ISOTEEN Capsule

For the treatment of severe nodulocystica acne. The drug should be reserved for patients who are unresponsive to conventional acne therapies.

Dosage and administration

- Initial dose: 0.5mg/kg daily given for 4 weeks. Because efficacy and adverse effects are variable according to patients, observe patients’ condition during administering.

- Maintenance dose: 0.5-1mg/kg day according to patients. 1.0mg/kg/day as maximum dose should be only administered within limited duration.

- The usual duration of a course of Isotretinoin therapy in the treatment is 16 weeks. Symptoms may take a turn for the better after discontinuance of treatments. A second course of therapy may be initiated if cystic acne persists; however, at least 8 weeks should elapse between courses to assess the degree of improvement and the need for further therapy.

- In case of low dose, one time a day. In case of high dose, Isotretinoin is given in divided doses a day during a meal.

1) Pregnant women, nursing mother and women suspected of being pregnant

2) Patients with renal and hepatic disorder

3) Patients with hypervitaminosis A

4) Patients with hyperlipidemia

5) Patients who are hypersensitive to this drug and its ingredient

(See the package insert about the details.)

Most adverse effect occur in relation to the dose. Tolerance is satisfactory in the administration of adequate dose. Adverse effect was eliminated by discontinuance of administration and decrease of dose.

1) Hypervitaminosis A

2) Skin

3) Musculoskeletal

4) Pseudo tumor Cerebri

5) Sensimeter

6) Gastrointestinal

7) Liver and biliary system

8) Respiratory

9) Others

10) Peeling skin in the palm and plantar, skin infection, non-specific genitourinary findings, nonspecific gastrointestinal symptoms and increased sensitivity to fatigue and burns

11) When high dose was administered to patients in clinical trials for other disease except acne. A high prevalence of skeletal hyperostosis has been reported in children and adults. Minimal skeletal hyperostosis has also been observed in nodular acne patients treated with a single course (16 weeks) of therapy at recommended doses. This drug should be administered to patients with severe disease, only if he therapeutic benefits are estimated to outweigh any possible risks.

12) Spinal hyperostosis, calcification of spinal ligament and spinal compression have been observed in one patient who takes etretinate (it is retinoids) for several years. It should not be used for long-term therapy. Also it is used improperly for long time, these adverse effect occur.

13) The following adverse effects have been reported in the not more than 1% out of patients. However, correlation with this drug is not clear: hypopigmentation, rubeosis, hives, contusion, simple herpes, edema, hairy disorder, respiratory infection, weight loss, erythema nodosum, nail growth disorder, gingival bleeding, gingivitis, menstration disorder, optic neuritis, blepharitis, anemia, tremor cordis, tachycardia, sweat, syrigmus, voice change, emotionally unstable, dizziness, necrosis, somnolence, malaise, invalid, insomnia and paresthesia.

14) Depression has been rarely reported. No mechanism of action has been established. Make an observation carefully and if necessary, take an adequate measure.

15) Xerophthalmos in connection with keratitis has been rarely reported. So, in case of xerophthalmos, monitor whether or not keratitis reveals.

See the package insert about the details below.

1) Vitamin A: patients should be advised against taking vitamin A to avoid additive toxic effects.

2) Tetracyclines: should be avoided.

Teratogenicity of Isotretinoin is very high. Therefore, Isotretinoin must not be used by females who are pregnant or who may become pregnant while undergoing treatment. Although not every fetus exposed to Isotretinoin has resulted in a deformed child, there is an extremely high risk that a deformed infant 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.

Isotretinoin is contraindicated in females of childbearing potential unless the patient meets all of the following conditions:

Must have severe disfiguring nodular acne that is recalcitrant to standard therapies

Must be reliable in understanding and carrying out instructions

Must be capable of complying with the mandatory contraceptive measures

Must have received warnings of possibility of contraception failure and the hazards of taking Isotretinoin during pregnancy and within 1 month after the end of treatment

Must understand the upper caution

Must have a negative serum or urine pregnancy test within 11 days prior to the beginning treatment (Repeat the pregnancy test ad consultation about the contraception monthly. For realizing this, physician should not prescribe more than one medicine for one month)

Effective contraception must be used for at least 1 month before beginning treatment, during treatment, and for 1 month following discontinuation of treatment.

