Medically reviewed by Drugs.com. Last updated on May 13, 2020.
(eye soe TRET i noyn)
- 13-cis-Retinoic Acid
- 13-cis-Vitamin A Acid
- Cis-Retinoic Acid
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Absorica: 10 mg, 20 mg [contains soybean oil]
Absorica: 25 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #6 (sunset yellow), soybean oil, tartrazine (fd&c yellow #5)]
Absorica: 30 mg [contains soybean oil]
Absorica: 35 mg [contains fd&c blue #2 (indigotine), soybean oil]
Absorica: 40 mg [contains soybean oil]
Absorica LD: 8 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #10 (quinoline yellow), soybean oil]
Absorica LD: 16 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, soybean oil]
Absorica LD: 24 mg [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow), soybean oil]
Absorica LD: 32 mg [contains soybean oil]
Amnesteem: 10 mg, 20 mg, 40 mg [contains soybean oil]
Claravis: 10 mg [contains fd&c yellow #6 (sunset yellow), soybean oil]
Claravis: 20 mg, 30 mg [contains edetate disodium, soybean oil]
Claravis: 40 mg [contains edetate disodium, fd&c yellow #6 (sunset yellow), soybean oil]
Myorisan: 10 mg, 20 mg [contains soybean oil]
Myorisan: 30 mg
Myorisan: 40 mg [contains fd&c yellow #6 (sunset yellow), soybean oil]
Zenatane: 10 mg [contains brilliant blue fcf (fd&c blue #1), edetate disodium, fd&c yellow #10 (quinoline yellow), methylparaben, propylparaben, soybean oil]
Zenatane: 20 mg [contains edetate disodium, methylparaben, propylparaben, soybean oil]
Zenatane: 30 mg [contains edetate disodium, fd&c blue #2 aluminum lake, fd&c yellow #10 (quinoline yellow), methylparaben, propylparaben, soybean oil]
Zenatane: 40 mg [contains brilliant blue fcf (fd&c blue #1), edetate disodium, fd&c blue #2 (indigotine), fd&c yellow #10 (quinoline yellow), methylparaben, propylparaben, soybean oil]
Generic: 10 mg, 20 mg, 30 mg, 40 mg
Brand Names: U.S.
- Absorica LD
- Acne Products
- Antineoplastic Agent, Retinoic Acid Derivative
- Retinoic Acid Derivative
Reduces sebaceous gland size and reduces sebum production in acne treatment; in neuroblastoma, decreases cell proliferation and induces differentiation
Standard formulation: Enhanced with a high-fat meal.
Lidose formulation (Absorica): AUC0-t and Cmax increased 50% and 26%, respectively, under fed compared to fasting conditions.
Micronized formulation (Absorica LD): AUC0-t and Cmax increased 20% and 6%, respectively, under fed compared to fasting conditions.
Hepatic via CYP2B6, 2C8, 2C9, 3A4; forms metabolites; major metabolite: 4-oxo-isotretinoin (active)
Urine and feces (equal amounts)
Time to Peak
Standard formulation: 5.3 hours (fed); 3.2 hours (fasting).
Lidose formulation (Absorica): 6.4 hours (fed); 2.9 hours (fasting).
Micronized formulation (Absorica LD): Median: 5 hours (fed); 3.5 hours (fasting).
Standard formulation: Parent drug: 21 ± 8.2 hours; Metabolite: 24 ± 5.3 hours.
Lidose formulation (Absorica): Parent drug: 18 hours; Metabolite: 38 hours.
Micronized formulation (Absorica LD): Parent drug: ~24 hours; Metabolite: ~38 hours.
99% to 100%; primarily albumin
Use: Labeled Indications
Acne, severe recalcitrant nodular: Treatment of severe recalcitrant nodular acne unresponsive to conventional therapy (including systemic antibiotics).
