Orlip

Orlip has a peripheral principle of action; it is a drug used for obesity. The component orlistat is a specific substance that has a powerful inhibitory effect on gastrointestinal lipases (has a long-lasting effect).

The medicinal effect of the drug is realized inside the small intestine and gastric lumen – covalent bonds are formed with active serine regions of pancreatic and gastric lipases. In this case, the inactivated enzyme loses the ability to break down dietary fats that come in the form of triglycerides, and in addition, the effect on absorbed free fatty acids and monoglycerides. [ 1 ]

Indications Orlip

It is used in combination with a dietary regimen (moderate hypocaloric intake) in obese individuals (BMI ≥30 kg/m2) or overweight individuals (BMI ≥28 kg/m2), including those with risk factors associated with obesity.

Orlistat should be discontinued after 3 months if a weight loss of at least 5% compared to baseline is not recorded.

Release form

The drug is produced in the form of capsules, in the amount of 10 pieces inside a cell plate. There are 3 such plates in a box.

Pharmacokinetics

Absorption.

Tests in normal-weight and obese volunteers have shown that the effect of weight on absorption rates is extremely low. After 8 hours of oral administration of the drug, unchanged substance was not detected in the blood plasma, suggesting that its value is less than 5 ng/mol. [ 2 ]

Overall, when therapeutic doses of Orlip were administered, unchanged orlistat could only be detected sporadically in plasma; its levels were very low (<10 ng/mL or 0.02 μmol). No signs of accumulation were observed, confirming the poor absorption of the drug. [ 3 ]

Distribution processes.

The distribution volume cannot be determined because the drug is poorly absorbed. In vitro, the drug is more than 99% synthesized with blood intraplasmic protein (mostly with albumin and lipoproteins). Minimal volumes of orlistat pass into erythrocytes.

Exchange processes.

Information obtained from animal testing showed that the metabolic processes of orlistat are mainly realized through the walls of the gastrointestinal tract. About 42% of the minimum values of the drug undergoing general absorption in obese individuals are the 2 main metabolic products of Orlipa - M1 with M3.

Molecules of the M1 and M3 type have an open β-lactone ring and inhibit lipase activity quite weakly (1000 and 2500 times less than orlistat). Given this weak inhibitory effect and low plasma values (the average level is 26 and 108 ng/ml, respectively), these metabolic products are considered to have no medicinal activity after administration of therapeutic doses.

Excretion.

Unabsorbed drug is mainly eliminated in the feces (approximately 97% of the dose, 83% as unchanged drug).

Cumulative renal excretion of all substances that are structurally synthesized with orlistat is less than 2% of the portion. The term for complete excretion of the drug (with urine and feces) is 3-5 days. The proportions of the drug excretion routes in volunteers with excess and normal weight are completely analogous. Both metabolic elements M1 with M3 and orlistat can be excreted with bile.

Dosing and administration

Adults are prescribed to take 1 capsule of 0.12 g (washed down with plain water) immediately before, with or within an hour after a meal. If you skip a meal or eat low-fat food, you may skip taking Orlip.

Patients should eat a balanced diet, follow a hypocaloric diet in a moderate form, containing about 30% of calories (in the form of fats). It is necessary to eat a large amount of vegetables together with fruits. The daily volume of proteins with fats, as well as carbohydrates, should be divided into 3 daily meals.

Exceeding the standard dosage of the drug (0.12 g 3 times a day) does not cause potentiation of the drug's effect.

The use of orlistat leads to an increase in the secretion of fat with feces after 24-48 hours from the moment of taking the drug. At the end of therapy, the secretion of fat with feces returns to the original volume after 48-72 hours.

• Application for children

There is no information regarding the use of Orlip in pediatrics.

Use Orlip during pregnancy

There are no clinical data regarding the use of orlistat during pregnancy.

Animal testing has not shown any direct or indirect harmful effects with respect to pregnancy, fetal/embryonic development, parturition, or postnatal development. However, orlistat is still prohibited for use during this period.

There is no information regarding whether orlistat is excreted in human milk, which is why it is not prescribed during breastfeeding.

Contraindications

Contraindicated for use in chronic malabsorption syndrome or in cases of intolerance to the active ingredient or other components of the drug.

