Urgent advice: Call your doctor or go to A&E straight away if you take too much Tretin - even if you have no symptoms
If you need to go to your nearest A&E department, take the Tretin packet or leaflet inside it plus any remaining medicine with you.
DOSAGE AND ADMINISTRATION
Accutane (Tretin) should be administered with a meal (see PATIENT INFORMATION).
The recommended dosage range for Accutane (Tretin) 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 Accutane (Tretin) 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 Accutane (Tretin) 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 Accutane (Tretin) , even in low doses, has not been studied, and is not recommended. It is important that Accutane (Tretin) be given at the recommended doses for no longer than the recommended duration. The effect of long-term use of Accutane 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 : Accutane (Tretin) 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. Accutane (Tretin) 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 Accutane (Tretin) Medication Guide must be given to the patient each time Accutane (Tretin) is dispensed, as required by law. This Accutane (Tretin) Medication Guide is an important part of the risk management program for the patient.
Inflammatory Bowel Disease
Accutane (Tretin) has been associated with inflammatory bowel disease (including regional ileitis) in patients without a prior history of intestinal disorders. In some instances, symptoms have been reported to persist after Accutane (Tretin) treatment has been stopped. Patients experiencing abdominal pain, rectal bleeding or severe diarrhea should discontinue Accutane immediately (see ADVERSE REACTIONS: Gastrointestinal).
Impaired hearing has been reported in patients taking Accutane (Tretin) ; in some cases, the hearing impairment has been reported to persist after therapy has been discontinued. Mechanism(s) and causality for this event have not been established. Patients who experience tinnitus or hearing impairment should discontinue Accutane (Tretin) treatment and be referred for specialized care for further evaluation (see ADVERSE REACTIONS: Special Senses).
Tretin and Hair Loss
One major side effect of Tretin is that it dries tissues, causing dry skin, cracked lips, dry mucous membranes, and dry scalp.
It may thin hair or cause it to become dry, brittle, and fragile.
This happens because Tretin slows down or blocks the production and secretion of the body's on own natural oils.
According to anecdotal reports, Tretin may not only thin hair on the head but also on the face, causing a loss of eyelashes and eyebrows.
Some people may become bald.
Although hair may regrow a few months after stopping Tretin, some people report that it took several years.
Others say Tretin caused permanent hair loss.
Clinical Trials and Postmarketing Surveillance
The adverse reactions listed below reflect the experience from investigational studies of Accutane (Tretin) , and the postmarketing experience. The relationship of some of these events to Accutane (Tretin) therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving Accutane (Tretin) are similar to those described in patients taking very high doses of vitamin A (dryness of the skin and mucous membranes, eg, of the lips, nasal passage, and eyes).
Serious side effects
Serious side effects are rare and happen in less than 1 in 1,000 people.
Stop taking Tretin capsules and call a doctor straight away if you get:
- anxiety, aggression and violence, changes in mood, or suicidal thoughts - these can be signs of depression or other mental health problems
- severe pain in your stomach with or without diarrhoea, feeling or being sick (nausea or vomiting) - these can be signs of a serious problem called pancreatitis
- bloody diarrhoea – this may be a sign of gastrointestinal bleeding
- a serious skin rash that peels or has blisters - the skin rash may come with eye infections, ulcers, a fever, and headaches
- difficulty moving your arms or legs, and painful, swollen or bruised areas of the body, or dark pee - these can be signs of muscle weakness
- yellow skin or the whites of your eyes turn yellow, difficulty peeing, or feeling very tired - these are signs of liver or kidney problems
- a bad headache that doesn't go away and makes you feel sick or be sick
- sudden changes in eyesight, including not seeing as well at night
It's very rare, but Tretin capsules can sometimes cause depression or make it worse, and even make people feel suicidal.
Men and Tretin capsules
Men can safely take Tretin capsules if they and their partner are trying for a baby, or their partner is pregnant.
Tretin capsules don't seem to damage sperm. Only tiny amounts of Tretin get into semen, which is too little to harm the unborn baby.
Clinical studies of Tretin did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Although reported clinical experience has not identified differences in responses between elderly and younger patients, effects of aging might be expected to increase some risks associated with Tretin therapy (see WARNINGS and PRECAUTIONS).
5. Katz RA, Jorgensen H, Nigra TP. Elevation of serum triglyceride levels from oral Tretin in disorders of keratinization. Arch Dermatol 116:1369-1372, 1980.
6. Ellis CN, Madison KC, Pennes DR, Martel W, Voorhees JJ. Tretin therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol 10:1024-1029, 1984.
- Vitamin A: Because of the relationship of Accutane (Tretin) to vitamin A, patients should be advised against taking vitamin supplements containing vitamin A to avo >REFERENCES
7. Dicken CH, Connolly SM. Eruptive xanthomas associated with Tretin (13-cis-retinoic acid). Arch Dermatol 116:951-952, 1980.
What are the reasons for a slow response to Tretin?
Analysis of slow responders to Tretin shows that the cause is due to the presence of macrocomedones in the majority of cases 70%, although hyperandrogensim may also play a part in resistance to Tretin therapy. 48
An early post Tretin flare, 48 poor absorption, possibly differences in receptor sensitivity, colonization with Staphylococcal aureus, severe acne and unusual variants account for 25% of poor responders and the cause of poor response is unknown in about 5%.
