equetro

When discontinuing treatment, reduce dose gradually ( 2.6 , 5.6 ) Monitoring serum carbamazepine concentrations may be useful in dose selection and minimizing risk of toxicity ( 2.7 ) Swallow capsules whole or open capsules and sprinkle beads over food ( 2.8 ) Do not crush or chew the capsule or beads ( 2.8 ) 2.1 Pretreatment Screening Prior to initiating treatment with EQUETRO, test patients with ancestry in genetically at-risk populations for the presence of the HLA-B*1502 allele. The high resolution genotype test is positive if one or two HLA-B*1502 alleles are present. Avoid use of EQUETRO in patients testing positive for the allele, unless the benefit clearly outweighs the risk [see Boxed Warning , Warnings and Precautions ( 5.1 )] . Complete pretreatment blood counts, including platelets and possibly reticulocytes and serum iron, should be obtained as a baseline. If a patient in the course of treatment exhibits low or decreased white blood cell or platelet counts, the patient should be monitored closely. Discontinuation of EQUETRO should be considered if any evidence of significant bone marrow depression develops [see Warnings and Precautions ( 5.2 )]. Baseline and periodic evaluations of liver function, particularly in patients with a history of liver disease, must be performed during treatment with EQUETRO because liver damage may occur. Discontinue EQUETRO in cases of…

The following serious adverse reactions are discussed in more detail in other sections of the labeling: Serious Dermatologic Reactions: Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome [see Warnings and Precautions ( 5.1 ) Aplastic anemia/agranulocytosis [see Warnings and Precautions ( 5.2 )] Drug Reaction with Eosinophilia and Systemic Symptoms/Multiorgan Hypersensitivity [see Warnings and Precautions ( 5.3 )] Suicidal Behavior and Ideation [see Warnings and Precautions ( 5.4 )] Embryofetal Toxicity [see Warnings and Precautions ( 5.5 )] Abrupt Discontinuation and Seizure Risk [see Warnings and Precautions ( 5.6 )] Hyponatremia [see Warnings and Precautions ( 5.7 )] Cognitive and Motor Impairment [see Warnings and Precautions ( 5.8 )] Drug Interaction with Non-Nucleoside Reverse Transcriptase Inhibitors [see Warnings and Precautions ( 5.9 )] Liver Damage [see Warnings and Precautions ( 5.10 )] AV Heart Block [see Warnings and Precautions ( 5.11 )] Hepatic Porphyria [see Warnings and Precautions ( 5.12 )] Increased Intraocular Pressure [see Warnings and Precautions ( 5.13 )] Most common ( > 5% and 2 times placebo) adverse reactions were dizziness, somnolence, nausea, vomiting, ataxia, constipation, pruritus, dry mouth, asthenia, blurred vision, and speech disorder ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals LLC at 1-866-982-5438 or FDA…

Bone marrow depression [see Warnings and Precautions ( 5.2 ) ] . Known hypersensitivity to carbamazepine, such as anaphylaxis or serious hypersensitivity reaction [see Warnings and Precautions ( 5.3 ) ] . Known hypersensitivity to any of the tricyclic compounds (e.g., amitriptyline, desipramine, imipramine, protriptyline, and nortriptyline.) Hypersensitivity reactions include anaphylaxis and serious rash. Concomitant use of delavirdine or other non-nucleoside reverse transcriptase inhibitors that are substrates for CYP3A4. EQUETRO can substantially reduce the concentrations of these drugs through induction of CYP3A4. This can lead to loss of virologic response and possible resistance to these medications [see Warnings and Precautions ( 5.9 ) and Drug Interactions ( 7.2 ) ] . Concomitant use of monoamine oxidase inhibitors (MAOIs). Before beginning treatment with EQUETRO, MAOIs should be discontinued for a minimum of 14 days. Concomitant use can cause serotonin syndrome. Concomitant use of nefazodone. This may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect. Bone marrow depression ( 4 ) Known hypersensitivity to carbamazepine ( 4 ) Known hypersensitivity to tricyclic antidepressants ( 4 ) Concomitant use with monoamine oxidase inhibitors (MAOIs) or use within 14 days of discontinuing an MAOI ( 4 ) Concomitant use with delavirdine or other non-nucleoside reverse transcriptase inhibitors that are substrates for CYP3A4. EQUETRO decreases efficacy of these drugs ( 4 , 5.9 ) Concomitant use of nefazodone ( 4 )

