APREPITANT ETHYPHARM 80 MG HARD CAPSULES - summary of medicine characteristics

Aprepitant Ethypharm 80 mg hard capsules

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 80 mg capsule contains 80 mg of aprepitant.

Excipient with known effect

Each capsule contains 80 mg of sucrose (in the 80 mg capsule).

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Hard capsule.

The 80 mg capsule is size 2 capsule and has an opaque white cap and an opaque white body printed with “80 mg” in black ink.

4.1 Therapeutic indications

Prevention nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy in adults and adolescents from the age of 12.

Aprepitant Ethypharm 125 mg/80 mg is given as part of combination therapy (see section 4.2).

4.2 Posology and method of administration

Posology

Adults

Aprepitant Ethypharm is given for 3 days as part of a regimen that includes a corticosteroid and a 5-HT3 antagonist. The recommended dose is 125 mg orally once daily one hour before start of chemotherapy on Day 1 and 80 mg orally once daily on Days 2 and 3 in the morning.

The following regimens are recommended in adults for the prevention of nausea and vomiting associated with emetogenic cancer chemotherapy:

Highly Emetogenic Chemotherapy Regimen

Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1 and in the morning on Days 2 to 4. The dose of dexamethasone accounts for active substance interactions.

Moderately Emetogenic Chemotherapy Regimen

Dexamethasone should be administered 30 minutes prior to chemotherapy treatment on Day 1. The dose of dexamethasone accounts for active substance interactions.

Paediatric population

Adolescents (aged 12 through 17 years)

Aprepitant Ethypharm is given for 3 days as part of a regimen that includes a 5-HT3 antagonist. The recommended dose of capsules of Aprepitant Ethypharm is 125 mg orally on Day 1 and 80 mg orally on Days 2 and 3. Aprepitant Ethypharm is administered orally 1 hour prior to chemotherapy on Days 1, 2 and 3. If no chemotherapy is given on Days 2 and 3, Aprepitant Ethypharm should be administered in the morning. See the Summary of Product Characteristics (SmPC) for the selected 5-HT3 antagonist for appropriate dosing information. If a corticosteroid, such as dexamethasone, is co-administered with Aprepitant Ethypharm, the dose of the corticosteroid should be administered at 50% of the usual dose (see sections 4.5 and 5.1).

The safety and efficacy of the 80 mg and 125 mg capsules have not been demonstrated in children less than 12 years of age. No data are available.

General

Efficacy data in combination with other corticosteroids and 5-HT3 antagonists are limited. For additional information on the co-administration with corticosteroids, see section 4.5. Please refer to the SmPC of co-administered 5-HT3 antagonist medicinal products.

Special populations

Elderly (> 65 years)

No dose adjustment is necessary for the elderly (see section 5.2).

Gender

No dose adjustment is necessary based on gender (see section 5.2).

Renal impairment

No dose adjustment is necessary for patients with renal impairment or for patients with end stage renal disease undergoing haemodialysis (see section 5.2).

Hepatic impairment

No dose adjustment is necessary for patients with mild hepatic impairment. There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. Aprepitant should be used with caution in these patients (see sections 4.4 and 5.2).

Method of administration

The hard capsule should be swallowed whole.

Aprepitant Ethypharm may be taken with or without food.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Co-administration with pimozide, terfenadine, astemizole or cisapride (see section 4.5).

4.4 Special warnings and precautions for use

Patients with moderate to severe hepatic impairment

There are limited data in patients with moderate hepatic impairment and no data in patients with severe hepatic impairment. Aprepitant Ethypharm should be used with caution in these patients (see section 5.2).

CYP3A4 interactions

Aprepitant Ethypharm should be used with caution in patients receiving concomitant orally administered active substances that are metabolised primarily through CYP3A4 and with a narrow therapeutic range, such as cyclosporine, tacrolimus, sirolimus, everolimus, alfentanil, ergot alkaloid derivatives, fentanyl, and quinidine (see section 4.5). Additionally, concomitant administration with irinotecan should be approached with particular caution as the combination might result in increased toxicity.

