Lithium Carbonate

INDICATIONS AND USAGE Lithium carbonate extended-release tablets are indicated in the treatment of manic episodes of Bipolar Disorder. Bipolar Disorder, Manic (DSM-IV) is equivalent to Manic Depressive illness, Manic, in the older DSM-II terminology. Lithium carbonate extended-release tablets are also indicated as a maintenance treatment for individuals with a diagnosis of Bipolar Disorder. Maintenance therapy reduces the frequency of manic episodes and diminishes the intensity of those episodes which may occur. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, elation, poor judgment, aggressiveness, and possibly hostility. When given to a patient experiencing a manic episode, lithium may produce a normalization of symptomatology within 1 to 3 weeks.

DOSAGE AND ADMINISTRATION Acute Mania Optimal patient response can usually be established with 1,800 mg/day in the following dosages: 1 Can also be administered on 600 mg TID recommended dosing interval. ACUTE MANIA Morning Afternoon Nighttime Lithium Carbonate 3 tablets 3 tablets Extended-Release Tablets 1 (900 mg) (900 mg) Such doses will normally produce an effective serum lithium concentration ranging between 1.0 and 1.5 mEq/L. Dosage must be individualized according to serum concentrations and clinical response. Regular monitoring of the patient's clinical state and of serum lithium concentrations is necessary. Serum concentrations should be determined twice per week during the acute phase, and until the serum concentrations and clinical condition of the patient have been stabilized. Long-Term Control Desirable serum lithium concentrations are 0.6 to 1.2 mEq/L which can usually be achieved with 900 to 1,200 mg/day. Dosage will vary from one individual to another, but generally the following dosages will maintain this concentration: 1 Can be administered on TID recommended dosing interval up to 1,200 mg/day. LONG-TERM CONTROL Morning Afternoon Nighttime Lithium Carbonate 2 tablets 2 tablets Extended-Release Tablets 1 (600 mg) (600 mg) Serum lithium concentrations in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every two months. Patients abnormally sensitive to lithium may exhibit toxic signs at serum concentrations of 1.0 to 1.5 mEq/L. Geriatric patients often respond to reduced dosage, and may exhibit signs of toxicity at serum concentrations ordinarily tolerated by other patients. In general, 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. Important Considerations Blood samples for serum lithium determinations should be drawn immediately prior to the next dose when lithium concentrations are relatively stable (i.e., 8 to 12 hours after previous dose). Total reliance must not be placed on serum concentrations alone. Accurate patient evaluation requires both clinical and laboratory analysis. Lithium carbonate extended-release tablets must be swallowed whole and never chewed or crushed.

ADVERSE REACTIONS The occurrence and severity of adverse reactions are generally directly related to serum lithium concentrations and to individual patient sensitivity to lithium. They generally occur more frequently and with greater severity at higher concentrations. Adverse reactions may be encountered at serum lithium concentrations below 1.5 mEq/L. Mild to moderate adverse reactions may occur at concentrations from 1.5 to 2.5 mEq/L, and moderate to severe reactions may be seen at concentrations from 2.0 mEq/L and above. Fine hand tremor, polyuria, and mild thirst may occur during initial therapy for the acute manic phase and may persist throughout treatment. Transient and mild nausea and general discomfort may also appear during the first few days of lithium administration. These side effects usually subside with continued treatment or with a temporary reduction or cessation of dosage. If persistent, a cessation of lithium therapy may be required. Diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination may be early signs of lithium intoxication, and can occur at lithium concentrations below 2.0 mEq/L. At higher concentrations, giddiness, ataxia, blurred vision, tinnitus, and a large output of dilute urine may be seen. Serum lithium concentrations above 3.0 mEq/L may produce a complex clinical picture involving multiple organs and organ systems. Serum lithium concentrations should not be permitted to exceed 2.0 mEq/L during the acute treatment phase. The following reactions have been reported and appear to be related to serum lithium concentrations, including concentrations within the therapeutic range: Central Nervous System : tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreoathetotic movements, hyperactive deep tendon reflex, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes. Cardiovascular: cardiac arrhythmia, hypotension, peripheral circulatory collapse, bradycardia, sinus node dysfunction with severe bradycardia (which may result in syncope), Unmasking of Brugada Syndrome (see WARNINGS and PATIENT COUNSELING INFORMATION ). Gastrointestinal : anorexia, nausea, vomiting, diarrhea, gastritis, salivary gland swelling, abdominal pain, excessive salivation, flatulence, indigestion. Genitourinary : glycosuria, decreased creatinine clearance, albuminuria, oliguria, and symptoms of nephrogenic diabetes insipidus including polyuria, thirst and polydipsia. Dermatologic : drying and thinning of hair, alopecia, anesthesia of skin, acne, chronic folliculitis, xerosis cutis, psoriasis or its exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS). Autonomic Nervous System : blurred vision, dry mouth, impotence/sexual dysfunction. Thyroid Abnormalities : euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T3 and T4. 131 Iodine uptake may be elevated (see PRECAUTIONS ). Paradoxically, rare cases of hyperthyroidism have been reported. EEG Changes : diffuse slowing, widening of frequency spectrum, potentiation and disorganization of background rhythm. EKG Changes : reversible flattening, isoelectricity or inversion of T-waves. Miscellaneous : fatigue, lethargy, transient scotomata, exophthalmos, dehydration, weight loss, leucocytosis, headache, transient hyperglycemia, hypercalcemia, hyperparathyroidism, albuminuria, excessive weight gain, edematous swelling of ankles or wrists, metallic taste, dysgeusia/taste distortion, salty taste, thirst, swollen lips, …

