Amnesteem and Night Sweats

Amnesteem has a tendency to cause sweating, flushing  and many other side effects that make it difficult to get a good nights sleep. Here you will find the warnings, precautions, and side effects attributed to this drug.

 

CONTRAINDICATlONS AND WARNINGS Amnesteem capsules must not be used by females who are pregnant. Although not every fetus exposed to isotretinoin has resulted in a deformed child, there is an extremely high risk that a deformed infant can result if pregnancy occurs while taking isotretinoin capsules in any amount even for short periods of time. Potentially any fetus exposed during pregnancy can be affected. Presently, there are no accurate means of determining, after isotretinoin exposure, which fetus has been affected and which fetus has not been affected. Major human fetal abnormalities related to isotretinoin administration in females have been documented. There is an increased risk of spontaneous abortion. In addition, 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 certain of the abnormalities previously noted. Cases of IQ scores less than 85 with or without obvious CNS abnormalities have also been reported. Amnesteem is contraindicated in females of childbearing potential unless the patient meets all of the following conditions: Must NOT be pregnant or breast-feeding. Must be capable of complying with the mandatory contraceptive measures required for Amnesteem therapy and understand behaviors associated with an increased risk of pregnancy. Must be reliable in understanding and carrying out instructions. Amnesteem must be prescribed under the System to Prevent Isotretinoin-Related Issues of Teratogenicity™ (S.P.I.R.I.T.™). To prescribe Amnesteem, the prescriber must obtain a supply of yellow self-adhesive isotretinoin qualification stickers. To obtain these stickers: Read the booklet entitled System to Prevent Isotretinoin-Related Issues of Teratogenicity (S.P.I.R.I.T.) Guide to Best Practices. Sign and return the completed S.P.I.R.I.T. Letter of Understanding containing the following Prescriber Checklist: I know the risk and severity of fetal injury/birth defects from isotretinoin I know how to diagnose and treat the various presentations of acne I know the risk factors for unplanned pregnancy and the effective measures for avoidance of unplanned pregnancy It is the informed patient's responsibility to avoid pregnancy during Amnesteem therapy and for 1 month after stopping Amnesteem. To help patients have the knowledge and tools to do so: Before beginning treatment of female patients with Amnesteem I will refer for expert, detailed pregnancy prevention counseling and prescribing, reimbursed by Bertek Pharmaceuticals Inc., OR I have the expertise to perform this function and elect to do so I understand, and will properly use throughout the Amnesteem treatment course, the S.P.I.R.I.T. procedures for Amnesteem, including monthly pregnancy avoidance counseling, pregnancy testing and use of the yellow self-adhesive isotretinoin qualification stickers To use the yellow self-adhesive isotretinoin qualification stickers: Amnesteem should not be prescribed or dispensed to any patient (male or female) without a yellow self-adhesive isotretinoin qualification sticker. For female patients, the yellow self-adhesive isotretinoin qualification sticker signifies that she: Must have had 2 negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial Amnesteem prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for Amnesteem. The second pregnancy test (a confirmation test) should be done during the first 5 days of the menstrual period immediately preceding the beginning of Amnesteem therapy. For patients with amenorrhea, the second test should be done at least 11 days after the last act of unprotected sexual intercourse (without using 2 effective forms of contraception). Each month of therapy, the patient must have a negative result from a urine or serum pregnancy test. A pregnancy test must be repeated every month prior to the female patient receiving each prescription. Must have selected and have committed to use 2 forms of effective contraception simultaneously, at least 1 of which must be a primary form, unless absolute abstinence is the chosen method, or the patient has undergone a hysterectomy. Patients must use 2 forms of effective contraception for at least 1 month prior to initiation of Amnesteem therapy, during Amnesteem therapy, and for 1 month after discontinuing Amnesteem therapy. Counseling about contraception and behaviors associated with an increased risk of pregnancy must be repeated on a monthly basis. Effective forms of contraception include both primary and secondary forms of contraception. Primary forms of contraception include: tubal ligation, partner's vasectomy, intrauterine devices, birth control pills, and topical/injectable/implantable/insertable hormonal birth control products. Secondary forms of contraception include diaphragms, latex condoms, and cervical caps; each must be used with a spermicide. Any birth control method can fail. Therefore, it is critically important that women of childbearing potential use 2 effective forms of contraception simultaneously. A drug interaction that decreases effectiveness of hormonal contraceptives has not been entirely ruled out for isotretinoin. Although hormonal contraceptives are highly effective, there have been reports of pregnancy from women who have used oral contraceptives, as well as topical/injectable/implantable/insertable hormonal birth control products. These reports occurred while these patients were taking isotretinoin. These reports are more frequent for women who use only a single method of contraception. Patients must receive written warnings about the rates of possible contraception failure (included in patient education kits). Prescribers are advised to consult the package insert of any medication administered concomitantly with hormonal contraceptives, since some medications may decrease the effectiveness of these birth control products. Patients should be prospectively cautioned not to self-medicate with the herbal supplement St. John's Wort because a possible interaction has been suggested with hormonal contraceptives based on reports of breakthrough bleeding on oral contraceptives shortly after starting St. John's Wort. Pregnancies have been reported by users of combined hormonal contraceptives who also used some form of St. John's Wort (see PRECAUTIONS ). Must have signed a Patient Information/Consent form that contains warnings about the risk of potential birth defects if the fetus is exposed to isotretinoin. Must have been informed of the purpose and importance of participating in the Isotretinoin Survey and have been given the opportunity to enroll (see PRECAUTIONS ). The yellow self-adhesive isotretinoin qualification sticker documents that the female patient is qualified, and includes the date of qualification, patient gender, cut-off date for filling the prescription, and up to a 30-day supply limit with no refills. These yellow self-adhesive isotretinoin qualification stickers should also be used for male patients. If a pregnancy does occur during treatment of a woman with Amnesteem, the prescriber and patient should discuss the desirability of continuing the pregnancy. Prescribers are strongly encouraged to report all cases of pregnancy to Bertek Medical Services @ 1-800-809-8237 where a Bertek Pregnancy Prevention Initiative Specialist will be available to discuss Bertek pregnancy information, or prescribers may contact the Food and Drug Administration MedWatch Program @ 1-800-FDA-1088. Amnesteem should be prescribed only by prescribers who have demonstrated special competence in the diagnosis and treatment of severe recalcitrant nodular acne, are experienced in the use of systemic retinoids, have read the S.P.I.R.I.T. Guide to Best Practices , signed and returned the completed S.P.I.R.I.T. Letter of Understanding , and obtained yellow self-adhesive isotretinoin qualification stickers. Amnesteem should not be prescribed or dispensed without a yellow self-adhesive isotretinoin qualification sticker. INFORMATION FOR PHARMACISTS: AMNESTEEM MUST ONLY BE DISPENSED: IN NO MORE THAN A 30-DAY SUPPLY ONLY ON PRESENTATION OF AN ISOTRETINOIN CAPSULES PRESCRIPTION WITH A YELLOW SELF-ADHESIVE ISOTRETINOIN QUALIFICATION STICKER WITHIN 7 DAYS OF THE QUALIFICATION DATE REFILLS REQUIRE A NEW PRESCRIPTION WITH A YELLOW SELF-ADHESIVE ISOTRETINOIN QUALIFICATION STICKER NO TELEPHONE OR COMPUTERIZED PRESCRIPTIONS ARE PERMITTED. AN AMNESTEEM MEDICATION GUIDE MUST BE GIVEN TO THE PATIENT EACH TIME AMNESTEEM IS DISPENSED, AS REQUIRED BY LAW. THIS AMNESTEEM MEDICATION GUIDE IS AN IMPORTANT PART OF THE RISK MANAGEMENT PROGRAM FOR THE PATIENT.

