Equetro

Dosage Forms And Strengths

EQUETRO (carbamazepine) extended-release capsules for oral administration is supplied in three dosage strengths:

• 100 mg — Two-piece hard gelatin capsule yellow opaque cap with bluish green opaque body printed with SPD417 on one end and SPD417 and 100 mg on the other in white ink
• 200 mg — Two-piece hard gelatin capsule yellow opaque cap with blue opaque body printed with SPD417 on one end and SPD417 and 200 mg on the other in white ink.
• 300 mg — Two-piece hard gelatin capsule yellow opaque cap with blue body printed with SPD417 on one end and SPD417 and 300 mg on the other in white ink.

Storage And Handling

EQUETRO (carbamazepine) extended-release capsules are supplied in three dosage strengths.

• 100 mg — Two-piece hard gelatin capsule yellow opaque cap with bluish green opaque body printed with SPD417 on one end and SPD417 and 100 mg on the other in white ink: Supplied in bottles of 120 NDC 30698-419-12
• 200 mg — Two-piece hard gelatin capsule yellow opaque cap with blue opaque body printed with SPD417 on one end and SPD417 and 200 mg on the other in white ink: Supplied in bottles of 120 NDC 30698-421-12
• 300 mg — Two-piece hard gelatin capsule yellow opaque cap with blue body printed with SPD417 on one end and SPD417 and 300 mg on the other in white ink: Supplied in bottles of 120 NDC 30698-423-12

Store at 25° C (77° F); excursions permitted to 15–30° C (59–86° F) [see USP controlled room temperature].

Protect from light and moisture

Manufactured for Validus Pharmaceuticals LLC, 119 Cherry Hill Road, Suite 310, Parsippany, NJ 07054. Revised: Sep 2016

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you are taking:

• cimetidine, danazol, diltiazem, macrolides, erythromycin, troleandomycin, clarithromycin, fluoxetine, fluvoxamine, nefazodone, trazodone, loxapine, olanzapine, quetiapine, loratadine, terfenadine, omeprazole, oxybutynin, dantrolene, isoniazid, niacinamide, nicotinamide, ibuprofen, propoxyphene, azoles (e.g., ketaconazole, itraconazole, fluconazole, voriconazole), acetazolamide, verapamil, ticlopidine, grapefruit juice, protease inhibitors, valproate.

The medicines listed above may inhibit the metabolism of carbamazepine, thereby increasing the levels of carbamazepine in your body.

There are other medicines that may increase the rate of metabolism of carbamazepine, thereby decreasing the amount of carbamazepine available in your body. They include:

• cisplatin, doxorubicin HCl, felbamate, fosphenytoin, rifampin, phenobarbital, phenytoin, primidone, methsuximide, theophylline, aminophylline.

Carbamazepine may cause an increase in the metabolism of other medicines. In doing so, carbamazepine causes, or would be expected to cause, decreased levels of the following:

• acetaminophen, alprazolam, bupropion, dihydropyridine calcium channel blockers (e.g., felodipine), citalopram, cyclosporine, corticosteroids (e.g., prednisolone, dexamethasone), clonazepam, clozapine, dicumarol, doxycycline, ethosuximide, everolimus, haloperidol, imatinib, itraconazole, lamotrigine, levothyroxine, methadone, methsuximide, midazolam, olanzapine, oral and other hormonal contraceptives, oxcarbazepine, phensuximide, phenytoin, praziquantel, protease inhibitors, risperidone, theophylline, tiagabine, topiramate, tramadol, trazodone, tricyclic antidepressants (e.g., imipramine, amitriptyline, nortriptyline), valproate, warfarin, ziprasidone, zonisamide.

If you must take one of the above medicines along with carbamazepine, your doctor may adjust your dosage.

Other medicines that may interact with carbamazepine include:

• nefazodone
• lithium
• isoniazid
• diuretics (hydrochlorothiazide, furosemide)
• pancuronium
• hormonal contraceptives

This is not a complete list of carbamazepine interactions. Ask your doctor or pharmacist for more information.

