BETAMETHASONE ZENTIVA 0,05 % S buv en gouttes Fl/30ml

Oral drops solution.

Betamethasone ........................................................................................................................................... 0,05%

For a bottle of 30 ml.

Excipients with known effects: sorbitol, sucrose, propylene glycol.

Excipients:

DISEASES OR CONDITIONS :

I-COLLAGEN DISEASES-CONNECTIVE TISSUE DISORDERS

Evolving flares of systemic diseases, including: disseminated lupus erythematosus, vasculitis, polymyositis, visceral sarcoidosis.

II-DERMATOLOGICAL

a-severe autoimmune bullous dermatoses, in particular pemphigus and bullous pemphigoid;

b-severe forms of infantile haemangiomas;

c-certain forms of lichen planus;

d-certain acute urticarias;

e-severe forms of neutrophilic dermatoses.

III- DIGESTIVE

a-progressive episodes of ulcerative colitis and Crohn's disease;

b-chronic active autoimmune hepatitis (with or without cirrhosis);

c-severe acute alcoholic hepatitis, histologically proven.

IV-ENDOCRINE

a-severe subacute De Quervain's thyroiditis;

b-certain hypercalcaemias.

V- HAEMATOLOGICAL

a-severe immunological thrombocytopenic purpuras;

b-autoimmune haemolytic anaemias;

c-in combination with various chemotherapies in the treatment of malignant lymphoid haemopathies;

d-acquired or congenital chronic erythroblastopenias.

VI-INFECTIOUS

a-tuberculous pericarditis and severe forms of tuberculosis putting vital prognosis at risk;

b-pneumopathy with Pneumocystis carinii with severe hypoxia.

VII-NEOPLASTIC

a-anti-emetic treatment during antineoplastic chemotherapy;

b-oedematous and inflammatory flare associated with antineoplastic treatments (radiotherapy and chemotherapy).

VIII-NEPHROLOGICAL

a-nephrotic syndrome with minimal glomerular lesions;

b-nephrotic syndrome of primary focal and segmental hyalinosis;

c-stage III and IV lupus nephropathy;

d-intrarenal granulomatous sarcoidosis;

e-vasculitis with renal involvement;

f-primary extracapillary glomerulonephritis.

IX-NEUROLOGICAL

a-myasthenia;

b-cerebral oedema of tumoral cause;

c-chronic, idiopathic, inflammatory polyradiculoneuritis;

d-infantile spasms (West syndrome) / Lennox-Gastaut syndrome;

e-multiple sclerosis flare, as a follow-on from intravenous corticosteroid therapy.

X-OPHTHALMOLOGICAL

a-severe anterior and posterior uveitis;

b-oedematous exophthalmos;

c-certain optic neuropathies, as a follow-on from intravenous corticosteroid therapy (in this indication, oral administration as first-line treatment is not recommended).

XI-ENT

a-certain serous otitis;

b-nasal sinus polyposis;

c-certain acute or chronic sinusitis;

d-seasonal allergic rhinitis in short courses;

e-acute stridulous laryngitis (subglottic laryngitis) in children.

XII-RESPIRATORY

a-persistent asthma, preferably in short courses in case of failure of inhaled treatment at high doses;

b-exacerbations of asthma, particularly severe acute asthma;

c-chronic obstructive pulmonary disease in assessment of the reversibility of the obstructive syndrome

d-progressive sarcoidosis;

e-diffuse interstitial pulmonary fibroses.

XIII-RHEUMATOLOGICAL

a-rheumatoid arthritis and certain polyarthritis;

b-polymyalgia rheumatica and giant cell arteritis (Horton's disease);

c-acute rheumatic fever;

d-severe and refractory cervico-brachial neuralgias.

XIV-ORGAN AND ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

a-prophylaxis or treatment of graft rejection;

b-prophylaxis or treatment of graft-versus-host disease.

Dosage

FOR INFANTS AND CHILDREN ONLY.

Oral use.

40 drops correspond to 1 ml of solution and to 0,5 mg of betamethasone.

Anti-inflammatory equivalence (equipotency) for 5 mg of prednisone: 0,75 mg of betamethasone.

The dropper pipette must not be used to administer this medicine. The drops must be poured with the dropper pipette into a glass of water before administration. The solution is preferably taken at the end of a meal.

The dosage must be adapted to the condition and to the child's weight.

