Active ingredients: Isotretinoin
ISORIAC 10 mg
ISORIAC 20 mg soft capsules
Indications Why is Isoriac used? What is it for?
ISORIAC contains isotretinoin, which is the active substance, belonging to a class of medicines known as retinoids.
ISORIAC is indicated for the treatment of severe forms of acne (such as nodular acne and acne conglobata or acne with the risk of permanent scar formation) resistant to both standard therapy with oral antibiotics and local treatment (cream, gel, ointment or lotion ).
ISORIAC should only be prescribed by or under the supervision of physicians who have experience in the use and control of retinoids in the treatment of severe acne.
ISORIAC is not indicated for the treatment of prepubertal acne and is not recommended for patients under 12 years of age.
Contraindications When Isoriac should not be used
Do not take ISORIAC if:
- You are pregnant or breastfeeding, are planning to become pregnant or are of childbearing age and are not observing all the pregnancy prevention measures provided for with this treatment (see "Pregnancy and breastfeeding, Important" below).
- You are allergic to isotretinoin or any of the other ingredients of this medicine (listed in section 6), especially peanuts or soy.
- You suffer from liver failure (severe liver disease).
- In case of hypervitaminosis A (very high level of vitamin A in the body).
- It has high levels of lipids in the blood (cholesterol, triglycerides).
- He's taking an antibiotic from the tetracycline family.
- You are taking vitamin A or other retinoids (acitretin, alitretinoin).
Precautions for use What you need to know before taking Isoriac
Talk to your doctor or pharmacist before taking ISORIAC if:
- You suffer or have suffered from depression or other mental problems.
- You have kidney problems. Your doctor can adjust the dosage of isotretinoin.
- You are overweight or have diabetes mellitus, have high cholesterol or triglyceride levels, or are a heavy alcohol user. In these cases, an increase in the levels of lipids and glycerides in the blood can be observed. In the presence of any of these situations, the doctor may order periodic blood tests. Monitor your blood glucose levels closely throughout the treatment if you have diabetes mellitus.
- He has liver problems. ISORIAC can increase the levels of transaminases (liver enzymes). Your doctor will order regular blood tests before and during treatment to check the health of your liver. A continuous elevation of these enzymes may prompt the physician to reduce the dosage of ISORIAC or to discontinue treatment.
- You suffer or have suffered from intestinal disorders.
Stop treatment immediately and consult a doctor quickly:
- If pregnancy occurs during treatment or in the month following discontinuation of treatment.
- If you have:
- Difficulty in breathing, itching and / or rash. These symptoms may be due to an allergic reaction.
- Headache with nausea, vomiting or decreased vision.
- Severe stomach pain, nausea or vomiting, or severe cases of diarrhea with blood in the stool.
- Difficulty urinating or inability to urinate.
- Reduced night vision and / or visual disturbances.
- Psychiatric disorders, particularly signs of depression (deep feelings of sadness or crying fits, thinking that you are hurting yourself (self-harm) or isolating yourself (self-isolation) from family or friends).
- If you notice yellowing of the eyes or skin and a feeling of dizziness.
Interactions Which drugs or foods can modify the effect of Isoriac
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including medicines obtained without a prescription.
Do not take a drug containing vitamin A or tetracyclines while on ISORIAC therapy.
Concomitant administration of isotretinoin and topical keratolytics or anti-acne exfoliating agents should be avoided because it may increase local irritation.
Warnings It is important to know that:
Use during pregnancy and lactation
The use of ISORIAC is strictly prohibited during pregnancy and breastfeeding (see section "Pregnancy and breastfeeding, Important").
Special warnings for male patients
There are no special conditions for prescribing this drug to male patients: there is no evidence to suggest any effects on the fertility or offspring of male patients taking isotretinoin. Remember that you should not share the drug with anyone. other, especially with women.
Driving and using machines
Be careful when driving vehicles or using machines at night; night vision may be reduced during therapy, sometimes suddenly.
Visual impairment rarely persists after discontinuation of therapy.
ISORIAC contains soybean oil
Do not take this medicine if you have a peanut or soya allergy.
Tips for everyday life:
- Apply ointments or moisturizers to the skin and use a lip balm during therapy for dry skin or lips.
- In general, avoid applying irritating products to the skin (eg peeling creams) during therapy.
- Avoid excessive sun exposure: ISORIAC can increase sensitivity to the sun during treatment.
- However, if sun exposure cannot be avoided, apply a sunscreen cream (with an SPF of at least 15).
- Do not use UV lamps or sun beds or showers.
- Avoid waxing during treatment and for at least 6 months after stopping it. Also avoid surgical dermabrasion or laser therapy (cosmetic procedures aimed at smoothing the skin to reduce scars or signs of aging). These procedures can cause skin scarring, skin hypo / hyperpigmentation (discoloration or high coloration of the skin) or peeling of the epidermis.
- Wear glasses rather than contact lenses throughout the treatment period if your eyes are very dry.
- You may need to wear sunglasses to protect your eyes from glare.
- Be careful when driving vehicles or using machines at night, as changes in vision (reduced night vision) occur suddenly.
- Refrain from strenuous physical activity during treatment with ISORIAC as joint or muscle pain may sometimes occur during treatment.
- Refrain from donating blood during therapy and for at least one month after stopping therapy. If a pregnant woman receives donated blood from a patient taking the drug, her baby could be born with severe malformations.
Pregnancy and breastfeeding, Important
Pregnancy and breastfeeding are an absolute contraindication to isotretinoin treatment.
