients with decreased renal function, the recommended starting dose is 30 mg (5 mL) once daily for patients 2 to 11 years of age, and 15 mg (2.5 mL) once daily for patients 6 months to less than 2 years of age.

Adults and Children (aged 12 years and over)

Recommended dose is 180 mg once daily. A dose of 60 mg once daily is recommended as the starting dose in patients with decreased renal function.

Note: mL = millilitres

Contraindications

Fexofenadine suspension is contraindicated in patients with known hypersensitivity to any of the ingredients. Rare cases of hypersensitivity reactions with manifestations such as angioedema, chest tightness, dyspnea, flushing and systemic anaphylaxis have been reported.

Special Warnings and Precautions for Use

Drug Interactions

Co-administration of fexofenadine with erythromycin or ketoconazole resulted in no significant increases in QTc. Administration of an antacid containing aluminium or magnesium hydroxide gels should be 2 hours before or after administration of fexofenadine. No interaction between fexofenadine and omeprazole has been observed.

Drug Interaction with Erythromycin and Ketoconazole

Fexofenadine has been shown to exhibit minimal (ca. 5%) metabolism. However, co–administration of fexofenadine hydrochloride with either ketoconazole or erythromycin led to increased plasma concentrations of fexofenadine. Fexofenadine had no effect on the pharmacokinetics of either erythromycin or ketoconazole. In 2 separate studies in healthy adult subjects, fexofenadine hydrochloride 120 mg twice daily (240 mg total daily dose) was coadministered with either erythromycin 500 mg every 8 hours or ketoconazole 400 mg once daily under steady-state conditions to healthy adult subjects (n=24, each study). No differences in adverse events or QTc interval were observed when subjects were administered fexofenadine hydrochloride alone or in combination with either erythromycin or ketoconazole. The findings of these studies are summarized in the following table:

Table 1: Effects on Steady-State Fexofenadine Pharmacokinetics after 7 Days of Coadministration with Fexofenadine Hydrochloride 120 mg Every 12 Hours in Healthy Adult Subjects (n=24)

Concomitant Drug	CmaxSS (Peak plasma concentration)	AUCss(0-12h) (Extent of systemic exposure)
Erythromycin (500 mg every 8 hrs)	+82%	+109%
Ketoconazole (400 mg once daily)	+135%	+164%

The changes in plasma levels were within the range of plasma levels achieved in adequate and well-controlled clinical trials.

The mechanism of these interactions has been evaluated in in vitro, in situ, and in vivo animal models. These studies indicate that ketoconazole or erythromycin co-administration enhances fexofenadine gastrointestinal absorption. This observed increase in the bioavailability of fexofenadine may be due to transport-related effects, such as P-glycoprotein. In vivo animal studies also suggest that in addition to enhancing absorption, ketoconazole decreases fexofenadine gastrointestinal secretion, while erythromycin may also decrease biliary excretion.

Drug Interactions with Antacids

Administration of 120 mg of fexofenadine hydrochloride (2 × 60 mg capsule) within 15 minutes of an aluminium- and magnesium-containing antacid (Maalox^®) decreased fexofenadine AUC by 41% and C_max by 43%. Fexofenadine hydrochloride should not be taken closely in time with aluminium- and magnesium-containing antacids.

Interactions with Fruit Juices

Use in Special Populations

Patients with Renal Impairment

Based on increases in bioavailability and half-life, a dose of 60 mg once daily is recommended as the starting dose in adult patients with decreased renal function (mild, moderate or severe renal impairment). For pediatric patients with decreased renal function (mild, moderate or severe renal impairment), the recommended starting dose of fexofenadine hydrochloride is 30 mg once daily for patients 2 to 11 years of age and 15 mg once daily for patients 6 months to less than 2 years of age.

Patients with Hepatic Impairment

The pharmacokinetics of fexofenadine in subjects with hepatic disease did not differ substantially from that observed in healthy subjects.

