LAMOTRIGINE tablet, extended release

Maa: Yhdysvallat

Kieli: englanti

Lähde: NLM (National Library of Medicine)

Aktiivinen ainesosa:

LAMOTRIGINE (UNII: U3H27498KS) (LAMOTRIGINE - UNII:U3H27498KS)

Saatavilla:

NorthStar Rx LLC

INN (Kansainvälinen yleisnimi):

LAMOTRIGINE

Koostumus:

LAMOTRIGINE 25 mg

Antoreitti:

ORAL

Prescription tyyppi:

PRESCRIPTION DRUG

Käyttöaiheet:

Lamotrigine extended-release tablets are indicated as adjunctive therapy for primary generalized tonic-clonic (PGTC) seizures and partial-onset seizures with or without secondary generalization in patients aged 13 years and older. Lamotrigine extended-release tablets are indicated for conversion to monotherapy in patients aged 13 years and older with partial-onset seizures who are receiving treatment with a single antiepileptic drug (AED). Safety and effectiveness of lamotrigine extended-release tablets have not been established (1) as initial monotherapy or (2) for simultaneous conversion to monotherapy from 2 or more concomitant AEDs. Safety and effectiveness of lamotrigine extended-release tablets for use in patients younger than 13 years have not been established. Lamotrigine extended-release tablets are contraindicated in patients who have demonstrated hypersensitivity (e.g., rash, angioedema, acute urticaria, extensive pruritus, mucosal ulceration) to the drug or its ingredients [see Boxed Warning, Warnings and Precautions (5.1, 5.3 ) ]. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AEDs, including lamotrigine extended-release tablets, during pregnancy. Encourage women who are taking lamotrigine extended-release tablets, during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/.  Risk Summary Data from several prospective pregnancy exposure registries and epidemiological studies of pregnant women have not detected an increased frequency of major congenital malformations or a consistent pattern of malformations among women exposed to lamotrigine compared with the general population (see Data). In animal studies, administration of lamotrigine during pregnancy resulted in developmental toxicity (increased mortality, decreased body weight, increased structural variation, neurobehavioral abnormalities) at doses lower than those administered clinically. Lamotrigine decreased fetal folate concentrations in rats, an effect known to be associated with adverse pregnancy outcomes in animals and humans (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations As with other AEDs, physiological changes during pregnancy may affect lamotrigine concentrations and/or therapeutic effect. There have been reports of decreased lamotrigine concentrations during pregnancy and restoration of pre-pregnancy concentrations after delivery. Dose adjustments may be necessary to maintain clinical response. Data Human Data: Data from several international pregnancy registries have not shown an increased risk for malformations overall. The International Lamotrigine Pregnancy Registry reported major congenital malformations in 2.2% (95% CI: 1.6%, 3.1%) of 1,558 infants exposed to lamotrigine monotherapy in the first trimester of pregnancy. The NAAED Pregnancy Registry reported major congenital malformations among 2% of 1,562 infants exposed to lamotrigine monotherapy in the first trimester. EURAP, a large international pregnancy registry focused outside of North America, reported major birth defects in 2.9% (95% CI: 2.3%, 3.7%) of 2,514 exposures to lamotrigine monotherapy in the first trimester. The frequency of major congenital malformations was similar to estimates from the general population. The NAAED Pregnancy Registry observed an increased risk of isolated oral clefts: among 2,200 infants exposed to lamotrigine early in pregnancy, the risk of oral clefts was 3.2 per 1,000 (95% CI: 1.4, 6.3), a 3-fold increased risk versus unexposed healthy controls. This finding has not been observed in other large international pregnancy registries. Furthermore, a case-control study based on 21 congenital anomaly registries covering over 10 million births in Europe reported an adjusted odds ratio for isolated oral clefts with lamotrigine exposure of 1.45 (95% CI: 0.8, 2.63). Several meta-analyses have not reported an increased risk of major congenital malformations following lamotrigine exposure in pregnancy compared with healthy and disease-matched controls. No patterns of specific malformation types were observed. The same meta-analyses evaluated the risk of additional maternal and infant outcomes including fetal death, stillbirth, preterm birth, small for gestational age, and neurodevelopmental delay. Although there are no data suggesting an increased risk of these outcomes with lamotrigine monotherapy exposure, differences in outcome definition, ascertainment methods, and comparator groups limit the conclusions that can be drawn. Animal Data: When lamotrigine was administered to pregnant mice, rats, or rabbits during the period of organogenesis (oral doses of up to 125, 25, and 30 mg/kg, respectively), reduced fetal body weight and increased incidences of fetal skeletal variations were seen in mice and rats at doses that were also maternally toxic. The no-effect doses for embryofetal developmental toxicity in mice, rats, and rabbits (75, 6.25, and 30 mg/kg, respectively) are similar to (mice and rabbits) or less than (rats) the human dose of 400 mg/day on a body surface area (mg/m2 ) basis. In a study in which pregnant rats were administered lamotrigine (oral doses of 0, 5, or 25 mg/kg) during the period of organogenesis and offspring were evaluated postnatally, neurobehavioral abnormalities were observed in exposed offspring at both doses. The lowest effect dose for developmental neurotoxicity in rats is less than the human dose of 400 mg/day on a mg/m2 basis. Maternal toxicity was