Oralsone (Aciclovir,Hydrocortisone)

Uses

• Herpes Zoster

• Genital Herpes

• Chickenpox

• Herpes Simplex Infections

• Herpes Simplex Encephalitis

Hydrocortisone is used for the use in the following conditions: Primary or secondary adrenocortical insufficiency, Acute adrenocortical insufficiency, Shock unresponsive to conventional therapy, Congenital adrenal hyperplasia, Hypercalcemia associated with cancer, Nonsuppurative thyroiditis, Rheumatic Disorders, Dermatologic Diseases (Allergic States, Severe seborrheic dermatitis, Severe psoriasis, Pemphigus, Severe erythema multiforme), Control of severe or incapacitating allergic conditions (Bronchial asthma, Contact dermatitis, Atopic dermatitis, Serum sickness, Seasonal or perennial allergic rhinitis, Drug hypersensitivity reactions, Urticarial transfusion reactions, Acute noninfectious laryngeal edema), Ophthalmic Diseases (Herpes zoster ophthalmicus, Iritis, iridocyclitis, Chorioretinitis, Diffuse posterior uveitis and choroiditis, Optic neuritis), Gastrointestinal Diseases, Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, Loeffler's syndrome, Aspiration pneumonitis, Hematologic Disorders (Acquired, autoimmune hemolytic anemia, Idiopathic thrombocytopenic purpura in adults, Secondary thrombocytopenia, Erythroblastopenia), Neoplastic Diseases (Leukemias and lymphomas in adults, Acute leukemia of childhood), Edematous States, Acute exacerbations of multiple sclerosis

Oralsone (Aciclovir,Hydrocortisone) is also used to associated treatment for these conditions: Acute Gouty Arthritis, Acute Otitis Externa, Adrenal Insufficiency, Allergic Rhinitis (AR), Allergic corneal marginal ulcers, Anal Fissures, Ankylosing Spondylitis (AS), Anterior Segment Inflammation, Aspiration Pneumonitis, Asthma, Atopic Dermatitis (AD), Berylliosis, Bullous dermatitis herpetiformis, Chorioretinitis, Choroiditis, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Corneal Inflammation, Crohn's Disease (CD), Dermatitis, Dermatitis exfoliative generalised, Dermatitis, Contact, Dermatomyositis, Dermatosis, Drug hypersensitivity reaction, Epicondylitis, Erythroblastopenia, Hemorrhoids, Herpes Labialis, Hypercalcemia of Malignancy, Idiopathic Thrombocytopenic Purpura, Infection of the Fenestration Cavity, Infection of the Mastoidectomy Cavity, Iridocyclitis, Iritis, Itching caused by Hemorrhoids, Itching of the Anus, Leukemia, Acute, Leukemias, Loeffler's syndrome, Lymphomas NEC, Malignant Lymphomas, Mycosis Fungoides (MF), Ophthalmia, Sympathetic, Optic Neuritis, Pain caused by Hemorrhoids, Pemphigus, Post-traumatic Osteoarthritis, Primary adrenocortical insufficiency, Proctitis, Proteinuria, Psoriatic Arthritis, Rectal inflammations NEC, Rheumatic heart disease, unspecified, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Seasonal Allergic Conjunctivitis, Secondary adrenocortical insufficiency, Secondary thrombocytopenia, Serum Sickness, Severe Seborrheic Dermatitis, Skin Diseases, Stevens-Johnson Syndrome, Synovitis, Systemic Lupus Erythematosus (SLE), Trichinosis, Tuberculous Meningitis, Ulcerative Colitis, Acquired immune hemolytic anemia, Acute Bursitis, Acute Tenosynovitis, Acute rheumatic carditis, Cryptitis, Disseminated Pulmonary Tuberculosis, Fulminating Pulmonary Tuberculosis, Itching skin, Non-suppurative Thyroiditis, Severe Erythema multiforme, Severe Psoriasis, Subacute Bursitis, Superficial infection of the external auditory canal with inflammation, Symptomatic Sarcoidosis, Systemic Dermatomyositis, Varicella-zoster virus acute retinal necrosis, Palliative

How Oralsone (Aciclovir,Hydrocortisone) works

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.[A187463] Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.[A187463]

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.[A187463]

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.[A187463] High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.[A187463]

Dosage

Oralsone (Aciclovir,Hydrocortisone) dosage

The total daily dosage of Aciclovir should be based on the type or severity of infection and given in equally divided doses based on consideration of degree of susceptibility of the pathogens, renal function and body-weight.

