Hey there,

I'm a newbie to this forum and all I can say is wow! there's a lot of juicy info in here =D Anway about me...I've just started Accutane this past week...I have mild acne with occasional flare-ups...I'd say maybe once every 2 months? But the flare-ups get pretty bad...i get some of those cystic types + my skin gets pretty oily...and then it magically disappears....but enough is enough - I went to my doc and asked for accutane, and volia...here I am, one week later.....no major changes...other than mildly dry skin, and dry lips.....

One thing I wanted to share with you guys, is that I noticed that a lot of info here is pulled from the web.....I found this amazing book "Clinical Derm by Habif" on MD Consult (I'm a med student)...here's the info on Accutane that they give...its quite interesting, because they give you all the indications for using it, how your doc. should be using etc......anyway here it is - hope this helps!:


Isotretinoin
Isotretinoin (Accutane, Amnesteen, Sotret 10-, 20-, 40-mg capsules; 13-cis retinoic acid), an oral retinoid related to vitamin A, is a very effective agent for control of acne and in the induction of long-term remissions, but it is not suitable for all types of acne. Isotretinoin affects all major etiologic factors implicated in acne. It dramatically reduces sebum excretion, follicular keratinization, and ductal and surface P. acnes counts. These effects are maintained during treatment and persist at variable levels after therapy. A full list of indications and guidelines for treatment are found in Table 7-4 and Box 7-4 . A number of side effects occur during treatment.[60] Isotretinoin is a potent teratogen; pregnancy must be avoided during treatment. Isotretinoin is not mutagenic; female patients should be assured that they may safely get pregnant but should wait for at least 1 month after stopping isotretinoin. Age is not a limiting factor in patient selection.

INDICATIONS
Severe, recalcitrant cystic or nodular and inflammatory acne.
A few patients with severe disease respond to oral antibiotics and vigorous drying therapy with a combination of agents such as benzoyl peroxide and sulfacetamide/sulfur lotion. Those who do not respond after a short trial of this conventional therapy should be treated with isotretinoin to minimize scarring.

Moderate acne unresponsive to conventional therapy.
Moderate acne usually responds to antibiotics (e.g., tetracycline or doxycycline) plus topical agents. Change to a different antibiotic (e.g., minocycline 100 mg twice daily) if response is poor after 3 months. Change to isotretinoin if response is unsatisfactory after two consecutive 3-month courses of antibiotics. Patients who have a relapse during or after two courses of antibiotics are also candidates for isotretinoin.

Patients who scar.
Any patient who scars should be considered for isotretinoin therapy. Acne scars leave a permanent mark on the skin and psyche.

Excessive oiliness.
Excessive oiliness is disturbing and can last for years. Antibiotics and topical therapy may provide some relief, but isotretinoin's effect is dramatic. Relief may last for months or years; some patients require a second or third course of treatment. Some patients respond
TABLE 7-4 -- Dosage of Isotretinoin by Body Weight Body weight Total mg/day
Kilograms Pounds 0.5 mg/kg 1 mg/kg 2 mg/kg
40 88 20 40 80
50 110 25 50 100
60 132 30 60 120
70 154 35 70 140
80 176 40 80 160
90 198 45 90 180
100 220 50 100 200




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to a long-term low-dose regimen such as 10 mg every other or every third day.

Severely depressed or dysmorphophobic patients.
Some patients, even with minor acne, are depressed. Those who do not respond to conventional therapy are candidates for isotretinoin. They respond well to isotretinoin, although some may relapse quickly and require repeat courses. [61]

Sebaceous hyperplasia.
Patients with numerous facial lesions of sebaceous hyperplasia may experience a dramatic clearing with a low dosage of isotretinoin. A typical patient is age 40 to 50 and has more than 50 lesions on the forehead and cheeks. Start with 10 mg qd and lower the dosage once control is achieved. Many patients are maintained on 10 mg every other or every third day. Lesions reappear weeks or months after stopping treatment.