ISORIAC is teratogenic. This means that if a pregnancy begins during the course of isotretinoin therapy or during the month following therapy, this drug can cause severe malformations in the baby:
Diagram of possible external malformations in case of pregnancy during treatment with isotretinoin: lack of ears or ears set very low, large head and small chin, eye abnormalities, palate malformations.
Internal malformations: They are also frequent. They affect the heart, thymus, nervous system and parathyroid glands. This drug can also cause miscarriage.
You must not take ISORIAC:
- If you are pregnant or if you are planning to become pregnant during therapy or in the month following discontinuation of therapy.
- If you are breastfeeding, as isotretinoin can pass into breast milk and harm the baby.
PREGNANCY PREVENTION PROGRAM
Isoriac is contraindicated in women of childbearing age unless all the conditions of the Pregnancy Prevention Program are met.
ISORIAC prescription and conditions of administration for women of childbearing age:
- He understood the teratogenic risk.
- She understood the reasons why she shouldn't get pregnant. The doctor has provided her with information on the measures to be taken to avoid pregnancy and has also provided her with a brochure on the various methods of contraception. If necessary, your doctor may refer you to a gynecologist.
- He agreed to use at least one and preferably two effective methods of contraception, including a barrier method:
- for at least 1 month before starting ISORIAC therapy,
- for the entire duration of therapy,
- for 1 month after stopping therapy.
You must use contraception even if you are not sexually active or if you are not menstruating.
- He understands the need for a follow-up medical examination every month and agrees to this. In this context, your doctor will prescribe a pregnancy test:
- Before starting ISORIAC. The test should be done during the first 3 days of your menstrual cycle (period).
- every month during therapy,
- 5 weeks after stopping it.
The result of each test must be negative: You must not become pregnant at any time during or in the month following therapy.
- She must sign (herself or the adult who answers for her) a consent form regarding therapy and contraception, considering that:
- She was informed of the risks associated with ISORIAC therapy,
- Agree to abide by the Pregnancy Prevention Program
Dosage and method of use How to use Isoriac: Dosage
Dosage:
Always take ISORIAC exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
The usual starting dose is 0.5 mg for each kilogram of body weight per day (0.5 mg / kg / day).
For most patients, the dose is between 0.5 and 1.0 mg / kg / day.
If it seems to you that the effect of ISORIAC is too strong or too weak, please inform your doctor.
The capsules should be taken once or twice a day with meals. Swallow the capsules whole without chewing or sucking them.
Patients with severe renal insufficiency
In patients with severe renal insufficiency, treatment should start at a lower dose (e.g. 10 mg / day).
Use in children
ISORIAC is not indicated for the treatment of prepubertal acne and is not recommended in patients less than 12 years of age.
Patients with intolerance
In patients who show severe intolerance to the recommended dose, the doctor may continue treatment at the highest tolerated dose.
Duration of treatment
An ISORIAC cycle lasts from 16 to 24 weeks. The skin can continue to improve for up to 8 weeks after the end of the treatment.
Therefore, wait at least the end of this 8 week period before starting a new course of treatment, if necessary. For most patients, only one course is sufficient.
If you forget to take ISORIAC:
Do not take a double dose to make up for a forgotten dose of Isoriac.
Then resume your usual dosing schedule. If you have any further questions on the use of this medicine, consult your doctor or pharmacist.
Overdose What to do if you have taken too much Isoriac
If you have taken more ISORIAC than you should, symptoms of hypervitaminosis A may appear, manifesting as severe headache, nausea or vomiting, sleepiness, irritability and itching.
Contact your doctor, pharmacist or the nearest hospital as soon as possible.
Side Effects What are the side effects of Isoriac
Like all medicines, ISORIAC can cause side effects, although not everybody gets them.
These effects often subside during the course of treatment or after stopping or changing the dose (consult your doctor). Your doctor can help you deal with the situation.
Some side effects can be serious
- In rare cases, some patients have suffered from depression or aggravated depression while taking isotretinoin, or soon after stopping isotretinoin, or have developed other severe mental problems.
Symptoms include sadness, anxiety, mood swings, crying fits, irritability, loss of pleasure or interest in sports or social activities, excessive or insufficient sleep, changes in body weight or appetite, minor school or work performance or concentration problems.
In very few cases, some patients have thought about hurting themselves (self-harm) or ending their lives (suicidal thoughts), sometimes by putting them into action. Some of these patients have been reported to have no signs of depression.
Very rarely, there have been reports of patients becoming aggressive or violent on ISORIAC. Tell your doctor about any mental disorder you have had in the past, including depression, suicidal instincts or psychosis (loss of contact with reality, for example hearing voices or seeing things that are not there), or if a member of your family suffers or has suffered from a mental problem.
Tell your doctor if you are taking medicines for any of these conditions. If you think you are developing any of these mental conditions, contact your doctor immediately. You may be advised to stop taking isotretinoin.
However, stopping isotretinoin may not be enough to relieve symptoms and you may need additional help, which your doctor can give you.
- Sudden allergic reaction that poses a threat to life (anaphylactic reactions).
- Severe skin rashes (erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis), which are potentially life-threatening and require immediate medical attention. These initially manifest as circular patches often with blisters in the center, usually on the arms and hands or legs and feet, more severe rashes may include blistering on the chest and back. Additional symptoms such as eye infections (conjunctivitis) or ulcers in the mouth, throat or nose may occur. Severe forms of skin rashes can develop into very extensive peeling which can be life-threatening. These severe rashes are often preceded by headache, fever, body aches (flu-like symptoms).