Side effects Orlip

Side effects include:

• damage to the nervous system function: headaches usually develop;
• disorders associated with the respiratory tract, sternum and mediastinum organs: lesions of the lower and upper respiratory system often occur;
• problems with the gastrointestinal tract: often there are fatty discharges from the rectum, pain or discomfort in the abdominal area, bloating accompanied by the release of a small amount of feces, steatorrhea, loose stools, oily discharge, imperative urge to defecate and increased frequency of defecation. Often there may be soft stools, damage to the gums or teeth, discomfort or pain in the rectum and fecal incontinence;
• renal and urinary disorders: infection of the urinary tract often occurs;
• problems with metabolic processes: hypoglycemia usually develops;
• invasions and other infections: flu often appears;
• systemic symptoms: weakness is often observed;
• disorders associated with the mammary glands and reproductive function: dysmenorrhea often appears;
• mental problems: anxiety is often noted.

Overdose

Clinical tests in people with normal weight and obesity, taking 1-time portions of 0.8 g of orlistat or multiple doses of 0.4 g 3 times a day for 15 days, did not show the development of noticeable negative symptoms. In addition, obese people have experience of taking the drug 3 times a day at a dosage of 0.24 g for six months.

Typically, in case of drug overdose during post-marketing testing, negative signs were absent or were similar to those observed when administering therapeutic doses of the drug.

In cases of severe poisoning, the patient's condition should be monitored for 24 hours. Data from animal and human testing suggest that the overall effect, which may be related to the lipase-inhibiting effect of orlistat, usually disappears quickly.

Interactions with other drugs

Cyclosporine.

The combination of the drug with cyclosporine leads to a decrease in the plasma indices of the latter. As a result, the immunosuppressive activity of cyclosporine may be weakened. For this reason, such a combination is prohibited. However, if there is a strict need to use these substances simultaneously, it is necessary to regularly monitor the plasma values of cyclosporine. Monitoring of cyclosporine indices in blood plasma should be performed until they stabilize.

Acarbose.

Because the pharmacokinetic interaction of the drug with acarbose has not been studied, they cannot be combined.

Oral anticoagulants.

The combination of drugs with warfarin and other anticoagulants requires regular monitoring of INR values.

Fat-soluble vitamins.

Administration with orlistat causes a decrease in the absorption of retinol, calciferol, tocopherol and vitamin K. At the same time, in most patients who used the medication for up to 4 full years, normal levels of these vitamins, as well as β-carotene, were noted in clinical tests.

To ensure adequate nutrition for those on a weight control diet, it is necessary to include more vegetables and fruits in their diet, as well as take multivitamin supplements.

If you need multivitamins, they should be taken at least 2 hours after taking orlistat or in the evening before bedtime.

Amiodarone.

Combination of the drug with amiodarone resulted in a small decrease in the plasma levels of the latter in a small number of volunteers. In people using amiodarone, the clinical significance of this symptom has not been clarified, but it may sometimes be important. In people combining Orlip with amiodarone, clinical observation and ECG monitoring should be increased.

Other combinations.

Administration of the drug with anticonvulsants (lamotrigine or valproate) sometimes results in seizures. The relationship between these phenomena has not been determined, but patients should be monitored for possible changes in the intensity or frequency of seizures.

Occasionally, hypothyroidism or weakening of its control occurs. The mechanism of this disorder has not been proven, but weakening of absorption of levothyroxine or iodine salts may occur.

There is information about the decrease in the therapeutic activity of antiretroviral drugs in people with HIV, antipsychotics (including lithium) and antidepressants, coinciding with the beginning of treatment with the drug in people with adequately controlled pathologies. Because of this, before starting therapy, it is necessary to carefully assess any possible complications for such patients.

Orlistat can indirectly reduce the activity of oral contraception, which can sometimes lead to unplanned conception. In severe cases of diarrhea, additional contraceptive measures should be used.

Storage conditions

Orlip should be stored in a dark, dry place, out of the reach of children, at a temperature in the range of 10-20˚C.

Shelf life

Orlip is approved for use for a period of 36 months from the date of sale of the therapeutic product.

Analogues

The analogs of the drug are Xenical, Orlikel and Xenistat with Olistat.

Reviews

Orlip receives mixed reviews from patients. It is considered effective as a means of losing excess weight, but at the same time, a large number and high intensity of side effects are noted during its use.