Cosavil

Uses

Paracetamol IV is used for the management of mild to moderate pain, the management of moderate to severe pain with adjunctive opioid analgesics, the reduction of fever.

Paracetamol is a non-salicylate antipyretic and non-opioid analgesic agent. Paracetamol IV injection is a sterile, clear, colorless, non pyrogenic, isotonic formulation of Paracetamol intended for intravenous infusion.

Pheniramine is a competitive H1 histamine receptor antagonist. Like other alkylamine antihistamines it is also antagonist of muscarinic cholinergic receptors and possesses local anesthetic properties. However, the concentration required for the latter effect is probably not achieved at therapeutic dose

Pheniramine Maleate is used for allergic conditions (hypersensitivity reactions) such as:

• Hay fever (pollinosis) with attacks of sneezing, itching, running of the nose, conjunctivitis.
• Urticaria with pruritus and reddening, wealing and swelling of the skin.
• Eczema of nervous origin (neurodermatitis) with pruritus.

Cosavil is also used to associated treatment for these conditions: Acute Gouty Arthritis, Acute Musculoskeletal Pain, Allergies, Ankylosing Spondylitis (AS), Arthritis, Chills, Cold, Cold Symptoms, Common Cold, Common Cold/Flu, Cough, Cough caused by Common Cold, Coughing caused by Flu caused by Influenza, Dyskinesia of the Biliary Tract, Dyskinesia of the Urinary Tract, Febrile Convulsions, Febrile Illness Acute, Fever, Fibromyalgia Syndrome, Flu caused by Influenza, Headache, Joint dislocations, Menstrual Distress (Dysmenorrhea), Mild pain, Muscle Inflammation, Muscle Injuries, Muscle Spasms, Musculoskeletal Pain, Nasal Congestion, Neuralgia, Osteoarthritis (OA), Pain, Pollen Allergy, Postoperative pain, Premenstrual cramps, Rheumatoid Arthritis, Rhinopharyngitis, Rhinorrhoea, Severe Pain, Sinusitis, Soreness, Muscle, Spasms, Spastic Pain of the Gastrointestinal Tract, Sprains, Tension Headache, Toothache, Upper Respiratory Tract Infection, Whiplash Syndrome, Acute Torticollis, Mild to moderate pain, Minor aches and pains, Minor pain, Moderate Pain, Airway secretion clearance therapy, Antispasmodic, BronchodilationAllergic Skin Reaction, Allergic urticaria, Anaphylaxis, Angioedema, Burns first degree, Common Cold, Congestion of the Conjunctivas, Dermatitis, Eczematous, Drug hypersensitivity reaction, Flu caused by Influenza, Insect Bites, Neurodermatitis, Ocular Irritation, Red eye, Seasonal Allergic Conjunctivitis, Sunburn, Urticaria

How Cosavil works

Pheniramine competes with histamine for the histamine H1 receptor, acting as an inverse agonist once bound. The reduction in H1 receptor activity is responsible for reduced itching as well as reduced vasodilation and capillary leakage leading to less redness and edema. This can be seen in the suppression of the histamine-induced wheal (swelling) and flare (vasodilation) response. Inverse agonism of the H1 receptor in the CNS is also responsible for the sedation produced by first-generation antihistamines like pheniramine. The binding of pheniramine to H4 receptors, and subsequent inverse agonism, may also contribute to reduced itching by antagonizing inflammation.

Dosage

Cosavil dosage

Adults and adolescents weighing 50 kg and over: the recommended dosage of Paracetamol IV is 1000 mg every 6 hours or 650 mg every 4 hours, with a maximum single dose of Paracetamol IV of 1000 mg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 4000 mg per day.

Adults and adolescents weighing under 50 kg: the recommended dosage of Paracetamol IV is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of Paracetamol IV of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 75 mg/kg per day.

Children >2 to 12 years of age: the recommended dosage of Paracetamol IV is 15 mg/kg every 6 hours or 12.5 mg/kg every 4 hours, with a maximum single dose of Paracetamol IV of 15 mg/kg, a minimum dosing interval of 4 hours, and a maximum daily dose of Paracetamol of 75 mg/kg per day.