Off Label Uses
Data from a randomized, controlled comparative study supports the use of isotretinoin (conventional and low-dose regimen) in patients with moderate acne. However, side-effects were more frequent in the conventional regimen compared to the low-dose regimen, and results suggested that the low-dose regimen had higher patient satisfaction. The authors concluded that low-dose isotretinoin is most suitable for patients with moderate acne when considering tolerability, efficacy, and patient satisfaction [Lee 2011]. A prospective, non-comparative, open-label study in patients with moderate acne also found low-dose isotretinoin was effective (defined as complete or almost complete remission of acne lesions) with a low incidence of severe side effects [Amichai 2006].
Based on the American Academy of Dermatology guidelines of care for acne vulgaris management, isotretinoin is an effective and recommended treatment for moderate degrees of treatment-resistant acne or acne that produces physical scarring or psychological distress.
Cutaneous T-cell lymphomas
Data from small clinical trials in patients with cutaneous T-cell lymphoma (mycosis fungoides) suggests that isotretinoin (in combination with interferon alfa-2b) may be beneficial in the treatment of this condition [Duvic 2003], [Knobler 1991]. Additional trials may be necessary to further define the role of isotretinoin in this setting.
Squamous cell skin cancer (prevention in high-risk patients)
Clinical experience suggests that oral retinoids may be useful for prevention of squamous cell skin cancer in high-risk patients. Acitretin may be the preferred agent in certain patient populations; however, due to a shortened half-life, isotretinoin may be preferred (with appropriate pregnancy testing and contraception) in females of reproductive potential [Otley 2006]. Additional data is necessary to further define the role of isotretinoin in this setting.
Hypersensitivity to isotretinoin or any component of the formulation; sensitivity to parabens (Zenatane only) or vitamin A; pregnancy.
Canadian labeling: Additional contraindications not in the US labeling: Breastfeeding, hepatic or renal insufficiency, hypervitaminosis A, excessive hyperlipidemia, concurrent tetracycline therapy.
Documentation of allergenic cross-reactivity for retinoids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Note: Isotretinoin products are available in different formulations; a standard formulation (eg, Amnesteem, Claravis, Myorisan, Zenatane) that requires administration with food and lidose (Absorica) and micronized (Absorica LD) formulations that may be administered with or without food. Standard formulations are not bioequivalent to lidose or micronized formulations. Lidose and micronized formulations are not substitutable with one another due to differences in bioavailability.
Note: All dosing is based on use of a standard or lidose formulation unless otherwise indicated.
Acne (severe recalcitrant nodular):
0.5 mg/kg/day in 2 divided doses for 1 month, then increase to 1 mg/kg/day in 2 divided doses as tolerated. Continue until a total cumulative dose of 120 to 150 mg/kg is reached (AAD [Zaenglein 2016]).
Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice.
Standard or lidose formulation: 0.5 to 1 mg/kg/day in 2 divided doses. Adults with very severe disease/scarring or primarily involves the trunk may require dosage adjustment up to 2 mg/kg/day, as tolerated.
Micronized formulation: 0.4 to 0.8 mg/kg/day in 2 divided doses. Adults with very severe disease/scarring or primarily involves the trunk may require dosage adjustment up to 1.6 mg/kg/day, as tolerated.
Acne (moderate) (off-label use): Oral: Low-dose regimens: 20 mg/day (~0.3 to 0.4 mg/kg/day) for 6 months (Amichai 2006) or 0.25 to 0.4 mg/kg daily for 24 weeks (Lee 2011)
Cutaneous T-cell lymphomas (off-label use): Oral: Induction: 1 mg/kg/day (in 2 divided doses and in combination with interferon alfa-2b) for 3 to 4 months (Duvic 2003; Knobler 1991). If response occurs, may continue therapy for an additional 3 months; if response continues after 6 months of therapy, may administer isotretinoin and interferon alfa-2b at a 50% reduced dose for an additional 3 months, followed by interferon alfa-2b maintenance therapy (Knobler 1991). Additional trials may be necessary to further define the role of isotretinoin in the management of this condition.