• Initial treatment: 0,075 mg/kg/day, i.e. 6 drops/kg/day to 0,3 mg/kg/day of betamethasone, i.e. 24 drops/kg/day (0,5 to 2 mg/kg/day prednisone equivalent).

For information: 150 to 600 drops for a child weighing 25 kg.

• Maintenance treatment: 0,03 mg/kg/day (i.e. 3 drops/kg/day).

For information: 75 drops for a child weighing 25 kg.

Alternate-day corticosteroid therapy (one day without corticosteroid and the second day with a dose double the daily dose that would otherwise have been required) is used in children to try to limit growth retardation. This alternate-day regimen can only be considered after control of the inflammatory disease with high corticosteroid doses, and when no rebound is observed during tapering.

IN GENERAL

The "loading dose" treatment must be continued until sustained control of the disease. The dose reduction must be slow. Achieving withdrawal is the aim sought. Maintaining a maintenance dose (minimum effective dose) is a compromise that is sometimes necessary.

For prolonged treatment and high doses, the initial doses may be divided into two daily intakes. Subsequently, the daily dose may be administered as a single intake, preferably in the morning during a meal.

DISCONTINUATION OF TREATMENT

The pace of withdrawal depends mainly on the duration of treatment, the starting dose and the disease.

The treatment leads to suppression of ACTH and cortisol secretion, sometimes with lasting adrenal insufficiency. When weaning, discontinuation must be carried out gradually, in steps, because of the risk of relapse: reduction of 10% every 8 to 15 days on average.

For short courses of less than 10 days, stopping the treatment does not require tapering.

During dose tapering (prolonged course): at a dose of 5 to 7 mg prednisone equivalent, when the underlying disease no longer requires corticosteroid therapy, it is advisable to replace the synthetic corticosteroid with 20 mg/day of hydrocortisone until recovery of corticotropic function. If corticosteroid therapy must be maintained at a dose below 5 mg prednisone equivalent per day, a small dose of hydrocortisone may be added to reach a hydrocortisone equivalent of 20 to 30 mg per day. When the patient is only on hydrocortisone, the corticotropic axis can be tested by endocrine tests. These tests alone do not rule out the possibility of adrenal insufficiency occurring during stress.

Under hydrocortisone or even after discontinuation, the patient must be informed of the need to increase the usual dose or to resume substitution treatment (for example 100 mg of hydrocortisone intramuscularly every 6 to 8 hours) in the event of stress: surgical intervention, trauma, infection.

Method of administration

Put the drops in a little water. The solution is preferably taken at the end of a meal.

This medicine is generally contraindicated in the following situations: (however, there is no absolute contraindication for corticotherapy with a vital indication.)

• Hypersensitivity to betamethasone or to any of the excipients mentioned in section Composition,

• Any infectious condition except for the specified indications (see section Indications),

• Certain ongoing viral infections (notably hepatitis, herpes, chickenpox, shingles),

• Psychotic states not yet controlled by treatment,

• Live vaccines,

This medicine is generally not recommended in combination with non-antiarrhythmic medicines causing torsades de pointes (see section Interactions).

Special warnings

• In cases of gastroduodenal ulcer, corticotherapy is not contraindicated if anti-ulcer treatment is given concomitantly.

In the case of a history of ulcer, corticosteroid therapy may be prescribed, with clinical monitoring and, if necessary, after fibroscopy.

• Corticotherapy may promote the occurrence of various infectious complications due notably to bacteria, yeasts and parasites. The occurrence of malignant strongyloidiasis is a significant risk. All subjects coming from an endemic area (tropical or subtropical region, southern Europe) must have a stool parasitological examination and systematic eradication treatment before corticotherapy.

Evolving signs of infection may be masked by corticosteroid therapy.

Before starting treatment, it is important to rule out any possibility of a visceral focus, notably tuberculosis, and to monitor during treatment for the appearance of infectious pathologies.

In case of past tuberculosis, prophylactic anti-tuberculosis treatment is necessary if there are significant radiological sequelae and if one cannot ensure that a well-conducted treatment of 6 months with rifampicin has been given.

• The use of corticosteroids requires particularly appropriate monitoring, notably in elderly subjects and in cases of ulcerative colitis (risk of perforation), recent intestinal anastomoses, renal insufficiency, hepatic insufficiency, osteoporosis, myasthenia gravis.

• Visual disturbances: visual disturbances may occur during systemic or local corticotherapy. In cases of blurred vision or the appearance of any other visual symptom during corticotherapy, an ophthalmological examination is required to look for cataract, glaucoma, or a rarer lesion such as central serous chorioretinopathy, described with the administration of systemic or local corticosteroids.