Macrocomedones may be subtle and should be detected under a suitable lamp with the skin stretched. They should be identified before systemic Tretin is started as an acute flare of acne may ensue if left untreated before embarking on Tretin. 48 Treatment requires light cautery or hyfrecation. A local anaesthetic cream should be applied to the lesions for the requisite time beneath an occlusive dressing and then the lesions touched gently with light cautery 49 or hyfrecation. This procedure should initially be performed on a test area of 10 cm 2 , to ensure that the patient does not develop scarring or hypo- or hyperpigmentation.
When macrocomedones are not the cause of poor response, the dosage of Tretin should be carefully considered as some patients will suffer a deterioration in their acne at the start of a course of Tretin. 50 If the poor response or worsening acne is thought to be due to an early post Tretin flare which is well reported, an antibiotic can be used in combination with Tretin such as erythromycin 1 g daily or trimethoprim 200–300 mg b.d. 50 Tetracyclines should be avoided in combination with Tretin due to a possible increased risk of benign intracranial hypertension. 51
If the acne is very inflammatory, then a significant reduction in the dose of Tretin and addition of oral steroids may be required (e.g. 0.5–1.0 mg/kg/day for 2–3 weeks). In other patients it may be appropriate to increase the dose of Tretin providing that the side effects are tolerated.
Some patients do not appear to metabolize Tretin as well as others and therefore may require higher doses. Adherence to therapy must also be considered. Mucocutaneous side effects particularly cheilitis are usually a good measure of absorption.
Unusual variants may lead to slow response and some female patients with hormonal dysfunction, due, for example, to polycystic ovarian syndrome, may need additional treatment with an hormonal preparation such as co-cyprindiol.
Persistent deep pustules in about 1% of patients may be due to Staphylococcal aureus, and bacterial swabs should always be examined and appropriate anti-staphylococcal therapy prescribed. Some patients have multiple reasons for the slow response.
Further courses of therapy are usually successful when required. There are no reports of cumulative toxicity from using repeat courses and tachyphylaxis has not been noted.
Tretin is contraindicated in female patients who are pregnant. To receive Tretin all patients must meet all of the following conditions:
- Must be registered with the iPLEDGE program by the prescriber
- Must understand that severe birth defects can occur with the use of Tretin by female patients
- Must be reliable in understanding and carrying out instructions
- Must sign a Patient Information/Informed Consent (for all patients) form that contains warnings about the potential risks associated with Tretin
- Must fill and pick up the prescription within 7 days of the date of specimen collection for the pregnancy test for female patients of childbearing potential
- Must fill and pick up the prescription within 30 days of the office visit for male patients and female patients not of childbearing potential
- Must not donate blood while on Tretin and for 1 month after treatment has ended
- Must not share Tretin with anyone, even someone who has similar symptoms
Tretin is indicated to treat severe recalcitrant nodular acne and patients ≥12 years enrolled in the iPLEDGE program. Label,12
The pharmacodynamics of Tretin are poorly understood. Label
Mechanism of action
Tretin produces its effects through altering progress through the cell cycle, cell differentiation, survival, and apoptosis. 4 These actions reduce sebum production, preventing the blockage of pores, and growth of acne causing bacteria. 4 Tretin and 4-oxo-Tretin both significantly reduce the production of sebum. 4,Label Tretin has little to no affinity for retinol binding proteins (RBPs) and retinoic ac >4 Tretinoin and 4-oxo-tretinion bind to the RAR-γ receptor, which is suspected to be part of the action of acne treatment by Tretin. 4 Tretin induces apoptosis in sebocytes, leading to a decrease in sebum production. 4 Tretin also reduces the formation of comedones by reducing hyperkeratinization through an unknown mechanism. 4 Tretin does not directly kill bacteria but it does reduce the size of sebum ducts and makes the microenvironment less hospitable to acne causing bacteria. 4 It may also increase immune mechanisms and alter chemotaxis of monocytes to reduce inflammation. 4
There is preliminary ev >9
Target Actions Organism U Retinoic acid receptor alpha
Significant systemic effects are uncommon ( Table 5 ); headaches may uncommonly be an early feature of benign intracranial hyper-tension and arthralgia is seen most frequently in those patients participating in regular and heavy excercise. Tetracyclines, including doxycycline and minocycline, must not be prescribed with Tretin, as both drugs may produce benign intracranial hypertension. 51 , 58 Systemic side effects are usually well controlled by dose reduction and concomitant the use of non-steroidal anti-inflammatory drugs or aspirin. There is a long list of very uncommon systemic side effects a detailed review of these is beyond the scope of this chapter.
How does Tretin work?
In acne, Tretin:
- Reduces sebum production
- Shrinks the sebaceous glands
- Reduces follicular occlusion
- Inhibits the growth of bacteria
- Has anti- inflammatory properties.
Visual problems should be carefully monitored. All Accutane (Tretin) patients experiencing visual difficulties should discontinue Accutane (Tretin) treatment and have an ophthalmological examination (see ADVERSE REACTIONS: Special Senses).
Precautions when taking Tretin
- Tretin should be used with caution during breastfeeding.
- Commercial pilots may be subject to flying restrictions if they take Tretin.
- High dose Tretin in very young children has been associated with premature epiphyseal closure, leading to shorter stature (this is not seen in the low dose used for the treatment of acne).
Does acne ever fail to clear on Tretin?
Although Tretin is usually very effective for acne, occasionally it responds unexpectedly slowly and incompletely. Poor response is associated with: