what r the side effects of roaccutane for a 15 year old?

Question

i have bad acne and i heard tht roaccutane works pretty gd but i hear tht it has bad side effects

Answer 1

3.3.1 Cardiovascular Effects

Cardiovascular finding

Chest pain

Vasculitis

3.3.1.A Cardiovascular finding
1) Chest pain and vasculitis have been reported with isotretinoin therapy.
2) In a case report, a patient receiving isotretinoin 1 milligram per kilogram daily for severe acne developed RIGHT BRANCH BUNDLE BLOCK (RBBB) associated with SINUS TACHYCARDIA. Discontinuation of isotretinoin resolved all signs and symptoms. Reintroduction of isotretinoin 10 days later induced RBBB again, which resolved upon drug discontinuation (Charalabopoulos et al, 2003).

3.3.1.B Chest pain
1) Summary
a) Transient chest pain has been associated with isotretinoin therapy; symptoms are usually reversible after discontinuation of therapy (Prod Info Accutane(R), 2000b).

3.3.1.C Vasculitis
1) Summary
a) A few reports of vasculitis have been reported in patients receiving isotretinoin (Prod Info Accutane(R), 2000b). It has occurred in patients taking isotretinoin in doses of 0.5 to 1.1 milligrams/kilogram/day. Reports indicate that vasculitis has occurred 14 to 16 weeks into therapy (Epstein & McNutt NS Beallo, 1987). However, in one case, the patient received isotretinoin for 6 months, and vasculitis did not appear until 6 months after treatment was stopped (Reynolds et al, 1989).
2) LITERATURE REPORTS
a) CUTANEOUS NECROTIZING VASCULITIS was reported in two patients taking isotretinoin. Symptoms gradually resolved with appropriate therapy and discontinuance of the drug; prednisone was a successful adjunct in one case (Dwyer et al, 1989).

3.3.2 Dermatologic Effects

Cheilitis

Cheilosis

Chloasma

Dermatitis

Dermatological finding

Eruptive xanthoma

Erythroderma

Fragile skin

Hair finding

Lip finding

Nail damage

Opportunistic infection, Skin

Photosensitivity

Pityriasis rosea

Pyoderma gangrenosum

Scar of skin

3.3.2.A Cheilitis
1) Summary
a) Cheilitis (inflammation of the lips) may occur in up to 90% of the patients treated with isotretinoin (Prod Info Accutane(R), 2000b; Johnson & Rapini, 1987; Reuter & Hellriegel, 1983; Windhorst & Nigra, 1982a; Jones et al, 1983).

3.3.2.B Cheilosis
1) LITERATURE REPORTS
a) Dry or chapped lips are seen in almost all patients treated with isotretinoin. Onset occurs within days of starting isotretinoin (McLane, 2001).

3.3.2.C Chloasma
1) Summary
a) Abnormal skin pigmentation has occurred with isotretinoin use (Prod Info Accutane(R), 2000b). Melasma developed after 4 weeks of isotretinoin 70 milligrams daily. The patient completed a 6-month course of therapy, isotretinoin was discontinued, and the melasma resolved 1 month later (Burke & Carmichael, 1996).

3.3.2.D Dermatitis
1) Summary
a) FACIAL DERMATITIS and general DESQUAMATION have rarely or infrequently been reported with therapeutic isotretinoin use. The effects appeared to be dose related, with an increased incidence at higher doses (1 milligram/kilogram/day (mg/kg/day)) as compared to lower doses (0.1 mg/kg/day) (Jones et al, 1980aa; Farrell et al, 1980b). Isotretinoin-induced rubber glove dermatitis was reported in one case (Williams & Wright, 1994).

3.3.2.E Dermatological finding
1) Summary
a) BRUISING, DRY SKIN, peeling of palms and soles, PRURITUS, PYOGENIC GRANULOMA, RASH, URTICARIA, and abnormal wound healing have occurred with isotretinoin use (Prod Info Accutane(R), 2000b; Azurdia & Sharpe, 1999; Windhorst & Nigra, 1982a; Reuter, 1984; Jones et al, 1983). One author reported that 97% of patients receiving isotretinoin developed mucocutaneous symptoms (McElwee et al, 1991). Other dermatologic adverse effects that have occurred infrequently or rarely include PARONYCHIA, PSEUDOPROPHYRIA, URTICARIA, varicella- zoster infection, ERYTHEMA NODOSUM, ERYTHEMA MULTIFORME, and ONYCHOLYSIS (Bigby & Stern, 1988e). SCALP FOLLICULITIS, PYODERMA, and FACIAL SCARRING, which cleared with corticosteroid therapy have also been noted (Dicken & Connolly, 1980; Farrell et al, 1980b; Hughes & Cunliffe, 1990; Helfman et al, 1984; Katz & Mac Farlane, 1994; Riordan et al, 1993).
2) Nail changes, photosensitivity, dry or chapped lips, opportunistic skin infections, pyoderma gangrenosum, pruritus, dermatitis, hair changes, skin fragility, inflammatory and eruptive skin disorders, dryness of the skin and mucous membranes may be noted with isotretinoin therapy.
3) LITERATURE REPORTS
a) In a review of 2 isotretinoin clinical trials, the incidence of dry skin, localized exfoliation, erythematous rash, and dermatitis accounted for over 90% of patients who had adverse events in the skin and subcutaneous tissue body system (McLane, 2001).

3.3.2.F Eruptive xanthoma
1) Summary
a) Eruptive xanthomas, which cleared with corticosteroid therapy, have occurred with isotretinoin therapy (Prod Info Accutane(R), 2000b; Reuter & Hellriegel, 1983; Dicken & Connolly, 1980).
2) LITERATURE REPORTS
a) A patient receiving isotretinoin 120 milligrams (mg) twice daily for 16 weeks developed eruptive xanthomas on the thighs, knees and arms. The patient's serum triglyceride level was 4,768 milligrams/deciliter (mg/dL) (normal 169 mg/dL). The xanthomas were gone 11 weeks post-discontinuation. Elevated triglyceride levels may be a predisposing factor in the development of xanthomas (Dicken & Connolly, 1980).

3.3.2.G Erythroderma
1) Summary
a) Isotretinoin has also aggravated erythroderma in 3 of 4 patients with Sezary syndrome. After 2 weeks of therapy 3 patients had increasing redness and exfoliation which continued for 2 to 3 months after therapy was stopped (Wantzin & Thomsen, 1985).

3.3.2.H Fragile skin
1) Summary
a) CASE REPORT - 39-year-old women experienced linear erosions and skin fragility at the site of waxing 3 weeks after starting isotretinoin therapy. The lesions resolved within a few weeks without scarring. It appears that there may be potential problems associated with isotretinoin and cosmetic waxing procedures (Romo, 1991). The manufacturer has suggested that wax epilation and skin resurfacing procedures should be avoided during isotretinoin therapy and for at least 6 months thereafter due to skin fragility and the risk of scarring (Prod Info Accutane(R), 2000b).

3.3.2.I Hair finding
1) Summary
a) HAIR THINNING, which in rare cases may persist following discontinuation of therapy, hair abnormalities, ALOPECIA, HIRSUTISM, and DRY HAIR have been reported with isotretinoin therapy (Peck et al, 1979a; Prod Info Accutane(R), 2000b). Two cases of PILI TORTI (twisted hair) were reported in patients receiving isotretinoin doses of 0.7 mg to 2 milligrams/kilogram/day for 3 months (Hays & Camisa, 1985). A few cases of CURLING HAIR have also been noted (van der Pijl et al, 1996)(Bunker et al, 1989).
2) LITERATURE REPORTS
a) Three pancreas-kidney transplant recipients developed CURLING HAIR after 2 to 3 months of isotretinoin therapy (60 to 100 milligrams/day). Patients were 12 to 13 months post-transplant before isotretinoin was started. Patients were receiving triple immunosuppressive therapy and other medications concurrently. Azathioprine has been associated with curling hair as a regrowth phenomenon which may suggest a synergistic effect with isotretinoin (van der Pijl et al, 1996).
b) A 46-year-old woman taking 1 milligram/kilogram of isotretinoin daily for one year developed progressive curling of the hair. It returned to its normal state 6 months after treatment was discontinued (Bunker et al, 1989).