SERIOUS DERMATOLOGIC REACTIONS AND HLA-B*1502 ALLELE

• SERIOUS AND SOMETIMES FATAL DERMATOLOGIC REACTIONS, INCLUDING TOXIC EPIDERMAL NECROLYSIS (TEN) AND STEVENS-JOHNSON SYNDROME (SJS), HAVE BEEN REPORTED DURING TREATMENT WITH Carbamazepine. 
• THESE REACTIONS ARE ESTIMATED TO OCCUR IN 1 TO 6 PER 10,000 NEW USERS IN COUNTRIES WITH MAINLY CAUCASIAN POPULATIONS, BUT THE RISK IN SOME ASIAN COUNTRIES IS ESTIMATED TO BE ABOUT 10 TIMES HIGHER. STUDIES IN PATIENTS OF CHINESE ANCESTRY HAVE FOUND A STRONG ASSOCIATION BETWEEN THE RISK OF DEVELOPING SJS/TEN AND THE PRESENCE OF HLA-B*1502, AN INHERITED ALLELIC VARIANT OF THE HLA-B GENE. 
• HLA-B*1502 IS FOUND ALMOST EXCLUSIVELY IN PATIENTS WITH ANCESTRY ACROSS BROAD AREAS OF ASIA. PATIENTS WITH ANCESTRY IN GENETICALLY AT-RISK POPULATIONS SHOULD BE SCREENED FOR THE PRESENCE OF HLA-B*1502 PRIOR TO INITIATING TREATMENT WITH Carbamazepine. 
• PATIENTS TESTING POSITIVE FOR THE ALLELE SHOULD NOT BE TREATED WITH Carbamazepine UNLESS THE BENEFIT CLEARLY OUTWEIGHS THE RISK.

APLASTIC ANEMIA AND AGRANULOCYTOSIS

• APLASTIC ANEMIA AND AGRANULOCYTOSIS HAVE BEEN REPORTED IN ASSOCIATION WITH THE USE OF Carbamazepine. DATA FROM A POPULATION-BASED CASE CONTROL STUDY DEMONSTRATE THAT THE RISK OF DEVELOPING THESE REACTIONS IS 5-8 TIMES GREATER THAN IN THE GENERAL POPULATION. HOWEVER, THE OVERALL RISK OF THESE REACTIONS IN THE UNTREATED GENERAL POPULATION IS LOW, APPROXIMATELY SIX PATIENTS PER ONE MILLION POPULATION PER YEAR FOR AGRANULOCYTOSIS AND TWO PATIENTS PER ONE MILLION POPULATION PER YEAR FOR APLASTIC ANEMIA.
• ALTHOUGH REPORTS OF TRANSIENT OR PERSISTENT DECREASED PLATELET OR WHITE BLOOD CELL COUNTS ARE NOT UNCOMMON IN ASSOCIATION WITH THE USE OF Carbamazepine, DATA ARE NOT AVAILABLE TO ESTIMATE ACCURATELY THEIR INCIDENCE OR OUTCOME. HOWEVER, THE VAST MAJORITY OF THE CASES OF LEUKOPENIA HAVE NOT PROGRESSED TO THE MORE SERIOUS CONDITIONS OF APLASTIC ANEMIA OR AGRANULOCYTOSIS.
• BECAUSE OF THE VERY LOW INCIDENCE OF AGRANULOCYTOSIS AND APLASTIC ANEMIA, THE VAST MAJORITY OF MINOR HEMATOLOGIC CHANGES OBSERVED IN MONITORING OF PATIENTS ON Carbamazepine ARE UNLIKELY TO SIGNAL THE OCCURRENCE OF EITHER ABNORMALITY. NONETHELESS, COMPLETE PRETREATMENT HEMATOLOGICAL TESTING 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 THE DRUG SHOULD BE CONSIDERED IF ANY EVIDENCE OF SIGNIFICANT BONE MARROW DEPRESSION DEVELOPS.

This section provides information on the proper use of a number of products that contain carbamazepine. It may not be specific to Equetro. Please read with care.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine comes with a Medication Guide Read and follow the instructions carefully. Ask your doctor if you have any questions.

Carbamazepine should be taken with meals to lessen the chance of stomach upset (nausea and vomiting).

Carbamazepine extended-release capsules do not need to be taken with meals unless they upset your stomach. The contents of the extended-release capsules may be sprinkled over a teaspoon of applesauce or other similar food. The capsule or its contents should not be crushed or chewed.

The extended-release tablets must be swallowed whole and should not be crushed or chewed. Do not take extended-release tablets that are damaged or have chips or cracks.

Grapefruit and grapefruit juice may increase the effects of this medicine by increasing the amount in the body. You should not eat grapefruit or drink grapefruit juice while you are taking this medicine.

If you are taking this medicine for pain relief:

• Carbamazepine is not an ordinary pain reliever. It should be used only when a doctor prescribes it for certain kinds of pain. Do not take carbamazepine for any other aches or pains.

If you are taking Tegretol® oral suspension:

• Shake the oral suspension well before each use. Measure your dose with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.
• Do not take any other liquid medicines at the same time that you take your dose of Tegretol® without first checking with your doctor.

Tegretol® tablets works differently than Tegretol® oral suspension, even at the same dose (number of milligrams). Do not switch from the tablets to the oral suspension unless your doctor tells you to.

Tegretol® may be used alone or together with other seizure medicines. Ask your doctor first before taking any other seizure medicine together with Tegretol®.