Pregnant Women

Risk Summary

Fexofenadine hydrochloride oral suspension is not intended for use in females of reproductive potential; however, other formulations have been approved for use in adults. The available data from published literature and pharmacovigilance cases with fexofenadine hydrochloride use during pregnancy have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Animal reproduction studies were conducted in rats and rabbits with terfenadine, which is rapidly converted in vivo to fexofenadine. Estimated fexofenadine exposures were calculated and expressed relative to the maximum recommended human dose (MRHD) of fexofenadine hydrochloride. No adverse developmental effects were observed with oral administration of terfenadine to pregnant rats and rabbits during organogenesis at dose exposures up to 4 and 30 times, respectively, the human exposure at the MRHD of fexofenadine hydrochloride. Administration of terfenadine to rats 2 weeks prior to mating through weaning resulted in post-implantation loss and decreased postnatal growth and survival at maternal dose exposures greater than or equal to 3 times the human exposure at the MRHD of fexofenadine hydrochloride. Administration of fexofenadine hydrochloride to mice 2 weeks prior to mating through weaning resulted in no adverse developmental effects at exposures up to 15 times the human exposure at the MRHD.  

Lactating Women

It is not known if fexofenadine is excreted in human milk. There are no adequate and well-controlled studies in women during lactation. Because many drugs are excreted in human milk, caution should be exercised when fexofenadine hydrochloride is administered to females of reproductive potential. There is no information available on the effects of the drug on the breastfed infant or on milk production.

Paediatric Patients

The safety of fexofenadine hydrochloride at a dose of 30 mg twice daily has been demonstrated in 438 paediatric subjects (6 years to 11 years of age) in two placebo-controlled 2-week seasonal allergic rhinitis trials. The safety of fexofenadine hydrochloride at doses of 15 mg and 30 mg given once and twice a day has been demonstrated in 969 paediatric subjects (6 months to 5 years of age) with allergic rhinitis in three pharmacokinetic studies and three safety studies. The safety of fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in subjects (6 months to 11 years of age) is based on a cross-study comparison of the pharmacokinetics of fexofenadine hydrochloride in adult and paediatric subjects and on the safety profile of fexofenadine in both adult and pediatric subjects at doses equal to or higher than the recommended dose.

The effectiveness of fexofenadine hydrochloride for the treatment of seasonal allergic rhinitis in subjects (6 to 11 years of age) was demonstrated in 1 trial (n=411) in which fexofenadine hydrochloride tablets 30 mg twice daily significantly reduced total symptom scores compared with placebo, along with extrapolation of demonstrated efficacy in subjects aged 12 years and above, and the pharmacokinetic comparisons in adults and children. The effectiveness of fexofenadine hydrochloride 30 mg twice daily for the treatment of seasonal allergic rhinitis in patients (2 to 5 years of age) is based on the pharmacokinetic comparisons in adult and paediatric subjects and an extrapolation of the demonstrated efficacy of fexofenadine hydrochloride in adult subjects with this condition and the likelihood that the disease course, pathophysiology, and the drug’s effect are substantially similar in paediatric patients to those in adult patients. The effectiveness of fexofenadine hydrochloride for the treatment of chronic idiopathic urticaria in patients 6 months to 11 years of age is based on the pharmacokinetic comparisons in adults and children and an extrapolation of the demonstrated efficacy of fexofenadine hydrochloride in adults with this condition and the likelihood that the disease course, pathophysiology and the drug’s effect are substantially similar in children to that of adult patients. Administration of a 15 mg dose of fexofenadine hydrochloride to paediatric subjects (6 months to less than 2 years of age) and a 30 mg dose to paediatric subjects (2 to 11 years of age) produced exposures comparable with those seen with a dose of 60 mg administered to adults.

The safety and effectiveness of fexofenadine hydrochloride in paediatric patients under 6 months of age have not been established.

Geriatric Patients

This drug is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Effects on Ability to Drive and Use Machines

Based on the pharmacodynamic profile and reported adverse reactions, it is unlikely that fexofenadine hydrochloride will produce an effect on the ability to drive or use machines. In objective tests, fexofenadine has been shown to have no significant effects on central nervous system function. This means that patients may drive or perform tasks that require concentration. However, in order to identify sensitive people who, have an unusual reaction to medicinal products, it is advisable to check the individual response before driving or performing complicated tasks.

Undesirable Effects

Clinical Trials Experience

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 trials of another drug and may not reflect the rates observed in practice.