Co-administration with warfarin (a CYP2C9 substrate)

In patients on chronic warfarin therapy, the International Normalised Ratio (INR) should be monitored closely during treatment with Aprepitant Ethypharm and for 14 days following each 3-day course of Aprepitant Ethypharm (see section 4.5).

Co-administration with hormonal contraceptives

The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of Aprepitant Ethypharm. Alternative non-hormonal back-up methods of contraception should be used during treatment with Aprepitant Ethypharm and for 2 months following the last dose of Aprepitant Ethypharm (see section 4.5).

Excipients

Aprepitant Ethypharm capsules contain sucrose. Patients with rare hereditary problems of fructose intolerance, glucose- galactose malabsorption or sucroseisomaltase insufficiency should not take this medicine.

4.5 Interaction with other medicinal products and other forms of interaction

4.6 Fertility, pregnancy and lactation

Contraception in males and females

The efficacy of hormonal contraceptives may be reduced during and for 28 days after administration of aprepitant. Alternative non-hormonal back-up methods of contraception should be used during treatment with aprepitant and for 2 months following the last dose of aprepitant (see sections 4.4 and 4.5).

Pregnancy

For aprepitant no clinical data on exposed pregnancies are available. The potential for reproductive toxicity of aprepitant has not been fully characterised, since exposure levels above the therapeutic exposure in humans at the 125 mg/80 mg dose could not be attained in animal studies. These studies did not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see section 5.3). The potential effects on reproduction of alterations in neurokinin regulation are unknown. Aprepitant should not be used during pregnancy unless clearly necessary.

Breast-feeding

Aprepitant is excreted in the milk of lactating rats. It is not known whether aprepitant is excreted in human milk; therefore, breast-feeding is not recommended during treatment with Aprepitant Ethypharm.

Fertility

The potential for effects of aprepitant on fertility has not been fully characterised because exposure levels above the therapeutic exposure in humans could not be attained in animal studies. These fertility studies did not indicate direct or indirect harmful effects with respect to mating performance, fertility, embryonic/foetal development, or sperm count and motility (see section 5.3).

4.7 Effects on ability to drive and use machines

Aprepitant Ethypharm may have minor influence on the ability to drive, cycle and use machines. Dizziness and fatigue may occur following administration of Aprepitant Ethypharm (see section 4.8).

4.8 Undesirable effects

Summary of the safety profile

The safety profile of aprepitant was evaluated in approximately 6,500 adults in more than 50 studies and 184 children and adolescents in 2 pivotal paediatric clinical trials.

The most common adverse reactions reported at a greater incidence in adults treated with the aprepitant regimen than with standard therapy in patients receiving Highly Emetogenic Chemotherapy (HEC) were: hiccups (4.6% versus 2.9%), alanine aminotransferase (ALT) increased (2.8% versus 1.1%), dyspepsia (2.6% versus 2.0%), constipation (2.4% versus 2.0%), headache (2.0% versus 1.8%), and decreased appetite (2.0% versus 0.5%). The most common adverse reaction reported at a greater incidence in patients treated with the aprepitant regimen than with standard therapy in patients receiving Moderately Emetogenic Chemotherapy (MEC) was fatigue (1.4% versus 0.9%).

The most common adverse reactions reported at a greater incidence in paediatric patients treated with the aprepitant regimen than with the control regimen while receiving emetogenic cancer chemotherapy were hiccups (3.3% versus 0.0%) and flushing (1.1% versus 0.0%).

Tabulated list of adverse reactions

The following adverse reactions were observed in a pooled analysis of the HEC and MEC studies at a greater incidence with aprepitant than with standard therapy in adults or paediatric patients or in postmarketing use. The frequency categories given in the table are based on the studies in adults; the observed frequencies in the paediatric studies were similar or lower, unless shown in the table. Some less common ADRs in the adult population were not observed in the paediatric studies.

Frequencies are defined as: very common (> 1/10); common (> 1/100 to < 1/10); uncommon (> 1/1,000 to < 1/100); rare (> 1/10,000 to < 1/1,000) and very rare (< 1/10,000), not known (cannot be estimated from the available data).

Nausea and vomiting were efficacy parameters in the first 5 days of postchemotherapy treatment and were reported as adverse reactions only thereafter.

