EFMODY 10mg modified-release capsules medication leaflet

Efmody 5 mg modified-release hard capsules

Efmody 10 mg modified-release hard capsules

Efmody 5 mg modified-release hard capsules

Each modified-release hard capsule contains 5 mg hydrocortisone.

Efmody 10 mg modified-release hard capsules

Each modified-release hard capsule contains 10 mg hydrocortisone.

For the full list of excipients, see section 6.1.

Modified-release hard capsules

Efmody 5 mg modified-release hard capsules

A capsule (approximately19 mm long) with an opaque blue cap and opaque white body printed with“CHC 5 mg” containing white to off white granules.

Efmody 10 mg modified-release hard capsules

A capsule (approximately19 mm long) with an opaque green cap and opaque white body printed with“CHC 10 mg” containing white to off white granules.

Efmody is indicated in adolescents aged 12 years and over and adults for the:

* Treatment of adrenal insufficiency (AI)

* Treatment of congenital adrenal hyperplasia (CAH)

Treatment should be initiated by physicians experienced in the management of AI and/or CAH.

As maintenance therapy the dose must be individualised according to the response of the individualpatient. The lowest possible dose should be used.

Monitoring of the clinical response is necessary and patients should be observed closely for signs thatmight require dose adjustment, including changes in clinical status resulting from remissions orexacerbations of the disease, changes in electrolytes particularly hypokalaemia (see section 4.4) orhyponatraemia, individual responsiveness to the medicinal product, and the effect of stress (e.g.

surgery, infection, trauma). As the treatment has a modified-release profile when blood tests are usedto monitor clinical response in CAH; assessment of the evening dose should be done with a morningblood test and assessment of the morning dose should be done with an early afternoon blood test.

During excessive physical and/or mental stress it may be necessary to increase the dose of Efmody,and/or add additional immediate release hydrocortisone especially in the afternoon or evening.

Dose adjustments should be considered in case of concomitant use of potent CYP3A4 inducers orinhibitors (see section 4.5).

Treatment in AI and CAH

Recommended replacement doses of hydrocortisone are 10-15 mg/m2/day (CAH) and 8-10 mg/m2/day(other forms of AI) in adolescents aged 12 years and over who have not completed growth, and15-25 mg/day in adolescents who have completed growth and adult patients with AI or CAH. Inpatients with some remaining endogenous cortisol production a lower dose may be sufficient.

At initiation the total daily dose should be split into two doses with two thirds to three quarters of thedose given in the evening at bedtime and the rest given in the morning. Patients should then be titratedbased on their individual response.

Efmody can be taken with or without food (see section 5.2).

Changing from conventional oral glucocorticoid treatment to hydrocortisone modified-release hardcapsules

When changing patients from other oral hydrocortisone replacement therapy to Efmody, the identicaltotal daily dose should be given, but the dose should be given in two doses with two thirds to threequarters of the dose given in the evening at bedtime and the rest given in the morning.

When changing patients from other glucocorticoids to hydrocortisone modified-release hard capsulesan appropriate conversion factor should be used, and the patient monitored for response carefully.

Conversion to hydrocortisone modified-release hard capsules might elicit symptoms of adrenalinsufficiency or overreplacement during dose optimisation.

A starting dose exceeding 40 mg per day of hydrocortisone is not recommended.

During serious trauma, intercurrent illness or periods of stress

In severe situations, an increase in dose is immediately required and oral administration ofhydrocortisone must be replaced with parenteral treatment (see section 4.4).

In less severe situations when parenteral administration of hydrocortisone is not required, duringperiods of physical and/or mental stress, additional immediate release hydrocortisone (IRHC) at thesame total daily dose as Efmody should be given in three divided doses (i.e. a doubled total daily doseof hydrocortisone is given). Efmody should be continued with the usual regimen to allow for easyreturn to the normal replacement dose of hydrocortisone once additional hydrocortisone is no longerrequired.

In case of long-term increases in hydrocortisone daily dose due to prolonged periods of stress orillness, the additional hydrocortisone should be carefully weaned off.

If a dose of Efmody is missed, it is recommended that it be taken as soon as possible.

Limited clinical data on the safety and efficacy of Efmody are available in elderly patients (over theage of 65 years) with AI or with CAH. There are no data available in patients over the age of75 years.

There is no need for dose adjustment in patients with mild to moderate renal impairment. In patientswith severe renal impairment monitoring of the clinical response is recommended and adjustment ofdose may be necessary (see section 4.4).

