Acnotin

Isotretinoin.

Each softgel capsule contains Isotretinoin USP 10 mg or 20 mg.
Isotretinoin is 13-cis retinoic acid. It is a synthetic stereoisomer of all-trans retinoic acid (tretinoin). It is a yellow-orange to orange crystalline powder with a molecular weight of 300.44.

Pharmacology: The exact mechanism of action of isotretinoin is not known. However, isotretinoin reduces sebaceous gland size and inhibits sebaceous gland activity, thereby decreasing sebum secretion. In addition, isotretinoin has been shown to have anti-keratinizing and anti-inflammatory actions. The exact role of these actions in clinical improvement of cystic acne is not known, especially with respect to prolonged remissions.
Rapidly absorbed from the gastrointestinal tract. Taking isotretinoin with food increases bioavailability relative to fasting conditions, probably as a result of easier absorption of this highly lipophilic medication.
Isotretinoin is metabolized in liver and possibly in the gut wall. The major identified metabolite in blood and urine is 4-oxo-isotretinoin, other identified metabolites are tretinoin and 4-oxo-tretinoin.
Isotretinoin appears to be eliminated almost exclusively by hepatic metabolism and biliary excretion.

Isotretinoin is a retinoid for systemic treatment of acne. It is indicated for severe forms of nodulo-cystic acne which are resistant to previous therapy, particularly cystic acne and acne conglobata, especially when the lesions involve the trunk.

The therapy should be started with 0.5 to 1 mg/kg body weight daily with meals in 2 divided doses for 15-20 weeks.
The maximum dose is 2 mg/kg body weight daily. There should be an interval of at least 2 months before restarting treatment.

Signs of hypervitaminosis A could appear in cases of accidental overdose. Evacuation of the stomach may be indicated in the first few hours after overdosage. The symptoms have been abdominal pain, dizziness, intracranial pressure, headache, severe, nausea, vomiting, irritability, itchy skin.
Treatment of overdose: To decrease absorption - Evacuation of stomach should be considered within 2 hours of ingestion of acute overdose. Medication should be discontinued in patients with symptoms of overdose who were given therapeutic doses.
Monitoring: Monitor for increased intracranial pressure.
Female patients of childbearing potential should have a pregnancy test at time of overdose and 1 month later; if positive, teratogenic risk and continuance of pregnancy should be discussed.
Blood samples should be collected and isotretinoin and metabolite concentrations determined.

Hepatic and renal insufficiency, hypervitaminosis A; patients with excessively elevated blood lipid values; hypersensitivity to isotretinoin.
Blood donation by patients during and within 1 month of cessation of isotretinoin treatment to women of childbearing potential should be avoided.
Pregnancy, Nursing Mother: Isotretinoin is highly teratogenic. It is therefore contraindicated in women who are pregnant or who may become pregnant while undergoing treatment. There is an extremely high risk that a deformed infant will result if pregnancy occurs while taking isotretinoin in any amount even for short periods. Potentially all exposed fetuses can be affected. Major human fetal abnormalities related to isotretinoin administration have been documented, including hydrocephalus, microcephalus, abnormalities of the external ear (micropinna, small or absent external auditory canals), microphthalmia, cardiovascular abnormalities and cerebellar malformation.
As isotretinoin is highly lipophilic, the passage of the drug in human milk is very likely. Because of the potential for adverse effects, the use of isotretinoin should be avoided in nursing mothers.
It is recommended that the patient use two forms of effective contraception to prevent pregnancy, starting 1 month before initiation of treatment, during treatment, and for 1 month after discontinuation of treatment. Testing serve to remind the patient of the importance of avoiding pregnancy. If pregnancy occurs, patient should be counseled on whether to continue the pregnancy. Isotretinoin therapy starts only on the second or third day of the next normal period.
Warning: Adhere strictly to precautions; Pregnancy forbidden; Risk of malformation.

Psychiatric Disorders: Acnotin may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. No mechanism of action has been established for these events. Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need.
Therefore, prior to initiation of Acnotin therapy, patients and family members should be asked about any history of psychiatric disorder, and at each visit during therapy patients should be assessed for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation may be necessary. Patients should stop Acnotin and the patients or a family member should promptly contact their prescriber if the patient develops depression, mood disturbance, psychosis, or aggression, without waiting until the next visit.
Serious Skin Reactions: There have been reports of erythema multiforme and severe skin reactions [eg, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)] associated with isotretinoin use. These events may be serious and result in death, life-threatening events, hospitalization, or disability. Patients should be monitored closely for severe skin reactions, and discontinuation of isotretinoin should be considered if warranted.