Description of selected adverse reactions

The adverse reactions profiles in adults in the Multiple-Cycle extension of HEC and MEC studies for up to 6 additional cycles of chemotherapy were generally similar to those observed in Cycle 1.

In an additional active-controlled clinical study in 1,169 adult patients receiving aprepitant and HEC, the adverse reactions profile was generally similar to that seen in the other HEC studies with aprepitant.

Additional adverse reactions were observed in adult patients treated with aprepitant for postoperative nausea and vomiting (PONV) and a greater incidence than with ondansetron: abdominal pain upper, bowel sounds abnormal, constipation, dysarthria, dyspnoea, hypoaesthesia, insomnia, miosis, nausea, sensory disturbance, stomach discomfort, sub-ileus*, visual acuity reduced, wheezing.

*Reported in patients taking a higher dose of aprepitant.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

5   PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiemetics and antinauseants, ATC code: A04AD12

Aprepitant is a selective high-affinity antagonist at human substance P neurokinin 1 (NK1) receptors.

3-day regimen of aprepitant in adults

In 2 randomised, double-blind studies encompassing a total of 1,094 adult patients receiving chemotherapy that included cisplatin > 70 mg/m2, aprepitant in combination with an ondansetron/de­xamethasone regimen (see section 4.2) was compared with a standard regimen (placebo plus ondansetron 32 mg intravenously administered on Day 1 plus dexamethasone 20 mg orally on Day 1 and 8 mg orally twice daily on Days 2 to 4). Although a 32 mg intravenous dose of ondansetron was used in clinical trials, this is no longer the recommended dose. See the product information for the selected 5-HT3 antagonist for appropriate dosing information.

Efficacy was based on evaluation of the following composite measure: complete response (defined as no emetic episodes and no use of rescue therapy) primarily during Cycle 1. The results were evaluated for each individual study and for the 2 studies combined.

A summary of the key study results from the combined analysis is shown in Table 1.

Table 1

Percent of adult patients receiving Highly Emetogenic Chemotherapy responding by treatment group and phase – Cycle 1

INDIVIDUAL MEASURES

No emesis (no emetic episodes regardless of use of rescue therapy)

* The confidence intervals were calculated with no adjustment for gender and concomitant chemotherapy, which were included in the primary analysis of odds ratios and logistic models.

t One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and delayed phase analyses; one patient in the Standard regimen only had data in the delayed phase and was excluded from the overall and acute phase analyses.

The estimated time to first emesis in the combined analysis is depicted by the Kaplan-Meier plot in Figure 1.

Figure 1

Percent of adult patients receiving Highly Emetogenic Chemotherapy who remain

emesis free over time – Cycle 1

Statistically significant differences in efficacy were also observed in each of the 2 individual studies.

In the same 2 clinical studies, 851 adult patients continued into the Multiple-Cycle extension for up to 5 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently maintained during all cycles.

In a randomised, double-blind study in a total of 866 adult patients (864 females, 2 males) receiving chemotherapy that included cyclophosphamide 750–1,500 mg/m2; or cyclophosphamide 500–1,500 mg/m2 and doxorubicin (< 60 mg/m2) or epirubicin (< 100 mg/m2), aprepitant in combination with an ondansetron/de­xamethasone regimen (see section 4.2) was compared with standard therapy (placebo plus ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).

Efficacy was based on evaluation of the composite measure: complete response (defined as no emetic episodes and no use of rescue therapy) primarily during Cycle 1.

A summary of the key study results is shown in Table 2.

Table 2

Percent of adult patients responding by treatment group and phase – Cycle 1

Moderately Emetogenic Chemotherapy

Aprepitant regimen

Standard therapy

Differences*

Complete response (no emesis and no rescue therapy)

INDIVIDUAL MEASURES

No emesis (no emetic episodes regardless of use of rescue therapy)

* The confidence intervals were calculated with no adjustment for age category (< 55 years, > 55 years) and investigator group, which were included in the primary analysis of odds ratios and logistic models.

t One patient in the Aprepitant regimen only had data in the acute phase and was excluded from the overall and delayed phase analyses.

