Defocart Uses, Dosage, Side Effects, Food Interaction and all others data.
Defocart provides anti-inflammatory action by inhibiting Phospholipase A2 enzyme which is responsible for prostaglandin synthesis. Besides Defocart decreases the release of certain chemicals that are important in the immune system. By decreasing the release of these chemicals Defocart provides immunosuppressive action.
Defocart exerts anti-inflammatory activity in DMD, likely improving various symptoms, including muscle weakness and cardiorespiratory symptoms in addition to delaying their onset. This allows for an increased quality of life and prevents the necessity for surgical procedures, such as those for scoliosis, which is associated with DMD. Studies showed significant preservation of muscle mass in patients generally treated with 0.9 mg/kg/day of deflazacort compared to a control group. The following findings are based on clinical studies using deflazacort on a long term basis:
Effects on muscle strength
At age 16, individuals treated with long-term deflazacort had 63 ± 4% score in muscle strength compared to a mean muscle strength score of 31 ± 3% for control patients. Significant improvements in climbing stairs and rising from a supine position were also seen in patients taking deflazacort.
|Deflazacort Other Names
|Emflaza, Exondys 51, Amondys 45, Vyondys 53, eteplirsen, golodirsen
The protein binding of the active metabolite of deflazacort is approximately 40%.
|Solitaire Pharmacia Pvt Ltd
|September 19, 2023 at 7:00 am
- Anaphylaxis, asthma, severe hypersensitivity reactions
- Rheumatoid arthritis, juvenile chronic arthritis, polymyalgia rheumatica
- Systemic lupus erythematosus, dermatomyositis, mixed connective tissue disease (other than systemic sclerosis), polyarteritis nodosa, sarcoidosis
- Pemphigus, bullous pemphigoid, pyoderma gangrenosum
- Minimal change nephrotic syndrome, acute interstitial nephritis
- Rheumatic carditis
- Ulcerative colitis, Crohn's disease
- Uveitis, optic neuritis
- Autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura
- Acute and lymphatic leukaemia, malignant lymphoma, multiple myeloma
- Immune suppression in transplantation
Defocart is also used to associated treatment for these conditions: Duchenne's Muscular Dystrophy (DMD)
How Defocart works
Defocart is a corticosteroid prodrug with an active metabolite, 21-deflazacort, which binds to the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects on the body. The exact mechanism by which deflazacort exerts its therapeutic effects in patients with DMD is unknown but likely occurs via its anti-inflammatory activities.
- For acute disorders: up to 120 mg/day Defocart may need to be given initially. Maintenance doses in most conditions are within the range 3-18 mg/day.
- Rheumatoid arthritis: The maintenance dose is usually within the range 3-18 mg/day. The smallest effective dose should be used and increased if necessary.
- Bronchial asthma: In the treatment of an acute attack, high doses of 48-72 mg/day may be needed depending on severity and gradually reduced once the attack has been controlled. For maintenance in chronic asthma, doses should be titrated to the lowest dose that controls symptoms.
- Other conditions: The dose of Defocart depends on clinical need titrated to the lowest effective dose for maintenance. Starting doses may be estimated on the basis of ratio of 5 mg prednisone or prednisolone to 6 mg Defocart.
Alternate day administration may be appropriate. Doses of Defocart usually lie in the range 0.25-1.5 mg/kg/day. The following ranges provide general guidance:
- Juvenile chronic arthritis: The usual maintenance dose is between 0.25 to 1.0 mg/kg/day.
- Nephrotic syndrome: Initial dose of usually 1.5 mg/kg/day followed by down titration according to clinical need.
- Bronchial asthma: The initial dose should be between 0.25 - 1.0 mg/kg on alternate days.
- Defocart withdrawal: In patients who have received more than physiological doses of systemic corticosteroids (approximately 9 mg per day 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.
After administration occasionally GI disturbances like dyspepsia, nausea; musculoskeletal disorders like myopathy; depressed mood, skin atrophy, acne etc. may occur.
The LD50 for the oral dose is 5200 mg/kg (mouse); Oral TDLO (woman): 0.12 mg/kg
A note on altered endocrine function and immunosuppression
Defocart, as a steroid prodrug used over a long-term period, can cause hormone imbalance leading to diseases such as Cushing's Syndrome and hypothalamic-pituitary-adrenal axis suppression. It can also predispose to infection, as it promotes immunosuppression. It is important to monitor for hormonal imbalance and infection and provide necessary treatment if they occur.
Mutagenicity assays were negative in various laboratory and in vivo assays performed on rats. Chronic use in mice for 2 years in one study resulted in a higher rate of osteoma and osteosarcomas in mice receiving 0.06, 0.12, 0.25, 0.50, or 1.0 mg/kg of deflazacort daily.
