Respred is indicated for the conditions of respiratory diseases, allergic states, and rheumatic disorder, collagen diseases, endocrine disorders, ophthalmic diseases, hematologic disorders and neoplastic diseases.

The lowest dosage that will produce an acceptable result should be used (See section 4.4); when it is possible to reduce the dosage, this must be accomplished by stages. During prolonged therapy, any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy they may need to be temporarily re-introduced.

Adults:
The dose used will depend upon the disease, its severity, and the clinical response obtained. The following regimens are for guidance only. Divided dosage is usually employed.

• Short-term treatment:

          20 to 30 mg daily for the first few days, subsequently reducing the daily dosage by 2.5 or 5 mg every two to five days, depending upon the response.

• Rheumatoid arthritis:

          7.5 to 10 mg daily. For maintenance therapy, the lowest effective dosage is used.

In pediatric patients:

The initial dose of prednisolone sodium phosphate syrup may vary depending on the specific disease entity being treated. The range of initial doses is 0.14 to 2 mg/kg/day in three or four divided doses (4 to 60 mg/m²bsa/day).

The standard regimen used to treat nephrotic syndrome in pediatric patients is 60 mg/m²/day given in three divided doses for 4 weeks, followed by 4 weeks of single dose alternate-day therapy at 40 mg/m²/day.

The National Heart, Lung, and Blood Institute (NHLBI) recommended dosing for systemic prednisone, prednisolone or methylprednisolone in children whose asthma is uncontrolled by inhaled corticosteroids and long-acting bronchodilators is 1 - 2 mg/kg/day in single or divided doses. It is further recommended that short course, or “burst” therapy, be continued until a child achieves a peak expiratory flow rate of 80% of his or her personal best or symptoms resolve. This usually requires 3 to 10 days of treatment, although it can take longer. There is no evidence that tapering the dose after improvement will prevent a relapse.”

Adrenal cortical atrophy develops during prolonged therapy and may persist for years after stopping treatment.

Withdrawal of corticosteroids 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.

Suppression of the HPA axis and other undesirable effects may be minimized 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 dosage section).

Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The clinical presentation may often be atypical and serious infections such as septicemia and tuberculosis may be masked and may reach an advanced stage before being recognized.

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 immunization with varicella zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 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 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. The antibody response to other vaccines may be diminished.

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy.

Discontinuation of corticosteroids may result in clinical remission.

Because of the possibility of fluid retention, care must be taken when corticosteroids are administered to patients with renal insufficiency or hypertension or congestive heart failure.

Corticosteroids may worsen diabetes mellitus, osteoporosis, 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 history of severe affective disorders (especially a previous history of steroid psychosis), previous steroid myopathy, peptic ulceration, hypothyroidism, recent myocardial infarction or patients with a history of tuberculosis.

In patients with liver failure, blood levels of corticosteroid may be increased, as with other drugs which are metabolized in the liver. Frequent patient monitoring is therefore necessary.

Use in Children:

Corticosteroids cause dose-related growth retardation in infancy, childhood and adolescence, which may be irreversible.

Use in the Elderly:

The common adverse effects of systemic corticosteroids may be associated with more serious consequences in old age, especially osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.

Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids (see Section 4.8 Undesirable effects). Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/systemic exposure (see also Section 4.5 Interaction with other medicinal products and other forms of interaction), 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, although such reactions have been reported infrequently.

Particular care is required when considering the use of systemic corticosteroids 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.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Patients should carry 'Steroid treatment' cards which give clear guidance on the precautions to be taken to minimize risk and which provide details of prescriber, drug, dosage and the duration of treatment."

Withdrawal

In patients who have received more than physiological doses of systemic corticosteroids (approximately 7.5 mg prednisolone or equivalent) for greater than 3 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 is reduced. Clinical assessment of disease activity may be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids but there is uncertainty about HPA suppression, the dose of systemic corticosteroid may be reduced rapidly to physiological doses. Once a daily dose equivalent to 7.5 mg of prednisolone is reached, dose reduction should be slower to allow the HPA-axis to recover.

Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 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, or equivalent for 3 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 should be considered even after courses lasting 3 weeks or less:

• Patients who have had repeated courses of systemic corticosteroids, particularly if taken for greater than 3 weeks.
• When a short course has been prescribed within one year of cessation of long-term therapy (months or years).
• Patients who may have reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy.
• Patients receiving doses of systemic corticosteroid greater than 40 mg daily of prednisolone.
• Patients repeatedly taking doses in the evening.

During prolonged therapy, any intercurrent illness, trauma or surgical procedure will require a temporary increase in dosage; if corticosteroids have been stopped following prolonged therapy they may need to be temporarily reintroduced.

• Rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone, ephedrine and aminoglutethimide enhance the metabolism of corticosteroids and its therapeutic effects may be reduced. Therefore, it may be necessary to adjust the dose accordingly.
• Mifepristone may reduce the effect of corticosteroids for 3 - 4 days.
• Erythromycin and ketoconazole may inhibit the metabolism of some corticosteroids.
• Ciclosporin increases plasma concentration of prednisolone. The same effect is possible with ritonavir.
• Oestrogens and other oral contraceptives may potentiate the effects of glucocorticoids and dosage adjustments may be required if oral contraceptives are added to or withdrawn from a stable dosage regimen.
• The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonized by corticosteroids. The growth promoting effect of somatotropin may be inhibited by the concomitant use of corticosteroids.
• Steroids may reduce the effects of anticholinesterases in myasthenia gravis and cholecystographic x-ray media.
• The efficacy of coumarin anticoagulants and warfarin may be enhanced by concurrent corticosteroid 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 increases the risk of gastro-intestinal bleeding and ulceration.
• The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication.
• The hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics, and carbenoxolone, are enhanced by corticosteroids. The risk of hypokalaemia is increased with theophylline and amphotericin. Corticosteroids should not be given concomitantly with amphotericin, unless required to control reactions.
• The risk of hypokalaemia also increases if high doses of corticosteroids 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.
• Concomitant use with methotrexate may increase the risk of haematological toxicity.
• High doses of corticosteroids impair the immune response and so live vaccines should be avoided (see also warnings).

Pregnancy:

The ability of corticosteroids to cross placenta varies between individual drugs, however, 88% of prednisolone is inactivated as it crosses the placenta.

Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development including cleft palate, intra-uterine growth retardation and effects on brain growth and development. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man. However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids might increase the risk of intrauterine growth retardation. Hypoadrenalism might, in theory, occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important.

As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks. When corticosteroids are essential however, patients with normal pregnancies may be treated as though they were in the non-gravid state. Patients with pre-eclampsia or fluid retention require close monitoring.”

Breastfeeding:

Corticosteroids are excreted in small amounts in breast milk. However, doses of up to 40 mg daily of prednisolone are unlikely to cause systemic effects in the infant. Infants of mothers taking higher doses than this may have a degree of adrenal suppression but the benefits of breast feeding are likely to outweigh any theoretical risk.”

None known.

The incidence of predictable undesirable effects, including hypothalamo-pituitary-adrenal (HPA) suppression, correlates with the relative potency of the drug, 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.

Infections and Infestations

Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, recurrence of dormant tuberculosis (see section 4.4).

Neoplasms benign, malignant and unspecified (incl. cysts and polyps)

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.

Blood and lymphatic system disorders

Leukocytosis.

Immune system disorders

Hypersensitivity including anaphylaxis has been reported.

Endocrine disorders

Suppression of the HPA axis.

Cushingoid.

Impaired carbohydrate intolerance with increased requirement for anti-diabetic therapy, manifestation of latent diabetes mellitus.

Metabolism and nutrition disorders

Sodium and water retention, hypokalaemia, hypokalaemic alkalosis, increased appetite, negative protein and calcium balance.

Psychiatric disorders

Euphoric mood, psychological dependence, depressed mood, insomnia, aggravation of schizophrenia.

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 - 6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.

Nervous system disorders

Dizziness, headache.

Increased intracranial pressure with papilloedema in children (pseudotumour cerebri) - usually after treatment withdrawal.

Aggravation of epilepsy.

Eye disorders

Glaucoma, papilloedema, posterior subcapsular cataracts, central serous chorioretinopathy, exophthalmos, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal diseases.

Ear and labyrinth disorders

Vertigo.

Cardiac disorders

Myocardial rupture following recent myocardial infarction.

Congestive cardiac failure (in susceptible patients).

Vascular disorders

Hypertension, embolism.

Respiratory, thoracic and mediastinal disorders

Hiccups.

Gastrointestinal disorders

Dyspepsia, nausea, vomiting, abdominal distension, abdominal pain, diarrhoea, oesophageal ulceration, candidiasis, pancreatitis acute.

Peptic ulceration with perforation and haemorrhage.

Skin and subcutaneous tissue disorders

Skin Atrophy, skin striae, acne, telangiectasia, hyperhidrosis, rash, pruritus, urticaria, hirsutism.

Musculoskeletal and connective tissue disorders

Myopathy, osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, myalgia.

Growth retardation in infancy, childhood and adolescence.

Reproductive system and breast disorders

Menstruation irregular, amenorrhoea.

General disorders and administration site conditions

Impaired healing, malaise.

Investigations

Weight increased.

