Flukit

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.

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.

Promethazine Theoclate Tablets are an anti-emetic (anti-sickness drug) which helps to prevent, and treat nausea and vomiting, including travel sickness, and vertigo. Promethazine Theoclate contains promethazine which belongs to a group of medicines called phenothiazines. Your doctor may prescribe this medicine for giddiness or light-headedness (vertigo), or for sickness after an operation, and in such cases the tablets should be taken as instructed by your doctor.

Flukit 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 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 therapyAllergic urticaria, Anaphylaxis, Cough, Dermographism, Motion Sickness, Nasal Congestion, Postoperative pain, Seasonal Allergic Conjunctivitis, Seasonal Allergic Rhinitis, Vasomotor Rhinitis, Acute Allergic Reactions, Dry cough, Perioperative nausea and vomiting, Upper respiratory symptoms, Sedative therapy, Adjunct to anesthesia and analgesiaHeadache, Mild pain, Rhinorrhoea, Sneezing

How Flukit works

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.

Promethazine is a an antagonist of histamine H1, post-synaptic mesolimbic dopamine, alpha adrenergic, muscarinic, and NMDA receptors. The antihistamine action is used to treat allergic reactions. Antagonism of muscarinic and NMDA receptors contribute to its use as a sleep aid, as well as for anxiety and tension. Antagonism of histamine H1, muscarinic, and dopamine receptors in the medullary vomiting center make promethazine useful in the treatment of nausea and vomiting.

Dosage

Flukit 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.

To prevent travel sickness on short journeys: Promethazine Theoclate should be taken at least one or two hours before travelling. Adults and children aged over 10 yearsshould take one tablet. Children aged 5 to 10 years should be given half a tablet.

To prevent travel sickness onlong journeys: Promethazine Theoclate should be taken at bedtime each night during the journey, startingthe night before you travel.Adults and childrenaged over 10 yearsshould take one tablet.Children aged 5 to 10 years should be given half a tablet.

To treat travel sickness:Adults and children over 10 years should take one tablet as soon as you feel sick, followed by a second tablet the same evening. Take a third tablet the following evening if necessary. Children aged 5 to 10 years should treated in the same way, but with half a tablet each time.

For sickness and vomiting due to other causes, and for treating vertigo: Adults and children aged over 10 years should take one tablet up to three times aday. Children aged 5 to 10 years should be given half a tablet up to three times a day.Alternativelyyou should follow the instructions given by your doctor.

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.

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with promethazine. Just because a side effect is stated here does not mean that all people using Promethazine Theoclate will experience that or any side effect.

• Drowsiness or feeling tired.
• Dizziness.
• Restlessness.
• Headache.
• Nightmares.
• Blurred vision.
• Difficulty passing urine.
• Dry mouth.
• Confusion.
• Feeling disorientated.
• Unexpected increase in excitability in children.
• Increased sensitivity of the skin to sunlight (photosensitivity). If affected you should avoid sun lamps and direct sunlight while you are taking this medicine.
• Loss of appetite.
• Awareness of your heartbeat (palpitations).
• Abnormal heartbeats (arrhythmias).
• Low blood pressure (hypotension).
• Abnormal movements of the hands, legs, face, neck and tongue, eg tremor, twitching, rigidity (extrapyramidal effects).
• Blood disorders.

Toxicity

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.

The intraperitoneal LD₅₀ in rats is 170mg/kg and in mice is 160mg/kg. The subcutaneous LD₅₀ in rats is 400mg/kg and in mice is 240mg/kg. The oral LD₅₀ in mice is 255mg/kg.

Patients experiencing an overdose of promethazine may present with mild central nervous system and cardiovascular depression, hypotension, respiratory depression, unconciousness, hyperreflexia, hypertonia, ataxia, athetosis, extensor-plantar reflexes, convulsions, dry mouth, flushing, gastrointestinal symptoms, and fixed, dilated pupils. Treat overdoses with symptomatic and supportive treatment, which may include activated charcoal, sodium sulfate, magnesium sulfate, controlled ventilation, diazepam, intravenous fluids, vasopressors, norepinephrine, phenylephrine, anticholinergic antiparkinsonian agents, diphenhydramine, barbiturates, or oxygen.

Oral, rat LD50: 1890 mg/kg

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.

