Oftan Dexamethason

Neurology

Cerebral oedema caused by brain tumours, neurosurgery, bacterial meningitis, brain abscess.

Pulmonary and respiratory diseases

Severe acute asthma attack.

Dermatology

Oral initial treatment of extensive, severe, acute skin diseases that respond to glucocorticoids, such as erythroderma, pemphigus vulgaris, acute eczema.

Autoimmune disorders/rheumatology

Oral initial treatment of autoimmune diseases, such as systemic lupus erythematosus (especially visceral forms).

Severely progressive form of active rheumatoid arthritis, e.g. rapidly destructive forms and/or with extra-articular manifestations.

Infectology

Severe infections with toxic conditions (e.g. tuberculosis, typhoid) only with concomitant anti-infective therapy.

Oncology

Palliative treatment of malignant tumours.

Endocrinology

Congenital adrenogenital syndrome in adulthood.

Posology

Dosage depends on the nature and severity of the disease and the individual response of the patient to treatment. In general, relatively high initial doses are administered, and they should be significantly higher in acute severe forms than in chronic diseases.

Unless otherwise prescribed, the following dosage recommendations apply:

- Cerebral oedema: Depending on the cause and severity, initial dose of 8-10 mg (up to 80 mg) i.v., followed by 16-24 mg (up to 48 mg)/day orally, divided into 3-4 (up to 6) individual doses for 4-8 days. A longer-term, lower-dose administration of Oftan Dexamethason Krka may be required during irradiation and in the conservative treatment of inoperable brain tumours.

- Cerebral oedema due to bacterial meningitis: 0.15 mg/kg body weight every 6 hours for 4 days, children: 0.4 mg/kg body weight every 12 hours for 2 days, starting before the first antibiotics.

- Severe acute asthma attack: Adults: 8-20 mg, then, if necessary, 8 mg every 4 hours. Children: 0.15-0.3 mg/kg body weight.

- Acute skin diseases: Depending on the nature and extent of the disease, daily doses of 8-40 mg. Followed by treatment with decreasing doses.

- Active phases of rheumatic systemic diseases: systemic lupus erythematosus 6-16 mg/day.

- Severely progressive form of active rheumatoid arthritis: in rapidly destructive forms 12-16 mg/day, in extra-articular manifestations 6-12 mg/day

- Severe infectious diseases, toxic states (e.g. tuberculosis, typhoid): 4-20 mg for a few days, only with concomitant anti-infective therapy.

- Palliative treatment of malignant tumours: initially 8-16 mg/day, in prolonged treatment 4-12 mg/day.

- Congenital adrenogenital syndrome in adulthood: 0.25-0.75 mg/day as a single dose. If necessary, addition of a mineralcorticoid (fludrocortisone). In cases of particular physical stress (e.g. trauma, surgery), intercurrent infections, etc., a 2- to 3-fold dose increase may be required and under extreme stress (e.g. birth) a 10-fold increase.

The tablets should not be split to adjust doses. If patients need a dose that cannot be provided by one or more tablets of 0.5mg, other appropriate formulations should be used.

Method of administration

The tablets should be taken during or after a meal. They should be swallowed whole, with a sufficient amount of liquid. The daily dose should be administered as a single dose in the morning, if possible (circadian therapy). In patients who require a high-dose therapy because of their disease, multiple daily dosing is often required to achieve maximum effect.

Depending on the underlying disease, clinical symptoms and response to therapy, the dose can be reduced at a faster or slower rate and the therapy stopped, or the patient is stabilised on a maintenance dose as low as possible and, if necessary, adrenal axis monitored. Basically, the dose and duration of treatment should be kept as high and long as necessary, but as low and short as possible. In principle, the dose should be reduced gradually.

In long-term therapy which is deemed necessary following initial treatment, patients should be switched to prednisone/prednisolone, because this leads to lower adrenal suppression.

In hypothyroidism or liver cirrhosis, low doses may be sufficient or a dose reduction may be necessary.

Depending on the dose and duration of therapy, adrenocortical insufficiency caused by glucocorticoid therapy can continue for several months and in individual cases more than a year after cessation of therapy. In cases of particular physical stress situations (trauma, surgery, childbirth, etc.) during treatment with Oftan Dexamethason Krka, a temporary increase in dose may be required. Because of the potential risk in stress situations, patients on extended therapy should be issued a steroid card. Also in prolonged adrenal insufficiency after cessation of treatment, the administration of glucocorticoids may be necessary in physical stress situations. In case of intended withdrawal, treatment-induced acute adrenal insufficiency may be minimized by slow dose reduction.