If you develop a rash or these skin symptoms, stop taking Isoriac and contact your doctor immediately.
All other side effects are listed below according to their frequency.
Very common side effects: may affect more than 1 in 10 people
- Low red blood cell count (anemia), decreased platelet count, increased platelet count.
- Increased sedimentation rate (an indicator of acute inflammation).
- Increase in fatty acids (increase in blood triglycerides), decrease in the protein component of lipoproteins (decrease in high-density lipoproteins -HDL).
- Increase in liver enzymes (increase in transaminases). In such cases, the doctor may need to order blood tests and take necessary measures.
- Red sores or deep fissures in the corners of the mouth or lips, skin inflammation, dry skin, localized peeling, itching, red skin rash, skin fragility. • Infection of the eyelids, discharge from the itchy eyes and crusted eyelids (conjunctivitis), eye irritation and dry eyes.
- Back pain, muscle and joint pain. It is therefore prudent to reduce strenuous exercise during treatment. All these effects are reversible upon discontinuation of treatment.
Common side effects: may affect up to 1 in 10 people
- Elevation of blood glucose and a type of fat (cholesterol), presence of protein or blood in the urine.
- Low white blood cell count which can make you more susceptible to infections.
- Headache.
- Nasal dryness, nosebleeds and nasopharyngitis.
Rare side effects: may affect up to 1 in 1,000 people
- Allergic skin reactions, hypersensitivity.
- Hair loss (alopecia).
Very rare side effects: may affect up to 1 in 10,000 people
- Inflammation of the pancreas or gastrointestinal bleeding or inflammatory bowel disease. If you have severe abdominal pain, with or without bloody diarrhea, nausea and vomiting, stop taking isotretinoin and contact your doctor as soon as possible.
- Liver disease (hepatitis) including nausea, vomiting, loss of appetite, generally feeling unwell, fever, itching, yellowing of the skin and eyes.
- Kidney disease including severe fatigue, difficulty urinating or even inability to urinate and swollen eyelids. If you experience these symptoms while on isotretinoin, stop the treatment and contact your doctor.
- Too high blood sugar levels (diabetes), with symptoms including excessive thirst, passing a greatly increased amount of urine, increased appetite with weight loss, feeling tired, drowsy, weakness, depression, irritability and general malaise In this case, contact your doctor.
- Benign intracranial hypertension has occurred in patients receiving concomitant treatment with isotretinoin and some antibiotics (tetracyclines). This hypertension is manifested by persistent headaches with nausea, vomiting or blurred vision. Stop taking ISORIAC and consult your doctor as soon as possible.
- Fits (convulsions).
- Narrowing or blockage of blood vessels.
- Worsening of acne in the first weeks of treatment with inflammatory lesions on the skin, severe form of acne (acne fulminant). However, in general, the continuation of treatment will be accompanied by the alleviation of acne and other symptoms.
- Inflammation of the colon.
- Localized bacterial infections can occur.
- Facial erythema, rash.
- Hair disorders, abnormal hair growth, nail plate abnormalities, infected cuticles.
- Benign vascular lesions of the skin and mucous membranes.
- Increased sensitivity to the sun. Increased pigmentation, excessive sweating.
- Enlargement of the lymph nodes.
- High levels of uric acid in the blood which can cause gout.
- The medicine can impair night vision and visual disturbances may suddenly occur. These effects rarely persist after the end of treatment.
- Impaired color vision, intense eye irritation, corneal opacity, irritation or a feeling of something in the eye (keratitis), blurred vision, difficulty seeing (cataracts), increased sensitivity to light, visual disturbances and poor tolerance to contact lenses. You may need sunglasses to prevent your eyes from being dazzled.If the medicine causes you even the slightest difficulty in seeing, tell your doctor quickly.
- Hearing impairment
- Dry throat, nausea, abnormal change in voice (hoarseness).
- Malaise.
- Disease affecting mainly the joints with pain and swelling, bone abnormalities, growth retardation and reduced bone density, soft tissue calcification, inflammation of the tendons. The blood levels of an enzyme (creatine phosphokinase), released during the breakdown of muscle fibers, can be increased in the case of intense physical exertion in patients treated with isotretinoin, breakdown of muscle tissue which can lead to kidney problems.
- Somnolence, dizziness.
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. You can also report side effects directly via the national reporting system at www.agenziafarmaco.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use ISORIAC after the expiry date which is stated on the pack. The expiry date refers to the last day of the month.
Do not store above 25 ° C. Store in the original container. Keep the container tightly closed to protect from light.
At the end of the treatment, return any remaining capsules to the pharmacist.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other Information
What ISORIAC
ISORIAC 10 mg, 20 mg, soft capsule
- The active ingredient is:
For a 10 mg soft capsule: isotretinoin ......................................... ..... 10 mg
For a 20 mg soft capsule: isotretinoin ......................................... ..... 20 mg
- The other ingredients are: refined soybean oil, hydrogenated vegetable oil, yellow beeswax.
Composition of the 10 mg capsule shell: gelatin, glycerol, purified water, red iron oxide (E172).
Composition of the 20 mg capsule shell: gelatin, glycerol, purified water, red iron oxide (E172), yellow iron oxide (E172), 25% titanium dioxide (E171) in glycerol.
Composition of the black ink: SDA 35 alcohol, propylene glycol, black iron oxide, polyvinyl acetate phthalate, water, isopropyl alcohol, polyethylene glycol, ammonium hydroxide.
Description of the appearance of ISORIAC and contents of the pack
This medicine is supplied in the form of soft capsules in packs of 30.