In the same clinical study, 744 adult patients continued into the Multiple-Cycle extension for up to 3 additional cycles of chemotherapy. The efficacy of the aprepitant regimen was apparently maintained during all cycles.

In a second multicentre, randomised, double-blind, parallel-group, clinical study, the aprepitant regimen was compared with standard therapy in 848 adult patients (652 females, 196 males) receiving a chemotherapy regimen that included any intravenous dose of oxaliplatin, carboplatin, epirubicin, idarubicin, ifosfamide, irinotecan, daunorubicin, doxorubicin; cyclophosphamide intravenously (< 1,500 mg/m2); or cytarabine intravenously (> 1 g/m2). Patients receiving the aprepitant regimen were receiving chemotherapy for a variety of tumour types including 52% with breast cancer, 21% with gastrointestinal cancers including colorectal cancer, 13% with lung cancer and 6% with gynaecological cancers. The aprepitant regimen in combination with an ondansetron/de­xamethasone regimen (see section 4.2) was compared with standard therapy (placebo in combination with ondansetron 8 mg orally (twice on Day 1, and every 12 hours on Days 2 and 3) plus dexamethasone 20 mg orally on Day 1).

Efficacy was based on the evaluation of the following primary and key secondary endpoints: No vomiting in the overall period (0 to 120 hours post-chemotherapy), evaluation of safety and tolerability of the aprepitant regimen for chemotherapy induced nausea and vomiting (CINV), and complete response (defined as no vomiting and no use of rescue therapy) in the overall period (0 to 120 hours postchemotherapy). Additionally, no significant nausea in the overall period (0 to 120 hours post-chemotherapy) was evaluated as an exploratory endpoint, and in the acute and delayed phases as a post-hoc analysis.

A summary of the key study results is shown in Table 3.

Table 3

Percent of adult patients responding by treatment group and phase for Study 2 –

Cycle 1

Moderately Emetogenic Chemotherapy

Complete response (no emesis and no rescue therapy)

No emesis (no emetic episodes regardless of use of rescue therapy)

The confidence intervals were calculated with no adjustment for gender and region, which were included in the primary analysis using logistic models.

The benefit of aprepitant combination therapy in the full study population was mainly driven by the results observed in patients with poor control with the standard regimen such as in women, even though the results were numerically better regardless of age, tumour type or gender. Complete response to the aprepitant regimen and standard therapy, respectively, was reached in 209/324 (65%) and 161/320 (50%) in women and 83/101 (82%) and 68/87 (78%) of men.

Paediatric population

In a randomised, double-blind, active comparator-controlled clinical study that included 302 children and adolescents (aged 6 months to 17 years) receiving moderately or highly emetogenic chemotherapy, the aprepitant regimen was compared to a control regimen for the prevention of CINV.

The efficacy of the aprepitant regimen was evaluated in a single cycle (Cycle 1). Patients had the opportunity to receive open-label aprepitant in subsequent cycles (Optional Cycles 2–6); however efficacy was not assessed in these optional cycles. The aprepitant regimen for adolescents aged 12 through 17 years (n=47) consisted of aprepitant capsules 125 mg orally on Day 1 and 80 mg/day on Days 2 and 3 in combination with ondansetron on Day 1. The aprepitant regimen for children aged 6 months to less than 12 years (n=105) consisted of aprepitant powder for oral suspension 3.0 mg/kg (up to 125 mg) orally on Day 1 and 2.0 mg/kg (up to 80 mg) orally on Days 2 and 3 in combination with ondansetron on Day 1. The control regimen in adolescents aged 12 through 17 years (n=48) and children aged 6 months to less than 12 years (n=102) consisted of placebo for aprepitant on Days 1, 2 and 3 in combination with ondansetron on Day 1. Aprepitant or placebo and ondansetron were administered 1 hour and 30 minutes prior to initiation of chemotherapy, respectively. Intravenous dexamethasone was permitted as part of the antiemetic regimen for paediatric patients in both age groups, at the discretion of the physician. A dose reduction (50%) of dexamethasone was required for paediatric patients receiving aprepitant. No dose reduction was required for paediatric patients receiving the control regimen. Of the paediatric patients, 29% in the aprepitant regimen and 28% in the control regimen used dexamethasone as part of the regimen in Cycle 1.