10.1 Human Experience Lowest known lethal dose of carbamazepine: adults, greater than 60 grams (39-year-old man). Highest known doses survived: adults, 30 grams (31-year-old woman); children, 10 grams (6-year-old boy); small children, 5 grams (3-year-old girl). Signs and Symptoms: The first signs and symptoms of carbamazepine overdose appear after 1 to 3 hours. Neuromuscular disturbances are the most prominent. Cardiovascular disorders are generally milder, and severe cardiac complications occur only when very high doses (greater than 60 grams) have been ingested. Respiration: Irregular breathing, respiratory depression. Cardiovascular System: Tachycardia, hypotension or hypertension, shock, conduction disorders. Nervous System and Muscles: Impairment of consciousness ranging in severity to deep coma. Convulsions, especially in small children. Motor restlessness, muscular twitching, tremor, athetoid movements, opisthotonos, ataxia, drowsiness, dizziness, mydriasis, nystagmus, adiadochokinesia, ballism, psychomotor disturbances, dysmetria. Initial hyperreflexia, followed by hyporeflexia. Gastrointestinal Tract: Nausea, vomiting. Kidneys and Bladder: Anuria or oliguria, urinary retention. Laboratory Findings: Isolated instances of overdosage have included leukocytosis, reduced leukocyte count, glycosuria, and acetonuria. ECG may show dysrhythmias. Combined Poisoning: When…