 

DESCRIPTION

Isotretinoin, a retinoid, is available as Amnesteem in 10 mg, 20 mg and 40 mg soft gelatin capsules for oral administration. Each capsule contains yellow wax, butylated hydroxyanisole, edetate disodium, hydrogenated vegetable oil, and soybean oil. Gelatin capsules contain glycerin, with the following dye systems: 10 mg - red iron oxide paste and black ink; 20 mg - red iron oxide paste, yellow iron oxide paste, titanium dioxide and black ink; 40 mg - red iron oxide paste, yellow iron oxide paste, titanium dioxide, and black ink.

Chemically, isotretinoin is 13- cis -retinoic acid and is related to both retinoic acid and retinol (vitamin A). It is a yellow to orange crystalline powder with a molecular weight of 300.44. The structural formula is:

PRECAUTIONS

The Amnesteem Pregnancy Prevention Risk Management Programs consist of the System to Prevent Isotretinoin-Related Issues of Teratogenicity (S.P.I.R.I.T.) and the Amnesteem Pregnancy Prevention Initiative. S.P.I.R.I.T. should be followed for prescribing Amnesteem with the goal of preventing fetal exposure to isotretinoin. It consists of: 1) reading the booklet entitled System to Prevent Isotretinoin-Related Issues of Teratogenicity (S.P.I.R.I.T.) Guide to Best Practices , 2) signing and returning the completed S.P.I.R.I.T. Letter of Understanding containing the Prescriber Checklist, 3) a yellow self-adhesive isotretinoin qualification sticker to be affixed to the prescription page. In addition, the patient education material, A Personal Guide to Your Prescription , should be used with each patient. The following further describes each component:

