Isotretinoin

Isotretinoin is a retinoid indicated for the treatment of severe recalcitrant nodular acne.

Isotretinoin is available under the following different brand names: Amnesteem, Claravis, Myorisan, Absorica, and Zenatane.

Dosages of Isotretinoin

Adult and Pediatric Dosage Forms and Strengths

Capsule

• 10mg (Absorica, Amnesteem, Claravis, Myorisan, Zenatane)
• 20mg (Absorica, Amnesteem, Claravis, Myorisan, Zenatane)
• 25mg (Absorica)
• 30mg (Absorica, Claravis)
• 35mg (Absorica)
• 40mg (Absorica, Amnesteem, Claravis, Myorisan, Zenatane)

Dosage Considerations – Should be Given as Follows:

Severe, Recalcitrant Nodular Acne

Severe nodular acne unresponsive to conventional therapy, including systemic antibiotics

Adult: 0.5-1 mg/kg/day orally divided twice daily for 15-20 weeks 

Dose up to 2 mg/kg/day (as tolerated) if disease is very severe with scarring or is primarily manifested on the trunk

Children under 12 years: Safety and efficacy not established

Children 12 years and older: 0.5-1 mg/kg/day orally divided twice daily for 15-20 weeks 

Dose up to 2 mg/kg/day (as tolerated) if disease is very severe with scarring or is primarily manifested on the trunk

Dosing considerations

More than 2 months after discontinuation: If warranted by persistent or recurring, severe nodular acne, may initiate a 2nd course of therapy If total nodule count is reduced by greater than 70% prior to completing 15-20 weeks, may discontinue drug

Administration

Swallow capsule whole with full glass of water to reduce esophageal irritation

Amnesteem, Claravis, Myorisan: Take with food (significantly improves absorption)

Absorica: May be taken with or without food

Common side effects of isotretinoin include:

• Chapped lips
• Dry skin
• Dry mouth
• Dry nose
• Nosebleed
• Itching
• Pink eye (conjunctivitis, including swollen eyelids [blepharoconjunctivitis])
• Irritation
• Increased erythrocyte sedimentation rates
• Thinning of hair (which has persisted in rare instances)
• Palmoplantar desquamation
• Skin fragility
• Skin infections (e.g., nail infections)
• Rash (including redness, scaly patches, eczema)
• Photosensitivity
• Hypertriglyceridemia
• Bone or joint pain
• Generalized muscle aches
• Joint pain
• Decreased HDLs
• Increased liver function tests (LFTs)
• Increased creatine phosphokinase (CPK)
• Decreased hemoglobin concentration and hematocrit
• Decreased erythrocyte and leukocyte counts
• Increased platelet count
• Decreased bone mineral density
• Premature epiphyseal closure

Other side effects of isotretinoin include:

• Lethargy
• Fatigue
• Headache
• Loss of appetite
• Nausea
• Vomiting
• Increased appetite
• Thirst

Serious side effects of isotretinoin include:

• Increased brain pressure (severe headache, blurred vision, dizziness, nausea, vomiting, seizures, or stroke)
• Rash with a fever
• Blisters on legs, arms or face and/or sores in your mouth, throat, nose, eyes, or if your skin begins to peel
• Severe stomach, chest, or bowel pain

Trouble swallowing or painful swallowing New or worsening heartburn Diarrhea Rectal bleeding Yellowing of your skin or eyes (jaundice) Dark urine Back pain Broken bones Hearing problems Vision problems Blood sugar problems

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Isotretinoin has no known severe interactions with other drugs.
• Serious interactions of isotretinoin include:
  • demeclocycline
  • doxycycline
  • lymecycline
  •  minocycline
  • oxytetracycline
  • tetracycline
• Moderate interactions of isotretinoin include:
  • methotrexate
  • mifepristone
  • mipomersen
  • teriflunomide
  • tobramycin inhaled
  • vitamin A
•  Mild interactions of isotretinoin include:
  • calcium acetate
  • calcium carbonate
  • calcium chloride
  • calcium citrate
  • calcium gluconate
  • carbamazepine
  • ciprofloxacin
  • fleroxacin
  • gemifloxacin
  • levofloxacin
  • moxifloxacin
  • norfloxacin
  • ofloxacin

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist. Check with your physician if you have health questions or concerns.