Each 10 mg capsule has a red / brown gelatin shell with a bright yellow / orange content and is printed with the "I 10" logo on one side.
Each 20 mg capsule has a two-tone red / brown and cream gelatin shell with a bright yellow / orange content and is printed with the "I 20" logo on one side.
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
ISORIAC
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
ISORIAC 10 mg, soft capsule
Each soft capsule contains 10 mg of isotretinoin
For a complete list of excipients, see section 6.1.
ISORIAC 20 mg, soft capsule
Each soft capsule contains 20 mg of isotretinoin
For a complete list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Soft capsules.
Each 10 mg capsule has a red / brown gelatin shell with a bright yellow / orange content and is printed with the logo "l10" on one side.
Each 20 mg capsule features a red / brown and cream bicolor opaque gelatin shell with a bright yellow / orange content and is printed with the "l 20" logo on one side.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Severe forms of acne (such as nodular and conglobate acne or acne at risk of permanent scarring) resistant to adequate courses of standard therapy with systemic antibacterials and topical treatment.
04.2 Posology and method of administration
Isotretinoin should only be prescribed by or under the supervision of physicians experienced in the use of systemic retinoids for the treatment of severe acne and fully aware of the risks of isotretinoin therapy and the required controls.
The capsules should be taken with food once or twice a day.
Adults including adolescents and the elderly:
Isotretinoin therapy should be initiated with a daily dosage of 0.5 mg / kg.
The therapeutic response to isotretinoin and some of the adverse events are dose-related and differ between patients. Therefore, individual dose adjustment is required during therapy. For most patients, the daily dosage ranges from 0.5-1.0. mg / Kg.
Prolonged remission over time and the incidence of relapses are more closely related to the total dose administered than to the duration of treatment or daily dose. It has been demonstrated that no substantial additional benefit is to be expected from treatment with a cumulative dose greater than 120-150 mg / kg The duration of treatment will depend on the individual daily dosage.A treatment course of 16-24 weeks is generally sufficient to achieve remission.
In the majority of patients, the complete disappearance of acne is achieved with a single course of treatment. In the case of an evident relapse, the opportunity of a further course of therapy with isotretinoin using the same daily dose and the same can be considered. cumulative dosage. Since further improvement in acne can be observed for up to 8 weeks after stopping treatment, no further course of therapy should be considered until at least this period has elapsed.
Patients with severe renal insufficiency
In patients with severe renal insufficiency, treatment should be started at a lower dose (e.g. 10 mg / day). The dose should then be increased up to 1 mg / kg / day or up to the maximum tolerated dose by the patient (see section 4.4 "Special warnings and special precautions for use").
Children
Isotretinoin is not indicated for the treatment of prepubertal acne and is not recommended for patients under 12 years of age.
Patients with intolerances
In patients with severe intolerance to the recommended dosage, treatment can be continued at a lower dosage, resulting in a longer duration of therapy and a higher risk of relapse. In order to obtain the maximum possible efficacy in these patients, administration should normally be continued with the maximum tolerated dosage.
04.3 Contraindications
Isotretinoin is contraindicated in pregnant or breastfeeding women (see section 4.6 Pregnancy and lactation ").
Isotretinoin is contraindicated in women of childbearing potential unless all conditions of the Pregnancy Prevention Program are met (see section 4.4 "Special warnings and appropriate precautions for use").
Isotretinoin is also contraindicated in patients:
- With liver failure
- With excessively high blood lipid values
- With hypervitaminosis A.
- With hypersensitivity to isotretinoin or to one of the excipients of the product
- With allergy to peanut or soybean oil, since ISORIAC contains soybean oil
- In concomitant treatment with tetracyclines (see section 4.5 "Interaction with other medicinal products and other forms of interaction")
04.4 Special warnings and appropriate precautions for use
Pregnancy Prevention Program
This medicinal product is TERATOGEN
Isotretinoin is contraindicated in women of childbearing potential unless all of the following conditions of the Pregnancy Prevention Program are met:
The patient suffers from severe acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to adequate courses of standard therapy with systemic antibacterials and topical treatment (see section 4.1 "Therapeutic indications").
The patient understands the teratogenic risk.
The patient understands the need for rigorous checks on a monthly basis.
The patient understands and accepts the need for effective contraception, without interruption, 1 month before the start of treatment, for the duration of treatment and for 1 month after the end of treatment. At least one and preferably two methods of contraception should be used. complementary, including a barrier method.
Even in the case of amenorrhea, the patient must follow all the warnings for effective contraception.
The patient must be able to observe effective contraceptive measures.
The patient is informed and understands the possible consequences of pregnancy and the need to consult a doctor quickly if there is a risk of pregnancy.
The patient understands the need and agrees to carry out a pregnancy test before, during and 5 weeks after the end of the treatment.
The patient acknowledges that she has understood the risks and necessary precautions associated with the use of isotretinoin.
These conditions also apply to women who are not sexually active, unless the prescriber considers that there are well-founded reasons that exclude any risk of pregnancy.
The prescriber must ensure that:
The patient adheres to the conditions for pregnancy prevention as outlined above, including confirmation that she has an adequate level of understanding.
The patient has acknowledged the aforementioned conditions.
The patient has used at least one and preferably two methods of effective contraception including a barrier method for at least 1 month prior to the start of treatment and is continuing to use effective contraception throughout the treatment period and for at least 1 month after treatment. interruption of treatment.
Negative pregnancy test results have been obtained before, during and 5 weeks after the end of treatment. The dates and results of the pregnancy tests must be documented in the patient's dossier.