1. The S.P.I.R.I.T. Guide to Best Practices includes: isotretinoin teratogenic potential, information on pregnancy testing, specific information about effective contraception, the limitations of contraceptive methods and behaviors associated with an increased risk of contraceptive failure and pregnancy, the methods to evaluate pregnancy risk, and the method to complete a qualified Amnesteem prescription.
2. The S.P.I.R.I.T. Letter of Understanding attests that Amnesteem prescribers understand that isotretinoin is a teratogen, have read the S.P.I.R.I.T. Guide to Best Practices , understand their responsibilities in preventing exposure of pregnant females to isotretinoin and the procedures for qualifying female patients as defined in the boxed CONTRAINDICATIONS AND WARNINGS .
   The Prescriber Checklist attests that Amnesteem prescribers know the risk and severity of injury/birth defects from isotretinoin; know how to diagnose and treat the various presentations of acne; know the risk factors for unplanned pregnancy and the effective measures for avoidance; will refer the patient for, or provide, detailed pregnancy prevention counseling to help the patient have knowledge and tools needed to fulfill their ultimate responsibility to avoid becoming pregnant; understand and properly use throughout the isotretinoin capsules treatment course, the revised risk management procedures, including monthly pregnancy avoidance counseling, pregnancy testing, and use of qualified prescriptions with the yellow self-adhesive isotretinoin qualification sticker.
3. The yellow self-adhesive isotretinoin qualification sticker is used as documentation that the prescriber has qualified the female patient according to the qualification criteria (see boxed CONTRAINDICATIONS AND WARNINGS ).
4. Amnesteem Pregnancy Prevention Initiative is a systematic approach to comprehensive patient education about their responsibilities and includes education for contraception compliance and reinforcement of educational messages. The Amnesteem Pregnancy Prevention Initiative includes information on the risks and benefits of isotretinoin which is linked to the Amnesteem Medication Guide dispensed by pharmacists with each prescription.
   Male and female patients are provided with separate booklets. Each booklet contains information on Amnesteem therapy, including precautions and warnings, an Informed Consent/Patient Agreement form, and a toll-free line which provides Amnesteem information in English and Spanish.
   The booklet for male patients, A Personal Guide to Your Prescription for Men , also includes information about male reproduction, a warning not to share Amnesteem with others or to donate blood during Amnesteem therapy and for 1 month following discontinuation of Amnesteem.
   The booklet for female patients, A Personal Guide to Your Prescription for Women , also includes a referral program that offers females free contraception counseling, reimbursed by Bertek Pharmaceuticals Inc., by a reproductive specialist; a second Patient Information/Consent form concerning birth defects, obtaining her consent to be treated within this agreement; an enrollment form for the Isotretinoin Survey; and a qualification checklist affirming the conditions under which female patients may receive Amnesteem. In addition, there is information on the types of contraceptive methods, the selection and use of appropriate, effective contraception, and the rates of possible contraceptive failure; a toll-free contraception counseling line; and patient education videos -- the video Don't Risk It: The importance of preventing pregnancy while you're taking Amnesteem® , and the video Birth Defects and Amnesteem®: Things You Should Know.

General

Although an effect of isotretinoin on bone loss is not established, physicians should use caution when prescribing Amnesteem to patients with a genetic predisposition for age-related osteoporosis, a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism. This would include patients diagnosed with anorexia nervosa and those who are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects vitamin D metabolism, such as systemic corticosteroids and any anticonvulsant.

Patients may be at increased risk when participating in sports with repetitive impact where the risks of spondylolisthesis with and without pars fractures and hip growth plate injuries in early and late adolescence are known. There are spontaneous reports of fractures and/or delayed healing in patients while on treatment with isotretinoin or following cessation of treatment with isotretinoin while involved in these activities. While causality to isotretinoin has not been established, an effect cannot be ruled out.

