Sibutramine Hydrochloride Monohydrate (Meridia)
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Sibutramine Hydrochloride Monohydrate (Meridia)

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

MERIDIA
(sibutramine hydrochloride) Capsule

MERIDIA®
(sibutramine hydrochloride monohydrate) Capsule

DRUG DESCRIPTION

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-α-(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].

What are the possible side effects of sibutramine (Meridia)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using sibutramine and call your doctor at once if you have a serious side effect such as:

  • fast, pounding, or uneven heartbeats;
  • new or worsening shortness of breath;
  • agitation, hallucinations, fever, tremor, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, dilated pupils;
  • very stiff (rigid) muscles, high fever, sweating, confusion, feeling like you might pass...

Read All Potential Side Effects and See Pictures of Meridia »

What are the precautions when taking sibutramine hydrochloride monohydrate (Meridia)?

Before taking sibutramine, tell your doctor or pharmacist if you are allergic to it or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: eating disorders (e.g., anorexia nervosa, bulimia nervosa), uncontrolled or poorly controlled high blood pressure, heart or blood vessel disease (e.g., coronary artery disease, history of heart attack or angina, congestive heart failure, abnormal heart rhythms, poor circulation in the arms/legs), stroke or TIA (transient ischemic attack).

Before using this medication,...

Read All Potential Precautions of Meridia »

Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

INDICATIONS

MERIDIA (sibutramine hydrochloride monohydrate) 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 (sibutramine hydrochloride monohydrate) 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.

BMI   25 26 27 28 29 30 31 32 33 34 35 40
  W E I G H T (lbs)
4'10" 119 124 129 134 138 143 149 153 158 163 167 191
4'11" 124 128 133 138 143 148 154 158 164 169 173 198
5' 128 133 138 143 148 153 159 164 169 175 179 204
5'1" 132 137 143 148 153 158 165 169 175 180 185 211
5'2" 136 142 147 153 158 164 170 175 181 186 191 218
H 5'3" 141 146 152 158 163 169 175 181 187 192 197 225
5'4" 145 151 157 163 169 174 181 187 193 199 204 232
E 5'5" 150 156 162 168 174 180 187 193 199 205 210 240
5'6" 155 161 167 173 179 186 192 199 205 211 216 247
I 5'7" 159 166 172 178 185 191 198 205 211 218 223 255
5'8" 164 171 177 184 190 197 204 211 218 224 230 262
G 5'9" 169 176 182 189 196 203 210 217 224 231 236 270
5'10" 174 181 188 195 202 207 216 223 230 237 243 278
H 5'11" 179 186 193 200 208 215 222 230 237 244 250 286
6' 184 191 199 206 213 221 228 236 244 251 258 294
T 6'1" 189 197 204 212 219 227 236 243 251 258 265 302
6'2" 194 202 210 218 225 233 241 250 258 265 272 311
6'3" 200 208 216 224 232 240 248 256 264 272 279 319

DOSAGE AND ADMINISTRATION

The recommended starting dose of MERIDIA (sibutramine hydrochloride monohydrate) 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 (sibutramine hydrochloride monohydrate) was given in the morning.

Analysis of numerous variable s 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 (sibutramine hydrochloride monohydrate) 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 (sibutramine hydrochloride monohydrate) . 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 (sibutramine hydrochloride monohydrate) 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 (sibutramine hydrochloride monohydrate) .

The safety and effectiveness of MERIDIA (sibutramine hydrochloride monohydrate) , as demonstrated in double-blind, placebo-controlled trials, have not been determined beyond 2 years at this time.

HOW SUPPLIED

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 (sibutramine hydrochloride monohydrate) ” 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 (sibutramine hydrochloride monohydrate) ” 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 (sibutramine hydrochloride monohydrate) ” on the cap and “-15-” on the body, in bottles of 30 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.

Manufactured for Abbott Laboratories, North Chicago, IL 60064 USA by KNOLL LLC B.V. Jayuya, PR, 00664.

Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

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
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 incr ease 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 premarketing studies.

Body as a Whole: fever.

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-cont rolled 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 trea ted patients and in 0.2% of placebo-treated patients in premarketing 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 premarketing 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, psychosis, mania, suicidal ideation and suicide have been reported rarely in patients on sibutramine treatment. However, a relationship has not been established between these events and the use of sibutramine. If any of these events should occur during treatment with sibutramine, discontinuation should be considered.

Hypersensitivity

Allergic hypersensitivity reactions ranging from mild skin eruptions and urticaria to angioedema and anaphylaxis have been reported (see CONTRAINDICATIONS and PATIENT INFORMATION, 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.

Nervous System: abnormal dreams, abnormal gait, amnesia, anger, cerebrovascular accident, concentration impaired, confusion, depression aggravated, Gilles de la Tourette's syndrome, hypesthesia, libido decreased, libido increased, mood changes, nightmares, 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, otitisexterna, 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 (sibutramine hydrochloride monohydrate) 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).

Read the Meridia (sibutramine hydrochloride monohydrate) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

CNS Active Drugs

The use of MERIDIA (sibutramine hydrochloride monohydrate) 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 (sibutramine hydrochloride monohydrate) 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 (sibutramine hydrochloride monohydrate) . Similarly, at least 2 weeks should elapse between discontinuation of MERIDIA (sibutramine hydrochloride monohydrate) and initiation of treatment with a MAOI.

The rare, but serious, constellation of symptoms term ed “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 inclu de 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 (sibutramine hydrochloride monohydrate) 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 (sibutramine hydrochloride monohydrate) 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 (sibutramine hydrochloride monohydrate) 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.

Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

WARNINGS

Concomitant Cardiovascular Disease

Due to an increased risk of heart attack and stroke in patients with cardiovascular disease, MERIDIA (sibutramine hydrochloride monohydrate) should not be used in patients with a history of coronary artery disease, congestive heart failure, arrhythmias, or stroke.

Blood Pressure and Pulse

MERIDIA (sibutramine hydrochloride monohydrate) SUBSTANTIALLY INCREASES BLOOD PRESSURE AND/OR PULSE RATE IN SOME PATIENTS. REGULAR MONITORING OF BLOOD PRESSURE AND PULSE RATE IS REQ UIRED WHEN PRESCRIBING MERIDIA (sibutramine hydrochloride monohydrate) .

In placebo-controlled obesity studies, sibutramine 5 to 20 mg once daily was associated with mean increases in systolic and diastolic blood pressure of approximately 1 to 3 mm Hg relative to placebo, and with mean increases in pulse rate relative to placebo of approximately 4 to 5 beats per minute. Larger increases were seen in some patients, particularly when therapy with sibutramine was initiated at the higher doses (see table below). In premarketing placebo-controlled obesity studies, 0.4% of patients treated with sibutramine were discontinued f or hypertension (SBP ≥ 160 mm Hg or DBP ≥ 95 mm Hg), compared with 0.4% in the placebo group, and 0.4 % of patients treated with sibutramine were discontinued for tachycardia (pulse rate ≥ 100bpm), compared with 0.1% in the placebo group. Blood pressure and pulse should be measured prior to starting therapy with MERIDIA (sibutramine hydrochloride monohydrate) and should be monitored at regular intervals thereafter. For patients who experience a sustained increase in blood pressure or pulse rate while receiving MERIDIA (sibutramine hydrochloride monohydrate) , either dose reduction or discontinuation should be considered. MERIDIA (sibutramine hydrochloride monohydrate) should be given with caution to those patients with a history of hypertension (see DOSAGE AND ADMINISTRATION), and should not be given to patients with uncontrolled or poorly controlled hypertension.

Percent Outliers in Studies 1 and 2

Dose (mg) SBP % Outliers*
DBP Pulse
Placebo 9 7 12
5 6 20 16
10 12 15 28
15 13 17 24
20 14 22 37
* Outlier defined as increase from baseline of ≥ 15 mm Hg for three consecutive visits (SBP), ≥ 10 mm Hg for three consecutive visits (DBP), or pulse ≥ 10 bpm for three consecutive visits.

Potential Interaction With Monoamine Oxidase Inhibitors

MERIDIA (sibutramine hydrochloride monohydrate) is a norepinephrine, serotonin and dopamine reuptake inhibitor and should not be used concomitantly with MAOIs (see PRECAUTIONS: DRUG INTERACTIONS subsection). There should be at least a 2-week interval after stopping MAOIs before commencing treatment with MERIDIA (sibutramine hydrochloride monohydrate) . Similarly, there should be at least a 2-week interval after stopping MERIDIA (sibutramine hydrochloride monohydrate) before starting treatment with MAOIs.

Serotonin Syndrome or Neuroleptic Malignant Syndrome (NMS)-Like Reactions

The development of a potentially life-threatening serotonin syndrome, or Neuroleptic Malignant Syndrome (NMS)-like reactions, has been reported with SNRIs and SSRIs alone, including MERIDIA (sibutramine hydrochloride monohydrate) treatment, but particularly with concomitant use of serotonergic drugs (including triptans), with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms [e.g., nausea, vomiting, diarrhea] (seePRECAUTIONS: DRUG INTERACTIONS). Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.

