Isosupra

Brand Name

Isosupra

Generic name

Isotretinoin 

Dosage Form

Hard capsule, Lidose: 16mg

Brand Name

Isosupra

Generic name

Isotretinoin

Dosage Form

Hard capsule, Lidose: 16mg

Indication & Usage

Isosupra is a Retinoic Acid Derivative product that is indicated for sever forms of acne (such as nodular or conglobate acne or acne at risk of permanent scanning) resistant to adequate courses of standard therapy with systemic anti-bacterials and topical therapy.

Dosage & Administration

Isotretinoin should only be prescribed by or under the supervision of physicians with expertise in the use of systemic retinoids for the treatment of severe acne and full understanding of the risk of Isotretinoin therapy and monitoring requirements.

The capsule should be taken with food once or twice daily. Isotretinoin bioavailability increased if taken with food or milk.

Adult including adolescents and elderly:

Isotretinoin therapy should be started at a dose of 0.4 mg/kg daily. The therapeutic response to isotretinoin and some of the adverse effects are dose-related and vary between patients. This necessitates individual dosage adjustment during therapy. For most patients, the dose ranges from 0.4 and 0.8 mg/kg per day.

Long-term remission and relapse rates are more closely related to the total dose administered than to either duration of treatment or daily dose. It has been shown than no substantial additional benefit is to be expected beyond a cumulative treatment dose of 96-120 mg/kg. The duration of treatment will depend on the individual daily dose. A treatment course of 16-24 weeks is normally sufficient to achieve remission.

In the majority of patients, complete of the acne is obtained with a single treatment course. In the event of a definite relapse a future course of isotretinoin therapy may be considered using the same daily dose and cumulative treatment dose. As further improvement of the acne can be observed up to 8 weeks after discontinuation of treatment, a further course of treatment should not 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: 8 mg/day). The dose should then be increased up to 0.8 mg/kg/day, or until the patient is receiving the maximum tolerated dose.

Children:

Isotretinoin 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, treatment may be continued at lower dose with the consequences of a longer therapy duration and a higher risk of relapse. In order to achieve the maximum possible efficacy in these patients the dose should normally be continued at the highest tolerated dose.

Adverse reactions

Very common (≥1/10):

Blood and lymphatic system disorders; Thrombocytopenia, anaemia, thrombocytosis, red blood cell sedimentation rate increased

Eye disorders; Blepharitis, conjunctivitis, dry eye, eye irritation

Hepatobiliary disorders; Transaminase increased

Skin and subcutaneous tissues disorders; Pruritus, rash erythematous, dermatitis, cheilitis, dry skin, localized exfoliation, skin fragility (risk of frictional trauma)

Musculo-skeletal and connective tissue disorders; Arthralgia, myalgia, back pain (particularly in children and adolescent patients)

Investigations; Blood triglycerides increased, high density lipoprotein decreased

Common (≥1/100% to 1/10):

Blood and lymphatic system disorders; Neutropenia

Nervous system disorders; Headache

Respiratory, thoracic and mediastinal disorders; Nasopharyngitis, epistaxis, nasal dryness

Investigations; Blood cholesterol increased, blood glucose increased, hematuria, proteinuria

Rare (≥1/10,000 to <1/1,000):

Immune system disorders; Anaphylactic reactions, hypersensitivity, allergic skin reaction

Psychiatric disorders; Depression, depression aggravated, aggressive tendencies, anxiety, mood alterations.

Skin and subcutaneous tissues disorders; Alopecia

Very Rare (< 1/10,000):

Infections; Gram positive (mucocutaneous) bacterial infection

Blood and lymphatic system disorders; Lymphadenopathy

Metabolism and nutrition disorders; Diabetes mellitus, hyperuricemia

Psychiatric disorders; Suicide, suicide attempt, suicidal ideation, psychotic disorder, abnormal behavior

Nervous system disorders; benign intracranial hypertension, convulsions, drowsiness, dizziness

Eye disorders; Papilloedema (as sign of benign intracranial hypertension), cataract, colour blindness (color vision deficiencies), contact lens intolerance, corneal opacity, decreased night vision, keratitis, photophobia, visual disturbances, blurred vision.