3.3.2.J Lip finding
1) Summary
a) Mucosal denudation of the lips was reported in a 19-year-old patient receiving isotretinoin therapy. After 4 weeks of isotretinoin 30 milligrams (mg) twice daily (1 milligram/kilogram/day) the patient complained of severe swelling of the lips, with associated pain, oozing, and bleeding for 16 hours. The upper and lower lips were approximately 3 times normal size. Labial cultures were negative for organisms and viruses. Within 1 week the labial mucosa re-epithelialized. Follow up at 3 months demonstrated no evidence of scarring (Graham & Barrett, 1999).

3.3.2.K Nail damage
1) Summary
a) Retinoids may rarely or infrequently cause various nail changes including splitting, softening, shedding of the nail, and chronic paronychia (Patel & Anstey, 2000; Bottomley & Cunliffe, 1992a).
2) LITERATURE REPORTS
a) Median canaliform dystrophy of Heller was diagnosed in a 31-year-old woman who had been taking isotretinoin (1 milligram/kilogram daily) to treat severe nodulocystic acne. She noticed fragility of all fingernails after 8 weeks of treatment and had developed a fir tree-like nail dystrophy extending from the cuticle. One year after completion of treatment with isotretinoin nail growth had returned to normal (Patel & Anstey, 2000).
b) A patient developed a central ridge and proximal splitting of the nails on three separate administrations of isotretinoin. The nail changes occurred after 6 weeks of therapy in each case (Bottomley & Cunliffe, 1992a).

3.3.2.L Opportunistic infection, Skin
1) Summary
a) Staphylococci aureus cutaneous infections have been reported in several patients during or after treatment with isotretinoin. Most cases occurred several weeks after treatment began. It is not totally understood why patients receiving isotretinoin have an increased risk to S. aureus cutaneous infections. One factor may be that breaks in the corneal layer from isotretinoin induce xerosis and could provide an entry for infection. Another factor may be a possible reduction in neutrophil killing of staphylococci (Boffa et al, 1994).

3.3.2.M Photosensitivity
1) Summary
a) Patients treated with isotretinoin will have an increased susceptibility to sunburn and patients should be advised to avoid prolonged exposure to UV rays or sunlight (Prod Info Accutane(R), 2000b; Reynolds, 2000).
2) LITERATURE REPORTS
a) A case of isotretinoin-induced photosensitivity in a patient receiving 1 milligram/kilogram/day with no previous history of photosensitivity was reported (McCormack & Turner, 1983). In contrast, the results of phototesting up to 15 patients taking 1 milligram/kilogram/day of isotretinoin for up to 4 weeks failed to associate isotretinoin with photosensitivity reactions (Diffey et al, 1985)(Wong et al, 1985).

3.3.2.N Pityriasis rosea
1) Summary
a) Isotretinoin therapy has rarely or infrequently been associated with an eruption simulating acute pityriasis rosea, which resolved upon dosage reduction. The lesions were characterized by psoriasiform hyperplasia and had no histologic resemblance to pityriasis rosea (Helfman et al, 1984).

3.3.2.O Pyoderma gangrenosum
1) Summary
a) CASE REPORT - Pyoderma gangrenosum was reported in a 17- year-old male being treated with isotretinoin (Gangaram et al, 1997).

3.3.2.P Scar of skin
1) Summary
a) KELOID and HYPERTROPHIC SCAR FORMATION was reported in a 16-year-old who received pulsed dye laser treatment for a capillary vascular malformation and isotretinoin therapy. Pulsed dye laser treatment was administered without the knowledge that the patient was concomitantly using isotretinoin. The authors suggest that a thorough patient history be obtained prior to pulsed dye laser treatment (Bernestein, 1997).

3.3.3 Endocrine/Metabolic Effects

Disorder of fluid AND/OR electrolyte

Endocrine finding

Hypercalcemia

Hyperglycemia

Hyperthyroidism

Lipids abnormal

Metabolic finding

Thyroglossal duct cyst

3.3.3.A Disorder of fluid AND/OR electrolyte
1) A single case of hypercalcemia has been noted with high dose therapeutic isotretinoin.

3.3.3.B Endocrine finding
1) Hyperglycemia, thyroglossal duct cyst and thyrotoxicosis have been reported in patients treated with therapeutic doses of isotretinoin.

3.3.3.C Hypercalcemia
1) Summary
a) One case of hypercalcemia has been reported in a patient receiving isotretinoin therapy; a causal relationship was not established (Valentic et al, 1983). A literature search from 1983 to 1993 did not reveal any further information on isotretinoin induced hypercalcemia.
2) LITERATURE REPORTS
a) Hypercalcemia was reported in a 19-year-old male with cystic acne receiving isotretinoin. The patient was given 30 milligrams (mg) isotretinoin twice daily (0.9 milligrams/kilogram/day (mg/kg/day)) increased gradually to 60 mg every morning and 50 mg at bedtime in the second month. After approximately 4 months of therapy, serum calcium levels had increased to 11.5 milligrams/deciliter (mg/dL), over a baseline of 9.4 mg/dL prior to therapy. Calcium levels continued to increase with continued therapy to 12.3 mg/dL in 1 week. Isotretinoin was discontinued followed by a decrease in serum calcium to 10.5 mg/dL within 3 days. The patient also developed anemia during isotretinoin treatment, however a cause-effect relationship was unclear. The patient was re-challenged with isotretinoin at a lower dose without reoccurrence of hypercalcemia. Although isotretinoin could not be definitely implicated in this case, monitoring of serum calcium levels is advisable during isotretinoin therapy since hypervitaminosis A has caused hypercalcemia (Valentic et al, 1983).

3.3.3.D Hyperglycemia
1) Summary
a) ELEVATED BLOOD SUGAR has been reported in less than 10% of patients (114 cases) receiving isotretinoin; monitor blood sugars in susceptible patients (Prod Info Accutane(R), 2000b).
2) LITERATURE REPORTS
a) Three weeks after starting isotretinoin 20 millirgams (mg) daily, a 32-year-old woman developed diabetes mellitus. Immunosuppressive-induced (eg, prednisolone 10 mg, azathioprine 50 mg, cyclosporin A 150 mg) acne developed following renal transplant and was unresponsive to a reduction in prednisolone dose or topical tretinoin. This patient had stable renal function, normal blood glucose levels despite steroid therapy, and no family history of diabetes mellitus. At initial presentation, the blood glucose level was 31.9 millimoles/liter, and ketonuria was present. Diabetic ketoacidosis was treated with insulin which was required at six months for control of diabetes mellitus. In this patient, the authors believe that diabetes mellitus was due to isotretinoin because of the close temporal relationship (Timperley et al, 1996).

3.3.3.E Hyperthyroidism
1) Summary
a) CASE REPORT - A 26-year-old male developed THYROTOXICOSIS while receiving isotretinoin 40 milligrams daily. Thyroid function returned to normal within 2 months after isotretinoin therapy had been discontinued (Minuk & Jackson, 1986).