Glaucoma

Because MERIDIA (sibutramine hydrochloride monohydrate) can cause mydriasis, it should be used with caution in patients with narrow angle glaucoma.

Miscellaneous

Organic causes of obesity (e.g., untreated hypothyroidism) should be excluded before prescribing MERIDIA (sibutramine hydrochloride monohydrate) .

PRECAUTIONS

Pulmonary Hypertension

Certain centrally-acting weight loss agents that cause release of serotonin from nerve terminals have been associated with pulmonary hypertension (PPH), a rare but lethal disease. In premarketing clinical studies, no cases of PPH have been reported with sibutramine capsules. Because of the low incidence of this disease in the underlying population, however, it is not known whether or not MERIDIA (sibutramine hydrochloride monohydrate) may cause this disease.

Seizures

During premarketing testing, seizures were reported in < 0.1% of sibutramine treated patients. MERIDIA (sibutramine hydrochloride monohydrate) should be used cautiously in patients with a history of seizures. It should be discontinued in any patient who develops seizures.

Bleeding

There have been reports of bleeding in patients taking sibutramine. While a causal relationship is unclear, caution is advised in patients predisposed to bleeding events and those taking concomitant medications known to affect hemostasis or platelet function.

Gallstones

Weight loss can precipitate or exacerbate gallstone formation.

Renal Impairment

MERIDIA (sibutramine hydrochloride monohydrate) should be used with caution in patients with mild to moderate renal impairment. MERIDIA (sibutramine hydrochloride monohydrate) should not be used in patients with severe renal impairment, including those with end stage renal disease on dialysis (see Pharmacokinetics - Special Populations - Renal Insufficiency).

Hepatic Dysfunction

Patients with severe hepatic dysfunction have not been systematically studied; MERIDIA (sibutramine hydrochloride monohydrate) should therefore not be used in such patients.

Interference With Cognitive and Motor Performance

Although sibutramine did not affect psychomotor or cognitive performance in healthy volunteers, any CNS active drug has the potential to impair judgment, thinking or motor skills.

Information For Patients

Physicians should instruct their patients to read the Medication Guide before starting therapy with MERIDIA (sibutramine hydrochloride monohydrate) and to reread it each time the prescription is renewed.

Physicians should also discuss with their patients any part of the package insert that is relevant to them. In particular, the importance of keeping appointments for follow-up visits should be emphasized.

Patients should be advised to notify their physician if they develop a rash, hives, or other allergic reactions.

Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, especially weight-reducing agents, decongestants, antidepressants, cough suppressants, lithium, dihydroergotamine, sumatriptan (Imitrex®), or tryptophan, since there is a potential for interactions.

Patients should be reminded of the importance of having their blood pressure and pulse monitored at regular intervals.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity

Sibutramine was administered in the diet to mice (1.25, 5 or 20 mg/kg/day) and rats (1, 3, or 9 mg/kg/day) for two years generating combined maximum plasma AUC's of the two major active metabolites equivalent to 0.4 and 16 times, respectively, those following a daily human dose of 15 mg. There was no evidence of carcinogenicity in mice or in female rats. In male rats there was a higher incidence of benign tumors of the testicular interstitial cells; such tumors are commonly seen in rats and are hormonally mediated. The relevance of these tumors to humans is not known.

Mutagenicity

Sibutramine was not mutagenic in the Ames test, in vitro Chinese hamster V79 cell mutation assay, in vitro clastogenicity assay in human lymphocytes or micronucleus assay in mice. Its two major active metabolites were found to have equivocal bacterial mutagenic activity in the Ames test. However, both metabolites gave consistently negative results in the in vitro Chinese hamster V79 cell mutation assay, in vitro clastogenicity assay in human lymphocytes, in vitro DNA-repair assay in HeLa cells, micronucleus assay in mice and in vivo unscheduled DNA-synthesis assay in rat hepatocytes.

Impairment of Fertility

In rats, there were no effects on fertility at doses generating combined plasma AUC's of the two major active metabolites up to 32 times those following a human dose of 15 mg. At 13 times the human combined AUC, there was maternal toxicity, and the dams' nest-building behavior was impaired, leading to a higher incidence of perinatal mortality; there was no effect at approximately 4 times the human combined AUC.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Radiolabeled studies in animals indicated that tissue distribution was unaffected by pregnancy, with relatively low transfer to the fetus. In rats, there was no evidence of teratogenicity at doses of 1, 3, o r 10 mg/kg/day generating combined plasma AUC's of the two major active metabolites up to approximately 32 times those following the human dose of 15 mg. In rabbits dosed at 3, 15, or 75 mg/kg/day, plasma AUC's greater than approximately 5 times those following the human dose of 15 mg caused maternal toxicity. At markedly toxic doses, Dutch Belted rabbits had a slightly higher than control incidence of pups with a broad short snout, short rounded pinnae, short tail and, in so me, shorter thickened long bones in the limbs; at comparably high doses in New Zealand White rabbits, one study showed a slightly higher than control incidence of pups with cardiovascular anomalies while a second study showed a lower incidence than in the control group.

No adequate and well controlled studies with sibutramine have been conducted in pregnant women. The use of MERIDIA (sibutramine hydrochloride monohydrate) during pregnancy is not recommended. Women of childbearing potential should employ adequate contraception while taking MERIDIA (sibutramine hydrochloride monohydrate) . Patients should be advised to n otify their physician if they become pregnant or intend to become p regnant while taking MERIDIA (sibutramine hydrochloride monohydrate) .

Nursing Mothers

It is not known whether sibutramine or its metabolites are excreted in human milk. MERIDIA (sibutramine hydrochloride monohydrate) is not recommended for use in nursing mothers. Patients should be advised to notify their physician if they are breast-feeding.

Pediatric Use

The efficacy of sibutramine in adolescents who are obese has not been adequately studied.

Sibutramine's mechanism of action inhibiting the reuptake of serotonin and norepinephrine is similar to the mechanism of action of some antidepressants. Pooled analyses of short-term placebo-controlled trials of antidepressants in children and adolescents with major depressive disorder (MD D), obsessive compulsive disorder (OCD), and other psychiatric disorders have revealed a greater risk of adverse events representing suicidal behavior or thinking during the first few months of treatment in those receiving antidepressants. The average risk of such events in patients receiving antidepressants was 4%, twice the placebo risk of 2%.

No placebo-controlled trials of sibutramine have been conducted in children or adolescents with MDD, OCD, or other psychiatric disorders. In a study of adole scents with obesity in which 368 patients were treated with sibutramine and 130 patients with placebo, one patient in the sibutr amine group and one patient in the placebo group attempted suicide. Suicidal ideation was reported by 2 sibutramine-treated patients and none of the placebo patients. It is unknown if sibutramine increases the risk of suicidal behavior or thinking in pediatric patients.

The data are inadequate to recommend the use of sibutramine for the treatment of obesity in pediatric patients.

Geriatric Use

Clinical studies of sibutramine did not include sufficient numbers of patients over 65 years of age. Sibutramine is contraindicated in this group of patients (see CONTRAINDICATIONS). Pharmacokinetics in elderly patients are discussed in “CLINICAL PHARMACOLOGY.”

Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

OVERDOSE

Overdose Management

There is limited experience of overdose with sibutramine. The most frequently noted adverse events associated with overdose are tachycardia, hypertension, headache and dizziness. Tre atment should consist of general measures employed in the management of overdosage: an airway should be established as needed; cardiac and vital sign monitoring is recommended; general symptomatic and supportive measures should be instituted. Cautious use of β-blockers may be indicated to control elevated blood pressure or tachycardia. The results from a study in patients with end-stage renal disease on dialysis showed that sibutramine metabolites were not eliminated to a significant degree with hemodialysis. (see Pharmacokinetics - Special Populations - Renal Insufficiency).

CONTRAINDICATIONS

MERIDIA (sibutramine hydrochloride monohydrate) is contraindicated in patients:

  • with a history of coronary artery disease (e.g., angina, history of myocardial infarction), congestive heart failure, tachycardia, peripheral arterial occlusive disease, arrhythmia or cerebrovascular disease (stroke or transient ischemic attack (TIA)) (see WARNINGS).
  • with inadequately controlled hypertension > 145/90 mm Hg (see WARNINGS).
  • over 65 years of age.
  • receiving monoamine oxidase inhibitors (MAOIs) (see WARNINGS).
  • with hypersensitivity to sibutramine or any of the inactive ingredients of MERIDIA (sibutramine hydrochloride monohydrate) .
  • who have a major eating disorder (anorexia nervosa or bulimia nervosa).
  • taking other centrally acting weight loss drugs.

Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

CLINICAL PHARMACOLOGY

Mode of Action

Sibutramine produces its therapeutic effects by norepinephrine, serotonin and dopamine reuptake inhibition. Sibutramine and its major pharmacologically active metabolites (M1 and M2) do not act via release of monoamines.

Pharmacodynamics

Sibutramine exerts its pharmacological actions predominantly via its secondary (M1) and primary (M2) amine metabolites. The parent compound, sibutramine, is a potent inhibitor of serotonin (5­hydroxytryptamine, 5-HT) and norepinephrine reuptake in vivo, but not in vitro . However, metabolites M1 and M2 inhibit the reuptake of these neurotransmitters both in vitro and in vivo.

In human brain tissue, M1 and M2 also inhibit dopamine reuptake in vitro , but with ~3-fold lower potency than for the reuptake inhibition of serotonin or norepinephrine.

Potencies of Sibutramine, M1 and M2 as In Vitro Inhibitors of Monoamine Reuptake in Human Brain Potency to Inhibit Monoamine Reuptake (Ki;nM)

  Serotonin Norepinephrine Dopamine
Sibutramine 298 5451 943
M1 15 20 49
M2 20 15 45

A study using plasma samples taken from sibutramine-treated volunteers showed monoamine reuptake inhibition of norepinephrine > serotonin > dopamine; maximum inhibitions were norepinephrine = 73%, serotonin = 54% and dopamine = 16%.

Sibutramine and its metabolites (M1 and M2) are not serotonin, norepinephrine or dopamine releasing agents. Following chronic administration of sibutramine to rats, no depletion of brain monoamines has been observed.

Sibutramine, M1 and M2 exhibit no evidence of anticholinergic or antihistaminergic actions. In addition, receptor binding profiles show that sibutramine, M1 and M2 have low affinity for serotonin (5-HT1, 5­HT1A, 5-HT1B, 5-HT2A, 5-HT2C), norepinephrine (β, β1, β3, α1 and α2), dopamine (D1 and D2), benzodiazepine, and glutamate (NMDA) receptors. These compounds also lack monoamine oxidase inhibitory activity in vitro and in vivo.

Pharmacokinetics

Absorption

Sibutramine is rapidly absorbed from the GI tract (Tmax of 1.2 hours) following oral administration and undergoes extensive first-pass metabolism in the liver (oral clearance of 1750 L/h and half-life of 1.1 h) to form the pharmacologically active mono- and di-desmethyl metabolites M1 and M2. Peak plasma concentrations of M1 and M2 are reached within 3 to 4 hours. On the basis of mass balance studies, on average, at least 77% of a single oral dose of sibutramine is absorbed. The absolute bioavailability of sibutramine has not been determined.

Distribution

Radiolabeled studies in animals indicated rapid and extensive distribution into tissues: highest concentrations of radiolabeled material were found in the eliminating organs, liver and kidney. In vitro, sibutramine, M1 and M2 are extensively bound (97%, 94% and 94%, respectively) to human plasma proteins at plasma concentrations seen following therapeutic doses.

Metabolism

Sibutramine is metabolized in the liver principally by the cytochrome P450 (3A4) isoenzyme, to desmethyl metabolites, M1 and M2. These active metabolites are further metabolized by hydroxylation and conjugation to pharmacologically inactive metabolites, M5 and M6. Following oral administration of radiolabeled sibutramine, essentially all of the peak radiolabeled material in plasma was accounted for by unchanged sibutramine (3%), M1 (6%), M2 (12%), M5 (52%), and M6 (27%).

M1 and M2 plasma concentrations reached steady-state within four days of dosing and were approximately two-fold higher than following a single dose. The elimination half-lives of M1 and M2, 14 and 16 hours, respectively, were unchanged following repeated dosing.

Excretion

Approximately 85% (range 68-95%) of a single orally administered radiolabeled dose was excreted in urine and feces over a 15-day collection period with the majority of the dose (77%) excreted in the urine. Major metabolites in urine were M5 and M6; unchanged sibutramine, M1, and M2 were not detected. The primary route of excretion for M1 and M2 is hepatic metabolism and for M5 and M6 is renal excretion.

Summary of Pharmacokinetic Parameters
Mean (% CV) and 95% Confidence Intervals of Pharmacokinetic Parameters (Dose = 15mg)

Study Population Cmax
(ng/mL)
Tmax
(h)
AUC†
(ng*h/mL)

(h)
Metabolite M1
Target Population:
Obese Subjects (n = 18) 4.0 (42) 3.6 (28) 25.5 (63) – –
  3.2 - 4.8 3.1 - 4.1 18.1 - 32.9  
Special Population:
Moderate Hepatic Impairment (n = 12) 2.2 (36) 3.3 (33) 18.7 (65) – –
  1.8 - 2.7 2.7 - 3.9 11.9 - 25.5  
Metabolite M2
Target Population:
Obese Subjects (n = 18) 6.4 (28) 3.5 (17) 92.1 (26) 17.2 (58)
5.6 - 7.2 3.2 - 3.8 81.2 - 103 12.5 - 21.8
Special Population:
Moderate Hepatic Impairment (n = 12) 4.3 (37) 3.8 (34) 90.5 (27) 22.7 (30)
3.4 - 5.2 3.1 - 4.5 76.9 - 104 18.9 - 26.5
† Calculated only up to 24 hr for M1.

Effect of Food

Administration of a single 20 mg dose of sibutramine with a standard breakfast resulted in reduced peak M1 and M2 concentrations (by 27% and 32%, respectively) and delayed the time to peak by approximately three hours. However, the AUCs of M1 and M2 were not significantly altered.

Special Populations

Geriatric

Plasma concentrations of M1 and M2 were similar between elderly (ages 61 to 77 yr) and young (ages 19 to 30 yr) subjects following a single 15-mg oral sibutramine dose. Plasma concentrations of the inactive metabolites M5 and M6 were higher in the elderly; these differences are not likely to be of clinical significance. Sibutramine is contraindicated in patients over 65 years of age (see CONTRAINDICATIONS).

Pediatric

The safety and effectiveness of sibutramine in pediatric patients under 16 years old have not been established.

Gender

Pooled pharmacokinetic parameters from 54 young, healthy volunteers (37 males and 17 females) receiving a 15-mg oral dose of sibutramine showed the mean Cmax and AUC of M1 and M2 to be slightly ( ≤ 19% and ≤ 36%, respectively) higher in females than males. Somewhat higher steady-state trough plasma levels were observed in female obese patients from a large clinical efficacy trial. However, these differences are not likely to be of clinical significance. Dosage adjustment based upon the gender of a patient is not necessary (see DOSAGE AND ADMINISTRATION).

Race

The relationship between race and steady-state trough M1 and M2 plasma concentrations was examined in a clinical trial in obese patients. A trend towards higher concentrations in Black patients over Caucasian patients was noted for M1 and M2. However, these differences are not considered to be of clinical significance.

Renal Insufficiency

The disposition of sibutramine metabolites (M1, M2, M5 and M6) following a single oral dose of sibutramine was studied in patients with varying degrees of renal function. Sibutramine itself was not measurable.

In patients with moderate and severe renal impairment, the AUC values of the active metabolite M 1 were 24 to 46% higher and the AUC values of M2 were similar as compared to healthy subjects. Cross- study comparison showed that the patients with end - stage renal disease on dialysis had similar AUC values of M1 but approximately half of the AUC values of M2 measured in healthy subjects (CLcr ≥ 80 mL/ min). The AUC values of inactive metabolites M5 and M6 increased 2 - 3 fold (range 1 - to 7 - fold) in patients with moderate impairment (30 mL/ min < CLcr = 60 mL/ min) and 8 - 11 fold (range 5 - to 15 - fold) in patients with severe impairment (CLcr ≤ 30 mL/ min) as compared to healthy subjects. Cross - study comparison showed that the AUC values of M5 and M6 increased 22 -33 fold in patients with end - stage renal disease on dialysis as compared to healthy subjects. Approximately 1% of the oral dose was recovered in the dialysate as a combination of M5 and M6during the hemodialysis process, while M1 and M2 were not measurable in the dialysate.

Sibutramine should not be used in patients with severe renal impairment, including those with end-stage renal disease on dialysis.

Hepatic Insufficiency

In 12 patients with moderate hepatic impairment receiving a single 15-mg oral dose of sibutramine, the combined AUCs of M1 and M2 were increased by 24% compared to healthy subjects while M5 and M6 plasma concentrations were unchanged. The observed differences in M1 and M2 concentrations do not warrant dosage adjustment in patients with mild to moderate hepatic impairment. Sibutramine should not be used in patients with severe hepatic dysfunction.

Drug-Drug Interactions

In vitro studies indicated that the cytochrome P450 (3A4)-mediated metabolism of sibutramine was inhibited by ketoconazole and to a lesser extent by erythromycin. Phase 1 clinical trials were conducted to assess the interactions of sibutramine with drugs that are substrates and/or inhibitors of various cytochrome P450 isozymes. The potential for studied interactions is described below.