Ear and labyrinth disorders; Hearing impaired

Vascular disorders; Vasculitis (for example Wegener's granulomatosis, allergic vasculitis)

Respiratory, thoracic and mediastinal disorders; Bronchospasm (particularly in patients with asthma), hoarseness

Gastrointestinal disorders; Inflammatory bowel disease, colitis, ileitis, pancreatitis, gastrointestinal haemorrhage, haemorrhagic diarrhoea, nausea dry throat

Hepatobiliary disorders; Hepatitis

Skin and subcutaneous tissues disorders; Acne fulminans, acne aggravated (acne flare), erythema (facial), exanthema, hair disorders, hirsutism, nail dystrophy, paronychia, photosensitivity reaction, pyogenic granuloma, skin hyperpigmentation, sweating increased

Musculo-skeletal and connective tissue disorders; Arthritis, calcinosis (calcification of ligaments and tendons), epiphyses premature fusion, exostosis, (hyperostosis), reduced bone density, tendonitis

Renal and urinary disorders; Glomerulonephritis

General disorders and administration site conditions; Granulation tissue (increased formation of), malaise

Investigations; Blood creatine phosphokinase increased

Not known (Frequency not defined):

Cardiovascular: Cerebrovascular accident, chest pain, edema, flushing, palpitations, syncope, tachycardia, thrombosis

Central nervous system; Aggressive behavior, attempted suicide, depression, dizziness, drowsiness, emotional lability, fatigue, headache, insomnia, lethargy, malaise, nervousness, paresthesia, pseudo tumor cerebri, psychosis, seizure, suicidal ideation, vasculitis (renal), violent behavior

Dermatologic; Acne fulminans, allergic skin reaction, alopecia, cheilitis, diaphoresis, eczema, eruptive xanthoma, facial erythema, hair disease, hirsutism, hyperpigmentation, hypopigmentation, nail disease, paronychia, pruritus, pyogenic granuloma, scaling of skin of feet, skin atrophy, skin photosensitivity, skin rash, sunburn (increased susceptibility), superficial peeling of palms, xeroderma

Endocrine & metabolic; Decreased HDL cholesterol, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum cholesterol, increased serum glucose, hyperuricemia, menstrual disease, weight loss

Gastrointestinal; Colitis, esophagitis, esophageal ulcer, gastrointestinal symptoms (nonspecific), gingival hemorrhage, gingivitis, inflammatory bowel disease, nausea, pancreatitis, xerostomia

Genitourinary; Genitourinary disease (nonspecific findings), hematuria, proteinuria, pyuria

Hematologic & oncologic; Anemia, bruise, lymphadenopathy, neutropenia, purpura, and thrombocytopenia

Hepatic; Increased serum alkaline phosphatase, increased serum ALT, increased serum AST, hepatitis

Hypersensitivity; Anaphylaxis, hypersensitivity reaction

Infection; Herpes simplex infection (disseminated), infection

Neuromuscular & skeletal; Arthralgia, arthritis, bone disease, calcification of ligament, calcification of tendon, decreased bone mineral density, increased creatine phosphokinase, myalgia, premature epiphyseal closure, skeletal hyperostosis, tendonitis, weakness

Ophthalmic; Cataract, corneal opacity, keratitis, nocturnal amblyopia, optic neuritis, photophobia, vision color changes, visual disturbance

Otic; Auditory impairment, tinnitus

Renal; Glomerulonephritis

Respiratory; Bronchospasm, dry nose, epistaxis, respiratory tract infection, voice disorder, Wegener's granulomatosis

Miscellaneous; Wound healing impairment

<1%, post marketing, and/or case reports:

Agranulocytosis, contact lens intolerance, decreased visual acuity, dry eye syndrome, erythema multiform, eye pain, eyelid disease (Meibomian gland dysfunction/atrophy; Neudorfer 2012), myopia, rhabdomyolysis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Contraindications

Isotretinoin is contraindicated in women who are pregnant or breastfeeding.