DOSAGE.
The severity of the side effects of isotretinoin is proportional to the daily dose. Start with lower dosages and progressively increase the dosage in accordance with the tolerance. Treatment is usually begun at 0.5 mg/kg a day and increased to 1.0 mg/kg a day.

The cumulative dose may be more important than the duration of therapy. A cumulative dose of greater than 120 mg/kg is associated with significantly better long-term remission.[62] This dosage level can be achieved by either 1 mg/kg/day for 4 months or a smaller dosage for a longer period. The therapeutic benefit from a total cumulative dose of more than 150 mg/kg is virtually nonexistent.[63] Analysis of 9 years of experience demonstrated that 1 mg/kg/day of isotretinoin for 4 months resulted in the longest remissions Relapse rates in patients receiving 0.5 mg/kg/day were approximately 40% and those receiving 1.0 mg/kg/day were approximately 20%. Younger patients, males, and patients with truncal acne derive maximum benefit from the higher dosages. In these patients, dosages less than 0.5 mg/kg/day for a standard 4-month course are associated with a high relapse rate. Treat older patients with facial acne with a dosage of 0.5 mg/kg/day. Double the dosage if there is no response at the end of 2 months. Intermittent dosing may be useful for patients over the age of 25 with mild-to-moderate facial acne that is unresponsive to or that relapses rapidly after conventional antibiotic therapy. Treat with isotretinoin, 0.5 mg/kg a day, for 1 week in every 4 weeks for a total of 6 months. [64] Very low-dose isotretinoin may be a useful therapeutic option in rare patients who continue to suffer with acne into their 60s and 70s. Isotretinoin, 0.25 mg/kg a day, for 6 months is well tolerated and effective.[65] Side effects in all patients depend on the dosage and can be controlled through reduction.

DURATION OF THERAPY.
A standard course of isotretinoin therapy is 16 to 20 weeks. Approximately 85% of patients are clear at the end of 16 weeks; 15% require longer treatment. Side effects are related to the dosage. Treat for a longer duration at a lower dosage if mucocutaneous side effects become troublesome. Patients with large, closed comedones may respond slowly and relapse early with inflammatory papules. Another ill-defined group responds slowly and requires up to 9 months until the condition begins to clear.

RELAPSE AND REPEAT COURSES OF ISOTRETINOIN.
Approximately 39% of patients relapse and require oral antibiotics (23%) or additional isotretinoin (16%). Relapse usually occurs within the first 3 years after isotretinoin is stopped; most often during the first 18 months after therapy. Some patients require multiple courses of therapy. The response to repeat therapy is consistently successful, and side effects are similar to those of previous courses. Repeat courses of isotretinoin seem to be safe.

ISOTRETINOIN THERAPY.
Patients are seen every 4 weeks. Isotretinoin is given in two divided doses daily, preferably with meals. Many patients experience a moderate to severe flare of acne during the initial weeks of treatment. This adverse reaction can be minimized by starting at 10 to 20 mg twice each day and gradually increasing the dosage during the first 4 to 6 weeks. Treatment is discontinued at the end of 16 to 20 weeks, and the patient is observed for 2 to 5 months. Those with persistently severe acne may receive a second course of treatment after the posttreatment observation period.

Response to therapy.
At dosages of 1 mg/kg/day, sebum production decreases to approximately 10% of pretreatment values and the sebaceous glands decrease in size.[66] Maximum inhibition is reached by the third or fourth week. Within a week, patients normally notice drying and chapping of facial skin and skin oiliness disappears quickly. These effects persist for an indefinite period when therapy is discontinued.

During the first month, there is usually a reduction in superficial lesions such as papules and pustules. New cysts evolve and disappear quickly. A significant reduction in the number of cysts normally takes at least 8 weeks. Facial lesions respond faster than trunk lesions.

RESISTANT PATIENTS.
Younger patients (14 to 19 years of age) and those who have severe acne relapse more often.[67] Truncal acne relapses more often than facial acne. A return of the reduced sebum excretion rate to within 10% of the pretreatment level is a poor prognostic factor.[68] Patients with microcystic acne (whiteheads) and women with gyneco-endocrinologic problems are resistant to treatment. Women who do not clear after a total cumulative dose of 150 mg/kg need laboratory and clinical evaluation of their endocrinologic status. They may benefit from antiandrogen therapy.

