Neotrex Overdose

• Overdose of Neotrex in details
• Neotrex warnings
• Neotrex precautions
• Neotrex reviews

What happens if I overdose Neotrex?

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include dizziness; facial flushing; headache; loss of balance; stomach pain; vomiting.

Proper storage of Neotrex:

Store Neotrex at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store in a tightly closed container. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Neotrex out of the reach of children and away from pets.

Overdose of Neotrex in details

The oral LD of Neotrex is greater than 4000 mg/kg in rats and mice ( > 600 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the rat dose for total body surface area and > 300 times the recommended clinical dose of 1.0 mg/kg/day after normalization of the mouse dose for total body surface area) and is approximately 1960 mg/kg in rabbits (653 times the recommended clinical dose of 1.0 mg/kg/day after normalization for total body surface area). In humans, overdosage has been associated with vomiting, facial flushing, cheilosis, abdominal pain, headache, dizziness, and ataxia. These symptoms quickly resolve without apparent residual effects.

Neotrex (Neotrex) causes serious birth defects at any dosage. Female patients of childbearing potential who present with Neotrex overdose must be evaluated for pregnancy. Patients who are pregnant should receive counseling about the risks to the fetus, as described in the Boxed CONTRAINDICATIONS AND WARNINGS. Non-pregnant patients must be warned to avoid pregnancy for at least one month and receive contraceptive counseling as described in PRECAUTIONS. Educational materials for such patients can be obtained by calling the manufacturer. Because an overdose would be expected to result in higher levels of Neotrex in semen than found during a normal treatment course, male patients should use a condom, or avoid reproductive sexual activity with a female patient who is or might become pregnant, for 1 month after the overdose. All patients with Neotrex overdose should not donate blood for at least 1 month.

What should I avoid while taking Neotrex?

Do not take a vitamin or mineral supplement that contains vitamin A, unless your doctor tells you to.

Do not donate blood while taking Neotrex (Eqv-Absorica) and for at least 30 days after you stop taking it. Donated blood that is later given to a pregnant woman could lead to birth defects in her baby if the blood contains any level of Neotrex (Eqv-Absorica).

While you are taking Neotrex (Eqv-Absorica) and for at least 6 months after your last dose: Do not use wax hair removers or have dermabrasion or laser skin treatments. Scarring may result.

Neotrex (Eqv-Absorica) could make you sunburn more easily. Avoid sunlight or tanning beds. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Avoid driving or hazardous activity until you know how Neotrex (Eqv-Absorica) (Eqv-Absorica) will affect you. Neotrex (Eqv-Absorica) may impair your vision, especially at night.

Neotrex warnings

Psychiatric Disorders

Neotrex (Neotrex) may cause depression, psychosis and, rarely, suicidal ideation, suicide attempts, suicide, and aggressive and/or violent behaviors. No mechanism of action has been established for these events. Prescribers should read the brochure, Recognizing Psychiatric Disorders in Adolescents and Young Adults: A Guide for Prescribers of Neotrex. Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. Therefore, prior to initiation of Neotrex (Neotrex) therapy, patients and family members should be asked about any history of psychiatric disorder, and at each visit during therapy patients should be assessed for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation may be necessary. Signs and symptoms of depression, as described in the brochure (“Recognizing Psychiatric Disorders in Adolescents and Young Adults”), include sad mood, hopelessness, feelings of guilt, worthlessness or helplessness, loss of pleasure or interest in activities, fatigue, difficulty concentrating, change in sleep pattern, change in weight or appetite, suicidal thoughts or attempts, restlessness, irritability, acting on dangerous impulses, and persistent physical symptoms unresponsive to treatment. Patients should stop Neotrex (Neotrex) and the patient or a family member should promptly contact their prescriber if the patient develops depression, mood disturbance, psychosis, or aggression, without waiting until the next visit. Discontinuation of Neotrex (Neotrex) therapy may be insufficient; further evaluation may be necessary. While such monitoring may be helpful, it may not detect all patients at risk. 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 Neotrex (Neotrex) therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of Neotrex (Neotrex) therapy.

Pseudotumor Cerebri

Neotrex (Neotrex) use has been associated with a number of cases of pseudotumor cerebri (benign intracranial hypertension), some of which involved concomitant use of tetracyclines. Concomitant treatment with tetracyclines should therefore be avoided. Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea and vomiting, and visual disturbances. Patients with these symptoms should be screened for papilledema and, if present, they should be told to discontinue Neotrex (Neotrex) immediately and be referred to a neurologist for further diagnosis and care.

