Source: Health Products Regulatory Authority (ZA) Revision Year: 2022 Publisher: PHARMACARE LIMITED, Healthcare Park, Woodlands Drive, Woodmead 2191
ASPELONE is contraindicated in:
Patients who have received more than physiological doses of systemic corticosteroids, such as prednisolone, as in ASPELONE, (approximately 7,5 mg prednisolone or equivalent), for greater than three weeks, withdrawal should not be abrupt. How dose reduction should be carried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids, such as prednisolone, as in ASPELONE is reduced. Clinical assessment of disease activity may be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids, such as prednisolone, as in ASPELONE, but there is uncertainty about HPA suppression, the dose of systemic corticosteroid, such as prednisolone, as in ASPELONE, may be reduced rapidly to physiological doses. Once a daily dose equivalent to 7,5 mg (2,5 ml) prednisolone, as in ASPELONE, is reached, dose reduction should be slower to allow the HPA axis to recover.
Abrupt withdrawal of systemic corticosteroid treatment, such as prednisolone, as in ASPELONE, which has continued up to three weeks is appropriate if it is considered that the disease is unlikely to relapse.
Abrupt withdrawal of doses of up to 40 mg daily of prednisolone, as in ASPELONE, or equivalent for three weeks is unlikely to lead to clinically relevant HPA axis suppression, in the majority of patients. In the following patient groups, gradual withdrawal of systemic corticosteroid therapy, such as ASPELONE should be considered even after courses lasting three weeks or less:
Adrenal cortical atrophy develops during prolonged therapy and may persist for years after stopping treatment. Withdrawal of corticosteroids, such as ASPELONE, after prolonged therapy must therefore always be gradual to avoid acute adrenal insufficiency, being tapered off over weeks or months according to the dose and duration of treatment. During prolonged therapy any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids, such as ASPELONE have been stopped following prolonged therapy they may need to be temporarily re-introduced (see section 4.8).
Bradycardia is a rare but serious adverse effect of corticosteroids, such as prednisolone, as in ASPELONE, that may be both symptomatic and asymptomatic. It is most likely to occur with high doses of corticosteroids, such as prednisolone, as in ASPELONE, however, bradycardia can occur even with standard doses of oral corticosteroids, such as prednisolone, as in ASPELONE, and is reversible with dose reduction or discontinuation. Furthermore, patients with pre-existing cardiac or renal problems or electrolyte imbalance are at high risk of experiencing bradycardia (see section 4.8). The degree of risk may be increased by the concomitant use of other medicines that causes bradycardia as an adverse event.
Suppression of the HPA axis and other undesirable effects may be minimised by using the lowest effective dose for the minimum period and by administering the daily requirement as a single morning dose or whenever possible as a single morning dose on alternate days. Frequent patient review is required to appropriately titrate the dose against disease activity (see section 4.2).
Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The resultant opportunistic infections may be fatal. The clinical presentation may often be atypical and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognised.
Chickenpox is of particular concern since this normally minor illness may be fatal in immunosuppressed patients. Patients without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed they should seek urgent medical attention. If the patient is a child, parents must be given the above advice. Passive immunisation with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids such as prednisolone, as in ASPELONE, or who have used them within the previous three months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids, such as prednisolone, as in ASPELONE, should not be stopped and the dose may need to be increased.
Patients should be advised to take particular care to avoid exposure to measles and to seek immediate advice if exposure occurs. Prophylaxis with intramuscular normal immunoglobulin may be needed.
Live vaccines should not be given to individuals with impaired immune responsiveness caused by high doses of corticosteroids, such as prednisolone, as in ASPELONE. The antibody response to other vaccines may be diminished (see section 4.3).
Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid, such as prednisolone, as in ASPELONE, therapy. Discontinuation of corticosteroids, such as prednisolone, as in ASPELONE, may result in clinical remission.
Chronic immunosuppression (e.g. in the setting of organ transplantation), has been associated with an increased risk ofmalignancy.
Due to the possibility of fluid retention, care must be taken when corticosteroids, such as prednisolone, as in ASPELONE are administered to patients with renal insufficiency or hypertension or congestive heart failure.
Corticosteroids, such as prednisolone, as in ASPELONE may worsen diabetes mellitus, hypertension, glaucoma and epilepsy and therefore patients with these conditions or a family history of them should be monitored frequently.
Care is required and frequent patient monitoring necessary where there is a previous steroid myopathy, hypothyroidism or recent myocardial infarction.
In patients with liver failure, blood levels of corticosteroid, such as prednisolone, as in ASPELONE may be increased, as with other medicines which are metabolised in the liver.
Frequent patient monitoring is therefore necessary.
Systemic ASPELONE should be used with caution in the elderly and in patients with heart failure, a recent myocardial infarction, hypertension, diabetes mellitus, epilepsy, glaucoma, hypothyroidism, heart failure, osteoporosis, peptic ulceration, psychoses or severe affective disorders and renal impairment, susceptibility to infection and thinning of the skin.