PSYCHOSOCIAL IMPLICATIONS.
Patients successfully treated with isotretinoin have significant posttreatment gains in social assertiveness and self-esteem.[69] There is also a significant reduction in anxiety and depression.[70]

Patients with minimal facial acne but with symptoms of dysmorphophobia (inappropriate depression and/or anxiety response to mild acne) are often treated with long-term antibiotic therapy with no perceived improvement. These patients


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respond to isotretinoin in that they are satisfied with the cosmetic results achieved. The incidence of relapse is greater than that of other acne patients and often requires additional therapy in the form of antibiotics or further isotretinoin.[61]

LABORATORY STUDIES.
Pregnancy tests, triglyceride tests, complete blood cell counts, and liver function tests are performed on patients taking isotretinoin ( Table 7-5 ); pregnancy tests are performed at each 4-week follow-up.

SIDE EFFECTS.
Side effects occur frequently, are dose-dependent, and are reversible shortly after discontinuing treatment. Patients with side effects can be managed at a lower dosage for a period long enough to reach the 120 mg/kg cumulative dose level. Explain to patients that the long-term benefit is related to the cumulative dosage, not to the duration of therapy.

The incidence of side effects was documented in a large study ( Table 7-6 ). Patients in that study stopped isotretinoin for the following reasons: mucous/skin effects (2.5%), elevated triglyceride levels (2.0%), musculoskeletal effects (1.3%), headaches (1.1%), elevated liver enzyme levels (0.6%), amenorrhea (0.4%), and other (0.5%).

Teratogenicity.
PREGNANCY PREVENTION PROGRAM. Isotretinoin is a potent teratogen primarily involving craniofacial, cardiac, thymic, and central nervous system structures. [71] A number of physicians inadvertently prescribed isotretinoin to pregnant women, which resulted in birth defects.[72]

Women should be educated about the risks to the fetus and the need for adequate contraception. Some physicians will not prescribe isotretinoin to women of child-bearing age
TABLE 7-5 -- Laboratory Tests with Isotretinoin Test Comments
Pregnancy Two urine or serum pregnancy tests before a prescription is given. The first is performed at the office, the second performed on the second day of her next menstrual cycle or 11 days after her last unprotected act of sexual intercourse, whichever is later. Additional tests are conducted monthly during treatment.
Triglyceride level * Performed during pretreatment, after 2–3 weeks of treatment, and then at 4-week intervals. If levels exceed 350 to 400 mg/dL, repeat blood lipids at 2- to 3-week intervals. Stop if the value exceeds 700 to 800 mg/dL to reduce the risk of pancreatitis
Complete blood cell count Performed before treatment and after 4–6 weeks of treatment
Liver function* * Performed before treatment and after 4–6 weeks of treatment
* Liver and lipid abnormalities rarely necessitate dosage reduction.



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unless they are taking oral contraceptives. Others withhold isotretinoin if abortion is not an option. Isotretinoin is not mutagenic, nor is it stored in tissue. It is recommended that contraception be continued for 1 month after stopping isotretinoin. Patients can be reassured that conception is safe after this 1-month period. One study showed that from the fourth month of treatment onward, a statistically significant increase in the mean sperm density, sperm morphology, and motility were not affected. One year after treatment there was no evidence of any negative influence of 6 months of treatment with isotretinoin on spermatogenesis.[73]

The S.M.A.R.T. Guide to Best Practices (System to Manage Accutane Related Teratogenicity) is a program developed to assist the clinician and patient in fulfilling the requirements for Accutane pregnancy prevention risk management and in understanding contraindications and warnings. Female patients are qualified under the guidelines of this program to receive an isotretinoin prescription. Physicians must register with Roche Laboratories to receive yellow Accutane Qualification Stickers that are placed on each prescription. A similar program is available for the branded generic forms of isotretinoin (Amnesteen, Sotret).

