Orlift Tab

Uses

(Clopidogrel) is used for the reduction of atherosclerotic events (myocardial infarction, ischaemic stroke, and vascular death) in patients with atherosclerosis documented by recent stroke, recent myocardial infarction, or established peripheral arterial disease.

Orlistat is used for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet. Orlistat is also used for the reduction of the risk of weight regain after prior weight loss. Orlistat 120 mg is used for obese patients with an initial body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia) and Orlistat 60 mg is used for overweight & obese patients with an initial body mass index (BMI) ≥25 kg/m2.

Orlift Tab is also used to associated treatment for these conditions: Acute Coronary Syndrome (ACS), Acute Myocardial Infarction (AMI), Cardiovascular Events, Atherothrombotic eventsWeight Gain, Weight Reduction

How Orlift Tab works

Clopidogrel is metabolized to its active form by carboxylesterase-1. The active form is a platelet inhibitor that irreversibly binds to P2Y₁₂ ADP receptors on platelets. This binding prevents ADP binding to P2Y₁₂ receptors, activation of the glycoprotein GPIIb/IIIa complex, and platelet aggregation.

Orlistat is a potent and selective inhibitor of various lipase enzymes responsible for the metabolism of fat. It acts in the gastrointestinal (GI) tract via covalent binding to the serine residues located on the active site of both gastric and pancreatic lipase. When orlistat is taken with food containing fat, it partially inhibits the hydrolysis of triglycerides. This decreases absorption of monoaclglycerides and free fatty acids, contributing to weight maintenance and weight loss.

Dosage

Orlift Tab dosage

The recommended dose of Lopirel (Clopidogrel) is 75 mg once daily with or without food.

The recommended dose of Orlistat is one 60 mg or 120 mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal). The patient should be on a nutritionally balanced, reduced-calorie diet that contains approximately 30% of calories from fat. The daily intake of fat, carbohydrate, and protein should be distributed over three main meals. If a meal is occasionally missed or contains no fat, the dose of Orlistat can be omitted.

Because Orlistat has been shown to reduce the absorption of some fat-soluble vitamins and beta-carotene, patients should be counseled to take a multivitamin containing fat-soluble vitamin to ensure adequate nutrition. The vitamin supplement should be taken at least 2 hours before or after the administration of Orlistat, such as at bedtime.

Side Effects

Generally Clopidogrel is well tolerated. However, a few common side effects i.e. Influenza-like symptoms, headache, upper respiratory tract infection, dizziness, muscle and back pain, and rash may occur.

Commonly-observed adverse events associated with the use of Orlistat include oily spotting, flatus with discharge, fecal urgency, fatty/oily stool, oily evacuation, increased defecation, fecal incontinence.

Toxicity

A single dose of clopidogrel at 1500-2000mg/kg was lethal to mice and rats while 3000mg/kg was lethal to baboons. Symptoms of overdose include vomiting, breathing difficulty, gastrointestinal hemorrhage, and prostration. Clopidogrel is irreversibly bound to platelets for their lifetime, which is approximately 11 days. Overdoses of clopidogrel can be treated with platelet transfusions to restore clotting ability.

The oral LD50 of orlistat is >5000 mg/kg in rats. Single orlistat doses of 800 mg and multiple doses of up to 400 mg three times a day for 15 days have been administered to healthy weight and obese subjects without clinically significant adverse findings. In addition, doses of 240 mg three times a day have been given to obese patients for 6 months without a significant adverse effects. Post-marketing reports of overdoses cases indicate no adverse events or adverse events that are similar to those reported with the recommended dose. If a significant overdose with orlistat occurs, the patient should be observed for at least 24 hours. Based on the results of clinical studies, systemic effects caused by orlistat are likely to be rapidly reversible.

Precaution

As with other anti-platelet agents, Clopidogrel should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery, or other pathological conditions. Clopidogrel should be discontinued 7 days prior to surgery. Clopidogrel should be used with caution in hepatically impaired patients who may have bleeding diatheses.

Patients should be advised to adhere to dietary guidelines. gastrointestinal events may increase when orlistat is taken with a diet high in fat (>30% of calories from fat). The daily intake of fat should be distributed over three main meals. If a meal is missed, the dose of orlistat may be omitted.

Interaction

Concomitant use of Heparin, Warfarin and NSAIDs with Clopidogrel should be undertaken with caution. Clopidogrel potentiate the effect of Aspirin on collagen-induced platelet aggregation. The safety of chronic concomitant administration of Aspirin and Clopidogrel has not been established.

