Brand name : MERIDIA®
(sibutramine hydrochloride monohydrate) Capsules
CS-IV
Most important fact about Meridia - without a prior
prescription available now:
MERIDIA® (sibutramine hydrochloride monohydrate) is an orally administered
agent for the treatment of obesity. Chemically, the active ingredient
is a racemic mixture of the (+) and (-) enantiomers of cyclobutanemethanamine,
1-(4-chlorophenyl)-N,N-dimethyl-a-(2-methylpropyl)-, hydrochloride, monohydrate,
and has an empirical formula of C17H29Cl2NO. Its molecular weight is
334.33.
The structural formula is shown below:Meridia (sibutramine hydrochloride
monohydrate) structural formula illustration.Sibutramine hydrochloride
monohydrate is a white to cream crystalline powder with a solubility
of 2.9 mg/mL in pH 5.2 water. Its octanol: water
partition coefficient is 30.9 at pH 5.0.
Each MERIDIA capsule contains 5 mg, 10 mg, and 15 mg of sibutramine
hydrochloride monohydrate. It also contains as inactive ingredients:
lactose monohydrate, NF; microcrystalline cellulose, NF; colloidal silicon
dioxide, NF; and magnesium stearate, NF in a hard-gelatin capsule [which
contains titanium dioxide, USP; gelatin; FD&C Blue No. 2 (5- and
10-mg capsules only); D&C Yellow No. 10 (5- and 15-mg capsules only),
and other inactive ingredients].
INDICATIONS
MERIDIA is indicated for the management of obesity, including weight
loss and maintenance of weight loss, and should be used in conjunction
with a reduced calorie diet. MERIDIA is recommended for obese patients
with an initial body mass index = 30 kg/m2, or = 27 kg/m2 in the presence
of other risk factors (e.g., diabetes, dyslipidemia, controlled hypertension).Below
is a chart of Body Mass Index (BMI) based on various heights and weights.BMI
is calculated by taking the patient's weight, in kg, and dividing by
the patient's height, in meters, squared. Metric conversions are
as follows: pounds ÷ 2.2 = kg; inches × 0.0254 = meters.
DOSAGE AND ADMINISTRATION Meridia sibutramine
The recommended starting dose of MERIDIA is 10 mg administered once
daily with or without food. If there is inadequate weight loss, the
dose may be titrated after four weeks to a total of 15 mg once daily.
The 5 mg dose should be reserved for patients who do not tolerate the
10 mg dose. Blood pressure and heart rate changes should be taken into
account when making decisions regarding dose titration (see WARNINGS
and PRECAUTIONS).Doses above 15 mg daily are not recommended. In most
of the clinical trials, MERIDIA was given in the morning.
Analysis of numerous variables has indicated that approximately 60%
of patients who lose at least 4 pounds in the first 4 weeks of treatment
with a given dose of MERIDIA in combination with a reduced-calorie
diet lose at least 5% (placebo-subtracted) of their initial body weight
by the end of 6 months to 1 year of treatment on that dose of MERIDIA.
Conversely, approximately 80% of patients who do not lose at least
4 pounds in the first 4 weeks of treatment with a given dose of MERIDIA
do not lose at least 5% (placebo-subtracted) of their initial body
weight by the end of 6 months to 1 year of treatment on that dose.
If a patient has not lost at least 4 pounds in the first 4 weeks of
treatment, the physician should consider reevaluation of therapy which
may include increasing the dose or discontinuation of MERIDIA.The safety
and effectiveness of MERIDIA, as demonstrated in double-blind, placebo-controlled
trials, have not been determined beyond 2 years
at this time.
HOW SUPPLIED
Meridia MERIDIA® (sibutramine hydrochloride monohydrate) Capsules contain
5 mg, 10 mg, or 15 mg sibutramine hydrochloride monohydrate and are supplied
as follows:
5 mg, NDC 0074-2456-12, blue/yellow capsules imprinted with "MERIDIA" on
the cap and "-5-" on the body, in bottles of 30 capsules.10 mg,
NDC 0074-2457-12, blue/white capsules imprinted with "MERIDIA" on
the cap and "-10-" on the body, in bottles of 30 capsules.15
mg, NDC 0074-2458-12, yellow/white capsules imprinted with "MERIDIA" on
the cap and "-15-" on the body, in bottles of 30 capsules.5 mg,
NDC 0074-2456-13, blue/yellow capsules imprinted with "MERIDIA" on
the cap and "-5-" on the body, in bottles of 100 capsules.10
mg, NDC 0074-2457-13, blue/white capsules imprinted with "MERIDIA" on
the cap and "-10-" on the body, in bottles of 100 capsules.15
mg, NDC 0074-2458-13, yellow/white capsules imprinted with "MERIDIA" on
the cap and "-15-" on the body, in bottles of 100 capsules.
