Contrast Allergy PreMed Pack

Uses

Diphenhydramine is used for the treatment of followings:

• Seasonal, perennial, vasomotor rhinitis
• Urticaria, angioneurotic oedema, anaphylaxis
• Pruiritic conditions
• Premedication for emesis and motion sickness
• Miscellaneous like meniere's disease and parkinsonism

Prednisone is a corticosteroid used to treat inflammation or immune-mediated reactions and to treat endocrine or neoplastic diseases.

Prednisone is indicated as an anti-inflammatory or immunosuppressive drug for allergic, dermatologic, gastrointestinal, hematologic, ophthalmologic, nervous system, renal, respiratory, rheumatologic, infectious, endocrine, or neoplastic conditions as well as in organ transplant.

Contrast Allergy PreMed Pack is also used to associated treatment for these conditions: Allergic Rhinitis (AR), Allergic cough, Allergies, Anaphylaxis, Angioedema, Common Cold, Common Cold/Flu, Conjunctival irritation, Cough, Cough Variant Asthma, Cough caused by Common Cold, Eye allergy, Fever, Insect Bites, Insect Stings, Insomnia, Irritative cough, Itching of the nose, Itching of the throat, Motion Sickness, Nasal Congestion, Oral Mucositis, Pain, Parkinsonian Syndromes, Pollen Allergy, Productive cough, Pruritus, Rash, Rhinorrhoea, Sinus Congestion, Sinus headache, Skin Irritation, Sneezing, Sunburn, Symptoms of Acute Bronchitis Accompanied by Coughing, Upper respiratory tract hypersensitivity reaction, site unspecified, Urticaria, Dermatographism, Dry cough, Watery itchy eyes, Airway secretion clearance therapy, ExpectorantAcne Vulgaris, Acute Gouty Arthritis, Acute Lymphoblastic Leukaemias (ALL), Aggressive Lymphoma, Allergic Bronchopulmonary Aspergillosis, Allergic Rhinitis (AR), Allergic corneal marginal ulcers, Alveolitis, Extrinsic Allergic, Ankylosing Spondylitis (AS), Anterior Segment Inflammation, Aspiration Pneumonitis, Asthma, Atopic Dermatitis (AD), Bell's Palsy, Berylliosis, Bullous dermatitis herpetiformis, Chorioretinitis, Chronic Obstructive Airways Disease Exacerbated, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Corneal Inflammation, Crohn's Disease (CD), Dermatitis exfoliative generalised, Dermatitis, Contact, Dermatomyositis, Disseminated tuberculosis, Drug hypersensitivity reaction, Edema of the cerebrum, Epicondylitis, Erythroblastopenia, Giant Cell Arteritis (GCA), Hepatitis, Autoimmune, Hypercalcemia of Malignancy, Idiopathic Thrombocytopenic Purpura, Iridocyclitis, Iritis, Leukemia, Acute, Leukemias, Loeffler's syndrome, Malignant Lymphomas, Metastatic Castration Resistant Prostate Cancer, Multiple sclerosis exacerbation, Mycosis Fungoides (MF), Ocular Inflammation, Ophthalmia, Sympathetic, Optic Neuritis, Pain caused by Herpes zoster, Pemphigus, Pericarditis, Pneumocystis Jirovecii Pneumonia, Polymyalgia Rheumatica, Primary adrenocortical insufficiency, Proteinuria, Psoriatic Arthritis, Pulmonary Fibrosis, Pure Red Cell Aplasia, Relapsing Polychondritis, Rheumatic heart disease, unspecified, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Seasonal Allergic Conjunctivitis, Secondary adrenocortical insufficiency, Secondary thrombocytopenia, Serum Sickness, Severe Seborrheic Dermatitis, Sjögren's Syndrome, Stevens-Johnson Syndrome, Systemic Lupus Erythematosus (SLE), Takayasu's Disease, Thyroid Eye Disease, Thyroiditis, Thyrotoxicosis, Trichinosis, Tuberculous Meningitis, Ulcerative Colitis, Uveitis, Vasculitis, Acquired immune hemolytic anemia, Acute Bursitis, Acute Tenosynovitis, Bronchiolitis obliterans organizing pneumonia, Fulminating Tuberculosis, Idiopathic eosinophilic pneumonias, Non-suppurative Thyroiditis, Severe Psoriasis, Solid organ rejection, Subacute Bursitis, Symptomatic Sarcoidosis, Synovitis of osteoarthritis, Systemic Dermatomyositis, Varicella-zoster virus acute retinal necrosis