The safety data described below reflect exposure to fexofenadine hydrochloride in 5083 patients in trials for allergic rhinitis and chronic idiopathic urticaria. In these trials, 3010 patients 12 years of age and older with seasonal allergic rhinitis were exposed to fexofenadine hydrochloride at doses of 20 to 240 mg twice daily or 120 to 180 mg once daily. A total of 646 patients 6 to 11 years of age with seasonal allergic rhinitis were exposed to fexofenadine hydrochloride at doses of 15 to 60 mg twice daily. The duration of treatment in these trials was 2 weeks. A total of 534 patients 6 months to 5 years of age with allergic rhinitis were exposed to fexofenadine hydrochloride at doses of 15 to 30 mg twice daily. The duration of treatment in these trials ranged from 1 day to 2 weeks. There were 893 patients 12 years of age and older with chronic idiopathic urticaria exposed to fexofenadine hydrochloride at doses of 20 to 240 mg twice daily or 180 mg once daily. The duration of treatment in these trials was 4 weeks.

Seasonal Allergic Rhinitis

Adults

In placebo-controlled seasonal allergic rhinitis clinical trials in subjects 12 years of age and older, which included 2,461 subjects receiving fexofenadine hydrochloride capsules at doses of 20 mg to 240 mg twice daily, adverse events were similar in fexofenadine hydrochloride- and placebo-treated subjects. All adverse events that were reported by greater than 1% of subjects who received the recommended daily dose of fexofenadine hydrochloride (60 mg capsules twice daily), and that were more common with fexofenadine hydrochloride than placebo, are listed in Table 2.

In a placebo-controlled clinical study in the United States, which included 570 subjects aged 12 years and older receiving fexofenadine hydrochloride tablets at doses of 120 or 180 mg once daily, adverse events were similar in fexofenadine hydrochloride- and placebo-treated subjects. Table 1 also lists adverse experiences that were reported by greater than 2% of subjects treated with fexofenadine hydrochloride tablets at doses of 180 mg once daily and that were more common with fexofenadine hydrochloride than placebo.

The incidence of adverse events, including drowsiness, was not dose-related and was similar across subgroups defined by age, gender, and race.

Table 2: Adverse Events in Subjects Aged 12 Years and Older Reported in Placebo-controlled Seasonal Allergic Rhinitis Clinical Trials in the United States

Twice-daily dosing with fexofenadine hydrochloride tablets at rates of greater than 2%

Twice-daily dosing with fexofenadine hydrochloride capsules at rates of greater than 1%
Adverse reaction	Fexofenadine hydrochloride 60 mg Twice Daily (n=680) Frequency	Placebo Twice Daily (n=674) Frequency
Dysmenorrhea	1.5%	0.3%
Once-daily dosing with fexofenadine hydrochloride tablets at rates of greater than 2%
Adverse reaction	Fexofenadine hydrochloride 180 mg Once Daily	Placebo
	(n=283)	(n=293)
	Frequency	Frequency
Headache	10.3%	7.2%
Back Pain	2.5%	1.4%

The frequency and magnitude of laboratory abnormalities were similar in fexofenadine hydrochloride- and placebo-treated subjects.

Paediatric Patients

Table 3 lists adverse experiences in subjects aged 6 years to 11 years of age which were reported by greater than 2% of subjects treated with fexofenadine hydrochloride tablets at a dose of 30 mg twice daily in placebo-controlled seasonal allergic rhinitis studies in the United States and Canada that were more common with fexofenadine hydrochloride than placebo.

Table 3: Adverse Events Reported in Placebo-controlled Seasonal Allergic Rhinitis Studies in Paediatric Subjects Aged 6 Years to 11 Years in the United States and Canada at rates greater than 2%

Adverse reaction	Fexofenadine hydrochloride 30 mg Twice Daily (n=209) Frequency	Placebo (n=229) Frequency
Cough	3.8%	1.3%
Upper Respiratory Tract Infection	2.9%	0.9%
Pyrexia	2.4%	0.9%
Otitis Media	2.4%	0.0%

Table 4 lists adverse events in subjects 6 months to 5 years of age in three open single- and multiple-dose pharmacokinetic studies and three placebo-controlled safety studies with fexofenadine hydrochloride capsule content (484 subjects) and suspension (50 subjects) at doses of 15 mg (108 subjects) and 30 mg (426 subjects) given twice a day.