Storage
Store at 25°C (77°F); excursions permitted to 15°-30°C
(59°-86°F) [see USP controlled room temperature]. Protect capsules
from heat and moisture. Dispense in a tight, light-resistant container
as defined in USP.
SIDE EFFECTS
In placebo-controlled studies, 9% of patients treated with sibutramine
(n = 2068) and 7% of patients treated with placebo (n = 884) withdrew for
adverse events.
In placebo-controlled studies, the most common events were dry mouth,
anorexia, insomnia, constipation and headache. Adverse events in these
studies occurring in = 1% of sibutramine treated patients and more frequently
than in the placebo group are shown in the following table.
Obese Patients in Placebo-Controlled Studies
BODY SYSTEM Meridia sibutramine
Adverse Event Sibutramine
(n = 2068)
% Incidence Placebo
(n = 884)
% Incidence
BODY AS A WHOLE
Headache 30.3 18.6 ;
Back pain 8.2 5.5;;
Flu syndrome 8.2 5.8;;
Injury accident 5.9 4.1;
Asthenia 5.9 5.3;
Abdominal pain 4.5 3.6;;
Chest pain 1.8 1.2;
Neck pain 1.6 1.1;
Allergic reaction 1.5 0.8
CARDIOVASCULAR SYSTEM
Tachycardia 2.6 0.6;
Vasodilation 2.4 0.9;
Migraine 2.4 2.0
Hypertension/increased blood pressure 2.1 0.9
Palpitation 2.0 0.8;
DIGESTIVE SYSTEM ;
Anorexia 13.0 3.5;
Constipation 11.5 6.0;
Increased appetite 8.7 2.7;
Nausea 5.9 2.8;
Dyspepsia 5.0 2.6;
Gastritis 1.7 1.2;
Vomiting 1.5 1.4;
Rectal disorder 1.2 0.5;
;METABOLIC & NUTRITIONAL ;
Thirst 1.7 0.9
Generalized edema 1.2 0.8;
MUSCULOSKELETAL SYSTEM ;
Arthralgia 5.9 5.0
Myalgia 1.9 1.1:
Tenosynovitis 1.2 0.5 ;
Joint disorder 1.1 0.6
NERVOUS SYSTEM
Dry mouth 17.2 4.2;
Insomnia 10.7 4.5
Dizziness 7.0 3.4;
Nervousness 5.2 2.9;
Anxiety 4.5 3.4;Depression 4.3 2.5;
Paresthesia 2.0 0.5
Somnolence 1.7 0.9;
CNS stimulation 1.5 0.5;
Emotional lability 1.3 0.6;;
RESPIRATORY SYSTEM
Rhinitis 10.2 7.1;
Pharyngitis 10.0 8.4;
Sinusitis 5.0 2.6
Cough increase 3.8 3.3;
Laryngitis 1.3 0.9;
SKIN & APPENDAGES
Rash 3.8 2.5;
Sweating 2.5 0.9;
Herpes simplex 1.3 1.0
Acne 1.0 0.8;
SPECIAL SENSES ;
Taste perversion 2.2 0.8;
Ear disorder 1.7 0.9;
Ear pain 1.1 0.7
UROGENITAL SYSTEM ;
Dysmenorrhea 3.5 1.4;
Urinary tract infection 2.3 2.0;Vaginal monilia 1.2 0.5
Metrorrhagia 1.0 0.8 .The following additional adverse events were
reported in = 1% of all patients who received sibutramine in controlled
and uncontrolled
pre-marketing studies.
Meridia sibutramine Digestive
System
diarrhea, flatulence, gastroenteritis, tooth disorder.
Metabolic and Nutritional :peripheral edema.
Musculoskeletal System :arthritis.