3.3.3.F Lipids abnormal
1) Summary
a) Approximately 25% of patients receiving isotretinoin experienced an elevation in plasma triglycerides which is usually dose related. (Thirty-two out of 298 total subjects treated for all diagnoses showed an elevation of triglycerides above 500 milligrams percent (mg%); elevations above 800 milligrams/deciliter (mg/dL) have been associated with acute pancreatitis). About 15% of patients showed a decrease in serum high density lipoprotein (HDL) levels and about 7% of patients experienced minimal elevations of serum cholesterol (HYPERCHOLESTEREMIA) during treatment. The lipid response usually occurs within 4 weeks. Lipid level monitoring is required. If HYPERTRIGLYCERIDEMIA cannot be controlled to an acceptable level or if symptoms of pancreatitis occur, therapy should be discontinued. Abnormalities of serum triglycerides, HDL and cholesterol were reversible upon discontinuation of therapy (Prod Info Accutane(R), 2000b; McLane, 2001; Kemp et al, 1989; Marsden, 1989; Reuter, 1984; Kingston et al, 1983; Windhorst & Nigra, 1982a; Farrell et al, 1980b).
2) LITERATURE REPORTS
a) Marked abnormalities in triglyceride levels were reported in 25.6% of patients treated with isotretinoin (McLane, 2001).
b) Patients with increased risk for developing hypertriglyceridemia include those with diabetes mellitus, obesity, increased alcohol intake and familial history. The consequences of hypertriglyceridemia are not well understood, but may increase the patient's cardiovascular risk status. Therefore, every attempt should be made to control significant triglyceride elevation. Reversal of triglyceride elevations may be accomplished by reduction in weight, restriction of dietary fat and alcohol, and reduction in dose while continuing therapy (Prod Info Accutane(R), 2000b; McElwee et al, 1991).
c) One small study (n=13), failed to show any effect of isotretinoin on the metabolism of polyunsaturated fatty acids (Ostlere et al, 1996)
d) A significant increase in triglyceride levels has been reported in men and women receiving isotretinoin 1 to 1.8 milligrams/kilogram/day for 20 weeks for nodulocystic acne. Nine of 53 evaluable patients (17%) developed hypertriglyceridemia (200 to 600 milligrams/deciliter). Increases in low density lipoprotein (LDL) cholesterol levels were observed, as well as decreases in mean levels of high density lipoprotein (HDL) cholesterol. These changes were reversible with lipid and lipoprotein levels returning to normal 2 months after withdrawal of isotretinoin. It is suggested that with long-term treatment, the change in the ratio of LDL cholesterol to HDL cholesterol, as serum in this study (2.4 to 3.0), may be associated with an increased risk of cardiovascular disease (Bershad et al, 1985).
e) Increases in plasma triglyceride levels of 67% (and cholesterol levels of 16%) were reported during treatment of 20 men with nodulocystic acne with isotretinoin for 4 months (2 milligrams/kilogram/day (mg/kg/day) in divided doses for either 2, or 4 weeks, then 0.5 mg/kg/day for a total treatment time of 16 weeks). Very low density lipoprotein (VLDL) cholesterol increases of 56% were observed, as well as increases in low density lipoprotein (LDL) cholesterol of 22%; high density lipoprotein (HDL) decreases of 10% were observed. These data support close monitoring of plasma lipid and lipoprotein profiles during isotretinoin treatment, since elevations in LDL cholesterol and decreases in HDL cholesterol have been established as independent risk factors for premature coronary heart disease (Zech et al, 1983).
f) A patient who had a previous history of gestational hyperlipidemia (hypertriglyceridemia and hypercholesterolemia) developed hypertriglyceridemia and pancreatitis after receiving isotretinoin. After 6 weeks of treatment with isotretinoin for cystic acne the patient developed abdominal pain, intractable nausea and vomiting, and mild intravascular volume depletion. The serum triglyceride concentration was 5,490 milligrams/deciliter. Isotretinoin was discontinued, the patient was conservatively managed and 1 month later the serum triglyceride concentration was 102 milligrams/deciliter (McCarter & Chen, 1992).

3.3.3.G Metabolic finding
1) Lipid abnormalities may be seen with isotretinoin therapy.

3.3.3.H Thyroglossal duct cyst
1) Summary
a) After two courses of isotretinoin, a thyroglossal duct cyst was revealed and became enlarged. The cyst regressed after discontinuing the first course of treatment but had to be surgically removed during the second course of treatment. The cyst reappeared the second time 2 months after starting therapy (LaFontaine et al, 1995).

3.3.4 Gastrointestinal Effects

Gastrointestinal tract finding

Inflammatory bowel disease

Nausea and vomiting

Pancreatitis

3.3.4.A Gastrointestinal tract finding
1) Summary
a) DRY MOUTH, DRY NOSE, and EPISTAXIS may occur in up to 80% of nodular acne patients during isotretinoin therapy, and may be due to a change in salivary composition (Windhorst & Nigra, 1982a; Reynolds et al, 1991; Prod Info Accutane(R), 2000b). Isotretinoin has infrequently been associated with ANOREXIA and WEIGHT LOSS (Perry & McEvoy, 1983); however, an INCREASED APPETITE may also be seen (Peck et al, 1979a). TASTE ABNORMALITIES including LOSS OF TASTE have rarely been reported in patients (Halpern et al, 1996). Several studies have noted an increase in thirst with isotretinoin therapy (Windhorst & Nigra, 1982Peck et al, 1979).
2) Nausea, vomiting, mild GI bleeding, anorexia, weight loss, taste abnormalities, increased appetite, epistaxis, increased thirst, dry mouth and nose have been noted with therapeutic doses. Inflammatory bowel disease and pancreatitis have also occurred.

3.3.4.B Inflammatory bowel disease
1) Summary
a) Inflammatory bowel disease has been associated with isotretinoin therapy in patients without a prior history of intestinal disorders. Discontinue isotretinoin immediately if abdominal pain, rectal bleeding, or severe diarrhea occur (Prod Info Accutane(R), 2000b). There are a few reports of patients with chronic inflammatory bowel disease and acne who have been treated with isotretinoin and suffered no bowel- related adverse effects (Godfrey & James, 1990; Schleicher, 1985); (Macdonald & Cunliffe, 1989).
2) LITERATURE REPORTS
a) Over 200 cases of gastrointestinal adverse drug reactions occurring during or after treatment with isotretinoin have been reported to the Federal Drug Administration. These include CROHN'S DISEASE and ULCERATIVE COLITIS. Abnormalities may not appear until months to a year or more after the discontinuation of isotretinoin. It has been suggested that occult blood tests be added to routine blood testing for patients receiving isotretinoin (Prokop, 1999).
b) Isotretinoin 40 to 80 mg daily for approximately 4 weeks was associated with PROCTOSIGMOIDITIS in a 17-year-old boy with cystic acne. An increase in stool frequency was observed within several days of initiation of treatment, which persisted throughout therapy. Sigmoidoscopy demonstrated patchy mucosal inflammation with discrete APHTHOUS ULCERS; histologically, an acute focal superficial inflammatory infiltrate was observed. Withdrawal of the drug resulted in resolution of symptoms, and rechallenge again produced a similar attack of proctosigmoiditis (Martin et al, 1987).

3.3.4.C Nausea and vomiting
1) Summary
a) Nausea, vomiting, and mild GASTROINTESTINAL BLEEDING have been reported in patients receiving therapeutic isotretinoin doses (Reuter, 1984; Windhorst & Nigra, 1982a).

