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Anafranil (Clomipramine Hydrochloride) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Commonly Observed

The most commonly observed adverse events associated with the use of Anafranil and not seen at an equivalent incidence among placebo-treated patients were 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.

Leading to Discontinuation of Treatment

Approximately 20% of 3616 patients who received Anafranil in U.S. premarketing clinical trials discontinued treatment because of an adverse event. Approximately one-half of the patients who discontinued (9% of the total) had multiple complaints, none of which could be classified as primary. Where a primary reason for discontinuation could be identified, most patients discontinued because of nervous system complaints (5.4%), primarily somnolence. The second-most-frequent reason for discontinuation was digestive system complaints (1.3%), primarily vomiting and nausea.

There was no apparent relationship between the adverse events and elevated plasma drug concentrations.

Incidence in Controlled Clinical Trials

The following table enumerates adverse events that occurred at an incidence of 1% or greater among patients with OCD who received Anafranil in adult or pediatric placebo-controlled clinical trials. The frequencies were obtained from pooled data of clinical trials involving either adults receiving Anafranil (N=322) or placebo (N=319) or children treated with Anafranil (N=46) or placebo (N=44). The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice, in which patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, provide the physician with a basis for estimating the relative contribution of drug and nondrug factors to the incidence of side effects in the populations studied.

Incidence of Treatment-Emergent Adverse Experience in Placebo-Controlled Clinical Trials (Percentage of Patients Reporting Event)
 

*Events reported by at least 1% of Anafranil patients are included.

   Adults    Children and Adolescents
 Body System/
Adverse Event*
 Anafranil
(N=322)
 Placebo
(N=319)
   Anafranil
(N=46)
 Placebo
(N=44)
         
 Nervous System        
 Somnolence  54  16  46  11
 Tremor  54  2  33  2
 Dizziness  54  14  41  14
 Headache  52  41  28  34
 Insomnia  25  15  11  7
 Libido change  21  3  -  -
 Nervousness  18  2  4  2
 Myoclonus  13  -  2  -
 Increased appetite  11  2  -  2
 Paresthesia  9  3  2  2
 Memory impairment  9  1  7  2
 Anxiety  9  4  2  -
 Twitching  7  1  4  5
 Impaired concentration  5  2  -  -
 Depression  5  1  -  -
 Hypertonia  4  1  2  -
 Sleep disorder  4  -  9  5
 Psychosomatic disorder  3  -  -  -
 Yawning  3  -  -  -
 Confusion  3  -  2  -
 Speech disorder  3  -  -  -
 Abnormal dreaming  3  -  -  2
 Agitation  3  -  -  -
 Migraine  3  -  -  -
 Depersonalization  2  -  2  -
 Irritability  2  2  2  -
 Emotional lability  2  -  -  2
 Panic reaction  1  -  2  -
 Aggressive reaction  -  -  2  -
 Paresis  -  -  2  -
         
 Skin and Appendages        
 Increased sweating  29  3  9  -
 Rash  8  1  4  2
 Pruritus  6  -  2  2
 Dermatitis  2  -  -  2
 Acne  2  2  -  5
 Dry skin  2  -  -  5
 Urticaria  1  -  -  -
 Abnormal skin odor  -  -  2  -
         
 Digestive System        
 Dry mouth  84  17  63  16
 Constipation  47  11  22  9
 Nausea  33  14  9  11
 Dyspepsia  22  10  13  2
 Diarrhea  13  9  7  5
 Anorexia  12  -  22  2
 Abdominal pain  11  9  13  16
 Vomiting  7  2  7  -
 Flatulence  6  3  -  2
 Tooth disorder  5  -  -  -
 Gastrointestinal disorder  2  -  -  2
 Dysphagia  2  -  -  -
 Esophagitis  1  -  -  -
 Eructation  -  -  2  2
 Ulcerative stomatitis  -  -  2  -
         
 Body as a Whole        
 Fatigue  39  18  35  9
 Weight increase  18  1  2  -
 Flushing  8  -  7  -
 Hot flushes  5  -  2  -
 Chest pain  4  4  7  -
 Fever  4  -  2  7
 Allergy  3  3  7  5
 Pain  3  2  4  2
 Local edema  2  4  -  -
 Chills  2  1  -  -
 Weight decrease  -  -  7  -
 Otitis media  -  -  4  5
 Asthenia  -  -  2  -
 Halitosis  -  -  2  -
         
 Cardiovascular System        
 Postural hypotension  6  -  4  -
 Palpitation  4  2  4  -
 Tachycardia  4  -  2  -
 Syncope  -  -  2  -
         
