Active ingredients: Acitretin
Neotigason 10 mg hard capsules
Neotigason 25 mg hard capsules
Indications Why is Neotigason used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Retinoids for the treatment of psoriasis
THERAPEUTIC INDICATIONS
Severe forms of psoriasis, including forms accompanied by arthropathy.
Disorders of keratinization, such as ichthyosiform states, palmoplantar keratoderma, Darier's disease and lichen planus.
Other dermatoses sensitive to Neotigason therapy.
Contraindications When Neotigason should not be used
- Hypersensitivity to the active substance, to other retinoids, or to any of the excipients.
- Neotigason is highly teratogenic and should not be given to pregnant women. The same applies to women of childbearing potential, unless they are on an effective contraceptive regimen for 4 weeks before starting treatment, during treatment and for three years after stopping treatment (see "Pregnancy and breastfeeding". ).
- Feeding time.
- Severely impaired liver function.
- Severely impaired renal function.
- Constantly elevated serum lipid values.
- Since both acitretin and tetracyclines can cause increased intracranial pressure, their simultaneous use is contraindicated (see "Interactions").
- An increased risk of hepatitis has been reported following concomitant therapies with methotrexate and etretinate; consequently, the simultaneous intake of methotrexate and acitretin is also contraindicated (see "Interactions").
- The administration of acitretin concomitantly with that of vitamin A or other retinoids is contraindicated due to the risk of developing hypervitaminosis A (see "Interactions").
Precautions for use What you need to know before taking Neotigason
The physician must provide all patients, women and men, with detailed information regarding the risk of teratogenicity and the strict contraceptive measures to be adopted.
Clinical data have shown that etretinate can be formed from the simultaneous intake of acitretin and ethyl alcohol. Etretinate is highly teratogenic and has a longer half-life (approximately 120 days) than acitretin.
Women of childbearing potential should therefore not ingest alcohol (in beverages, food or drugs) during acitretin therapy and for two months after the end of acitretin therapy. Contraceptive measures and pregnancy tests should be performed for 3 years after stopping treatment with acitretin (see "Pregnancy and breastfeeding"). Women of childbearing potential should not receive transfused blood from patients treated with acitretin.
Therefore the donation of blood from patients treated with acitretin is prohibited during treatment with acitretin and for three years after its discontinuation.
Due to the risk of fetal malformations, the medicine should not be given to other people. Unused or expired product should be returned to the pharmacy for disposal.
Liver function checks should be performed prior to initiation of acitretin treatment, every 1-2 weeks during the first two months, and every three months thereafter during treatment.
In the event that hepatic function is impaired, the monitoring will be repeated at weekly intervals. If, following these checks, the pathological values remain unchanged or worsen further, therapy with acitretin will be interrupted. However, it is advisable to continue monitoring liver function for at least another three months (see "Undesirable effects").
Serum cholesterol and (fasting) serum triglyceride values should be checked before starting treatment, one month after starting treatment, and every three months thereafter during treatment.
A reduction in night vision was observed during treatment with acitretin. Patients should be informed of this possible side effect and warned to be careful when driving or using machines at night. Vision problems should be carefully monitored (see “Undesirable Effects”).
Rare cases of benign intracranial hypertension have been reported. Patients with severe headache, nausea, vomiting and visual disturbances should immediately discontinue acitretin treatment and undergo neurological evaluation and treatment (see "Undesirable Effects").
In adults, particularly in the elderly, on long-term acitretin therapy, appropriate checks should be periodically performed in view of the possible onset of alterations in ossification processes (see "Undesirable effects"). In case of ossification problems, the physician should discuss with the patient the possibility of continuing the therapy, based on the evaluation of the risk / benefit ratio.
There have been occasional reports of bone changes in children, including premature epiphyseal sealing, hyperostosis, and extraosseous skeletal calcification after long-term treatment with etretinate; these effects can be anticipated with the use of acitretin. Therefore, in children, growth parameters and skeletal development should be carefully monitored.
It should be emphasized that, to date, not all the possible consequences of long-term treatment with acitretin are known.
The effects of UV rays are accentuated by retinoid therapy; therefore patients should avoid excessive exposure to sunlight and the uncontrolled use of sunlamps. If necessary, a sunscreen with a high SPF of at least 15 should be used.
Treatment with high doses of retinoids can cause mood changes including irritability, aggression and depression.