• A pheochromocytoma crisis, which may be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should be administered to patients in whom the presence of a pheochromocytoma is suspected or confirmed only after appropriate assessment of the benefit/risk ratio.

• This medicine contains sucrose. Its use is not recommended in patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase/isomaltase deficiency.

• This medicine contains sorbitol. Its use is not recommended in patients with fructose intolerance (a rare hereditary disease).

• This medicine contains propylene glycol and may cause symptoms similar to those caused by alcohol.

Precautions for use

• In case of long-term corticosteroid treatment:

• A diet low in rapidly absorbed sugars and high in protein should be combined, due to the hyperglycaemic effect and protein catabolism with negative nitrogen balance.
• Hydrosodium retention is usual, partly responsible for a possible rise in blood pressure. Sodium intake should be reduced for daily dosages above 15 or 20 mg prednisone equivalent and moderated in long-term treatments at low doses.
• Potassium supplementation is justified only for high-dose treatments, prescribed for a long duration, or in case of risk of rhythm disturbances or association with a hypokalaemic treatment.
• The patient must systematically have an intake of calcium and vitamin D
• When corticosteroid therapy is essential, diabetes and arterial hypertension are not contraindications, but the treatment may cause their imbalance. Their management should be reassessed.
• Patients should avoid contact with individuals suffering from chickenpox or measles.

• Attention is drawn to athletes, as this specialty contains an active substance that may induce a positive reaction in tests carried out during anti-doping controls.

Combinations not recommended

+ Medicines causing torsades de pointes (astemizole, bepridil, erythromycin IV, halofantrine, pentamidine, sparfloxacin, sultopride, terfenadine, vincamine)

Use substances that do not carry the risk of causing torsades de pointes in cases of hypokalaemia.

Associations requiring precautions for use

+ Acetylsalicylic acid by general route and, by extrapolation, other salicylates

Decrease in salicylaemia during treatment with corticoids and risk of salicylate overdose after its discontinuation, due to increased elimination of salicylates by corticoids.

Adjust salicylate doses during the combination and after discontinuation of corticoid treatment.

 + Antiarrhythmics causing torsades de pointes (amiodarone, bretylium, disopyramide, quinidine-like agents, sotalol).

Hypokalaemia is a predisposing factor, as are bradycardia and a pre-existing long QT interval.

Prevent hypokalaemia and correct it if necessary; monitor the QT interval. In case of torsades, do not administer antiarrhythmics (electrical overdrive pacing).

+ Oral anticoagulants

Possible impact of corticotherapy on the metabolism of oral anticoagulants and on that of coagulation factors.

Corticosteroid-specific bleeding risk (gastrointestinal mucosa, vascular fragility) at high doses or with prolonged treatment longer than 10 days.

When the combination is justified, reinforce monitoring: biological check at 8th day, then every 15 days during corticosteroid therapy and after its discontinuation.

+ Other potassium-lowering agents (potassium-depleting diuretics alone or in combination, stimulant laxatives, amphotericin B (IV route))

Increased risk of hypokalaemia through additive effect.

Monitor serum potassium and correct if necessary, especially in cases of digitalis therapy.

+ Digitalis glycosides

Hypokalaemia favouring the toxic effects of digitalis.

Monitor serum potassium, correct if necessary, and possibly ECG.

+ Heparins by parenteral route

Increased by heparin of the corticosteroid-specific bleeding risk (gastrointestinal mucosa, vascular fragility) at high doses or with prolonged treatment longer than 10 days.

The combination must be justified; reinforce monitoring.

+ Enzyme inducers: carbamazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampicin.

Decrease in plasma levels and efficacy of corticosteroids through increased hepatic metabolism. The consequences are particularly significant in Addisonian patients and in cases of transplantation.

Clinical and biological monitoring; adjust corticosteroid dosage during the combination and after discontinuation of the enzyme inducer.

+ Insulin, metformin, hypoglycaemic sulfonylureas

Elevation of blood glucose, sometimes with ketosis (decreased glucose tolerance caused by corticosteroids).

Inform the patient and reinforce blood and urine self-monitoring, especially at the start of treatment.

Possibly adjust the antidiabetic dosage during corticosteroid treatment and after its discontinuation.

