Side Effects of Meridia (sibutramine)

Meridia (sibutramine) is an appetite suppressant used to manage obesity, including weight loss and maintenance of weight loss, and is used in conjunction with a reduced calorie diet.

Meridia is recommended for obese patients with an initial body mass index 30 kg/m2 or greater, or 27 kg/m2 or greater in the presence of other risk factors (e.g., diabetes, dyslipidemia, controlled hypertension). Meridia is no longer available in the U.S. because of the risk of serious cardiovascular problems in some people who take it.

Common side effects of Meridia include:

• constipation,
• inability to sleep,
• headache,
• dry mouth,
• abdominal pain,
• acne,
• rash,
• chest pain,
• anxiety,
• joint pain,
• back pain,
• excitation,
• sweating,
• dizziness,
• drowsiness,
• changes in taste,
• irregular or painful menstrual periods,
• flu-like syndrome,
• increased cough,
• muscle pain,
• nausea,
• vomiting,
• neck pain,
• nervousness,
• palpitations,
• tingling of the extremities,
• sore throat,
• sinus congestion, and
• abnormal liver tests.

Serious side effects of Meridia include:

• serious cardiovascular problems,
• substantial increases in blood pressure (hypertension),
• depression,
• psychosis,
• mania,
• suicidal thoughts and suicide.

Drug interactions of Meridia include the following, which can result in decreased conversion and effectiveness of Meridia:

• ketoconazole,
• cimetidine,
• erythromycin,
• clarithromycin,
• danazol,
• diltiazem,
• fluconazole,
• fluoxetine,
• itraconazole,
• propoxyphene,
• troleandomycin, and
• verapamil.

Meridia should not be used with monoamine oxidase inhibitors (MAOIs), and there should be at least a 2-week interval between stopping MAO inhibitors and starting Meridia due to the risk of serotonin syndrome. Similarly, there should be at least a 2-week interval after stopping Meridia and starting an MAOI.

Serotonin syndrome may also occur if Meridia is taken at the same time as medications used for migraines such as

• sumatriptan,
• zolmitriptan,
• dihydroergotamine (DHE),
• dextromethorphan (found in many cough medications such as Robitussin-DM),
• meperidine,
• pentazocine,
• fentanyl, or
• lithium.

No adequate studies with Meridia have been done in pregnant women. The use of Meridia during pregnancy, therefore, is not recommended. Women who could become pregnant should use adequate contraception while taking Meridia.

It is unknown if Meridia or its active products accumulate in breast milk. Meridia, therefore, is not recommended for use while breastfeeding.

WARNING

Sibutramine substantially increases blood pressure and/or pulse rate in some patients. Regular monitoring of blood pressure and pulse rate is required when prescribing sibutramine.

• 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.
• Blood pressure and pulse should be measured prior to starting therapy with sibutramine and should be monitored at regular intervals thereafter.
• For patients who experience a sustained increase in blood pressure or pulse rate while receiving sibutramine, either dose reduction or discontinuation should be considered.
• Meridia should be given with caution to those patients with a history of hypertension, and should not be given to patients with uncontrolled or poorly controlled hypertension.

Common side effects

In general, sibutramine is well-tolerated. The most common side effects have been:

• constipation,
• inability to sleep,
• headache,
• dry mouth,
• abdominal pain,
• acne,
• rash,
• chest pain,
• anxiety,
• joint pain,
• back pain,
• excitation,
• depression,
• sweating,
• dizziness,
• drowsiness,
• changes in taste,
• irregular or painful menstrual periods,
• flu-like syndrome,
• increased cough,
• muscle pain,
• nausea,
• vomiting,
• neck pain,
• nervousness,
• palpitations,
• tingling of the extremities,
• sore throat, and
• sinus congestion.

Abnormal liver tests have been reported in 1 in 60 persons who receive sibutramine.

Other important side effects include:

• depression,
• psychosis,
• mania,
• suicidal thoughts and
• suicide

However, it has not been established that sibutramine caused these events. If any of these events occur during treatment, sibutramine probably should be discontinued.

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

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.

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).

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.
• 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.
• 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 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 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.