May reduce the absorption of iodine salts and/or levothyroxine, fat-soluble vit (A, D, E, K) and beta carotene. May decrease plasma levels of ciclosporin and amiodarone. May decrease the efficacy of antiepileptic drugs (e.g. valproate, lamotrigine), antiretrovirals, antidepressants, antipsychotics (including lithium). Additive effect on glycaemic control with antidiabetics. May cause hormonal contraceptive failure. May enhance the anticoagulant effect of warfarin.

Volume of Distribution

The apparent volume of distribution of clopidogrel is 39,240±33,520L.

Volume of distribution cannot be obtained because the absorption of orlistat is minimal. Orlistat is minimally distributed to erythrocytes and is primarily bound to proteins.

Elimination Route

A 75mg oral dose of clopidogrel is 50% absorbed from the intestine. Clopidogrel can be taken with or without food. A meal decreases the AUC of the active metabolite by 57%. The active metabolite of clopidogrel reaches a maximum concentration after 30-60 minutes. Clopidogrel reached a C_max of 2.04±2.0ng/mL in 1.40±1.07h.

The AUC for a 300mg oral dose of clopidogrel was 45.1±16.2ng*h/mL for poor metabolizers, 65.6±19.1ng*h/mL for intermediate metabolizers, and 104.3±57.3ng*h/mL for extensive metabolizers. The C_max was 31.3±13ng/mL for poor metabolizers, 43.9±14ng/mL for intermediate metabolizers, and 60.8±34.3ng/mL for extensive metabolizers.

The systemic absorption and exposure of orlistat is low, however, systemic absorption of the drug is not required for orlistat activity. After an oral dose with 360 mg of radiolabeled orlistat, plasma radioactivity achieved a peak at about 8 hours. Plasma concentrations of unchanged parent drug were close to the lower end of detection limits (15

Half Life

That half life of clopidogrel is approximately 6 hours following a 75mg oral dose while the half life of the active metabolite is approximately 30 minutes.

The half-life of orlistat of the small amount of absorbed orlistat ranges between 1-2 hours.

Clearance

The clearance of a 75mg oral dose was 18,960±15,890L/h and for a 300mg oral dose was 16,980±10,410L/h.

Elimination Route

An oral dose of radiolabelled clopidogrel is excreted 50% in the urine and 46% in the feces over 5 days. The remainder of clopidogrel is irreversibly bound to platelets for their lifetime, or approximately 8-11 days.

After single oral dose of radiolabled orlistat in both normal weight and obese volunteers fecal excretion of the unabsorbed drug was found to be the major route of elimination with 11,20 Fecal elimination of orlistat is estimated between 95-97%. Complete excretion by both routes occurs within in 3 to 5 days.

Pregnancy & Breastfeeding use

Pregnancy: There are no adequate and well-controlled studies of Clopidogrel in pregnant women. However, Clopidogrel should be used during pregnancy only if clearly needed.

Lactation: Clopidogrel is not recommended for use while breast-feeding. It is not known for sure whether Clopidogrel is excreted in breast milk, although it is suspected that it is.

Pregnancy Category X. Orlistat is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm.

It is not known whether Orlistat is present in human milk or not. Caution should be exercised when Orlistat is administered to a nursing woman.

Contraindication

Clopidogrel is contraindicated in patients with a hypersensitivity to the drug substance or any component of the product, and those with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.

Orlistat is contraindicated in Pregnancy, Patients with chronic malabsorption syndrome, Patients with cholestasis, Patients with known hypersensitivity to Orlistat or to any component of this product.

Special Warning

Use in children: Safety and effectiveness of Clopidogrel in pediatric population have not been established.

Pediatric use: Safety and effectiveness in pediatric patients below the age of 12 have not been established.

Acute Overdose

In the event of over dosage no adverse effects were reported and no therapy was substituted.

Symptoms: Prolonged bleeding time and subsequent bleeding complications.

Management: May restore clotting ability with platelet transfusion.

Single doses of 800 mg and multiple doses of up to 400 mg three times a day for 15 days have been studied in normal weight and obese subjects without significant adverse findings. If a significant overdose of orlistat occur, it is recommended that the patient be observed for 24 hours. Based on human and animal studies, any systemic effects attributable to the lipase inhibiting properties of orlistat should be rapidly reversible

Storage Condition

Store at 25° C.

Store below 25°C; excursions permitted to 15° to 30°C. Keep the medicine out of reach of children.

Innovators Monograph

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