+ Isoniazid (described for prednisolone)

Decrease in plasma levels of isoniazid. Proposed mechanism: increased hepatic metabolism of isoniazid and decreased metabolism of glucocorticoids.

Clinical and biological monitoring.

+ Gastrointestinal antacids: salts, oxides and hydroxides of magnesium, aluminum and calcium (described for prednisolone, dexamethasone).

Decreased digestive absorption of glucocorticoids.

Take gastrointestinal topicals at a distance from glucocorticoids (more than 2 hours if possible).

+ CYP3A inhibitors

Concomitant administration of CYP3A inhibitors, including products containing cobicistat, is expected to increase the risk of systemic side effects. The combination should be avoided, unless the benefits outweigh the increased risk of systemic side effects of corticosteroids; in this case, patients should be monitored for possible systemic side effects of corticosteroids.

Associations to be taken into account

+ Antihypertensives

Decreased antihypertensive effect (sodium and water retention by corticosteroids).

+ Interferon alpha

Risk of inhibition of the action of interferon.

+ Live attenuated vaccines

Risk of generalised disease, possibly fatal. This risk is increased in subjects already immunocompromised by the underlying disease.

Use an inactivated vaccine where one exists (poliomyelitis).

Pregnancy

In animals, experimentation shows a teratogenic effect that varies according to species.

In humans, transplacental passage occurs. However, epidemiological studies have not detected any malformation risk associated with corticosteroid use during the first trimester.

During chronic diseases requiring treatment throughout pregnancy, a slight intrauterine growth retardation is possible. Neonatal adrenal insufficiency has been exceptionally observed after high-dose corticosteroid therapy.

A period of clinical (weight, diuresis) and biological monitoring of the newborn is warranted.

Consequently, corticosteroids may be prescribed during pregnancy if necessary.

Breast-feeding

In case of treatment at high doses and chronically, breastfeeding is not recommended.

Fertility

Not applicable.

Paediatric population

They are mainly to be feared at high doses or during prolonged treatment lasting several months :

• Hydro-electrolytic disorders: hypokalaemia, metabolic alkalosis, hydrosodium retention, arterial hypertension, congestive heart failure.

• Endocrine and metabolic disorders: iatrogenic Cushing's syndrome, inertia of ACTH secretion, corticoadrenal atrophy sometimes permanent, decreased glucose tolerance, unmasking of latent diabetes, growth arrest in children, menstrual irregularities, onset of crises related to the presence of pheochromocytoma (class effect of corticosteroids – See section Warnings and precautions).

• Musculoskeletal disorders: muscular atrophy preceded by muscular weakness (increased protein catabolism), osteoporosis, pathological fractures in particular vertebral compression fractures, aseptic osteonecrosis of the femoral heads.

• Digestive disorders: hiccups, gastroduodenal ulcers, small intestine ulceration, perforations and digestive haemorrhage; acute pancreatitis has been reported, especially in children.

• Skin disorders: acne, purpura, ecchymosis, hypertrichosis, delayed wound healing and angioedema.

• Neuropsychiatric disorders:

• Frequently: euphoria, insomnia, excitation;
• Rarely: manic-type episodes, confusional or confusional-oneiric states, convulsions (systemic or intrathecal route).
• Depressive state on treatment discontinuation.

• Ocular disorders: blurred vision, certain forms of glaucoma and cataract, chorioretinopathies (see section Warnings and precautions).

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 national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr

Treatment of acute overdose includes gastric lavage and induction of vomiting, followed by symptomatic treatment if necessary.

Pharmacotherapeutic class: Glucocorticoid - systemic use.

(H: Non-sex hormones)

Physiological glucocorticoids (cortisone and hydrocortisone) are essential metabolic hormones. Synthetic corticosteroids, including this specialty, are used mainly for their anti-inflammatory effect.

At high doses, they reduce the immune response. Their metabolic and sodium-retaining effect is lower than that of hydrocortisone.

Betamethasone is absorbed from the digestive tract. Protein binding is of the order of 60%.

Betamethasone is metabolised in the liver and eliminated by the kidney. The plasma half-life of betamethasone is of the order of 5 hours. The biological half-life is 36 to 54 hours.

Before opening: 24 months.

After opening: 8 weeks.

No special storage conditions.

Use in the paediatric population

No special requirements.

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

List I

Marketing authorisation (AMM)

CIP 3400938947366 (Fl/30ml).

Price:

2,89 euros (Fl/30ml).

Social Security reimbursement at 65%.
Collection.