The common adverse effects of systemic corticosteroids, such as prednisolone, as in ASPELONE, may be associated with more serious consequences in old age. Close clinical supervision is required to avoid life-threatening reactions.
Patients on long-term corticosteroid treatment, such as prednisolone, as in ASPELONE, should be assessed on a regular basis for hypertension, hypokalaemia, glycosuria, gastric discomfort and mental disturbances. They may require potassium supplementation and their dietary intake of sodium may need to be reduced.
Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids, such as prednisolone, as in ASPELONE (see section 4.8). Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/systemic exposure (see section 4.5), although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most adverse reactions resolve after either dose reduction or withdrawal of the medicine, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, such as prednisolone, as in ASPELONE, although such reactions have been reported infrequently.
Particular care is required when considering the use of systemic corticosteroids, such as prednisolone, as in ASPELONE in patients with existing or a previous history of severe affective disorders in themselves or in their first-degree relatives. These would include depressive or manic-depressive illness and previous steroid psychosis.
Visual disturbance may be reported with systemic corticosteroids, such as prednisolone, as in ASPELONE, 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 corticosteroids, such as prednisolone, as in ASPELONE.
Caution is required in patients with systemic sclerosis because of an increased incidence of (possibly fatal) scleroderma renal crisis with hypertension and decreased urinary output observed with a daily dose of 15 mg or more prednisolone, such as prednisolone, as in ASPELONE. Blood pressure and renal function (s-creatinine) should therefore be routinely checked. When renal crisis is suspected, blood pressure should be carefully controlled.
ASPELONE alters the response to anti-coagulants and increases the requirements for antidiabetic or anti-hypertensive medicines (see section 4.5).
ASPELONE may lead to a reduced effect of antimuscarinics in the treatment of myasthenia gravis (see section 4.5).
Corticosteroids, such as prednisolone, as in ASPELONE cause dose-related growth retardation in infancy, childhood and adolescence, which may be irreversible.
ASPELONE contains sorbitol and glycerol and may have a laxative effect. The additive effect of concomitantly administered medicines containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. The content of sorbitol in medicines for oral use may affect the bioavailability of other medicines for oral use administered concomitantly.
Patients with hereditary fructose (sorbitol) intolerance (HFI) must not be given ASPELONE unless strictly necessary.
Co-administration with any substrate for alcohol dehydrogenase such as ethanol may induce serious adverse effects in neonates. and in children less than 5 years old.
Medical monitoring is required in patients with impaired renal or hepatic functions because various adverse events attributed to propylene glycol have been reported such as renal dysfunction (acute tubular necrosis), acute renal failure and liver dysfunction.
ASPELONE contains sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate and may cause allergic reactions (possibly delayed).
Co-treatment with CYP3A inhibitors, including cobicistat-containing medicines, is expected to increase the risk of systemic side effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid, such as prednisolone, as in ASPELONE, side effects, in which case patients should be monitored for systemic corticosteroid, such as prednisolone, as in ASPELONE, side effects.
Rifampicin, rifabutin, carbamazepine, barbiturates, phenobarbitone, immunosuppressants, phenytoin, primidone, ephedrine and aminoglutethimide enhance the metabolism of corticosteroids, such as prednisolone, as in ASPELONE and its therapeutic effects may be reduced.
Mifepristone may reduce the effect of corticosteroids, such as prednisolone, as in ASPELONE for 3 to 4 days.
Erythromycin and ketoconazole may inhibit the metabolism of some corticosteroids, such as prednisolone, as in ASPELONE.
Ciclosporin increases plasma concentration of prednisolone, as in ASPELONE. The same effect is possible with ritonavir.
Oestrogens and other oral contraceptives may potentiate the effects of glucocorticoids, such as prednisolone, as in ASPELONE and dosage adjustments may be required if oral contraceptives are added to or withdrawn from a stable dosage regimen. Plasma levels of corticosteroids, such as prednisolone, as in ASPELONE, may be elevated by oral contraceptives.
ASPELONE increases the requirements for anti-diabetic or anti-hypertensive medicines (see section 4.4).
The desired effects of hypoglycemic medicines (including insulin), anti-hypertensives and diuretics are antagonised by corticosteroids, such as prednisolone, as in ASPELONE.
The growth promoting effect of somatotropin may be inhibited by the concomitant use of corticosteroids, such as prednisolone, as in ASPELONE.
Steroids, such as prednisolone, as in ASPELONE may reduce the effects of anticholinesterases/antimuscarinics in the treatment of myasthenia gravis and cholecystographic x-ray media.
The efficacy of coumarin anticoagulants and warfarin may be enhanced by concurrent corticosteroid, such as prednisolone, as in ASPELONE, therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.
Concomitant use of aspirin and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) with corticosteroids, such as prednisolone, as in ASPELONE, increases the risk of gastrointestinal bleeding and ulceration.