Contraception
Patients should be fully informed about pregnancy prevention and should be referred for contraception counseling if they are not using effective contraception.
At a minimum, patients with a potential risk of pregnancy should use at least one effective method of contraception. The patient should preferably use two complementary methods of contraception including a barrier method. Contraception must be continued for at least 1 month after discontinuation of isotretinoin treatment, even in patients with amenorrhea.
Pregnancy test
In accordance with local practice, medically supervised pregnancy tests with a minimum sensitivity of 25 mIU / ml are recommended during the first three days of the menstrual cycle as described below.
Before starting therapy:
In order to exclude the possibility of pregnancy before the start of contraception, it is recommended to perform an early pregnancy test under medical supervision and to record the date and the result. In patients with irregular cycles, the time to perform this test of pregnancy should reflect the patient's sexual activity and should be performed approximately 3 weeks after the last unprotected intercourse. The prescriber should instruct the patient about contraception.
A medically supervised pregnancy test should also be performed during the isotretinoin prescribed visit or in the 3 days prior to the visit and should be postponed until the patient has used effective contraception for at least 1 month. testing must ensure that the patient is not pregnant when starting treatment with isotretinoin.
Control visits
Follow-up visits must be arranged at 28-day intervals. The need to repeat medically supervised pregnancy tests every month should be determined in accordance with local practice, taking into account the patient's sexual activity and recent menstrual history (menstrual irregularities, missed periods or amenorrhea). Where indicated Control pregnancy tests should be performed on the day of the prescription visit or in the 3 days prior to the visit.
End of treatment
Five weeks after stopping treatment, patients will have to undergo a final pregnancy test to rule out pregnancy.
Restrictions on Prescribing and Distribution
Prescriptions of isotretinoin to women of childbearing age should be limited to 30 days of treatment and continuation of therapy requires a new prescription. Ideally, the pregnancy test run, prescription issue and isotretinoin dispensing should occur on the same day. Distribution of isotretinoin should occur within 7 days of prescription at the latest.
Male patients
Available data suggest that the level of maternal exposure to semen and semen of patients taking isotretinoin is not of a magnitude to be associated with the teratogenic effects of isotretinoin.
Male patients should remember not to share their care with anyone else, especially female individuals.
Additional precautions
Patients should be advised not to give this medicine to another person and to return any unused capsules to their pharmacist at the end of treatment.
Patients should not donate blood during therapy and in the month following discontinuation of isotretinoin treatment due to the potential risk to the fetus of a pregnant woman receiving the transfusion.
Study material
The Marketing Authorization Holder, to help prescribers, pharmacists and patients avoid fetal exposure to isotretinoin, will provide information material to reinforce the warnings relating to the teratogenicity of isotretinoin, to provide advice on the contraception before the start of therapy and to provide information on the need for pregnancy tests.
Complete information regarding the teratogenic risk and strict pregnancy prevention measures, as required by the Pregnancy Prevention Program, must be provided by the physician to all patients, both male and female.
Psychiatric disorders
Cases of depression, aggravated depression, anxiety, aggressive tendencies, mood swings, psychotic symptoms and, very rarely, suicidal thoughts, suicide attempts and suicide have been reported in patients treated with isotretinoin (see section 4.8 "Undesirable effects" ).Particular attention should be paid to patients with a history of depression and all patients should be monitored for signs of depression and referred for appropriate treatment. if necessary. However, discontinuation of isotretinoin may be insufficient to relieve symptoms and therefore further psychiatric or psychological evaluation may be required.
Skin and subcutaneous tissue disorders
Acute exacerbation of acne has occasionally been observed during the initial period, but this subsides with continued treatment, usually within 7-10 days, and usually does not require dosage adjustments.
Exposure to intense sunlight or UV rays should be avoided. If necessary, a product with a high protection factor of at least 15 SPF should be used.
Aggressive chemical dermabrasion and laser skin treatment should be avoided in patients treated with isotretinoin for a period of 5-6 months after the end of therapy due to the risk of hypertrophic scarring in atypical areas and more rarely of hyper- or hypopigmentation. post inflammatory in the treated areas. Waxing should be avoided in patients treated with isotretinoin for a period of at least 6 months after treatment due to the risk of epidermal stripping.
Concomitant administration of isotretinoin and topical keratolytics or anti-acne exfoliating agents should be avoided because it may increase local irritation.
Patients should be advised to use a skin ointment or moisturizer and lip emollient from the start of treatment as isotretinoin is likely to cause dry skin and lips.
Eye disorders
Dry eyes, corneal opacity, decreased night vision and keratitis usually resolve after discontinuation of therapy. Dry eyes can be reduced by applying a lubricating eye ointment or by applying artificial tears. Contact lens intolerance may occur and the patient may need to wear glasses during treatment.
Cases of decreased night vision have also been reported and the onset in some patients was sudden (see section 4.7 "Effects on ability to drive and" use machines "). Patients who report having visual disturbances should be referred for evaluation by an experienced ophthalmologist. Treatment with isotretinoin may need to be discontinued.
Musculoskeletal and connective tissue disorders
Cases of myalgia, arthralgia and increased serum creatine phosphokinase have been reported in patients treated with isotretinoin, particularly in those who perform strenuous physical activity (see section 4.8 "Undesirable effects").
Alterations to the bones including premature closure of the epiphyses, hyperostosis and calcification of tendons and ligaments have occurred after several years of administration of very high dosages for the treatment of keratinization disorders. the duration of treatment and the cumulative total dose were usually much higher than those recommended for the treatment of acne.