How Contrast Allergy PreMed Pack works

Diphenhydramine predominantly works via the antagonism of H1 (Histamine 1) receptors . Such H1 receptors are located on respiratory smooth muscles, vascular endothelial cells, the gastrointestinal tract (GIT), cardiac tissue, immune cells, the uterus, and the central nervous system (CNS) neurons . When the H1 receptor is stimulated in these tissues it produces a variety of actions including increased vascular permeability, promotion of vasodilation causing flushing, decreased atrioventricular (AV) node conduction time, stimulation of sensory nerves of airways producing coughing, smooth muscle contraction of bronchi and the GIT, and eosinophilic chemotaxis that promotes the allergic immune response .

Ultimately, diphenhydramine functions as an inverse agonist at H1 receptors, and subsequently reverses effects of histamine on capillaries, reducing allergic reaction symptoms . Moreover, since diphenhydramine is a first-generation antihistamine, it readily crosses the blood-brain barrier and inversely agonizes the H1 CNS receptors, resulting in drowsiness, and suppressing the medullary cough center .

Furthermore, H1 receptors are similar to muscarinic receptors . Consequently, diphenhydramine also acts as an antimuscarinic . It does so by behaving as a competitive antagonist of muscarinic acetylcholine receptors, resulting in its use as an antiparkinson medication .

Lastly, diphenhydramine has also demonstrated activity as an intracellular sodium channel blocker, resulting in possible local anesthetic properties .

Prednisone is first metabolized in the liver to its active form, prednisolone, a glucocorticoid agonist corticosteroid.

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

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.

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

Dosage

Contrast Allergy PreMed Pack dosage

Adult-

• Most allergic conditions: 25-50 mg three times a day with a further 50 mg at night.

Children-

• 1 to 5 years of age: 5 mg i.e., 2.5 ml of elixir 4 times a day
• More than 6 years of age: 10 mg i.e. 5 ml of elixir 4 times a day

Side Effects

Side effect includes sedation, dizziness, tinnitus, fatigue, ataxia, blurred vision, diplopia, euphoria, and epigastric discomfort.

Toxicity

Overdose is expected to result in effects similar to the adverse effects that are ordinarily associated with the use of diphenhydramine, including drowsiness, hyperpyrexia, and anticholinergic effects, among others . Additional symptoms during overdose may include mydriasis, fever, flushing, agitation, tremor, dystonic reactions, hallucinations and ECG changes . Large overdose may cause rhabdomyolysis, convulsions, delirium, toxic psychosis, arrhythmias, coma and cardiovascular collapse . Moreover, with higher doses, and particularly in children, symptoms of CNS excitation including hallucinations and convulsions may appear; with massive doses, coma or cardiovascular collapse may follow .

Although diphenhydramine has been in widespread use for many years without ill consequence, it is known to cross the placenta and has been detected in breast milk . This medication should therefore only be used when the potential benefit of treatment to the mother exceeds any possible hazards to the developing fetus or suckling infant .

Pharmacokinetic studies indicate no major differences in the distribution or elimination of diphenhydramine compared to younger adults . Nevertheless, diphenhydramine should be used with caution in the elderly, who are more likely to experience adverse effects . Avoid use in elderly patients with confusion .

The results of a review on the use of diphenhydramine in renal failure suggest that in moderate to severe renal failure, the dose interval should be extended by a period dependent on Glomerular filtration rate (GFR) .

After intravenous administration of 0.8 mg/kg diphenhydramine, a prolonged half-life was noted in patients with chronic liver disease which correlated with the severity of the disease . However, the mean plasma clearance and apparent volume of distribution were not significantly affected .

LD₅₀=500 mg/kg (orally in rats). Considerable overdosage can lead to myocardial infarction (heart attack), serious ventricular dysrhythmias, coma and death.

