AKNEKUTAN

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Active material: Isotretinoin
When ATH: D10BA01
CCF: Drug for the treatment of acne. Retinoid
ICD-10 codes (testimony): L70
Manufacturer: JADRAN Galenic Laboratory d.d. (Croatia)

DOSAGE FORM, COMPOSITION AND PACKAGING

Capsules hard gelatin, №3, Brown color; contents of capsules – paste waxy orange-yellow.

	1 caps.
isotretinoin	8 mg

Excipients: Gelyutsir^® 50/13 (mixture of stearic acid esters of polyoxyethylene glycerol), purified soybean oil, Span 80^® (sorbitan oleate – mixed esters of oleic acid and sorbitol).

The composition of the body and cap of the capsule: gelatin, iron oxide red dye (E172), Titanium dioxide (E171).

10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (5) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.
14 PC. – blisters (1) – packs cardboard.
14 PC. – blisters (2) – packs cardboard.
14 PC. – blisters (4) – packs cardboard.
14 PC. – blisters (7) – packs cardboard.

Capsules hard gelatin, №1, white housing, cap – green color; contents of capsules – paste waxy orange-yellow.

	1 caps.
isotretinoin	16 mg

Excipients: Gelyutsir^® 50/13 (mixture of stearic acid esters of polyoxyethylene glycerol), purified soybean oil, Span 80^® (sorbitan oleate – mixed esters of oleic acid and sorbitol).

The composition of the shell capsules: gelatin, Titanium dioxide (E171).
The composition of the capsule caps: gelatin, Titanium dioxide (E171), dye iron oxide yellow (E172), indigokarmin (E132).

Pharmacological action

Drug for the treatment of acne. Isotretinoin – stereoisomer of all-trans retinoic acid (tretinoin).

The exact mechanism of action of isotretinoin has not yet been identified, however found, that the improvement of the clinical picture of severe acne is associated with suppression of sebaceous gland activity and a histologically confirmed decrease in their size.

Sebum – the main substrate for the growth of Propionibacterium acnes, Therefore, reducing the formation of sebum inhibits bacterial colonization of the duct. Aknekutan inhibits proliferation of sebocytes and acts on the acne, restoring the normal process of cell differentiation, It stimulates the regeneration processes. Besides, proven anti-inflammatory effect of isotretinoin on the skin.

Pharmacokinetics

Absorption

After oral administration, absorption of volatile, bioavailability is low and variable (due to the proportion of the dissolved drug isotretinoin, and may also increase when taking the drug with meals). In patients with acne C_makh at steady state after receiving a dose of isotretinoin 80 mg on an empty stomach was 310 ng / ml (range 188-473 ng / ml) and achieved through 2-4 no. Isotretinoin concentration in plasma 1.7 times higher, than in blood, due to poor penetration of isotretinoin into red blood cells.

Distribution

Plasma protein binding (mostly to albumin) – 99.9%.

C_ssisotretinoin in the blood of patients with severe forms of acne, by taking the drug 40 mg 2 times / day, ranged from 120 ng / ml to 200 ng / ml. Concentrations of 4-oxo-isotretinoin (osnovnogo metabolite) in these patients 2.5 times higher than those. The concentration of isotretinoin in the epidermis 2 times lower, than serum.

Metabolism

It is metabolized to form 3 the main biologically active metabolites – 4-oxo-isotretinoin (major metabolite), tretinoin (all-trans-retinoic acid) and 4-oxo-retinoic, and less significant metabolites, which also include glucuronide. As in vivo isotretinoin and tretinoin reversibly transformed into each other, metabolism of tretinoin is linked to the metabolism of isotretinoin. 20-30% isotretinoin dose is metabolised by isomerisation. The pharmacokinetics of isotretinoin in man can play a significant role enterohepatic circulation.