High-risk patients:
In patients suffering from diabetes, alcoholism, obesity, or who have cardiovascular risk factors or lipid metabolism disorders being treated with acitretin, more frequent monitoring of serum lipid and / or blood glucose and other values is necessary. cardiovascular risk indices, for example blood pressure.
In diabetic subjects, retinoids can improve or worsen glucose tolerance; consequently, blood glucose should be checked more frequently than normal in the initial stages of treatment.
In all high-risk patients in whom cardiovascular risk indices fail to return to normal or further deteriorate, dose reduction or discontinuation of acitretin therapy should be considered.
Interactions Which drugs or foods can change the effect of Neotigason
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Concomitant administration of methotrexate, tetracyclines or vitamin A and other retinoids with acitretin is contraindicated, see "Contraindications".
Low-dose progesterone-only preparations (minipills) may be an inadequate method of contraception during treatment with acitretin, see "Pregnancy and breastfeeding".
No interactions have been observed with estrogen / progestogen combination oral contraceptives.
In a study conducted in healthy volunteers, the concomitant intake of a single dose of acitretin and alcohol resulted in the formation of highly teratogenic etretinate. The mechanism of such a metabolic process has not been elucidated and therefore it is not known whether it is possible. interaction with other substances. Women of childbearing potential should therefore not ingest alcohol (in beverages, food or drugs) during acitretin therapy and for two months after stopping acitretin therapy (see "Precautions for use").
In case of concomitant therapy with acitretin and phenytoin it should be borne in mind that acitretin reduces the protein binding of phenytoin. The clinical relevance of this is not yet known.
No further interactions between acitretin and other substances (e.g. digoxin, cimetidine) have been observed so far.
Studies on the effect of acitretin on the protein binding of coumarin anticoagulants (warfarin) did not show any type of interaction.
Warnings It is important to know that:
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy and breastfeeding
Women of childbearing potential / Contraception in males and females
Acitretin is highly teratogenic. Its use is contraindicated in women who may become pregnant during treatment or within three years of its termination. The risk of giving birth to a malformed child is extraordinarily high if acitretin has been administered before or during pregnancy, regardless of the duration of treatment and the posology.
Acitretin is contraindicated in any woman of childbearing potential except when all of the following are present:
- The patient has a severe keratinization alteration, resistant to standard therapies;
- Is able to understand and follow the instructions given by the doctor;
- Is able to use the agreed contraceptive measure reliably and continuously without making mistakes;
- It is imperative that every woman of childbearing potential undergoing acitretin therapy is in constant use of an effective contraceptive (preferably two complementary methods) to be started 4 weeks before and to be continued throughout treatment and for three years after its discontinuation. The patient should contact a physician immediately in case of suspected pregnancy.
- Therapy should not be started until the second or third day of the next menstrual period;
- Before starting therapy, a negative pregnancy test (minimum sensitivity of 25 mIU / ml) should be obtained up to three days before the first dose is given. During therapy, pregnancy tests should be scheduled at 28-day intervals. A negative pregnancy test no older than three days is mandatory at these visits before making the prescription. After discontinuation of therapy, pregnancy testing should be performed every 1-3 months for a period of 3 years following the last dose.
- Before the start of therapy, the doctor must inform the patient of childbearing age in detail about the precautionary measures to be taken, about the risks of very serious fetal malformations and about the possible consequences of a pregnancy begun during treatment with acitretin as well as in the three years. subsequent to the interruption of the same;
- Continued use of effective contraceptives should be implemented each time therapy is repeated, regardless of the length of the treatment period, and continued for three years after the end of therapy;
- In case of pregnancy, despite these precautions, there is a high risk of serious malformations for the fetus (for example: craniofacial defects, cardiac and vascular or CNS malformations, skeletal and thymic defects) and an increased incidence of spontaneous abortions. This risk occurs mainly during treatment with acitretin and in the 2 months following treatment. Up to 3 years after stopping acitretin treatment, the risk is lower (particularly in women who have not consumed alcohol), but cannot be completely excluded due to the possible formation of etretinate.
- Women of childbearing potential should therefore not ingest alcohol (in beverages, food or drugs) during acitretin therapy and for two months after stopping acitretin therapy (see "Precautions for use" and "Interactions").
The primary method of contraception is a combined hormonal contraceptive or an intrauterine device and it is recommended to use a condom or diaphragm as well. Low-dose progesterone-only preparations (minipills) are not recommended due to possible interference with their contraceptive effect.