Nervous System : agitation, leg cramps, hypertonia, thinking abnormal.
Respiratory System :bronchitis, dyspnea.
Skin and Appendages :pruritus.
Special Senses:amblyopia.
Urogenital System :menstrual disorders.
Other Adverse Events:Clinical Studies
Seizures :Convulsions were reported as an adverse event in three of 2068
(0.1%) sibutramine treated patients and in none of 884 placebo-treated
patients
in placebo-controlled premarketing obesity studies. Two of the three patients
with seizures had potentially predisposing factors (one had a prior history
of epilepsy; one had a subsequent diagnosis of brain tumor). The incidence
in all subjects who received sibutramine (three of 4,588 subjects) was
less than 0.1%.
Ecchymosis/Bleeding Disorders:Ecchymosis (bruising) was observed in 0.7%
of sibutramine treated patients and in 0.2% of placebo-treated patients
in pre-marketing placebo-controlled
obesity studies. One patient had prolonged bleeding of a small amount which
occurred during minor facial surgery. Sibutramine may have an effect on
platelet function due to its effect on serotonin uptake.
Interstitial Nephritis:Acute interstitial nephritis (confirmed by biopsy)
was reported in one obese patient receiving sibutramine during pre-marketing
studies. After
discontinuation of the medication, dialysis and oral corticosteroids were
administered; renal function normalized. The patient made a full recovery.
Altered Laboratory Findings:Abnormal liver function tests, including increases
in AST, ALT, GGT, LDH, alkaline phosphatase and bilirubin, were reported
as adverse events in
1.6% of sibutramine-treated obese patients in placebo-controlled trials
compared with 0.8% of placebo patients. In these studies, potentially clinically
significant values (total bilirubin = 2 mg/dL; ALT, AST, GGT, LDH, or alkaline
phosphatase = 3 × upper limit of normal) occurred in 0% (alkaline
phosphatase) to 0.6% (ALT) of the sibutramine treated patients and in none
of the placebo-treated patients. Abnormal values tended to be sporadic,
often diminished with continued treatment, and did not show a clear dose-response
relationship.
Postmarketing Reports
Voluntary reports of adverse events temporally associated with the use
of sibutramine are listed below. It is important to emphasize that although
these events occurred during treatment with sibutramine, they may have
no causal relationship with the drug. Obesity itself, concurrent disease
states/risk factors, or weight reduction may be associated with an increased
risk for some of these events.
Psychiatric
Cases of depression, suicidal ideation and suicide have been reported
rarely in patients on sibutramine treatment. However, a relationship has
not been established between the occurrence of depression and/or suicidal
ideation and the use of sibutramine. If depression occurs during treatment
with sibutramine, further evaluation may be necessary.
Hypersensitivity
Allergic hypersensitivity reactions ranging from mild skin eruptions and
urticaria to angioedema and anaphylaxis have been reported (see CONTRAINDICATIONS
and PRECAUTIONS-Information For Patients, and other reports of allergic
reactions listed below).
Other Postmarketing Reported Events:
Body as a Whole
anaphylactic shock, anaphylactoid reaction, chest pressure, chest tightness,
facial edema, limb pain, sudden unexplained death.
Cardiovascular System
angina pectoris, atrial fibrillation, congestive heart failure, heart
arrest, heart rate decreased, myocardial infarction, supraventricular tachycardia,
syncope, torsade de pointes, vascular headache, ventricular tachycardia,
ventricular extrasystoles, ventricular fibrillation.
Digestive System
cholecystitis, cholelithiasis, duodenal ulcer, eructation, gastrointestinal
hemorrhage, increased salivation, intestinal obstruction, mouth ulcer,
stomach ulcer, tongue edema.Endocrine System:goiter, hyperthyroidism, hypothyroidism.Hemic
and Lymphatic System :anemia, leukopenia, lymphadenopathy, petechiae, thrombocytopenia.Metabolic
and Nutritional :hyperglycemia, hypoglycemia.Musculoskeletal System:arthrosis,
bursitis.
abnormal dreams, abnormal gait, amnesia, anger, cerebrovascular accident,
concentration impaired, confusion, depression aggravated, Gilles de la
Tourette's syndrome, hypesthesia, libido decreased, libido increased, manic
reaction, mood changes, nightmares, serotonin syndrome, short term memory
loss, speech disorder, transient ischemic attack, tremor, twitch, vertigo.
