Aknetrent

ABSORICA is a retinoid indicated for the treatment of severe recalcitrant nodular acne in patients 12 years of age and older. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition, means “many” as opposed to “few or several” nodules. Because of significant adverse reactions associated with its use, ABSORICA should be reserved for patients with multiple severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, ABSORICA is indicated only for those female patients who are not pregnant, because ABSORICA can cause severe birth defects.

Limitations of Use

A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients. If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience with isotretinoin has shown that patients may continue to improve following treatment with isotretinoin. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth.

As a part of the iPLEDGE program, ABSORICA may only be administered to patients enrolled in the program.

Severe Recalcitrant Nodular Acne

Aknetrent (isotretinoin) is indicated for the treatment of severe recalcitrant nodular acne. Nodules are inflammatory lesions with a diameter of 5 mm or greater. The nodules may become suppurative or hemorrhagic. “Severe,” by definition,² means “many” as opposed to “few or several” nodules. Because of significant adverse effects associated with its use, Aknetrent (isotretinoin) should be reserved for patients with severe nodular acne who are unresponsive to conventional therapy, including systemic antibiotics. In addition, Aknetrent (isotretinoin) is indicated only for those female patients who are not pregnant, because Aknetrent (isotretinoin) can cause severe birth defects (see Boxed CONTRAINDICATIONS AND WARNINGS).

A single course of therapy for 15 to 20 weeks has been shown to result in complete and prolonged remission of disease in many patients.^1,3,4 If a second course of therapy is needed, it should not be initiated until at least 8 weeks after completion of the first course, because experience has shown that patients may continue to improve while off Aknetrent (isotretinoin). The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure).

Severe forms of acne (such as nodular or conglobate acne or acne at risk of permanent scarring) resistant to adequate courses of standard therapy with systemic anti-bacterials and topical therapy.

Severe forms of 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 therapy.

Aknetrent Gel is intended for use in the treatment of mild to moderate inflammatory and non-flammatory acne vulgaris.

Healthcare professionals who prescribe ABSORICA must be certified in the iPLEDGE program and must comply with the required monitoring to ensure safe use of ABSORICA.

The required laboratory testing must be completed prior to dosing ABSORICA.

Pregnancy Testing, and Contraceptive measures must be followed prior to dosing ABSORICA.

Recommended Dosage

The recommended dosage range for ABSORICA is 0.5 to 1 mg/kg/day given in two divided doses without regard to meals for 15 to 20 weeks (see Table 1). To decrease the risk of esophageal irritation, patients should swallow the capsules with a full glass of liquid.

The safety of once daily dosing with ABSORICA has not been established. Once daily dosing is not recommended.

Table 1: ABSORICA Dosing by Body Weight (Based on Administration With or Without Food)

Dosage Range

In trials comparing 0.1, 0.5, and 1 mg/kg/day, it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects, some of which may be dose-related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2 mg/kg/day, as tolerated.

Duration Of Use

A normal course of treatment is 15 – 20 weeks. If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of ABSORICA, even in low doses, has not been studied, and is not recommended. It is important that ABSORICA be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of ABSORICA on bone loss is unknown.

Laboratory Testing

Pregnancy Testing

Lipid Profile

Perform a fasting lipid profile including triglycerides prior to use of ABSORICA.

Liver Function Test

Perform liver function tests prior to use of ABSORICA.

Aknetrent (isotretinoin) should be administered with a meal (see PATIENT INFORMATION).

The recommended dosage range for Aknetrent (isotretinoin) is 0.5 to 1.0 mg/kg/day given in two divided doses with food for 15 to 20 weeks. In studies comparing 0.1, 0.5, and 1.0 mg/kg/day,⁸ it was found that all dosages provided initial clearing of disease, but there was a greater need for retreatment with the lower dosages. During treatment, the dose may be adjusted according to response of the disease and/or the appearance of clinical side effects — some of which may be dose related. Adult patients whose disease is very severe with scarring or is primarily manifested on the trunk may require dose adjustments up to 2.0 mg/kg/day, as tolerated. Failure to take Aknetrent (isotretinoin) with food will significantly decrease absorption. Before upward dose adjustments are made, the patients should be questioned about their compliance with food instructions.

The safety of once daily dosing with Aknetrent (isotretinoin) has not been established. Once daily dosing is not recommended.

If the total nodule count has been reduced by more than 70% prior to completing 15 to 20 weeks of treatment, the drug may be discontinued. After a period of 2 months or more off therapy, and if warranted by persistent or recurring severe nodular acne, a second course of therapy may be initiated. The optimal interval before retreatment has not been defined for patients who have not completed skeletal growth. Long-term use of Aknetrent (isotretinoin) , even in low doses, has not been studied, and is not recommended. It is important that Aknetrent (isotretinoin) be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of Aknetrent on bone loss is unknown (see WARNINGS: Skeletal: Bone Mineral Density, Hyperostosis, and Premature Epiphyseal Closure).

Contraceptive measures must be followed for any subsequent course of therapy (see PRECAUTIONS).

Table 4 : Aknetrent (isotretinoin) Dosing by Body Weight (Based on Administration With Food)

INFORMATION FOR PHARMACISTS

Access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866495-0654) to obtain an authorization and the “do not dispense to patient after” date. Aknetrent (isotretinoin) must only be dispensed in no more than a 30-day supply.

REFILLS REQUIRE A NEW PRESCRIPTION AND A NEW AUTHORIZATION FROM THE iPLEDGE SYSTEM.

An Aknetrent (isotretinoin) Medication Guide must be given to the patient each time Aknetrent (isotretinoin) is dispensed, as required by law. This Aknetrent (isotretinoin) Medication Guide is an important part of the risk management program for the patient.

Posology

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 a full understanding of the risks of isotretinoin therapy and monitoring requirements.

The capsules should be taken with food once or twice daily.

Paediatric Population

Aknetrent should not be used for the treatment of prepubertal acne and is not recommended in children less than 12 years of age due to a lack of data on efficacy and safety.

Adults including adolescents and the elderly:

Isotretinoin therapy should be started at a dose of 0.5 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 0.5-1.0 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 that no substantial additional benefit is to be expected beyond a cumulative treatment dose of 120-150 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 clearing of the acne is obtained with a single treatment course. In the event of a definite relapse a further 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 renal impairment

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 until the patient is receiving the maximum tolerated dose.

Patients with intolerance

In patients who show severe intolerance to the recommended dose, treatment may be continued at a 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.

Posology

Aknetrent 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 a full understanding of the risks of Aknetrent therapy and monitoring requirements.

The capsules should be taken with food once or twice daily.

Adults including adolescents and the elderly:

Aknetrent therapy should be started at a dose of 0.5 mg/kg daily. The therapeutic response to Aknetrent 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 0.5-1.0 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 that no substantial additional benefit is to be expected beyond a cumulative treatment dose of 120-150 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 clearing of the acne is obtained with a single treatment course. In the event of a definite relapse a further course of Aknetrent 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 renal impairment

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 until the patient is receiving the maximum tolerated dose.

Paediatric population

Aknetrent is not indicated for the treatment of prepubertal acne and is not recommended in patients less than 12 years of age due to a lack of data on efficacy and safety.

Patients with intolerance

In patients who show severe intolerance to the recommended dose, treatment may be continued at a 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.

Method of administration

Oral use.

Adults and adolescents

Apply Aknetrent Gel sparingly over the entire affected area once or twice daily, preferably after washing and drying the skin.

If undue irritation (redness, peeling, or discomfort) occurs, patients should reduce frequency of application or temporarily interrupt treatment. The normal frequency of application should be resumed once the irritation subsides. Treatment should be discontinued if the irritation persists.

Patients should be advised that 6-8 weeks of treatment may be required before the therapeutic effect is observed.

Patients should wash their hands after application of Aknetrent Gel.

Patients should be advised that excessive application will not improve efficacy, but may increase the risk of skin irritation.

This product is flammable. Keep the gel away from open fire and flames and all sources of ignition during and immediately after you've used it

Use in Children

The safety and efficacy of topical isotretinoin in children prior to puberty have not been established, therefore isotretinoin is not recommended for use in this population.

Use in the Elderly

No specific recommendations as acne vulgaris rarely presents in the elderly.

Pregnancy

ABSORICA can cause fetal harm when administered to a pregnant woman. Major congenital malformations, spontaneous abortions, and premature births have been documented following pregnancy exposure to isotretinoin in any amount and even for short periods of time. ABSORICA is contraindicated in females who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued and the patient should be apprised of the potential hazard to the fetus.

Hypersensitivity

Hypersensitivity to this product (or Vitamin A, given the chemical similarity to isotretinoin) or to any of its components.

Pregnancy

Category X. See Boxed CONTRAINDICATIONS AND WARNINGS.

Allergic Reactions

Aknetrent (isotretinoin) is contraindicated in patients who are hypersensitive to this medication or to any of its components. Aknetrent (isotretinoin) should not be given to patients who are sensitive to parabens, which are used as preservatives in the gelatin capsule (see PRECAUTIONS: Hypersensitivity).

Isotretinoin is contraindicated in women who are pregnant or breastfeeding.

Isotretinoin is contraindicated in women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met.

Isotretinoin is also contraindicated in patients

- With hepatic insufficiency

- With excessively elevated blood lipid values

- With hypervitaminosis A

- Receiving concomitant treatment with tetracyclines.

Aknetrent is contraindicated in women who are pregnant or breast-feeding.

Aknetrent is contraindicated in women of childbearing potential unless all of the conditions of the Pregnancy Prevention Programme are met.

Aknetrent is also contraindicated in patients

With hepatic insufficiency

With excessively elevated blood lipid values

With hypervitaminosis A

With hypersensitivity to Aknetrent or to any of the excipients

Receiving concomitant treatment with tetracyclines

Allergic to peanut or soya oil as Aknetrent contains soya-bean oil

Aknetrent Gel is contraindicated in pregnancy and lactation.