For male patients treated with acitretin, available data based on maternal exposure to semen and semen indicate a minimal, if any, risk of teratogenic effects.
Pregnancy
Acitretin is contraindicated in pregnant women (see "Contraindications").
Feeding time
Acitretin should not be given to breastfeeding women (see "Contraindications").
Effects on ability to drive and use machines
A reduction in night vision has been observed during treatment with Neotigason (see "Undesirable effects"). Patients should be informed of this possible problem and advised to exercise caution when driving or using machines at night.
Important information about some of the ingredients of Neotigason
Neotigason contains glucose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
This medicinal product contains less than 1mmol (23 mg) sodium per dose, ie it is essentially "sodium-free".
Dosage and method of use How to use Neotigason: Dosage
Neotigason should only be prescribed by physicians who are experienced in the use of systemic retinoids and are aware of the risk of teratogenicity associated with treatment with acitretin.
Dosage
Due to differences in the absorption and degree of metabolism of acitretin, the dosage regimen will need to be individually adapted. These directives can be given purely as an indication.
Adults
Initial therapy:
25-30 mg / day for two to four weeks (1 capsule of 25 mg or 3 capsules of 10 mg).
Maintenance therapy:
The maintenance dose will be established on the basis of clinical efficacy and tolerability. In general, 25-50 mg / day administered for a further six to eight weeks achieves optimal therapeutic results.
It may sometimes be necessary to increase the dose up to a maximum of 75 mg / day (3 capsules of 25 mg). In patients with sufficient regression of psoriatic lesions, therapy can be discontinued. Any relapses will be treated as described above.
In the treatment of keratinization disorders it is often necessary to continue maintenance even if at very low doses (even lower than 20 mg / day and not higher than 50 mg / day).
Children
In the case of long-term treatments, in consideration of the possible onset of side effects of a certain severity, the risk / benefit ratio must be carefully evaluated. Acitretin should only be used when alternative therapies are not effective.
Dosage should be based on body weight. A daily administration of 0.5 mg / kg is suggested. Doses up to 1 mg / kg / day may sometimes be necessary for limited periods. A total of 35 mg / day should not be exceeded. Maintenance therapy should be performed at the minimum effective dose in consideration of the possible onset, in long-term treatments, of side effects.
Combined therapy
The combination of Neotigason with other therapies and the resulting individual response may justify a reduction in the dosage of the drug.
Simultaneous use of standard topical therapies does not interfere with Neotigason and can therefore continue.
Method of administration
The capsules should preferably be taken once a day with a meal or with a little milk.
Overdose What to do if you have taken too much Neotigason
In the event of acute overdose, Neotigason therapy should be discontinued immediately.
Symptoms of overdose are identical to those of acute hypervitaminosis A, i.e. headache, dizziness, nausea or vomiting, drowsiness, irritability and itching. Given the basic acute toxicity of the preparation it is not necessary to adopt particular treatments.
If you have any questions about the use of Neotigason, ask your doctor or pharmacist.
In case of accidental intake of an excessive dose of Neotigason, notify your doctor immediately or go to the nearest hospital.
Side Effects What are the side effects of Neotigason
Like all medicines, Neotigason can cause side effects, although not everybody gets them.
Undesirable effects have been observed in most patients starting acitretin therapy. However, these effects tend to disappear by reducing the dosage or discontinuing therapy. Sometimes an initial worsening of psoriasis symptoms was also observed at the start of treatment.
The most frequently observed side effects are symptoms of hypervitaminosis A, such as dry lips, which can be relieved by applying an ointment.
Undesirable effects reported for acitretin in clinical trials or as post-marketing events are listed below by system organ class and by frequency.