Aciclovir Tablet

• Acute Herpes Zoster:

800 mg every 4 hours, 5 times daily for 7 to 10 days.

• Genital Herpes:

Initial Genital Herpes: 200 mg every 4 hours, 5 times daily for 10 days.

Chronic suppressive therapy for recurrent disease: 400 mg 2 times daily for up to 12 months.

Intermittent therapy: 200 mg every 4 hours, 5 times daily for 5 days.

• Chickenpox:

Children (2 years of age and older): 20 mg/kg/dose 4 times daily (80 mg/kg/day) for 5 days.

Adults and Children (>40 kg): 800 mg 4 times daily for 5 days.

Aciclovir IV

The required dose of Aciclovir IV should be administered by slow intravenous infusion over a one-hour period.

• Herpes Simplex (HSV-1 and HSV-2) Infections:

Adults and Adolescents (≥12 years): 5 mg/kg, 8 hourly for 7 days.

Pediatrics (<12 years): 10 mg/kg 8 hourly for 7 days.

• Severe Initial Herpes Genitalis:

Adults and Adolescents (≥12 years): 5 mg/kg 8 hourly for 5 days.

• Herpes Simplex Encephalitis:

Adults and Adolescents (≥12 years): 10 mg/kg 8 hourly for 10 days.

Pediatrics (3 months to 12 years of age): 20 mg/kg 8 hourly for 10 days.

• Neonatal Herpes Simplex (Birth to 3 months):

10 mg/kg 8 hourly for 10 days.

• Varicella Zoster:

Adults and Adolescents (≥12 years): 10 mg/kg 8 hourly for 7 days.

Pediatrics (<12 years): 20 mg/kg 8 hourly for 7 days.

Dose adjustment of Tablet for patients with acute or chronic renal impairment, based on Creatinine Clearance, Cr Cl (mL/min/1.73 m2):

For Cr Cl= > 25 : 800 mg 4 hourly 5 times daily

For Cr Cl = 10 to 25 : 200 mg 4 hourly 5 times daily or 400 mg 12 hourly or 800 mg 8 hourly

For Cr Cl = 0 to 10 : 200 mg 12 hourly or 400 mg 12 hourly or 800 mg 12 hourly

Dose adjustment of IV for patients with acute or chronic renal impairment, based on Creatinine Clearance, Cr Cl (mL/min/1.73 m2):

For Cr Cl = > 50 : 100% of recommended dose, 8 hourly

For Cr Cl = 25 to 50 : 100% of recommended dose, 12 hourly

For Cr Cl = 10 to 25 : 100% of recommended dose, 24 hourly

For Cr Cl = 0 to 10 : 50% of recommended dose, 24 hourly

Caution: Rapid or bolus intravenous injection must be avoided. Intramuscular or subcutaneous injection must be avoided.

Reconstitution procedure of IV infusion

Vial containing 250 mg Aciclovir will be reconstituted with 50 ml infusion solution and vial containing 500 mg Aciclovir will be reconstituted with 100 ml infusion solution. Besides, Vial containing 1 gm Aciclovir will be reconstituted with 250 ml infusion solution. 10 ml of the infusion solution will be added to the vial containing 250 mg, 500 mg and 1 gm Aciclovir. Shake well and transfer the required amount of solution to the infusion container. The final concentration of Aciclovir will be not more than 5 mg/ml.

The reconstituted solution should be used within 12 hours. Refrigeration of reconstituted solution may result in the formation of a precipitate which will re-dissolve at room temperature.

Compatible infusion fluids

Sodium Chloride Intravenous Infusion BP (0.45% and 0.9% w/v)

Sodium Chloride (0.18% w/v) and Glucose (4% w/v) Intravenous Infusion BP

Sodium Chloride (0.45% w/v) and Glucose (2.5% w/v) Intravenous Infusion BP

Hartmann\\\'s Solution

Tablet: The initial dosage of Hydrocortisone Tablets may vary from 20 mg to 240 mg of hydrocortisone per day depending on the specific disease entity being treated. In situations of less severity, lower doses will generally suffice, while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, Hydrocortisone Tablets should be discontinued and the patient transferred to other appropriate therapy.