Squamous cell skin cancer, prevention in high-risk patients (off-label use): Oral: Initial: 0.25 mg/kg every other day for 1 month, then 0.25 mg/kg daily for one month, then 0.5 mg/kg daily. Adjust dose as needed based on tolerance; higher doses may be more effective for severe skin cancer (Otley 2006). Additional data may be necessary to further define the role of isotretinoin in this setting.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Refer to adult dosing.
Note: The product formulation of Absorica LD (micronized) is not bioequivalent to other capsule formulations of isotretinoin (eg, Absorica, or softgel formulations: generics, Amnesteem, Claravis, Myorisan, Zenatane) and should not be substituted on a mg:mg basis.
Acne vulgaris, severe recalcitrant nodular: Children ≥12 years and Adolescents:
Softgel capsule (eg, generics, Amnesteem, Claravis, Myorisan, Zenatane) or hard-gelatin capsule (Absorica):
Initial: Oral: 0.5 mg/kg/day in 2 divided doses for 4 weeks, then increase dose to 1 mg/kg/day in 2 divided doses (AAD [Zaenglein 2016]; AAP [Eichenfield 2013]); for severe extensive cases (involving trunk, nuchal region, lower back, buttocks, thighs) may require higher doses up to 2 mg/kg/day in 2 divided doses (manufacturer labeling).
Duration of therapy: Typically 15 to 20 weeks depending upon daily dose; a target cumulative dose range of 120 to 150 mg/kg has been recommended based on observed lower relapse rates with courses ≥120 mg/kg and the plateau effect observed with higher cumulative total doses of >150 mg/kg (AAD [Zaenglein 2016]).
Repeat course: In older adolescents who have completed skeletal growth, a second course of isotretinoin may be repeated after a period of ≥2 months off therapy for persistent or recurring severe nodular acne; for younger patients who have not completed skeletal growth, the optimal interval before retreatment has not been defined.
Micronized hard-gelatin capsule (eg, Absorica LD): Oral: 0.4 to 0.8 mg/kg/day in 2 divided doses. In adults with severe, extensive cases (involving trunk, nuchal region, lower back, buttocks, thighs), higher doses up to 1.6 mg/kg/day in 2 divided doses have been used; pediatric data specific to the micronized dosage form is lacking. Duration of therapy is typically 15 to 20 weeks, until the total cyst count decreased by 70%, whichever is sooner. Based on experience with other isotretinoin dosage forms, in older adolescents who have completed skeletal growth, a second course of isotretinoin may be repeated after a period of ≥2 months off therapy for persistent or recurring severe nodular acne; for younger patients who have not completed skeletal growth, the optimal interval before retreatment has not been defined.
Acne vulgaris, moderate: Limited data available: Children ≥12 years and Adolescents: Softgel capsule (eg, generics, Amnesteem, Claravis, Myorisan, Zenatane) and hard-gelatin capsule (Absorica): Oral: 0.25 to 0.4 mg/kg/day continued for 6 to 12 months (AAD [Zaenglein 2016]; Amichai 2006).
Neuroblastoma, maintenance: Limited data available: Infants, Children, and Adolescents: Softgel capsule (eg, generics, Amnesteem, Claravis, Myorisan, Zenatane) and hard-gelatin capsule (Absorica): Oral: 80 mg/m2/dose every 12 hours for the last 2 weeks (14 consecutive days) of a 4-week cycle for 6 cycles; dinutuximab therapy is administered during the first week of the 4-week cycle (Yu 2010); begin after continuation chemotherapy or transplantation (Matthay 1999).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
For patients unable to swallow the capsules whole, an oral liquid may be prepared with softgel capsules (not recommended by the manufacturers) by one of the following methods:
Place capsules (softgel formulations only) in small container and add warm (~37°C [97°F]) water or milk to cover capsule(s); wait 2 to 3 minutes until capsule is softened and then drink the milk or water with the softened capsule, or swallow softened capsule.
Puncture capsule (softgel formulations only) with needle or cut with scissors; squeeze capsule contents into 5 to 10 mL of milk or tube feed formula; draw mixture up into oral syringe and administer via feeding tube; flush feeding tube with ≥30 mL additional milk or tube feeding formula.