Ketoconazole

Concomitant administration of 200 mg doses of ketoconazole twice daily and 20 mg sibutramine once daily for 7 days in 12 uncomplicated obese subjects resulted in moderate increases in AUC and Cmax of 58% and 36% for M1 and of 20% and 19% for M2, respectively.

Erythromycin

The steady-state pharmacokinetics of sibutramine and metabolites M1 and M2 were evaluated in 12 uncomplicated obese subjects following concomitant administration of 500 mg of erythromycin three times daily and 20 mg of sibutramine once daily for 7 days. Concomitant erythromycin resulted in small increases in the AUC (less than 14%) for M1 and M2. A small reduction in Cmax for M1 (11%) and a slight increase in Cmax for M2 (10%) were observed.

Cimetidine

Concomitant administration of cimetidine 400 mg twice daily and sibutramine 15 mg once daily for 7 days in 12 volunteers resulted in small increases in combined (M1 and M2) plasma Cmax (3.4%) and AUC (7.3%).

Simvastatin

Steady-state pharmacokinetics of sibutramine and metabolites M1 and M2 were evaluated in 27 healthy volunteers after the administration of simvastatin 20 mg once daily in the evening and sibutramine 15 mg once daily in the morning for 7 days. Simvastatin had no significant effect on plasma Cmax and AUC of M2 or M1 and M2 combined. The Cmax (16%) and AUC (12%) of M1 were slightly decreased. Simvastatin slightly decreased sibutramine Cmax (14%) and AUC (21%). Sibutramine increased the AUC (7%) of the pharmacologically active moiety, simvastatin acid and reduced the Cmax (25%) and AUC (15%) of inactive simvastatin.

Omeprazole

Steady-state pharmacokinetics of sibutramine and metabolites M1 and M2 were evaluated in 26 healthy volunteers after the co-administration of omeprazole 20 mg once daily and sibutramine 15 mg once daily for 7 days. Omeprazole slightly increased plasma Cmax and AUC of M1 and M2 combined (approximately 15%). M2 Cmax and AUC were not significantly affected whereas M1 Cmax (30%) and AUC (40%) were modestly increased. Plasma Cmax (57%) and AUC (67%) of unchanged sibutramine were moderately increased. Sibutramine had no significant effect on omeprazole pharmacokineti cs.

Olanzapine

Steady-state pharmacokinetics of sibutramine and metabolites M1 and M2 were evaluated in 24 healthy volunteers after the co-administration of sibutramine 15 mg once daily with olanzapine 5 mg twice daily for 3 days and 10 mg once daily thereafter for 7 days. Olanza pine had no significant effect on plasma Cmax and AUC of M2 and M1 and M2 combined, or the AUC of M1. Olanzapine slightly increased M1 Cmax (19%), and moderately increased sibutramine Cmax (47%) and AUC (63%). Sibutramine had no significant effect on olanzapine pharmacokinetics.

Lorazepam

Steady-state pharmacokinetics of sibutramine and metabolites M1 and M2 after sibutramine 15 mg once daily for 11 days were compared in 25 healthy volunteers in the presence or absence of lorazepam 2 mg twice daily for 3 days plus one morning dose. Lorazepam had no significant effect on the pharmacokinetics of sibutramine metabolites M1 and M2. Sibutramine had no significant effect on lorazepam pharmacokinetics.

Drugs Highly Bound to Plasma Proteins

Although sibutramine and its active metabolites M1 and M2 are extensively bound to plasma proteins ( ≥ 94%), the low therapeutic concentrations and basic characteristics of these compounds make themunlikely to result in clinically significant protein binding interactions with other highly protein bound drugs such as warfarin and phenytoin. In vitro protein binding interaction studies have not been conducted.

Clinical Studies

Observational epidemiologic studies have established a relationship between obesity and the risks for cardiovascular disease, non-insulin depende nt diabetes mellitus (NIDDM), certain forms of cancer, gallstones, certain respiratory disorders, and an increase in overall mortality. These studies suggest that weight loss, if maintained, may produce health benefits for some patients with chronic obesity who may also be at risk for other diseases.

The long-term effects of sibutramine on the morbidity and mortality associated with obesity have not been established. Weight loss was examined in 11 double-blind, placebo-controlled obesity trials (BMI range across all studies 27-43) with study durations of 12 to 52 weeks and doses ranging from 1 to 30 mg once daily. Weight was significantly reduced in a dose-related manner in sibutramine­treated patients compared to placebo over the dose range of 5 to 20 mg once daily. In two 12-month studies, maximal weight loss was achieved by 6 months and statistically significant weight loss was maintained over 12 months. The amount of placebo-subtracted weight loss achieved on sibutramine was consistent across studies.

Analysis of the data in three long-term ( ≥ 6 months) obesity trials indicates that patients who lose at least 4 pounds in the first 4 weeks of therapy with a given dose of sibutramine are most likely to achieve significant long-term weight loss on that dose of sibutramine. Approximately 60% of such patients went on to achieve a placebo-subtracted weight loss of ≥ 5% of their initial body weight by month 6. Conversely, of those patients on a given dose of sibutramine who did not lose at least 4 pounds in the first 4 weeks of therapy, approximately 80% did not go on to achieve a placebo-subtracted weight loss of ≥ 5% of their initial body weight on that dose by month 6.

Significant dose-related reductions in waist circumference, an indicator of intra-abdominal fat, have also been observed over 6 and 12 months in placebo-controlled clinical trials. In a 12-week placebo-controlled study of non-insulin dependent diabetes mellitus patients randomized to placebo or 15 mg per day of sibutramine, Dual Energy X-Ray Absorptiometry (DEXA) assessment of changes in body composition showed that total body fat mass decreased by 1.8 kg in the sibutramine group versus 0.2 kg in the placebo group (p < 0.001). Similarly, truncal (android) fat mass decreased by 0.6 kg in the sibutramine group versus 0.1 kg in the placebo group (p < 0.01). The changes in lean mass, fasting blood sugar, and HbA1 were not statistically significantly different between the two groups.

Eleven double-blind, placebo-controlled obesity trials with study durations of 12 to 52 weeks have provided evidence that sibutramine does not adversely affect glycemia, serum lipid profiles, or se rum uric acid in obese patients. Treatment with sibutramine (5 to 20 mg once daily) is associated with mean increases in blood pressure of 1 to 3 mm Hg and with mean increases in pulse rate of 4 to 5 beats per minute relative to placebo. These findings are similar in normotensives and in patients with hypertension controlled with medication. Those patients who lose significant ( ≥ 5% weight loss ) amounts of weight on sibutramine tend to have smaller increases in blood pressure and pulse rate (see WARNINGS).

In Study 1, a 6-month, double-blind, placebo-controlled study in obese patients, Study 2, a 1-year, double-blind, placebo-controll ed study in obese patients, and Study 3, a 1-year, double-blind, placebo-controlled study in obese patients who lost at least 6 kg on a 4-week very low calorie diet (VLCD), sibutramine produced significant reductions in weight, as shown below . In the two 1-year studies, maximal weight loss was achieved by 6 months and statistically significant weight loss was maintained over 12 months.

Mean Weight Loss (lbs) in the Six-Month and One-Year Trials

Study/Patient Group Placebo (n) S ibutramine(mg)
5 (n) 10 (n) 15 (n) 20 (n)
Study 1
  All patients* 2.0 6.6 9.7 12.1 13.6
(142) (148) (148) (150) (145)
  Completers** 2.9 8.1 12.1 15.4 18.0
(84) (103) (95) (94) (89)
  Early responders*** 8.5 13.0 16.0 18.2 20.1
(17) (60) (64) (73) (76)
Study 2
  All patients* 3.5   9.8 14.0  
(157)   (154) (152)  
  Completers** 4.8   13.6 15.2  
(76)   (80) (93)  
  Early responders*** 10.7   18.2 18.8  
(24)   (57) (76)  
Study 3****
  All patients* 15.2   28.4    
(78)   (81)    
  Completers** 16.7   29.7    
(48)   (60)    
  Early responders*** 21.5   33.0    
(22)   (46)    
* Data for all patients who received study drug and who had any post-baseline measurement (last observation carried forward analysis).
** Data for patients who completed the entire 6-month (Study 1) or one-year period of dosing and have data recorded for the month 6 (Study 1) or month 12 visit.
*** Data for patients who lost at least 4 lbs in the first 4 weeks of treatment and completed the study.
**** Weight loss data shown describe changes in weight from the pre-VLCD; mean weight loss during the 4-week VLCD was 16.9 lbs for sibutramine and 16.3 lbs for placebo.

