SELECTIVE SEROTONIN REUPTAKE INHIBITOR

COMPOSITION
GIGGLE 10 mg
Each film coated tablet contains citalopram (as hydrobromide) USP 10mg
GIGGLE 20 mg
Each film coated tablet contains citalopram (as hydrobromide) USP 20mg

DRUG DESCRIPTION
Giggle (citalopram HBr) is an orally administered selective serotonin reuptake inhibitor (SSRI) with a chemical structure unrelated to that of other SSRIs or of tricyclic, tetracyclic, or other available antidepressant agents. Citalopram HBr is a racemic bicyclic phthalane derivative designated (±)-1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile, HBr with the following structural formula:

The molecular formula is C20H22BrFN2O and its molecular weight is 405.35.
Citalopram HBr occurs as a fine, white to off-white powder. Citalopram HBr is sparingly soluble in water and soluble in ethanol.
Giggle (citalopram hydrobromide) is available as tablets

INDICATIONS
Giggle (citalopram HBr) is indicated for the treatment of depression.

DOSAGE AND ADMINISTRATION
Initial Treatment
Giggle (citalopram HBr) should be administered at an initial dose of 20 mg once daily, generally with an increase to a dose of 40 mg/day. Dose increases should usually occur in increments of 20 mg at intervals of no less than one week.Giggle should be administered once daily, in the morning or evening, with or without food.

Special Populations
20 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment, with titration to 40 mg/day only for nonresponding patients.

No dosage adjustment is necessary for patients with mild or moderate renal impairment. Giggle should be used with caution in patients with severe renal impairment.

Treatment of Pregnant Women During the Third Trimester
Neonates exposed to Giggle and other SSRIs or SNRIs, late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. When treating pregnant women with Giggle during the third trimester, the physician should carefully consider the potential risks and benefits of treatment.

Maintenance Treatment
It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacologic therapy.

ADVERSE REACTIONS
The only commonly observed adverse event that occurred in Giggle patients with an incidence of 5% or greater and at least twice the incidence in placebo patients was Ejaculation disorder (primarily ejaculatory delay) in male patients.

BODY SYSTEM ADVERSE EVENTS
Autonomic Nervous System Disorders : Dry Mouth, Sweating Increased.
Central & Peripheral Nervous System Disorders : Tremor.
Gastrointestinal Disorders : Nausea, Diarrhea, Dyspepsia, Vomiting, Abdominal Pain.
Cardiovascular : Tachycardia, Postural hypotension.
Skin and Appendages Disorders : Rash, Pruritus.
General : Fatigue, Fever.
Musculoskeletal System Disorders : Arthralgia, Myalgia.
Psychiatric Disorders : Somnolence,Insomnia, Anxiety, Anorexia, Agitation, Dysmenorrhea.
Respiratory System Disorders : Upper Respiratory Tract Infection,Rhinitis, Sinusitis
Urogenital : Ejaculation Disorder, Impotence.
Endocrine Disorders : Hypothyroidism, goiter, gynecomastia.

DRUG INTERACTIONS
Based on the mechanism of action of SNRIs and SSRIs including Giggle, and the potential for serotonin syndrome, caution is advised when Giggle is coadministered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol. The concomitant use of Giggle with other SSRIs, SNRIs or trytophan is not recommended.

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

WARNINGS
Clinical Worsening and Suicide Risk : Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their Depression, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs.

PRECAUTIONS
Discontinuation of Treatment with Giggle : There have been spontaneous reports of adverse events occurring upon discontinuation of Giggle, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizzines , sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, insomnia, and hypomania. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered.
Risk of bleeding : Patients should be cautioned about the concomitant use of Giggle and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding.

Use during pregnancy and lactation : There are no adequate and well-controlled studies in pregnant women; therefore Giggle, should be used with caution during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is categorized as pregnancy category C. Information on the excretion of Giggle in the breast milk exist but is insufficient for assessment of the risk of child. Hence, caution should be recommended.
Clinical Worsening and Suicide Risk : Patients should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring.

