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

Oral drops solution.

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

For a bottle of 30 ml.

Excipients with known effect: this medicine contains 12,60 g of sorbitol, 8,9556 g of sucrose, 10,50 g of propylene glycol, 0,03 g of sodium benzoate and 36,6 mg of sodium per bottle.

Excipients:

INDICATIONS OR DISEASES:

I- COLLAGEN DISEASES-CONNECTIVE TISSUE

Evolving flares of systemic diseases, notably: 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- evolving flares of haemorrhagic rectocolitis 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 threatening the vital prognosis

b- pneumonia due to Pneumocystis carinii with severe hypoxia

VII- NEOPLASTIC

a- antiemetic 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- vasculitides 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- relapsing multiple sclerosis, following intravenous corticosteroid therapy

X- OPHTHALMOLOGICAL

a- severe anterior and posterior uveitis

b- oedematous exophthalmos

c- certain optic neuropathies, following intravenous corticosteroid therapy (in this indication, oral route as first intention is not recommended)

XI- ENT

a- certain serous otitis media

b- nasosinusal 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- asthma exacerbations, in particular severe acute asthma

c- chronic obstructive pulmonary disease under evaluation for reversibility of the obstructive syndrome

d- progressive sarcoidosis

e- diffuse interstitial pulmonary fibroses

XIII- RHEUMATOLOGICAL

a- rheumatoid arthritis and certain polyarthritides

b- polymyalgia rheumatica-like pseudo-polyarthritis and giant cell arteritis (Horton disease)

c- acute rheumatic fever

d- severe and refractory cervicobrachial neuralgia

XIV- ORGAN AND ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

a- prophylaxis or treatment of graft rejection

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

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.

Place the drops in a glass of water. The solution is preferably taken at the end of a meal.

FOR INFANTS AND CHILDREN ONLY

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

• Initial (loading) 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 guidance: 150 to 600 drops for a child of 25 kg.

• Maintenance treatment: 0,03 mg/kg/day (i.e. 3 drops/kg/day).
For guidance: 75 drops for a child of 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.

General

The "loading dose" treatment must be continued until durable control of the disease. The tapering must be slow. Achieving withdrawal is the goal sought. Maintenance of a maintenance dose (minimum effective dose) is sometimes a necessary compromise.

For prolonged, high-dose treatment, 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 with a meal.

Discontinuation of treatment

The rate 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. During withdrawal, discontinuation must be done 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 dosage 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 with endocrine tests. These tests alone do not rule out the possibility of adrenal insufficiency occurring during stress.

Under hydrocortisone or even remote from discontinuation, the patient must be warned of the need to increase the usual dosage or to resume replacement therapy (for example 100 mg of hydrocortisone intramuscularly every 6 to 8 hours) in case of stress: surgical intervention, trauma, infection.

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

• hypersensitivity to the active substance or to any of the excipients listed in section Composition ;

• any infectious state, excluding the specified indications (see section Indications) ;

• certain active 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

• 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.

• In case of gastroduodenal ulcer, corticosteroid therapy is not contraindicated if anti-ulcer treatment is associated.

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

• Corticosteroid therapy may promote the occurrence of various infectious complications due in particular to bacteria, yeasts and parasites. The occurrence of malignant strongyloidiasis is a significant risk.

All subjects coming from an endemic area (tropical and subtropical regions, southern Europe) must have a stool parasitological examination and systematic eradication treatment before corticosteroid therapy.

The evolving signs of an 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 for the appearance of infectious pathologies during treatment.

In case of old tuberculosis, prophylactic anti-tuberculosis treatment is necessary if significant radiological sequelae exist and if it cannot be ensured 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.

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 ingredient that may induce a positive reaction in tests carried out during anti-doping controls.

• Visual disturbances may occur during corticosteroid therapy by systemic or local route (notably nasal, inhaled and intra-ocular). In case of blurred vision or onset of any other visual symptom during corticosteroid therapy, an ophthalmological examination is required to look for visual disorders, notably cataract, glaucoma, or a rarer lesion such as central serous chorioretinopathy, described with the administration of systemic or local corticosteroids.

Excipients with known effect

This medicine contains 8,9556 g of sucrose per vial. This should be taken into account for patients with diabetes mellitus. It may be harmful to teeth. Patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase/isomaltase deficiency (rare hereditary diseases) must not take this medicine.

This medicine contains 12,60 g of sorbitol per vial. Patients with hereditary fructose intolerance (HFI) must not take/receive this medicine. Sorbitol may cause gastrointestinal discomfort and a mild laxative effect.

This medicine contains 10,50 g of propylene glycol per vial. If your child is under 5 years old, ask your doctor or pharmacist before giving this medicine, especially if they are receiving other medicines containing propylene glycol or alcohol. If you suffer from a liver or kidney disease, take this medicine only on the advice of your doctor. Your doctor may carry out additional tests while you are taking this medicine.

This medicine contains 0.03 g of sodium benzoate per vial. Sodium benzoate may increase the risk of jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks).

This medicine contains 36,6 mg of sodium per vial, which is equivalent to 1,8 % of the maximum recommended daily dietary intake of 2 g of sodium per adult set by the WHO.

Combinations not recommended

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

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

+ 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 that case, patients must be monitored to detect any systemic side effects of corticosteroids.

Associations subject to Precautions for use

+ Systemic acetylsalicylic acid and, by extrapolation, other salicylates 

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

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

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

Hypokalemia is a contributing factor, as are bradycardia and a pre-existing long QT interval.

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

+ Oral anticoagulants 

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

Bleeding risk specific to corticosteroid therapy (digestive mucosa, vascular fragility) at high doses or during prolonged treatment exceeding 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, intravenous amphotericin B) 

Increased risk of hypokalemia through additive effect.

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

+ Digitalis glycosides 

Hypokalemia promotes the toxic effects of digitalis.

Monitor serum potassium, correct it if necessary, and possibly perform an ECG.

+ Parenteral heparins 

Potentiation by heparin of the bleeding risk specific to corticosteroid therapy (gastrointestinal mucosa, vascular fragility) at high doses or during prolonged treatment exceeding 10 days.

The combination must be justified and monitoring reinforced.

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

Decrease in plasma levels and efficacy of corticosteroids due to increased hepatic metabolism. The consequences are particularly significant in patients with Addison's disease and in cases of transplantation.

Clinical and biological monitoring, adjustment of the corticosteroid dose 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 dose of the antidiabetic agent 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, aluminium and calcium (described for prednisolone and dexamethasone)

Decreased gastrointestinal absorption of glucocorticoids.

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

Associations to be taken into account

+ Antihypertensives 

Decrease in antihypertensive effect (sodium and water retention caused by corticosteroids).

+ Interferon alfa

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.

They are mainly to be feared at high doses or during prolonged treatment over 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, revelation of latent diabetes, growth arrest in children, menstrual irregularities.

• 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, ulceration of the small intestine, 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 discontinuation of treatment.

• Ocular disorders: certain forms of glaucoma and cataract; blurred vision (see also 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 reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - 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, ATC code: H02AB01.

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 decrease the immune response. Their metabolic and sodium-retaining effect is less than that of hydrocortisone.

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

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

Before opening: 24 months.

After opening: 8 weeks.

This medicine does not require any particular storage precautions.

No special requirements.

List I

Marketing authorisation (AMM)

CIP 3400938947076 (Fl/30ml).

Price:

2,89 euros (Fl/30ml).

Social Security reimbursement at 65%.
Collection.