 Respiratory System        
 Pharyngitis  14  9  -  5
 Rhinitis  12  10  7  9
 Sinusitis  6  4  2  5
 Coughing  6  6  4  5
 Bronchospasm  2  -  7  2
 Epistaxis  2  -  -  2
 Dyspnea  -  -  2  -
 Laryngitis  -  1  2  -
         
 Urogenital System        
  Male and Female Patients Combined      
 Micturition disorder  14  2  4  2
 Urinary tract infection  6  1  -  -
 Micturition frequency  5  3  -  -
 Urinary retention  2  -  7  -
 Dysuria  2  2  -  -
 Cystitis  2  -  -  -
  Female Patients Only  (N=182)  (N=167)  (N=10)  (N=21)
 Dysmenorrhea  12  14  10  10
 Lactation (nonpuerperal)  4  -  -  -
 Menstrual disorder  4  2  -  -
 Vaginitis  2  -  -  -
 Leukorrhea  2  -  -  -
 Breast enlargement  2  -  -  -
 Breast pain  1  -  -  -
 Amenorrhea  1  -  -  -
  Male Patients Only  (N=140)  (N=152)  (N=36)  (N=23)
 Ejaculation failure  42  2  6  -
 Impotence  20  3  -  -
         
 Special Senses        
 Abnormal vision  18  4  7  2
 Taste perversion  8  -  4  -
 Tinnitus  6  -  4  -
 Abnormal lacrimation  3  2  -  -
 Mydriasis  2  -  -  -
 Conjunctivitis  1  -  -  -
 Anisocoria  -  -  2  -
 Blepharospasm  -  -  2  -
 Ocular allergy  -  -  2  -
 Vestibular disorder  -  -  2  2
         
 Musculoskeletal        
 Myalgia  13  9  -  -
 Back pain  6  6  -  -
 Arthralgia  3  5  -  -
 Muscle weakness  1  -  2  -
         
 Hemic and Lymphatic        
 Purpura  3  -  -  -
 Anemia  -  -  2  2
         
 Metabolic and Nutritional        
 Thirst  2  2  -  2
         

Other Events Observed During the Premarketing Evaluation of Anafranil

During clinical testing in the U.S., multiple doses of Anafranil were administered to approximately 3600 subjects. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.

In the tabulations that follow, a modified World Health Organization dictionary of terminology has been used to classify reported adverse events. The frequencies presented, therefore, represent the proportion of the 3525 individuals exposed to Anafranil who experienced an event of the type cited on at least one occasion while receiving Anafranil. All events are included except those already listed in the previous table, those reported in terms so general as to be uninformative, and those in which an association with the drug was remote. It is important to emphasize that although the events reported occurred during treatment with Anafranil, they were not necessarily caused by it.

Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in less than 1/1000 patients.

Body as a Whole Infrequent - general edema, increased susceptibility to infection, malaise. Rare - dependent edema, withdrawal syndrome.

Cardiovascular System Infrequent - abnormal ECG, arrhythmia, bradycardia, cardiac arrest, extrasystoles, pallor. Rare - aneurysm, atrial flutter, bundle branch block, cardiac failure, cerebral hemorrhage, heart block, myocardial infarction, myocardial ischemia, peripheral ischemia, thrombophlebitis, vasospasm, ventricular tachycardia.

Digestive System Infrequent - abnormal hepatic function, blood in stool, colitis, duodenitis, gastric ulcer, gastritis, gastroesophageal reflux, gingivitis, glossitis, hemorrhoids, hepatitis, increased saliva, irritable bowel syndrome, peptic ulcer, rectal hemorrhage, tongue ulceration, tooth caries. Rare - cheilitis, chronic enteritis, discolored feces, gastric dilatation, gingival bleeding, hiccup, intestinal obstruction, oral/pharyngeal edema, paralytic ileus, salivary gland enlargement.

Endocrine System Infrequent - hypothyroidism. Rare - goiter, gynecomastia, hyperthyroidism.

Hemic and Lymphatic System Infrequent - lymphadenopathy. Rare - leukemoid reaction, lymphoma-like disorder, marrow depression.

Metabolic and Nutritional Disorder Infrequent - dehydration, diabetes mellitus, gout, hypercholesterolemia, hyperglycemia, hyperuricemia, hypokalemia. Rare - fat intolerance, glycosuria.

Musculoskeletal System Infrequent - arthrosis. Rare - dystonia, exostosis, lupus erythematosus rash, bruising, myopathy, myositis, polyarteritis nodosa, torticollis.

