Fenomet

Uses

Intubation of the small intestine, Premedication for radiologic examination of the upper gastrointestinal tract, Prophylaxis of chemotherapy-induced nausea and vomiting, Nausea and vomiting associated with cancer chemotherapy or radiotherapy, Diabetic gastric stasis, Gastro-oesophageal reflux disease, Diabetic gastric stasis, Prophylaxis of postoperative nausea and vomiting

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.

Fenomet is also used to associated treatment for these conditions: Chemotherapy-Induced Nausea and Vomiting (CINV), Diabetic Gastroparesis, Dyspepsia, Flatulence, Gastroesophageal Reflux, Gastroparesis, Hiccups, Hyperacidity, Migraine, Nausea and vomiting, Post Operative Nausea and Vomiting (PONV), Acute, recurrent Diabetic Gastroparesis, Gastric bezoar, Radiation therapy induced nausea and vomiting, Facilitation of small bowel intubation therapy, Gastric emptying for radiologic proceduresAcute 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, Bronchodilation

How Fenomet works

Metoclopramide causes antiemetic effects by inhibiting dopamine D2 and serotonin 5-HT3 receptors in the chemoreceptor trigger zone (CTZ) located in the area postrema of the brain. Administration of this drug leads to prokinetic effects via inhibitory actions on presynaptic and postsynaptic D2 receptors, agonism of serotonin 5-HT4 receptors, and antagonism of muscarinic receptor inhibition. This action enhances the release of acetylcholine, causing increased lower esophageal sphincter (LES) and gastric tone, accelerating gastric emptying and transit through the gut. Metoclopramide antagonizes the dopamine D2 receptors. Dopamine exerts relaxant effect on the gastrointestinal tract through binding to muscular D2 receptors.

Dosage

Fenomet dosage

Intravenous-Intubation of the small intestine, Premedication for radiologic examination of the upper gastrointestinal tract:

• Adult: 10 mg as a single dose by slow inj over 1-2 min.
• Child: <6 yr 0.1 mg/kg as a single dose; 6-14 yr 2.5-5 mg as a single dose.

Prophylaxis of chemotherapy-induced nausea and vomiting:

• Adult: For highly emetogenic drugs/regimens: Initially, 2 mg/kg by slow inj over at least 15 min, 30 min before chemotherapy. Repeat 2 hrly for 2 doses, then 3 hrly for 3 doses. For less emetogenic drugs/regimens: 1 mg/kg may be used. Max duration: 5 days.

Oral-

Nausea and vomiting associated with cancer chemotherapy or radiotherapy:

• Adult: 10 mg, up to tid. Max duration: 5 days.

Diabetic gastric stasis:

• Adult: 10 mg 4 times daily for 2-8 wk.

Gastro-oesophageal reflux disease:

• Adult: 10-15 mg 4 times daily, depending on severity of symptoms. If symptoms are intermittent, may give single doses of 20 mg prior to provoking situation. Max duration: 12 wk.
• Elderly: 5 mg/dose.

Parenteral-

Diabetic gastric stasis:

• Adult: 10 mg 4 times daily by IM inj or slow IV inj over 1-2 min for up to 10 days. Convert to oral admin when symptoms subside sufficiently.

Prophylaxis of postoperative nausea and vomiting:

• Adult: 10 mg as a single dose by IM or slow IV inj over at least 3 min.
• Child: 1-3 yr 10-14 kg: 1 mg tid; >3-5 yr 15-19 kg: 2 mg tid; >5-9 yr 20-29 kg: 2.5 mg tid; >9-18 yr 30-60 kg: 5 mg tid. Max duration: 48 hr.

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.

Should be taken on an empty stomach. Take ½ hr before meals.

Side Effects

Extrapyramidal symptoms (usually acute dystonic reactions); parkinsonism; tardive dyskinesia; restlessness, drowsiness, dizziness, anxiety, confusion, tremor; hallucinations (rare); depression w/ suicidal ideation; hypotension, HTN, GI disturbances, dyspnoea, visual disturbances, urinary frequency and incontinence, headache; hypersensitivity reactions (rash, bronchospasm, angioedema); galactorrhoea or related disorders; blood disorders; transient increase in plasma-aldosterone concentration. IV: Cardiac conduction disorders, transient flushing of face and upper body (high dose).