Information for Patients and Prescribers

• Patients should be instructed to read the Medication Guide supplied as required by law when isotretinoin capsules are dispensed. The complete text of the Medication Guide is reprinted at the end of this document. For additional information, patients should also read the Patient Product Information, Important Information Concerning Your Treatment with Amnesteem . All patients should sign the Informed Consent/Patient Agreement.
• Females of childbearing potential should be instructed that they must not be pregnant when Amnesteem therapy is initiated, and that they should use 2 forms of effective contraception 1 month before starting Amnesteem, while taking Amnesteem, and for 1 month after Amnesteem has been stopped. They should also sign a consent form prior to beginning Amnesteem therapy. They should be given an opportunity to enroll in the Isotretinoin Survey and to review the patient videotapes provided by Bertek Pharmaceuticals Inc. to the prescriber. The videos include information about contraception, the most common reasons that contraception fails, and the importance of using 2 forms of effective contraception when taking teratogenic drugs and comprehensive information about types of potential birth defects which could occur if a woman who is pregnant takes isotretinoin at any time during pregnancy. Female patients should be seen by their prescribers monthly and have a urine or serum pregnancy test performed each month during treatment to confirm negative pregnancy status before another Amnesteem prescription is written (see boxed CONTRAINDICATIONS AND WARNINGS ).
• Isotretinoin is found in the semen of male patients taking isotretinoin capsules, but the amount delivered to a female partner would be about 1 million times lower than an oral dose of 40 mg. While the no-effect limit for isotretinoin-induced embryopathy is unknown, 20 years of postmarketing reports include 4 with isolated defects compatible with features of retinoid exposed fetuses. None of these cases had the combination of malformations characteristic of retinoid exposure, and all had other possible explanations for the defects observed.
• Patients may report mental health problems or family history of psychiatric disorders. These reports should be discussed with the patient and/or the patient's family. A referral to a mental health professional may be necessary. The physician should consider whether or not Amnesteem therapy is appropriate in this setting (see WARNINGS: Psychiatric Disorders).
• Patients should be informed that they must not share Amnesteem with anyone else because of the risk of birth defects and other serious adverse events.
• Patients should not donate blood during therapy and for 1 month following discontinuance of the drug because the blood might be given to a pregnant woman whose fetus must not be exposed to isotretinoin.
• Patients should be reminded to take Amnesteem with a meal (see DOSAGE AND ADMINISTRATION ). To decrease the risk of esophageal irritation, patients should swallow the capsules with a full glass of liquid.
• Patients should be informed that transient exacerbation (flare) of acne has been seen, generally during the initial period of therapy.
• Wax epilation and skin resurfacing procedures (such as dermabrasion, laser) should be avoided during Amnesteem therapy and for at least 6 months thereafter due to the possibility of scarring (see ADVERSE REACTIONS : Skin and Appendages ).
• Patients should be advised to avoid prolonged exposure to UV rays or sunlight.
• Patients should be informed that they may experience decreased tolerance to contact lenses during and after therapy.
• Patients should be informed that approximately 16% of patients treated with isotretinoin in a clinical trial developed musculoskeletal symptoms (including arthralgia) during treatment. In general, these symptoms were mild to moderate, but occasionally required discontinuation of the drug. Transient pain in the chest has been reported less frequently. In the clinical trial, these symptoms generally cleared rapidly after discontinuation of isotretinoin, but in some cases persisted (see ADVERSE REACTIONS : Musculoskeletal ). There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity (see Laboratory Tests : CPK)
• Pediatric patients and their caregivers should be informed that approximately 29% (104/358) of pediatric patients treated with isotretinoin developed back pain. Back pain was severe in 13.5% (14/104) of the cases and occurred at a higher frequency in female than male patients. Arthralgias were experienced in 22% (79/358) of pediatric-patients. Arthralgias were severe in 7.6% (6/79) of patients. Appropriate evaluation of the musculoskeletal system should be done in patients who present with these symptoms during or after a course of isotretinoin. Consideration should be given to discontinuation of isotretinoin if any significant abnormality is found.
• Neutropenia and rare cases of agranulocystosis have been reported. Amnesteem should be discontinued if clinically significant decreases in white cell counts occur.

Hypersensitivity

Anaphylactic reactions and other allergic reactions have been reported. Cutaneous allergic reactions and serious cases of allergic vasculitis, often with purpura (bruises and red patches) of the extremities and extracutaneous involvement (including renal) have been reported. Severe allergic reaction necessitates discontinuation of therapy and appropriate medical management.

ADVERSE REACTIONS

Clinical Trials and Postmarketing Surveillance

The adverse reactions listed below reflect the experience from investigational studies of isotretinoin, and the postmarketing experience. The relationship of some of these events to isotretinoin therapy is unknown. Many of the side effects and adverse reactions seen in patients receiving isotretinoin are similar to those described in patients taking very high doses of vitamin A (dryness of the skin and mucous membranes, e.g., of the lips, nasal passage, and eyes).

Dose Relationship

Cheilitis and hypertriglyceridemia are usually dose related. Most adverse reactions reported in clinical trials were reversible when therapy was discontinued; however, some persisted after cessation of therapy (see WARNINGS and ADVERSE REACTIONS ).