Studies in vitro have shown, that in making isotretinoin 4-oxo-isotretinoin, and tretinoin involves several CYP enzymes. However, none of isoforms, apparently, does not play a dominant role. Isotretinoin and its metabolites do not significantly affect the activity of CYP enzymes.

Deduction

T_1/2 the terminal phase for isotretinoin average – 19 no. T_1/2 terminal phase to 4-oxo-isotretinoin average – 29 no.

Isotretinoin is excreted by the kidneys and bile in approximately equal amounts. It refers to natural (physiological) Retinoids. The endogenous concentrations of retinoids are restored after about 2 weeks after taking the drug.

Pharmacokinetics in special clinical situations

Since the data on the pharmacokinetics of the drug in patients with impaired liver function are limited, Isotretinoin is contraindicated in these patients.

Renal failure mild to moderate severity did not affect the pharmacokinetics of isotretinoin.

Testimony

- Severe forms of acne (nodulocystic, konglobatnıe, acne scarring risk);

- Acne, not amenable to other forms of therapy.

Dosage regimen

Inside, preferably during meals, 1-2 times / day.

Therapeutic efficacy Aknekutana and its side effects are dose-related and vary between patients. This necessitates individual selection of doses during treatment.

The initial dose Aknekutana – 400 ug / kg / day, in some cases up to 800 ug / kg / day. At severe forms of the disease or acne trunk It may be required to dose 2 mg / kg / day.

Optimal exchange rate cumulative dose – 100-120 mg / kg. Complete remission is usually achieved for 16-24 weeks. When poor tolerability of the recommended dose treatment can be continued at a lower dose, but more durable. Most patients with acne disappear completely after a single course of treatment.

At relapse may conduct re-treatment at the same daily dose and cumulative. A second course is prescribed not earlier 8 weeks after the first, tk. improvement may carry a deferred character.

At chronic renal failure severe initial dose should be reduced to 8 mg / day.

Side effect

Most side effects are dose dependent. Usually, side effects are reversible after dose adjustment or discontinuation of the drug, but some may persist after cessation of treatment.

Symptoms, associated with hypervitaminosis A: xerosis, mucosas, incl. lips (cheilitis), nasal (bleeding), larynx and pharynx (hoarseness), eye (conjunctivitis, reversible corneal opacities and intolerance to contact lenses).

Dermatological reactions: peeling of the skin of palms and soles, rash, itch, facial erythema / dermatitis, Sweating, pyogenic granuloma, paronixii, onihodistrofii, increased proliferation of granulation tissue, persistent hair thinning, reversible hair loss, fulminant forms of acne, girsutizm, giperpigmentatsiya, photosensitivity, light injuries to the skin. Early treatment may occur exacerbation of acne, continuing for several weeks.

On the part of the musculoskeletal system: muscle pain with an increase in serum CPK or without, joint pain, hyperostosis, arthritis, calcification of ligaments and tendons, tendinitы.

CNS: excessive fatigue, headache, intracranial hypertension (pseudotumor of the brain: headache, nausea, vomiting, blurred vision, swelling of the optic nerve), seizures; rarely – depression, psychosis, suicidal thoughts.

From the senses: xerophthalmia, individual cases of violations of visual acuity, photophobia, violation of dark adaptation (alleviation of twilight); rarely – violation of color (going after drug withdrawal), lentikulyarnaya cataracts, keratit, .Aloe, conjunctivitis, eye irritation, optic neuritis, swelling of the optic nerve (as a manifestation of intracranial hypertension); impaired hearing at certain frequencies of sound, difficulty wearing contact lenses.

From the digestive system: dryness of the oral mucosa, Bleeding from the gums, gingivitis, nausea, diarrhea, inflammatory bowel disease (colitis, ileitis), bleeding; pancreatitis (particularly hypertriglyceridemia with concomitant higher 800 mg / dL). Described rare cases of pancreatitis with fatal outcome. Noted transient and reversible increases in liver transaminases, individual cases of hepatitis. In many cases, these changes do not go beyond the limits of normal and returned to baseline parameters during treatment, However, in some situations, there was a need to reduce the dose or cancel Aknekutan.