Warnings

Embryofetal toxicity:

• Do not use in female patients who are or may become pregnant, because therapy poses an extremely high risk for severe birth effects (with any dose or duration)
• Documented embryofetal effects include internal and external abnormalities, IQ scores of less than 85, spontaneous abortion, premature birth, and fetal death
• Documented external abnormalities include skull abnormality, ear abnormalities (including anotia, micropinna, small or absent external auditory canals), eye abnormalities (including microphthalmia), facial dysmorphia, and cleft palate
• Documented internal abnormalities include CNS abnormalities (including cerebral abnormalities, cerebellar malformation, hydrocephalus, microcephaly, cranial nerve deficit), cardiovascular abnormalities, thymus gland abnormality, and parathyroid hormone deficiency
• Discontinue immediately if pregnancy occurs and refer patient to an obstetrician-gynecologist experienced in reproductive toxicity for evaluation
• Potentially any fetus exposed during pregnancy can be affected, but there are no accurate methods to determine whether an exposed fetus has been affected

Restricted distribution program:

• Prescribers must register with iPLEDGE, an FDA-approved risk management program designed to minimize pregnancy exposures to isotretinoin (enhancement of earlier riskMAP [risk minimization action plan]); patients must be registered and meet all requirements of iPLEDGE
• Patients of childbearing potential must not be pregnant or breastfeeding, must be capable of complying with approved contraceptive methods, and must be reliable in following instructions

This medication contains isotretinoin. Do not take Amnesteem, Claravis, Myorisan, Absorica, or Zenatane if you are allergic to isotretinoin or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

Pregnancy (see Warnings)

Hypersensitivity to isotretinoin or vitamin A

Effects of Drug Abuse

No information available

Short-Term Effects

• See "What Are Side Effects Associated with Using Isotretinoin?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Isotretinoin?"

Cautions

Significant adverse effects are associated with isotretinoin use.

Embryofetal toxicity; major congenital malformations, spontaneous abortions, and premature births documented (see Warnings).

Do not donate blood during therapy and for 1 month after discontinuing treatment, because of embryofetal toxicity risk.

Restricted distribution program (iPLEDGE), a risk management program to minimize pregnancy exposure, has been implemented (see Warnings).

Microdosed, progesterone-only preparations ('minipills') are an inadequate method of contraception during treatment.

Depression and psychosis reported; rare reports of suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors.

Pseudotumor cerebri reported; some reports involved concomitant tetracycline use.

Serious skin reactions reported (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).

Acute pancreatitis reported with either elevated or normal serum triglyceride levels, including rare instances of fatal hemorrhagic pancreatitis; discontinue if unable to control hypertriglyceridemia.

Increased triglycerides and total cholesterol levels reported; whereas, decreased HDL-cholesterol reported.

Hearing impairment reported and may persist after discontinuing therapy.

Hepatitis may occur; mild to moderate liver enzymes elevations also reported.

Associated with inflammatory bowel disease (including regional ileitis); discontinue immediately if abdominal pain, rectal bleeding, or severe diarrhea occurs.

Negative effect on bone mineral density reported; caution with childhood osteoporosis, osteomalacia, chronic corticosteroid use, or anorexia nervosa.

Musculoskeletal symptoms, including arthralgia, may occur.

Skeletal hyperostosis observed in clinical trial for keratinization disorders.

Premature epiphyseal closure reported spontaneously with normal doses.

Ocular abnormalities observed, including corneal opacities, decreased night vision, and dry eye.

Hypersensitivity reactions (e.g., anaphylactic, cutaneous, allergic vasculitis) reported; severe allergic reaction requires discontinuation and medical management.

Laboratory monitoring:

• Pretreatment monitoring: Liver function tests (LFTs) (1 day before starting initiating therapy), 2 pregnancy tests (negative result 2 weeks before), and fasting lipid profile (including triglycerides)
• During treatment: Monitor LFTs and lipids at weekly or biweekly intervals until response to isotretinoin established
• Blood glucose, creatine phosphokinase (CPK) (particularly in those undergoing vigorous physical activity)
• Ongoing negative pregnancy tests required according to iPLEDGE rules

Pregnancy and Lactation

Do not use isotretinoin in pregnancy. The risks involved outweigh potential benefits. Safer alternatives exist. (See Warnings)

It is unknown whether isotretinoin is distributed into breast milk. Because of the potential for serious adverse reactions in nursing infants, do not administer isotretinoin to women who are breastfeeding.