Plasma lipid abnormalities.
Isotretinoin therapy induces an elevation of plasma triglycerides. In one study of patients (ages 14 to 40 years) treated for 20 weeks with 1 mg/kg/day, the maximum mean triglyceride levels increased 46.3 mg/dL in men and 52.3 mg/dL in women. In that study, two of 53 patients had a triglyceride elevation over 500 mg/dL, and eight had elevations of 200 to 500 mg/dL. Triglyceride levels increase after 6 weeks of therapy and continue to increase while therapy continues.[74] Age, gender, and
TABLE 7-6 -- Frequency of Mucocutaneous and Musculoskeletal Events in 404 Subjects * Event Frequency, No
Cheilitis 96
Dry skin 87
Pruritus 23
Dry mouth 29
Dry nose 40
Epistaxis 33
Conjunctivitis 40
Musculoskeletal symptoms 42
Rash 16
Hair thinning 6
Peeling 6
From McElwee NE, et al: Arch Dermatol 1991; 127:341.
* Mean initial isotretinoin dose was 1 mg/kg. Most commonly used initial dosage regimen for males is 80 or 120 mg/day, and 80 or 40 mg/day for females.



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weighted dose do not appear to be risk factors for triglyceride elevations. Overweight subjects are six times more likely to develop significant elevations in serum triglyceride, and subjects with elevated baseline triglyceride levels are 4.3 times more likely to develop significant elevations.[75] Plasma lipid and lipoprotein levels return to baseline by 8 weeks after treatment. [76]

Bony changes.
Asymptomatic hyperostoses (spurs) of the spine and extremities can be documented radiographically in some patients but do not seem to be of concern with a standard course of isotretinoin therapy. [77] [78] [79] This toxicity is common and related to dose and to duration of treatment and age. It increases with age. Approximately 10% of patients who are treated for acne with standard courses develop detectable changes.[80] With higher doses, changes are more prominent. After long-term treatment (5 years), they can be found in most patients. Premature epiphyseal closure is rare. It has occurred at the higher doses and decreases with age, occurring only in children. Studies verified that there are no lasting changes in calcium homeostasis or bone mineralization as a result of a single course of isotretinoin for acne.[81]

Cheilitis.
Cheilitis is the most common side effect, occurring in virtually all patients. Application of emollients should be started with the initiation of therapy to minimize drying.

OTHER EFFECTS.
Approximately 40% of patients develop an elevated sedimentation rate during treatment. Isotretinoin does not specifically affect skeletal or myocardial muscles, although 28% of patients complain of musculoskeletal symptoms.[81] Isotretinoin contains the preservative parabens; those patients with a proven allergy to parabens cannot receive isotretinoin. Exuberant granulation tissue may occur at the sites of healing acne lesions and is more likely to develop in patients who have preexisting crusted, draining, or ulcerated lesions. Granulation tissue can be controlled with intralesional steroid injections or silver nitrate sticks. Severe dry skin or eczema commonly occurs on the backs of the hands. Routine use of moisturizers and infrequent washing is recommended. Group V topical steroids treat the eczema.

Depression.
In 1998, the manufacturers of isotretinoin, in conjunction with the FDA, announced a new warning. “Psychiatric disorders: isotretinoin may cause depression, psychosis and rarely, suicidal ideation, suicide attempts and suicide. Discontinuation of isotretinoin therapy may be insufficient; further evaluation may be necessary. No mechanism of action has been established for these events.� The product labeling now states, “Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy.� No cause-and-effect relationship between isotretinoin and depression has been demonstrated in the literature. Clinicians should be aware of this potential side effect, particularly in patients at risk, such as those with a history of depression.

Prednisone
Prednisone has a limited but definite place in the management of acne. Nodulocystic acne can be resistant to all forms of conventional topical and antibiotic therapy. Nodulocystic acne can be destructive, producing widespread disfigurement through scarring. Intervention with powerful antiinflammatory agents should not be postponed in the case of rapidly advancing disease. Deep cysts improve only slowly with isotretinoin, and much permanent damage can be done while waiting for an effect.