Maintenance of weight loss with sibutramine was examined in a 2-year, double-blind, placebo-controlled trial. After a 6-month run-in phase in which all patients received sibutramine 10 mg (mean weight loss, 26 lbs.), patients were randomized to sibutramine (10 to 20 mg, 352 patients) or placebo (115 patients). The mean weight loss from initial body weight to endpoint was 21 lbs. and 12 lbs. for sibutramine and placebo patients, respectively. A statistically significantly (p < 0.001) greater proportion of sibutramine treated patients, 75%, 62%, and 43%, maintained at least 80% of their initial weight loss at 12, 18, and 24 months, respectively, compared with the placebo group (38%, 23%, and 16%). Also 67%, 37%, 17%, and 9% of sibutramine treated patients compared with 49%, 19%, 5%, and 3% of placebo patients lost ≥ 5%, ≥ 10%, ≥ 15%, and ≥ 20%, respectively, of their initial body weight at endpoint. From endpoint to the post-study follow-up visit (about 1 month), weight regain was approximately 4 lbs for the sibutramine patients and approximately 2 lbs for the placebo patients.

Sibutramine induced weight loss has been accompanied by beneficial changes in serum lipids that are similar to those seen with nonpharmacologically-mediated weight loss. A combined, weighted analysis of the changes in serum lipids in 11 placebo-controlled obesity studies ranging in length from 12 to 52 weeks is shown below for the last observation carried forward (LOCF) analysis.

Combined Analysis (11 Studies) of Changes in Serum Lipids – LOCF

Category TG
% (n)
CHOL
% (n)
LDL-C
% (n)
HDL-C
% (n)
All Placebo 0.53 (475) -1.53 (475) -0.09 (233) -0.56 (248)
  < 5% Weight Loss 4.52 (382) -0.42 (382) -0.70 (205) -0.71 (217)
  ≥ 5% Weight Loss -15.30 (92) -6.23 (92) -6.19 (27) 0.94 (30 )
All Sibutramine -8.75 (1164) -2.21 (1165) -1.85 (642) 4.13 (664)
  < 5% Weight Loss -0.54 (547) 0.17 (548) -0.37 (320) 3.19 (331)
  ≥ 5% Weight Loss -16.59 (612) -4.87 (612) -4.56 (317) 4.68 (328)

Baseline mean values:

Placebo: TG 187 mg/dL; CHOL 221 mg/dL; LDL-C 140 mg/dL; HDL-C 47 mg/dL Sibutramine: TG 172 mg/dL; CHOL 215 mg/dL; LDL-C 140 mg/dL; HDL-C 47 mg/dL TG: Triglycerides, CHOL: Cholesterol, LDL-C Low Density Lipoprotein-Cholesterol HDL-C: High Density Lipoprotein-Cholesterol

Sibutramine induced weight loss has been accompanied by reductions in serum uric acid. Certain centrally-acting weight loss agents that cause release of serotonin from nerve terminals have been associated with cardiac valve dysfunction. The possible occurrence of cardiac valve disease w as specifically investigated in two studies. In one study 2-D and color Doppler echocardiography we re performed on 210 patients (mean age, 54 years) receiving sibutramine 15 mg or placebo daily for periods of 2 weeks to 16 months (mean duration of treatment, 7.6 months). In patients without a prior history of valvular heart disease, the incidence of valvular heart disease was 3/132 (2.3%) in the sibutramine treatment group (all three cases were mild aortic insufficiency) and 2/77 (2.6%) in the placebo treatment group (one case of mild aortic insufficiency and one case of severe aortic insufficiency). In another study, 25 patients underwent 2-D and color Doppler echocardiography before treatment with sibutramine and again after treatment with sibutramine 5 to 30 mg daily for three months; there were no cases of valvular heart disease.

The effect of sibutramine 15 mg once daily on measures of 24-hour blood pressure was evaluated in 12-week placebo-controlled study. Twenty-six male and female, primarily Cauasian individuals ac with an average BMI of 34 kg/m² and an average age of 39 years underwent 24-hour ambulatory blood pressure monitoring (ABPM). The mean changes from baseline to Week 12 in various measures of ABPM are shown in the following table.

Parameter mm Hg Systolic Diastolic
Placebo
n=12
Sibutramine Placebo Sibutramine
15 mg
n=14
20 mg
n=16
15 mg
n=12
20 mg
n=16
Daytime 0.2 3.9 4.4 0.5 5.0 5.7
Nighttime -0.3 4.1 6.4 -1.0 4.3 5.4
Early am -0.9 9.4 5.3 -3.0 6.7 5.8
24-hour mean -0.1 4.0 4.7 0.1 5.0 5.6

Normal diurnal variation of blood pressure was maintained.

Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

PATIENT INFORMATION

MEDICATION GUIDE

MERIDIA®
(mer-ID-dee-uh)
(sibutramine hydrochloride monohydrate) Capsules

Read this Medication Guide before you start taking MERIDIA (sibutramine hydrochloride monohydrate) and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information I should know about MERIDIA (sibutramine hydrochloride monohydrate) ?

MERIDIA (sibutramine hydrochloride monohydrate) can cause serious side effects including a large increase in your blood pressure or heart rate (pulse). Do not take MERIDIA (sibutramine hydrochloride monohydrate) if your blood pressure is not well controlled. Call your doctor right away if you check your blood pressure and it is higher than normal for you, or if you have symptoms of high blood pressure such as headache, dizziness or blurred vision.

Before you start taking MERIDIA (sibutramine hydrochloride monohydrate) , your doctor should check your blood pressure and heart rate. Your doctor should continue checking your blood pressure regularly while you are taking MERIDIA (sibutramine hydrochloride monohydrate) . It is important that you have regular check-ups while you are taking MERIDIA (sibutramine hydrochloride monohydrate) .

What is MERIDIA (sibutramine hydrochloride monohydrate) ?

MERIDIA (sibutramine hydrochloride monohydrate) is a prescription medicine used to help overweight or obese people lose weight and keep the weight off. MERIDIA (sibutramine hydrochloride monohydrate) should be used together with a low calorie diet.

MERIDIA (sibutramine hydrochloride monohydrate) contains sibutramine, a substance that people can become addicted to. Keep your MERIDIA (sibutramine hydrochloride monohydrate) in a safe place to protect it from theft. Never give your MERIDIA (sibutramine hydrochloride monohydrate) to anyone else, because it may cause death or harm them. Selling or giving away this medicine is against the law.

The use of MERIDIA (sibutramine hydrochloride monohydrate) for more than 2 years has not been studied.

It is not known if MERIDIA (sibutramine hydrochloride monohydrate) is safe and effective in children younger than 16 years old.

Who should not take MERIDIA (sibutramine hydrochloride monohydrate) ?

Do not take MERIDIA (sibutramine hydrochloride monohydrate) if you:

  • • have or have had, heart problems, including:
  • have or have ever had, a stroke or symptoms of a stroke
  • uncontrolled high blood pressure (above 145/90)
  • are over age 65
  • are taking or have taken a type of medicine used to treat depression called a monoamine oxidase inhibitor (MAOI) in the past 2 weeks. Do not take MAOIs for at least 2 weeks before using MERIDIA (sibutramine hydrochloride monohydrate) . Do not take MAOIs for at least 2 weeks after stopping MERIDIA (sibutramine hydrochloride monohydrate) . Ask your doctor or pharmacist if you are not sure if any of your medicines are MAOIs.
  • have an eating problem called anorexia nervosa or bulimia nervosa.
  • are taking certain other weight loss medicines.
  • are allergic to sibutramine hydrochloride monohydrate or any other ingredients in MERIDIA (sibutramine hydrochloride monohydrate) . See the end of this Medication Guide for a complete list of ingredients in MERIDIA (sibutramine hydrochloride monohydrate) .

Talk to your doctor before taking this medicine if you have any of these conditions.

What should I tell my doctor before taking MERIDIA (sibutramine hydrochloride monohydrate) ?

Before you take MERIDIA (sibutramine hydrochloride monohydrate) , tell your doctor if you:

  • have liver or kidney problems
  • have glaucoma
  • have or had seizures (convulsions, fits)
  • have bleeding problems
  • have or had gallstones
  • are pregnant or plan to become pregnant. It is not known if MERIDIA (sibutramine hydrochloride monohydrate) will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant. If you can become pregnant, you should use birth control while taking MERIDIA (sibutramine hydrochloride monohydrate) . Tell your doctor right away if you become pregnant while taking MERIDIA (sibutramine hydrochloride monohydrate) .
  • are breastfeeding or plan to breastfeed. It is not known if MERIDIA (sibutramine hydrochloride monohydrate) passes into your breast milk. You and your doctor should decide if you will take MERIDIA (sibutramine hydrochloride monohydrate) or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Using MERIDIA (sibutramine hydrochloride monohydrate) with certain other medicines may affect how MERIDIA (sibutramine hydrochloride monohydrate) or the other medicines work. Using MERIDIA (sibutramine hydrochloride monohydrate) with other medicines can cause serious side effects.