Body as a Whole

allergic reactions, including vasculitis, systemic hypersensitivity (see PRECAUTIONS: Hypersensitivity ), edema, fatigue, lymphadenopathy, weight loss

Cardiovascular

palpitation, tachycardia, vascular thrombotic disease, stroke

Endocrine/Metabolic

hypertriglyceridemia (see WARNINGS: Lipids ), alterations in blood sugar levels (see PRECAUTIONS: Laboratory Tests )

Gastrointestinal

inflammatory bowel disease (see WARNINGS: Inflammatory Bowel Disease ), hepatitis (see WARNINGS: Hepatotoxicity ), pancreatitis (see WARNINGS: Lipids ), bleeding and inflammation of the gums, colitis, esophagitis/esophageal ulceration, ileitis, nausea, other nonspecific gastrointestinal symptoms

Hematologic

allergic reactions (see PRECAUTIONS: Hypersensitivity ), anemia, thrombocytopenia, neutropenia, rare reports of agranulocytosis (see PRECAUTIONS: Information for Patients and Prescribers ). See PRECAUTIONS: Laboratory Tests for other hematological parameters.

Musculoskeletal

skeletal hyperostosis, calcification of tendons and ligaments, premature epiphyseal closure, decreases in bone mineral density (see WARNINGS: Skeletal ), musculoskeletal symptoms (sometimes severe) including back pain and arthralgia (see PRECAUTIONS: Information for Patients and Prescribers ), transient pain in the chest (see PRECAUTIONS: Information for Patients and Prescribers ), arthritis, tendonitis, other types of bone abnormalities, elevations of CPK/rare reports of rhabdomyolysis (see PRECAUTIONS: Laboratory Tests ).

Neurological

pseudotumor cerebri (see WARNINGS: Pseudotumor Cerebri ), dizziness, drowsiness, headache, insomnia, lethargy, malaise, nervousness, paresthesias, seizures, stroke, syncope, weakness

Psychiatric

suicidal ideation, suicide attempts, suicide, depression, psychosis, aggression, violent behaviors (see WARNINGS: Psychiatric Disorders ), emotional instability

Of the patients reporting depression, some reported that the depression subsided with discontinuation of therapy and recurred with reinstitution of therapy.

Reproductive System

abnormal menses

Respiratory

bronchospasms (with or without a history of asthma), respiratory infection, voice alteration

Skin and Appendages

acne fulminans, alopecia (which in some cases persists), bruising, cheilitis (dry lips), dry mouth, dry nose, dry skin, epistaxis, eruptive xanthomas ⁷ flushing, fragility of skin, hair abnormalities, hirsutism, hyperpigmentation and hypopigmentation, infections (including disseminated herpes simplex), nail dystrophy, paronychia, peeling of palms and soles, photoallergic/photosensitizing reactions, pruritus, pyogenic granuloma, rash (including facial erythema, seborrhea, and eczema), sunburn susceptibility
increased, sweating, urticaria, vasculitis (including Wegener's granulomatosis; see PRECAUTIONS: Hypersensitivity ), abnormal wound healing (delayed healing or exuberant granulation tissue with crusting; see PRECAUTIONS: Information for Patients and Prescribers )

Special Senses :

Hearing:   hearing impairment (see WARNINGS: Hearing Impairment ), tinnitus

Vision:   corneal opacities (see WARNINGS: Corneal Opacities), decreased night vision which may persist (see WARNINGS: Decreased Night Vision), cataracts, color vision disorder, conjunctivitis, dry eyes, eyelid inflammation, keratitis, optic neuritis, photophobia, visual disturbances

Urinary System

glomerulonephritis (see PRECAUTIONS: Hypersensitivity ), nonspecific urogenital findings (see PRECAUTIONS: Laboratory Tests for other urological parameters)

Laboratory

Elevation of plasma triglycerides (see WARNINGS: Lipids ), decrease in serum high-density lipoprotein (HDL) levels, elevations of serum cholesterol during treatment

Increased alkaline phosphatase, SGOT (AST), SGPT (ALT), GGTP or LDH (see WARNINGS: Hepatotoxicity )

Elevation of fasting blood sugar, elevations of CPK (see PRECAUTIONS: Laboratory Tests ), hyperuricemia

Decreases in red blood cell parameters, decreases in white blood cell counts (including severe neutropenia and rare reports of agranulocytosis; see PRECAUTIONS: Information for Patients and Prescribers ), elevated sedimentation rates, elevated platelet counts, thrombocytopenia