Isotretinoin is contraindicated in women of childbearing potential unless all the condition of the pregnancy prevention program are met.

Isotretinoin is also contraindicated in patient with hypersensitivity to isotretinoin or to any of excipients. Isosupra contains soya oil. Therefore, Isosupra is contraindicated in patients allergic to peanut or soya.

Isotretinoin is also contraindicated in patients:

  • With hepatic insufficiency
  • With excessively elevated blood lipid values
  • With hypervitaminosis A
  • Receiving concomitant treatment with tetracyclines

Drug interactions

  • Vitamin A: Patients should not take vitamin A as concurrent medication due to the risk of developing hypervitaminosis A. Risk X: Avoid combination
  • Tetracyclines: Cases of benign intracranial hypertension (pseudotumor cerebri) have been reported with concomitant use of isotretinoin and tetracyclines. Therefore, concomitant treatment with tetracyclines must be avoided.
  • Concurrent administration of isotretinoin with topical keratolytic or exfoliative anti-acne agents should be avoided as local irritation may increase.
  • Alcohol: May enhance the adverse/toxic effect of Isotretinoin (Systemic). Specifically, the risk for elevated triglyceride concentrations may be increased. Risk C: Monitor therapy
  • Aminolevulinic Acid (Systemic & Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic).
  • Estrogen Derivatives (Contraceptive): Retinoic Acid Derivatives may diminish the therapeutic effect of Estrogen Derivatives (Contraceptive). Two forms of contraception are recommended in females of child-bearing potential during retinoic acid derivative therapy.

Warnings & Precautions

Pregnancy prevention program

The medicinal product is TERATOGENIC.

Isotretinoin is contraindicated in women of childbearing potential unless the following conditions of the pregnancy prevention program are met.:

  • She understands the teratogenic risk
  • She understands the need for rigorous follow-up, on a monthly basis.
  • She understands and accepts the need for effective contraceptive contraception, without interruption, 1 month before starting treatment, throughout the duration of treatment and 1 month after the end of treatment. At least one and preferably two complementary forms of contraception including a barrier method should be used.
  • Even if she has amenorrhea she must follow all of the advice on effective contraception.
  • She should be capable of complying with effective contraceptive measures.
  • She is informed and understand the potential consequences of pregnancy and the need to rapidly consult if there is a risk of pregnancy.
  • She understands the need and accepts to understand the need and accepts to undergo pregnancy testing before, during and 5 weeks after the end of treatment.
  • She has acknowledged that she has understood the hazards and necessary precautions associated with the use of isotretinoin.

The conditions also concern women who are not currently sexually active unless the prescriber considers that there are compelling reasons to indicate that there is no risk of pregnancy.

The prescriber must ensure that:

  • The patient complies with the conditions for pregnancy prevention as listed above, including confirmation that she has adequate level of understanding.
  • The patient has acknowledged the aforementioned conditions.
  • The patient has obey the pregnancy protection program.
  • Negative pregnancy test results have been obtained before, during and 5 week after the end of treatment. The dates and results of pregnancy test should be documented.

Pregnancy testing:

According to local practice, medically supervised pregnancy tests with a minimum sensitivity 25mIU/ml are recommended to be performed in the first 3 days of the menstrual cycle, as follows.

Prior to starting therapy:

In order to exclude the possibility of pregnancy prior to starting contraception, it is recommended that an initial medically supervised pregnancy test should be performed and its date and result recorded. In patients without regular menses, the timing of this pregnancy test should reflected the sexual activity of the patient and should be undertaken approximately 3 weeks after the patient last had unprotected sexual intercourse. The prescriber should educate the patient about contraception.