Table 4: Adverse Events Reported in Placebo-controlled Studies in Paediatric Subjects with Allergic Rhinitis Aged 6 Months to 5 Years of Age at Rates Greater Than 2%

Adverse reaction	Fexofenadine hydrochloride 15 mg Twice Daily (n=108) Frequency	Fexofenadine hydrochloride 30 mg Twice Daily (n=426) Frequency	Fexofenadine hydrochloride Total Twice Daily (n=534) Frequency	Placebo (n=430) Frequency
Vomiting	12.0%	4.2%	5.8%	8.6%
Diarrhea	3.7%	2.8%	3.0%	2.6%
Somnolence/Fatigue	2.8%	0.9%	1.3%	0.2%
Rhinorrhea	0.9%	2.1%	1.9%	0.9%

Chronic Idiopathic Urticaria

Adverse events reported by subjects (12 years of age and older) in placebo-controlled chronic idiopathic urticaria studies were similar to those reported in placebo-controlled seasonal allergic rhinitis studies.

In placebo-controlled chronic idiopathic urticaria clinical trials, which included 726 subjects (12 years of age and older) receiving fexofenadine hydrochloride tablets at doses of 20 to 240 mg twice daily, adverse events were similar in fexofenadine hydrochloride- and placebo-treated patients. Table 4 lists adverse experiences in subjects (aged 12 years and older), which were reported by greater than 2% of subjects treated with fexofenadine hydrochloride 60 mg tablets twice daily in controlled clinical studies in the United States and Canada and that were more common with fexofenadine hydrochloride than placebo.

In a placebo-controlled clinical study in the United States, which included 167 subjects (aged 12 years and older) receiving fexofenadine hydrochloride 180 mg tablets, adverse events were similar in fexofenadine hydrochloride- and placebo-treated subjects. Table 5 also lists adverse experiences that were reported by greater than 2% of subjects treated with fexofenadine hydrochloride tablets at doses of 180 mg once daily and that were more common with fexofenadine hydrochloride than placebo.

The safety of fexofenadine hydrochloride in the treatment of chronic idiopathic urticaria in paediatric patients (6 months to 11 years of age) is based on the safety profile of fexofenadine hydrochloride in adults and paediatric patients at doses equal to or higher than the recommended dose.

Table 5: Adverse Events Reported in Subjects 12 Years of Age and Older in Placebo-controlled Chronic Idiopathic Urticaria Studies

Twice-daily dosing with fexofenadine hydrochloride in studies in the United States and Canada at rates of greater than 2%
Adverse reaction	Fexofenadine hydrochloride 60 mg Twice Daily (n=191) Frequency	Placebo (n=183) Frequency
Dizziness	2.1%	1.1%
Back Pain	2.1%	1.1%
Stomach discomfort	2.1%	0.6%
Pain in extremity	2.1%	0.0%
Once-daily dosing with fexofenadine hydrochloride in a study in the United States at rates of greater than 2%
Adverse reaction	Fexofenadine hydrochloride 180 mg Once Daily (n=167) Frequency	Placebo (n=92) Frequency
Headache	4.8%	3.3%

The safety of fexofenadine hydrochloride in the treatment of chronic idiopathic urticaria in pediatric patients 6 months to 11 years of age is based on the safety profile of fexofenadine hydrochloride in adults and pediatric patients at doses equal to or higher than the recommended dose [see Use in Specific Populations].

Postmarketing Experience

In addition to the adverse reactions reported during clinical studies and listed above, the following adverse events have been identified during postapproval use of fexofenadine hydrochloride. Because these events 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. Events that have been reported rarely during postmarketing experience include: insomnia, nervousness, sleep disorders or paroniria, and hypersensitivity reactions (including anaphylaxis, urticaria, angioedema, chest tightness, dyspnea, flushing, pruritus, and rash).

Reporting of Side Effects

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the National Pharmacovigilance Programme of India by calling on 1800 180 3024 or report to Cipla Ltd. on 1800 267 7779. By reporting side effects, you can help provide more information on the safety of this product.

Overdose

Reports of fexofenadine hydrochloride overdose have been infrequent and contain limited information. However, dizziness, drowsiness, and dry mouth have been reported. Single doses of fexofenadine hydrochloride up to 800 mg (6 healthy subjects at this dose level), and doses up to 690 mg twice daily for 1 month (3 healthy subjects at this dose level) or 240 mg once daily for 1 year (234 healthy subjects at this dose level) were administered without the development of clinically significant adverse events as compared with placebo.

In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Following administration of terfenadine, haemodialysis did not effectively remove fexofenadine, the major active metabolite of terfenadine, from blood (up to 1.7% removed).

PHARMACOLOGICAL PROPERTIES

Mechanism of Action

Fexofenadine hydrochloride, the major active metabolite of terfenadine, is an antihistamine with selective peripheral H₁-receptor antagonist activity.