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.

Toxicity

The rat oral LD50 of metoclopramide is 750 mg/kg.

Some symptoms of an overdose with metoclopramide include drowsiness, disorientation, and extrapyramidal reactions. Drugs that manage Parkinson's disease or anticholinergic drugs or antihistamines with anticholinergic properties should be employed to treat extrapyramidal symptoms. Normally, these symptoms subside within 24 hours. Unintentional overdose in infants receiving the oral solution of metoclopramide resulted in seizures, extrapyramidal symptoms, in addition to a lethargic state.

In addition, methemoglobinemia has been found to occur in premature and full-term neonates after a metoclopramide overdose. Intravenous methylene blue may treat metoclopramide-associated methemoglobinemia. It is important to note that methylene blue administration may lead to hemolytic anemia in patients who suffer from G6PD deficiency, which can result in fatality. Dialysis has not been shown to be effective in sufficiently eliminating metoclopramide in an overdose situation due to low plasma distribution of this drug.

Precaution

Patients with underlying neurological conditions, cardiac conduction disturbances, uncorrected electrolyte imbalance, bradycardia. Renal and hepatic impairment. Elderly, childn. Pregnancy and lactation.

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.

Interaction

Antagonistic effect with anticholinergics and morphine derivatives. Potentiation of sedative effects with CNS depressants. Additive effect with other neuroleptics on the occurrence of extrapyramydal disorders. May increase the risk of serotonin syndrome with serotonergic drugs (e.g. SSRIs). May decrease digoxin bioavailability. May increase ciclosporin bioavailability. May prolong the neuromuscular blocking effect of mivacurium and suxamethonium. Increased exposure levels with strong CYP2D6 inhibitors (e.g. fluoxetine). May reduce plasma concentration of atovaquone.

Volume of Distribution

The volume of distribution of metoclopramide is approximately 3.5 L/kg. This implies a high level of tissue distribution. Metoclopramide crosses the placental barrier and can cause extrapyramidal symptoms in the fetus.

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

Metoclopramide is rapidly absorbed in the gastrointestinal tract with an absorption rate of about 84%. The bioavailability of the oral preparation is reported to be about 40.7%, but can range from 30-100%.

Nasal metoclopramide is 47% bioavailable. A 15mg dose reaches a C_max of 41.0 ng/mL, with a T_max of 1.25 h, and an AUC of 367 ng*h/mL.

Half Life

The mean elimination half-life of metoclopramide in people with healthy renal function ranges from 5 to 6 hours but is prolonged in patients with renal impairment. Downward dose adjustment should be considered.

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.

Clearance

The renal clearance of metoclopramide is 0.16 L/h/kg with a total clearance of 0.7 L/h/kg. Clinical studies showed that the clearance of metoclopramide may be reduced by up to 50% in patients with renal impairment. After high intravenous doses, total metoclopramide clearance ranged from 0.31 to 0.69 L/kg/h.

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

About 85% of an orally administered dose was measured in the urine within 72 hours during a pharmacokinetic study. An average of 18% to 22% of 10-20 mg dose was recovered as free drug within 3 days of administration.

Pregnancy & Breastfeeding use

Category B: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).

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.

Contraindication

GI haemorrhage, mechanical obstruction or GI perforation; confirmed or suspected pheochromocytoma; history of neuroleptic or metoclopramide-induced tardive dyskinesia; epilepsy, Parkinson's disease; history of methaemoglobinaemia with metoclopramide or of NADH cytochrome-b5 deficiency. Concomitant use with levodopa or dopaminergic agonists.

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

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: Extrapyramidal disorders, drowsiness, decreased level of consciousness, confusion, hallucination, cardiorespiratory arrest.

Management: Symptomatic treatment with continuous monitoring of CV and resp functions. In case of extrapyramidal symptoms, treatment is symptomatic (benzodiazepines in childn and/or anticholinergic antiparkinsonian medicinal products in adults).

Storage Condition

Store between 20-25°C. Protect from light.

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.

Innovators Monograph

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