The antiemetic activity of aprepitant was evaluated over a 5-day (120 hour) period following the initiation of chemotherapy on Day 1. The primary endpoint was complete response in the delayed phase (25 to 120 hours following initiation of chemotherapy) in Cycle 1. A summary of the key study results are shown in Table 4.

Table 4

Number (%) of paediatric patients with complete response and no vomiting by treatment group and phase – Cycle 1 (Intent to treat population)

The estimated time to first vomiting after initiation of chemotherapy treatment was longer with the aprepitant regimen (estimated median time to first vomiting was 94.5 hours) compared with the control regimen group (estimated median time to first vomiting was 26.0 hours) as depicted in the Kaplan-Meier curves in Figure 2.

Figure 2

Time to first vomiting episode from start of chemotherapy administration – paediatric patients in the overall phase-Cycle 1 (Intent to treat population)

Time (hours) Since the First Chemotherapy Administration

An analysis of efficacy in subpopulations in Cycle 1 demonstrated that, regardless of age category, gender, use of dexamethasone for antiemetic prophylaxis, and emetogenicity of chemotherapy, the aprepitant regimen provided better control than the control regimen with respect to the complete response endpoints.

5.2

Aprepitant displays non-linear pharmacokinetics. Both clearance and absolute bioavailability decrease with increasing dose.

Absorption

The mean absolute oral bioavailability of aprepitant is 67% for the 80 mg capsule and 59% for the 125 mg capsule. The mean peak plasma concentration (Cmax) of aprepitant occurred at approximately 4 hours (tmax). Oral administration of the capsule with an approximately 800 Kcal standard breakfast resulted in an up to 40% increase in AUC of aprepitant. This increase is not considered clinically relevant.

The pharmacokinetics of aprepitant is non-linear across the clinical dose range. In healthy young adults, the increase in AUC0-co was 26% greater than dose proportional between 80 mg and 125 mg single doses administered in the fed state.

Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 and 3, the AUC0–24hr (mean±SD) was

19.6 ± 2.5 pg»h/mL and 21.2 ± 6.3 pg»h/mL on Days 1 and 3, respectively. Cmax was 1.6 ± 0.36 pg/mL and 1.4 ± 0.22 pg/mL on Days 1 and 3, respectively.

Distribution

Aprepitant is highly protein bound, with a mean of 97%. The geometric mean apparent volume of distribution at steady state (Vdss) is approximately 66 L in humans.

Biotransformation

Aprepitant undergoes extensive metabolism. In healthy young adults, aprepitant accounts for approximately 19% of the radioactivity in plasma over 72 hours following a single intravenous administration 100 mg dose of [14C]-fosaprepitant, a prodrug for aprepitant, indicating a substantial presence of metabolites in the plasma. Twelve metabolites of aprepitant have been identified in human plasma. The metabolism of aprepitant occurs largely via oxidation at the morpholine ring and its side chains and the resultant metabolites were only weakly active. In vitro studies using human liver microsomes indicate that aprepitant is metabolised primarily by CYP3A4 and potentially with minor contribution by CYP1A2 and CYP2C19.

Elimination

Aprepitant is not excreted unchanged in urine. Metabolites are excreted in urine and via biliary excretion in faeces. Following a single intravenously administered 100 mg dose of [14C ]-fosaprepitant, a prodrug for aprepitant, to healthy subjects, 57% of the radioactivity was recovered in urine and 45% in faeces.

The plasma clearance of aprepitant is dose-dependent, decreasing with increased dose and ranged from approximately 60 to 72 mL/min in the therapeutic dose range. The terminal half-life ranged from approximately 9 to 13 hours.

Pharmacokinetics in special population

Elderly: Following oral administration of a single 125 mg dose of aprepitant on Day 1 and 80 mg once daily on Days 2 through 5, the AUC0–24hr of aprepitant was 21% higher on Day 1 and 36% higher on Day 5 in elderly (> 65 years) relative to younger adults. The Cmax was 10% higher on Day 1 and 24% higher on Day 5 in elderly relative to younger adults. These differences are not considered clinically meaningful. No dose adjustment for aprepitant is necessary in elderly patients.