Benign intracranial hypertension
Cases of benign intracranial hypertension have been reported, some of them related to "concomitant use of tetracyclines" (see sections 4.3 "Contraindications" and 4.5 "Interactions with other medicinal products and other forms of interaction"). Signs and symptoms of benign intracranial hypertension include headache, nausea and vomiting, visual disturbances and papilledema Patients who develop benign intracranial hypertension should immediately discontinue isotretinoin.
Hepatobiliary disorders
Liver enzymes should be checked prior to treatment, 1 month after initiation of treatment, and at 3 month intervals thereafter, unless more frequent monitoring is clinically indicated. Cases of transient and reversible transaminase elevations have been reported. In many cases these changes remained within normal values and then returned to baseline levels during treatment. However, in the case of a clinically relevant and persistent increase in transaminase levels, a dose reduction should be considered. or stopping treatment.
Kidney failure
Renal insufficiency and renal impairment do not alter the pharmacokinetics of isotretinoin. Therefore, isotretinoin can be administered to patients with renal insufficiency. However, it is recommended that patients are initially treated with a low dose and then brought up to the maximum tolerated dose (see section 4.2 "Posology and method of administration". ).
Lipid metabolism
Serum lipids (fasting values) should be checked prior to treatment, 1 month after initiation of treatment, and at 3 month intervals thereafter, unless more frequent monitoring is clinically indicated. Elevated serum lipid values generally they return to normal with dose reduction or discontinuation of treatment and may also respond to dietary measures.
Isotretinoin has been associated with increased plasma triglyceride values. Isotretinoin should be discontinued if hypertriglyceridaemia cannot be maintained within an acceptable range or if symptoms of pancreatitis occur (see section 4.8 "Undesirable effects") Values above 800 mg / dL or 9 mmol / L are sometimes related to acute pancreatitis, which can be fatal.
Gastrointestinal disorders
Isotretinoin has been associated with inflammatory bowel states (including regional ileitis) in patients with no history of intestinal disorders. Patients who experience severe (bleeding) diarrhea should immediately stop taking isotretinoin.
Allergic reactions
Anaphylactic reactions have been reported rarely, in some cases after previous topical exposure to retinoids. Allergic skin reactions have been reported infrequently. Severe cases of allergic vasculitis, often with purpura (bruises and red spots) of the extremities, have been reported and cases of extracutaneous involvement have been reported. Severe allergic reactions require discontinuation of treatment and careful monitoring.
High-risk patients
More frequent monitoring of serum lipid and / or blood glucose levels is required in patients with diabetes, obesity, alcoholism or lipid metabolism disorders who are undergoing treatment with isotretinoin. Cases of increased fasting blood glucose values have been reported during isotretinoin therapy and new cases of diabetes have been diagnosed.
04.5 Interactions with other medicinal products and other forms of interaction
Patients should not take vitamin A as concomitant therapy due to the danger of developing "hypervitaminosis A."
Cases of benign intracranial hypertension (pseudotumor cerebri) have been reported with the concomitant use of isotretinoin and tetracyclines. Consequently, concomitant treatments with tetracyclines should be avoided (see section 4.3 "Contraindications" and section 4.4 "Special warnings and precautions for use" ").
04.6 Pregnancy and breastfeeding
Fetal malformations associated with "isotretinoin exposure" include central nervous system malformations (hydrocephalus, cerebellum malformations / abnormalities, microcephalus), facial dysmorphism, cleft palate, external ear abnormalities (absence of the external ear, reduction or absence of canals auditory), eye anomalies (microphthalmia), cardiovascular anomalies (cone-truncated malformations such as tetralogy of Fallot, transposition of the great vessels, septal defects), anomalies of the thymus and parathyroid glands. There has also been an increase in cases of spontaneous abortion.
If pregnancy occurs in a woman treated with isotretinoin, treatment should be discontinued and the patient referred to a specialist or experienced in teratology for evaluation and advice.
Feeding time:
Isotretinoin is highly lipophilic therefore passage of isotretinoin into human milk is very likely. Due to the potential for adverse events in the mother and exposed infant, the use of isotretinoin is contraindicated in nursing mothers.
04.7 Effects on ability to drive and use machines
There have been several cases of decreased night vision during isotretinoin therapy and on rare occasions these have continued after therapy (see section 4.4 "Special warnings and special precautions for use" and section 4.8 "Undesirable effects"). in some patients the onset of this effect was sudden, patients should be made aware of this potential problem and they should be advised to take special care while driving or using machines.
04.8 Undesirable effects
The following symptoms are the most commonly reported undesirable effects related to the use of isotretinoin: dryness of the mucous membranes, for example of the lips (cheilitis), of the nasal mucosa (epistaxis), of the eyes (conjunctivitis), dryness of the skin. Some of the side effects associated with the use of isotretinoin are related to the dosage. Side effects are usually reversible on dose reduction or discontinuation of treatment, however some may persist even after treatment is stopped.
The incidence of adverse events was calculated on all clinical trials including 824 patients and on the basis of post-marketing data .
04.9 Overdose
Isotretinoin is a derivative of vitamin A. Although the acute toxicity of isotretinoin is low, symptoms of hypervitaminosis A may occur in the event of accidental overdose. Symptoms of acute vitamin A toxicity include severe headache, nausea or vomiting, drowsiness, irritability and itching. Signs and symptoms of accidental or deliberate isotretinoin overdose would likely be similar. It is reasonable to assume that these symptoms are reversible and subside without the need for treatment.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: anti-acne preparation for systemic use
ATC code: D10BA01
Mechanism of action
Isotretinoin is a stereoisomer of all-trans retinoic acid (tretinoin). The exact mechanism of action of isotretinoin has not yet been clarified in detail, but it has been shown that the improvement observed in the clinical picture of severe acne is associated with the suppression of the activity of the sebaceous glands and a reduction in volume. of the glands themselves, histologically proven. Furthermore, a cutaneous anti-inflammatory effect of isotretinoin has been demonstrated.