Both enantiomers of fexofenadine hydrochloride displayed approximately equipotent antihistaminic effects. Fexofenadine hydrochloride inhibited antigen-induced bronchospasm in sensitised guinea pigs and histamine release from peritoneal mast cells in rats. The clinical significance of these findings is unknown. In laboratory animals, no anticholinergic or alpha₁-adrenergic blocking effects were observed. Moreover, no sedative or other central nervous system effects were observed. Radiolabelled tissue distribution studies in rats indicated that fexofenadine does not cross the blood-brain barrier.

Pharmacodynamic Properties

Wheal and Flare

Human histamine skin wheal and flare studies following single and twice-daily doses of 20 and 40 mg fexofenadine hydrochloride demonstrated that the drug exhibits an antihistamine effect by 1 hour, achieves maximum effect at 2–3 hours, and an effect is still seen at 12 hours. There was no evidence of tolerance to these effects after 28 days of dosing. The clinical significance of these observations is unknown.

Histamine skin wheal and flare studies in subjects 7 to 12 years of age showed that following a single dose of 30 or 60 mg, antihistamine effect was observed at 1 hour and reached a maximum by 3 hours. Greater than 49% inhibition of wheal area, and 74% inhibition of flare area were maintained for 8 hours following the 30 mg and 60 mg dose.  

No statistically significant increase in mean QT_c interval compared with placebo was observed in 714 subjects with seasonal allergic rhinitis given fexofenadine hydrochloride capsules in doses of 60–240 mg twice daily for 2 weeks. Paediatric subjects from two placebo-controlled trials (n=855) treated with up to 60 mg fexofenadine hydrochloride twice daily demonstrated no significant treatment- or dose-related increases in QT_c.

In addition, no statistically significant increase in mean QT_c interval compared with placebo was observed in 40 healthy subjects given fexofenadine hydrochloride as an oral solution at doses up to 400 mg twice daily for 6 days, or in 230 healthy subjects given fexofenadine hydrochloride 240 mg once daily for 1 year. In subjects with chronic idiopathic urticaria, there were no clinically relevant differences for any ECG intervals, including QT_c, between those treated with fexofenadine hydrochloride 180 mg once daily (n=163) and those treated with placebo (n=91) for 4 weeks.

Pharmacokinetic Properties

The pharmacokinetics of fexofenadine hydrochloride in subjects with seasonal allergic rhinitis and subjects with chronic urticaria were similar to those in healthy subjects.

Absorption

Following oral administration of a 30 mg dose of Fexofenadine hydrochloride to healthy adult subjects, the mean C_max was 118.0 ng/mL and occurred at approximately 1.0 hour. The administration of 30 mg Fexofenadine hydrochloride with a high-fat meal decreased the AUC and the mean C_max by approximately 30 and 47%, respectively, in healthy adult subjects.

Distribution

Fexofenadine hydrochloride is 60–70% bound to plasma proteins, primarily albumin, and α₁-acid glycoprotein.

Metabolism

Approximately 5% of the total dose of fexofenadine hydrochloride was eliminated by hepatic metabolism.

Elimination

The mean elimination half-life of fexofenadine was 14.4 hours following administration of 60 mg twice daily in healthy subjects.

Human mass balance studies documented a recovery of approximately 80% and 11% of the [¹⁴C] fexofenadine hydrochloride dose in the faeces and urine, respectively. Because the absolute bioavailability of fexofenadine hydrochloride has not been established, it is unknown if the faecal component represents primarily unabsorbed drug or the result of biliary excretion.

Special Populations

Pharmacokinetics in renally and hepatically impaired subjects and geriatric subjects, obtained after a single dose of 80 mg fexofenadine hydrochloride, were compared to those from healthy subjects in a separate study of similar design.

Patients with Renal Impairment

In subjects with mild to moderate (creatinine clearance 41-80 mL/min) and severe (creatinine clearance 11-40 mL/min) renal impairment, peak plasma concentrations of fexofenadine were 87% and 111% greater, respectively, and mean elimination half-lives were 59% and 72% longer, respectively, than observed in healthy subjects. Peak plasma concentrations in subjects on dialysis (creatinine clearance ≤10 mL/min) were 82% greater and half-life was 31% longer than observed in healthy subjects. Based on increases in bioavailability and half-life, a dose of 60 mg once daily is recommended as the starting dose in adult patients with decreased renal function. For pediatric patients with decreased renal function, the recommended starting dose of fexofenadine hydrochloride is 30 mg once daily for patients 2 to 11 years of age and 15 mg once daily for patients 6 months to less than 2 years of age [see Posology and Method of Administration].

