Lamictal CD

Lamictal CD - General Information

Lamictal CD is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. For epilepsy it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Lamictal CD also acts as a mood stabilizer. It is the first medication since lithium granted Food and Drug Administration (FDA) approval for the maintenance treatment of bipolar type I. Chemically unrelated to other anticonvulsants, lamotrigine has relatively few side-effects and does not require blood monitoring. The exact way lamotrigine works is unknown. [Wikipedia]

 

Pharmacology of Lamictal CD

Lamictal CD, an antiepileptic drug (AED) of the phenyltriazine class, is chemically unrelated to existing antiepileptic drugs. Lamictal CD is also used in the treatment of depression and bipolar disorder. Lamictal CD is thought to exert its anticonvulsant effect by stabilizing presynaptic neuronal membranes. Lamictal CD inhibits sodium currents by selectively binding to the inactivated state of the sodium channel and subsequently suppresses the release of the excilatory amino acid, glutamate.

 

Lamictal CD for patients

Please read this leaflet carefully before you take LAMICTAL and read the leaflet provided with any refill, in case any information has changed. This leaflet provides a summary of the information about your medicine. Please do not throw away this leaflet until you have finished your medicine. This leaflet does not contain all the information about LAMICTAL and is not meant to take the place of talking with your doctor. If you have any questions about LAMICTAL, ask your doctor or pharmacist.

Information About Your Medicine:

The name of your medicine is LAMICTAL (lamotrigine). The decision to use LAMICTAL is one that you and your doctor should make together. When taking lamotrigine, it is important to follow your doctor's instructions.

1. The Purpose of Your Medicine:

For Patients With Epilepsy: LAMICTAL is intended to be used either alone or in combination with other medicines to treat seizures in people aged 2 years or older.

For Patients With Bipolar Disorder: LAMICTAL is used as maintenance treatment of Bipolar I Disorder to delay the time to occurrence of mood episodes in people aged 18 years or older treated for acute mood episodes with standard therapy.

2. Who Should Not Take LAMICTAL:

You should not take LAMICTAL if you had an allergic reaction to it in the past.

3. Side Effects to Watch for:

· Most people who take LAMICTAL tolerate it well. Common side effects with LAMICTAL include dizziness, headache, blurred or double vision, lack of coordination, sleepiness, nausea, vomiting, insomnia, and rash. LAMICTAL may cause other side effects not listed in this leaflet. If you develop any side effects or symptoms you are concerned about or need more information, call your doctor.

· Although most patients who develop rash while receiving LAMICTAL have mild to moderate symptoms, some individuals may develop a serious skin reaction that requires hospitalization. Rarely, deaths have been reported. These serious skin reactions are most likely to happen within the first 8 weeks of treatment with LAMICTAL. Serious skin reactions occur more often in children than in adults.

· Rashes may be more likely to occur if you: (1) take LAMICTAL in combination with valproate [DEPAKENE (valproic acid) or DEPAKOTE (divalproex sodium)], (2) take a higher starting dose of LAMICTAL than your doctor prescribed, or (3) increase your dose of LAMICTAL faster than prescribed.

· It is not possible to predict whether a mild rash will develop into a more serious reaction.

Therefore, if you experience a skin rash, hives, fever, swollen lymph glands, painful sores in the mouth or around the eyes, or swelling of lips or tongue, tell a doctor immediately, since these symptoms may be the first signs of a serious reaction. A doctor should evaluate your condition and decide if you should continue taking LAMICTAL.

4. The Use of LAMICTAL During Pregnancy and Breast-feeding:

The effects of LAMICTAL during pregnancy are not known at this time. If you are pregnant or are planning to become pregnant, talk to your doctor. Some LAMICTAL passes into breast milk and the effects of this on infants are unknown. Therefore, if you are breast-feeding, you should discuss this with your doctor to determine if you should continue to take LAMICTAL.

5. How to Use LAMICTAL:

· It is important to take LAMICTAL exactly as instructed by your doctor. The dose of LAMICTAL must be increased slowly. It may take several weeks or months before your final dosage can be determined by your doctor, based on your response.

· Do not increase your dose of LAMICTAL or take more frequent doses than those indicated by your doctor. Contact your doctor, if you stop taking LAMICTAL for any reason. Do not restart without consulting your doctor.

· If you miss a dose of LAMICTAL, do not double your next dose.

· Do NOT stop taking LAMICTAL or any of your other medicines unless instructed by your doctor.

