Pilorute

Uses

Calcium Dobesilate is a vasoactive drug that presumes effects on endothelial integrity, capillary permeability and blood viscosity. It decreases capillary hyperpermeability, decreases platelet aggregation (clotting - adhesion of platelets) and reduces the serum viscosity, which improves blood circulation and blood supply to tissues and organs.

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

Phenylephrine is an alpha-1 adrenergic agonist used in the management of hypotension, generally in the surgical setting associated with the use of anesthetics.

Phenylephrine injections are indicated to treat hypotension caused by shock or anesthesia, an ophthalmic formulation is indicated to dilate pupils and induce vasoconstriction, an intranasal formulation is used to treat congestion, and a topical formulation is used to treat hemorrhoids. Off-label uses include situations that require local blood flow restriction such as the treatment of priapism.

Zinc Oxide helps to To treat or prevent skin irritations (e.g., burns, bed sore, cuts, poison ivy, diaper rash). Protects chafed skin due to diaper rash and helps seal out wetness.

Pilorute 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, PalliativeAllergic Rhinitis (AR), Anorectal discomfort, Cold, Common Cold, Common Cold/Flu, Congestion of the Conjunctivas, Conjunctivitis allergic, Cough, Cough caused by Common Cold, Eye allergy, Eye redness, Fever, Flu caused by Influenza, Headache, Headache caused by Allergies, Headache caused by Common Cold, Headache caused by Pollen Allergy, Hemorrhoids, Hypotension, Irritative cough, Itching of the nose, Itching of the throat, Laryngotracheitis, Nasal Congestion, Nose discomfort, Ocular Inflammation, Ocular Irritation, Paroxysmal Supraventricular Tachycardia, Pollen Allergy, Respiratory tract congestion, Respiratory tract irritation, Rhinopharyngitis, Rhinorrhoea, Seasonal Allergies, Shock, Cardiogenic, Sinus Congestion, Sinus pressure, Sinusitis, Sneezing, Sore Throat, Tracheobronchitis, Upper respiratory tract hypersensitivity reaction, site unspecified, Vasomotor Rhinitis, Aching caused by Flu caused by Influenza, Bronchial congestion, Itchy throat, Minor aches and pains, Watery itchy eyes, Airway secretion clearance therapy, Antihistamine, Dilatation of the pupil, Vasoconstrictor in regional analgesia therapyAcute Wounds, Burns first degree, Burns second degree, Dermatitis, Eczematous, Diaper Rash, Herpes Labialis, Injuries to the Nipple (Fissures and Cracks) Resulting Breastfeeding, Intertrigo, Pain, Pruritus, Sensitive Skin, Skin Irritation, Skin candida, Sunburn, Wounds, Chafing, Damaged skin, Dry, cracked skin, Facial rash, Heat rash, Superficial Wounds, Watery skin lesions, Astringent, Nutritional supplementation

How Pilorute 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]

Phenylephrine is an alpha-1 adrenergic agonist that mediates vasoconstriction and mydriasis depending on the route and location of administration. Systemic exposure to phenylephrine also leads to agonism of alpha-1 adrenergic receptors, raising systolic and diastolic pressure as well as peripheral vascular resistance. Increased blood pressure stimulates the vagus nerve, causing reflex bradycardia.

It acts by providing a physical barrier to prevent skin irritation and help heal damaged skin.

Dosage

Pilorute dosage

Dobesil capsule once or twice daily should be taken with the main meal. Treatment duration, which generally between a few weeks to several months, depends on the disease and its evolution. Dosage should be adapted individually according to the severity of the disease.

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.

Apply thin layer topically every 8 hourly. Change wet and soiled diapers, promptly cleans the diaper area, allow to dry and apply ointment liberally as often as necessary, with each diaper change, especially at bedtime or any time when exposure to wet diapers may be prolonged.

Side Effects

Rarely gastrointestinal disorders including nausea and diarrhea, skin reactions, fever, articular pain and in very rare cases agranulocytosis have been reported. These reactions are generally spontaneously reversible after treatment withdrawal.

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.

Usually well tolerated. Extremely low frequency of hypersensitivity reaction.

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.

Patients experiencing and overdose may present with headache, hypertension, reflex bradycardia, tingling limbs, cardiac arrhythmias, and a feeling of fullness in the head. Overdose may be treated by supportive care and discontinuing phenylephrine, chronotropic medications, and vasodilators. Subcutaneous phentolamine may be used to treat tissue extravasation.

Acute oral toxicity (LD50): 7950 mg/kg [Mouse].

Precaution

Dosage should be reduced in case of severe renal insufficiency requiring dialysis. In patient with agranulocytosis, this medication can decrease the number of white blood cells which affect the body’s ability to fight against various infections. If patients experience flu-like symptoms such as cough, sore throat, fever and others, they are advised to seek medical care as soon as possible.

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.

For external use only. Avoid contact with the eyes. Stop use and ask a doctor if condition worsens or does not improve within 7 days. Keep out of the reach of children. If swallowed, get medical help or contact a poison control center right away

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.

The volume of distribution of phenylephrine is 340L.

Intended for local use only, no systemic absorption.

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.

Phenylephrine is 38% orally bioavailable. Clinically significant systemic absorption of ophthalmic formulations is possible, especially at higher strengths and when the cornea is damaged.

No significant percutaneous absorption from topically applied zinc oxide.

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.

Intravenous phenylephrine has an effective half life of 5 minutes and an elimination half life of 2.5 hours.

Intended for local use only, no systemic absorption.

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.

Phenylephrine has an average clearance of 2100mL/min.

Intended for local use only, no systemic absorption.

Elimination Route

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

86% of a dose of phenylephrine is recovered in the urine with 16% as the unmetabolized drug, 57% as the inactive meta-hydroxymendelic acid, and 8% as inactive sulfate conjugates.

Intended for local use only, no systemic absorption.

Pregnancy & Breastfeeding use

The safety of Calcium Dobesilate during pregnancy and lactation has not been established. As it is not known whether calcium dobesilate crosses the placental barrier in humans, the drug should be administered during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. Avoid breastfeeding while using this medicine.

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.

This medication should be used with precautions only if clearly needed during pregnancy or while breast feeding

Contraindication

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

Known hypersensitivity to any component of the preparation

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.

Acute Overdose

The clinical signs of a possible overdose are not known. If overdose occurs, seek medical advice immediately.

No overdose related problem is yet reported.

Storage Condition

Store in a cool and dry place, away from light. Keep out of the reach of children.

Store at 15-30°C.

keep in a cool and dry place, away from light.

Innovators Monograph

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