Patients with Hepatic Impairment

The pharmacokinetics of fexofenadine hydrochloride in subjects with hepatic impairment did not differ substantially from that observed in healthy subjects.

Pediatric Patients

A population pharmacokinetic analysis was performed with data from 77 pediatric subjects (6 months to 12 years of age) with allergic rhinitis and 136 adult subjects. The individual apparent oral clearance estimates of fexofenadine were on average 44% and 36% lower in pediatric subjects 6 to 12 years (n=14) and 2 to 5 years of age (n=21), respectively, compared to adult subjects.

Administration of a 15 mg dose of fexofenadine hydrochloride to pediatric subjects 6 months to less than 2 years of age and a 30 mg dose to pediatric subjects 2 to 11 years of age produced exposures comparable to those seen with a dose of 60 mg administered to adults.

Effect of Gender

Across several trials, no clinically significant gender-related differences were observed in the pharmacokinetics of fexofenadine.

NONCLINICAL PROPERTIES

Animal Toxicology or Pharmacology

Carcinogenesis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of fexofenadine was assessed using terfenadine studies with adequate fexofenadine exposure (based on plasma area-under-the-concentration vs time [AUC] values). No evidence of carcinogenicity was observed in an 18-month study in mice and in a 24-month study in rats at oral doses up to 150 mg/kg of terfenadine (which led to fexofenadine exposures that were approximately 3 and 5 times the exposure at the maximum recommended daily oral dose of fexofenadine hydrochloride in adults [180 mg] and children [60 mg], respectively).

In in vitro (Bacterial Reverse Mutation, CHO/HGPRT Forward Mutation, and Rat Lymphocyte Chromosomal Aberration assays) and in vivo (Mouse Bone Marrow Micronucleus assay) tests, fexofenadine hydrochloride revealed no evidence of mutagenicity.

In a male fertility study, rats were treated beginning 63 days prior to mating with terfenadine at doses of 50, 150, and 300 mg/kg/day (up to 4 times the exposure at the MRHD of fexofenadine hydrochloride). No adverse effects on male fertility were observed. In a fertility, pre- and postnatal development study, male and female rats were administered terfenadine at oral doses of 50, 150, and 300 mg/kg/day. Males were dosed 81 days prior to and through mating and females were dosed from 14 days prior to mating through weaning. Dose-related reductions in implants and increases in postimplantation losses were observed at oral doses of ≥150 mg/kg/day of terfenadine (≥3 times the exposure at the MRHD of fexofenadine hydrochloride). These adverse effects were associated with maternal toxicity with findings of decreased body weight gain and decreased food consumption. In a mouse dietary fertility study, male mice received fexofenadine hydrochloride 28 days prior to and throughout mating and female mice received fexofenadine hydrochloride 14 days prior to and throughout mating, gestation, and weaning. There was no effect on male or female fertility at average oral doses up to 4438 mg/kg/day (up to 13 times the exposure at the MRHD).

DESCRIPTION

Fexofenadine hydrochloride, the active ingredient in FEXIGRA Oral Suspension, is a histamine H₁ receptor antagonist with the chemical name (±)-4-[1 hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α, α-dimethyl benzeneacetic acid hydrochloride.

 

The molecular weight is 538.13 and the empirical formula is C₃₂H₃₉NO₄•HCl.

Fexofenadine hydrochloride is a white to off-white crystalline powder. It is freely soluble in methanol and ethanol, slightly soluble in chloroform and water, and insoluble in hexane. Fexofenadine hydrochloride is a racemate and exists as a zwitterion in aqueous media at physiological pH.

PHARMACEUTICAL PARTICULARS

Incompatibilities

Not applicable.

Shelf-life

As on the pack

Packaging Information

FEXIGRA Oral Suspension ………. Each bottle contains 100 mL of suspension

Storage and Handling Instructions

Store at a temperature not exceeding 30^oC. Protect from light and moisture. Keep out of the reach of children.

PATIENT COUNSELLING INFORMATION

• What is FEXIGRA Oral Suspension?