Serious Skin Reactions

There have been post-marketing reports of erythema multiforme and severe skin reactions [eg, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)] associated with Neotrex use. These events may be serious and result in death, life-threatening events, hospitalization, or disability. Patients should be monitored closely for severe skin reactions, and discontinuation of Neotrex (Neotrex) should be considered if warranted.

Pancreatitis

Acute pancreatitis has been reported in patients with either elevated or normal serum triglyceride levels. In rare instances, fatal hemorrhagic pancreatitis has been reported. Neotrex (Neotrex) should be stopped if hypertriglyceridemia cannot be controlled at an acceptable level or if symptoms of pancreatitis occur.

Lipids

Elevations of serum triglycerides in excess of 800 mg/dL have been reported in patients treated with Neotrex (Neotrex). Marked elevations of serum triglycerides were reported in approximately 25% of patients receiving Neotrex (Neotrex) in clinical trials. In addition, approximately 15% developed a decrease in high-density lipoproteins and about 7% showed an increase in cholesterol levels. In clinical trials, the effects on triglycerides, HDL, and cholesterol were reversible upon cessation of Neotrex (Neotrex) therapy. Some patients have been able to reverse triglyceride elevation by reduction in weight, restriction of dietary fat and alcohol, and reduction in dose while continuing Neotrex (Neotrex). Minimal skeletal hyperostosis and calcification of ligaments and tendons have also been observed by x-ray in prospective studies of nodular acne patients treated with a single course of therapy at recommended doses. The skeletal effects of multiple Neotrex (Neotrex) treatment courses for acne are unknown.

In a clinical study of 217 pediatric patients (12 to 17 years) with severe recalcitrant nodular acne, hyperostosis was not observed after 16 to 20 weeks of treatment with approximately 1 mg/kg/day of Neotrex (Neotrex) given in two divided doses. Hyperostosis may require a longer time frame to appear. The clinical course and significance remain unknown.

Premature Epiphyseal Closure

There are spontaneous reports of premature epiphyseal closure in acne patients receiving recommended doses of Neotrex (Neotrex). The effect of multiple courses of Neotrex (Neotrex) on epiphyseal closure is unknown.

Vision Impairment

Visual problems should be carefully monitored. All Neotrex (Neotrex) patients experiencing visual difficulties should discontinue Neotrex (Neotrex) treatment and have an ophthalmological examination.

Corneal Opacities

Corneal opacities have occurred in patients receiving Neotrex (Neotrex) for acne and more frequently when higher drug dosages were used in patients with disorders of keratinization. The corneal opacities that have been observed in clinical trial patients treated with Neotrex (Neotrex) have either completely resolved or were resolving at follow-up 6 to 7 weeks after discontinuation of the drug.

Decreased Night Vision

Decreased night vision has been reported during Neotrex (Neotrex) therapy and in some instances the event has persisted after therapy was discontinued. Because the onset in some patients was sudden, patients should be advised of this potential problem and warned to be cautious when driving or operating any vehicle at night.

What should I discuss with my healthcare provider before taking Neotrex?

• If you are allergic to Neotrex (Neotrex (systemic)); any part of Neotrex (Neotrex (systemic)); or any other drugs, foods, or substances. Tell your doctor about the allergy and what signs you had.
• If you are able to get pregnant and are not using 2 kinds of birth control.
• If you are planning to get pregnant within 1 month before treatment, during treatment, or within 1 month after your last dose.
• If you are breast-feeding. Do not breast-feed for some time after getting Neotrex (Neotrex (systemic)). Talk with your doctor to see how long to avoid breast-feeding after getting Neotrex (Neotrex (systemic)).
• If you are taking any of these drugs: Demeclocycline, doxycycline, minocycline, tetracycline, a product that has vitamin A in it, a product that is like vitamin A, or St. John's wort.

This is not a list of all drugs or health problems that interact with Neotrex (Neotrex (systemic)).