Effectiveness
The hypercorneification of the epithelial lining of the pilo-sebaceous unit causes a detachment of the corneocytes inside the duct and its blockage by keratin and excess sebum. This is followed by the formation of a blackhead and possibly inflammatory lesions. Isotretinoin inhibits the proliferation of sebocytes and appears to act on acne by re-setting the differentiation program. Sebum is the main substrate for the development of Propionibacterium acnes so that the reduced production of sebum inhibits bacterial colonization of the duct.
05.2 Pharmacokinetic properties
Absorption
Absorption of isotretinoin from the gastrointestinal tract is variable and linear with respect to dose over the therapeutic range. The absolute bioavailability of isotretinoin has not been determined as the compound is not available as a preparation for human intravenous use, but extrapolation of data from studies in dogs seems to suggest a fairly low and variable systemic bioavailability. When isotretinoin is taken with food, bioavailability is double that of fasting.
Distribution
Isotretinoin is extensively bound to plasma proteins, especially albumin (99.9%). The volume of distribution of isotretinoin in humans has not been determined as isotretinoin is not available as an intravenous preparation for human use. In humans, there are few data on the distribution of isotretinoin in tissues. Concentrations of isotretinoin in the epidermis are only half of those found in serum. Concentrations of isotretinoin in plasma are approximately 1.7 times those of all blood due to poor penetration of isotretinoin into red blood cells.
Metabolism
Following oral administration of isotretinoin, three major metabolites have been identified in plasma: 4-oxo-isotretinoin, tretinoin (all-trans retinoic acid) and 4 oxo-tretinoin. These metabolites exhibited biological activity in several tests in vitro. In a clinical study, 4-oxo-isotretinoin was shown to make a significant contribution to isotretinoin activity (reduction in sebum excretion with no effect on plasma levels of isotretinoin and tretinoin). Other minor metabolites include conjugated glucuronides. The major metabolite is 4-oxo-isotretinoin with plasma concentrations at steady state, which are 2.5 times higher than those of the parent compound.
Isotretinoin and tretinoin (all-trans retinoic acid) are metabolised reversibly (interconverted) and the metabolism of tretinoin is therefore linked to that of isotretinoin. It has been estimated that 20-30% of an isotretinoin dose is metabolized by isomerization.
The enterohepatic circulation may play a significant role in the pharmacokinetics of isotretinoin in humans. Studies in vitro on metabolism have shown that various CYP enzymes are involved in the metabolism of isotretinoin to 4-oxo-isotretinoin and tretinoin. No isoform seems to play a predominant role. Isotretinoin and its metabolites do not significantly influence CYP activity.
Elimination
After oral administration of radio-labeled isotretinoin, approximately equal fractions of the dose were recovered in the urine and faeces. Following oral administration of isotretinoin, the terminal elimination half-life of the unchanged product in patients with acne has an average of 19 hours. The terminal elimination half-life of 4-oxo-isotretinoin is longer, with a mean value of 29 hours.
Isotretinoin is a physiological retinoid: endogenous concentrations of retinoids are reached approximately within two weeks after the end of isotretinoin therapy.
Pharmacokinetics in particular populations
Since isotretinoin is contraindicated in patients with hepatic insufficiency, little information exists on the kinetics of isotretinoin in this patient population. Renal insufficiency significantly reduces the plasma clearance of isotretinoin or 4-oxo-isotretinoin.
05.3 Preclinical safety data
Acute toxicity
The acute oral toxicity of isotretinoin has been determined in various animal species. The LD50 is approximately 2000 mg / kg in rabbits, approximately 3000 mg / kg in mice and over 4000 mg / kg in rats.
Chronic toxicity
A long-term 2-year study in rats (isotretinoin dosage 2, 8 and 32 mg / kg / day) showed partial hair loss and elevated plasma triglyceride levels in the higher dose groups. The spectrum of side effects of isotretinoin in rodents therefore resembles that of vitamin A, but does not include the strong calcification of tissues and organs observed with vitamin A in rats. The alterations in liver cells observed with vitamin A they do not occur with isotretinoin.
All observed side effects from hypervitaminosis A syndrome resolved spontaneously after discontinuation of isotretinoin. Even animals in poor general condition recovered almost completely within 1-2 weeks.
Teratogenicity
Like other vitamin A derivatives, isotretinoin has been shown to be teratogenic and embryotoxic in animal experiments.
Due to the teratogenic potential of isotretinoin, there are therapeutic consequences for administration to women of childbearing potential (see section 4.3 "Contraindications", section 4.4 "Special warnings and special precautions for use" and section 4.6 "Pregnancy and lactation") .
Fertility
In therapeutic dosages, isotretinoin has no effect on the number, mobility and morphology of spermatozoa and does not affect the formation and development of the embryo which is formed from the spermatozoa of men treated with isotretinoin.
Mutagenicity
Isotretinoin was not shown to be mutagenic or carcinogenic respectively in tests in vitro or in vivo in animals.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Soybean oil, hydrogenated vegetable oil, yellow beeswax.