Especially tell your doctor if you take:

  • a monoamine oxidase inhibitors (MAOIs) medicine. See "Who should not take MERIDIA (sibutramine hydrochloride monohydrate) ?"
  • other weight loss medicines
  • cough and cold medicines
  • migraine headache medicines like sumatriptan (Imitrex, Imitrex Statdose) or dihydroergotamine (D.H.E 45, Migranal)
  • medicines to treat depression
  • narcotic pain medicines
  • lithium (Lithobid)
  • tryptophan
  • medicines that thin the blood

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get new medicine.

How should I take MERIDIA (sibutramine hydrochloride monohydrate) ?

  • Take MERIDIA (sibutramine hydrochloride monohydrate) exactly as your doctor tells you to.
  • Take MERIDIA (sibutramine hydrochloride monohydrate) 1 time a day.
  • If you miss a dose of MERIDIA (sibutramine hydrochloride monohydrate) , just skip it. Do not take an extra dose to make up for missed doses.
  • If you take too much MERIDIA (sibutramine hydrochloride monohydrate) , call your doctor or Poison Control Center right away, or go to the emergency room.
  • Your doctor may change your dose if needed.
  • Take MERIDIA (sibutramine hydrochloride monohydrate) with or without food.
  • You should see your doctor regularly for check-ups.

What should I avoid while taking MERIDIA (sibutramine hydrochloride monohydrate) ?

  • Do not drive, operate heavy machinery or do other dangerous activities until you know how MERIDIA (sibutramine hydrochloride monohydrate) affects you.
  • Do not have more than two standard alcoholic drinks per day while you take MERIDIA (sibutramine hydrochloride monohydrate) . What are the possible side effects of MERIDIA (sibutramine hydrochloride monohydrate) ?

MERIDIA (sibutramine hydrochloride monohydrate) may cause serious side effects, including:

  • See "What is the most important information I should know about MERIDIA (sibutramine hydrochloride monohydrate) ?"
  • serotonin syndrome. Serotonin syndrome may happen when people take MERIDIA (sibutramine hydrochloride monohydrate) with certain other medicines that affect a brain chemical called serotonin. Do not take other medicines with MERIDIA (sibutramine hydrochloride monohydrate) unless your doctor has told you to. Get medical help right away if you have any of the following symptoms:
    • feel weak, restless, confused, or anxious
    • lose consciousness (faint)
    • have a fever, vomiting, sweating, shivering or shaking
    • have a fast heartbeat
  • seizures (convulsions, fits)
  • bleeding. Bleeding may happen if you have a condition that causes bleeding or if you take a blood thinning medicine.

Certain weight loss medicines have a rare but life-threatening problem that affects blood pressure in the lungs (pulmonary hypertension). It is not known if MERIDIA (sibutramine hydrochloride monohydrate) may cause this problem because pulmonary hypertension is so rare. Call your doctor right away if you have new or worsening shortness of breath.

The most common side effects of MERIDIA (sibutramine hydrochloride monohydrate) include:

  • dry mouth
  • loss of appetite
  • trouble sleeping
  • constipation
  • headache

Tell your doctor if you get a rash or hives while taking MERIDIA (sibutramine hydrochloride monohydrate) . You may be having an allergic reaction.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the side effects of MERIDIA (sibutramine hydrochloride monohydrate) . For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store MERIDIA (sibutramine hydrochloride monohydrate) ?

  • Store MERIDIA (sibutramine hydrochloride monohydrate) between 59° F to 86° F (15°C to 30° C).
  • Keep MERIDIA (sibutramine hydrochloride monohydrate) capsules dry and away from heat.
  • Keep MERIDIA (sibutramine hydrochloride monohydrate) in a tightly closed container, and keep MERIDIA (sibutramine hydrochloride monohydrate) out of the light.
  • Safely throw away medicine that is out of date or no longer needed.

Keep MERIDIA (sibutramine hydrochloride monohydrate) and all medicines out of reach of children.

General information about MERIDIA (sibutramine hydrochloride monohydrate) .

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use MERIDIA (sibutramine hydrochloride monohydrate) for a condition for which it was not prescribed. Do not give MERIDIA (sibutramine hydrochloride monohydrate) to other people, even if they have the same symptoms you have. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about MERIDIA (sibutramine hydrochloride monohydrate) . If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about MERIDIA (sibutramine hydrochloride monohydrate) that is written for health professionals.

For more information, go to www.Meridia (sibutramine hydrochloride monohydrate) .net, or call 1-800-633-9110.

What are the ingredients in MERIDIA?

Active ingredient: sibutramine hydrochloride monohydrate

Inactive ingredients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate.

Hard-gelatin capsule: titanium dioxide, gelatin, FD&C Blue No. 2 (5 mg and 10 mg capsules only), D&C Yellow No. 10 (5 mg and 15 mg capsules only), and other inactive ingredients.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Rev. 07/2010

Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.

>

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

PATIENT INFORMATION

MEDICATION GUIDE

MERIDIA®
(mer-ID-dee-uh)
(sibutramine hydrochloride monohydrate) Capsules

Read this Medication Guide before you start taking MERIDIA (sibutramine hydrochloride monohydrate) and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information I should know about MERIDIA (sibutramine hydrochloride monohydrate) ?

MERIDIA (sibutramine hydrochloride monohydrate) can cause serious side effects including a large increase in your blood pressure or heart rate (pulse). Do not take MERIDIA (sibutramine hydrochloride monohydrate) if your blood pressure is not well controlled. Call your doctor right away if you check your blood pressure and it is higher than normal for you, or if you have symptoms of high blood pressure such as headache, dizziness or blurred vision.

Before you start taking MERIDIA (sibutramine hydrochloride monohydrate) , your doctor should check your blood pressure and heart rate. Your doctor should continue checking your blood pressure regularly while you are taking MERIDIA (sibutramine hydrochloride monohydrate) . It is important that you have regular check-ups while you are taking MERIDIA (sibutramine hydrochloride monohydrate) .

What is MERIDIA (sibutramine hydrochloride monohydrate) ?

MERIDIA (sibutramine hydrochloride monohydrate) is a prescription medicine used to help overweight or obese people lose weight and keep the weight off. MERIDIA (sibutramine hydrochloride monohydrate) should be used together with a low calorie diet.

MERIDIA (sibutramine hydrochloride monohydrate) contains sibutramine, a substance that people can become addicted to. Keep your MERIDIA (sibutramine hydrochloride monohydrate) in a safe place to protect it from theft. Never give your MERIDIA (sibutramine hydrochloride monohydrate) to anyone else, because it may cause death or harm them. Selling or giving away this medicine is against the law.

The use of MERIDIA (sibutramine hydrochloride monohydrate) for more than 2 years has not been studied.

It is not known if MERIDIA (sibutramine hydrochloride monohydrate) is safe and effective in children younger than 16 years old.

Who should not take MERIDIA (sibutramine hydrochloride monohydrate) ?

Do not take MERIDIA (sibutramine hydrochloride monohydrate) if you:

  • • have or have had, heart problems, including:
  • have or have ever had, a stroke or symptoms of a stroke
  • uncontrolled high blood pressure (above 145/90)
  • are over age 65
  • are taking or have taken a type of medicine used to treat depression called a monoamine oxidase inhibitor (MAOI) in the past 2 weeks. Do not take MAOIs for at least 2 weeks before using MERIDIA (sibutramine hydrochloride monohydrate) . Do not take MAOIs for at least 2 weeks after stopping MERIDIA (sibutramine hydrochloride monohydrate) . Ask your doctor or pharmacist if you are not sure if any of your medicines are MAOIs.
  • have an eating problem called anorexia nervosa or bulimia nervosa.
  • are taking certain other weight loss medicines.
  • are allergic to sibutramine hydrochloride monohydrate or any other ingredients in MERIDIA (sibutramine hydrochloride monohydrate) . See the end of this Medication Guide for a complete list of ingredients in MERIDIA (sibutramine hydrochloride monohydrate) .

Talk to your doctor before taking this medicine if you have any of these conditions.

What should I tell my doctor before taking MERIDIA (sibutramine hydrochloride monohydrate) ?

Before you take MERIDIA (sibutramine hydrochloride monohydrate) , tell your doctor if you:

  • have liver or kidney problems
  • have glaucoma
  • have or had seizures (convulsions, fits)
  • have bleeding problems
  • have or had gallstones
  • are pregnant or plan to become pregnant. It is not known if MERIDIA (sibutramine hydrochloride monohydrate) will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant. If you can become pregnant, you should use birth control while taking MERIDIA (sibutramine hydrochloride monohydrate) . Tell your doctor right away if you become pregnant while taking MERIDIA (sibutramine hydrochloride monohydrate) .
  • are breastfeeding or plan to breastfeed. It is not known if MERIDIA (sibutramine hydrochloride monohydrate) passes into your breast milk. You and your doctor should decide if you will take MERIDIA (sibutramine hydrochloride monohydrate) or breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Using MERIDIA (sibutramine hydrochloride monohydrate) with certain other medicines may affect how MERIDIA (sibutramine hydrochloride monohydrate) or the other medicines work. Using MERIDIA (sibutramine hydrochloride monohydrate) with other medicines can cause serious side effects.