3.3.4.D Pancreatitis
1) Summary
a) Serum triglycerides levels above 800 milligrams/deciliter have been associated with acute pancreatitis. Isotretinoin can cause a rise in serum triglycerides in 25% of patients (Prod Info Accutane(R), 2000b). Rare cases of fatal hemorrhagic pancreatitis have been reported. Acute pancreatitis has been documented in patients with either normal or elevated serum triglycerides. Accutane(R) therapy should be stopped if hypertriglyceridemia cannot be controlled to an acceptable level or if symptoms of pancreatitis occur (Prod Info Accutane(R), 2000b).
2) Incidence: rare
3) LITERATURE REPORTS
a) A patient who had a previous history of gestational hyperlipidemia (hypertriglyceridemia and hypercholesterolemia) developed hypertriglyceridemia and pancreatitis after receiving isotretinoin. After 6 weeks of treatment with isotretinoin for cystic acne the patient developed abdominal pain, intractable nausea and vomiting, and mild intravascular volume depletion. The serum triglyceride concentration was 5,490 milligrams/deciliter. Isotretinoin was discontinued, the patient was conservatively managed and 1 month later the serum triglyceride concentration was 102 milligrams/deciliter (McCarter & Chen, 1992).
b) Pancreatitis secondary to hypertriglyceridemia was described in a 43-year-old woman following isotretinoin therapy (40 milligrams (mg) orally twice daily) for approximately 7 weeks. Serum triglycerides were 83 millimoles/liter (mmol/L) (normal, 0.45 to 1.8) and serum cholesterol was 23 mmol/L (normal, 3.9 to 8.5). The patient subsequently developed diabetic ketoacidosis and ARDS (adult respiratory distress syndrome). A CT scan of the abdomen revealed severe diffuse pancreatitis. Plasmapheresis was initiated to rapidly lower serum lipids, and the patient subsequently improved with supportive treatment. It is suggested that baseline and serial lipid determinations be undertaken in isotretinoin-treated patients to monitor for the occurrence of hyperlipidemia (Flynn et al, 1987).

3.3.5 Hematologic Effects

Anemia

Bleeding

Erythrocytosis

ESR raised

Hematology finding

Leukopenia

Thrombocytopenia

3.3.5.A Anemia
1) Summary
a) It has been reported that isotretinoin can decrease erythrocyte count, hemoglobin concentration, and hematocrit in 10% to 20% of patients (Prod Info Accutane(R), 2000b; Perry & McEvoy, 1983; Peck et al, 1979a). A significant decrease in hemoglobin concentration was noted in a study involving 90 patients receiving 0.5 to 0.75 milligrams/kilogram/day of isotretinoin. The decrease in hemoglobin concentration was found to be reversible upon discontinuation of treatment (Michaelsson et al, 1986).

3.3.5.B Bleeding
1) Summary
a) Bleeding and bruising have been reported with isotretinoin therapy (Prod Info Accutane(R), 2000b). During treatment for cystic acne, a patient with hemophilia A experienced an increase in the number of bleeding episodes and the amount of factor VIII administered. It was felt that the cause of bleeding may have been stimulation of plasminogen activator activity by isotretinoin (Dootson et al, 1992).

3.3.5.C Erythrocytosis
1) Summary
a) Polycythemia was reported in a 58-year old man during the tenth month of treatment with isotretinoin at a dosage of 20 milligrams/day (initial doses were 180 mg/day for 3 months and 80 mg/day for 6 months). Three months after discontinuation of isotretinoin the hemoglobin and hematocrit returned to normal values (Cakmakci et al, 2001).

3.3.5.D ESR raised
1) Summary
a) Elevated ERYTHROCYTE SEDIMENTATION RATES (ESR) have been reported in up to 40% of patients (Prod Info Accutane(R), 2000b).

3.3.5.E Hematology finding
1) Elevated erythrocyte sedimentation rates (ESR) have been reported in up to 40% of patients. Bleeding, bruising, anemia, and myelosuppression have been reported with isotretinoin therapy. Elevated platelets, a single case of agranulocytosis, and polycythemia have also been noted.

3.3.5.F Leukopenia
1) Summary
a) Leukopenia and NEUTROPENIA have been reported in patients taking 0.5 milligrams to 0.95 milligrams/kilogram/day of isotretinoin. A single case of AGRANULOCYTOSIS with questionable association with isotretinoin therapy has been reported (Prod Info Accutane(R), 2000b; Waisman, 1988). Accutane(R) therapy should be discontinued if clinically significant decreases in white cell counts occur (Prod Info Accutane(R), 2000b).
2) LITERATURE REPORTS
a) Agranulocytosis was described in a 16-year-old boy following administration of isotretinoin 40 to 80 milligrams daily for approximately 9 weeks. Following withdrawal of the drug, granulocyte count began to improve within 3 days and normalized within 4 weeks (Waisman, 1988). However, in the absence of re-challenge, is unclear if isotretinoin was the actual cause of this patient's granulocytopenia. In addition, the patient never developed symptoms in the presence of severe granulocytopenia, except for slight fatigue, making one question the possibility of laboratory error. Accutane(R) therapy should be discontinued if clinically significant decreases in white cell counts occur (Prod Info Accutane(R), 2000b).
b) In one case, when therapy was withdrawn after 18 weeks, the neutrophil and leukocyte count increased sharply only to be followed by another decrease in both (Friedman, 1987).
c) Another study involved 90 patients taking isotretinoin for 3 to 6 months. Significant decreases in neutrophils and leukocytes occurred, but were reversible and dose-related (Michaelsson et al, 1986).

3.3.5.G Thrombocytopenia
1) Summary
a) Elevated platelet counts and thrombocytopenia have been reported. Thrombocytopenia has been reported in less than 10% of patients (Prod Info Accutane(R), 2000b).
2) LITERATURE REPORTS
a) A 20-year-old man with no personal or family history of bleeding disorder and no recent viral or bacterial infection presented with severe epistaxis and a petechial rash involving the face and thighs. Physical, biochemical, and immunologic investigations revealed no underlying abnormalities. A bone marrow aspirate demonstrated the presence of increased megakaryocytes, which were also larger than normal, but no erythroid or myeloid abnormalities. Two weeks before hospital admission, the patient had been placed on oral isotretinoin (dose unstated) for severe acne vulgaris; this medication was discontinued at the time of admission. Platelet counts subsequently increased spontaneously and steadily from 15 x 10(9)/liter on admission to 400 x 10(9)/liter seven days later (Hesdorffer et al, 1986).
b) Thrombocytopenia was described in a 15-year-old Hispanic adolescent with cystic acne following isotretinoin 60 milligram (mg) daily (1 milligram/kilogram (mg/kg)/day) for approximately 2 weeks. Withdrawal of isotretinoin resulted in increases in platelet count to normal values over the next 10 days. Re-challenge with 60 mg isotretinoin resulted in recurrence of thrombocytopenia within 1 day, with subsequent return to normal values in approximately 10 days. This appears to be the first case report of thrombocytopenia secondary to isotretinoin (Johnson & Rapini, 1987).

3.3.6 Hepatic Effects

Hepatotoxicity

Liver finding

3.3.6.A Hepatotoxicity
1) Summary
a) During clinical trials with isotretinoin, HEPATITIS was been reported in several cases. Increases in alkaline phosphatase, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-Glutamyl transpeptidase (GGTP), or lactic dehydrogenase (LDH) have also occurred in approximately 15% of patients. Liver function tests are required. Isotretinoin therapy should be discontinued if hepatitis is suspected or if laboratory values do no normalize (McLane, 2001; Prod Info Accutane(R), 2000b; McElwee et al, 1991; Jones et al, 1980; Jones et al, 1980aa; Reed et al, 1979a; Katz et al, 1980).

3.3.6.B Liver finding
1) Hepatitis and abnormal liver enzymes have been reported with isotretinoin use.

3.3.8 Musculoskeletal Effects

Achilles tendinitis

Arthralgia

Arthritis

Bone finding

Decreased body growth

Drug-induced myopathy

Musculoskeletal finding

Systemic onset juvenile chronic arthritis

3.3.8.A Achilles tendinitis
1) Summary
a) Three cases of acute Achilles tendinitis in patients receiving isotretinoin for acne vulgaris have been reported. Doses ranged from 0.25 milligram to 1 milligram/kilogram/day. Symptoms included acute pain, swelling, and tenderness. Modification of dose regimens allowed all 3 patients to continue therapy. Some patients receiving isotretinoin may have increased CPK levels following vigorous physical activity (Prod Info Accutane(R), 2000b); (Bottomley & Cunliffe, 1991).