Puncture capsule (softgel formulations only) with needle or cut with scissors and draw contents into oral syringe; add 1 to 5 mL of medium chain triglyceride, soybean, or safflower oil to the oral syringe; mix gently and administer via feeding tube; flush feeding tube with ≥30 mL milk or tube feeding formula.Lam MS. Extemporaneous compounding of oral liquid dosage formulations and alternative drug delivery methods for anticancer drugs. Pharmacotherapy. 2011;31(2):164-192.21275495
Oral: Administer standard formulation with a meal; lidose (Absorica) or micronized (Absorica LD) formulations may be taken without regard to meals. According to the manufacturer's labeling, capsules should be swallowed whole with a full glass of liquid; do not chew or suck on the capsule. For patients unable to swallow capsule whole, an oral liquid may be prepared (see "Extemporaneously Prepared"); may irritate esophagus if contents are removed from the capsule. Safety of once-daily dosing of isotretinoin has not been established and is not recommended.
Neuroblastoma (off-label use): In a pharmacokinetic study, the end of the capsule was punctured/cut and capsule contents extruded into ice cream or yogurt if patients were unable to swallow capsules whole; if capsule is opened, contents must be consumed immediately to avoid degradation (Veal 2007). Refer to "Extemporaneously Prepared" for additional information.
Standard formulation should be taken with food; lidose (Absorica) or micronized formulations (Absorica LD) may be taken without regard to meals. Limit intake of vitamin A; avoid use of other vitamin A products. Some formulations may contain soybean oil.
Store at 20°C to 25°C (68°F to 77° F); excursions permitted between 15°C to 30°C (59°F to 86°F). Protect from light.
Alcohol (Ethyl): May enhance the adverse/toxic effect of ISOtretinoin (Systemic). Specifically, the risk for elevated triglyceride concentrations may be increased. Monitor therapy
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy
Mipomersen: ISOtretinoin (Systemic) may enhance the hepatotoxic effect of Mipomersen. Monitor therapy
Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination
Multivitamins/Minerals (with AE, No Iron): May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy
Progestins (Contraceptive): Retinoic Acid Derivatives may diminish the therapeutic effect of Progestins (Contraceptive). Retinoic Acid Derivatives may decrease the serum concentration of Progestins (Contraceptive). Management: Two forms of effective contraception should be used in patients receiving retinoic acid derivatives. Microdosed progesterone-only preparations (ie, minipills that do not contain estrogen) are considered an inadequate method of contraception. Consider therapy modification
Tetracyclines: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. The development of pseudotumor cerebri is of particular concern. Avoid combination
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy
Vitamin A: May enhance the adverse/toxic effect of Retinoic Acid Derivatives. Avoid combination
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Endocrine & metabolic: Increased serum triglycerides (25% including cases reported >800 mg/dL), increased creatine phosphokinase in blood specimen (adults: 24%; adolescents: 12%), decreased HDL cholesterol (15%)
Hepatic: Increased liver enzymes (15%)
Neuromuscular & skeletal: Back pain (children: 29%), arthralgia (≤22%), musculoskeletal disease (16%)
1% to 10%:
Endocrine & metabolic: Increased serum cholesterol (7%)
Neuromuscular & skeletal: Decreased bone mineral density (adolescents: 9%), severe arthralgia (children: 8%)
Frequency not defined:
Cardiovascular: Cerebrovascular accident, chest pain, edema, flushing, palpitations, syncope, tachycardia, thrombosis, vasculitis
Dermatologic: Acne fulminans, alopecia, cheilitis, cheilosis, contact dermatitis, dermatitis, diaphoresis, eczema, erythema of skin, facial erythema, fragile skin, hair disease, nail disease, paronychia, pruritus, pyogenic granuloma, scaling of skin of feet, seborrhea, skin photosensitivity, skin rash, sunburn, superficial peeling of palms, urticaria, xeroderma
Endocrine & metabolic: Altered serum glucose, decreased libido, eruptive xanthoma, hirsutism, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased LDL cholesterol, increased serum glucose, hyperuricemia, menstrual disease, weight loss