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Cytochrome (CYP) 3A4 inhibitors, epoxide hydrolase inhibitors, CYP3A4 inducers, drugs metabolized by CYP1A2 or CYP3A4 (oral contraceptives, delavirdine, nefazodone), phenytoin, CNS depressants, lithium, chloroquine, mefloquine ( 7.1 , 7.2 , 7.3 ) Equetro may decrease the effectiveness of hormonal contraceptives. Use alternative form of birth control ( 7.2 ) 7.1 Pharmacokinetic Effect s of other Drugs on EQ U ETRO Drugs that Inhibit Cytochrome P450 3A4 (CYP3A4) EQUETRO is metabolized primarily by CYP3A4 to the active carbamazepine-10,11-epoxide, which is further metabolized to the trans-diol by epoxide hydrolase. Inhibitors of CYP 3A4 and/or epoxide hydrolase can increase plasma levels of EQUETRO and its active metabolites, increasing plasma concentrations of EQUETRO and the risk of adverse reactions. It may be necessary to reduce the EQUETRO dose if used concomitantly with inhibitors of CYP3A4 and/or epoxide hydrolase. The following drugs are CYP3A4 inhibitors: Acetazolamide, aprepitant, azole antifungals (e.g., ketoconazole, itraconazole, fluconazole, voriconazole ) , cimetidine, ciprofloxacin, clarithromycin, dalfopristin, danazol, dantrolene, delavirdine, diltiazem, erythromycin, fluoxetine, fluvoxamine, grapefruit juice, ibuprofen, isoniazid, loratadine, nefazodone, niacinamide, nicotinamide, olanzapine, omeprazole, oxybutynin, quinine, quinupristin, ticlopidine, troleandomycin, valproate, verapamil, zileuton. Drugs that Inhibit Epoxide H ydrolase and CYP3A4 Clarithromycin, erythromycin, loxapine, quetiapine, and valproate also inhibit epoxide hydrolase, resulting in increased levels of the active metabolite carbamazepine-10,11-epoxide [see Clinical Pharmacology ( 12.3 )] . Drugs that Induce CYP3A4 CYP3A4 inducers can decrease serum concentrations of EQUETRO and decrease its effectiveness. It may be necessary to increase the dose of EQUETRO if used concomitantly with a CYP3A4 inducer. Such drugs include the following: Aminophylline, c isplatin, doxorubicin, felbamate, phosphenytoin, methsuximide , phenobarbital, phenytoin, primidone, rifampin and theophylline. 7.2 Pharmacokinetic Effect s of EQUETRO on other Drugs EQUETRO is a potent inducer of hepatic 3A4 and is also known to be an inducer of CYP1A2, 2B6, 2C9/19 and may therefore reduce plasma concentrations of co-medications mainly metabolized by CYP 1A2, 2B6, 2C9/19 and 3A4, through induction of their metabolism. When used concomitantly with EQUETRO, monitoring of concentrations or dosage adjustment of these agents may be necessary. EQUETRO decreases the concentrations of the following drugs through induction of their metabolism: Hormonal Contraceptives (CYP3A4 Substrates) EQUETRO is a strong inducer of CYP3A4. EQUETRO can increase the metabolism of certain hormonal contraceptives (through CYP3A4 induction) such as oral and subdermal implant contraceptives, leading to significantly lower plasma concentrations of hormones. This can cause contraceptive failure or breakthrough bleeding. Consider alternatives to oral and subdermal implant contraceptives that are significantly affected by induction of CYP3A4; or consider alternatives to EQUETRO [see Warnings and Precautions ( 5.5 ) and Use in Specific Populations ( 8.3 )] . Delavirdine and other Non-Nucleoside Reverse Transcriptase Inhibitors (CYP3A4 Substrates) Through induction of CYP3A4, EQUETRO increases the metabolism of delavirdine and certain non-nucleoside reverse transcriptase inhibitors and significantly reduces the plasma concentrations of these drugs. This can cause inadequate antiviral activity, loss of virologic response, and possible resistance to delavirdine or other non-nucleoside reverse transcriptase inhibitors. Therefore, the use of EQUETRO with these non-nucleoside reverse transcriptase inhibitors is contraindicated [see Contraindications ( 4 ) and Warnings and Precautions ( 5.9 )] . Nefazodone (CYP3A4 Substrate) The use of EQUETRO is contraindicated with the use of nefazodone because the concomitant use may result in insufficient plasma concentrations of nefazodone and its active metabolite to achieve a therapeutic effect of nefazodone. Warfarin (CYP1A2 and CYP3A4 Substrate) Through induction of CYP1A2 and CYP3A4, EQUETRO decreases the concentration of warfarin and decreases its anticoagulant effectiveness. Aripiprazole When carbamazepine is added to aripiprazole, the aripiprazole dose should be doubled. Additional dose increases should be based on clinical evaluation. If carbamazepine is later withdrawn, the aripiprazole dose should be reduced. Tacrolimus When carbamazepine is used with tacrolimus, monitoring of tacrolimus blood concentrations and appropriate dosage adjustments are recommended. Temsirolimus The use of concomitant strong CYP3A4 inducers such as carbamazepine should be avoided with temsirolimus. If patients must be coadministered carbamazepine with temsirolimus, an adjustment of temsirolimus dosage should be considered. Lapatinib The use of carbamazepine with lapatinib should generally be avoided. If carbamazepine is started in a patient already taking lapatinib, the dose of lapatinib should be gradually titrated up. If carbamazepine is discontinued, the lapatinib dose should be reduced. HIV Protease Inhibitors Due to strong induction of CYP3A4 caused by carbamazepine, use of EQUETRO with HIV protease inhibitors is not recommended. Other CYP1A2 and CYP3A4 Substrates EQUETRO induces CYP1A2 and CYP3A4, leading to decreased concentrations of drugs metabolized by CYP3A4 or CYP1A2. It may be necessary to increase the doses of such drugs when used concomitantly with EQUETRO. Drugs metabolized by CYP3A4 or CYP1A2 include the following: Acetaminophen, albendazole, alprazolam, aprepitant, buprenorphone, bupropion, buspirone, citalopram, clobazam, clonazepam, clozapine, cyclosporin, delavirdine, desipramine, diazepam, dicumarol, dihydropyridine calcium channel blockers (e.g., felodipine), doxycycline, ethosuximide, everolimus, felbamate, glucocorticoids, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, lorazepam, methadone, methsuxamide, mianserin, midazolam, mirtazapine, nefazodone, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, paliperidone, phenytoin, praziquantel, quetiapine, risperidone, sertraline, sirolimus, tadalafil, theophylline, topiramate, tiagabine, tramadol, triazolam, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), trazodone, valproate, warfarin , ziprasidone, and zonisamide. EQUETRO increases the plasma levels of the following drugs by inhibition of their metabolism : Clomipramine, P henytoin, and P rimidone EQUETRO can increase the concentrations of clomipramine, phenytoin, and primidone. If a patient has been titrated to a stable dosage on one of these agents in this category, and then begins treatment with EQUETRO, it may be necessary to decrease the dose of these drugs. Phenytoin Phenytoin levels have been reported to increase or decrease in the presence of carbamazepine. There are multiple pharmacokinetic mechanisms for changes in phenytoin levels when used concomitantly with EQUETRO. Monitor phenytoin serum levels carefully when used concomitantly with EQUETRO. Cyclophosphamide Cyclophosphamide is an inactive prodrug and is converted to its active metabolite in part by CYP3A. The rate of metabolism and the leukopenic activity of cyclophosphamide are reportedly increased by chronic co-administration of CYP3A4 inducers. There is a potential for increased cyclophosphamide toxicity when coadministered with carbamazepine. 7.3 Pharmacodynamic Drug Interactions M onoamine O xidase I nhibitors Concomitant treatment with EQUETRO is contraindicated during use of an MAOI or within 14 days after discontinuing an MAOI. Concomitant use can cause serotonin syndrome. Lithium Concomitant administration of EQUETRO and lithium can increase the risk of neurotoxic adverse reactions. Consider reducing the dose of lithium or EQUETRO when using these drugs concomitantly. Isoniazid Concomitant use of carbamazepine and isoniazid has been reported to increase isoniazid-induced hepatotoxicity. CNS Depressants The concomitant use of EQUETRO and other CNS depressants can increase the risk of respiratory depression, profound sedation, hypotension, and syncope. CNS depressants include: alcohol, opioid analgesics, benzodiazepines, tricyclic antidepressants, sedative/hypnotics, anticonvulsants, antipsychotics, antihistamines, anticholinergics, alpha and beta blockers, general anesthetics, muscle relaxants, and illicit CNS depressants. Consider reducing the dose of CNS depressants or EQUETRO when using these drugs concomitantly. Chloroquine and Mefloquine The anti-malarial drugs chloroquine and mefloquine can antagonize the activity of EQUETRO. N e uromuscular Blocking Agents Resistance to the neuromuscular blocking action of the nondepolarizing neuromuscular blocking agents pancuronium, vecuronium, rocuronium and cisatracurium has occurred in patients chronically administered carbamazepine. Whether or not carbamazepine has the same effect on other nondepolarizing agents is unknown. Patients should be monitored closely for more rapid recovery from neuromuscular blockade than expected, and infusion rate requirements may be higher.