Drug Interactions Diuretic-, ACE-, and ARB-induced sodium loss may increase serum lithium concentrations. Start with lower doses of lithium or reduce dosage, while frequently monitoring serum lithium concentrations and signs of lithium toxicity. See WARNINGS for additional caution information. Concomitant administration of lithium with serotonergic drugs can precipitate serotonin syndrome. Monitor patients for signs and symptoms of serotonin syndrome, particularly during lithium initiation. If serotonin syndrome occurs, consider discontinuation of lithium and/or concomitant serotonergic drugs. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), and monoamine oxidase inhibitors (MAOI). Concomitant administration of methyldopa, phenytoin, or carbamazepine with lithium may increase the risk of adverse reactions with these drugs. The following drugs can lower serum lithium concentrations by increasing urinary lithium excretion: acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate. Concomitant extended use of iodide preparations, especially potassium iodide, with lithium may produce hypothyroidism. Concurrent use of calcium channel blocking agents with lithium may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus. Concurrent use of metronidazole with lithium may provoke lithium toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely. Concurrent use of fluoxetine with lithium has resulted in both increased and decreased serum lithium concentrations. Patients receiving such combined therapy should be monitored closely. Nonsteroidal anti-inflammatory drugs (NSAIDs): Lithium levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, lithium toxicity has resulted from interactions between a NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly steady-state plasma lithium concentrations. There is also evidence that other nonsteroidal anti-inflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg BID with celecoxib 200 mg BID as compared to subjects receiving lithium alone. Concomitant use of lithium with a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor may decrease serum lithium concentrations. Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. Lithium may impair mental and/or physical abilities. Patients should be cautioned about activities requiring alertness (e.g., operating vehicles or machinery).

DESCRIPTION Lithium carbonate extended-release tablets contain lithium carbonate, a white odorless alkaline powder with molecular formula Li 2 CO 3 and molecular weight 73.89. Lithium is an element of the alkali-metal group with atomic number 3, atomic weight 6.94, and an emission line at 671 nm on the flame photometer. Each beige-colored, film-coated, extended-release tablet contains 300 mg of lithium carbonate. This slowly dissolving film-coated tablet is designed to give lower serum lithium peak concentrations than obtained with conventional oral lithium dosage forms. Inactive ingredients consist of calcium stearate, FD&C Blue No. 2 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, hypromellose, polydextrose, polyethylene glycol, povidone, sodium chloride, sodium lauryl sulfate, sodium starch glycolate, sorbitol, titanium dioxide and triacetin. Meets USP Dissolution Test 4.

OVERDOSAGE The toxic concentrations for lithium (≥ 1.5 mEq/L) are close to the therapeutic concentrations. It is therefore important that patients and their families be cautioned to watch for early toxic symptoms and to discontinue the drug and inform the physician should they occur (see WARNINGS: Lithium Toxicity ). Treatment No specific antidote for lithium poisoning is known. Treatment is supportive. Early symptoms of lithium toxicity can usually be treated by reduction or cessation of dosage of the drug and resumption of the treatment at a lower dose after 24 to 48 hours. In severe cases of lithium poisoning, the first and foremost goal of treatment consists of elimination of this ion from the patient. Treatment is essentially the same as that used in barbiturate poisoning: 1) gastric lavage, 2) correction of fluid and electrolyte imbalance and, 3) regulation of kidney functioning. Urea, mannitol, and aminophylline all produce significant increases in lithium excretion. Hemodialysis is an effective and rapid means of removing the ion from the severely toxic patient. However, patient recovery may be slow. Infection prophylaxis, regular chest X-rays, and preservation of adequate respiration are essential.

HOW SUPPLIED Lithium Carbonate Extended-Release Tablets, USP 300 mg, are supplied as light pink to pink colored circular, biconvex, coated tablets debossed with ‘223’ on one side and plain on the other side. Bottle of 100 with child-resistant closure NDC 68462-223-01 Storage Conditions Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30° C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from moisture and store in a dry place. Keep tablets in original/pharmacy container. Dispense in a tight, child-resistant container (USP). Manufactured by: Glenmark Pharmaceuticals Limited Colvale-Bardez, Goa 403513, India Manufactured for: Glenmark Pharmaceuticals Inc., USA Mahwah, NJ 07430 Questions? 1 (888) 721-7115 www.glenmarkpharma-us.com October 2022