Through immunosuppression, treatment with Oftan Dexamethason Krka can lead to an increased risk of bacterial, viral, parasitic, opportunistic and fungal infections. It can mask the symptoms of an existing or developing infection, thereby making a diagnosis more difficult. Latent infections, like tuberculosis or hepatitis B, can be reactivated.

Treatment with Oftan Dexamethason Krka should only be implemented in the event of the strongest indications and, if necessary, additional targeted anti-infective treatment administered for the following illnesses:

- Acute viral infections (Herpes zoster, Herpes simplex, Varicella, herpetic keratitis)

- HBsAG-positive chronic active hepatitis

- Approximately 8 weeks prior to 2 weeks after vaccinations with live vaccines

- Systemic mycoses and parasitoses (e.g. nematodes)

- In patients with suspected or confirmed strongyloidiasis (infection with threadworms), glucocorticoids can lead to activation and mass proliferation of these parasites

- Poliomyelitis

- Lymphadenitis after BCG vaccination

- Acute and chronic bacterial infections

- In a history of tuberculosis (reactivation risk), use only under tuberculostatic protection

In addition, treatment with Oftan Dexamethason Krka should only be implemented under strong indications and, if necessary, additional specific treatment must be implemented for:

- Gastrointestinal ulcers

- Osteoporosis

- Severe cardiac insufficiency

- High blood pressure that is difficult to regulate

- Diabetes mellitus that is difficult to regulate

- Psychiatric disorders (also in the past), including suicidality: neurological or psychiatric monitoring is recommended

- Narrow- and wide-angle glaucoma, ophthalmic monitoring and adjunctive therapy are recommended

- Corneal ulcerations and corneal injuries, ophthalmic monitoring and adjunctive therapy are recommended

Because of the risk of an intestinal perforation, Oftan Dexamethason Krka may only be used under urgent indication and under appropriate monitoring for:

- Severe ulcerative colitis with threatened perforation, possibly without peritoneal irritation

- Diverticulitis

- Enteroenterostomy (immediately postoperatively)

Signs of peritoneal irritation after gastrointestinal perforation may be absent in patients receiving high doses of glucocorticoids.

The possibility of a higher need for insulin or oral antidiabetics must be taken into consideration when administering Oftan Dexamethason Krka to diabetics.

Regular blood pressure monitoring is necessary during treatment with Oftan Dexamethason Krka, particularly during administration of higher doses and in patients with high blood pressure that is difficult to regulate.

Because of the risk of deterioration, patients with severe cardiac insufficiency should be carefully monitored.

With high doses of Oftan Dexamethason bradycardia may occur.

Severe anaphylactic reactions may occur.

The risk of tendon disorders, tendinitis and tendon rupture is increased when fluoroquinolones and glucocorticoids are administered together.

A concurrent myasthenia gravis may initially worsen during treatment with Oftan Dexamethason Krka.

Vaccinations with inactivated vaccines are generally possible. However, it should be noted that the immune response and thus the vaccine may be compromised at higher doses of corticosteroids.

During long-term therapy with Oftan Dexamethason Krka, regular medical checkups (including ophthalmologic every three months) are indicated.

At high doses, sufficient calcium intake and sodium restriction should be ensured and serum potassium levels should be monitored.

Depending on the dose and duration of treatment, a negative effect on calcium metabolism can be expected; therefore, the prevention of osteoporosis is recommended. This applies especially to patients with concomitant risk factors, such as familial predisposition, advanced age, postmenopausal period, insufficient protein and calcium intake, heavy smoking, excessive alcohol consumption and lack of physical activity. Prevention consists of sufficient calcium and vitamin D intake and physical activity. In already existing osteoporosis, additional drug therapy should be considered.

Upon termination of long-term administration of glucocorticoids, the following risks must be taken into account: exacerbation or relapse of the underlying disease, acute adrenal insufficiency, cortisone withdrawal syndrome.

Certain viral diseases (chickenpox, measles) may be very severe in patients treated with glucocorticoids. Immunocompromised patients without previous chickenpox or measles infection are particularly at risk. If these patients have contact with people infected with measles or chickenpox while undergoing treatment with Oftan Dexamethason Krka, a preventative treatment should be introduced, if necessary.

In post marketing experience tumour lysis syndrome (TLS) has been reported in patients with haematological malignancies following the use of Oftan Dexamethason alone or in combination with other chemotherapeutic agents. Patient at high risk of TLS, such as patients with high proliferative rate, high tumour burden, and high sensitivity to cytotoxic agents, should be monitored closely and appropriate precaution taken.

Visual disturbance

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

Paediatric population

In the growth phase of children, the benefit-risk balance of treatment with Oftan Dexamethason Krka should be carefully weighed.