Especially tell your doctor if you take:

  • a monoamine oxidase inhibitors (MAOIs) medicine. See "Who should not take MERIDIA (sibutramine hydrochloride monohydrate) ?"
  • other weight loss medicines
  • cough and cold medicines
  • migraine headache medicines like sumatriptan (Imitrex, Imitrex Statdose) or dihydroergotamine (D.H.E 45, Migranal)
  • medicines to treat depression
  • narcotic pain medicines
  • lithium (Lithobid)
  • tryptophan
  • medicines that thin the blood

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get new medicine.

How should I take MERIDIA (sibutramine hydrochloride monohydrate) ?

  • Take MERIDIA (sibutramine hydrochloride monohydrate) exactly as your doctor tells you to.
  • Take MERIDIA (sibutramine hydrochloride monohydrate) 1 time a day.
  • If you miss a dose of MERIDIA (sibutramine hydrochloride monohydrate) , just skip it. Do not take an extra dose to make up for missed doses.
  • If you take too much MERIDIA (sibutramine hydrochloride monohydrate) , call your doctor or Poison Control Center right away, or go to the emergency room.
  • Your doctor may change your dose if needed.
  • Take MERIDIA (sibutramine hydrochloride monohydrate) with or without food.
  • You should see your doctor regularly for check-ups.

What should I avoid while taking MERIDIA (sibutramine hydrochloride monohydrate) ?

  • Do not drive, operate heavy machinery or do other dangerous activities until you know how MERIDIA (sibutramine hydrochloride monohydrate) affects you.
  • Do not have more than two standard alcoholic drinks per day while you take MERIDIA (sibutramine hydrochloride monohydrate) . What are the possible side effects of MERIDIA (sibutramine hydrochloride monohydrate) ?

MERIDIA (sibutramine hydrochloride monohydrate) may cause serious side effects, including:

  • See "What is the most important information I should know about MERIDIA (sibutramine hydrochloride monohydrate) ?"
  • serotonin syndrome. Serotonin syndrome may happen when people take MERIDIA (sibutramine hydrochloride monohydrate) with certain other medicines that affect a brain chemical called serotonin. Do not take other medicines with MERIDIA (sibutramine hydrochloride monohydrate) unless your doctor has told you to. Get medical help right away if you have any of the following symptoms:
    • feel weak, restless, confused, or anxious
    • lose consciousness (faint)
    • have a fever, vomiting, sweating, shivering or shaking
    • have a fast heartbeat
  • seizures (convulsions, fits)
  • bleeding. Bleeding may happen if you have a condition that causes bleeding or if you take a blood thinning medicine.

Certain weight loss medicines have a rare but life-threatening problem that affects blood pressure in the lungs (pulmonary hypertension). It is not known if MERIDIA (sibutramine hydrochloride monohydrate) may cause this problem because pulmonary hypertension is so rare. Call your doctor right away if you have new or worsening shortness of breath.

The most common side effects of MERIDIA (sibutramine hydrochloride monohydrate) include:

  • dry mouth
  • loss of appetite
  • trouble sleeping
  • constipation
  • headache

Tell your doctor if you get a rash or hives while taking MERIDIA (sibutramine hydrochloride monohydrate) . You may be having an allergic reaction.

Tell your doctor if you have any side effect that bothers you or that does not go away.

These are not all the side effects of MERIDIA (sibutramine hydrochloride monohydrate) . For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store MERIDIA (sibutramine hydrochloride monohydrate) ?

  • Store MERIDIA (sibutramine hydrochloride monohydrate) between 59° F to 86° F (15°C to 30° C).
  • Keep MERIDIA (sibutramine hydrochloride monohydrate) capsules dry and away from heat.
  • Keep MERIDIA (sibutramine hydrochloride monohydrate) in a tightly closed container, and keep MERIDIA (sibutramine hydrochloride monohydrate) out of the light.
  • Safely throw away medicine that is out of date or no longer needed.

Keep MERIDIA (sibutramine hydrochloride monohydrate) and all medicines out of reach of children.

General information about MERIDIA (sibutramine hydrochloride monohydrate) .

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use MERIDIA (sibutramine hydrochloride monohydrate) for a condition for which it was not prescribed. Do not give MERIDIA (sibutramine hydrochloride monohydrate) to other people, even if they have the same symptoms you have. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about MERIDIA (sibutramine hydrochloride monohydrate) . If you would like more information, talk with your doctor. You can also ask your doctor or pharmacist for information about MERIDIA (sibutramine hydrochloride monohydrate) that is written for health professionals.

For more information, go to www.Meridia (sibutramine hydrochloride monohydrate) .net, or call 1-800-633-9110.

What are the ingredients in MERIDIA?

Active ingredient: sibutramine hydrochloride monohydrate

Inactive ingredients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate.

Hard-gelatin capsule: titanium dioxide, gelatin, FD&C Blue No. 2 (5 mg and 10 mg capsules only), D&C Yellow No. 10 (5 mg and 15 mg capsules only), and other inactive ingredients.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Rev. 07/2010

Last reviewed on RxList: 1/31/2011
This monograph has been modified to include the generic and brand name in many instances.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

Disclaimer

Meridia Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

SIBUTRAMINE - ORAL

(sye-BYOU-truh-meen)

COMMON BRAND NAME(S): Meridia

USES: This drug has been withdrawn from the US and Canadian markets due to problems with safety (increased risk of heart attack and stroke). Talk with your doctor about stopping sibutramine now and about other treatment options.

This medication is used along with a low-calorie diet to help people with obesity lose weight. Reducing excess weight helps to prevent or control complications such as heart disease, diabetes, and joint pain. Sibutramine works by affecting the area in your brain that controls hunger, providing you with a sense of fullness and satisfaction.

Discuss the risks and benefits of sibutramine with your doctor.

This drug should not be used in adults 65 years or older.

HOW TO USE: Read the Medication Guide provided by your pharmacist before you start using sibutramine and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth, usually once daily with or without food, or as directed by your doctor.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day. Dosage is based on your medical condition and response to therapy.

Do not increase your dose, take it more frequently, or use it for a longer period of time than prescribed. Do not suddenly stop using this drug without your doctor's approval. Your dose may need to be gradually reduced, especially if you have been taking this medication for a long time. Consult your doctor or pharmacist for more details.

When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

Since this medication can increase your blood pressure and heart rate (pulse), it is important to have regular check-ups to monitor these readings before starting and during treatment with sibutramine. Your doctor will also monitor your weight loss progress and check for side effects (usually checking after 4 weeks, and then after 3-6 months of treatment or as directed) to decide if continued treatment is safe and effective for you.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

Disclaimer

Meridia Consumer (continued)

SIDE EFFECTS: Dry mouth, increased appetite, nausea, strange taste in the mouth, upset stomach, constipation, trouble sleeping, dizziness, drowsiness, menstrual cramps/pain, headache, flushing, or joint/muscle pain may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: fast/pounding/irregular heartbeat, numbness/tingling of the hands or feet, mental/mood changes (e.g., excitement, restlessness, confusion, depression, rare thoughts of suicide).

Tell your doctor immediately if any of these rare but very serious side effects occur: change in the amount or color of urine, easy or unusual bruising/bleeding, black stools, vomit that looks like coffee grounds, yellowing eyes or skin, unexplained fever, shaking, unusual sweating, swelling of the arms/legs.

Seek immediate medical attention if any of these rare but very serious side effects occur: seizures, chest pain, weakness on one side of the body, vision changes, trouble breathing.

Sibutramine may rarely cause a very serious condition called serotonin syndrome. Taking sibutramine with "triptans" used to treat migraine headaches (e.g., sumatriptan, eletriptan) or certain antidepressants including SSRIs (e.g., citalopram, fluoxetine, paroxetine) and NSRIs (e.g., duloxetine, venlafaxine) increases the risk of this reaction. Before taking sibutramine, tell your doctor if you take any of these medications. Serotonin syndrome may be more likely when you start or increase the dose of any of these medications. Seek immediate medical attention if you develop some of the following symptoms: severe mental/mood changes (e.g., hallucinations, unusual restlessness), loss of coordination, fast heartbeat, severe dizziness, unexplained fever, severe nausea/vomiting/diarrhea, twitchy muscles.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Meridia (sibutramine hydrochloride monohydrate) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking sibutramine, tell your doctor or pharmacist if you are allergic to it or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: eating disorders (e.g., anorexia nervosa, bulimia nervosa), uncontrolled or poorly controlled high blood pressure, heart or blood vessel disease (e.g., coronary artery disease, history of heart attack or angina, congestive heart failure, abnormal heart rhythms, poor circulation in the arms/legs), stroke or TIA (transient ischemic attack).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood pressure, glaucoma (narrow angle type), untreated underactive thyroid disease, liver disease, kidney disease, gallstones, seizure disorder, bleeding disorders, depression, drug abuse.