Use in pregnancy
There are no sufficient data to support the administration of deflazacort during pregnancy. Corticosteroid drugs such as deflazacort should only be used during pregnancy only if the benefits of therapy outweigh the potential risks.
Use in lactation
Corticosteroids, when administered systemically, are excreted in the breastmilk. Exposure may lead to disturbances in bone development and growth and endocrine disturbances in the exposed infant.
The following clinical conditions require special caution and frequent patient monitoring is necessary: Adrenal suppression and infection, child, adolescents, elderly, history of TB and steroid myopathy, hypertension, recent myocardial infarction, congestive heart failure, liver failure, renal impairment, diabetes mellitus and glaucoma (including family history), osteoporosis, corneal perforation, epilepsy, peptic ulcer, hypothyroidism, pregnancy and lactation.
Defocart is metabolized in the liver. It is recommended to increase the maintenance dose of Defocart if drugs which are liver enzyme inducers are co-administered, e.g. rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone and aminoglutethimide. For drugs which inhibit liver enzymes, (e.g. ketoconazole) it may be possible to reduce the maintenance dose of Defocart.
- Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of deflazacort.
- Avoid St. John's Wort. This herb induces CYP3A metabolism and may reduce serum levels of deflazacort.
- Take with or without food. The tablets may be crushed and mixed with applesauce and consumed immediately.
[Moderate] GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of 21-desdeflazacort, the active metabolite of deflazacort that is formed by esterases after oral administration and further metabolized by CYP450 3A4 to several inactive metabolites.
The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism in the gut wall by certain compounds present in grapefruit.
In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands.
Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
Increased systemic exposure to 21-desdeflazacort may increase the risk of corticosteroid adverse effects such as hypercorticism, hyperglycemia, adrenal suppression, immunosuppression, hypertension, salt and water retention, electrolyte abnormalities, behavioral and mood disturbances, posterior subcapsular cataracts, glaucoma, bone loss, and growth retardation in children and adolescents.
br> MANAGEMENT: Defocart should not be administered with grapefruit juice.
Defocart Cholesterol interaction
[Moderate] Corticosteroids may elevate serum triglyceride and LDL cholesterol levels if used for longer than brief periods.
Patients with preexisting hyperlipidemia may require closer monitoring during prolonged corticosteroid therapy, and adjustments made accordingly in their lipid-lowering regimen.
Defocart Hypertension interaction
[Moderate] Corticosteroids may cause hypernatremia, hypokalemia, fluid retention, and elevation in blood pressure.
These mineralocorticoid effects are most significant with fludrocortisone, followed by hydrocortisone and cortisone, then by prednisone and prednisolone.
The remaining corticosteroids, betamethasone, dexamethasone, methylprednisolone, and triamcinolone, have little mineralocorticoid activities.
However, large doses of any corticosteroid can demonstrate these effects, particularly if given for longer than brief periods.
Therapy with corticosteroids should be administered cautiously in patients with preexisting fluid retention, hypertension, congestive heart failure, and Dietary sodium restriction and potassium supplementation may be advisable.
Dietary sodium restriction and potassium supplementation may be advisable.
Defocart Drug Interaction
Major: diltiazemModerate: metoprolol, metoprololUnknown: aripiprazole, zoledronic acid, alpha-lipoic acid, hydroxyzine, multivitamin, mycophenolate mofetil, sulfamethoxazole / trimethoprim, ubiquinone, albuterol / ipratropium, glucose, levothyroxine, levocarnitine, lithium, omega-3 polyunsaturated fatty acids, acetaminophen, thiamine, cholecalciferol
Defocart Disease Interaction
Major: GI perforation, infections, prematurity, PUD, vaccination, Deflazacort hepatic impairmentModerate: (+) tuberculin test, cirrhosis, depression/psychoses, diabetes, electrolyte imbalance, fluid retention, hyperadrenocorticalism, hyperlipidemia, hypothyroidism, MI, myasthenia gravis, myopathy, ocular herpes simplex, ocular toxicities, osteoporosis, scleroderma, strongyloidiasis, thromboembolism
Volume of Distribution
One study determined the volume of distribution to be 204 ± 84 L.
Defocart is rapidly absorbed after oral administration with peak concentration occurring within 1-2 hours. One pharmacokinetic study determined an AUC (area under the curve) of 280 ng/ml · h.
The bioavailability of both the oral suspension and tablet are similar. In clinical studies, coadministration of deflazacort crushed with food or applesauce did not affect absorption or bioavailability.
The half-life of deflazacort ranges from 1.1 to 1.9 h
114 ±27 L/h, according to one noncompartmental pharmacokinetic study.
The clearance of corticosteroids is enhanced in hypothyroid patients and increased in patients with hyperthyroidism. Dosing adjustments may be considered according to thyroid status. A study of corticosteroid clearance was performed in patients with a creatinine clearance of 15 mL/min or less, and determined that the active metabolite of deflazacort, 21-deflazacort was similar to that in patients with normal renal clearance.