Isotretinoin should only be prescribed by physicians who are experienced in the use of systemic retinoids, preferably dermatologists, and understand the risk of teratogenicity if isotretinoin is used during pregnancy.
Liver function should be checked before and 1 month after the start of treatment, and subsequently at 3-monthly intervals.
Serum lipids (fasting value) should also be checked (before and 1 month after the start of therapy, and also at the end of the 3- to 4-months treatment period).
Checking with physician anytime vision problems occur; wearing contact lenses may be uncomfortable. Vision impairment can occur including photophobia, blurred vision, or dryness of eyes. Vision problems can make driving a car or operating machinery dangerous.
A careful evaluation of the risk/benefit ratio should be carried out in every patient and isotretinoin administration should be restricted to severe cases.
Since acne is an androgen-dependent disease, contraceptives containing an androgen progestational substance, such as one derived form 19-nortestosterone (norsteroid), particularly in the presence of gyneco-endocrinological problems should be avoided.
Dermabrasion should be avoided in patients on isotretinoin and for a period of 5-6 months after treatment because of the risk of hypertrophic scarring in atypical areas.
Wax epilation should be avoided in patients on isotretinoin and for a period of 5-6 months after treatment because of the risk of dermatitis.
Special Patient Groups: In high-risk patients (with diabetes, obesity, alcoholism or disorders of lipid metabolism) undergoing treatment with isotretinoin, more frequent checks of the relevant laboratory parameters will be necessary.
In known or suspected diabetics, frequent determination of blood glucose levels is recommended. Although no causal relationship has been established, elevated fasting blood sugars have been reported, and new cases of diabetes have been diagnosed during isotretinoin therapy.
Dental problems can occur resulting from dryness of mouth and may increase dental disease, including tooth decay, gum disease, and fungus infections; regular dental appointments are needed and use of sugarless candy or saliva substitute or melting ice in mouth may be necessary to lessen dental problems.

Most of the adverse reactions of isotretinoin are dose-related. With the recommended dosage, the risk/benefit ratio is generally acceptable considering the severity of the disease.
Incidence more frequent: chelitis (scaling, redness, burning, pain and other signs of inflammation of lips), epistaxis (nosebleeds) and skin infection.
Symptoms Associated with Hypervitaminosis A: The following symptoms are the most frequently reported: Dryness of the skin, dryness of the mucosae, eg of the lips, the nasal mucosa (epistaxis), the eyes (conjunctivitis, reversible corneal opacities and intolerance to contact lenses).
Skin and Appendages Disorders: Exanthema, pruritus, dermatitis facialis, sweating, pyogenic granuloma, paronychia, nail dystrophy, increased formation of granulation tissue, persistent hair thinning, reversible alopecia, acne fulminans, hirsutism, hyperpigmentation, photosensitivity.
Musculoskeletal System Disorder: Muscle pain, joint pain, hyperostosis and other bone changes, tendinitis.
Psychiatric and Central Nervous System Disorders: Behavioral disorders, depression, headache, increased intracranial pressure, seizures.
Sensory Disorders: Isolated cases of visual disturbances, impaired hearing at certain frequencies, photophobia, dark adaptation disturbances (decreased night vision), lenticular cataract, keratitis.
Gastrointestinal System Disorders: Nausea, inflammatory bowel disease, eg colitis, ileitis and hemorrhage have been reported to occur.
Liver and Biliary System Disorders: Transitory and reversible increases in transaminases, some cases of hepatitis. In many such cases, the changes have been within the normal range and values have returned to baseline levels during treatment. In other cases, however, it has been necessary to reduce the dose or discontinue treatment with isotretinoin.
Respiratory System Disorders: Bronchospasm.
Disorders of the Blood: Decrease in white cell count, red blood cell parameters, increase or decrease in platelet count, elevated sedimentation rate.
Laboratory Findings: Increase in serum triglyceride and cholesterol levels, hyperuricemia. Decreases in HDL have also been observed, particularly at high dosages and in predisposed patients (with a family history of lipid-metabolism disorders, diabetes, obesity or alcoholism). These changes too, are dose-related, and values return to normal on reduction of the dosage or withdrawal of the drug. Every patient should be warned about the possible occurrence of adverse effects.
Resistance Mechanism Disorders: Local or systemic infections due to gram-positive microorganisms (Staphylococcus aureus).
Miscellaneous Reactions: Lymphadenopathy, hematuria, and proteinuria, pancreatitis (especially patients with high serum triglyceride levels (>800 mg) treated with isotretinoin are at risk of developing pancreatitis), vasculitis (eg. Wegener's granulomatosis).
Bleeding or inflammation of gums; cataracts or corneal opacities.
Sexual dysfunction including erectile dysfunction and decreased libido.

Concurrent therapy of isotretinoin and vitamin A must be avoided as symptoms of hypervitaminosis A may be intensified.
Rare cases of benign intracranial hypertension 'pseudotumor cerebri' have been reported after isotretinoin and after tetracyclines. Supplementary treatment with tetracyclines should therefore be avoided.
The effect of microdosed progesterone preparations may be diminished by interaction with isotretinoin. Therefore microdosed progesterone preparations should not be used.

Store below 25°C in a dry place, away from direct sunlight.

Acne Treatment Preparations

D10BA01 - isotretinoin ; Belongs to the class of systemic retinoid preparations used in the treatment of acne.

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