observed at the higher dose tested. When pregnant rats were administered lamotrigine (oral doses of 0, 5, 10, or 20 mg/kg) during the latter part of gestation and throughout lactation, increased offspring mortality (including stillbirths) was seen at all doses. The lowest effect dose for pre- and post-natal developmental toxicity in rats is less than the human dose of 400 mg/day on a mg/m2  basis. Maternal toxicity was observed at the 2 highest doses tested. When administered to pregnant rats, lamotrigine decreased fetal folate concentrations at doses greater than or equal to 5 mg/kg/day, which is less than the human dose of 400 mg/day on a mg/m2  basis. Risk Summary Lamotrigine is present in milk from lactating women taking lamotrigine extended-release tablets (see Data). Neonates and young infants are at risk for high serum levels because maternal serum and milk levels can rise to high levels postpartum if lamotrigine dosage has been increased during pregnancy but is not reduced after delivery to the pre-pregnancy dosage. Glucuronidation is required for drug clearance. Glucuronidation capacity is immature in the infant and this may also contribute to the level of lamotrigine exposure. Events including rash, apnea, drowsiness, poor sucking, and poor weight gain (requiring hospitalization in some cases) have been reported in infants who have been human milk-fed by mothers using lamotrigine; whether or not these events were caused by lamotrigine is unknown. No data are available on the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for lamotrigine extended-release tablets and any potential adverse effects on the breastfed infant from lamotrigine extended-release tablets or from the underlying maternal condition. Clinical Considerations Human milk-fed infants should be closely monitored for adverse events resulting from lamotrigine. Measurement of infant serum levels should be performed to rule out toxicity if concerns arise. Human milk-feeding should be discontinued in infants with lamotrigine toxicity. Data Data from multiple small studies indicate that lamotrigine plasma levels in nursing infants have been reported to be as high as 50% of maternal plasma concentrations. Lamotrigine extended-release tablets are indicated as adjunctive therapy for PGTC and partial- onset seizures with or without secondary generalization in patients aged 13 years and older. Safety and effectiveness of lamotrigine extended-release tablets for any use in patients younger than 13 years have not been established. Immediate-release lamotrigine is indicated for adjunctive therapy in patients aged 2 years and older for partial-onset seizures, the generalized seizures of Lennox-Gastaut syndrome, and PGTC seizures. Safety and efficacy of immediate-release lamotrigine used as adjunctive treatment for partial-onset seizures, were not demonstrated in a small, randomized, double-blind, placebo-controlled, withdrawal trial in very young pediatric patients (aged 1 to 24 months). Immediate-release lamotrigine was associated with an increased risk for infectious adverse reactions (lamotrigine 37%, placebo 5%), and respiratory adverse reactions (lamotrigine 26%, placebo 5%). Infectious adverse reactions included bronchiolitis, bronchitis, ear infection, eye infection, otitis externa, pharyngitis, urinary tract infection, and viral infection. Respiratory adverse reactions included nasal congestion, cough, and apnea. Juvenile Animal Data In a juvenile animal study in which lamotrigine (oral doses of 0, 5, 15, or 30 mg/kg) was administered to young rats from postnatal day 7 to 62, decreased viability and growth were seen at the highest dose tested and long-term neurobehavioral abnormalities (decreased locomotor activity, increased reactivity, and learning deficits in animals tested as adults) were observed at the 2 highest doses. The no-effect dose for adverse developmental effects in juvenile animals is less than the human dose of 400 mg/day on a mg/m2  basis. Clinical trials of lamotrigine extended-release tablets for epilepsy did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients or exhibit a different safety profile than that of younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Experience in patients with hepatic impairment is limited. Based on a clinical pharmacology study with immediate-release lamotrigine in 24 subjects with mild, moderate, and severe liver impairment [see Clinical Pharmacology (12.3) ], the following general recommendations can be made. No dosage adjustment is needed in patients with mild liver impairment. Initial, escalation, and maintenance doses should generally be reduced by approximately 25% in patients with moderate and severe liver impairment without ascites and 50% in patients with severe liver impairment with ascites. Escalation and maintenance doses may be adjusted according to clinical response [see Dosage and Administration (2.1) ].  Lamotrigine is metabolized mainly by glucuronic acid conjugation, with the majority of the metabolites being recovered in the urine. In a small study comparing a single dose of immediate-release lamotrigine in subjects with varying degrees of renal impairment with healthy volunteers, the plasma half-life of lamotrigine was approximately twice as long in the subjects with chronic renal failure  [see Clinical Pharmacology (12.3) ].   Initial doses of lamotrigine extended-release tablets should be based on patients' AED regimens; reduced maintenance doses may be effective for patients with significant renal impairment. Few patients with severe renal impairment have been evaluated during chronic treatment with lamotrigine. Because there is inadequate experience in this population, lamotrigine extended-release tablets should be used with caution in these patients [see Dosage and Administration (2.1) ].