· Use caution before driving a car or operating complex, hazardous machinery until you know if LAMICTAL affects your ability to perform these tasks.

· If you have epilepsy, tell your doctor if your seizures get worse or if you have any new types of seizures.

· Always tell your doctor and pharmacist if you are taking or plan to take any other prescription or over-the-counter medicines.

6. How to Take LAMICTAL:

LAMICTAL Tablets should be swallowed whole. Chewing the tablets may leave a bitter taste. LAMICTAL Chewable Dispersible Tablets may be swallowed whole, chewed, or mixed in water or diluted fruit juice. If the tablets are chewed, consume a small amount of water or diluted fruit juice to aid in swallowing.

To disperse LAMICTAL Chewable Dispersible Tablets, add the tablets to a small amount of liquid (1 teaspoon, or enough to cover the medication) in a glass or spoon. Approximately 1 minute later, when the tablets are completely dispersed, mix the solution and take the entire amount immediately.

7. Storing Your Medicine:

Store LAMICTAL at room temperature away from heat and light. Always keep your medicines out of the reach of children.

This medicine was prescribed for your use only to treat seizures or to treat Bipolar Disorder. Do not give the drug to others.

If your doctor decides to stop your treatment, do not keep any leftover medicine unless your doctor tells you to. Throw away your medicine as instructed.

 

Lamictal CD Interactions

Effects of Lamotrigine on the Pharmacokinetics of Other Drugs:

LAMICTAL Added to Carbamazepine: LAMICTAL has no appreciable effect on steady-state carbamazepine plasma concentration. Limited clinical data suggest there is a higher incidence of dizziness, diplopia, ataxia, and blurred vision in patients receiving carbamazepine with LAMICTAL than in patients receiving other EIAEDs with LAMICTAL. The mechanism of this interaction is unclear. The effect of lamotrigine on plasma concentrations of carbamazepine-epoxide is unclear. In a small subset of patients (n = 7) studied in a placebo-controlled trial, lamotrigine had no effect on carbamazepine-epoxide plasma concentrations, but in a small, uncontrolled study (n = 9), carbamazepine-epoxide levels were seen to increase.

LAMICTAL Added to Valproate: When LAMICTAL was administered to 18 healthy volunteers receiving valproate in a pharmacokinetic study, the trough steady-state valproate concentrations in plasma decreased by an average of 25% over a 3-week period, and then stabilized. However, adding LAMICTAL to the existing therapy did not cause a change in plasma valproate concentrations in either adult or pediatric patients in controlled clinical trials.

LAMICTAL Added to Lithium: The pharmacokinetics of lithium were not altered in healthy subjects (n = 20) by co-administration of 100 mg/day lamotrigine for 6 days.

LAMICTAL Added to Phenytoin: LAMICTAL has no appreciable effect on steady-state phenytoin plasma concentrations in patients with epilepsy.

Results of in vitro experiments suggest that lamotrigine does not reduce the clearance of drugs eliminated predominantly by CYP2D6.

Effects of Other Drugs on the Pharmacokinetics of Lamotrigine:.

Valproate Added to LAMICTAL: The addition of valproate increases lamotrigine steady-state concentrations in normal volunteers by slightly more than 2-fold.

Enzyme-Inducing Antiepileptic Drugs (e.g., carbamazepine, phenytoin, phenobarbital, primidone) Added to LAMICTAL: The addition of EIAEDs decreases lamotrigine steady-state concentrations by approximately 40%.

Bupropion Added to LAMICTAL: The pharmacokinetics of a 100-mg single dose of lamotrigine in 12 healthy volunteers were not changed by co-administration of bupropion at 300 mg/day starting 11 days before the lamotrigine dose.

Other Psychotropic Drugs Added to LAMICTAL: Results of in vitro experiments suggest that clearance of lamotrigine is unlikely to be reduced by concomitant administration of amitriptyline, clonazepam, clozapine, fluoxetine, haloperidol, lorazepam, phenelzine, risperidone, sertraline, or trazodone.

Interactions With Folate Inhibitors: Lamotrigine is an inhibitor of dihydrofolate reductase. Prescribers should be aware of this action when prescribing other medications that inhibit folate metabolism.

Interactions With Oral Contraceptives: In women taking lamotrigine, there have been reports of decreased lamotrigine concentrations following introduction of oral contraceptives and reports of increased lamotrigine concentrations following withdrawal of oral contraceptives. Dosage adjustments may be necessary to maintain clinical response when starting or stopping oral contraceptives during lamotrigine therapy.