Promethazine Theoclate tablets can make some people feel drowsy, dizzy, confused or disorientated and this may reduce your ability to drive or operate machinery safely. Do not drive or operate machinery until you know how this medicine affects you and you are sure it won't affect your performance. If your child is affected in this way they should avoid potentially hazardous activities such as riding bikes. You should not leave your child unattended after giving them this medicine.

Avoid drinking alcohol while taking Promethazine Theoclate because this is likely to make the above effects more likely or worse.

Promethazine Theoclate tablets may make your skin more sensitive to sunlight than usual, so you should avoid exposing your skin to direct sunlight or sunlamps until you know how your skin reacts. If you can't avoid strong sunlight you should use a sunscreen lotion or make sure your skin is protected with clothing.

This medicine may interfere with some pregnancy tests, causing false negative or false positive results.

If you are due to have any skin prick tests to diagnose allergies you should stop taking Promethazine Theoclate at least 72 hours before the tests. This is because antihistamines can prevent or lessen the skin reactions that indicate an allergy, and so can make the test results unreliable.

Interaction

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start taking Promethazine Theoclate. Similarly, check with your doctor or pharmacist before taking any new medicines while taking Promethazine Theoclate, to make sure that the combination is safe.

Promethazine Theoclate should not be taken by anyone who has taken a type of antidepressant called a monoamine oxidase inhibitor (MAOI), eg phenelzine, tranylcypromine, isocarboxazid, in the previous 14 days.

You are more likely to feel drowsy if you take Promethazine Theoclate with any of the following (which can also cause drowsiness):

• alcohol
• antipsychotic medicines, eg chlorpromazine
• barbiturates, eg phenobarbital
• benzodiazepines, eg diazepam, temazepam
• sedating antihistamines, eg chlorphenamine, brompheniramine, hydroxyzine
• sleeping tablets, eg zopiclone
• strong opioid painkillers, eg morphine, codeine, dihydrocodeine, tramadol
• tricyclic antidepressants, eg amitriptyline.

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.

The volume of distribution of phenylephrine is 340L.

The volume of distribution of promethazine is approximately 970L or 30L/kg.

Elimination Route

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

A 25mg dose of intramuscular promethazine reaches a C_max of 22ng/mL. Intravenous promethazine reaches a C_max of 10.0ng/mL, with a T_max of 4-10h, and an AUC of 14,466ng*h/mL. Oral promethazine is only 25% bioavailable due to first pass metabolism. Oral promethazine reaches a C_max of 2.4-18.0ng/mL, with a T_max of 1.5-3h, and an AUC of 11,511ng*h/mL.

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.

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

The elimination half life of promethazine is approximately 12-15h.

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).

Phenylephrine has an average clearance of 2100mL/min.

The intravenous clearance of promethazine is approximately 1.14L/min. The renal clearance of promethazine is 5.9mL/min and the renal clearance of promethazine sulfoxide is 90.4mL/min.

Elimination Route

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.

An intravenous dose of promethazine is 0.64% eliminated in the urine as the unchanged parent drug, 0.02-2.02% in the urine as desmethylpromethazine, 10% in the urine as promethazine sulfoxide.

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.

If you are pregnant you should not take Promethazine Theoclate without consulting your doctor first. Promethazine Theoclate should only be used during pregnancy if essential, and only if the expected benefit to the mother outweighs any potential risks to the developing baby. It should not be used during the last two weeks of pregnancy, because if taken during this time it may cause irritability or excitement in the baby after birth. Seek further medical advice from your doctor.

Small amounts of Promethazine Theoclate may pass into breast milk. This is not expected to be harmful to a nursing infant with occasional short-term use of Promethazine Theoclate, but there is a risk that it may cause drowsiness, irritability or excitement in a newborn baby. If you are breastfeeding you should not take Promethazine Theoclate without getting medical advice from your doctor first.

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

• Children under five years of age.
• People with reduced awareness, slow reactions or extreme drowsiness caused by medicines or illnesses that reduce activity in the central nervous system.
• People who have taken a type of medicine called a monoamine-oxidase inhibitor antidepressant (MAOI) in the past 14 days.
• Children and adolescents who have signs and symptoms suggestive of Reye's syndrome.
• People who are allergic to any ingredients of the tablets.
• Promethazine Theoclate tablets contain lactose and should not be taken by people with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.

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.

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.

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

Innovators Monograph

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