Brand name : MERIDIA®
(sibutramine hydrochloride monohydrate) Capsules
CS-IV

Most important fact about Meridia - without a prior prescription available now:

MERIDIA® (sibutramine hydrochloride monohydrate) is an orally administered agent for the treatment of obesity. Chemically, the active ingredient is a racemic mixture of the (+) and (-) enantiomers of cyclobutanemethanamine, 1-(4-chlorophenyl)-N,N-dimethyl-a-(2-methylpropyl)-, hydrochloride, monohydrate, and has an empirical formula of C17H29Cl2NO. Its molecular weight is 334.33.

The structural formula is shown below:Meridia (sibutramine hydrochloride monohydrate) structural formula illustration.Sibutramine hydrochloride monohydrate is a white to cream crystalline powder with a solubility of 2.9 mg/mL in pH 5.2 water. Its octanol: water partition coefficient is 30.9 at pH 5.0.

Each MERIDIA capsule contains 5 mg, 10 mg, and 15 mg of sibutramine hydrochloride monohydrate. It also contains as inactive ingredients: lactose monohydrate, NF; microcrystalline cellulose, NF; colloidal silicon dioxide, NF; and magnesium stearate, NF in a hard-gelatin capsule [which contains titanium dioxide, USP; gelatin; FD&C Blue No. 2 (5- and 10-mg capsules only); D&C Yellow No. 10 (5- and 15-mg capsules only), and other inactive ingredients].
INDICATIONS

MERIDIA is indicated for the management of obesity, including weight loss and maintenance of weight loss, and should be used in conjunction with a reduced calorie diet. MERIDIA is recommended for obese patients with an initial body mass index = 30 kg/m2, or = 27 kg/m2 in the presence of other risk factors (e.g., diabetes, dyslipidemia, controlled hypertension).Below is a chart of Body Mass Index (BMI) based on various heights and weights.BMI is calculated by taking the patient's weight, in kg, and dividing by the patient's height, in meters, squared. Metric conversions are as follows: pounds ÷ 2.2 = kg; inches × 0.0254 = meters.

DOSAGE AND ADMINISTRATION Meridia sibutramine

The recommended starting dose of MERIDIA is 10 mg administered once daily with or without food. If there is inadequate weight loss, the dose may be titrated after four weeks to a total of 15 mg once daily. The 5 mg dose should be reserved for patients who do not tolerate the 10 mg dose. Blood pressure and heart rate changes should be taken into account when making decisions regarding dose titration (see WARNINGS and PRECAUTIONS).Doses above 15 mg daily are not recommended. In most of the clinical trials, MERIDIA was given in the morning.

Analysis of numerous variables has indicated that approximately 60% of patients who lose at least 4 pounds in the first 4 weeks of treatment with a given dose of MERIDIA in combination with a reduced-calorie diet lose at least 5% (placebo-subtracted) of their initial body weight by the end of 6 months to 1 year of treatment on that dose of MERIDIA. Conversely, approximately 80% of patients who do not lose at least 4 pounds in the first 4 weeks of treatment with a given dose of MERIDIA do not lose at least 5% (placebo-subtracted) of their initial body weight by the end of 6 months to 1 year of treatment on that dose. If a patient has not lost at least 4 pounds in the first 4 weeks of treatment, the physician should consider reevaluation of therapy which may include increasing the dose or discontinuation of MERIDIA.The safety and effectiveness of MERIDIA, as demonstrated in double-blind, placebo-controlled trials, have not been determined beyond 2 years at this time.