Injury, poisoning and procedural complications

Tendon rupture, contusion (bruising).

Withdrawal Symptoms

Too rapid a reduction of corticosteroid 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 therapy include benign intracranial hypertension with headache and vomiting and papilloedema caused by cerebral oedema.

Latent rhinitis or eczema may be unmasked.

• To reports any side effect(s):
• Saudi Arabia:
• The National Pharmacovigilance and Drug Safety Centre (NPC)
  • Fax: +966-11-205-7662
  • Call NPC at +966-11-2038222, Exts.: 2317-2356-2353-2354-2334-2340.
  • Toll free phone: 8002490000
  • E-mail: npc.drug@sfda.gov.sa
  • Website: www.sfda.gov.sa/npc
• Other GCC States:
• Please contact the relevant competent authority.

.

Pharmacotherapeutic group:

Pharmacotherapeutic group: glucocorticoids, ATC code: H02AB06

Naturally occurring glucocorticoids (hydrocortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Prednisolone is a synthetic adrenocortical steroid drug with predominantly glucocorticoid properties. Some of these properties reproduce the physiological actions of endogenous glucocorticosteroids, but others do not necessarily reflect any of the adrenal hormones' normal functions; they are seen only after administration of large therapeutic doses of the drug. The pharmacological effects of prednisolone which are due to its glucocorticoid properties include: promotion of gluconeogenesis; increased deposition of glycogen in the liver; inhibition of the utilization of glucose; anti-insulin activity; increased catabolism of protein; increased lipolysis; stimulation of fat synthesis and storage; increased glomerular filtration rate and resulting increase in urinary excretion of urate (creatinine excretion remains unchanged); and increased calcium excretion.

Depressed production of eosinophils and lymphocytes occurs, but erythropoiesis and production of polymorphonuclear leukocytes are stimulated. Inflammatory processes (edema, fibrin deposition, capillary dilatation, migration of leukocytes and phagocytosis) and the later stages of wound healing (capillary proliferation, deposition of collagen, cicatrization) are inhibited. Prednisolone can stimulate secretion of various components of gastric juice. Suppression of the production of corticotropin may lead to suppression of endogenous corticosteroids. Prednisolone has slight mineralocorticoid activity, whereby entry of sodium into cells and loss of intracellular potassium is stimulated. This is particularly evident in the kidney, where rapid ion exchange leads to sodium retention and hypertension.

Prednisolone is rapidly and well absorbed from the gastrointestinal tract following oral administration. Prednisolone sodium phosphate Solution produces a 14% higher peak plasma level of prednisolone which occurs 20% faster than that seen with tablets. Prednisolone is 70 - 90% protein-bound in the plasma and it is eliminated from the plasma with a half-life of 2 to 4 hours. It is metabolized mainly in the liver and excreted in the urine as sulfate and glucuronide conjugates.

The systemic availability, metabolism and elimination of prednisolone after administration of single weight-based doses (0.8 mg/kg) of intravenous (IV) prednisolone. Results showed that the systemic availability of total and unbound prednisolone, as well as interconversion between prednisolone and prednisone were independent of age. The mean unbound fraction of prednisolone was higher, and the steady-state volume of distribution (V_ss) of unbound prednisolone was reduced in elderly patients. Plasma prednisolone concentrations were higher in elderly subjects, and the higher AUCs of total and unbound prednisolone were most likely reflective of an impaired metabolic clearance, evidenced by reduced fractional urinary clearance of 6ß-hydroxyprednisolone. Despite these findings of higher total and unbound prednisolone concentrations, elderly subjects had higher AUCs of cortisol, suggesting that the elderly population is less sensitive to suppression of endogenous cortisol or their capacity for hepatic inactivation of cortisol is diminished.

Not known.

Edetate disodium

Liquid sorbitol (non-crystalline)

Methyl paraben

Dibasic sodium phosphate

Sucrose

Monobasic sodium phosphate

Propylene glycol

Redberry flavour

Saccharin sodium

Purified water

Not stated.

Keep out of the reach and sight of children.

Do not store above 30°C.

Do not use Respred after the expiry date which is stated on the label.

Do not use Respred if you notice that it is not clear flavored liquid.

Once opened, store below 30°C and use within 3 months.

Keep this medicine in the original packaging, in order to protect from light.

Do not use this medicine if you notice any visible signs of damage to the bottle or deterioration in your medicine. Return it to your pharmacist.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

Primary packing material - Bottle amber colored glass and the cap made from polyethylene and polypropylene. The cap & bottle are mechanically sealed to prevent from any foreign contamination, measuring cup of 15 ml capacity provided.

Secondary packing material is white color corrugated box.

No special requirements.