There is no need for dose adjustment in patients with mild to moderate hepatic impairment. In patientswith severe hepatic impairment monitoring of the clinical response is recommended and adjustment ofdose may be necessary (see section 4.4).

No clinical data on the safety and efficacy of Efmody are available in children aged below 12 years.

Other hydrocortisone containing medicinal products are available for children below 12 years of age.

Limited clinical data on the safety and efficacy of Efmody are available in adolescents aged 12 to 18years.

In the clinical development programme 2 patients ≤ 18 years of age have been treated with Efmody for

CAH. Their response was comparable to that of patients > 18 years of age.

Oral use.

Patients should be advised to swallow the modified-release hard capsules with water to wash thecapsules down.

The capsules should not be chewed as chewing the capsule could affect the release profile.

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

Adrenal crisis

Acute adrenal insufficiency may develop in patients with known adrenal insufficiency or CAH whoare on inadequate daily doses or in situations with increased cortisol need. Therefore, patients shouldbe advised of the signs and symptoms of acute adrenal insufficiency and of adrenal crisis and the needto seek immediate medical attention. Sudden discontinuation of therapy with hydrocortisone riskstriggering an adrenal crisis and death.

During adrenal crisis parenteral, preferably intravenous administration of hydrocortisone in highdoses, together with sodium chloride 9 mg/ml (0.9%) solution for infusion, should be administeredaccording to current treatment guidelines.

Pre-operatively, during serious trauma or during intercurrent illness

Pre-operatively, anaesthetists must be informed if the patient is taking corticosteroids or haspreviously taken corticosteroids.

Parenteral administration of hydrocortisone is warranted during transient illness episodes such assevere infections, in particular gastroenteritis associated with vomiting and/or diarrhoea, high fever ofany aetiology or extensive physical stress, such as for instance serious accidents and surgery undergeneral anaesthesia. Where parenteral hydrocortisone is required, the patient should be treated in afacility with resuscitation facilities in case of evolving adrenal crisis.

In less severe situations when parenteral administration of hydrocortisone is not required, for instancelow grade infections, moderate fever of any aetiology and stressful situations such as minor surgicalprocedures, there should be high awareness of the risk of developing acute adrenal insufficiency.

Infection should not be more likely at a replacement dose of hydrocortisone, but all infections shouldbe taken seriously, and an increase in steroid dose be initiated early (see section 4.2). Patients with AIor CAH are at risk of life-threatening adrenal crisis during infection so clinical suspicion of infectionshould be high and specialist advice should be sought early.

Treatment schedules of corticosteroids for people with AI or CAH do not cause immunosuppressionand are not, therefore, contraindications for administration of live vaccines.

Adverse reactions to corticosteroid replacement therapy

Most adverse reactions to corticosteroids are dose and duration of exposure related. Adverse reactionsare therefore less likely when using corticosteroids as replacement therapy. High (supra-physiological)doses of hydrocortisone can cause elevation of blood pressure, salt and water retention, and increasedexcretion of potassium.

Long-term treatment with higher than physiological hydrocortisone doses can lead to clinical featuresresembling Cushing´s syndrome with increased adiposity, abdominal obesity, hypertension anddiabetes, and thus result in an increased risk of cardiovascular morbidity and mortality.

Patients should be warned of the signs of diabetes and the need to seek medical advice if they occur.

All glucocorticoids increase calcium excretion and reduce the bone-remodelling rate. Long-termglucocorticoid replacement therapy may therefore reduce bone mineral density (see section 4.8).

Patients should be warned that potentially severe psychiatric adverse reactions; euphoria, mania,psychosis with hallucinations and delirium have been seen in adult patients at replacement doses ofhydrocortisone (see section 4.8). Symptoms typically emerge within a few days or weeks of startingthe treatment. Risks may be higher with high doses/systemic exposure (see also section 4.5), althoughdose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactionsrecover after either dose reduction or withdrawal, although specific treatment may be necessary.

Patients should be encouraged to seek medical advice if worrying psychological symptoms develop,especially if depressed mood or suicidal ideation is suspected. Patients should also be alert to possiblepsychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal ofsystemic steroids, although such reactions have been reported infrequently.

Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroids, medicaladvice should be sought immediately in the case of anaphylactoid symptoms (see section 4.8).

Gastric emptying and motility disorders

Hydrocortisone modified-release hard capsules are not recommended in patients with increasedgastrointestinal motility, i.e. chronic diarrhoea, due to the risk of impaired cortisol exposure. There areno data in patients with confirmed slow gastric emptying or decreased motility disease/disorder. Theclinical response should be monitored in patients with these conditions.