The net effects of drug interactions with LAMICTAL are summarized in Table 3.

Table 3. Summary of Drug Interactions With LAMICTAL
Drug	Drug Plasma Concentration With Adjunctive LAMICTAL*	Lamotrigine Plasma Concentration With Adjunctive Drugs
Phenytoin (PHT)	«	¯
Carbamazepine (CBZ)	«	¯
CBZ epoxide	?
Valproate	¯	-
Valproate + PHT and/or CBZ	Not assessed	«
Lithium	«	Not assessed
Bupropion	Not assessed	«
*From adjunctive clinical trials and volunteer studies.
Net effects were estimated by comparing the mean clearance values obtained in adjunctive clinical trials and volunteers studies.
Not administered, but an active metabolite of carbamazepine.
« = No significant effect.
? = Conflicting data.

Drug/Laboratory Test Interactions: None known.

Carcinogenesis, Mutagenesis, Impairment of Fertility: No evidence of carcinogenicity was seen in 1 mouse study or 2 rat studies following oral administration of lamotrigine for up to 2 years at maximum tolerated doses (30 mg/kg per day for mice and 10 to 15 mg/kg per day for rats, doses that are equivalent to 90 mg/m² and 60 to 90 mg/m², respectively). Steady-state plasma concentrations ranged from 1 to 4 mcg/mL in the mouse study and 1 to 10 mcg/mL in the rat study. Plasma concentrations associated with the recommended human doses of 300 to 500 mg/day are generally in the range of 2 to 5 mcg/mL, but concentrations as high as 19 mcg/mL have been recorded.

Lamotrigine was not mutagenic in the presence or absence of metabolic activation when tested in 2 gene mutation assays (the Ames test and the in vitro mammalian mouse lymphoma assay). In 2 cytogenetic assays (the in vitro human lymphocyte assay and the in vivo rat bone marrow assay), lamotrigine did not increase the incidence of structural or numerical chromosomal abnormalities.

No evidence of impairment of fertility was detected in rats given oral doses of lamotrigine up to 2.4 times the highest usual human maintenance dose of 8.33 mg/kg per day or 0.4 times the human dose on a mg/m² basis. The effect of lamotrigine on human fertility is unknown.

Pregnancy: Teratogenic Effects: Pregnancy Category C. No evidence of teratogenicity was found in mice, rats, or rabbits when lamotrigine was orally administered to pregnant animals during the period of organogenesis at doses up to 1.2, 0.5, and 1.1 times, respectively, on a mg/m² basis, the highest usual human maintenance dose (i.e., 500 mg/day). However, maternal toxicity and secondary fetal toxicity producing reduced fetal weight and/or delayed ossification were seen in mice and rats, but not in rabbits at these doses. Teratology studies were also conducted using bolus intravenous administration of the isethionate salt of lamotrigine in rats and rabbits. In rat dams administered an intravenous dose at 0.6 times the highest usual human maintenance dose, the incidence of intrauterine death without signs of teratogenicity was increased.

A behavioral teratology study was conducted in rats dosed during the period of organogenesis. At day 21 postpartum, offspring of dams receiving 5 mg/kg per day or higher displayed a significantly longer latent period for open field exploration and a lower frequency of rearing. In a swimming maze test performed on days 39 to 44 postpartum, time to completion was increased in offspring of dams receiving 25 mg/kg per day. These doses represent 0.1 and 0.5 times the clinical dose on a mg/m² basis, respectively.

Lamotrigine did not affect fertility, teratogenesis, or postnatal development when rats were dosed prior to and during mating, and throughout gestation and lactation at doses equivalent to 0.4 times the highest usual human maintenance dose on a mg/m² basis.

When pregnant rats were orally dosed at 0.1, 0.14, or 0.3 times the highest human maintenance dose (on a mg/m² basis) during the latter part of gestation (days 15 to 20), maternal toxicity and fetal death were seen. In dams, food consumption and weight gain were reduced, and the gestation period was slightly prolonged (22.6 vs. 22.0 days in the control group). Stillborn pups were found in all 3 drug-treated groups with the highest number in the high-dose group. Postnatal death was also seen, but only in the 2 highest doses, and occurred between day 1 and 20. Some of these deaths appear to be drug-related and not secondary to the maternal toxicity. A no-observed-effect level (NOEL) could not be determined for this study.