The respiratory system: rarely – bronchospasm (more frequently in patients with a history of asthma).

From the hematopoietic system: anemia, decrease in hematocrit, leukopenia, neutropenia, increase or decrease the number of platelets, ESR acceleration.

Laboratory findings: hypertriglyceridemia, hypercholesterolemia, hyperuricemia, lowering HDL; rarely – giperglikemiâ. During the reception Aknekutana have reported cases of new-onset diabetes. In some patients,, especially engaged in intense physical activity, describes some cases increasing the activity of CK in the serum.

Infection: local or systemic infection, caused by Gram-positive pathogens (Staphylococcus aureus).

Other: lymphadenopathy, hematuria, proteinuria, vasculitis (granulematoz Wegener, sensitization vasculitis), Systemic hypersensitivity reactions, glomerulonephritis.

Teratogenic and embryotoxic effects: congenital malformations – Hydro- and microcephaly, hypoplasia of the cranial nerves, microphthalmia, malformations of the cardiovascular system, parathyroid glands, violation of the skeleton (immaturity palьcevыh phalanges, Skull, cervical vertebrae, femur, ankles, forearm, facial skull, cleft palate), low position of the ears, hypoplasia of ears, hypoplasia or complete absence of the external auditory meatus, herniation of brain and spinal cord, coossification, fusion of the fingers and toes, violations of the thymus gland; fetal death in the perinatal period, miscarriage, Abortions, premature closure of the epiphyseal growth zones; in animal – pheochromocytoma.

Contraindications

- Pregnancy, installed and planned (possible teratogenic and fetotoxic effects);

- Lactation (breast-feeding);

- Liver failure;

- Hypervitaminosis A;

- Severe hyperlipidemia;

- Soputstvuyushtaya therapy tetratsiklinami;

- Hypersensitivity to the drug or its components.

Aknekutan not indicated for the treatment of acne during puberty and is not recommended for use for children under 12 years.

FROM caution should be prescribed for patients with diabetes, history of depression, obesity, lipid metabolism disorders, alcoholism.

Pregnancy and lactation

Pregnancy – absolute contraindication for treatment Aknekutanom.

If pregnancy occurs, despite warnings, during treatment or within one month after the end of therapy, there is a great risk of having a child with severe developmental disabilities.

Isotretinoin – drug with strong teratogenic. If pregnancy occurs at the time, when a woman takes oral isotretinoin (at any dose, even for a short time), there is a great risk of having a child with developmental disabilities.

Aknekutan contraindicated women of childbearing age, if the woman's condition does not satisfy all of the following criteria:

- A severe form of acne, resistant to conventional therapies;

- The patient must understand and follow the instructions of the doctor;

- The patient must inform the doctor about the dangers of becoming pregnant during treatment Aknekutanom, within one month after the consultation and urgent cases of suspected pregnancy;

- The patient must be advised of the possible failure of contraception;

- The patient must prove, that understands the precautions;

- The patient must understand the need to continuously use effective methods of contraception for one month before treatment Aknekutanom, during treatment and for one month after the end of; desirably used simultaneously 2 different methods of contraception, including barrier;

- The patient must be received significant negative pregnancy test within 11 days prior to dosing; pregnancy test is highly recommended monthly during treatment and after 5 weeks after the end of therapy;

- The patient should begin treatment Aknekutanom only 2-3 day of the next normal menstrual cycle;

- The patient must understand the need for mandatory medical visits each month;

- The treatment of recurrent disease the patient should always use the same effective methods of contraception for one month before treatment Aknekutanom, during treatment and for one month after its completion, as well as through the same reliable pregnancy test;

- The patient must fully understand the need for precautions, and confirm their understanding and desire to use reliable methods of contraception, she explained to the doctor.