PREDNISONE THERAPY.
The dosage and duration of prednisone treatment is determined by the patient's response. The following program has been successful for treating extensive, rapidly advancing, painful cystic acne. Prednisone should be started at 40 to 60 mg per day given in divided doses twice daily. This dosage is maintained until the majority of lesions are significantly improved. Dosage is tapered. The dosage is lowered to 30 mg given as a single dose in the morning. The dosage can be tapered by 5 mg each week until 20 mg is reached, at which point prednisone can be further tapered to 30 mg every other day and withdrawn in 5-mg increments every 4 days. Patients with acne severe enough to require prednisone usually require isotretinoin for lasting control. Both drugs can be started simultaneously.

Thankyou for posting this EXCELLENT informatiion. I will add a link to it from the 'Accutane FAQ' pinned at the top of the forum as soon as I can.

No Probs! And although I'm not a doctor, if you have any questions let me know...i'll see if me and my minute knowledge of medicine can help ...cheers

Hi,

Thanks so much for posting this information. I had a question--I'm not sure if this is known, but why does Accutane continue to work after your treatment is over? If something permanent has changed (for example a permanent shrinking of the oil glands), would it lead to any adverse long-term side effects? ~Gypsy

Thanks for the info! I'm on antibiotics right now, and I'm really worried that if/when they stop working, I'll have to take accutane. I'm scared of it. Plus, once I had a bad poisoning, and my liver numbers went up for a period of time. Then they went down again, and they say if i've had liver issues I shouldn't take accutane. I just don't know what to do..

thanks for the cool info

Hey Teplo,


Which antibiotics are you using?

If the antibiotics your using are working for you, thats great....but as you probably know, bacteria tend to be able to develop resistance to drugs overtime....that's one some people change antibiotics every so often...one way that some of the docs at my hospital test for bacterial resistance is that they culture some of the pustles/cysts, and then give the appropriate antibiotic....

The choice to take antibiotics long-term is up to the patient - I believe it is safe to take low-dose antibiotics for extended periods of time...if a high dose is taken...its usually tapered down....

With respect to your liver...do you know which liver "numbers" were abnormal? AST/ALP/GT/ALT/bilirubin?

If its ALP or GT, its most likely do to something cholestastic in nature, where as if it was AST or ALT, then its due to hepatocelluar damage....which is more impt. if we're talking about drug metabolism here.....the liver is an amazing organ...your can drink your butt off, destroy one of its lobe, poison it with drugs, etc....but will the liver die? Nope...not unless you exceeds its threshold....the liver can regenerate any damaged tissue up to a certain extent....so, this liver damage you're talking about, if the liver "numbers" went down, might actually be non-existent now....when your liver enzymes went up, perhaps they were due to alcohol, drugs (eg. NSAID overuse, antibiotic overuse), hepatitis (just giving you a diffrential here...).....you should check your liver enzymes b4 going accutane to get a baseline function of your liver...if they're abnormal, i think you should talk to your doctor and find out.....if they're not, I dont think there should be a contraindication for going on accutane....

Btw, did they do any liver function tests on you? eg. serum albumin or prothrombin time? I think if you have "liver problems" such as acute/chronic hepatitis, cirrohsis, infection eg. malaria - then you should NOT go on accutane as the ability of the liver to biotransform/elminate drugs is impaired....

Hey Gypsy...not to sure about the answer to your question....I do know that accutane continues to work after your treatment...that is it continues to work at least to 2 months after the date you stop taking pills (thats why the recommened latency period btw the 2nd treatment is minimum 8 weeks)....in terms of why, might be do the fact that accutane still remains in your body (T1/2 is ~ 21 hrs...but depending on what your dosage was...maybe by the end of 2 months...there's still VERY VERY small amounts that can still influence your glands...but not enuff to influence female fertility)....

As for permanent changes....some, if not most people get a permanant change in their skin/oil glands/keritinaztion process etc...thats why they get less acne! Which is not a bad thing of course....

i hope this answer's your question??