Tuoteyhteenveto:

Lamotrigine extended-release tablets USP, 25 mg are yellow colored round, biconvex tablets imprinted in black ink with ‘R717’ on one side and plain on the other side and are supplied as unit-of-use bottles of 30’s. Bottles of 30                                       NDC 16714-623-01 Lamotrigine extended-release tablets USP, 50 mg are light green colored round, biconvex tablets imprinted in black ink with ‘R718’ on one side and plain on the other side and are supplied as unit-of-use bottles of 30’s. Bottles of 30                                       NDC 16714-624-01 Lamotrigine extended-release tablets USP, 100 mg are orange colored round, biconvex tablets imprinted in black ink with ‘R719’ on one side and plain on the other side  and are supplied as unit-of-use bottles of 30’s. Bottles of 30                                       NDC 16714-625-01 Lamotrigine extended-release tablets USP, 200 mg are blue colored round, biconvex tablets imprinted in black ink with ‘R720’ on one side and plain on the other side and are supplied as unit-of-use bottles of 30’s. Bottles of 30                                       NDC 16714-626-01 Lamotrigine extended-release tablets USP, 250 mg are purple colored, oval shaped, biconvex tablets imprinted with ‘R419’ on one side and plain on the other side and are supplied as unit-of-use bottles of 30’s. Bottles of 30                                       NDC 16714-893-01 Lamotrigine extended-release tablets USP, 300 mg are grey colored modified capsule shaped, biconvex tablets imprinted with ‘R428’ on one side and plain on the other side and are supplied as unit-of-use bottles of 30’s. Bottles of 30                                        NDC 16714-627-01 Storage Store at 20°to 25° C (68° to77° F); [See USP Controlled Room Temperature].