3.3.8.B Arthralgia
1) Summary
a) Musculoskeletal symptoms including arthralgia are observed in approximately 16% of patients receiving isotretinoin (Prod Info Accutane(R), 2000b; Perry & McEvoy, 1983; Windhorst & Nigra, 1982a). Discontinuation of therapy is occasionally required and in some cases, symptoms may persist following termination of treatment (Prod Info Accutane(R), 2000b).

3.3.8.C Arthritis
1) Summary
a) Arthritis has rarely been reported (Matsuoka et al, 1984; Camisa, 1986); (Hodak, 1986). Arthritis associated with isotretinoin therapy may be treated with steroid injections and nonsteroidal antiinflammatory medications. Arthritis usually resolves after discontinuation and may resolve during therapy (Hughes, 1993). One hypothesis of synovitis involves the induction of lysosomal membrane solubilization and resultant cytopathic destruction of the synovium leading to increased sensitivity of the synovium to mechanical injury. Another explanation may be an immune dysfunction associated with isotretinoin (Hughes, 1993).
2) LITERATURE REPORTS
a) The occurrence of aseptic arthritis of the knee in a 34-year-old male following isotretinoin therapy for cystic acne (40 mg daily for 2 weeks, followed by 80 mg daily for 2 weeks) was reported. Withdrawal of isotretinoin resulted in resolution of the arthritic symptoms, in conjunction with ibuprofen therapy. Isotretinoin was re-instituted 10 days later (40 mg daily), producing aseptic arthritis of the ankle, which also resolved following withdrawal of the drug and ibuprofen therapy. The patient had no history of arthritis or other rheumatologic disorders (Camisa, 1986).
b) Acute ASEPTIC ARTHRITIS occurred in 2 male patients following the use of oral isotretinoin for acne in doses of 40 mg twice daily for 3 weeks to 2 months. Synovial fluid from one patient was non- inflammatory. The arthritis resolved in both patients without adverse sequelae, despite continuation of the drug in one patient. The manufacturer reports an incidence of 16% of transient arthralgias during isotretinoin therapy of cystic acne (Matsuoka et al, 1984).
c) It has been suggested that HLA-B27 determinations can be useful in predicting the development of skeletal toxicity from isotretinoin (Pochi, 1983). However, some disagree, since HLA-B27 antigens are not always associated with isotretinoin- induced skeletal toxicity. The use of HLA-B27 as a prognostic guide is not indicated at this time (Yue & Khan, 1983).

3.3.8.D Bone finding
1) Summary
a) There are reports of ossification disorders occurring that include HYPEROSTOSIS (Tangrea et al, 1992)(Archer et al, 1989; Kilcoyne, 1988; Ellis et al, 1988; Carey et al, 1988).
2) LITERATURE REPORTS
a) Isotretinoin used for 20 weeks for the treatment of severe acne vulgaris did not appear to have an adverse effect on bone mineralization. Patients were age 19 to 35 years (Margolis et al, 1996).
b) Low dose, long term (0.14 milligram/kilogram/day for 3 years) isotretinoin was studied for the prevention of basal cell carcinoma. Skeletal effects of isotretinoin were monitored for both placebo and isotretinoin treated patients. There was progression of hyperostotic changes in 40% of patients on isotretinoin as compared to 18% on placebo. High and low dose isotretinoin can cause or worsen hyperostotic abnormalities (Tangrea et al, 1992).
c) An ossification disorder resembling diffuse IDIOPATHIC SKELETAL HYPEROSTOSIS in 4 of 9 patients receiving isotretinoin 3 to 4 milligrams/kilogram/day (mg/kg/day) for ichthyosis has been described. Initial symptoms were primarily recurrent arthralgias and stiffness. The authors recommend the avoidance of high doses to avoid retinoid hyperostosis (Pittsley & Yoder, 1983). Additional studies involving patients taking higher doses of isotretinoin (1 to 3 mg/kg/day) for extended periods of time (2 to 7 years) have demonstrated an increased incidence of skeletal hyperostosis, with or without any other symptoms (Archer et al, 1989; Kilcoyne, 1988; Ellis et al, 1988; Carey et al, 1988).
d) In clinical trials of disorders of keratinization, 5 patients treated for over 2 years had skeletal abnormalities. These included hyperostosis with SPINE DEGENERATION in 3 adult patients, and 2 children who showed x-ray findings suggestive of possible premature closure of the epiphysis (Perry & McEvoy, 1983).
e) Skeletal toxicity is known to occur with isotretinoin doses in excess of 2 milligrams/kilogram/day. Doses of 0.5 milligrams/kilogram/day did not produce significant, long-term musculoskeletal changes (Carey et al, 1988).
f) Five of seven patients treated for keratinizing disorders with 3 milligrams/kilogram of isotretinoin for three years demonstrated irreversible skeletal hyperostosis and deformity (Pittsley & Yoder, 1983; Yoder, 1983).

3.3.8.E Decreased body growth
1) Summary
a) In pediatric isotretinoin use, it is important to carefully monitor epiphyseal changes both prior to and during therapy so as to be able to differentiate between drug-induced growth arrest and early puberty (Butenandt, 1995).
2) LITERATURE REPORTS
a) The occurrence of dense metaphyseal bands and GROWTH ARREST in a 9-year-old boy who received isotretinoin 4 to 5 mg/kg/day for approximately 5 months for the treatment of fibrodysplasia ossificans progressiva is described. Withdrawal of the drug resulted in gradual decrease of metaphyseal bands and resumption of clinical growth. It is suggested that this effect of isotretinoin may be related to alterations in the characteristic pattern of chondrocyte gene expression (Marini et al, 1988).

3.3.8.F Drug-induced myopathy
1) Summary
a) Skeletal muscle damage has rarely been reported (Matsuoka et al, 1984; Camisa, 1986); (Hodak, 1986). Acute myopathy developed in 2 patients (Fiallo & Tagliapetra, 1996) and clinical and electromyographic evidence of MUSCLE DAMAGE has been reported in 2 patients (Hodak, 1986).
2) LITERATURE REPORTS
a) Two patients with recalcitrant nodulocystic acne developed acute myopathy after treatment with isotretinoin 0.5 milligrams/kilogram daily (3 months and 15 days, respectively). Muscular weakness progressed to the inability to walk or get out of bed. Both patients fully recovered within 2 months (Fiallo & Tagliapietra, 1996).
b) Two patients taking 40 milligrams of isotretinoin daily for approximately 4 weeks developed muscle pain and moderate weakness starting a few days after initiation of treatment. Clinical and electromyographic evidence of muscle damage occurred. Withdrawal of isotretinoin resulted in abatement of muscle pain within several days. These data suggest that isotretinoin may cause reversible skeletal muscle damage. However, more studies are required to confirm these reports and determine possible mechanisms of this adverse effect (Hodak, 1986).
c) Isotretinoin 40 mg twice daily has been reported to cause a significant increase in CPK (creatine phosphokinase) concentrations (Lipinski & Schwimmer, 1985).

3.3.8.G Musculoskeletal finding
1) Summary
a) There are reports of musculoskeletal aches and pains, back pain, and arthralgia (McLane, 2001; Prod Info Accutane(R), 2000b)
2) Skeletal and growth abnormalities, arthritis, arthralgias, myopathy, tendinitis, back pain, musculoskeletal aches and pain, and drug-induced Still's disease have occurred with isotretinoin therapy. In pediatric isotretinoin use, it is important to carefully monitor epiphyseal changes both prior to and during therapy so as to be able to differentiate between drug-induced growth arrest and early puberty.
3) LITERATURE REPORTS
a) In a review of 2 isotretinoin trials (n=369), back pain was reported in 5.3% of patients. In general, musculoskeletal aches and pains are mild and transient (McLane, 2001).
b) The manufacturer reports that approximately 16% of treated patients develop mild to moderate musculoskeletal effects including arthralgia. Discontinuation of therapy is occasionally required and in some cases, symptoms may persist following termination of treatment (Prod Info Accutane(R), 2000b).

