IMPORTANT RISK INFORMATION
Suicidality and Antidepressant Drugs
Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of clomipramine hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Clomipramine hydrochloride is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD).
Anafranil is contraindicated:
- in patients with hypersensitivity to Anafranil or other tricyclic antidepressants.
- within 14 days of stopping an MAOI intended to treat psychiatric disorders. The use of MAOIs intended to treat psychiatric disorders with Anafranil or within 14 days of stopping treatment with Anafranil is also contraindicated because of an increased risk of serotonin syndrome.
- in patients who are being treated with linezolid or intravenous methylene blue because of an increased risk or serotonin syndrome.
- during the acute recovery period after a myocardial infarction.
WARNINGS and PRECAUTIONS
- All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
- Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers.
- Prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder.
- The development of serotonin syndrome has been reported with use of serotonin/norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs), including Anafranil, alone but particularly with concomitant use of other serotonergic drugs (triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, busiprone, and St. John's Wort) or medications that impair metabolism of serotonin (e.g. MAOIs, including linezolid and intravenous methylene blue).
- Seizures are a significant risk with use of Anafranil. Caution should be used in patents with a history of seizures or other predisposing factors e.g., brain damage, alcoholism, and other medications that may lower the seizure threshold.
- Physicians should discuss with patients the risk of taking Anafranil while engaging in activities in which sudden loss of consciousness could result in serious injury to the patient or others, e.g., the operation of complex machinery, driving, swimming, and climbing.
- Since depression is a commonly associated feature of OCD, the risk of suicide must be considered. Prescriptions for Anafranil should be written for the smallest quantity of capsules consistent with good patient management, in order to reduce the risk of overdose. Cardiovascular effects include modest orthostatic decreases in blood pressure and modest tachycardia (approximately 20% of patients). ECG abnormalities can be seen but were rarely associated with clinical symptoms.
- A variety of neuropsychiatric signs and symptoms including delusions, hallucinations, psychotic episodes, confusion, and paranoia have been reported in patients treated with Anafranil.
- Anafranil may precipitate an acute psychotic episode in patients with unrecognized schizophrenia.
- Precipitation of hypomania and mania has been reported in patients receiving Anafranil for the treatment of affective disorders. Activation of mania or hypomania has been reported in a small proportion of patients receiving other tricyclic antidepressants.
- Anafranil can be associated with elevations in SGOT and SGPT (1-3% respectively) of potential clinical importance. Most were not associated with other clinical findings for hepatic injury. Rare reports of more severe liver injury, some fatal, have been recorded in foreign postmarketing experience.
- Leukopenia, agranulocytosis, thrombocytopenia, anemia and pancytopenia have been reported with the use of Anafranil.
- Hyperthermia has been reported in patients receiving Anafranil. Most cases were in combination with other drugs, including neuroleptic agents.
- Sexual dysfunction, including ejaculatory failure and impotence, is common in males.
- Increases and decreases in weight can occur with use of Anafranil.
- Concurrent administration of Anafranil with electroconvulsive therapy may increase the risks.
- Prior to elective surgery with general anesthetics, therapy with Anafranil should be discontinued for as long as is clinically feasible, and the anesthetist should be advised.
- Caution use in patients with the following concomitant Illnesses:
- hyperthyroidism or patients on hyperthyroid medications due to possible cardiac toxicity.
- increased intraocular pressure, history of narrow-angle glaucoma or urinary retention due to anticholinergic properties of Anafranil.
- tumors of the adrenal medulla (e.g. pheochromocytoma, neuroblastoma) in whom the drug may provoke hypertensive crises.
- significant renal impairment.
- Withdrawal symptoms have been reported in association with abrupt discontinuation of Anafranil. It is recommended that the dosage be tapered gradually and the patient monitored carefully during discontinuation.
- Anafranil may exaggerate the effects of alcohol, barbiturates, or other CNS depressants.
- Deaths may occur from overdosage with this class of drugs.
- Serious adverse reactions may include clinical worsening of depression and suicidal ideation; seizures; serotonin syndrome; neuropsychiatric signs and symptoms including delusions, hallucinations, psychotic episodes, confusion, and paranoia; precipitation of mania or hypomania; severe liver injury; hematologic changes including leukopenia, agranulocytosis, thrombocytopenia, anemia, and pancytopenia; and hyperthermia.
- Common adverse reactions include gastrointestinal complaints, including dry mouth, constipation, nausea, dyspepsia, and anorexia; nervous system complaints, including somnolence, tremor, dizziness, nervousness, and myoclonus; genitourinary complaints, including changed libido, ejaculatory failure, impotence, and micturition disorder; and other miscellaneous complaints, including fatigue, sweating, increased appetite, weight gain, and visual changes.
USE IN SPECIFIC POPULATIONS
- Safety and effectiveness in the pediatric population other than pediatric patients with OCD have not been established.
- Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Ivory Body/Aqua-Blue Capsule
Clomipramine hydrochloride capsules
Ivory body imprinted in black with "M" in a box and aqua blue cap imprinted in black with "ANAFRANIL 50 mg"
For additional information on Anafranil™ (clomipramine hydrochloride) Capsules, USP 50 mg, call Customer Service at 1.800.325.8888 or Medical Information at 1.800.778.7898.