FEXIGRA Oral Suspension contains fexofenadine hydrochloride, which is a histamine H₁ receptor antagonist. It is indicated for the relief of symptoms associated with allergic rhinitis in children 2 to 11 years of age, and uncomplicated skin manifestations of chronic idiopathic urticaria in children 6 months to 11 years of age.

Do not take if you have an allergy to this drug

The products should not be used by patients who are hypersensitive to any of the ingredients.

Before you take FEXIGRA Oral Suspension, tell your HCP about other medications

If you are taking, have recently taken or might take any other medicine:

• Erythromycin (an antibiotic)
• Ketoconazole (a treatment for fungal infections)
• Indigestion remedies containing aluminum and magnesium may affect the action of fexofenadine hydrochloride by lowering the amount of medicinal product absorbed. It is recommended that you leave about 2 hours between the time that you take fexofenadine hydrochloride oral suspension and your indigestion remedy.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Do not take fexofenadine hydrochloride if you are pregnant, unless necessary. Fexofenadine hydrochloride oral suspension is not recommended during breast-feeding.

Driving and using machines

Fexofenadine hydrochloride oral suspension is unlikely to affect your ability to drive or operate machinery. However, you should check whether taking this suspension makes you feel sleepy or dizzy before driving or operating machinery.

• How to take FEXIGRA Oral Suspension

Patients and parents/carers of paediatric patients should be advised to shake the FEXIGRA Oral Suspension bottle well before each use. Use only with the enclosed dosing cup.

Allergic rhinitis

Children (2 to 11 years of age)

Recommended dose is 30 mg (5 mL) twice daily.

Allergic skin conditions (e.g. chronic urticaria)

Children (6 months to 11 years of age)

Recommended dose is 30 mg (5 mL) twice daily for patients 2 to 11 years of age, and 15 mg (2.5 mL) twice daily for patients 6 months to less than 2 years of age.

Note: mL = millilitres

Check with your doctor about dosage for  

• Adults 65 years of age and older
• Patients with kidney disease

Patients should be instructed to take FEXIGRA Oral Suspension only as prescribed. Do not exceed the recommended dose.

• What are the possible side effects?

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you get any of the following symptoms after taking this suspension, you should contact your doctor or pharmacist immediately as these may be signs of a serious allergic reaction:  swelling of the face, lips, tongue or throat and difficulty breathing.

The following side effects have also been reported:

• Common (may affect up to 1 in 10 people)
• Headache
• Drowsiness
• Feeling sick (nausea)
• Dizziness
• Dysmenorrhea
• Back Pain
• Cough
• Upper Respiratory Tract Infection
• Pyrexia
• Otitis Media
• Uncommon (may affect up to 1 in 100 people)
• Tiredness or sleepiness
• Not known (frequency cannot be estimated from the available data)
• Difficulty sleeping (insomnia)
• Sleeping disorders
• Bad dreams
• Nervousness
• Fast or irregular heartbeat
• Diarrhea
• Skin rash and itching
• Hives
• Serious allergic reaction, which can cause swelling of the face, lips, tongue or throat
• Difficulty breathing

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist or write to drugsafety@cipla.com. You can also report side effects directly via the National Pharmacovigilance Programme of India by calling on 1800 180 3024 or report to Cipla Ltd. on 1800 267 7779. By reporting side effects, you can help provide more information on the safety of this product.

• How to store FEXIGRA Oral Suspension

Do not take this medicine after the expiry date, which is stated on the blister and carton after EXP. The expiry date refers to the last day of the month. Protect from light. Keep out of the reach of children.

• General information about the safe and effective use of this drug

Tell your doctor before taking FEXIGRA Oral Suspension if you have

• problems with your liver or kidneys
• are elderly
• have heart problems, as fexofenadine, like other antihistamines, may cause your heart to beat faster (tachycardia) or you can feel your heart beating rapidly and irregularly (palpitations).
• What are the ingredients?

Each 5 mL (one teaspoonful) of FEXIGRA Oral Suspension contains fexofenadine hydrochloride 30 mg in a flavoured syrup base.

DETAILS OF THE MANUFACTURERS

Mfd. By Cipla Ltd.

Registered Office:

Cipla House, Peninsula Business Park,

Ganpatrao Kadam Marg

Lower Parel

Mumbai – 400 013, India

DETAILS OF PERMISSION OR LICENSE NUMBER WITH DATE

M.L. MNB/16/970 dated 10/03/17

DATE OF REVISION

07/10/2024