I'm using Mino now; I started antibiotics about 5 years ago, used Doxy for a little over a year, and it stopped working, then used Tetra, and it stopped working. Now I'm using Mino for about 2 years. It's working fine, and I'm trying to get it to work better by making sure to not eat any iron or calcium with the pill. But when it stops working I'm not sure what I'll do. I'm in college, and the derm here at the medical center thinks I have mild acne, and doesn't want to give me accutane. But when I first visited a derm back home, 5 years ago, my acne was so bad that she said I'll take accutane, but first we had to try the antibiotics as a formality.

I was hiking in Australia 4 years ago and had an allergic reaction to some plant. I was throwing up a lot basically. Back in the US, they did a bunch of tests and a liver test was one of them. After it they told me I had hepatitis, and I was like WTF? So they told me that all it means is "inflamation of the liver" and it's temporary. In 2 weeks I did the test again, and my liver was fine. Then in 2 weeks I did another one to make sure, and the numbers were up again! Then in another 2 weeks the test said that everything is fine. So then I was like fuck this.. and didn't do any more tests.

So I don't know if that's considered a risk factor if i were to go on accutane. What's this I'm reading about permanent vision and hearing damage as a side-effect? (from their site)

I wouldnt worry about it...liver numbers go up and down all the time....its the context and magnitude they change in that are relevant.....

Some accutane users get change in eye vision...most of them have difficulty seeing at nite...and some users get ear changes such as tinnitus.....if users get these signs, then they are advised to stop accutane and see an optho or otolargn.....almost all symptoms reverse when stopped...and only a small percentange will still have symptoms

Care to explain this?

My take is its 'resistant' in the sense that people in that age bracket are less likely to have permanent effects (ie relapse)? And that bodily (truncal) acne comes back more often than facial acne?



People with microcystic acne aren't affected by accutane? This doesn't make sense.

Cheers

Hey,
I have another question (and thanks for answering all these by the way)...why is it that some people get an initially bad breakout when starting Accutane? Meaning, what exactly is the drug doing to cause this? I've heard people discuss a "purging" process, but what does that mean exactly? That the Accutane is pushing things up to the surface that were already festering? Thanks! ~Gypsy

I've realised the derm I went to gave me a really low dosage. Only 20 mg of oratane (isotretinoin) for a week, once a day! Maybe it is a stronger kind?!

I think I already have scars. Do you think isotretinoin would help at all to diminish those?

I hate to be a bother and be another one to ask you a question but I have been taking accutane for one month now and the other day I went back for a follow up to my derm.
I was taking 40mg once a day (I personally thought was pretty high but the derm insisted) for that first month (today is the last day). Anyway she said that she is going to raise it to 60mg a day for the next month and I had to take 2 20mg pills in the morning and 1 20mg pill in the evening. My question is why? Why would she raise the dosage? I mean i'm doing great with what I am on right now I mean I still have a few white heads that pop up here and there and a papule or two but compared to before it has been a big improvment. She also said that if I do ok with the 60mg for this next month that she is going to raise it to 80mg which scares me even more. Is this right? should I be worried? Thanks for your help.

Hmm...Im not quite sure what your question is other than

1) People in the age bracket 14-19 are more likely to experience a recurrance of their acne, after a period of quiescence (thats what relapse means essentially), than other age groups...and of the acne that relapses, truncal acne comes back more often than facial acne (which is what you said)...........

2) with the white head thing, im actually surprised by it......yes, in theory, it doesnt make sense...i'll have to ask someone 'bout that one....

Hey Gypsy,

That's correct..well partially I believe...its not that Accutane is pushing things up that were already festering i.e. Accutane isnt accelerating the process of getting a breakout that would have happened any way if Accutane wasnt takin......instead, Accutane starts re-modelling the hairfollicles from the root, and gradually towards the skin...and it also dries the heck outta your skin, which can allow bacteria to penetrate into your skin and current hair follicles that are remodelling...which can cause this inital breakout.....also, by decreasing oil production, and having dry skin...suppose bacteria went in your pores, but there was no sebum production to "push" the bacteria out....that could also cause the breakout...