It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patients.After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response. It should be kept in mind that constant monitoring is needed in regard to drug dosage. If, after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually, rather than abruptly.

Injection:

• Adult: By IM injection or slow IV injection or infusion. The initial dose of Hydrocortisone sterile powder is 100 mg to 500 mg, depending on the severity of the condition. This dose may be repeated at intervals of 2, 4 or 6 hours as indicated by the patient's response and clinical condition.
• Children: By slow IV injection, up to 1 year 25 mg, 1-5 years 50 mg, 6-12 years 100 mg.

Side Effects

Rash, gastro-intestinal disturbances, rises in bilirubin and liver-related enzymes, increase in blood urea and creatinine, decreases in hematological indices, headache, neurological reactions, fatigue.

Hydrocortisone is generally well tolerated except in prolonged high doses. It may cause cardiac arrhythmia, esophageal candidiasis, menstrual irregularity, decreased carbohydrate & glucose tolerance, fluid retention, increased appetite, weight gain, euphoria, mood swings, depression, insomnia, acne etc.

Toxicity

Data regarding acute overdoses of glucocorticoids are rare. Chronic high doses of glucocorticoids can lead to the development of cataract, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency. Overdose may be treated by adjusting the dose or stopping the corticosteroid as well as initiating symptomatic and supportive treatment.

Precaution

Aciclovir should be administered with caution in patient with renal impairment and doses should be adjusted according to creatinine clearance.

Hydrocortisone should be used with caution in patients with a history of peptic ulceration as it increases the incidence of peptic ulceration. This drug should be used with caution in patients with congestive heart failure, hypertension, glaucoma, diabetic mellitus and epilepsy.

Interaction

Drug interaction of hydrocortisone has been reported with amphotericin B, potassium-depleting agents, macrolide antibiotics, warfarin, antidiabetics, isoniazid, digitalis glycosides, estrogens, barbiturates, phenytoin, carbamazepine, ketoconazole, aspirin etc.

Volume of Distribution

Total hydrocortisone has a volume of distribution of 39.82L, while the free fraction has a volume of distribution of 474.38L.

Elimination Route

Oral hydrocortisone at a dose of 0.2-0.3mg/kg/day reached a mean C_max of 32.69nmol/L with a mean AUC of 90.63h*nmol/L A 0.4-0.6mg/kg/day dose reached a mean C_max of 70.81nmol/L with a mean AUC of 199.11h*nmol/L. However, the pharmacokinetics of hydrocortisone can vary by 10 times from patient to patient.

Topical hydrocortisone cream is 4-19% bioavailable[8546995] with a T_max of 24h.

Hydrocortisone retention enemas are have a bioavailability of 0.810 for slow absorbers and 0.502 in rapid absorbers. Slow absorbers take up hydrocortisone at a rate of 0.361±0.255/h while fast absorbers take up hydrocortisone at a rate of 1.05±0.255/h.

A 20mg IV dose of hydrocortisone has an AUC of 1163±277ng*h/mL.

Half Life

Total hydrocortisone via the oral route has a half life of 2.15h while the free fraction has a half life of 1.39h. A 20mg IV dose of hydrocortisone has a terminal half life of 1.9±0.4h.

Clearance

Total hydrocortisone by the oral route has a mean clearance of 12.85L/h, while the free fraction has a mean clearance of 235.78L/h. A 20mg IV dose of hydrocortisone has a clearance of 18.2±4.2L/h.

Elimination Route

Corticosteroids are eliminated predominantly in the urine.[A187436] However, data regarding the exact proportion is not readily available.

Pregnancy & Breastfeeding use

Pregnancy category B & caution should be exercised when it is administered to a lactating mother.

Pregnancy category C. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in nursing mother: Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from corticosteroids, a decision should be made whether to continue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

Hydrocortisone is contraindicated in severe systemic fungal infections and patients with known hypersensitivity to any component of this product.

Special Warning

Use in elderly patients: Clinical studies were not done in patients’ aged 65 and above. In general dose selection for an elderly patients should be cautious, usually starting at the low end of the dosing range.

Storage Condition

Keep in a cool & dry place away from light. Keep drugs out of the reach of children.

Store at 15-30°C.

Innovators Monograph

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