Gastrointestinal: Abdominal pain, colitis, constipation, decreased appetite, diarrhea, esophagitis, esophageal ulcer, gingival hemorrhage, gingivitis, ileitis, inflammatory bowel disease, nausea, pancreatitis, vomiting, xerostomia
Genitourinary: Erectile dysfunction, gross hematuria, microscopic hematuria, proteinuria, pyuria, sexual disorder
Hematologic & oncologic: Anemia, bruise, decreased white blood cell count, increased erythrocyte sedimentation rate, lymphadenopathy, purpuric disease, severe neutropenia, thrombocythemia, thrombocytopenia
Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, increased serum bilirubin
Infection: Herpes simplex infection (disseminated), infection
Nervous system: Aggressive behavior, anxiety, auditory hallucinations, depression, dizziness, drowsiness, emotional lability, euphoria, fatigue, headache, idiopathic intracranial hypertension, insomnia, irritability, lethargy, malaise, nervousness, outbursts of anger, pain, panic attack, paresthesia, psychosis, seizure, suicidal ideation, suicidal tendencies, violent behavior, voice disorder
Neuromuscular & skeletal: Asthenia, arthritis, bone fracture, calcification of ligament, calcification of tendon, granulomatosis with polyangiitis, limb pain, musculoskeletal pain, myalgia, neck pain, osteopenia, osteoporosis, premature epiphyseal closure, skeletal hyperostosis, stiffness, tendinopathy
Ophthalmic: Asthenopia, blepharitis, blurred vision, cataract, conjunctivitis, corneal opacity, decreased visual acuity, eye irritation, eye pruritus, hordeolum, increased lacrimation, keratitis, ocular hyperemia, optic neuritis, photophobia, vision color changes, visual disturbance
Respiratory: Bronchospasm, dry nose, epistaxis, nasopharyngitis, respiratory tract infection, upper respiratory tract infection
Miscellaneous: Wound healing impairment
Postmarketing: Acute pancreatitis, agranulocytosis, allergic skin reaction, anaphylaxis, auditory impairment, dry eye syndrome, erythema multiforme, eyelid disease (meibomian gland dysfunction/atrophy; Neudorfer 2012), hepatitis, hypersensitivity angiitis, hypersensitivity reaction, intracranial hypertension (Tan 2019), night blindness, rhabdomyolysis, Stevens-Johnson syndrome, toxic epidermal necrolysis
ALERT: U.S. Boxed WarningPregnancy:
Isotretinoin can cause severe, life-threatening birth defects and is contraindicated in pregnancy. There is an extremely high risk that severe birth defects will result if pregnancy occurs while taking any amount of isotretinoin, even for short periods of time. Potentially, any fetus exposed during pregnancy can be affected. There are no accurate means of determining prenatally whether an exposed fetus has been affected.
Birth defects that have been documented following isotretinoin exposure include abnormalities of the face, eyes, ears, skull, CNS, cardiovascular system, and thymus and parathyroid glands. Cases of intelligence quotient (IQ) scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion, and premature births have been reported.
Documented external abnormalities include skull abnormality; ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (including microphthalmia); facial dysmorphia; cleft palate. Documented internal abnormalities include CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency. In some cases, death has occurred with some of the abnormalities previously noted.
If pregnancy does occur during treatment of a patient who is taking isotretinoin, isotretinoin must be discontinued immediately and the patient should be referred to an obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling.Special prescribing requirements:
Because of isotretinoin's teratogenicity and to minimize fetal exposure, isotretinoin is approved for marketing only under a special restricted distribution program approved by the Food and Drug Administration. This program is called iPLEDGE. Isotretinoin must only be prescribed by prescribers who are registered and activated with the iPLEDGE program. Isotretinoin must only be dispensed by a pharmacy registered and activated with iPLEDGE, and must only be dispensed to patients who are registered and meet all the requirements of iPLEDGE.