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Neotrex (Neotrex (systemic)) with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

Neotrex precautions

Neotrex (Neotrex) must only be prescribed by prescribers who are registered and activated with the iPLEDGE program. Neotrex (Neotrex) 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. Registered and activated pharmacies must receive Neotrex (Neotrex) only from wholesalers registered with iPLEDGE.

iPLEDGE program requirements for wholesalers, prescribers, and pharmacists are described below:

Wholesalers

For the purpose of the iPLEDGE program, the term wholesaler refers to wholesaler, distributor, and/or chain pharmacy distributor. To distribute Neotrex (Neotrex), wholesalers must be registered with iPLEDGE, and agree to meet all iPLEDGE requirements for wholesale distribution of Neotrex products. Wholesalers must register with iPLEDGE by signing and returning the iPLEDGE wholesaler agreement that affirms they will comply with all iPLEDGE requirements for distribution of Neotrex. These include:

• Registering prior to distributing Neotrex and re-registering annually thereafter
• Distributing only FDA approved Neotrex product
• Only shipping Neotrex to
  • wholesalers registered in the iPLEDGE program with prior written consent from the manufacturer or
  • pharmacies licensed in the US and registered and activated in the iPLEDGE program
• Notifying the Neotrex manufacturer (or delegate) of any non-registered and/or nonactivated pharmacy or unregistered wholesaler that attempts to order Neotrex
• Complying with inspection of wholesaler records for verification of compliance with the iPLEDGE program by the Neotrex manufacturer (or delegate)
• Returning to the manufacturer (or delegate) any undistributed product if registration is revoked by the manufacturer or if the wholesaler chooses to not re-register annually

Prescribers

To prescribe Neotrex, the prescriber must be registered and activated with the pregnancy risk management program iPLEDGE. Prescribers can register by signing and returning the completed registration form. Prescribers can only activate their registration by affirming that they meet requirements and will comply with all iPLEDGE requirements by attesting to the following points:

• I know the risk and severity of fetal injury/birth defects from Neotrex.
• I know the risk factors for unplanned pregnancy and the effective measures for avoidance of unplanned pregnancy.
• I have the expertise to provide the patient with detailed pregnancy prevention counseling or I will refer her to an expert for such counseling, reimbursed by the manufacturer.
• I will comply with the iPLEDGE program requirements described in the booklets entitled The Guide to Best Practices for the iPLEDGE Program and The iPLEDGE Program Prescriber Contraception Counseling Guide.
• Before beginning treatment of female patients of childbearing potential with Neotrex and on a monthly basis, the patient will be counseled to avoid pregnancy by using two forms of contraception simultaneously and continuously one month before, during, and one month after Neotrex therapy, unless the patient commits to continuous abstinence.
• I will not prescribe Neotrex to any female patient of childbearing potential until verifying she has a negative screening pregnancy test and monthly negative CLIA-certified (Clinical Laboratory Improvement Amendment) pregnancy tests. Patients should have a pregnancy test at the completion of the entire course of Neotrex and another pregnancy test 1 month later.
• I will report any pregnancy case that I become aware of while the female patient is on Neotrex or 1 month after the last dose to the pregnancy registry.

To prescribe Neotrex, the prescriber must access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654) to:

1. Register each patient in the iPLEDGE program.
2. Confirm monthly that each patient has received counseling and education.
3. For female patients of childbearing potential:
   • Enter patient's two chosen forms of contraception each month.
   • Enter monthly result from CLIA-certified laboratory conducted pregnancy test.

Neotrex must only be prescribed to female patients who are known not to be pregnant as confirmed by a negative CLIA-certified laboratory conducted pregnancy test.

Neotrex must only be dispensed by a pharmacy registered and activated with the pregnancy risk management program iPLEDGE and only when the registered patient meets all the requirements of the iPLEDGE program. Meeting the requirements for a female patient of childbearing potential signifies that she:

• Has been counseled and has signed a Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form that contains warnings about the risk of potential birth defects if the fetus is exposed to Neotrex. The patient must sign the informed consent form before starting treatment and patient counseling must also be done at that time and on a monthly basis thereafter.
• Has had two negative urine or serum pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial Neotrex prescription. The first test (a screening test) is obtained by the prescriber when the decision is made to pursue qualification of the patient for Neotrex. The second pregnancy test (a confirmation test) must be done in a CLIA-certified laboratory. The interval between the 2 tests should be at least 19 days.
  • For patients with regular menstrual cycles, the second pregnancy test should be done during the first 5 days of the menstrual period immediately preceding the beginning of Neotrex therapy and after the patient has used 2 forms of contraception for 1 month.
  • For patients with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding, the second pregnancy test must be done immediately preceding the beginning of Neotrex therapy and after the patient has used 2 forms of contraception for 1 month.
• Has had a negative result from a urine or serum pregnancy test in a CLIA-certified laboratory before receiving each subsequent course of Neotrex. A pregnancy test must be repeated every month, in a CLIA-certified laboratory, prior to the female patient receiving each prescription.
• Has selected and has committed to use 2 forms of effective contraception simultaneously, at least 1 of which must be a primary form, unless the patient commits to continuous abstinence from heterosexual contact, or the patient has undergone a hysterectomy or bilateral oophorectomy, or has been medically confirmed to be post-menopausal. Patients must use 2 forms of effective contraception for at least 1 month prior to initiation of Neotrex therapy, during Neotrex therapy, and for 1 month after discontinuing Neotrex therapy. Counseling about contraception and behaviors associated with an increased risk of pregnancy must be repeated on a monthly basis.

  If the patient has unprotected heterosexual intercourse at any time 1 month before, during, or 1 month after therapy, she must:

  1. Stop taking Neotrex (Neotrex) immediately, if on therapy
  2. Have a pregnancy test at least 19 days after the last act of unprotected heterosexual intercourse
  3. Start using 2 forms of effective contraception simultaneously again for 1 month before resuming Neotrex (Neotrex) therapy
  4. Have a second pregnancy test after using 2 forms of effective contraception for 1 month as described above depending on whether she has regular menses or not.

Effective forms of contraception include both primary and secondary forms of contraception:

Primary forms	Secondary forms
tubal sterilization partner's vasectomy intrauterine device hormonal (combination oral contraceptives, transdermal patch, injectables, implantables, or vaginal ring)	Barrier:
male latex condom with or without spermicide diaphragm with spermicide cervical cap with spermicide
Other:
vaginal sponge (contains spermicide)

Any birth control method can fail. There have been reports of pregnancy from female patients who have used oral contraceptives, as well as transdermal patch/injectable/implantable/vaginal ring hormonal birth control products; these pregnancies occurred while these patients were taking Neotrex (Neotrex). These reports are more frequent for female patients who use only a single method of contraception. Therefore, it is critically important that female patients of childbearing potential use 2 effective forms of contraception simultaneously. Patients must receive written warnings about the rates of possible contraception failure (included in patient education kits).

Using two forms of contraception simultaneously substantially reduces the chances that a female will become pregnant over the risk of pregnancy with either form alone. A drug interaction that decreases effectiveness of hormonal contraceptives has not been entirely ruled out for Neotrex. Although hormonal contraceptives are highly effective, 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.

If a pregnancy does occur during Neotrex treatment, Neotrex must be discontinued immediately. The patient should be referred to an Obstetrician-Gynecologist experienced in reproductive toxicity for further evaluation and counseling. Any suspected fetal exposure during or 1 month after Neotrex therapy must be reported immediately to the FDA via the MedWatch number 1-800-FDA-1088 and also to the iPLEDGE pregnancy registry at 1-866-495-0654 or via the internet (www.ipledgeprogram.com).

All Patients

Neotrex is contraindicated in female patients who are pregnant. To receive Neotrex all patients must meet all of the following conditions:

• Must be registered with the iPLEDGE program by the prescriber
• Must understand that severe birth defects can occur with the use of Neotrex by female patients
• Must be reliable in understanding and carrying out instructions
• Must sign a Patient Information/Informed Consent (for all patients) form that contains warnings about the potential risks associated with Neotrex
• Must fill and pick up the prescription within 7 days of the date of specimen collection for the pregnancy test for female patients of childbearing potential
• Must fill and pick up the prescription within 30 days of the office visit for male patients and female patients not of childbearing potential
• Must not donate blood while on Neotrex and for 1 month after treatment has ended
• Must not share Neotrex with anyone, even someone who has similar symptoms

Female Patients of Childbearing Potential

Neotrex is contraindicated in female patients who are pregnant. In addition to the requirements for all patients described above, female patients of childbearing potential must meet the following conditions:

• Must NOT be pregnant or breast-feeding
• Must comply with the required pregnancy testing at a CLIA-certified laboratory
• Must fill and pick up the prescription within 7 days of the date of specimen collection for the pregnancy test
• Must be capable of complying with the mandatory contraceptive measures required for Neotrex therapy, or commit to continuous abstinence from heterosexual intercourse, and understand behaviors associated with an increased risk of pregnancy
• Must understand that it is her responsibility to avoid pregnancy one month before, during and one month after Neotrex therapy
• Must have signed an additional Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form, before starting Neotrex, that contains warnings about the risk of potential birth defects if the fetus is exposed to Neotrex
• Must access the iPLEDGE system via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654), before starting Neotrex, on a monthly basis during therapy, and 1 month after the last dose to answer questions on the program requirements and to enter the patient's two chosen forms of contraception
• Must have been informed of the purpose and importance of providing information to the iPLEDGE program should she become pregnant while taking Neotrex or within 1 month of the last dose

Pharmacists

To dispense Neotrex, pharmacies must be registered and activated with the pregnancy risk management program iPLEDGE.

The Responsible Site Pharmacist must register the pharmacy by signing and returning the completed registration form. After registration, the Responsible Site Pharmacist can only activate the pharmacy registration by affirming that they meet requirements and will comply with all iPLEDGE requirements by attesting to the following points:

• I know the risk and severity of fetal injury/birth defects from Neotrex.
• I will train all pharmacists, who participate in the filling and dispensing of Neotrex prescriptions, on the iPLEDGE program requirements.
• I will comply and seek to ensure all pharmacists who participate in the filling and dispensing of Neotrex prescriptions comply with the iPLEDGE program requirements described in the booklet entitled Pharmacist Guide for the iPLEDGE Program.
• I will obtain Neotrex (Neotrex) product only from iPLEDGE registered wholesalers.
• I will not sell, buy, borrow, loan or otherwise transfer Neotrex in any manner to or from another pharmacy.
• I will return to the manufacturer (or delegate) any unused product if registration is revoked by the manufacturer or if the pharmacy chooses to not reactivate annually.
• I will not fill Neotrex for any party other than a qualified patient.

To dispense Neotrex, the pharmacist must:

1. be trained by the Responsible Site Pharmacist concerning the iPLEDGE program requirements.
2. obtain authorization from the iPLEDGE program via the internet (www.ipledgeprogram.com) or telephone (1-866-495-0654) for every Neotrex prescription. Authorization signifies that the patient has met all program requirements and is qualified to receive Neotrex.
3. write the Risk Management Authorization (RMA) number on the prescription.

Neotrex (Neotrex) must only be dispensed:

• in no more than a 30-day supply
• with an Neotrex Medication Guide
• after authorization from the iPLEDGE program
• prior to the “do not dispense to patient after” date provided by the iPLEDGE system (within 30 days of the office visit for male patients and female patients not of childbearing potential and within 7 days of the date of specimen collection for female patients of childbearing potential)
• with a new prescription for refills and another authorization from the iPLEDGE program (No automatic refills are allowed)

An Neotrex Medication Guide must be given to the patient each time Neotrex (Neotrex) is dispensed, as required by law. This Neotrex Medication Guide is an important part of the risk management program for the patients.

Neotrex (Neotrex) must not be prescribed, dispensed or otherwise obtained through the internet or any other means outside of the iPLEDGE program. Only FDA-approved Neotrex (Neotrex) products must be distributed, prescribed, dispensed, and used. Patients must fill Neotrex (Neotrex) prescriptions only at US licensed pharmacies.

A description of the iPLEDGE program educational materials available with iPLEDGE is provided below. The main goal of these educational materials is to explain the iPLEDGE program requirements and to reinforce the educational messages.