3.3.8.H Systemic onset juvenile chronic arthritis
1) Summary
a) Oral isotretinoin-induced Still's Disease (POLYARTICULAR JUVENILE RHEUMATOID ARTHRITIS) was reported in a 21-year-old male receiving treatment for 3 months for severe acne conglobata. Upon initiation of prednisolone therapy, symptoms rapidly resolved. Sulfasalazine therapy was started two weeks later. Prednisone was tapered and discontinued after 1 year. Sulfasalazine was continued and resulted with the patient in remission 6 months later (Leibovitch, 2000).
2) LITERATURE REPORTS
a) A case report described oral isotretinoin-induced Still's Disease. After being treated for 3 months for severe acne conglobata, a 21-year-old male patient presented with a fluctuating spiky fever that peaked (40 degrees Celsius) with the appearance of a macular rash on his trunk, neck, and extremities and vanished as the fever subsided. Other symptoms included, fatigue, a 7-kilogram weight loss, and diffuse articular pain causing limited range of motion. Physical examination and computed tomography scan revealed hepatosplenomegaly, two enlarged lymph nodes in the periportal area, and an enlarged lymph node in the left axilla. The results of a comprehensive series of serological tests were negative for infection. Lab results demonstrated microcytic anemia, an erythrocyte sedimentation rate of 70 millimeters/hour, a white blood cell count of 20 to 30 x 10(9)/liter with 90% polymorphonuclear cells, and elevated hepatic enzymes. Normal levels of serum complement were reported and rheumatoid factor and antinuclear antibodies were not found. Upon initiation of prednisolone 60 milligrams, symptoms rapidly resolved. Salazopyrine (sulfasalazine) therapy (2 grams daily) was started 2 weeks later and corticosteroid therapy was tapered and discontinued after 1 year. The patient was in remission while continuing salazopyrine therapy 6 months later (Leibovitch, 2000).

3.3.9 Neurologic Effects

Headache

Neurological finding

Pseudotumor cerebri

Somnolence

3.3.9.A Headache
1) Summary
a) Headache may occur with therapeutic isotretinoin doses (Bigby & Stern, 1988e; McLane, 2001; Lindemayr, 1986; Windhorst & Nigra, 1982a).
2) LITERATURE REPORTS
a) Headache was reported in 13.3% of patients treated with isotretinoin in one large trial (n=369). The mean duration of the headache was from 6 to 8 days (McLane, 2001).
b) The Adverse Drug Reaction Reporting System of the American Academy of Dermatology reported 104 suspected adverse reactions secondary to isotretinoin in 93 patients over a 4-year period (1982 to 1985) (Bigby & Stern, 1988e). Central nervous system adverse effects were described in 23 patients, with 12 being considered as definitely or probably related to isotretinoin. This included 10 reports of headache). In the majority of cases, the headaches occurred within the first week of treatment.

3.3.9.B Neurological finding
1) Summary
a) Isotretinoin therapy has been associated with SEIZURES, DIZZINESS, NERVOUSNESS, INSOMNIA, and PARESTHESIAS (Prod Info Accutane(R), 2000b; Perry & McEvoy, 1983; Windhorst & Nigra, 1982a). CONFUSION has rarely been reported (Marroni et al, 1993).
2) Isotretinoin therapy has been associated with seizures, dizziness, nervousness, insomnia, paresthesias, lethargy, fatigue, and headache. Pseudotumor cerebri and papilledema have also been reported in adults.

3.3.9.C Pseudotumor cerebri
1) Summary
a) Several cases of pseudotumor cerebri BENIGN INTRACRANIAL HYPERTENSION (or ELEVATED INTRACRANIAL PRESSURE) have been reported in patients receiving isotretinoin, usually associated with concomitant tetracycline therapy. PAPILLEDEMA, headache, nausea and vomiting and VISUAL DISTURBANCES have occurred as early signs and symptoms. Patients with these symptoms should be screened for papilledema and if a diagnosis is made, therapy should be immediately discontinued and the patient should be evaluated by a neurologist (Prod Info Accutane(R), 2000b; Roytman et al, 1988; Bigby & Stern, 1988e; Spector, 1984; FDA, 83).
2) LITERATURE REPORTS
a) A case of pseudotumor cerebri was reported that developed in a patient receiving 0.7 milligrams/kilogram/day of isotretinoin without concomitant use of tetracycline. Two months into therapy the patient developed severe headaches and dizzy spells. Isotretinoin therapy was stopped and administration of dexamethasone begun. Six weeks later the patient was symptom-free (Roytman et al, 1988).

3.3.9.D Somnolence
1) Summary
a) LETHARGY and FATIGUE have been noted with therapeutic isotretinoin doses (Prod Info Accutane(R), 2000b; Reuter, 1984; Windhorst & Nigra, 1982a).

3.3.10 Ophthalmic Effects

Conjunctivitis

Corneal opacity

Dry eyes

Excessive tear production

Eye / vision finding

Night blindness

Retinopathy

Subconjunctival hemorrhage

3.3.10.A Conjunctivitis
1) Summary
a) BLEPHAROCONJUNCTIVITIS has been reported in 20% to 43% of patients taking isotretinoin (1 to 2 milligrams/kilogram (mg/kg)). This side effect may be dose-related since patients receiving 0.1 mg/kg reported no ocular symptoms (Milson et al, 1982; Blackman et al, 1980). In another study of 14 patients receiving isotretinoin, 7 patients receiving 2mg/kg/day complained of conjunctivitis. It was not severe enough to require discontinuation of therapy (Peck et al, 1979a).

3.3.10.B Corneal opacity
1) Summary
a) The manufacturer reports in conjunction with other studies, that corneal opacities have developed in patients receiving isotretinoin. The occurrence was more frequent in patients receiving high doses with keratinization disorders. Resolution had completely occurred or was occurring 6 to 7 weeks after discontinuation of therapy (Prod Info Accutane(R), 2000b; Ellies et al, 2000; Fraunfelder, 1983; Weiss et al, 1981).
2) LITERATURE REPORTS
a) A healthy 39-year-old female experienced persistent corneal opacity following oral administration of isotretinoin for the treatment of severe cystic acne. The woman received oral isotretinoin 1 milligram/kilogram per day for greater than 5 months, with a total cumulative dose of 8300 milligrams. The patient had worn soft hydrophilic contact lens for 10 years, and an ophthalmology examination was negative for corneal opacity one month prior to initiating isotretinoin treatment. After approximately 2 months of isotretinoin treatment, gray deposits were observed on the left cornea. A more extensive evaluation after 5 months of isotretinoin treatment revealed thousands of rounded, gray, confluent lesions localized in the superficial stroma on the left eye and a clear cornea on the right eye. The gray lesions demonstrated a rectangular shape with one side adjacent to the superonasal corneoscleral limbus and did not involve the visual axis. There was no evidence of flare or uveitis and the conjunctiva appeared normal. Isotretinoin treatment and contact lens were immediately discontinued. Ophthalmologic examinations every 6 months for at least 6 years have established persistent corneal opacity with no change in the size, color, and shape of the lesions. The lesions remained asymptomatic and no corneal biopsy was completed (Ellies et al, 2000).
b) BILATERAL CORNEAL OPACITIES have been reported during treatment with isotretinoin in both humans and animals, and appear to be reversible after withdrawal treatment. Patients in whom corneal opacities have developed often have had an existing disorder of dermal keratinization (Fraunfelder, 1983; Weiss et al, 1981).