Frequencies are defined as:
- Very common (≥1 / 10)
- Common (≥1 / 100 to <1/10)
- Uncommon (≥1 / 1,000 to <1/100)
- Rare (≥1 / 10,000 to <1 / 1,000)
- Very rare (<1 / 10,000)
- Not known (frequency cannot be estimated from the available data)
Infections and infestations
- Frequency not known: Vulvo-vaginitis caused by Candida albicans
Disorders of the immune system
- Frequency not known: Hypersensitivity
Nervous system disorders
- Common: Headache
- Uncommon: Dizziness
- Rare: Peripheral neuropathy
- Very rare Benign intracranial hypertension (see "Precautions for use")
Eye disorders
- Very common: Dryness and inflammation of the mucous membranes (e.g. conjunctivitis, xerophthalmia), which can lead to intolerance to contact lenses
- Uncommon: Vision blurred
- Very rare: Night blindness (see "Precautions for use"), ulcerative keratitis
Ear and labyrinth disorders
- Frequency not known: Hearing impaired, tinnitus
Vascular pathologies
- Frequency not known: Flushing
Respiratory, thoracic and mediastinal disorders
- Very common: Dryness and inflammation of the mucous membranes (e.g. epistaxis and rhinitis)
Gastrointestinal disorders
- Very common: Dry mouth, thirst
- Common: Stomatitis, gastro-intestinal disturbances (e.g. abdominal pain, diarrhea, nausea, vomiting)
- Uncommon: Gingivitis
- Frequency not known: Dysgeusia, rectal haemorrhage
Hepatobiliary disorders
- Uncommon: Hepatitis
- Very rare: Jaundice
Skin and subcutaneous tissue disorders
- Very common: Cheilitis, pruritus, alopecia, skin exfoliation (all over the body, especially on the palms and under the feet)
- Common: Skin fragility, sticky skin, dermatitis, abnormal hair texture, brittle nails, paronychia, erythema
- Uncommon: fissures, bullous dermatitis, photosensitivity reactions
- Frequency not known: Pyogenic granuloma, madarosis, angioedema, urticaria
Musculoskeletal and connective tissue disorders
- Common: Arthralgia, myalgia
- Very rare: Bone pain, exostosis (maintenance treatment may lead to progression of previous spinal hyperostosis, new hyperostotic lesions and extraskeletal calcifications, as observed in long-term systemic treatment with retinoids) (see "Precautions for "use")
General disorders and administration site conditions
- Common: Peripheral edema
Diagnostic tests
- Very common: Abnormal liver function tests (transient, usually reversible, increase in alkaline transaminases and phosphatases) (see "Precautions for use"). Lipid abnormality (during treatment with high doses of acitretin, has occurred a reversible increase in serum triglycerides and cholesterol, especially in high-risk patients and in long-term treatment (see "Precautions for use"). An associated risk of atherogenesis cannot be excluded when these conditions persist).
Children
There have been occasional reports of bone changes in children, including premature epiphyseal sealing, hyperostosis and extraosseous skeletal calcification after long-term treatment with etretinate, these effects can also be anticipated with the use of acitretin. In children, the parameters of growth and development of the bones must be carefully monitored.
Diabetics
Retinoids can improve or worsen glucose tolerance (see "Precautions for use"). Following the instructions in the package leaflet reduces the risk of side effects.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Undesirable effects can also be reported directly via the national reporting system at “www.agenziafarmaco.gov.it/it/responsabili.” By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Expiry: see the expiry date printed on the package. Warning: do not use the medicine after the expiry date shown on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Conservation methods:
Store below 25 ° C. Store in the original container.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
KEEP THIS MEDICINAL PRODUCT OUT OF THE SIGHT AND REACH OF CHILDREN
Deadline "> Other information
COMPOSITION
Neotigason 10 mg hard capsules
One capsule contains:
- Active ingredient: 10 mg acitretin.
- Excipients: microcrystalline cellulose, dried liquid nebulized glucose, gelatin and sodium ascorbate.
- The capsule shell contains gelatin, titanium dioxide (E 171), red iron oxide (E 172), black iron oxide (E 172) and yellow iron oxide (E 172).
- The printing ink contains shellac, black iron oxide (E172), propylene glycol and ammonium hydroxide.
Neotigason 25 mg hard capsules
One capsule contains:
- Active ingredient: acitretin 25 mg.
- Excipients: microcrystalline cellulose, dried liquid nebulized glucose, gelatin and sodium ascorbate.
- The capsule shell contains gelatin, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172) and black iron oxide (E 172).
- The printing ink contains shellac, black iron hydroxide (E172), propylene glycol and ammonium hydroxide.
PHARMACEUTICAL FORM AND CONTENT
Hard capsules.
10 mg: capsules with brown cap and white body with "Actavis" printed in black on the cap and "10" printed in black on the body; size capsules 4.
25 mg: capsules with brown cap and yellow body with "Actavis" printed in black on the cap and "25" printed in black on the body; size 1 capsules.