Concerns related to adverse effects:
• Auditory impairment: Hearing impairment, which can continue after therapy is discontinued, may occur. Discontinue therapy if hearing impairment or tinnitus develops.
• Bone mineral density loss: May decrease bone mineral density; osteoporosis, osteopenia, bone fractures, and delayed healing of bone fractures have been reported. Use caution in patients with a genetic predisposition for bone loss (eg, age-related osteoporosis, history of childhood osteoporosis conditions, osteomalacia, other disorders of bone metabolism); including patients diagnosed with anorexia nervosa and those on concomitant medications that may cause drug-induced osteoporosis/osteomalacia and/or affect vitamin D metabolism (eg, systemic corticosteroids, anticonvulsants). Patients may be at increased risk when participating in activities with repetitive impact (such as sports) where the risk of spondylolisthesis with and without pars fractures and hip growth plate injuries in early and late adolescence are known.
• Dermatologic effects: Postmarketing reports of erythema multiforme and severe skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis), including fatalities, have been reported; monitor for severe skin reactions; discontinue use if severe skin reaction occurs.
• Growth effects: Skeletal hyperostosis and premature epiphyseal closure have also been reported with the use.
• Hematologic effects: Neutropenia and rare cases of agranulocytosis have been reported; discontinue if clinically significant decreases in white cell counts occur.
• Hepatic effects: Clinical hepatitis and mild to moderate elevated liver enzymes have been reported with use; liver enzymes may normalize with dosage reduction or with continued treatment. Discontinue therapy if hepatic enzymes do not normalize or if hepatitis is suspected.
• Hypersensitivity reactions: Anaphylaxis and other types of allergic reactions, including cutaneous reactions and serious cases of allergic vasculitis, often with purpura of the extremities and extracutaneous involvement (including renal), have been reported. Discontinue therapy if a serious allergic reaction occurs and institute appropriate medical management.
• Inflammatory bowel disease: Inflammatory bowel disease (IBD), including regional ileitis, has been reported in patients without a prior history of intestinal disorders; discontinue treatment immediately if abdominal pain, rectal bleeding, or severe diarrhea occurs. Of note, a position statement from the American Academy of Dermatology states that based on currently available data, there is insufficient evidence to prove either an association or a causal relationship between IBD and isotretinoin use (AAD 2016).
• Musculoskeletal effects: Musculoskeletal symptoms (including arthralgia) have been reported; generally symptoms were mild to moderate, but occasionally required discontinuation of therapy. Transient pain in the chest has occurred; symptoms generally cleared after discontinuation of therapy, but in some cases persisted. Rhabdomyolysis, some associated with strenuous physical activity, has been reported (rarely).
• Ocular effects: Vision impairment, corneal opacities, decreased tolerance to contact lenses (due to dry eyes), and decreased night vision have been reported with use; discontinue therapy in patients experiencing visual difficulties. Warn patients to be cautious when driving or operating machinery at night.
• Pancreatitis: Acute pancreatitis may occur in patients with normal or elevated triglyceride levels; fatal hemorrhagic pancreatitis (rare) has been reported; discontinue therapy if hypertriglyceridemia cannot be controlled at an acceptable level or symptoms of pancreatitis occurs.
• Photosensitivity: Avoid prolonged exposure to UV rays or sunlight.
• Pseudotumor cerebri: Retinoids have been associated with pseudotumor cerebri (benign intracranial hypertension), especially in children. Concurrent use of other drugs associated with this effect (eg, tetracyclines) may increase risk. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances; discontinue immediately and refer patient to a neurologist if papilledema occurs.
• Psychiatric effects: May cause depression, psychosis, mood disturbance, and rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. All patients should be observed closely for symptoms of depression or suicidal thoughts. Discontinue therapy if depression, mood disturbance, psychosis, or aggression develops. Discontinuation of treatment alone may not be sufficient, further evaluation may be necessary. Use with extreme caution in patients with a history of psychiatric disorder.