HOW SUPPLIED Meridia

MERIDIA® (sibutramine hydrochloride monohydrate) Capsules contain 5 mg, 10 mg, or 15 mg sibutramine hydrochloride monohydrate and are supplied as follows:

5 mg, NDC 0074-2456-12, blue/yellow capsules imprinted with "MERIDIA" on the cap and "-5-" on the body, in bottles of 30 capsules.10 mg, NDC 0074-2457-12, blue/white capsules imprinted with "MERIDIA" on the cap and "-10-" on the body, in bottles of 30 capsules.15 mg, NDC 0074-2458-12, yellow/white capsules imprinted with "MERIDIA" on the cap and "-15-" on the body, in bottles of 30 capsules.5 mg, NDC 0074-2456-13, blue/yellow capsules imprinted with "MERIDIA" on the cap and "-5-" on the body, in bottles of 100 capsules.10 mg, NDC 0074-2457-13, blue/white capsules imprinted with "MERIDIA" on the cap and "-10-" on the body, in bottles of 100 capsules.15 mg, NDC 0074-2458-13, yellow/white capsules imprinted with "MERIDIA" on the cap and "-15-" on the body, in bottles of 100 capsules.
Storage

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP controlled room temperature]. Protect capsules from heat and moisture. Dispense in a tight, light-resistant container as defined in USP.

SIDE EFFECTS

In placebo-controlled studies, 9% of patients treated with sibutramine (n = 2068) and 7% of patients treated with placebo (n = 884) withdrew for adverse events.

In placebo-controlled studies, the most common events were dry mouth, anorexia, insomnia, constipation and headache. Adverse events in these studies occurring in = 1% of sibutramine treated patients and more frequently than in the placebo group are shown in the following table.

Obese Patients in Placebo-Controlled Studies

BODY SYSTEM Meridia sibutramine
Adverse Event Sibutramine
(n = 2068)
% Incidence Placebo
(n = 884)
% Incidence
BODY AS A WHOLE
Headache 30.3 18.6 ; Back pain 8.2 5.5;; Flu syndrome 8.2 5.8;; Injury accident 5.9 4.1; Asthenia 5.9 5.3; Abdominal pain 4.5 3.6;; Chest pain 1.8 1.2; Neck pain 1.6 1.1; Allergic reaction 1.5 0.8
CARDIOVASCULAR SYSTEM
Tachycardia 2.6 0.6; Vasodilation 2.4 0.9; Migraine 2.4 2.0
Hypertension/increased blood pressure 2.1 0.9
Palpitation 2.0 0.8; DIGESTIVE SYSTEM ; Anorexia 13.0 3.5; Constipation 11.5 6.0; Increased appetite 8.7 2.7; Nausea 5.9 2.8; Dyspepsia 5.0 2.6; Gastritis 1.7 1.2; Vomiting 1.5 1.4; Rectal disorder 1.2 0.5; ;METABOLIC & NUTRITIONAL ; Thirst 1.7 0.9
Generalized edema 1.2 0.8; MUSCULOSKELETAL SYSTEM ; Arthralgia 5.9 5.0
Myalgia 1.9 1.1: Tenosynovitis 1.2 0.5 ; Joint disorder 1.1 0.6
NERVOUS SYSTEM Dry mouth 17.2 4.2; Insomnia 10.7 4.5
Dizziness 7.0 3.4; Nervousness 5.2 2.9; Anxiety 4.5 3.4;Depression 4.3 2.5; Paresthesia 2.0 0.5
Somnolence 1.7 0.9; CNS stimulation 1.5 0.5; Emotional lability 1.3 0.6;; RESPIRATORY SYSTEM
Rhinitis 10.2 7.1; Pharyngitis 10.0 8.4; Sinusitis 5.0 2.6
Cough increase 3.8 3.3; Laryngitis 1.3 0.9; SKIN & APPENDAGES
Rash 3.8 2.5; Sweating 2.5 0.9; Herpes simplex 1.3 1.0
Acne 1.0 0.8; SPECIAL SENSES ; Taste perversion 2.2 0.8; Ear disorder 1.7 0.9; Ear pain 1.1 0.7
UROGENITAL SYSTEM ; Dysmenorrhea 3.5 1.4; Urinary tract infection 2.3 2.0;Vaginal monilia 1.2 0.5
Metrorrhagia 1.0 0.8 .The following additional adverse events were reported in = 1% of all patients who received sibutramine in controlled and uncontrolled pre-marketing studies.