The renal clearance of salicylates is increased by corticosteroids, such as prednisolone, as in ASPELONE withdrawal may result in salicylate intoxication.
Serum concentrations of salicylates may be reduced.
Hypokalaemia may result from concurrent administration with potassium-depleting diuretics such as the thiazides, furosemide, or bronchodilator therapy with xanthines or beta2-receptor agonists.
The hypokalaemic effects of acetazolamide, loop diuretics, and carbenoxolone, are enhanced by corticosteroids, such as prednisolone, as in ASPELONE. The risk of hypokalaemia is increased with theophylline and amphotericin. Corticosteroids, such as prednisolone, as in ASPELONE should not be given concomitantly with amphotericin, unless required to control reactions.
The risk of hypokalaemia also increases if high doses of corticosteroids, such as prednisolone, as in ASPELONE are given with high doses of bambuterol, fenoterol, formoterol, ritodrine, salbutamol, salmeterol and terbutaline. The toxicity of cardiac glycosides is increased if hypokalaemia occurs with corticosteroids, such as prednisolone, as in ASPELONE.
Concomitant use with methotrexate may increase the risk of haematological toxicity. High doses of corticosteroids, such as prednisolone, as in ASPELONE, impairs the immune response therefore live vaccines should be avoided (see also section 4.3 and 4.4).
The use of ASPELONE is contraindicated in pregnancy and lactation (see section 4.3).
The ability of corticosteroids such as prednisolone, as in ASPELONE, to cross placenta varies between individual medicines, however, 88% of prednisolone, as in ASPELONE, is inactivated as it crosses the placenta.
Administration of corticosteroids, such as prednisolone, as in ASPELONE to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and effects on brain growth and development. There is no evidence that corticosteroids, such as prednisolone, as in ASPELONE, result in an increased incidence of congenital abnormalities, such as cleft palate/lip. However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids, such as prednisolone, as in ASPELONE, may increase the risk of intrauterine growth retardation.
Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids, such as prednisolone, as in ASPELONE but usually resolves spontaneously following birth and is rarely clinically important. Depression of hormone levels has been described in pregnancy but the significance of this finding is not clear.
Corticosteroids, such as prednisolone, as in ASPELONE are excreted in small amounts in breast milk.
Corticosteroids, such as prednisolone, as in ASPELONE may cause irregular menstruation or amenorrhoea.
ASPELONE has no or negligible influence on the ability to drive or operate machinery.
Since adverse reactions such as dizziness, headache and blurred vision have been reported in patients receiving ASPELONE, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain that ASPELONE does not adversely affect their ability to do so (see section 4.4 and 4.8).
The incidence of predictable undesirable effects, including hypothalamo-pituitary-adrenal (HPA) suppression, correlates with the relative potency of the medicine, dosage, timing of administration and the duration of treatment (see section 4.4).
The following side effects may be associated with the long-term systemic use of corticosteroids, such as prednisolone, as in ASPELONE.
Neoplasms benign, malignant and unspecified (including cysts and polyps): Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroids, such as prednisolone, as in ASPELONE therapy. Discontinuation of ASPELONE may result in clinical remission.
Endocrine disorders: Large doses of ASPELONE may cause Cushingoid manifestations. These manifestations include moon-face, buffalo hump, flushing, ecchymosis, increased bruising, striae and acne, hypertension, hypokalaemia, glycosuria, gastric discomfort and mental disturbances.
Metabolism and nutrition disorders: Hyperglycaemia may occur with accentuation or precipitation of the diabetic state. Diabetic patients may also require more insulin.
Psychiatric disorders: A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported. Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated to be 5 to 6%. Psychological effects have been reported on withdrawal of corticosteroids, such as prednisolone, as in ASPELONE; the frequency is unknown.
Scleroderma renal crisis: Amongst the different subpopulations the occurrence of scleroderma renal crisis varies. The highest risk has been reported in patients with diffuse systemic sclerosis. The lowest risk has been reported in patients with limited systemic sclerosis (2%) and juvenile onset systemic sclerosis (1%) (see section 4.4),
ASPELONE should be gradually discontinued after prolonged therapy as rapid withdrawal may cause acute adrenal insufficiency.
Too rapid a reduction of corticosteroid, such as prednisolone, as in ASPELONE, dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death (see section 4.4). A ‘withdrawal syndrome’ may also occur including fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight. In some instances, withdrawal symptoms may involve or resemble a clinical relapse of the disease for which the patient has been undergoing treatment. Other effects that may occur during withdrawal or change of corticosteroid, such as prednisolone, as in ASPELONE therapy include benign intracranial hypertension with headache and vomiting and papilloedema caused by cerebral oedema. Latent rhinitis or eczema may be unmasked.
Increased intracranial pressure with papilloedema in children (pseudotumour cerebri) usually after treatment withdrawal. Growth retardation in infancy, childhood and adolescence (see section 4.4).
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to: SAHPRA: https://www.sahpra.org.za/health-products-vigilance/
Not applicable.
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