1. The Guide to Best Practices for the iPLEDGE Program includes: Neotrex teratogenic potential, information on pregnancy testing, and the method to complete a qualified Neotrex prescription.
2. The iPLEDGE Program Prescriber Contraception Counseling Guide includes: specific information about effective contraception, the limitations of contraceptive methods, behaviors associated with an increased risk of contraceptive failure and pregnancy and the methods to evaluate pregnancy risk.
3. The Pharmacist Guide for the iPLEDGE Program includes: Neotrex teratogenic potential and the method to obtain authorization to dispense an Neotrex prescription.
4. The iPLEDGE program is a systematic approach to comprehensive patient education about their responsibilities and includes education for contraception compliance and reinforcement of educational messages. The iPLEDGE program includes information on the risks and benefits of Neotrex which is linked to the Medication Guide dispensed by pharmacists with each Neotrex prescription.
5. Female patients not of childbearing potential and male patients, and female patients of childbearing potential are provided with separate booklets. Each booklet contains information on Neotrex therapy including precautions and warnings, a Patient Information/Informed Consent (for all patients) form, and a toll-free line which provides Neotrex information in 2 languages.
6. The booklet for female patients not of childbearing potential and male patients, The iPLEDGE Program Guide to Neotrex for Male Patients and Female Patients Who Cannot Get Pregnant, also includes information about male reproduction and a warning not to share Neotrex with others or to donate blood during Neotrex therapy and for 1 month following discontinuation of Neotrex.
7. The booklet for female patients of childbearing potential, The iPLEDGE Program Guide to Neotrex for Female Patients Who Can Get Pregnant, includes a referral program that offers female patients free contraception counseling, reimbursed by the manufacturer, by a reproductive specialist; and a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form concerning birth defects.
8. The booklet, The iPLEDGE Program Birth Control Workbook includes information on the types of contraceptive methods, the selection and use of appropriate, effective contraception, the rates of possible contraceptive failure and a toll-free contraception counseling line.
9. In addition, there is a patient educational DVD with the following videos — “Be Prepared, Be Protected” and “Be Aware: The Risk of Pregnancy While on Neotrex”.

General

Although an effect of Neotrex (Neotrex) on bone loss is not established, physicians should use caution when prescribing Neotrex (Neotrex) 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 therapy with Neotrex (Neotrex) or following cessation of therapy with Neotrex (Neotrex) while involved in these activities. While causality to Neotrex (Neotrex) has not been established, an effect must not be ruled out.