Meridia sibutramine Digestive System

diarrhea, flatulence, gastroenteritis, tooth disorder.
Metabolic and Nutritional :peripheral edema.
Musculoskeletal System :arthritis.
Nervous System : agitation, leg cramps, hypertonia, thinking abnormal.
Respiratory System :bronchitis, dyspnea.
Skin and Appendages :pruritus.
Special Senses:amblyopia.
Urogenital System :menstrual disorders.
Other Adverse Events:Clinical Studies

Seizures :Convulsions were reported as an adverse event in three of 2068 (0.1%) sibutramine treated patients and in none of 884 placebo-treated patients in placebo-controlled premarketing obesity studies. Two of the three patients with seizures had potentially predisposing factors (one had a prior history of epilepsy; one had a subsequent diagnosis of brain tumor). The incidence in all subjects who received sibutramine (three of 4,588 subjects) was less than 0.1%.

Ecchymosis/Bleeding Disorders:Ecchymosis (bruising) was observed in 0.7% of sibutramine treated patients and in 0.2% of placebo-treated patients in pre-marketing placebo-controlled obesity studies. One patient had prolonged bleeding of a small amount which occurred during minor facial surgery. Sibutramine may have an effect on platelet function due to its effect on serotonin uptake.

Interstitial Nephritis:Acute interstitial nephritis (confirmed by biopsy) was reported in one obese patient receiving sibutramine during pre-marketing studies. After discontinuation of the medication, dialysis and oral corticosteroids were administered; renal function normalized. The patient made a full recovery.

Altered Laboratory Findings:Abnormal liver function tests, including increases in AST, ALT, GGT, LDH, alkaline phosphatase and bilirubin, were reported as adverse events in 1.6% of sibutramine-treated obese patients in placebo-controlled trials compared with 0.8% of placebo patients. In these studies, potentially clinically significant values (total bilirubin = 2 mg/dL; ALT, AST, GGT, LDH, or alkaline phosphatase = 3 × upper limit of normal) occurred in 0% (alkaline phosphatase) to 0.6% (ALT) of the sibutramine treated patients and in none of the placebo-treated patients. Abnormal values tended to be sporadic, often diminished with continued treatment, and did not show a clear dose-response relationship.
Postmarketing Reports

Voluntary reports of adverse events temporally associated with the use of sibutramine are listed below. It is important to emphasize that although these events occurred during treatment with sibutramine, they may have no causal relationship with the drug. Obesity itself, concurrent disease states/risk factors, or weight reduction may be associated with an increased risk for some of these events.
Psychiatric

Cases of depression, suicidal ideation and suicide have been reported rarely in patients on sibutramine treatment. However, a relationship has not been established between the occurrence of depression and/or suicidal ideation and the use of sibutramine. If depression occurs during treatment with sibutramine, further evaluation may be necessary.
Hypersensitivity

Allergic hypersensitivity reactions ranging from mild skin eruptions and urticaria to angioedema and anaphylaxis have been reported (see CONTRAINDICATIONS and PRECAUTIONS-Information For Patients, and other reports of allergic reactions listed below).
Other Postmarketing Reported Events:

Body as a Whole

anaphylactic shock, anaphylactoid reaction, chest pressure, chest tightness, facial edema, limb pain, sudden unexplained death.

Cardiovascular System

angina pectoris, atrial fibrillation, congestive heart failure, heart arrest, heart rate decreased, myocardial infarction, supraventricular tachycardia, syncope, torsade de pointes, vascular headache, ventricular tachycardia, ventricular extrasystoles, ventricular fibrillation.

Digestive System

cholecystitis, cholelithiasis, duodenal ulcer, eructation, gastrointestinal hemorrhage, increased salivation, intestinal obstruction, mouth ulcer, stomach ulcer, tongue edema.Endocrine System:goiter, hyperthyroidism, hypothyroidism.Hemic and Lymphatic System :anemia, leukopenia, lymphadenopathy, petechiae, thrombocytopenia.Metabolic and Nutritional :hyperglycemia, hypoglycemia.Musculoskeletal System:arthrosis, bursitis.

abnormal dreams, abnormal gait, amnesia, anger, cerebrovascular accident, concentration impaired, confusion, depression aggravated, Gilles de la Tourette's syndrome, hypesthesia, libido decreased, libido increased, manic reaction, mood changes, nightmares, serotonin syndrome, short term memory loss, speech disorder, transient ischemic attack, tremor, twitch, vertigo.