3.3.10.C Dry eyes
1) Summary
a) Dry and irritated eyes is a common problem (McLane, 2001; Prod Info Accutane(R), 2000b).
2) LITERATURE REPORTS
a) Dry or irritated eyes are reported in about one third of patients receiving isotretinoin (McLane, 2001).
b) The Adverse Drug Reaction Reporting System of the American Academy of Dermatology reported 104 suspected adverse reactions secondary to isotretinoin in 93 patients over a 4-year period (1982 to 1985) (Bigby & Stern, 1988e). Dry eyes occurred in 8 patients, with 2 of these being considered as probably related to isotretinoin. Patients experiencing visual difficulties should discontinue isotretinoin treatment and undergo an ophthalmological examination (Prod Info Accutane(R), 2000b).

3.3.10.D Excessive tear production
1) LITERATURE REPORTS
a) A case of unilateral watery eye was reported in a 19-year old man who was treated with isotretinoin for severe acne. An occluded lacrimal punctum accounted for his symptoms which appeared to be irreversible (Chua & Martin, 2001).

3.3.10.E Eye / vision finding
1) Summary
a) CATARACTS, and VISUAL DISTURBANCES have been reported in patients receiving isotretinoin. In addition, a decreased tolerance to contact lenses may occur during and after isotretinoin therapy. (Prod Info Accutane(R), 2000b; Denman et al, 1986; Grattan et al, 1987; Herman & Dyer, 1987). Acute transient MYOPIA has also been reported (Palestine, 1984).
2) Conjunctivitis, cataracts, dry eyes, subconjunctival hemorrhage, corneal opacity, night blindness, increased glare sensitivity, and other visual disturbances may be seen with therapeutic isotretinoin use. One case report includes epiphora.
3) LITERATURE REPORTS
a) ANTERIOR SUBCAPSULAR CATARACTS occurring in a 45-year-old female were associated with use of isotretinoin 40 mg twice daily for 14 weeks (Herman & Dyer, 1987).

3.3.10.F Night blindness
1) Summary
a) Significant decreases in the amplitude of a-waves of the scotopic electroretinogram (ERG) have been observed in some patients receiving isotretinoin over a period of several months for dermatological disorders. The decrease in night vision may have a sudden onset and may persist after of discontinuation of therapy. It is recommended that patients complaining of difficulty in night or color vision undergo ophthalmological examinations during isotretinoin therapy (Brown & Grattan, 1989).
2) LITERATURE REPORTS
a) Night blindness and excessive glare sensitivity was reported in 3 patients treated with isotretinoin 1 milligram/kilogram per day. It was theorized that isotretinoin may compete for normal retinol binding sites on cell surfaces or transport molecules (Reynolds, 2000).

3.3.10.G Retinopathy
1) Summary
a) In a small subset of 15 patients with cutaneous malignant melanoma participating in a double-blind clinical trial comparing isotretinoin or placebo in combination with interferon alfa, melanoma- associated retinopathy was the likely cause of abnormal visual symptoms in one patient rather than isotretinoin or interferon alfa-related retinopathy (Feigl et al, 2000).
2) LITERATURE REPORTS
a) Patients with cutaneous malignant melanoma enrolled in a randomized, double-blind, placebo-controlled trial were administered daily placebo or isotretinoin (20 milligrams (mg) for less than 73 kilograms (kg) body weight or 30 mg for greater than 73 kg body weight) and 3 million units of interferon alfa subcutaneously three times a week for 24 months. At the time of ophthalmologic examination, the patients had participated in the clinical trial for a mean period of 9 months. The most common ocular event documented was dry eyes. One 67-year-old patient receiving isotretinoin and interferon-alfa treatment complained of a sudden onset of blurred vision, shimmering light sensation, and night blindness after 12 months of participating in the clinical trial and therapy was discontinued. Follow-up examinations at 1, 3, and 6 months after onset of symptoms remained stable and showed no improvement. Due to the sudden onset and irreversibility of symptoms as well as pathological findings compared with other case reports in the literature, melanoma-associated retinopathy was with a high probability responsible for the abnormal retinal function in this patient (Feigl et al, 2000).

3.3.10.H Subconjunctival hemorrhage
1) Summary
a) CASE REPORT - A 39-year-old male developed subconjunctival hemorrhage in the left eye 6 weeks after beginning isotretinoin therapy to treat acne. The subconjunctival hemorrhage resolved within 3 weeks after reducing the dose of isotretinoin, and the patient was able to complete the 16-week course of therapy without further problems (Azurdia & Sharpe, 1999).

3.3.12 Psychiatric Effects

Mental disorder

Psychiatric sign or symptom

3.3.12.A Mental disorder
1) Summary
a) Isotretinoin therapy may cause DEPRESSION, PSYCHOSIS and rarely, SUICIDAL IDEATION, suicide attempts and suicide. Symptoms have subsided after discontinuation of therapy and recurred with isotretinoin re-challenge. Dream pattern changes was reported (McLane, 2001; Prod Info Accutane(R), 2000b; Ling & Highet, 2000); (Gatti et al, 1991)(Scheinman et al, 1990; Villalobos et al, 1989).
2) LITERATURE REPORTS
a) Two cases of sustained dreaming were reported in college students receiving isotretinoin for the treatment of cystic acne. The sustained dreams onset was within 2 to 3 weeks of initiation of isotretinoin and lasted 4 to 5 weeks with continued treatment (Gupta & Gupta, 2001).
b) One case report identifies a 36-year-old man who experienced an enhanced craving for cigarettes while receiving treatment with isotretinoin, which suggests the psychological adverse effects associated with isotretinoin may not be restricted to depression and its related features. The patient had been a smoker for 18 years and previously received a 4-month course of isotretinoin without incident at the age of 19. At the age of 36, the patient presented with recurrent acne and isotretinoin therapy was initiated at a dose of 1 milligram per kilogram daily. Three months later, the dose was reduced to 0.5 milligrams per kilogram due to a patient complaint of increased sweating of palms. A total course of 6 months was completed with an excellent response. Upon review, the patient reported an intense craving for cigarettes within 2 weeks of beginning therapy. Prior to therapy the patient smoked 10 cigarettes daily and during therapy his consumption increased to 40 per day. In addition, there was no reduction in the craving when the isotretinoin dose was reduced at 3 months. Since the patient did not report any increased levels of stress, fatigue, mood swings or other psychological changes, this case suggests that the increased craving for cigarettes may be a psychological change associated with isotretinoin (Ling & Highet, 2000).
c) One month following a successful 4-month course of treatment with isotretinoin (0.5 milligrams/kilogram/day) a patient developed severe depression that led to suicide (Gatti et al, 1991).
d) Of 700 patients receiving isotretinoin 0.3 to 0.7 milligrams/kilogram/day, 7 developed depression. The onset of depression was not related to dose or the length of therapy. When patients developed signs of depression, isotretinoin therapy was stopped and all symptoms disappeared within 2 to 7 days (Scheinman et al, 1990).
e) A 16-year-old male was started on isotretinoin 40 milligrams/day. On day 11 he began to experience hallucinations, paranoia, and incoherent speech. This behavior subsided when isotretinoin was stopped, but recurred when therapy was resumed (Villalobos et al, 1989).
f) The Adverse Drug Reaction Reporting System of the American Academy of Dermatology reported 23 suspected central nervous systems adverse reactions secondary to isotretinoin over a 4-year period (1982 to 1985). 12 of these cases being considered as definitely or probably related to isotretinoin. This included 1 case of depression and a single case of a DISULFIRAM-LIKE REACTION (Bigby & Stern, 1988e).

3.3.12.B Psychiatric sign or symptom
1) Isotretinoin therapy may cause depression, psychosis and rarely, suicidal ideation, suicide attempts and suicide. Dream pattern changes has been reported.

3.3.13 Renal Effects

Kidney disease

Kidney finding

Nephrolithiasis

Urethral finding

Urogenital finding

3.3.13.A Kidney disease
1) Renal calculi, proteinuria, hematuria, white cells in the urine, and hyperuricemia have been reported with isotretinoin therapy.
2) In a case report, a patient receiving isotretinoin 1 milligram per kilogram daily for severe acne developed URINE RETENTION. Discontinuation of isotretinoin resolved all signs and symptoms (Charalabopoulos et al, 2003).