A medically supervised pregnancy test should also be performed during the consultation when isotretinoin is prescribed or in the 3 days prior to the visit to prescriber, and should have been delayed until the patient had been using effective contraception for at least 1 month. This test should ensure the patient is not pregnant when she starts treatment with isotretinoin.

Follow up visit:

Follow up visits should be arranged 28 days intervals. The need for repeated medically supervised pregnancy tests every month should be determined according to local practice including consideration of the patient’s sexual activity and recent menstrual history (abnormal menses, missed periods and amenorrhea). Where indicated, follow up pregnancy tests should be performed on day of the prescribing visit or in the 3 days prior to the visit to prescriber.

End of treatment:

Five weeks after stopping treatment, women should undergo a final pregnancy test to exclude pregnancy.

Prescribing and dispending restrictions:

Prescriptions of isotretinoin for women of childbearing potential should be limited to 30 days of treatment and continuation of treatment requires a new prescription. Ideally, pregnancy testing, issuing a prescription and dispending of isotretinoin should occur on the same day. Dispending of isotretinoin should occur within a maximum of 7 days of the prescription.

Male patients:

The available data suggest that the level of maternal exposure from the semen of the patient receiving isotretinoin, is not a sufficient magnitude to be associated with the teratogenic effect of isotretinoin.

Male patients should be reminded that they must not share their medication with anyone, particularly not females.

Additional precautions:

Patients should not donate blood during therapy and for 1 month following discontinuation of isotretinoin because of the potential risk to a foetus of a pregnant transfusion recipient.

Psychiatric disorders:

Depression, depression aggravated, anxiety, aggressive tendencies, mood alteration, psychotic symptoms and very rarely, suicidal ideation, suicide attempts and suicide have been reported in patients treated with isotretinoin. Particular care needs to be taken in 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 alleviate symptoms and therefore further psychiatric of psychological evaluation may be necessary.

Skin and subcutaneous tissues disorders:

Acute exacerbation of acne is occasionally seen during the initial period but this subsides with continued treatment, usually within 7-10 days, and usually does not require dose adjustment.

Exposure to intense sunlight or to UV rays should be avoided. Where necessary a sun-protection product with a high protection factor of at least SPF 15 should be used.

Aggressive chemical dermabrasion and cutaneous laser treatment should be avoided in patients on isotretinoin for a period of 5-6 months after the end of treatment because of the risk of hypertrophic scarring in atypical areas and more rarely post inflammatory hyper or hypopigmentation in treated areas. Wax depilation should be avoided in patients on isotretinoin for at least a period of 6 months after treatment because of the risk of epithelial stripping.

Concurrent administration of isotretinoin with topical keratolytic or exfoliative anti-acne agents should be avoided as local irritation may increase.

Patients should be advised to use a skin moistening ointment or cream and lip balm from the start of treatment as isotretinoin is likely to cause dryness of the skin and lips. Patient should be advised of the signs and symptoms and monitored closely for sever skin reactions (e.g. erythema multiform, Steven-Johnson syndrome and toxic epidermal necrolysis). If any sever skin reaction is suspected, isotretinoin treatment should be discontinued.

Eye disorder:

Dry eyes, corneal opacities, decreased night vision and keratitis usually resolve after discontinuation of therapy. Intolerance to the contact lenses may occur. Patients experiencing visual difficulties should refer to an expert ophthalmological opinion. Withdrawal of isotretinoin may be necessary.

Musculo-skeletal and connective tissue disorders:

Myalgia, arthralgia, and increase serum creation phosphokinase values have been reported in patients receiving isotretinoin particularly in those undertaking vigorous physical activity.

Bone changes including premature epiphyseal closure, hyperostosis and calcification of tendons and ligaments have accrued after several years old administration at very high doses for treating disorders of keratinization. The dose level, duration of treatment and total cumulative dose in these patients generally exceeded those recommended for the treatment of acne.

Benign intracranial hypertension:

Cases of benign intracranial hypertension has been reported, some of which involved concomitant use of tetracyclins. Signs and symptoms include nausea and vomiting, visual disturbances and papilledema. Patients develop benign intracranial hypertension should discontinue isotretinoin.