Respiratory System :epistaxis, nasal congestion, respiratory disorder, yawn.

Skin and Appendages:alopecia, dermatitis, photosensitivity (skin), urticaria.

Special Senses :abnormal vision, blurred vision, dry eye, eye pain, increased intraocular pressure, otitis externa, otitis media, photosensitivity (eyes), tinnitus.

Urogenital System :abnormal ejaculation, hematuria, impotence, increased urinary frequency, micturition difficulty, urinary retention.
Drug Abuse And Dependence
Controlled Substance

MERIDIA is controlled in Schedule IV of the Controlled Substances Act (CSA).
Abuse and Physical and Psychological Dependence

Physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse (e.g., drug development of tolerance, incrementation of doses, drug seeking behavior).
Meridia sibutramine INTERACTIONS
CNS Active Drugs:

The use of MERIDIA in combination with other CNS-active drugs, particularly serotonergic agents, has not been systematically evaluated. Consequently, caution is advised if the concomitant administration of MERIDIA with other centrally-acting drugs is indicated (see CONTRAINDICATIONS and WARNINGS).

In patients receiving monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, selegiline) in combination with serotonergic agents (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine), there have been reports of serious, sometimes fatal, reactions ("serotonin syndrome;" see below). Because sibutramine inhibits serotonin reuptake, MERIDIA should not be used concomitantly with a MAOI (see CONTRAINDICATIONS). At least 2 weeks should elapse between discontinuation of a MAOI and initiation of treatment with MERIDIA. Similarly, at least 2 weeks should elapse between discontinuation of MERIDIA and initiation of treatment with a MAOI.

The rare, but serious, constellation of symptoms termed "serotonin syndrome" has also been reported with the concomitant use of selective serotonin reuptake inhibitors and agents for migraine therapy, such as Imitrex® (sumatriptan succinate) and dihydroergotamine, certain opioids, such as dextromethorphan, meperidine, pentazocine and fentanyl, lithium, or tryptophan. Serotonin syndrome has also been reported with the concomitant use of two serotonin reuptake inhibitors. The syndrome requires immediate medical attention and may include one or more of the following symptoms: excitement, hypomania, restlessness, loss of consciousness, confusion, disorientation, anxiety, agitation, motor weakness, myoclonus, tremor, hemiballismus, hyperreflexia, ataxia, dysarthria, incoordination, hyperthermia, shivering, pupillary dilation, diaphoresis, emesis, and tachycardia.

Because sibutramine inhibits serotonin reuptake, in general, it should not be administered with other serotonergic agents such as those listed above. However, if such a combination is clinically indicated, appropriate observation of the patient is warranted.
Drugs That May Raise Blood Pressure and/or Heart Rate

Concomitant use of MERIDIA and other agents that may raise blood pressure or heart rate have not been evaluated. These include certain decongestants, cough, cold, and allergy medications that contain agents such as ephedrine, or pseudoephedrine. Caution should be used when prescribing MERIDIA to patients who use these medications.
Alcohol

In a double-blind, placebo-controlled, crossover study in 19 volunteers, administration of a single dose of ethanol (0.5 mL/kg) together with 20 mg of sibutramine resulted in no psychomotor interactions of clinical significance between alcohol and sibutramine. However, the concomitant use of MERIDIA and excess alcohol is not recommended.
Oral Contraceptives

The suppression of ovulation by oral contraceptives was not inhibited by sibutramine. In a crossover study, 12 healthy female volunteers on oral steroid contraceptives received placebo in one period and 15 mg sibutramine in another period over the course of 8 weeks. No clinically significant systemic interaction was observed; therefore, no requirement for alternative contraceptive precautions are needed when patients taking oral contraceptives are concurrently prescribed sibutramine.