Nervous System Frequent - abnormal thinking, vertigo. Infrequent - abnormal coordination, abnormal EEG, abnormal gait, apathy, ataxia, coma, convulsions, delirium, delusion, dyskinesia, dysphonia, encephalopathy, euphoria, extrapyramidal disorder, hallucinations, hostility, hyperkinesia, hypnagogic hallucinations, hypokinesia, leg cramps, manic reaction, neuralgia, paranoia, phobic disorder, psychosis, sensory disturbance, somnambulism, stimulation, suicidal ideation, suicide attempt, teeth-grinding. Rare - anticholinergic syndrome, aphasia, apraxia, catalepsy, cholinergic syndrome, choreoathetosis, generalized spasm, hemiparesis, hyperesthesia, hyperreflexia, hypoesthesia, illusion, impaired impulse control, indecisiveness, mutism, neuropathy, nystagmus, oculogyric crisis, oculomotor nerve paralysis, schizophrenic reaction, stupor, suicide.

Respiratory System Infrequent - bronchitis, hyperventilation, increased sputum, pneumonia. Rare - cyanosis, hemoptysis, hypoventilation, laryngismus.

Skin and Appendages Infrequent - alopecia, cellulitis, cyst, eczema, erythematous rash, genital pruritus, maculopapular rash, photosensitivity reaction, psoriasis, pustular rash, skin discoloration. Rare - chloasma, folliculitis, hypertrichosis, piloerection, seborrhea, skin hypertrophy, skin ulceration.

Special Senses Infrequent - abnormal accommodation, deafness, diplopia, earache, eye pain, foreign body sensation, hyperacusis, parosmia, photophobia, scleritis, taste loss. Rare - blepharitis, chromatopsia, conjunctival hemorrhage, exophthalmos, glaucoma, keratitis, labyrinth disorder, night blindness, retinal disorder, strabismus, visual field defect.

Urogenital System Infrequent - endometriosis, epididymitis, hematuria, nocturia, oliguria, ovarian cyst, perineal pain, polyuria, prostatic disorder, renal calculus, renal pain, urethral disorder, urinary incontinence, uterine hemorrhage, vaginal hemorrhage. Rare - albuminuria, anorgasmy, breast engorgement, breast fibroadenosis, cervical dysplasia, endometrial hyperplasia, premature ejaculation, pyelonephritis, pyuria, renal cyst, uterine inflammation, vulvar disorder.

Postmarketing Experience

The following adverse drug reaction has been reported during post-approval use of Anafranil. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate frequency.

Eye Disorders – angle-closure glaucoma. 



REPORTS OF SUSPECTED ANAFRANIL SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Anafranil. The information is not vetted and should not be considered as verified clinical evidence.

Possible Anafranil side effects / adverse reactions in 66 year old female

Reported by a physician from Italy on 2011-10-10

Patient: 66 year old female

Reactions: Multiple Drug Overdose Intentional, Self Injurious Behaviour, Sopor

Suspect drug(s):
Anafranil
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-10-02
    End date: 2011-10-02

Flurazepam HCL
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-10-02
    End date: 2011-10-02

Haldol
    Dosage: 3 bottles of 0.2%
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2011-10-02
    End date: 2011-10-02



Possible Anafranil side effects / adverse reactions in 29 year old female

Reported by a pharmacist from Japan on 2011-10-18

Patient: 29 year old female

Reactions: Loss of Consciousness

Suspect drug(s):
Alprazolam

Anafranil

Dogmatyl

Zolpidem
    Administration route: Oral



Possible Anafranil side effects / adverse reactions in 22 year old male

Reported by a health professional (non-physician/pharmacist) from Italy on 2011-11-08

Patient: 22 year old male

Reactions: Vomiting, Multiple Drug Overdose Intentional, Sopor, Sluggishness

Suspect drug(s):
Alcohol
    Indication: Self Injurious Behaviour

Alprazolam
    Dosage: 5 tablets of alprazolam (tablets, 0.25 mg
    Administration route: Oral
    Indication: Self Injurious Behaviour

Anafranil
    Dosage: 5 tablets of clomipramine hydrochloride (tablets, 25 mg)
    Administration route: Oral
    Indication: Self Injurious Behaviour

Haldol
    Dosage: 0.2%
    Administration route: Oral
    Indication: Self Injurious Behaviour

Levobren
    Dosage: 10 tablets of levosulpiride (tablets, 25 mg),
    Administration route: Oral
    Indication: Self Injurious Behaviour



See index of all Anafranil side effect reports >>

Drug label data at the top of this Page last updated: 2014-06-30

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