Growth retardation

Corticosteroids may cause growth retardation in childhood and adolescence; this may be irreversible.

Treatment should be limited to the minimum dose required to achieve desired clinical response andwhen reduction in dose is possible, the reduction should be gradual. Excessive weight gain withdecreased height velocity or other symptoms or signs of Cushing syndrome indicate excessiveglucocorticoid replacement. Children require frequent assessment to assess growth, blood pressure,and general well-being.

Accelerated sexual maturation

Adolescents with CAH may show accelerated sexual maturation. Patients should be closelymonitored; and if signs of early puberty or accelerated sexual maturation are present, an increase indose should be considered. Careful and regular monitoring of adolescent patients with dose adjustmentaccording to the response of the individual patient is recommended.

Visual disturbance

Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presentswith symptoms such as blurred vision or other visual disturbances, the patient should be considered forreferral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucomaor rare diseases such as central serous chorioretinopathy which have been reported after use ofsystemic and topical corticosteroids.

Treatment of AI and CAH often warrants additional treatment with mineralocorticosteroids. Potassiumshould be monitored (see sections 4.5 and 4.8).

Precaution on fertility

In both men and women who have lower fertility due to CAH, fertility may be restored shortly afterbeginning treatment with Efmody, which can lead to unexpected pregnancies. Patients should beinformed of the potential for restored fertility when starting treatment with Efmody, to be able toconsider if a contraceptive measure is needed (see section 4.6).

Hydrocortisone is metabolised by cytochrome P450 3A4 (CYP3A4). Concomitant administration ofmedicinal products that are inhibitors or inducers of CYP3A4 may therefore lead to unwantedalterations in serum concentrations of hydrocortisone with the risk of adverse reactions, particularlyadrenal crisis. The need for dose adjustment when such medicinal products are used can be anticipatedand patients should be closely monitored.

Medicinal products inducing CYP3A4, requiring a potential increase in Efmody dosing, include butare not limited to:

- Anticonvulsants: phenytoin, carbamazepine and oxcarbazepine

- Antibiotics: rifampicin and rifabutin

- Barbiturates including phenobarbital and primidone

- Antiretroviral medicinal products: efavirenz and nevirapine

- Herbal medicinal products such as St. John's wort

Medicinal products/substances inhibiting CYP3A4, requiring a potential decrease in hydrocortisonedosing, include but are not limited to:

- Anti-fungals: itraconazole, posaconazole, voriconazole

- Antibiotics: erythromycin and clarithromycin

- Antiretroviral medicinal products: ritonavir

- Grapefruit juice

- Liquorice

The desired actions of hypoglycaemic medicinal products including insulin are antagonised bycorticosteroids.

Medicinal products/substances that affect the electrolyte balance may increase the risk ofhypokalaemia in patients taking Efmody. These include hypokalaemic diuretics, stimulant laxatives,mineralocorticosteroids (fludrocortisone), tetracosactide, intravenous amphotericin B and liquorice.

Hydrocortisone crosses the placenta. Hydrocortisone is preferentially metabolised by placental11βHSD2 to inactive cortisone reducing the fetal exposure. There are no indications that replacementtherapy with hydrocortisone in pregnant women is associated with harmful effects for the fetus.

Hydrocortisone for replacement therapy can be used during pregnancy.

Studies in animals have shown reproductive toxicity of corticosteroids (see section 5.3).

Hydrocortisone is excreted in human milk. However, the doses of hydrocortisone used for replacementtherapy probably do not clinically significantly affect the breastfed newborn/infants. Hydrocortisonefor replacement therapy can be used during breast-feeding.

In both men and women who have lower fertility due to CAH, fertility may be restored shortly afterbeginning treatment with Efmody. In women, a reduction of 17-OH progesterone and androstenedionewill lead to a corresponding fall in progesterone and testosterone which may restore menses/fertility.(see section 4.4).

Efmody has minor influence on the ability to drive and use machines. Fatigue and dizziness have beenreported (see section 4.8). Untreated and poorly replaced adrenal insufficiency may affect the ability todrive and use machines.

The adverse drug reactions reported to Efmody in the clinical trial programmes for AI and CAH, andfrom post-marketing surveillance of CAH are discussed in this section.

In the clinical trial programmes of AI and CAH, 284 adverse reactions were reported from203 Efmody-treated patients. Fatigue was reported very commonly, affecting 11.3% of patients.