• Diabetes: Use with caution in patients with diabetes mellitus; impaired glucose control has been reported.
• Hypertriglyceridemia: Marked elevations of serum triglycerides have been reported; use with caution in patients with hypertriglyceridemia or those who may be at high risk (eg, patients with diabetes, obesity, increased alcohol intake, family history of or those with lipid metabolism disorder). The effects on triglycerides, high-density lipoprotein, and cholesterol have been reversible upon discontinuation of therapy. Instruct patients to avoid or limit ethanol; may increase triglyceride levels if taken in excess.
• Pregnancy: [US Boxed Warnings]: Use of isotretinoin is contraindicated in patients who are pregnant. Birth defects (facial, eye, ear, skull, central nervous system, cardiovascular, thymus and parathyroid gland abnormalities) have been noted following isotretinoin exposure during pregnancy and the risk for severe birth defects is high, with any dose or even with short treatment duration. Low IQ scores have also been reported. The risk for spontaneous abortion and premature births is increased. Because of the high likelihood of teratogenic effects, all patients (male and female), prescribers, wholesalers, and dispensing pharmacists must register and be active in the iPLEDGE risk evaluation and mitigation strategy (REMS) program; do not prescribe isotretinoin for patients who are or who are likely to become pregnant while using the drug. If pregnancy occurs during therapy, isotretinoin should be discontinued immediately and the patient referred to an obstetrician-gynecologist specializing in reproductive toxicity.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Product interchange: Isotretinoin and tretinoin (which is also known as all-trans retinoic acid, or ATRA) may be confused, while both products may be used in cancer treatment, they are not interchangeable; verify product prior to dispensing and administration to prevent medication errors.
• Tartrazine: Some products may contain tartrazine (FD&C yellow no. 5), which may cause allergic reactions, including bronchial asthma, in certain individuals. Allergy is frequently seen in patients who also have an aspirin hypersensitivity.
• Blood donation: Patients should be instructed not to donate blood during therapy and for 1 month following discontinuation of therapy due to risk of donated blood being given to a pregnant patient.
• Experienced health care provider: This medication should only be prescribed by health care providers competent in treating severe recalcitrant nodular acne and experienced with the use of systemic retinoids.
• Long-term use: Safety of long-term use is not established and is not recommended; the effect on bone loss is unknown.
• REMS program: [US Boxed Warning]: Because of the high likelihood of teratogenic effects, all patients (male and female), prescribers, wholesalers, and dispensing pharmacists must register and be active in the iPLEDGE risk evaluation and mitigation strategy (REMS) management program; do not prescribe isotretinoin for patients who are or who are likely to become pregnant while using the drug.
• Skin resurfacing procedures: Avoid skin resurfacing procedures (eg, dermabrasion, laser) and wax epilation during therapy and for ≥6 months after discontinuation of isotretinoin due to the risk of scarring.
CBC with differential and platelet count, baseline sedimentation rate, glucose, CPK; signs of depression, mood alteration, psychosis, aggression, severe skin reactions; changes in vision
Pregnancy test (for all patients of childbearing potential): Two negative tests with a sensitivity of ≥25 milliunits/mL prior to beginning therapy (the second performed ≥19 days after the first test and performed during the first 5 days of the menstrual period immediately preceding the start of therapy); monthly tests to rule out pregnancy prior to refilling prescription and 1 month after discontinuation.
Lipids: Prior to treatment and at weekly or biweekly intervals until response to treatment is established. Test should not be performed <36 hours after consumption of ethanol.
Liver function tests: Prior to treatment and at weekly or biweekly intervals until response to treatment is established.
When used for oncology indications, monitor adherence.
[US Boxed Warning]: Isotretinoin must not be used by patients who may become pregnant.
Patients of childbearing potential must be able to comply with the guidelines of the iPLEDGE™ pregnancy prevention program. Females of childbearing potential must have 2 negative pregnancy tests with a sensitivity of ≥25 milliunits/mL prior to beginning therapy, and testing should continue monthly during therapy. Patients of childbearing potential should not become pregnant during therapy or for 1 month following discontinuation of isotretinoin. Upon discontinuation of treatment, patients of childbearing potential should have a pregnancy test after their last dose and again 1 month after their last dose.