Urinary excretion is the major route of deflazacort elimination, accounting for about about 70% of the excreted dose. The remainder of the dose (about 30%) is excreted in the feces. Elimination is almost completed by 24 hours post-dose. 21-deflazacort makes up about 18% of the eliminated drug in the urine.
Pregnancy & Breastfeeding use
Use in pregnancy: Defocart does cross the placenta. When administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks.
Use in lactation: Corticosteroids are excreted in breast milk. Doses up to 50 mg daily of Defocart are unlikely to cause systemic effects in the infant.
Hypersensitivity to or any of the ingredients. Patients receiving live virus immunisation.
Elderly: In elderly patients, no special precautions other than those usually adopted in patients receiving glucocorticoid therapy are necessary.
Hepatic impairment: In patients with hepatic impairment, blood levels of Defocart may be increased. Therefore the dose of Defocart should be carefully monitored and adjusted to the minimum effective dose.
Renal impairment: In renal impaired patients, no special precautions other than those usually adopted in patients receiving glucocorticoid therapy are necessary.
In patients who have received more than physiological doses of systemic corticosteroids (approximately 9mg per day or equivalent) for greater than 3 weeks, withdrawal should not be abrupt. How dose reduction should becarried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced.
Store in a cool (below 25° C.) and dry place , protected from light & moisture. Keep out of the reach of children.
What is Defocart used for?
Defocart is used to treat duchenne muscular dystrophy in adults and children 2 years of age and older.
How safe is Defocart?
Defocart can weaken your immune system, and you may get an infection more easily. You may need frequent medical tests. Your vision and bone mineral density may also need to be checked.Defocart may increase your risk of developing osteoporosis.
How does Defocart work?
Defocart works by reducing inflammation and by changing the way the immune system works.
What are the common side effects of Defocart?
Common side effects of Defocart are include:
- Cushingoid appearance
- Weight gain
- Increased appetite
- Upper respiratory tract infection
- Urinary frequency
Is Defocart safe during pregnancy?
Taking Defocart during early pregnancy may increase the risk of cleft lip and palate in a newborn. Tell your doctor if you are pregnant or plan to become pregnant. Taking Defocart at any time during pregnancy may affect adrenal gland hormones in the newborn baby.
Is Defocart safe during breastfeeding?
Higher doses may be expected to affect the degree of adrenal suppression and should be used with caution.There are no data on the effects on milk production.
Can I drink alcohol with Defocart?
Mixing alcohol with Defocart can cause nausea and vomiting, headaches, drowsiness, fainting, or loss of coordination. It also can put you at risk for internal bleeding, heart problems, and difficulties in breathing.
When should be taken of Defocart?
Defocart is usually taken once a day with or without food. Take Defocart at around the same time every day.
Can I take Defocart on empty stomach?
It can be taken on an empty stomach or after food.
Is Defocart harmful?
Defocart can weaken your immune system, and you may get an infection more easily.
Can I take Defocart for a long time?
People who use Defocart for a long time may develop glaucoma or cataracts. Talk to your doctor about the risks of using Defocart and how often you should have your eyes examined during your treatment.
How long does Defocart stay in my system?
Defocart elimination plasma half-life is 1.1 to 1.9 hours. Elimination takes place primarily through the kidneys; 70% of the administered dose is excreted in the urine.
Who should not take Defocart?
You should not use Defocart if you are allergic to it.Defocart should not be given to a child younger than 2 years old.
What happens if I miss a dose of Defocart?
Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.
Is Defocart a strong steroid?
Defocart is less potent than prednisone and is usually administered at proportionately higher doses.
Can I drive after taking Defocart?
Avoid driving if you experience dizziness after taking Defocart.
Is Defocart used for cough?
Defocart engaged in manufacturing and supplying an excellent range of Defocart for Cold and cough that is widely used as an anti-inflammatory and immunosuppressant.
Is Defocart an antibiotic?
Defocart is in a class of medications called cephalosporin antibiotics.
What happen If I suddenly stop taking Defocart?
Do not stop taking Defocart without talking to your doctor. Stopping the drug abruptly may cause symptoms such as loss of appetite, an upset stomach, vomiting, drowsiness, confusion, headache, fever, joint and muscle pain, peeling skin, and weight loss.
Is Defocart safe in diabetes?
These results indicate that Defocart, when employed in an anti-inflammatory dose equivalent to prednisone, should prove advantageous in insulin-treated diabetics who require steroid treatment.
Does Defocart increase blood sugar?
Glucocorticoid treatment produces a deterioration of blood glucose control in diabetics. Recent reports have indicated that Defocart is less diabetogenic than prednisone in healthy subjects.