OVERDOSE
•Symptoms most often accompanying citalopram overdose, alone or in combination with other drugs and/or alcohol, included dizziness, sweating, nausea, vomiting, tremor, somnolence, and sinus tachycardia. In more rare cases, observed symptoms included amnesia, confusion, coma, convulsions, hyperventilation, cyanosis, , and ECG changes (including QTC prolongation, nodal rhythm, ventricular arrhythmia),rhabdomyolysis. Acute renal failure has been very rarely reported accompanying overdose.

Management of Overdose
Establish and maintain an airway to ensure adequate ventilation and oxygenation. Gastric evacuation by lavage and use of activated charcoal should be considered. Careful observation and cardiac and vital sign monitoring are recommended, along with general symptomatic and supportive care. Due to the large volume of distribution of citalopram, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. There are no specific antidotes for Giggle.

CONTRAINDICATIONS
Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated.Concomitant use in patients taking pimozide is contraindicated.
Giggle (citalopram hydrobromide) is contraindicated in patients with a hypersensitivity to citalopram or any of the inactive ingredients in Giggle.

CLINICAL PHARMACOLOGY

• Pharmacodynamics
The mechanism of action of citalopram HBr as an antidepressant is presumed to be linked to potentiation of serotonergic activity in the central nervous system (•CNS) resulting from its inhibition of CNS neuronal reuptarke of serotonin (5-HT). Citalopram has no or very low affinity for 5-HT1A, 5-HT2A, dopamine D1 and D2, á1-, á2-, and â-adrenergic, histamine H1, gamma aminobutyric acid (GABA), muscarinic cholinergic, and benzodiazepine receptors.

Pharmacokinetics
The single- and multiple-dose pharmacokinetics of citalopram are linear and dose-proportional in a dose range of 10-60 mg/day. Biotransformation of citalopram is mainly Hepatic , with a mean terminal half-life of about 35 hours.
Absorption and Distribution : Following a single oral dose (40 mg tablet) of citalopram, peak blood levels occur at about 4 hours. The absolute bioavailability of citalopram was about 80% relative to dose, and absorption is not affected by food. The volume of distribution of citalopram is about 12 L/kg and the binding of citalopram (CT), demethylcitalopram (DCT) and didemethylcitalopram (DDCT) to human plasma is about 80%.
Metabolism and Elimination : Citalopram is metabolized to demethylcitalopram (DCT), didemethylcitalopram (DDCT), citalopram-N-oxide, and a deaminated propionic acid derivative. In humans, unchanged citalopram is the predominant compound in plasma. At steady state, the concentrations of citalopram's metabolites, DCT and DDCT, in plasma are approximately one-half and one-tenth, respectively, that of the parent drug.

Population Subgroups
Age - Citalopram pharmacokinetics in subjects 60 years of age were compared to younger subjects in two normal volunteer studies. In a single-dose study, citalopram AUC and half-life were increased in the elderly subjects by 30% and 50%, respectively, whereas in a multiple-dose study they were increased by 23% and 30%, respectively. 20 mg is the recommended dose for most elderly patients.
Gender - In clinical studies, no differences in steady state serum citalopram levels were seen between men and women. There were no gender differences in the pharmacokinetics of DCT and DDCT. No adjustment of dosage on the basis of gender is recommended.
Reduced hepatic function - Citalopram oral clearance was reduced by 37% and half-life was doubled in patients with reduced hepatic function compared to normal subjects. 20 mg is the recommended dose for most hepatically impaired patients.
Reduced renal function - In patients with mild to moderate renal function impairment, oral clearance of citalopram was reduced by 17% compared to normal subjects. No adjustment of dosage for such patients is recommended. No information is available about the pharmacokinetics of citalopram in patients with severely reduced renal function ( creatinine clearance < 20 mL/min).

STORAGE
Store at controlled room temperature below 300C.

HOW SUPPLIED
Giggle 10mg is supplied in pack of 14 tablets.
Giggle 20mg is supplied in pack of 14 tablets.