Neotigason 10 mg hard capsules: 30 capsules.
Neotigason 25 mg hard capsules: 20 capsules.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
NEOTIGASON HARD CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
10 mg hard capsules
one capsule contains: Active ingredient: 10 mg acitretin.
25 mg hard capsules
one capsule contains: Active ingredient: acitretin 25 mg.
Excipient with known effects: glucose, sodium ascorbate
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Hard capsules.
10 mg: capsules with brown cap and white body with "Actavis" printed in black on the cap and "10" printed in black on the body; size capsules 4.
25 mg: capsules with brown cap and yellow body with "Actavis" printed in black on the cap and "25" printed in black on the body; size 1 capsules.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Severe forms of psoriasis, including forms accompanied by arthropathy.
Disorders of keratinization, such as ichthyosiform states, palmoplantar keratoderma, Darier's disease lichen planus.
Other dermatoses sensitive to Neotigason therapy.
04.2 Posology and method of administration -
Neotigason should only be prescribed by physicians who are experienced in the use of systemic retinoids and are aware of the risk of teratogenicity associated with acitretin treatment. See section 4.6
Dosage
Due to differences in the absorption and degree of metabolism of acitretin, the dosage regimen will need to be individually adapted. These directives can be given purely as an indication.
Adults
Initial therapy:
25-30 mg / day for two to four weeks (1 capsule of 25 mg or 3 capsules of 10 mg).
Maintenance therapy:
The maintenance dose will be established on the basis of clinical efficacy and tolerability. In general, 25-50 mg / day administered for a further six to eight weeks achieves optimal therapeutic results.
It may sometimes be necessary to increase the dose up to a maximum of 75 mg / day (3 capsules of 25 mg).
In patients with sufficient regression of psoriatic lesions, therapy can be discontinued. Any relapses will be treated as described above.
In the treatment of keratinization disorders it is often necessary to continue maintenance even if at very low doses (even lower than 20 mg / day and not higher than 50 mg / day).
Children
In the case of long-term treatments, in consideration of the possible onset of side effects of a certain severity, the risk / benefit ratio must be carefully evaluated. Acitretin should only be used when alternative therapies are not effective.
Dosage should be based on body weight. A daily administration of 0.5 mg / kg is suggested. Doses up to 1 mg / kg / day may sometimes be necessary for limited periods. A total of 35 mg / day should not be exceeded. Maintenance therapy should be carried out at the minimum effective dose in consideration of the possible onset, in long-term treatments, of side effects.
Combined therapy:
The combination of Neotigason with other therapies and the resulting individual response may justify a reduction in the dosage of the drug.
Simultaneous use of standard topical therapies does not interfere with Neotigason and can therefore continue.
Method of administration
The capsules should preferably be taken once a day with a meal or with a little milk.
04.3 Contraindications -
Hypersensitivity to the active substance, to other retinoids, or to any of the excipients listed in section 6.1.
Acitretin is highly teratogenic and should not be administered to pregnant women. The same applies to women of childbearing potential, unless they undergo an effective contraceptive regimen for 4 weeks before starting treatment, during treatment. and for three years after its discontinuation (see section 4.6).
Feeding time.
Severely impaired liver function.
Severely impaired renal function.
Constantly elevated serum lipid values.
Since both acitretin and tetracyclines can cause an increase in intracranial pressure, their simultaneous use is contraindicated (see section 4.5).
An increased risk of hepatitis has been reported following concomitant therapies with methotrexate and etretinate; consequently the concomitant intake of methotrexate and acitretin is also contraindicated (see section 4.5).
Concurrent administration of acitretin with vitamin A or other retinoids is contraindicated due to the risk of developing hypervitaminosis A (see section 4.5).
04.4 Special warnings and appropriate precautions for use -
The physician must provide all patients, women and men, with detailed information regarding the risk of teratogenicity and the strict contraceptive measures to be adopted.
Clinical data have shown that etretinate can be formed from the simultaneous intake of acitretin and ethyl alcohol. Etretinate is highly teratogenic and has a longer half-life (approximately 120 days) than acitretin. Women of childbearing potential should therefore not ingest alcohol (in beverages, food or drugs) during acitretin therapy and for two months after the end of acitretin therapy. Contraceptive measures and pregnancy tests should be performed for 3 years after stopping treatment with acitretin (see sections 4.6 and 5.2).