ISORIAC 20 mg: Capsule shell : gelatin, glycerol, purified water, red iron oxide (E172), yellow iron oxide (E172), titanium dioxide (E171).
ISORIAC 10 mg: Capsule shell: gelatin, glycerol, purified water, red iron oxide (E172).
06.2 Incompatibility
Not applicable.
06.3 Period of validity
3 years
06.4 Special precautions for storage
Do not store above 25 ° C.
06.5 Nature of the immediate packaging and contents of the package
28, 30, 50, 56 and 60 soft capsules in thermoformed blisters (PVC / PE / PVDC) sealed with an aluminum foil.
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
At the end of the treatment, male and female patients should give the unused capsules to the pharmacist.
07.0 MARKETING AUTHORIZATION HOLDER
PIERRE FABRE ITALIA S.p.A. - Via G.G. Winckelmann, 1 - 20146 MILAN
08.0 MARKETING AUTHORIZATION NUMBER
10 mg soft capsules - 30 capsules in thermoformed blister (PVC / PE / PVDC) sealed with an opaque aluminum foil - AIC n. 037551025 / M
20 mg soft capsules - 30 capsules in thermoformed blister (PVC / PE / PVDC) sealed with an opaque aluminum foil - AIC n. 037551076 / M
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
September 2007
10.0 DATE OF REVISION OF THE TEXT
September 2007
11.0 FOR RADIO DRUGS, COMPLETE DATA ON THE INTERNAL RADIATION DOSIMETRY
12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON EXEMPORARY PREPARATION AND QUALITY CONTROL
March 2009
New prescribing modalities for isotretinoin-containing medicines for systemic use
Dear Doctor / Dear Doctor,
The Italian Medicines Agency wishes to provide you with a guide on the new ways of prescribing medicines containing isotretinoin for systemic use.
Isotretinoin is a medicine subject to the teratogenic risk prevention program approved by AIFA in 2005 (GU n.261 / 05 and subsequent amendments).
This Program, aimed at doctors, pharmacists and manufacturers, indicates the methods of prescribing, dispensing and distributing medicines containing isotretinoin for systemic use, information for patients on the risks associated with the use of the drug and on the need for contraceptive measures. adequate monitoring and management of any cases of pregnancy and / or suspected embryo-fetal exposure that have occurred.
The Technical Scientific Commission of the AIFA, in order to further strengthen the measures aimed at a more controlled and safe use of isotretinoin, has adopted a new method of prescribing medicines containing isotretinoin for systemic use (GU n ° 43/09) approving a specific "form for the prescription of" isotretinoin for systemic use "(see annex). This provision does not constitute a modification of the Risk Prevention Program.
The AIFA form for the prescription of isotretinoin for systemic use is divided into two parts, one for the dermatologist, who is entrusted with the first prescription, the other for the general practitioner (GP) or for the dermatologist himself in the case in which the patient is followed for the entire duration of the treatment by the specialist.
The dermatologist will have to:
• prescribe isotretinoin according to the authorized therapeutic indications such as severe forms of acne (such as nodular or conglobate acne or acne with the risk of permanent scarring) resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy;
• inform the patient of the teratogenic risk related to the use of isotretinoin;
• give the patient the guide to therapy and the guide to contraception;
• attach the patient's informed consent;
• verify that the patient has taken effective contraception one month before starting treatment with the drug.
If the patient agrees to undergo isotretinoin therapy, the dermatologist should recommend that the patient use effective contraception for at least one month before starting treatment; therapy should only be started after a negative pregnancy test has been performed. Date and test result must be recorded on the form. The test must be carried out during the first three days of the menstrual cycle following the visit to the doctor.
The GP or dermatologist will follow the patient for the entire duration of the therapy, verifying that the patient has adopted effective contraception, without interruption, before the start of the treatment, for the entire duration and for at least 1 month after the end of the treatment.
The form includes a section in which the GP or dermatologist must indicate the date and outcome of the pregnancy test.
After four weeks of continuous adoption of the chosen method of contraception, the patient should go to the doctor again for a prescription for isotretinoin. Another pregnancy test should be performed immediately before starting treatment.
Visits and checks by the GP or dermatologist must be scheduled at 28-day intervals.
The last pregnancy test should be performed five weeks after the end of isotretinoin treatment.
The pharmacist must dispense drugs containing isotretinoin for systemic use only on presentation of a medical prescription (both SSN prescription and white prescription) to be used only once.
The pharmacist must:
• dispense a new package of isotretinoin only following presentation of a new medical prescription.
• not accept telephone, fax or computerized requests for isotretinoin, requests for drug replenishment or distribution of samples.
The medical prescription (both on the SSN prescription and on the white prescription), which is valid for 7 days from the date of issue, must be indicated:
• the dosage;
• the certification date;
• the need for the drug for up to 30 days (expressed in mg / day).
The doctor is required to note on the prescription the date of the negative pregnancy test (date of certification) and that of the prescription, even when they coincide.
In the event that two different dates are placed on the prescription, the pharmacist should contact the doctor for clarification and, in any case, cautiously consider the 7-day validity of the prescription from the earliest date.
For male patients the risk management program should be followed for the applicable parts; for example, the limitations relating to the prescription (validity 7 days, therapy for a maximum of 30 days) and the acquisition of informed consent apply. In particular, the patient must be informed of the teratogenic risk of the drug and, therefore, not to be able to donate the own blood and not having to give isotretinoin to anyone.
The patient is required to return unused capsules to the pharmacist at the end of the therapy.
Reports of suspected adverse drug reactions should be sent to the pharmacovigilance manager of the facility to which they belong.