Headache (5.4%), and Dizziness (4.9%) were reported commonly. The most common adversereactions observed in CAH only clinical trial programme are weight increased (6.9%), increasedappetite (4.8%), decreased appetite (4.1%) , asthenia (4.1%), insomnia (4.1%) and carpal tunnelsyndrome (2.8%). Adverse reactions may respond to dose adjustment/ dose optimisation in someindividuals (see section 4.2). Two serious adverse reactions of hypokalaemia (2.2%) were reported inthe long-term extension study DIUR-006 for patients that were receiving a mineralocorticoid.

Events of adrenal insufficiency, including acute events, were reported in 7.9% of clinical trialparticipants without causal attribution. Acute adrenal insufficiency has been reported in CAH patientsas a post-marketing ADR for Efmody.

The adverse reactions reported for Efmody in the pooled population (n= 203) in the clinical trialprogramme for CAH and AI, and from post-marketing surveillance, are tabulated below. Frequenciesare 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), very rare (< 1/10 000), or not known (cannot be estimated from theavailable data). Within each frequency grouping, adverse reactions are presented in the order ofdecreasing seriousness.

Table 1. Adverse reactions

MedDRA system organclassification Event Frequency

Blood and Lymphatic System Increased tendency to bruise Uncommon

Disorders

Endocrine disorders Adrenocortical insufficiency Unknownincluding acute events1

Cushingoid Uncommon

Gastrointestinal disorders Abdominal pain upper Common

Nausea

General disorders and administration Fatigue Very commonsite conditions

Asthenia Common

Fat tissue increased

Oedema peripheral Uncommon

Swelling

Thirst

Infections and infestations Paronychia Uncommon

Investigations Blood potassium decreased Common

Blood testosterone decreased

Blood testosterone increased

Low density lipoprotein increased

Renin increased

Weight increased

Bone density decreased Uncommon

Osteocalcin decreased

Renin decreased

Urine output decreased

Metabolism and nutrition disorders Abnormal weight gain Common

Decreased appetite

Increased appetite

Impaired fasting glucose

Blood glucose increased Uncommon

Fluid retention

Hyperinsulinaemia

Hyperlipidaemia

Musculoskeletal and connective tissue Arthralgia Commondisorders Muscle fatigue

Muscle weakness

Myalgia

Pain in extremity

Nervous System Disorders Carpal tunnel syndrome Common

Dizziness

Hypoaesthesia

Paraesthesia

Somnolence Uncommon

Psychiatric disorders Abnormal dreams Common

Depressed mood

Insomnia

Irritability

Sleep disorder

Stress

Reproductive System and Breast Heavy menstrual bleed Uncommon

Disorders Menstruation irregular

Skin and subcutaneous tissue Acne Commondisorders Hirsutism

Hyperhidrosis Uncommon

Skin striae

Vascular Disorders Hypertension Uncommon1frequency based on postmarketing reports

Acute adrenal insufficiency should be monitored for and treated promptly in patients with adrenalinsufficiency (see sections 4.2 and 4.4).

Rare instances of anaphylactoid reactions have occurred in patients receiving corticosteroidsespecially when a patient has a history of allergies to medicinal products.

Historical cohorts of adults treated from childhood for AI and CAH have been found to have reducedbone mineral density and increased fracture rates (see section 4.4) - it is unclear if these relate tohydrocortisone therapy using current replacement regimens.

Historical cohorts of adults treated from childhood for AI and CAH have been found to have raisedcardiovascular risk factors and a higher risk of cerebrovascular disease than the general population - itis unclear if these relate to hydrocortisone therapy using current replacement regimens.

Limited paediatric patients were included in the clinical development programme for Efmody.

Hydrocortisone has been used for more than 60 years in paediatrics with a safety profile similar to thatin adults. Growth retardation has been seen in children treated with hydrocortisone for CAH and canbe caused by both the disorder and hydrocortisone. Accelerated sexual maturation has been seen inhydrocortisone-treated paediatric CAH patients and is associated with excess adrenal androgenproduction (see section 4.4).

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

Reports of acute toxicity and/or deaths following hydrocortisone overdose are rare. No antidote isavailable. Treatment is probably not indicated for reactions due to chronic poisoning unless the patienthas a condition that would render him/her unusually susceptible to ill effects from hydrocortisone. Inwhich case, symptomatic treatment should be instituted as necessary.