Therapy should be of limited duration or in case of long-term therapy, it should be carried out alternatingly.

Preterm neonates: Available evidence suggests long-term neurodevelopmental adverse events after early treatment (< 96 hours) of premature infants with chronic lung disease at starting doses of 0.25mg/kg twice daily.

Elderly patients

Because elderly patients are at an increased risk of osteoporosis, the benefit-risk balance of treatment with Oftan Dexamethason Krka should be carefully weighed.

Note

The use of Oftan Dexamethason Krka can lead to positive results in doping controls.

Oftan Dexamethason Krka contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

There have been no studies on the effects on the ability to drive and use machines.

- 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)

- Not known (cannot be estimated from the available data)

Hormone replacement therapy:

Low risk of undesirable effects with the use of recommended doses.

Pharmacotherapy:

The following undesirable effects may occur; they are highly dependent on the dose and duration of treatment, so their frequency cannot be specified:

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.

Symptoms

Acute intoxications with Oftan Dexamethason are not known. In case of chronic overdosing, an increase in undesirable effects, especially endocrine, metabolic and electrolyte-related effects, can be expected.

Management

There is no known antidote to Oftan Dexamethason.

Pharmacotherapeutic group: corticosteroids for systemic use, glucocorticoids, ATC code: H02AB02.

Mechanism of action

Oftan Dexamethason is a mono-fluorinated glucocorticoid with pronounced anti-allergic, anti-inflammatory and membrane-stabilizing properties and effects on carbohydrate, protein and fat metabolism.

Oftan Dexamethason has an approximately 7.5 times greater glucocorticoid effect than prednisolone, and compared to hydrocortisone it is 30 times more effective, lacking mineralocorticoid effects.

Glucocorticoids, such as Oftan Dexamethason, exert their biological effects by activating the transcription of corticosteroid-sensitive genes. The anti-inflammatory, immunosuppressive and anti-proliferative effects are caused by decreased formation, release and activity of inflammatory mediators, by the inhibition of specific functions and the migration of inflammatory cells. In addition, the effect of sensitized T lymphocytes and macrophages on target cells may be prevented by corticosteroids.

When long-term corticoid treatment is required, the possibility of induction of transient adrenal insufficiency must be considered. The suppression of the hypothalamic-pituitary-adrenal axis also depends on individual factors.

Absorption and distribution

After oral administration, Oftan Dexamethason is rapidly and almost completely absorbed in the stomach and small intestine. Its bioavailability is 80-90%. Maximum blood levels are reached between 60 and 120 minutes. The binding of Oftan Dexamethason to plasma albumins is dose-dependent. At very high doses, the largest portion circulates freely in the blood. In hypoalbuminaemia the proportion of the unbound (active) corticoid rises.

Biotransformation

The average (serum) elimination half-life of Oftan Dexamethason in adults is 250 minutes (+ 80 minutes). Due to its long biological half-life of more than 36 hours, daily continuous administration of Oftan Dexamethason can lead to accumulation and overdosing.

Elimination

The elimination is largely renal in the form of free Oftan Dexamethason alcohol. Oftan Dexamethason is partly metabolised, the metabolites are excreted as glucuronates or sulfates, also mainly by the kidneys.

Renal and hepatic impairment

Renal function impairment has no relevant effect on the clearance of Oftan Dexamethason. However, the elimination half-life is prolonged in severe liver disease.

Acute toxicity:

In mice and rats, the LD₅₀ for Oftan Dexamethason after a single oral dose is 16 g/kg body and over 3 g/kg body weight, respectively, within the first 7 days. Following a single subcutaneous dose, the LD₅₀ in mice is more than 700 mg/kg body weight and in rats about 120 mg/kg body weight, within the first 7 days.

Over a period of 21 days, these values become lower, which is interpreted as a consequence of serious infectious diseases caused by the hormone-induced immunosuppression.

Chronic toxicity:

There are no data on chronic toxicity in humans and animals. Corticoid-induced intoxications are not known. In longer-term treatment with doses above 1.5 mg/day, pronounced undesirable effects can be expected.

Mutagenic and tumorigenic potential:

The available study findings for glucocorticoids show no evidence of clinically relevant genotoxic properties.

Reproductive toxicity:

In animal studies, cleft palate was observed in rats, mice, hamsters, rabbits, dogs and primates; not in horses and sheep. In some cases these divergences were combined with defects of the central nervous system and of the heart. In primates, effects in the brain were seen after exposure. Moreover, intrauterine growth can be delayed. All these effects were seen at high dosages.

Not applicable.

No special requirements for disposal.