3.3.13.B Kidney finding
1) Summary
a) PROTEINURIA, HEMATURIA, white cells in the urine, and HYPERURICEMIA have been reported in patients receiving isotretinoin (Prod Info Accutane(R), 2000b).

3.3.13.C Nephrolithiasis
1) Summary
a) CASE REPORT - A 19-year-old male developed hypercalciuria, hyperuricuria, and nephrolithiasis associated with isotretinoin (1.4 milligrams/kilogram (mg/kg)) therapy of 16 weeks duration (Bigby & Stern, 1988e).

3.3.13.D Urethral finding
1) Summary
a) Doses of isotretinoin greater than 60 milligrams/square meter induced URETHRITIS (Reuter, 1984). Urethritis was reported in 2 male patients who were being treated with isotretinoin for acne vulgaris. After discontinuation and treatment with antibiotics, urethritis resolved (Edwards & Sonnex, 1997).

3.3.13.E Urogenital finding
1) Sexual dysfunction, menstrual irregularities, and urethritis have occurred with isotretinoin therapy.

3.3.14 Reproductive Effects

Disorder of menstruation

Sexual dysfunction

3.3.14.A Disorder of menstruation
1) Summary
a) The manufacturer reports that patients have experienced abnormal menses with therapeutic doses of isotretinoin (Prod Info Accutane(R), 2000b). AMENORRHEA, and MENORRHAGIA have also been reported in patients (Cox, 1988; Christmas, 1988).
2) LITERATURE REPORTS
a) AMENORRHEA was described in a 14-year-old girl with cystic acne after receiving isotretinoin for a period of 10 weeks (25 milligrams (mg) daily for the first month, followed by 40 mg daily thereafter). The patient experienced normal menstruation every 4 weeks for the 3 years preceding isotretinoin therapy. At time of drug withdrawal, a pregnancy test was negative. Menstruation occurred approximately 10 days after discontinuing isotretinoin, and was regular thereafter. This case report suggests that isotretinoin therapy can induce amenorrhea, which can be confused with pregnancy (Cox, 1988).
b) MENORRHAGIA has been reported in a 17-year-old woman receiving isotretinoin 0.5 milligrams/kilogram/day. Upon discontinuation of therapy her period returned to normal. When re-challenged with isotretinoin, menorrhagia returned (Christmas, 1988).

3.3.14.B Sexual dysfunction
1) Summary
a) Isotretinoin does not appear to affect sperm count, sperm morphology or sperm motility, serum testosterone levels, testicular size or gonadotropins (Torok et al, 1987; Perry & McEvoy, 1983; Peck et al, 1982b; Goldstein et al, 1982a). EJACULATORY FAILURE has been associated with isotretinoin therapy in 2 cases (Coleman & MacDonald, 1994). However, congenital anomalies have occurred in children born to fathers who received isotretinoin prior to or during conception, but it is impossible to implicate isotretinoin as the causative agent (Pers Comm, 1989).

3.3.15 Respiratory Effects

Bronchospasm

Epistaxis

Pleural effusion

Respiratory finding

3.3.15.A Bronchospasm
1) Summary
a) Bronchospasm (with or without history of asthma) has been reported in patients receiving isotretinoin (Prod Info Accutane(R), 2000b; Anon, 1996). A case of exercise-induced BRONCHOCONSTRICTION in a 20- year-old college track runner with no previous history of asthma was also reported. After 3 to 4 weeks of isotretinoin therapy the patient developed exercise-induced wheezing. Isotretinoin therapy was stopped and symptoms resolved. Upon re-challange with isotretinoin after track season, the exercise-induced wheezing returned (Fisher, 1985).

3.3.15.B Epistaxis
1) LITERATURE REPORTS
a) Nose bleeds and nasal dryness are very common in patients receiving isotretinoin (McLane, 2001).

3.3.15.C Pleural effusion
1) Summary
a) A 49-year-old woman developed an EOSINOPHILIC PLEURAL EFFUSION following chronic treatment with isotretinoin. After the drug was discontinued, symptomatic improvement resulted (Bunker et al, 1989). Another patient developed BILATERAL PLEURAL EFFUSION late in therapy, but the symptoms abated with the discontinuation of the drug (Milleron et al, 1996).
2) LITERATURE REPORTS
a) Eosinophilic pleural effusion was described in a 49-year-old woman with systemic sclerosis after receiving isotretinoin 1 milligram/kilogram/day for approximately 6 months. Withdrawal of the drug resulted in resolution of symptoms on chest x-ray within 3 months. It is speculated that isotretinoin may hasten the decline in pulmonary function in these patients (Bunker et al, 1989). However, in the absence of re-challenge, a definite cause-effect relationship was not established in this case.
b) Bilateral plural effusion was reported in a 41-year-old patient 6 months after therapy with isotretinoin 60 milligrams daily. Isotretinoin was discontinued and the patient improved. The chest x-ray returned to normal 4 weeks later (Milleron et al, 1996).

3.3.15.D Respiratory finding
1) Summary
a) RESPIRATORY INFECTIONS, and voice alteration have been reported in patients receiving isotretinoin. One case of asthma exacerbation has been associated with isotretinoin (Prod Info Accutane(R), 2000b; Anon, 1996). It has been suggested that retinoids may cause drying of the respiratory tract which may increase the tendency towards asthma in certain patients (Fisher, 1985).
2) Bronchospasm, pleural effusion, respiratory infections, drying of the respiratory tract, voice alterations, and nose bleeds have occurred with isotretinoin therapy.

Answer 2

Don't ever take the sleeping pills route!!

1. They will damage your liver big time and you can get into serious health problems.

2. You will get hooked up on them and you won't be able to have a normal life any more if you don't take your pills everyday.

The sleeping pills industry is damaging our health by capitalizing on our ignorance, and by distracting people from effective and natural ways to deal with this problem. I had been taking prescription sleep medications [Ambien] for over 5 years. It stopped working and I simply took more. Still did not work. Nights were very difficult - medication put me to sleep but I would wake up after 2–3 hours with a strong sympathetic response (fast pulse, pounding heartbeat, wide awake alert). It was a very difficult cycle to break. I was really in bad shape due to lack of sleep.

After years of struggling I was able to cure my insomnia naturally and pretty fast. I followed the Sleep Tracks sleep optimization program, here is their official web -site if you want to take a look: http://www.insomniacure.net

Ohhh..and Good Luck!

Answer 3

Typically, skin conditions such as eczema have to do with poor dieting. Learn here https://tr.im/mRHHN
Eczema food triggers such as eggs, fish, peanuts, and soy are known to help reduce flare-ups, but this can vary from person to person. These foods may also exacerbate eczema because many people cannot properly digest the proteins, which causes an allergic reaction.

Answer 4

the side effects are mainly dryness (usually severe dryness) use a lot of moisturizer and chapstick. read the ipledge binder, it has more detailed information.

i wouldn't worry too much about the liver or anything like that. your doctor will monitor you while you are on it with blood tests to make sure everything is going ok. my derm said that almost no one she has treated with accutane had to stop the medication.

Answer 5

Go for kettlebell workouts — the person burns 400 calories in 20 minutes.

Answer 6

good answer smiles, do you think a 15 year old teen is going to understand all that?
accutane is effective in treating acne, the worst side effect is the damage it does to your liver...you cannot take tylenol anymore, and you cannot drink alcohol.

Answer 7

When boredom, depression, or maybe stress causes cravings, find a nonfood way to meet them such as going on a walk, calling a friend, choosing a bath, reading a book, or even doing some yoga.

Answer 8

1

Answer 9

Muscle mass can burn more calories, so include three 20-minute strength-training sessions each week.

Answer 10

Add an extra five minutes in your cardio routine.

Answer 11

Mix up your routine avoiding weight-loss plateaus.