Pharmacotherapeutic group: Corticosteroids for systemic use; glucocorticoids. ATC code: H02AB09

Hydrocortisone is a glucocorticoid. Glucocorticoids have multiple effects in multiple tissues throughactions on the intracellular steroid receptors.

Hydrocortisone is a glucocorticoid and the synthetic form of endogenously produced cortisol.

Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readilyabsorbed from the gastro-intestinal tract. Cortisol is the principal corticosteroid secreted by the adrenalcortex. Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. They are alsoused for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoidscause profound and varied metabolic effects. In addition, they modify the body’s immune responses todiverse stimuli.

CAH

A double blind double dummy study (DIUR-014) of 53 participants with CAH (21 hydroxylasedeficiency) randomised participants to either twice daily Efmody or twice daily immediate releasehydrocortisone (IRHC) after 4 weeks run in on 30mg IRHC daily. At baseline (randomisation) 28.6 %of participants allocated to the IRHC cohort were in biochemical control compared to 52.0% ofparticipants allocated to Chronocort. Following randomisation participants had blinded titration ofdosing at 3 visits with dose reductions (in 5 mg steps at each visit) conducted if participants had 17-

OHP <300 ng/dL and A4 <150 ng/dL in men and <200 ng/dL in women. The difference between

Chronocort and IRHC treatment in the proportion of participants in biochemical response was 84.0%vs 14.3% at Week 10 and 72.0% vs 17.9% at Week 16. After 28 weeks the study demonstrated thatmore participants were biochemical responders with Efmody treatment (40.0%) compared to IHRCtreatment (14.3%) (p=0.015). Biochemical responders were defined as having a 0800hrs 17-OHPconcentration ≤ 1200 ng/dL (36.4 nmol/L) plus a 0800hrs A4 concentration ≤ 150 ng/dL (5.2 nmol/L)for men or ≤ 200 ng/dL (7.0 nmol/L) for women plus a total daily dose of hydrocortisone after 28weeks of randomized treatment of not more than 25 mg (if the participant was in biochemical controlat baseline) or not more than 30 mg (if the participant was not in biochemical control at (baseline..

Overall, participants had a lower mean daily dose following Efmody treatment (20.2 mg) compared to

IRHC treatment (26.0 mg) (p<0.001).

An open label study (DIUR-005) in 122 participants with CAH (21-hydroxylase deficiency)randomised to Efmody or continuation of standard care with blinded titration of dose and regularovernight profiles failed to meet its primary endpoint of superiority in change from baseline to 24weeks of the mean of the 24-hour standard deviation score (SDS) profile for 17-hydroxyprogesterone(17-OHP). The percentage of patients with controlled 09:00 hours 17-OHP (<36nmol/l) was 50% atbaseline and at 24 weeks was 91% in the Efmody cohort and 71% in the standard therapy cohort.

Efmody patients suffered no adrenal crises (compared to 3 in the control arm) and had fewer sick dayepisodes where increased dosing due to stress was required (26 vs 36 in the control arm) despitereporting more episodes of intercurrent infective or gastro-intestinal illness.

Figure 1. End of study geometric mean 24-hour profile of 17-OHP after 24 weeks intensive treatmentwith either Efmody (closed circles) or standard therapy (open circles).

Standard GC 24 weeks Efmody 24 weeks

A safety extension study of 91 patients with titration by investigators (DIUR-006) was characterisedby dose reductions with median daily dose of Efmody at 18 months (n=50) being 20 mg (from amedian baseline daily dose of 30 mg) with 17-OHP levels remaining in the clinically determinedoptimal range and androstenedione at or below the reference range for normal individual.

17-OHP nmol/l

AI

A double-blind, double- dummy crossover study in fifty eight primary adrenal insufficiencyparticipants compared the efficacy, safety and tolerability of twice daily Efmody and once-daily

Plenadren over a treatment period of up to two months, with two 4-week treatment periods.

Treatment order was randomised. At the end of 4 weeks treatment (periods 1 and 2), the medianserum cortisol was higher at the 07:00 timepoint during Efmody treatment (417.0 nmol/L) comparedto Plenadren treatment (6.04 nmol/L).

A profile plot of daytime salivary cortisone values from 7 to 22 hours clock time in different treatmentgroups is provided in Figure 2.