Women of childbearing potential should not receive transfused blood from patients treated with acitretin.Therefore the donation of blood from patients treated with acitretin is prohibited during treatment with acitretin and for three years after its discontinuation.
Due to the risk of fetal malformations, the medicine should not be given to other people. Unused or expired product should be returned to the pharmacy for disposal.
Liver function checks should be performed before the start of treatment with acitretin, every 1-2 weeks during the first two months and then every three months during treatment. In the event that liver function is impaired, monitoring will be repeated at intervals. If following these checks the pathological values remain unchanged or worsen further, therapy with acitretin will be interrupted. It is however advisable to continue monitoring liver function for at least another three months (see section 4.8).
Serum cholesterol and (fasting) serum triglyceride values should be checked before starting treatment, one month after starting treatment, and every three months thereafter during treatment.
A reduction in night vision was observed during treatment with acitretin. Patients should be informed of this possible undesirable effect and advised to be careful when driving or using machines at night. Vision problems should be carefully monitored (see section 4.8).
Rare cases of benign intracranial hypertension have been reported. Patients with severe headache, nausea, vomiting and visual disturbances should immediately discontinue acitretin treatment and undergo neurological evaluation and treatment (see section 4.8).
In adults, particularly in the elderly, on long-term acitretin therapy, appropriate checks should be periodically performed in view of the possible onset of alterations in ossification processes (see section 4.8). In case of ossification problems, the physician should discuss with the patient the possibility of continuing the therapy, based on the evaluation of the risk / benefit ratio.
There have been occasional reports of bone changes in children, including premature epiphyseal sealing, hyperostosis, and extraosseous skeletal calcification after long-term treatment with etretinate; these effects can be anticipated with the use of acitretin. Therefore, in children, growth parameters and skeletal development should be carefully monitored.
It should be emphasized that, to date, not all the possible consequences of long-term treatment with acitretin are known.
The effects of UV rays are accentuated by retinoid therapy; therefore patients should avoid excessive exposure to sunlight and the uncontrolled use of sunlamps. If necessary, a sunscreen with a high SPF of at least 15 should be used.
Treatment with high doses of retinoids can cause mood changes including irritability, aggression and depression.
High-risk patients:
In patients suffering from diabetes, alcoholism, obesity, or who have cardiovascular risk factors or lipid metabolism disorders being treated with acitretin, more frequent monitoring of serum lipid and / or blood glucose and other values is necessary. cardiovascular risk indices, for example blood pressure.
In diabetic subjects, retinoids can improve or worsen glucose tolerance; consequently, blood glucose should be checked more frequently than normal in the initial stages of treatment.
In all high-risk patients in whom cardiovascular risk indices fail to return to normal or further deteriorate, dose reduction or discontinuation of acitretin therapy should be considered.
Important information about some of the excipients
Contains glucose. Patients with rare glucose-galactose malabsorption problems should not take this medicine.
This medicinal product contains less than 1mmol (23 mg) sodium per dose, ie it is essentially "sodium-free".
04.5 Interactions with other medicinal products and other forms of interaction -
Concomitant administration of methotrexate, tetracyclines or vitamin A and other retinoids with acitretin is contraindicated, see section 4.3.
Low-dose progesterone-only preparations (minipills) may be an inadequate method of contraception during treatment with acitretin, see section 4.6. No interactions have been observed with estrogen / progestogen combination oral contraceptives.
In a study conducted in healthy volunteers, the concomitant intake of a single dose of acitretin and alcohol resulted in the formation of highly teratogenic etretinate. The mechanism of such a metabolic process has not been elucidated and therefore it is not known whether it is possible. interaction with other substances. Women of childbearing potential should therefore not ingest alcohol (in beverages, food or drugs) during acitretin therapy and for two months after the end of acitretin therapy. (see sections 4.4 and 5.2).
In case of concomitant therapy with acitretin and phenytoin it should be borne in mind that acitretin reduces the protein binding of phenytoin. The clinical relevance of this is not yet known.
No further interactions between acitretin and other substances (e.g. digoxin, cimetidine) have been observed so far.
Studies on the effect of acitretin on the protein binding of coumarin anticoagulants (warfarin) did not show any type of interaction.
04.6 Pregnancy and breastfeeding -
Women of childbearing potential / Contraception in males and females
Acitretin is highly teratogenic. Its use is contraindicated in women who may become pregnant during treatment or within three years of its termination. The risk of giving birth to a malformed child is extraordinarily high if acitretin has been administered before or during pregnancy, regardless of the duration of treatment and the posology.