The use of contraceptives by these guidelines during treatment with isotretinoin should be recommended even to those women, who usually do not use contraceptive methods because of infertility (except patients, after hysterectomy), amenorrhea, or who report, not sexually active.

The doctor must be sure, what:

- The patient suffers from a severe form of acne (nodulocystic, conglobata acne or acne scarring risk); acne, not amenable to other forms of therapy;

- A negative result is reliable pregnancy test before you start taking the drug, during therapy and after 5 weeks after the end of therapy; dates and results of pregnancy tests should be documented;

- Patient uses at least one, preferably two effective methods of contraception, including a barrier method, for one month before treatment Aknekutanom, during treatment and for one month after the end of;

- The patient is able to understand and perform all of the above requirements for protection from pregnancy;

- Patient meets all the above conditions.

Pregnancy test

In line with current practice, pregnancy tests with a minimum sensitivity 25 mME / ml should be carried out in the first 3 day of the menstrual cycle:

Prior to initiating therapy

To exclude the possibility of pregnancy prior to use of contraception and the date of the initial results of a pregnancy test should be registered doctor. Patients with irregular menstrual periods while holding pregnancy test depends on the sexual activity, it should be carried out 3 a week after unprotected intercourse. The physician should inform the patient about methods of contraception.

A pregnancy test is carried out on the day of the appointment or Aknekutana 3 the day before the visit of the patient to the doctor. Professionals should record the test results. The drug can be assigned only to patients, receive effective contraception for at least 1 months before the start of therapy Aknekutanom.

During therapy

The patient must visit the doctor every 28 days. The need monthly pregnancy testing are determined in accordance with local practice and taking into account sexual activity, previous menstrual disorders. Where indicated, a pregnancy test is carried out on the day of the visit or 3 days prior to the visit to the doctor, the test results must be registered.

End of treatment

Through 5 weeks after the end of therapy, a test to exclude pregnancy.

Recipe on Aknekutan woman, parity, It can be discharged only 30 days of treatment, continuation of treatment requires a new physician prescribing. It is recommended that a pregnancy test, and obtaining the prescription drug spending one day.

Aknekutana issuance in the pharmacy should be carried out only during the 7 days of a prescription.

Male patients

Existing evidence suggests, that women drug exposure, Received from the semen and seminal fluid of men, taking Aknekutan, It is not sufficient for the emergence of teratogenic effects Aknekutana. Men should exclude the possibility of ingestion by others, Especially Women.

If, despite the precautions taken, Aknekutanom during treatment or within one month after the end of, Yet pregnancy occurred, there is a high risk of very severe fetal malformation. In the event of pregnancy therapy is stopped Aknekutanom. It should discuss the advisability of maintaining it with the doctor, We are specializing in Teratology.

Lactation

As isotretinoin is highly lipophilic, very likely, it passes into breast milk. Because of the possible side effects Aknekutan should not be prescribed to nursing mothers.

Cautions

It is recommended to monitor liver function and liver enzymes before treatment, through 1 months after it began, and then every 3 months or indications. Noted transient and reversible increase of liver transaminases, in most cases in the normal range. If the level is higher than normal liver transaminases, necessary to reduce the dose or cancel.

It should also determine the level of fasting serum lipids before the treatment, through 1 months after initiation, and then every 3 months or indications. Typically, lipid concentrations normalized after dose reduction or discontinuation of therapy, and when dieting.

Should be monitored clinically significant elevated triglycerides, as they rise over 800 mg / dL or 9 mmol / l may be associated with the development of acute pancreatitis, possibly fatal. At the reception hypertriglyceridemia or symptoms of pancreatitis Aknekutan should be abolished.

In rare cases, patients, receiving Aknekutan, describes depression, psychotic symptoms, and very rarely – suicide attempts. Although their causal relationship to the use of the drug has not been established, Special care is needed in patients with a history of depression and watch all the patients on the subject of depression in the course of treatment, if necessary, direct them to the appropriate specialist. However, the cancellation Aknekutana may not result in the disappearance of symptoms and may need further observation and treatment by a specialist.