Although LAMICTAL was not found to be teratogenic in the above studies, lamotrigine decreases fetal folate concentrations in rats, an effect known to be associated with teratogenesis in animals and humans. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Non-Teratogenic Effects: As with other antiepileptic drugs, 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-partum concentrations after delivery. Dosage adjustments may be necessary to maintain clinical response.

Pregnancy Exposure Registry: To facilitate monitoring fetal outcomes of pregnant women exposed to lamotrigine, physicians are encouraged to register patients, before fetal outcome (e.g., ultrasound, results of amniocentesis, birth, etc.) is known, and can obtain information by calling the Lamotrigine Pregnancy Registry at (800) 336-2176 (toll-free). Patients can enroll themselves in the North American Antiepileptic Drug Pregnancy Registry by calling (888) 233-2334 (toll-free).

Labor and Delivery: The effect of LAMICTAL on labor and delivery in humans is unknown.

Use in Nursing Mothers: Preliminary data indicate that lamotrigine passes into human milk. Because the effects on the infant exposed to LAMICTAL by this route are unknown, breast-feeding while taking LAMICTAL is not recommended.

Pediatric Use: LAMICTAL is indicated as adjunctive therapy for partial seizures in patients above 2 years of age and for the generalized seizures of Lennox-Gastaut syndrome. Safety and effectiveness for other uses in patients with epilepsy below the age of 16 years have not been established.

Safety and effectiveness in patients below the age of 18 years with Bipolar Disorder has not been established.

Geriatric Use: Clinical studies of LAMICTAL for epilepsy and in Bipolar Disorder did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 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.

 

Lamictal CD Contraindications

LAMICTAL is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.

 

Additional information about Lamictal CD

Lamictal CD Indication: For the adjunctive treatment of partial seizures in epilepsy and generalized seizures of Lennox-Gastaut syndrome. Also for the maintenance treatment of bipolar I disorder and depression.
Mechanism Of Action: One proposed mechanism of action of Lamictal CD, the relevance of which remains to be established in humans, involves an effect on sodium channels. in vitro pharmacological studies suggest that lamotrigine inhibits voltage-sensitive sodium channels, thereby stabilizing neuronal membranes and consequently modulating presynaptic transmitter release of excitatory amino acids (e.g., glutamate and aspartate).
Drug Interactions: Carbamazepine Carbamazepine decreases the effect of lamotrigine
Clozapine Lamictal CD increases the effect and toxicity of clozapine
Desogestrel The oral contraceptive decreases the effect of lamotrigine
Ethinyl Estradiol The oral contraceptive decreases the effect of lamotrigine
Mestranol The oral contraceptive decreases the effect of lamotrigine
Norethindrone The oral contraceptive decreases the effect of lamotrigine
Divalproex sodium Valproic acid increases the effect of lamotrigine
Ethotoin Phenytoin may reduce levels of lamotrigine
Fosphenytoin Phenytoin may reduce levels of lamotrigine
Mephenytoin Phenytoin may reduce levels of lamotrigine
Phenytoin Phenytoin may reduce levels of lamotrigine
Rifampin Rifampin decreases levels of lamotrigine
Methsuximide Methsuximide decreases the effect of lamotrigine
Food Interactions: Take without regard to meals.
Generic Name: Lamotrigine
Synonyms: Lamotrigina [Spanish]; Lamotriginum [Latin]; GW 273293
Drug Category: Antimanic Agents; Antidepressants; Anticonvulsants; Analgesics; Calcium Channel Blockers; Excitatory Amino Acid Antagonists
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Lamotrigine: Lamictal; Lamictal CD; Lamictin;
Absorption: 98%
Toxicity (Overdose): LD₅₀=250 (mg/kg) (in rat, mice); LD₅₀>640 orally (mg/kg) (in rat, mice) (Sawyer). Symptoms of overdose include decreased level of consciousness, coma, delayed heartbeat, increased seizures, lack of coordination, and rolling eyeballs.
Protein Binding: 55%
Biotransformation: Hepatic
Half Life: 25 +/- 10 hours (healthy individuals); 42.9 hours (chronic renal failure)
Dosage Forms of Lamictal CD: Tablet Oral
Chemical IUPAC Name: 6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine
Chemical Formula: C9H7Cl2N5
Lamotrigine on Wikipedia: https://en.wikipedia.org/wiki/Lamotrigine
Organisms Affected: Humans and other mammals