All patients (male and female), must be registered in the iPLEDGE™ risk management program. Patients of childbearing potential must receive oral and written information reviewing the hazards of therapy and the effects that isotretinoin can have on a fetus. Therapy should not begin without 2 negative pregnancy tests ≥19 days apart. Two forms of contraception (a primary and secondary form as described in the iPLEDGE™ program materials) must be used simultaneously beginning 1 month prior to treatment, during treatment, and for 1 month after therapy is discontinued; limitations to their use must be explained. Micro-dosed progesterone products that do not contain an estrogen ("mini-pills") are not an acceptable form of contraception during isotretinoin treatment. Prescriptions should be written for no more than a 30-day supply, and pregnancy testing and counseling should be repeated monthly. During therapy, pregnancy tests must be conducted by a CLIA-certified laboratory. Prescriptions must be filled and picked up from the pharmacy within 7 days of specimen collection for pregnancy test for patients of childbearing potential. Prescriptions for patients of nonchildbearing potential (male and female) must be filled and picked up within 30 days of prescribing.
Any cases of accidental pregnancy should be reported to the iPLEDGE™ program or FDA MedWatch. All patients (male and female) must read and sign the informed consent material provided in the pregnancy prevention program.
Pregnancy Risk Factor
Isotretinoin and its metabolites can be detected in fetal tissue following maternal use during pregnancy (Benifla 1995; Kraft 1989).
Use is contraindicated in pregnant women. [US Boxed Warning]: Isotretinoin must not be used by patients who are pregnant. There is an extremely high risk that severe birth defects can result if pregnancy occurs while taking isotretinoin in any amount, even for short periods of time. Potentially, any fetus exposed during pregnancy can be affected. There are no accurate means of determining whether an exposed fetus has been affected. Birth defects that have been documented following isotretinoin exposure include abnormalities of the face, eyes, ears, skull, CNS, cardiovascular system, and thymus and parathyroid glands. Cases of intelligence quotient (IQ) scores less than 85 with or without other abnormalities have been reported. There is an increased risk of spontaneous abortion, and premature births have been reported. Documented external abnormalities include skull abnormality; ear abnormalities (including anotia, micropinna, small or absent external auditory canals); eye abnormalities (including microphthalmia); facial dysmorphia; cleft palate. Documented internal abnormalities include CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit); cardiovascular abnormalities; thymus gland abnormality; parathyroid hormone deficiency. In some cases, death has occurred with some of the abnormalities previously noted.
If pregnancy does occur during treatment of a patient who is taking isotretinoin, isotretinoin must be discontinued immediately and the patient should be referred to an obstetrician-gynecologist experienced in reproductive toxicity for further evaluation and counseling.
Any pregnancies should be reported to the iPLEDGE™ program (www.ipledgeprogram.com or 866-495-0654) and the FDA through MedWatch (800-FDA-1088).
What is this drug used for?
• It is used to treat pimples (acne).
• It may be given to you for other reasons. Talk with the doctor.
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Dry mouth
• Dry eyes
• Dry skin
• Dry lips
• Nasal irritation
• Poor night vision
• Contact lens discomfort
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight
• Depression like thoughts of suicide, anxiety, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Esophageal problems like chest pain, trouble swallowing, or heartburn.
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit.
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting.
• Behavioral changes
• Severe headache
• Severe diarrhea
• Rectal bleeding
• Rectal pain
• Severe abdominal pain
• Eye pain
• Muscle pain
• Muscle weakness
• Joint pain
• Bone pain
• Severe loss of strength and energy
• Unable to pass urine
• Change in amount of urine passed
• Back pain
• Swollen gland
• Abnormal heartbeat
• Fast heartbeat
• Trouble hearing
• Noise or ringing in the ears
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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- Drug class: miscellaneous antineoplastics
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