Acitretin is contraindicated in any woman of childbearing potential except when all of the following are present:
1. The patient has a severe keratinization alteration, resistant to standard therapies;
2. Is able to understand and follow the instructions given by the doctor;
3. Is able to use the agreed contraceptive measure reliably and continuously without failing;
4. It is imperative that every woman of childbearing potential undergoing acitretin therapy is in constant use of an effective contraceptive (preferably two complementary methods) to be started 4 weeks prior and continued throughout treatment and for three years after its discontinuation. The patient should contact a physician immediately in case of suspected pregnancy.
5. Therapy should not be started until the second or third day of the next menstrual period;
6. Before initiating therapy, a negative pregnancy test (minimum sensitivity of 25 mIU / ml) should be obtained up to three days before the first dose is administered. During therapy, pregnancy tests should be scheduled at 28-day intervals. A negative pregnancy test no older than three days is mandatory at these visits before making the prescription. After discontinuation of therapy, pregnancy testing should be performed every 1-3 months for a period of 3 years following the last dose.
7. Before the start of therapy, the doctor must inform the patient of childbearing age in detail about the precautionary measures to be taken, about the risks of very serious fetal malformations and about the possible consequences of a pregnancy started during treatment with acitretin as well as in three years following its interruption;
8. Continued use of effective contraceptives should be implemented each time therapy is repeated, regardless of the length of the treatment period, and continued for three years after the end of therapy;
9. In the event of pregnancy, despite these precautions, there is a high risk of serious malformations for the fetus (for example: craniofacial defects, cardiac and vascular or CNS malformations, skeletal and thymic defects) and an increased incidence of miscarriages spontaneous. This risk occurs mainly during treatment with acitretin and in the 2 months following treatment. Up to 3 years after stopping acitretin treatment, the risk is lower (particularly in women who have not consumed alcohol), but cannot be completely excluded due to the possible formation of etretinate.
10. Women of childbearing potential should therefore not ingest alcohol (in beverages, food or drugs) during acitretin therapy and for two months after the end of acitretin therapy (see sections 4.4, 4.5 and 4.5).
The primary method of contraception is a combined hormonal contraceptive or an intrauterine device and it is recommended to use a condom or diaphragm as well. Low-dose progesterone-only preparations (minipills) are not recommended due to possible interference with their contraceptive effect.
For male patients treated with acitretin, available data based on maternal exposure to semen and semen indicate a minimal, if any, risk of teratogenic effects.
Pregnancy
Acitretin is contraindicated in pregnant women (see section 4.3).
Feeding time
Acitretin must not be administered to breastfeeding women (see section 4.3).
04.7 Effects on ability to drive and use machines -
A reduction in night vision has been observed with Neotigason treatment (see section 4.8). Patients should be informed of this possible problem and advised to exercise caution when driving or using machines at night.
04.8 Undesirable effects -
Undesirable effects have been observed in most patients starting acitretin therapy. However, these effects tend to disappear by reducing the dosage or discontinuing therapy. Sometimes an initial worsening of psoriasis symptoms was also observed at the start of treatment.
The most frequently observed side effects are symptoms of hypervitaminosis A, such as dry lips, which can be relieved by applying an ointment.
Undesirable effects reported for acitretin in clinical trials or as post-marketing events are listed below by system organ class and by frequency. Frequencies are defined as:
Very common (≥1 / 10)
Common (≥1 / 100,
Uncommon (≥1 / 1,000 to
Rare (≥1 / 10,000,
Very rare (
Not known (frequency cannot be estimated from the available data).
Children
There have been occasional reports of bone changes in children, including premature epiphyseal sealing, hyperostosis and extraosseous skeletal calcification after long-term treatment with etretinate, these effects can also be anticipated with the use of acitretin.
In children, the parameters of growth and development of the bones must be carefully monitored.
Diabetics
Retinoids can improve or worsen glucose tolerance (see section 4.4).
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address:" www.agenziafarmaco.gov.it/it/responsabili ".
04.9 Overdose -
In the event of acute overdose, acitretin therapy should be discontinued immediately.