Hepatobiliary disorders:

Liver enzymes should be checked before treatment, 1 month after start of treatment and subsequently at 3 monthly intervals unless more frequent monitoring is clinically indicated. Transient and reversible increases in liver transaminase have been reported. In many cases these changes have been within normal range and values have returned to base line levels during treatment. However, in the event of persistent clinically relevant evaluation of transaminase levels, reduction of the dose or discontinuation of the treatment should be considered.

Renal insufficiency:

Renal insufficiency and renal failure do not affect the pharmacokinetics f isotretinoin. Therefore, isotretinoin can be given to patients with renal insufficiency. However, it is recommended that patients are started on a low dose and titrated up to the maximum tolerated dose.

Lipid metabolism:

Serum lipid (fasting value) should be checked before treatment 1 month after the start of treatment, and subsequently at 3 monthly intervals unless more frequent monitoring is clinically indicated. Elevated serum lipid values usually returns to normal on reduction of the dose or discontinuation of treatment and may also respond to dietary measures.

Isotretinoin has been associated with an increase in plasma triglyceride levels. It should be discontinued if hyperglyceridemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur. Levels in excess of 8g/L or 9 mmol/L are sometimes associated with acute pancreatitis which may be fatal.

Gastrointestinal disorders:

Isotretinoin has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. Patients experiencing severe (hemorrhagic) diarrhea should discontinue isotretinoin immediately.

Allergic reaction:

Anaphylactic reaction have been rarely reported, in some cases after previous topical exposure to retinoids. Allergic cutaneous reactions are reported infrequently. Serious cases of allergic vasculitis, often with purpura (bruises and red patches) of the extremities and extracutaneous involvement have been reported. Severe allergic reactions necessitate interruption of therapy and careful monitoring.

High risk patients:

In patients with diabetes, obesity, alcoholism or a lipid metabolism disorder undergoing treatment with isotretinoin, more frequent checks of serum values for lipids and/or blood glucose may be necessary. Elevated fasting blood sugar have been reported, and new cases of diabetes have been diagnosed during isotretinoin therapy.

Effects on ability to drive and use machines:

A number of cases of decreased night vision have occurred during isotretinoin therapy and in rare instances have persisted after therapy. Because the onset in some patients was sudden, patients should be advised of this potential problem and warned to be cautious when driving or operating machines.

Drowsiness, dizziness and visual disturbances have been reported very rarely. Patients should be warned that if they experience these effects, they should not drive, operate machinery or take part in any other activities where the symptoms could put either themselves or others at risk.

Pregnancy & Lactation

Pregnancy Category X.

Isotretinoin must not be used by women and adolescents who are pregnant or who may become pregnant. There is an extremely high risk that severe birth defects can result if pregnancy occurs while taking isotretinoin in any amount, even for short periods of time. Potentially, any fetus exposed during pregnancy can be affected. There are no accurate means of determining whether an exposed fetus has been affected.

Birth defects that have been documented following isotretinoin exposure include abnormalities of the face, eyes, ears, skull, CNS, cardiovascular system, and thymus and parathyroid glands. Cases of intelligence quotient (IQ) scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion, and premature births have been reported.

Documented external abnormalities include skull abnormality; ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (including microphthalmia); facial dysmorphia; cleft palate. Documented internal abnormalities include CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency. In some cases, death has occurred with some of the abnormalities previously noted.

If pregnancy does occur during treatment of a female patient who is taking isotretinoin, isotretinoin must be discontinued immediately and she should be referred to an obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling.

It is not known if isotretinoin is present in breast milk.

Storage condition

Keep in a cool and dry place, below 25°C

Packaging

Hard capsules supplied in a pack of 30

License Holder

SMB laboratories/ Belgium

Marketing Authorization Holder in IRAN

Koushan Pharmed

 

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    • Tel: +98 2188197145
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