In rare cases at the beginning of therapy, there was aggravation of acne, which takes place during the 7-10 days without dose adjustment.

In appointing the drug to any patient must first carefully weigh the potential benefits and risks.

Patients, receiving Aknekutan, recommended to use moisturizing ointment or cream to the body, lip balm to reduce dry skin and mucous membranes early in therapy.

While taking Aknekutana may be pain in muscles and joints, increase in serum CK, which may be accompanied by a reduction in tolerability intense exercise.

Avoid carrying out deep dermoabrazii chemical and laser treatment in patients, receiving Aknekutan, as well as for 5-6 months after treatment because of the possibility of scarring in atypical reinforced areas and the emergence of hyper- and hypopigmentation. During the treatment and for Aknekutanom 6 Months after hair removal can not be carried out using wax applications because of the risk of detachment of the epidermis, development of scarring and dermatitis.

Because some patients can experience a decrease in the severity of night vision, sometimes persists after the end of therapy, Patients should be informed about this condition, encouraging them to use caution when driving at night. Status of visual acuity should be carefully monitored. Dryness of the conjunctiva, pomutnenyya rohovytsы, deterioration of night vision and keratitis usually disappear after drug withdrawal. When dry mucous membranes of eyes, you can use applications moisturizing eye ointment or artificial tears product. It should be observed in patients with dryness of the conjunctiva for possible development of keratitis. Patients, complained of vision, should be sent to an ophthalmologist, and consider whether to cancel Aknekutana. At intolerance of contact lenses at the time of therapy should be used glasses.

It should limit the impact of the solar insolation and UV treatment. If necessary, use a sunscreen with a high protection factor of at least 15 SPF.

Described rare cases of benign intracranial hypertension (pseudotumor of the brain), incl. during concomitant use of tetracyclines. These patients should be lifted immediately Aknekutan.

In therapy Aknekutanom may cause inflammatory bowel disease. In patients with severe hemorrhagic diarrhea should immediately cancel Aknekutan.

Described rare cases of anaphylactic reactions, which arose only after previous topical retinoids. Severe allergic reactions necessitate discontinuation of the drug and close monitoring of patients.

Patients at high risk (diabetic, obesity, chronic alcoholism or lipid metabolism disorders) Aknekutanom the treatment may require more frequent laboratory monitoring of blood glucose and lipid. If you have diabetes or suspected, it is recommended more frequent blood glucose determination. Patients with diabetes are recommended more frequent monitoring of blood glucose.

During the treatment and for 30 days after it is necessary to completely eliminate the blood samples from potential donors in order to avoid any possibility of getting this blood pregnant patients (a high risk of teratogenic and embryotoxic action).

Effects on ability to drive vehicles and management mechanisms

During the period of treatment must be careful when driving and other lesson. potentially hazardous activities, require high concentration and speed of psychomotor reactions (when receiving the first dose).

Overdose

In case of overdose may be signs of hypervitaminosis A.

In the first few hours of the overdose may require gastric lavage.

Drug Interactions

Tetracycline antibiotics, GCS reduce the effectiveness Aknekutana.

The simultaneous use of drugs, which increase photosensitivity (incl. sulьfonamidami, Tetracycline, thiazide diuretics) increases the risk of sunburn.

Concomitant use with other retinoids (incl. acitretin, Tretinoin, retinolom, tazarotenom, adapalene) increases the risk of hypervitaminosis A.

Isotretinoin can weaken the efficacy of progesterone, so you should not use contraceptives, containing small doses of progesterone.

Interactions with local keratolytic agents for treating acne is not recommended due to the possible increase in local irritation.

Since tetracyclines increase the risk of increased intracranial pressure, simultaneous application of isotretinoin is contraindicated.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in a dry, protected from light, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 2 year. Do not use beyond the expiration date.

Vladimir Andreevich Didenko

1,183 12 minutes read