Symptoms of overdose are identical to those of acute hypervitaminosis A, i.e. headache, dizziness, nausea or vomiting, drowsiness, irritability and itching. Given the low acute toxicity of the preparation it is not necessary to adopt particular treatments.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Retinoids for the treatment of psoriasis,
ATC code: D05BB02
Acitretin, the active ingredient of Neotigason, is a synthetic aromatic analogue of retinoic acid. Clinical studies have confirmed that in psoriasis and keratinization disorders acitretin leads to normalization of epidermal cell proliferation, differentiation and keratinization with generally well tolerated side effects. Neotigason's action is symptomatic; the mechanism of action is still unknown.
05.2 "Pharmacokinetic properties -
Absorption
Acitretin reaches its peak plasma concentration 1 to 4 hours after drug administration. The bioavailability of a single orally administered dose is approximately 60% but can vary considerably from patient to patient (36-95 %); in any case it is higher when the drug is administered during meals.
Distribution
Acitretin is highly lipophilic and penetrates rapidly into tissues. The binding of the drug to plasma proteins exceeds 99%. Animal studies have shown that acitretin crosses the placental barrier in quantities sufficient to cause fetal malformations and, due to its lipophilicity, it can be assumed that it reaches breast milk in considerable quantities.
Metabolism
Acitretin is metabolised by isomerization to its 13 cis isomer (Are you there-acitretin) for glucuronidation and side chain cleavage.
Elimination
The elimination half-life in multiple-dose studies in patients 21 to 70 years of age was estimated on average to be approximately 50 hours for acitretin and 60 hours for its major metabolite, Are you there acitretin, also teratogenic. Starting from the extreme value of the elimination half-life observed for acitretin (96 hours) and for Are you there-acitretin (123 hours) and assuming linear kinetics it is possible to predict that over 99% of the substance will be excreted within 36 days from the administration of the last dose of chronic therapy. It should also be added that the plasma concentrations of acitretin and Are you there acitretin fall below the detection limit of the method (biliary and renal tract.
NOTE
In a study in healthy volunteers, the simultaneous intake of a single dose of acitretin and ethyl alcohol led to the formation of etretinate. This had already been observed in vitro. In recent studies, the formation of etretinate has also been observed in some patients treated with acitretin. Until this phenomenon has been fully explained, the pharmacokinetics of "etretinate" should be considered. Etrteinate is highly teratogenic and has a longer elimination half-life than acitretin (approximately 120 days).Therefore, women of childbearing potential should not ingest alcohol (in drinks, food or drugs) during acitretin therapy and for two months after the end of acitretin therapy. Contraceptive measures must be maintained for 3 years after the end of treatment with acitretin.
05.3 Preclinical safety data -
Safety studies of the drug did not reveal mutagenic or carcinogenic effects or direct toxicity problems on the liver. In animals, acitretin was found to be highly teratogenic even at low doses.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Neotigason 10 mg hard capsules
Microcrystalline cellulose, dried nebulized liquid glucose, gelatin and sodium ascorbate.
The capsule shell contains gelatin, titanium dioxide (E 171), red iron oxide (E 172), black iron oxide (E 172) and yellow iron oxide (E 172).
The printing ink contains shellac, black iron hydroxide (E172), propylene glycol and ammonium hydroxide.
Neotigason 25 mg hard capsules
Microcrystalline cellulose, dried nebulized liquid glucose, gelatin and sodium ascorbate.
The capsule shell contains gelatin, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172) and black iron oxide (E 172).
The printing ink contains shellac, black iron hydroxide (E172), propylene glycol and ammonium hydroxide.
06.2 Incompatibility "-
Not known.
06.3 Period of validity "-
3 years.
06.4 Special precautions for storage -
Store below 25 ° C. Store in the original container.
06.5 Nature of the immediate packaging and contents of the package -
Blister packs, in aluminum and plastic material, inserted in the cardboard box together with the package leaflet.
Neotigason 10 mg hard capsules: 30 capsules
Neotigason 25 mg hard capsules: 20 capsules
06.6 Instructions for use and handling -
No special instructions for disposal.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Aurobindo Pharma (Italy) s.r.l. - Via San Giuseppe, 102 - 21047 Saronno (Varese)
08.0 MARKETING AUTHORIZATION NUMBER -
Neotigason 10 mg hard capsules - 30 capsules: AIC n. 027480019
Neotigason 25 mg hard capsules - 20 capsules: AIC n. 027480021
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
Date of first authorization: 26.04.1997
10.0 DATE OF REVISION OF THE TEXT -
09/08/2016
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