Figure 2. Profile Plot of Daytime Salivary Cortisone levels in IRHC, Plenadren and Efmody(Chronocort) -treated subjects in Study DIUR-016-AI with overlaid Normative Data

Shaded area represents normative data from 14 healthy adults

IRHC: immediate-release hydrocortisone (Baseline)

Following a single oral administration in fasted dexamethasone-suppressed healthy adults, the rate ofabsorption of hydrocortisone from Efmody 20 mg was delayed and reduced compared to immediaterelease hydrocortisone tablets 20 mg, as reflected by a lower Cmax and a significantly longer Tmax for

Efmody (median Tmax for serum cortisol of 4.5 hours and 0.88 hours for Efmody and hydrocortisonetablets respectively). Efmody appeared to be more bioavailable relative to immediate releasehydrocortisone tablets, with overall exposure to serum cortisol and derived free cortisol approximately19% and 13% higher respectively for Efmody.

In the same population, food (high fat meal started 30 minutes before dosing) was found to delay andreduce the rate of absorption of hydrocortisone from Efmody 20 mg, as reflected by a longer Tmax(median Tmax for serum cortisol of 6.75 hours and 4.5 hours for fed and fasted subjects respectively)and lower Cmax (reduced by approximately 20% in fed subjects). Overall exposure appeared similar infed and fasted subjects (90% confidence intervals for the fed/fasted ratio of the geometric least squaremean of AUC0-t and AUC0-inf were within 80-125%). This effect is therefore not considered clinicallysignificant.

At least 90% of circulating hydrocortisone is reversibly bound to protein.

The binding is accounted for by two protein fractions. One, corticosteroid-binding globulin is aglycoprotein; the other is albumin.

Hydrocortisone is metabolised in the liver and most body tissues to hydrogenated and degraded formssuch as tetrahydrocortisone and tetrahydrocortisol which are excreted in the urine, mainly conjugatedas glucuronides, together with a very small proportion of unchanged hydrocortisone. Hydrocortisone isboth metabolised by and a regulator of CYP3A4.

In the fasted dexamethasone-suppressed healthy adult population described above, terminalelimination half-life values were similar for Efmody and hydrocortisone tablets (geometric mean t1/2for serum cortisol of 1.38 hours and 1.40 hours respectively). Clearance appeared higher forhydrocortisone tablets relative to Efmody (geometric mean CL/F for serum cortisol of 22.24 L/h and18.48 L/h respectively).

No studies have been conducted in patients with renal impairment.

No studies have been conducted in patients with hepatic impairment.

The pharmacokinetics of Efmody have not been studied in the paediatric population.

Administration of corticosteroids to pregnant animals can cause abnormalities of fetal developmentincluding cleft palate, intrauterine growth retardation and effects on brain growth and development.

Granules

Microcrystalline cellulose (E_461)

Povidone (E_1201)

Methacrylic acid-methyl methacrylate copolymer (1:2) (E_1205)

Methacrylic acid-methyl methacrylate copolymer (1:1) (E_1205)

Talc (E_553b)

Dibutyl sebacate

Capsule

Gelatin

Efmody 5 mg modified-release hard capsules (white/blue)

Titanium dioxide (E 171)

Indigotine (E 132)

Efmody 10 mg modified-release hard capsules (white/green)

Titanium dioxide (E 171)

Indigotine (E 132)

Yellow iron oxide (E 172)

Shellac

Black iron oxide (E 172)

Potassium hydroxide

Not applicable.

3 years

Store in the original package.

Keep the bottle tightly closed in order to protect from moisture.

This medicinal product does not require any special temperature storage conditions.

The capsules are provided in high-density polyethylene bottles with child resistant, tamper-evidentpolypropylene screw cap with integrated desiccant. Each bottle contains 50 modified-release hardcapsules.

Carton containing 1 bottle of 50 modified-release hard capsules.

Carton containing 2 bottles of 50 modified-release hard capsules (100 capsules).

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with localrequirements.

Immedica Netherlands B.V.

Van Heuven Goedhartlaan 935 A,1181LD Amstelveen,

The Netherlands

Efmody 5 mg modified-release hard capsules EU/1/21/1549/001 (50 capsules)

Efmody 10 mg modified-release hard capsules EU/1/21/1549/002 (50 capsules)

Efmody 5 mg modified-release hard capsules EU/1/21/1549/004 (100 (2x50) capsules)

Efmody 10 mg modified-release hard capsules EU/1/21/1549/005 (100 (2x50) capsules)

Date of first authorisation: 27 May 2021

Date of latest renewal: 09 January 2026

Detailed information on this medicinal product is available on the website of the European Medicines

Agency https://www.ema.europa.eu