Information for Patients

• Patients must be instructed to read the Medication Guide supplied as required by law when Neotrex (Neotrex) is dispensed. The complete text of the Medication Guide is reprinted at the end of this document. For additional information, patients must also be instructed to read the iPLEDGE program patient educational materials. All patients must sign the Patient Information/Informed Consent (for all patients) form.
• Female patients of childbearing potential must be instructed that they must not be pregnant when Neotrex (Neotrex) therapy is initiated, and that they should use 2 forms of effective contraception simultaneously for 1 month before starting Neotrex (Neotrex), while taking Neotrex (Neotrex), and for 1 month after Neotrex (Neotrex) has been stopped, unless they commit to continuous abstinence from heterosexual intercourse. They should also sign a second Patient Information/Informed Consent About Birth Defects (for female patients who can get pregnant) form prior to beginning Neotrex (Neotrex) therapy. They should be given an opportunity to view the patient DVD provided by the manufacturer to the prescriber. The DVD includes 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 female patient who is pregnant takes Neotrex (Neotrex) at any time during pregnancy. Female patients should be seen by their prescribers monthly and have a urine or serum pregnancy test, in a CLIA-certified laboratory, performed each month during treatment to confirm negative pregnancy status before another Neotrex prescription is written.
• Neotrex (Neotrex) is found in the semen of male patients taking Neotrex (Neotrex), 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 Neotrex induced embryopathy is unknown, 20 years of postmarketing reports include 4 with isolated defects compatible with features of retinoid exposed fetuses; however 2 of these reports were incomplete, and 2 had other possible explanations for the defects observed.
• Prescribers should be alert to the warning signs of psychiatric disorders to guide patients to receive the help they need. Therefore, prior to initiation of Neotrex (Neotrex) treatment, patients and family members should be asked about any history of psychiatric disorder, and at each visit during treatment patients should be assessed for symptoms of depression, mood disturbance, psychosis, or aggression to determine if further evaluation may be necessary. Signs and symptoms of depression include sad mood, hopelessness, feelings of guilt, worthlessness or helplessness, loss of pleasure or interest in activities, fatigue, difficulty concentrating, change in sleep pattern, change in weight or appetite, suicidal thoughts or attempts, restlessness, irritability, acting on dangerous impulses, and persistent physical symptoms unresponsive to treatment. Patients should stop Neotrex (Neotrex) and the patient or a family member should promptly contact their prescriber if the patient develops depression, mood disturbance, psychosis, or aggression, without waiting until the next visit. Discontinuation of Neotrex (Neotrex) treatment may be insufficient; further evaluation may be necessary. While such monitoring may be helpful, it may not detect all patients at risk. 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 Neotrex (Neotrex) therapy is appropriate in this setting; for some patients the risks may outweigh the benefits of Neotrex (Neotrex) therapy.
• Patients must be informed that some patients, while taking Neotrex (Neotrex) or soon after stopping Neotrex (Neotrex), have become depressed or developed other serious mental problems. Symptoms of depression include sad, “anxious” or empty mood, irritability, acting on dangerous impulses, anger, loss of pleasure or interest in social or sports activities, sleeping too much or too little, changes in weight or appetite, school or work performance going down, or trouble concentrating. Some patients taking Neotrex (Neotrex) have had thoughts about hurting themselves or putting an end to their own lives (suicidal thoughts). Some people tried to end their own lives. And some people have ended their own lives. There were reports that some of these people did not appear depressed. There have been reports of patients on Neotrex (Neotrex) becoming aggressive or violent. No one knows if Neotrex (Neotrex) caused these behaviors or if they would have happened even if the person did not take Neotrex (Neotrex). Some people have had other signs of depression while taking Neotrex (Neotrex).
• Patients must be informed that they must not share Neotrex (Neotrex) with anyone else because of the risk of birth defects and other serious adverse events.
• Patients must be informed not to donate blood during therapy and for 1 month following discontinuation of the drug because the blood might be given to a pregnant female patient whose fetus must not be exposed to Neotrex (Neotrex).
• Patients should be reminded to take Neotrex with a meal. 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 Neotrex (Neotrex) therapy and for at least 6 months thereafter due to the possibility of scarring.
• 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 Neotrex (Neotrex) 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 Neotrex (Neotrex), but in some cases persisted. There have been rare postmarketing reports of rhabdomyolysis, some associated with strenuous physical activity.
• Pediatric patients and their caregivers should be informed that approximately 29% (104/358) of pediatric patients treated with Neotrex (Neotrex) developed back pain. Back pain was severe in 13.5% (14/104) of the cases and occurred at a higher frequency in female patients 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 Neotrex (Neotrex). Consideration should be given to discontinuation of Neotrex (Neotrex) if any significant abnormality is found.
• Neutropenia and rare cases of agranulocytosis have been reported. Neotrex (Neotrex) should be discontinued if clinically significant decreases in white cell counts occur.
• Patients should be advised that severe skin reactions (Stevens-Johnson syndrome and toxic epidermal necrolysis) have been reported in post-marketing data. Neotrex (Neotrex) should be discontinued if clinically significant skin reactions 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.

Carcinogenesis, Mutagenesis and Impairment of Fertility

In male and female Fischer 344 rats given oral Neotrex at dosages of 8 or 32 mg/kg/day (1.3 to 5.3 times the recommended clinical dose of 1.0 mg/kg/day, respectively, after normalization for total body surface area) for greater than 18 months, there was a dose-related increased incidence of pheochromocytoma relative to controls. The incidence of adrenal medullary hyperplasia was also increased at the higher dosage in both sexes. The relatively high level of spontaneous pheochromocytomas occurring in the male Fischer 344 rat makes it an equivocal model for study of this tumor; therefore, the relevance of this tumor to the human population is uncertain.

The Ames test was conducted with Neotrex in two laboratories. The results of the tests in one laboratory were negative while in the second laboratory a weakly positive response (less than 1.6 x background) was noted in S. typhimurium TA100 when the assay was conducted with metabolic activation. No dose-response effect was seen and all other strains were negative. Additionally, other tests designed to assess genotoxicity (Chinese hamster cell assay, mouse micronucleus test, S. cerevisiae D assay, in vitro clastogenesis assay with human-derived lymphocytes, and unscheduled DNA synthesis assay) were all negative.

In rats, no adverse effects on gonadal function, fertility, conception rate, gestation or parturition were observed at oral dosages of Neotrex of 2, 8, or 32 mg/kg/day (0.3, 1.3, or 5.3 times the recommended clinical dose of 1.0 mg/kg/day, respectively, after normalization for total body surface area).