Gender: Following oral administration of a single 125 mg dose of aprepitant, the Cmax for aprepitant is 16% higher in females as compared with males. The half-life of aprepitant is 25% lower in females as compared with males and its tmax occurs at approximately the same time. These differences are not considered clinically meaningful. No dose adjustment for aprepitant is necessary based on gender.

Hepatic impairment: Mild hepatic impairment (Child-Pugh class A) does not affect the pharmacokinetics of aprepitant to a clinically relevant extent. No dose adjustment is necessary for patients with mild hepatic impairment. Conclusions regarding the influence of moderate hepatic impairment (Child-Pugh class B) on aprepitant pharmacokinetics cannot be drawn from available data. There are no clinical or pharmacokinetic data in patients with severe hepatic impairment (Child-Pugh class C).

Renal impairment: A single 240 mg dose of aprepitant was administered to patients with severe renal impairment (CrCl<30 mL/min) and to patients with end stage renal disease (ESRD) requiring haemodialysis.

In patients with severe renal impairment, the AUC0-co of total aprepitant (unbound and protein bound) decreased by 21% and Cmax decreased by 32%, relative to healthy subjects. In patients with ESRD undergoing haemodialysis, the AUC0-co of total aprepitant decreased by 42% and Cmax decreased by 32%. Due to modest decreases in protein binding of aprepitant in patients with renal disease, the AUC of pharmacologically active unbound aprepitant was not significantly affected in patients with renal impairment compared with healthy subjects. Haemodialysis conducted 4 or 48 hours after dosing had no significant effect on the pharmacokinetics of aprepitant; less than 0.2% of the dose was recovered in the dialysate.

No dose adjustment for aprepitant is necessary for patients with renal impairment or for patients with ESRD undergoing haemodialysis.

Paediatric population: As part of a 3-day regimen, dosing of aprepitant capsules (125/80/80-mg) in adolescent patients (aged 12 through 17 years) achieved an AUC0–24hr above 17 gg^hr/mL on Day 1 with concentrations (Cmin) at the end of Days 2 and 3 above 0.4 jig/mL in a majority of patients. The median peak plasma concentration (Cmax) was approximately 1.3 jig/mL on Day 1, occurring at approximately 4 hours. As part of a 3-day regimen, dosing of aprepitant powder for oral suspension (3/2/2-mg/kg) in patients aged 6 months to less than12 years achieved an AUC0–24hr above 17 gg^hr/mL on Day 1 with concentrations (Cmin) at the end of Days 2 and 3 above 0.1 jig/mL in a majority of patients. The median peak plasma concentration (Cmax) was approximately 1.2 jig/mL on Day 1, occurring between 5 and 7 hours.

A population pharmacokinetic analysis of aprepitant in paediatric patients (aged 6 months through 17 years) suggests that gender and race have no clinically meaningful effect on the pharmacokinetics of aprepitant.

Relationship between concentration and effect

Using a highly specific NK1-receptor tracer, positron emission tomography (PET) studies in healthy young men have shown that aprepitant penetrates into the brain and occupies NK1 receptors in a dose- and plasma-concentration-dependent manner. Aprepitant plasma concentrations achieved with the 3-day regimen of aprepitant in adults are predicted to provide greater than 95% occupancy of brain NK1 receptors.

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Capsule content

hydroxypropyl­cellulose

sodium laurilsulfate

sucrose

cellulose, microcrystalline.

Capsule shell (80 mg)

Titanium dioxide (E 171)

Gelatin

Printink ink:

Shellac

Ammonia solution, concentrated

Propylene glycol

Potassium hydroxide

Black iron oxide (E 172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

30 months.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Different pack sizes including different strengths are available.

PA/Aluminium/PVC/A­luminium blister containing one 80 mg capsule.

PA/Aluminium/PVC/A­luminium blister containing two 80 mg capsules. PA/Aluminium/PVC/A­luminium blister containing five 80 mg capsules Not all pack sizes may be marketed.

6.6 Special precautions for disposal