Data regarding acute overdoses of prednisone are rare but prolonged high doses of prednisone can lead to a higher incidence and severity of adverse effects such as mental symptoms, moon face, abnormal fat deposits, fluid retention, excessive appetite, weight gain, hypertrichosis, acne, striae, ecchymosis, increased sweating, pigmentation, dry scaly skin, thinning scalp hair, increased blood pressure, tachycardia, thrombophlebitis, decreased resistance to infection, negative nitrogen balance with delayed bone and wound healing, headache, weakness, menstrual disorders, accentuated menopausal symptoms, neuropathy, fractures, osteoporosis, peptic ulcer, decreased glucose tolerance, hypokalemia, and adrenal insufficiency.

Precaution

Caution should be exercised with patients in whom drowsiness is undesirable e.g., drivers, machine operators. Concomitant consumption of alcohol or central nervous system (CNS) depressants will potentiate drowsiness.

Interaction

Diphenhydramine administration significantly reduces the absorption of the antituberculous agent para-aminosalicyclic acid (PAS) from the gastrointestinal tract. CNS depressants may potentiate the sedative action of Diphenhydramine. Anticholinergic drugs may potentiate Diphenhydramine’s anticholinergic side effects.

Volume of Distribution

Diphenhydramine is widely distributed throughout the body, including the CNS . Following a 50 mg oral dose of diphenhydramine, the volume of distribution is in the range of 3.3 - 6.8 l/kg .

Data regarding the volume of distribution for prednisone is not readily available. However, a 0.15mg/kg dose of prednisolone has a volume of distribution of 29.3L, while a 0.30mg/kg dose has a volume of distribution of 44.2L.

Elimination Route

Diphenhydramine is quickly absorbed after oral administration with maximum activity occurring in approximately one hour . The oral bioavailability of diphenhydramine has been documented in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration .

Oral prednisone has a T_max of 2 hours, while the delayed-release formulation has a T_max of 6-6.5 hours. A 5mg dose of prednisone has an AUC of 572mL/min/1.73m^{2 Data regarding the C_max of prednisone is not readily available.}

Half Life

The elimination half-life ranges from 2.4-9.3 hours in healthy adults . The terminal elimination half-life is prolonged in liver cirrhosis .

Prednisone and its active metabolite prednisolone have half lives of 2-3 hours from both immediate and delayed release preparations.

Clearance

Values for plasma clearance of a 50 mg oral dose of diphenhydramine has been documented as lying in the range of 600-1300 ml/min .

Data regarding the clearance of prednisone is not readily available.

A 5.5µg/h/kg infusion of prednisolone has an average clearance of 0.066±0.12L/h/kg, while a 0.15±0.03L/h/kg infusion has an average clearance of 0.15L/h/kg.

Elimination Route

The metabolites of diphenhydramine are conjugated with glycine and glutamine and excreted in urine . Only about 1% of a single dose is excreted unchanged in urine . The medication is ultimately eliminated by the kidneys slowly, mainly as inactive metabolites .

Prednisone is excreted mainly in the urine as sulfate and glucuronide conjugates.

Pregnancy & Breastfeeding use

Category B: There are no adequate and well controlled studies in pregnant women using diphenhydramine hydrochloride. Therefore, diphenhydramine hydrochloride should be used in pregnancy only if clearly needed. Diphenhydramine hydrochloride has been reported to be excreted in breast milk and thus, use of diphenhydramine hydrochloride in lactating mother is not recommended.

Contraindication

Known hypersensitivity to Diphenhydramine Hydrochloride, Ammonium chloride is contra-indicated in presence of impaired hepatic or renal function.

Acute Overdose

Symptoms: Impaired consciousness; psychosis, seizures, antimuscarinic symptoms (e.g. mydriasis, tachycardia, tachyarrhythmias), resp failure, rhabdomyolysis; acute delirium with visual and auditory hallucination (topical).

Management: Supportive and symptomatic treatment. Convulsions and marked CNS stimulation may be treated with IV diazepam.

Storage Condition

Store between 15-30° C. Protect from moisture.

Innovators Monograph

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