Unless otherwise prescribed by the doctor, the following dosages are recommended for the different dosage forms:

Pheniramine Maleate Injection Solution: Except in life threatening conditions, the initial dose should be kept as low as possible: particularly in small children, a daily dose of 3 mg active substance per kg body weight should not be exceeded.

The following doses are administered once or twice daily:

• Adults and Young people aged 12 years or over:1.0-2.0 ml IV/IM.
• Children aged 1-2 years (about 11-14 kg body weight):0.5-0.7 ml IM only
• Children aged 3-5 years (about 20 kg body weight):0.8-1.3 ml IM only
• Children aged 6-11 years (upto about 25 kg body weight):1.0-1.5 ml IM only

Pheniramine Maleate Injection (45.5 mg/2 ml)

: This is administered to adults and young people aged 12 years or over either slowly by intravenous route (1 ml per minute) or intramuscularly. To infants and children up to 12 years old the injection must only be given intramuscularly. The recommended dose may be repeated at 12 hourly intervals until acute symptoms have subsided. Pheniramine Maleate can be combined with commercial calcium preparations but the compatibility should be tested in individual case.

Pheniramine Maleate Tablet (22.7 mg): In adults and young people of over 12 years of age it is advisable to begin treatment with 1 tablet 2-3 times daily after meals. If necessary, the daily dose may be increased to 2 tablets 3 times daily from the second day of treatment onwards.

Pheniramine Maleate Syrup (15 mg/5 ml): is particularly suitable for children. Children aged 1-3 years should receive half a measuring spoonful two or three times daily; children aged 4-12 years, 1 measuring spoonful 2 or 3 times daily; adults and young people 1-2 measuring spoonful of syrup twice or three times a day after meals. A daily dose of 3 mg/kg body weight must not be exceeded. Diabetics must bear in mind that Pheniramine Maleate Syrup contains carbohydrates which are equivalent to 1.75 gm glucose per measuring spoonful (5 ml)

Pheniramine Maleate RetardTablet (75 mg): The coated tablets have a prolonged action. In most adults and adolescent over 12 years of age 1 coated tablet taken after supper is sufficient to produce an antihistaminic effect that for up to 24 hours. Only in very resistant cases will it be necessary to give an additional coated tablet in the morning after breakfast. The tablets are swallowed whole with a little liquid.

Side Effects

As all paracetamol products, adverse drug reactions are rare (>1/10000, <1/1000) or very rare (<1/10000). Frequent adverse reactions at injection site have been reported during clinical trials (pain and burning sensation). Very rare cases of hypersensitivity reactions ranging from simple skin rash or urticaria to anaphylactic shock have been reported and require discontinuation of treatment. Cases of erythema, flushing, pruritus and tachycardia have been reported.

Occasionally there may be drowsiness, gastrointestinal complaints, dryness of mouth, palpitation, urinary retention or hypersensitivity reactions. In isolated cases, higher doses may produce hallucinations, restlessness or confusion; in small children, agitation.

In patients with narrow angle-glaucoma a rise in intraocular pressure is possible, which makes opthalmologic control necessary.

Even if used according to prescription, these preparations may reduce alertness to such an extent that the ability to cope with street traffic or operate machinery is impaired.

Toxicity

Case reports involving pheniramine overdosage mention the rare possibility of arrythmias, cutaneous eruptions, and rhabdomyolysis with acute kidney injury. The administration of activated charcoal effectively prevents the absorption of pheniramine as it largely adsorbs to the charcoal, therefore this may be of benefit in cases of overdose if provided early after ingestion.

Precaution

Administration of Paracetamol in doses higher than recommended may result in hepatic injury, including the risk of severe hepatotoxicity and death. Do not exceed the maximum recommended daily dose of Paracetamol. Use caution when administering Paracetamol in patients with the following conditions: hepatic impairment or active hepatic disease, alcoholism, chronic malnutrition, severe hypovolemia (e.g., due to dehydration or blood loss), or severe renal impairment (creatinine clearance < 30 ml/min). There were infrequent reports of life-threatening anaphylaxis requiring emergent medical attention. Discontinue Paracetamol IV immediately if symptoms associated with allergy or hypersensitivity occurs. Do not use Paracetamol IV in patients with Paracetamol allergy.