In dogs, testicular atrophy was noted after treatment with oral Neotrex for approximately 30 weeks at dosages of 20 or 60 mg/kg/day (10 or 30 times the recommended clinical dose of 1.0 mg/kg/day, respectively, after normalization for total body surface area). In general, there was microscopic evidence for appreciable depression of spermatogenesis but some sperm were observed in all testes examined and in no instance were completely atrophic tubules seen. In studies of 66 men, 30 of whom were patients with nodular acne under treatment with oral Neotrex, no significant changes were noted in the count or motility of spermatozoa in the ejaculate. In a study of 50 men (ages 17 to 32 years) receiving Neotrex (Neotrex) therapy for nodular acne, no significant effects were seen on ejaculate volume, sperm count, total sperm motility, morphology or seminal plasma fructose.

Pregnancy

Category X. See Boxed CONTRAINDICATIONS AND WARNINGS.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because of the potential for adverse effects, nursing mothers should not receive Neotrex (Neotrex).

Pediatric Use

The use of Neotrex (Neotrex) in pediatric patients less than 12 years of age has not been studied. The use of Neotrex (Neotrex) for the treatment of severe recalcitrant nodular acne in pediatric patients ages 12 to 17 years should be given careful consideration, especially for those patients where a known metabolic or structural bone disease exists. Use of Neotrex (Neotrex) in this age group for severe recalcitrant nodular acne is supported by evidence from a clinical study comparing 103 pediatric patients (13 to 17 years) to 197 adult patients ( ≥ 18 years). Results from this study demonstrated that Neotrex (Neotrex), at a dose of 1 mg/kg/day given in two divided doses, was equally effective in treating severe recalcitrant nodular acne in both pediatric and adult patients.

In studies with Neotrex (Neotrex), adverse reactions reported in pediatric patients were similar to those described in adults except for the increased incidence of back pain and arthralgia (both of which were sometimes severe) and myalgia in pediatric patients.

In an open-label clinical trial (N=217) of a single course of therapy with Neotrex (Neotrex) for severe recalcitrant nodular acne, bone density measurements at several skeletal sites were not significantly decreased (lumbar spine change > -4% and total hip change > -5%) or were increased in the majority of patients. One patient had a decrease in lumbar spine bone mineral density > 4% based on unadjusted data. Sixteen (7.9%) patients had decreases in lumbar spine bone mineral density > 4%, and all the other patients (92%) did not have significant decreases or had increases (adjusted for body mass index). Nine patients (4.5%) had a decrease in total hip bone mineral density > 5% based on unadjusted data. Twenty-one (10.6%) patients had decreases in total hip bone mineral density > 5%, and all the other patients (89%) did not have significant decreases or had increases (adjusted for body mass index). Follow-up studies performed in 8 of the patients with decreased bone mineral density for up to 11 months thereafter demonstrated increasing bone density in 5 patients at the lumbar spine, while the other 3 patients had lumbar spine bone density measurements below baseline values. Total hip bone mineral densities remained below baseline (range -1.6% to -7.6%) in 5 of 8 patients (62.5%).

In a separate open-label extension study of 10 patients, ages 13 to 18 years, who started a second course of Neotrex (Neotrex) 4 months after the first course, two patients showed a decrease in mean lumbar spine bone mineral density up to 3.25%.

Geriatric Use

Clinical studies of Neotrex did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Although reported clinical experience has not identified differences in responses between elderly and younger patients, effects of aging might be expected to increase some risks associated with Neotrex therapy.

REFERENCES

5. Katz RA, Jorgensen H, Nigra TP. Elevation of serum triglyceride levels from oral Neotrex in disorders of keratinization. Arch Dermatol 116:1369-1372, 1980.

6. Ellis CN, Madison KC, Pennes DR, Martel W, Voorhees JJ. Neotrex therapy is associated with early skeletal radiographic changes. J Am Acad Dermatol 10:1024-1029, 1984.

What happens if I miss a dose of Neotrex?

Skip the missed dose and take the medicine at your next regularly scheduled time. Do not take extra medicine to make up the missed dose.

References

1. DailyMed. "ISOTRETINOIN: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
2. DrugBank. "Isotretinoin". http://www.drugbank.ca/drugs/DB00982 (accessed September 17, 2018).
3. MeSH. "Teratogens". https://www.ncbi.nlm.nih.gov/mesh/68... (accessed September 17, 2018).

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Information checked by Dr. Sachin Kumar, MD Pharmacology