Valtuutuksen tilan:

Abbreviated New Drug Application

Pakkausseloste

LAMOTRIGINE- LAMOTRIGINE TABLET, EXTENDED RELEASE
NorthStar Rx LLC
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MEDICATION GUIDE
Lamotrigine Extended-Release Tablets, USP
(la-MOE-tri-jeen)
What is the most important information I should know about lamotrigine
extended-release tablets?
1. Lamotrigine extended-release tablets may cause a serious skin rash
that may cause you to be
hospitalized or even cause death.
There is no way to tell if a mild rash will become more serious. A
serious skin rash can happen at any
time during your treatment with lamotrigine extended-release tablets,
but is more likely to happen within
the first 2 to 8 weeks of treatment. Children aged between 2 and 16
years have a higher chance of getting
this serious skin rash while taking lamotrigine extended-release
tablets. Lamotrigine extended-release
tablets are not approved for use in children younger than 13 years.
The risk of getting a serious skin rash is higher if you:
• take lamotrigine extended-release tablets while taking valproate
[DEPAKENE (valproic acid) or
DEPAKOTE (divalproex sodium)].
• take a higher starting dose of lamotrigine extended-release
tablets than your healthcare provider
prescribed.
• increase your dose of lamotrigine extended-release tablets faster
than prescribed.
Call your healthcare provider right away if you have any of the
following:
• a skin rash
• blistering or peeling of your skin
• hives
• painful sores in your mouth or around your eyes
These symptoms may be the first signs of a serious skin reaction. A
healthcare provider should examine
you to decide if you should continue taking lamotrigine
extended-release tablets.
2. Other serious reactions, including serious blood problems or liver
problems. Lamotrigine extended-
release tablets can also cause other types of allergic reactions or
serious problems that may affect organs
and other parts of your body like your liver or blood cells. You may
or may not have a rash with these
types of reactions. Call your healthcare provider right away if you
have any of these symptoms:
• fev

Valmisteyhteenveto

LAMOTRIGINE- LAMOTRIGINE TABLET, EXTENDED RELEASE
NORTHSTAR RX LLC
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LAMOTRIGINE EXTENDED-
RELEASE TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR LAMOTRIGINE
EXTENDED-RELEASE TABLETS.
LAMOTRIGINE EXTENDED-RELEASE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1994
WARNING: SERIOUS SKIN RASHES
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
CASES OF LIFE-THREATENING SERIOUS RASHES, INCLUDING STEVENS-JOHNSON
SYNDROME AND TOXIC
EPIDERMAL NECROLYSIS, AND/OR RASH-RELATED DEATH HAVE BEEN CAUSED BY
LAMOTRIGINE. THE
RATE OF SERIOUS RASH IS GREATER IN PEDIATRIC PATIENTS THAN IN ADULTS.
ADDITIONAL FACTORS
THAT MAY INCREASE THE RISK OF RASH INCLUDE:
• COADMINISTRATION WITH VALPROATE.
• EXCEEDING RECOMMENDED INITIAL DOSE OF LAMOTRIGINE EXTENDED-RELEASE
TABLETS .
• EXCEEDING RECOMMENDED DOSE ESCALATION FOR LAMOTRIGINE
EXTENDED-RELEASE TABLETS.
(5.1)
BENIGN RASHES ARE ALSO CAUSED BY LAMOTRIGINE; HOWEVER, IT IS NOT
POSSIBLE TO PREDICT
WHICH RASHES WILL PROVE TO BE SERIOUS OR LIFE THREATENING. LAMOTRIGINE
EXTENDED-RELEASE
TABLETS SHOULD BE DISCONTINUED AT THE FIRST SIGN OF RASH, UNLESS THE
RASH IS CLEARLY NOT
DRUG RELATED. (5.1)
RECENT MAJOR CHANGES
Warnings and Precautions,
Cardiac Rhythm and Conduction Abnormalities (5.4) 3/2021
INDICATIONS AND USAGE
Lamotrigine extended-release tablets are indicated for:
adjunctive therapy for primary generalized tonic-clonic seizures and
partial-onset seizures with or
without secondary generalization in patients aged 13 years and older.
(1.1)
conversion to monotherapy in patients aged 13 years and older with
partial-onset seizures who are
receiving treatment with a single antiepileptic drug. (1.2)
Limitation of use: Safety and effectiveness in patients younger than
13 years have not been established.
(1.3)
DOSAGE AND ADMINISTRATION
Do not exceed the recommended initial dosage and subsequent dose
escalation. (2.1)
Initiation of adjunctive th