During pregnancy and lactation, pheniramine should be used only if strictly indicated, and after considering the benifit/risk ratio for mother and child.

Interaction

The effect of drugs which act on the central nervous system (e.g. tranquilizers, sedatives, neuroleptic agents and MAO inhibitors) and of alcohol may be potentiated.

Volume of Distribution

Volume of distribution is about 0.9L/kg. 10 to 20% of the drug is bound to red blood cells. Acetaminophen appears to be widely distributed throughout most body tissues except in fat.

Elimination Route

The administration of 30.5 mg of free base pheniramine resulted in a Cmax of 173-294 ng/L with a Tmax of 1-2.5 h.

Half Life

The half-life for adults is 2.5 h after an intravenous dose of 15 mg/kg. After an overdose, the half-life can range from 4 to 8 hours depending on the severity of injury to the liver, as it heavily metabolizes acetaminophen.

The terminal half-life of pheniramine administered via IV is 8-17 h.

Clearance

Adults: 0.27 L/h/kg following a 15 mg/kg intravenous (IV) dose. Children: 0.34 L/h/kg following a 15 mg/kg intravenous (IV dose).

Elimination Route

Pheniramine is eliminated by metabolism and via renal excretion. 24.3% of pheniramine is present in the urine as the parent drug.

Pregnancy & Breastfeeding use

Pregnancy Category C. There are no studies of intravenous Paracetamol in pregnant women; however, epidemiological data on oral Paracetamol use in pregnant women show no increased risk of major congenital malformations. Animal reproduction studies have not been conducted with IV Paracetamol and it is not known whether Paracetamol IV can cause fetal harm when administered to a pregnant woman. Paracetamol IV should be given to a pregnant woman only if clearly needed. There are no adequate and well-controlled studies with Paracetamol IV during labor and delivery; therefore, it should be used in such settings only after a careful benefit-risk assessment. While studies with Paracetamol IV have not been conducted, Paracetamol is secreted in human milk in small quantities after oral administration.

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus.

Contraindication

Paracetamol is contraindicated in patients with known hypersensitivity to its active ingredient or to any of the excipients in the intravenous formulation. Also contraindicated in patients with severe hepatic impairment or severe active liver disease

Hypersensitivity to pheniramine. The Syrup is contraindicated in patients hypersensitive to Methyl Hydroxybenzoate and Propyl Hydroxybenzoate. Prostatic hypertrophy with residual urine formation.

Special Warning

Pediatric Use: The safety and effectiveness of Paracetamol IV for the treatment of acute pain and fever in pediatric patients ages 2 years and older is supported by evidence from adequate and well-controlled studies of Paracetamol IV in adults.

Geriatric use: No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Patients with Hepatic Impairment: Paracetamol is contraindicated in patients with severe hepatic impairment or severe active liver disease and should be used with caution in patients with hepatic impairment or active liver disease. A reduced total daily dose of Paracetamol may be warranted.

Patients with Renal Impairment: In cases of severe renal impairment (creatinine clearance < 30 ml/min), longer dosing intervals and a reduced total daily dose of Paracetamol may be warranted.

Acute Overdose

Symptoms: Agitation and convulsions (especially in children), and restlessness, disorientation and hallucinations in adults. Accidental ingestion in small children has resulted in convulsions and in some cases fatal.

Treatment: No specific antidote; symptomatic and supportive. Gastric lavage may be useful for some time after ingestion. Do not use stimulants. Diazepam or short-acting barbiturates may be used to control convulsions. Vasopressors may be used for hypotension.

Storage Condition

Store in a cool & dry place & away from children. For single use only. The product should be used within 6 hours after opening. Do not refrigerate or freeze.

Keep all medicines out of the reach of children. To be dispensed only on the prescription of a registered physician. Do not use later than the date of expiry.

Innovators Monograph

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