Respiratory System :epistaxis, nasal congestion, respiratory disorder,
yawn.
Skin and Appendages:alopecia, dermatitis, photosensitivity
(skin), urticaria.
Special Senses :abnormal vision, blurred vision, dry eye, eye pain, increased
intraocular pressure, otitis externa, otitis media, photosensitivity (eyes),
tinnitus.
Urogenital System :abnormal ejaculation, hematuria, impotence, increased
urinary frequency, micturition difficulty, urinary retention.
Drug Abuse And Dependence
Controlled Substance
MERIDIA is controlled in Schedule IV of the Controlled Substances Act
(CSA).
Abuse and Physical and Psychological Dependence
Physicians should carefully evaluate patients for history of drug abuse
and follow such patients closely, observing them for signs of misuse or
abuse (e.g., drug development of tolerance, incrementation of doses, drug
seeking behavior).
Meridia sibutramine INTERACTIONS
CNS Active Drugs:
The use of MERIDIA in combination with other CNS-active drugs, particularly
serotonergic agents, has not been systematically evaluated. Consequently,
caution is advised if the concomitant administration of MERIDIA with other
centrally-acting drugs is indicated (see CONTRAINDICATIONS and WARNINGS).
In patients receiving monoamine oxidase inhibitors
(MAOIs) (e.g., phenelzine, selegiline) in combination with serotonergic
agents (e.g., fluoxetine,
fluvoxamine, paroxetine, sertraline, venlafaxine), there have been reports
of serious, sometimes fatal, reactions ("serotonin syndrome;" see
below). Because sibutramine inhibits serotonin reuptake, MERIDIA should
not be used concomitantly with a MAOI (see CONTRAINDICATIONS). At least
2 weeks should elapse between discontinuation of a MAOI and initiation
of treatment with MERIDIA. Similarly, at least 2 weeks should elapse between
discontinuation of MERIDIA and initiation of treatment with a MAOI.
The rare, but serious, constellation of symptoms termed "serotonin
syndrome" has also been reported with the concomitant use of selective
serotonin reuptake inhibitors and agents for migraine therapy, such as
Imitrex® (sumatriptan succinate) and dihydroergotamine, certain opioids,
such as dextromethorphan, meperidine, pentazocine and fentanyl, lithium,
or tryptophan. Serotonin syndrome has also been reported with the concomitant
use of two serotonin reuptake inhibitors. The syndrome requires immediate
medical attention and may include one or more of the following symptoms:
excitement, hypomania, restlessness, loss of consciousness, confusion,
disorientation, anxiety, agitation, motor weakness, myoclonus, tremor,
hemiballismus, hyperreflexia, ataxia, dysarthria, incoordination, hyperthermia,
shivering, pupillary dilation, diaphoresis, emesis, and tachycardia.
Because sibutramine inhibits serotonin reuptake, in general, it should
not be administered with other serotonergic agents such as those listed
above. However, if such a combination is clinically indicated, appropriate
observation of the patient is warranted.
Drugs That May Raise Blood Pressure and/or Heart Rate
Concomitant use of MERIDIA and other agents that may raise blood pressure
or heart rate have not been evaluated. These include certain decongestants,
cough, cold, and allergy medications that contain agents such as ephedrine,
or pseudoephedrine. Caution should be used when prescribing MERIDIA to
patients who use these medications.
Alcohol
In a double-blind, placebo-controlled, crossover study in 19 volunteers,
administration of a single dose of ethanol (0.5 mL/kg) together with 20
mg of sibutramine resulted in no psychomotor interactions of clinical significance
between alcohol and sibutramine. However, the concomitant use of MERIDIA
and excess alcohol is not recommended.
Oral Contraceptives
The suppression of ovulation by oral contraceptives was not inhibited
by sibutramine. In a crossover study, 12 healthy female volunteers on oral
steroid contraceptives received placebo in one period and 15 mg sibutramine
in another period over the course of 8 weeks. No clinically significant
systemic interaction was observed; therefore, no requirement for alternative
contraceptive precautions are needed when patients taking oral contraceptives
are concurrently prescribed sibutramine.