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Children may be at a greater risk for mental/mood changes (including rare thoughts of suicide) while using this drug.

This medication is not recommended for use during pregnancy. Women of child-bearing age should use effective birth control while taking this medication. Consult your doctor for more details.

It is not known whether this drug passes into breast milk. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

Disclaimer

Meridia Consumer (continued)

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medications because very serious interactions may occur: certain other weight loss medicines (e.g., diethylpropion, phentermine).

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting sibutramine.

Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) within 2 weeks before, during, and after treatment with this medication. In some cases a serious (possibly fatal) drug interaction may occur.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: antidepressants (e.g., citalopram, fluoxetine, venlafaxine), antipsychotics (including aripiprazole, phenothiazines such as chlorpromazine/thioridazine), dextromethorphan, drugs used to treat migraine headaches (e.g., sumatriptan, ergotamine), ketoconazole, lithium, certain narcotic pain medications (e.g., fentanyl, meperidine, pentazocine), tryptophan.

This medication may rarely increase your risk for serious bleeding, especially if you take other drugs such as "blood thinners" (e.g., warfarin) or anti-platelet drugs (e.g., aspirin, clopidogrel). Sibutramine is generally not used in patients with heart disease, however, if you are prescribed any of these drugs for heart attack or stroke prevention, continue taking them and consult your doctor on how to minimize your risk of bleeding.

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, herbal products) because they may contain ingredients that could increase your heart rate or blood pressure. These ingredients include pseudoephedrine, ephedrine, ephedra, and ma huang, among others. Ask your pharmacist about the safe use of these products.

Avoid drinking large amounts of beverages containing caffeine (coffee, tea, colas). Caffeine can increase the side effects of this medication (e.g., increase your heart rate).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Do not share this medication with others. It is against the law.

Have your blood pressure and heart rate (pulse) checked regularly while taking this medication. You can learn how to monitor your own blood pressure and pulse. Discuss this with your doctor.

For best results, this medication should be used along with an exercise program and reduced calorie diet as approved by your doctor. Behavior change counseling is also helpful. Consult your doctor for details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature (77 degrees F or 25 degrees C) away from heat and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised February 2012. Copyright(c) 2012 First Databank, Inc.

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

Meridia Patient Information Including Side Effects

Brand Names: Meridia

Generic Name: sibutramine (Pronunciation: si BUE tra meen)

What is sibutramine (Meridia)?

Sibutramine was withdrawn from the U.S. market in October 2010.

Sibutramine affects chemicals in the brain that affect weight maintenance.

Sibutramine is used together with diet and exercise to treat obesity that may be related to diabetes, high cholesterol, or high blood pressure.

Sibutramine may also be used for other purposes not listed in this medication guide.

Meridia 10 mg

blue/white, imprinted with MERIDIA, 10

What are the possible side effects of sibutramine (Meridia)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Stop using sibutramine and call your doctor at once if you have a serious side effect such as:

  • fast, pounding, or uneven heartbeats;
  • new or worsening shortness of breath;
  • agitation, hallucinations, fever, tremor, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, dilated pupils;
  • very stiff (rigid) muscles, high fever, sweating, confusion, feeling like you might pass out;
  • easy bruising or bleeding (nosebleeds, bleeding gums, or any bleeding that will not stop);
  • dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, seizure);
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, general ill feeling; or
  • sudden numbness or weakness (especially on one side of the body), problems with vision, speech, or balance.

Less serious side effects may include:

  • dry mouth, upset stomach;
  • changes in appetite;
  • constipation, stomach pain;
  • headache, back pain, joint pain;
  • feeling nervous, dizzy, or depressed;
  • flu symptoms, runny or stuffy nose, sore throat, cough;
  • warmth, redness, or tingly feeling under your skin;
  • trouble sleeping (insomnia); or
  • mild skin rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Meridia (sibutramine hydrochloride monohydrate) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about sibutramine (Meridia)?

Sibutramine was withdrawn from the U.S. market in October 2010.

Do not use sibutramine if you have taken an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) in the last 14 days. Serious, life threatening side effects can occur if you use sibutramine before the MAO inhibitor has cleared from your body.

You should not take sibutramine if you are allergic to it, or if you have severe or uncontrolled high blood pressure, an eating disorder (anorexia or bulimia), if you are taking stimulant diet pills, or if you have a history of coronary artery disease, stroke, or heart disease.

Before taking sibutramine, tell your doctor if you have glaucoma, high blood pressure, liver or kidney disease, depression, underactive thyroid, seizures, a bleeding disorder, a history of gallstones, or if you are older than 65 or younger than 16.

Tell your doctor about all prescription and over-the-counter medications you use, especially antidepressants, cold or allergy medication, narcotic pain medicine, or migraine headache medicines.

Tell your doctor if you do not lose at least 4 pounds after taking the medication for 4 weeks along with a low calorie diet.

Side Effects Centers

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

Meridia Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking sibutramine (Meridia)?

Do not use sibutramine if you have taken an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) in the last 14 days. Serious, life threatening side effects can occur if you use sibutramine before the MAO inhibitor has cleared from your body.

You should not take this medication if you are allergic to sibutramine, or if you have:

  • severe or uncontrolled hypertension (high blood pressure);
  • an eating disorder (anorexia or bulimia);
  • a history of coronary artery disease (atherosclerosis);
  • a history of heart disease (congestive heart failure, heart rhythm disorder);
  • a history of heart attack or stroke; or
  • if you are taking stimulant diet pills.

If you have any of these other conditions, you may need a sibutramine dose adjustment or special tests:

  • glaucoma;
  • high blood pressure;
  • liver disease;
  • kidney disease;
  • depression;
  • underactive thyroid;
  • epilepsy or seizure disorder;
  • a bleeding or blood clotting disorder;
  • a history of gallstones; or
  • if you are older than 65 or younger than 16.

FDA pregnancy category C. It is not known whether sibutramine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using sibutramine.

It is not known whether sibutramine passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Do not give this medication to anyone younger than 16 years old.

How should I take sibutramine (Meridia)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Sibutramine is usually taken once daily. Follow your doctor's instructions.

Your doctor may occasionally change your dose to make sure you get the best results.

Sibutramine can be taken with or without food.

You should lose at least 4 pounds during the first 4 weeks of taking sibutramine and eating a low calorie diet. Tell your doctor if you do not lose at least 4 pounds after taking the medication for 4 weeks.

Your blood pressure and pulse will need to be checked often. Visit your doctor regularly.

Sibutramine should not be taken for longer than 2 years.

Store at room temperature away from moisture, heat, and light.

Do not share sibutramine with another person. Keep the medication in a place where others cannot get to it.

Side Effects Centers

Discontinued Warning IconPlease Note: This Brand Name drug is no longer available in the US.
(Generic versions may still be available.)

Meridia Patient Information including If I Miss a Dose

What happens if I miss a dose (Meridia)?

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.

What happens if I overdose (Meridia)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include headache, dizziness, and fast heart rate.

What should I avoid while taking sibutramine (Meridia)?

Sibutramine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Do not take any other prescription or over-the-counter weight-loss products without your doctor's advice.

Avoid taking cough and cold or allergy medications while taking sibutramine.

Avoid drinking alcohol while taking sibutramine.

What other drugs will affect sibutramine (Meridia)?

Before using sibutramine, tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by sibutramine.

Ask your doctor before taking any decongestants, cough medicine, or other diet pills.

The following drugs can interact with sibutramine. Tell your doctor if you are using any of these:

  • lithium (Lithobid, Eskalith, and others);
  • tryptophan or L-tryptophan;
  • ketoconazole (Nizoral);
  • an antibiotic such as erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin);
  • an antidepressant such as citalopram (Celexa), desvenlafaxine (Pristiq), duloxetine (Cymbalta), fluoxetine (Prozac, Sarafem, Symbyax), paroxetine (Paxil), sertraline (Zoloft), venlafaxine (Effexor), and others;
  • ergot medicine such as dihydroergotamine (D.H.E. 45, Migranal Nasal Spray), ergonovine (Ergotrate), ergotamine (Ergomar), or methylergonovine (Methergine).
  • migraine headache medicine such as sumatriptan (Imitrex) or zolmitriptan (Zomig); or
  • narcotic pain medication such as fentanyl (Actiq, Duragesic, Fentora, Onsolis), meperidine (Demerol), pentazocine (Talwin).

This list is not complete and other drugs may interact with sibutramine. Tell your doctor about all medications you use. This includes prescription, over the counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about sibutramine.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 5.02. Revision date: 12/15/2010.

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