Do not take Equetro® capsules if you are also using Tegretol® suspension or tablets. These medicines should not be taken together because both medicines contains carbamazepine. Ask your doctor if you have any questions.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release capsules):
  • For bipolar disorder:
    • Adults—At first, 200 milligrams (mg) two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 1600 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For epilepsy:
    • Adults and children 12 years of age and older—At first, 200 milligrams (mg) two times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 500 to 800 mg two times a day.
    • Children younger than 12 years of age—Dose is based on body weight and must be determined by your doctor. However, the dose is usually not more than 1000 mg per day.
  • For trigeminal neuralgia:
    • Adults—At first, 200 milligrams (mg) once a day. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (extended-release tablets):
  • For epilepsy:
    • Adults—At first, 200 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
    • Children 6 to 12 years of age—At first, 100 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
    • Children younger than 6 years of age—Use and dose must be determined by your doctor.
  • For trigeminal neuralgia:
    • Adults—At first, 100 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (suspension):
  • For epilepsy:
    • Adults—100 milligrams (mg) or 1 teaspoon four times a day (400 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
    • Children 6 to 12 years of age—At first, 50 milligrams (mg) or one-half teaspoon four times a day (200 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
    • Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is 10 to 20 milligrams (mg) per kilogram (kg) of body weight per day, taken four times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 35 mg per kg of body weight per day.
  • For trigeminal neuralgia:
    • Adults—At first, 50 milligrams (mg) or one-half teaspoon four times a day (200 mg per day). Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage forms (tablets or chewable tablets):
  • For epilepsy:
    • Adults—At first, 200 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 to 1600 mg per day.
    • Children 6 to 12 years of age—At first, 100 mg two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1000 mg per day.
    • Children younger than 6 years of age—Dose is based on body weight and will be determined by your doctor. The dose is 10 to 20 milligrams (mg) per kilogram (kg) of body weight per day, taken two or three times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 35 mg per kg of body weight per day.
  • For trigeminal neuralgia:
    • Adults and teenagers—At first, 100 milligrams (mg) two times a day. Your doctor may adjust your dose if needed. However, the dose is usually not more than 1200 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• It is used to treat seizures.
• It is used to treat pain caused by a problem with a nerve in the face.
• It is used to treat bipolar problems.
• It may be given to you for other reasons. Talk with the doctor.

• If you have an allergy to carbamazepine or any other part of Equetro.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have had any of these health problems: Bone marrow disease or porphyria.
• If you are taking any of these drugs: Boceprevir, delavirdine, efavirenz, etravirine, nefazodone, nevirapine, rilpivirine, or another drug that has carbamazepine in it.
• If you have taken certain drugs used for low mood (depression) like isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease like selegiline or rasagiline in the last 14 days. Taking this medicine within 14 days of those drugs can cause very bad high blood pressure.
• If you are breast-feeding or plan to breast-feed.

This is not a list of all drugs or health problems that interact with Equetro.

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 this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Feeling sleepy.
• Upset stomach or throwing up.
• Dry mouth.
• Hard stools (constipation).
• Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

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)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The most commonly reported adverse reactions (>5% in the Equetro group and at least twice placebo) in the pooled 3-week placebo-controlled trials in patients with acute mania associated with Bipolar I Disorder (Studies 1 and 2) were dizziness, somnolence, nausea, vomiting, ataxia, constipation, pruritus, dry mouth, asthenia, blurred vision, and speech disorder [see Clinical Studies (14.1)]. The Equetro doses used were 400 to 1600 mg per day.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post approval use of Equetro. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Nervous System: confusion, diplopia, oculomotor disturbances, nystagmus, speech disturbances, abnormal involuntary movements, tinnitus.

Digestive System: gastric distress, abdominal pain, diarrhea, anorexia.

Laboratory Tests: thyroid function tests (T3, T4)- decreased values

Other: lupus erythematosus-like syndrome

One case of aseptic meningitis, accompanied by myoclonus and peripheral eosinophilia, has been reported in a patient taking carbamazepine in combination with other medications. The patient was successfully dechallenged, and the meningitis reappeared upon rechallenge with carbamazepine.

6.3 Additional Adverse Reactions Associated with Carbamazepine

The following is a list of additional adverse reactions identified in clinical trials or postmarketing reports of other forms of carbamazepine and not reported above for Equetro. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

Nervous System: Isolated cases of neuroleptic malignant syndrome have been reported in carbamazepine use both with and without concomitant use of other psychotropic drugs.

Skin: onychomadesis, acute generalized exanthematous pustulosis (AGEP).

To report SUSPECTED ADVERSE REACTIONS, contact Validus Pharmaceuticals LLC at 1-866-9VALIDUS(1-866-982-5438) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Common side effects of Equetro include: ataxia, dizziness, drowsiness, nausea, and vomiting. Other side effects include: pruritus, speech disturbance, amblyopia, and xerostomia. See below for a comprehensive list of adverse effects.