Treatment should be initiated in the second or third day of normal menstrual cycle.

In case of recurrence of symptoms, effective contraception must be used from 1 month before the beginning treatment to 1 month of discontinuance of treatment thereafter.

In case of patients who prevent conception or don’t have sexual relations because of sterility, it is recommended that patient prevent conception according to the upper condition while undergoing treatment. Patient must get the enough information about contraception.

In spite of these warnings, in case of being pregnant while undergoing treatment of within one month after the end of treatment, danger of deformed fetus (especially deformation of CNS, heart and large vessel) is very high. Cases of IQ scores less than 85 with or without obvious CNS abnormalities have been also reported. There is an increased risk of spontaneous abortion. If a pregnancy does occur during treatment, the prescriber and patient should discuss the desirability of continuing the pregnancy.

Major human fetal abnormalities related to this drug administration have been documented: hydrocephalus, microcephaly, external ear abnormalities (anotia, micropinna, small or absent external auditory canals), microphthalmia, cardiovascular abnormalities, facial dysmorphia, cleft palate, thymus gland abnormality, parathyroid hormone deficiency.

1) This drug should be prescribed only by prescribers who have special competence in the diagnosis and treatment of severe recalcitrant nodular acne are experienced in the use of systemic retinoids, and understand the risk of teratogenicity if these drugs is used during pregnancy.

1) If elevations of serum triglycerides in excess of 800mg/dL are occurred, acute pancreatitis occur. Therefore, control of elevations of serum triglycerides is recommended. If serum triglycerides is not controlled or acute pancreatitis occur, discontinue the administration of this drug.

2) This drug may cause depression, psychosis, rarely suicidal ideation and suicide attempts. No mechanism of action has been established, but take care of patients who have history of depression and make an observation carefully, if necessary, take an adequate measure.

3) Symptoms may get worse during a short period of time in the early therapy.

4) Concomitant use with epidermolysis or keratolysis treatment and ultraviolet therapy should be avoided, but, concomitant use with mild external agent can be used.

5) Patients must have a liver function test and serum triglyceride test for at least some day before beginning therapy, during therapy every 3 months, and after treatment during 1 month. Dangerous patients who have diabetes, obesity, alcoholism or lipid metabolism disorder must have move test.

6) It is desirable that blood glucose of patients who are diagnosed the case as diabetes or are suspected of taking diabetes should be examined.

7) Patients should not donate blood during therapy and for 1month following discontinuance of the drug because the blood might be given to other people.

8) Patients may experience decreased tolerance to contact lenses during therapy.

9) In case that high dose is administered for years, premature epiphyseal closure may occur. It is recommendable not to administer this product if sufficient therapeutic effect may be expected with other therapy.

10) Muscle pain and arthralgia may increase. This may be in connection with decrease of tolerance of active activity. (Elevation of serum CPK concentration has been reported in patients with active activity).

11) It is not desirable to administer progesterone (micro dose) as contraceptive method during therapy.

12) Patients should avoid severe excoriation for 5-6 months, because hypertrophic cicatrix may occur at nonspecific region.

13) Because of danger of scar and dermatitis, avoid the waxing during therapy and for 5-6 months after discontinuance of therapy.

14) Night vision was decreased during treatment and these conditions was rarely persisted after discontinuance of treatment. Because the onset in some patients was sudden, patients should be advised of this potential problem, and should be warned to be cautious when patients drive or operate any vehicle at night.

15) This drug has been associated with inflammatory bowel disease in patient without a prior history of intestinal disorder. It should be discontinued in patients who have experienced abdominal pain, rectal bleeding or severe diarrhoea.

16) Anaphylactic reactions have been reported in patients who are exposed at retinoid locally. Allergic reactions have been rarely reported. Cutaneous allergic reactions and serious cases of allergic vasculitis, often with purpura of extremities and extra cutaneous involvement have been reported. If allergic reaction occurs, discontinue the treatment and monitor carefully.