Verenigde Staten - Engels - NLM (National Library of Medicine)
LITHIUM CARBONATE- lithium carbonate capsule
Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to
therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be
available before initiating therapy. (see DOSAGE AND ADMINISTRATION).
Each capsule for oral administration contains 150 mg, 300 mg or 600 mg of lithium carbonate. In
addition, each capsule contains the following inactive ingredient:
150 mg: Talc.
300 mg: Talc.
600 mg: Colloidal Silicon Dioxide, Stearic Acid and Talc.
Capsule shell for the 150 mg potency contains: Gelatin and Titanium Dioxide.
Capsule shell for the 300 mg potency contains: D&C Yellow #10, FD&C Green #3, FD&C Red #40,
FD&C Yellow #6, Gelatin and Titanium Dioxide.
Capsule shell for the 600 mg potency contains: Titanium Dioxide, Gelatin and FD&C Red #40.
The printing ink contains: D&C Yellow #10, FD&C Blue #1, FD&C Blue #2, FD&C Red #40, n-Butyl
Alcohol, Pharmaceutical Glaze, Propylene Glycol, SDA-3A Alcohol, and Synthetic Black Iron Oxide.
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.
Lithium Carbonate is a white, light, alkaline powder with molecular formula Li
CO and molecular
Preclinical studies have shown that lithium alters sodium transport in nerve and muscle cells and effects
a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of
lithium action in mania is unknown.
INDICATIONS AND USAGE
Lithium is indicated in the treatment of manic episodes of Bipolar Disorder. Bipolar Disorder, Manic
(DSM-III) is equivalent to Manic Depressive illness, Manic, in the older DSM-II terminology.
Lithium is also indicated as a maintenance treatment for individuals with a diagnosis of Bipolar
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.
Lithium should generally not be given to patients with significant renal or cardiovascular disease,
severe debilitation or dehydration, or sodium depletion, and to patients receiving diuretics, since the
risk of lithium toxicity is very high in such patients. If the psychiatric indication is life-threatening, and
if such a patient fails to respond to other measures, lithium treatment may be undertaken with extreme
caution, including daily serum lithium determinations and adjustment to the usually low doses ordinarily
tolerated by these individuals. In such instances, hospitalization is a necessity.
Lithium may cause fetal harm when administered to a pregnant woman. There have been reports of
lithium having adverse effects on nidations in rats, embryo viability in mice, and metabolism in-vitro of
rat testis and human spermatozoa have been attributed to lithium, as have teratogenicity in submammalian
species and cleft palates in mice. Studies in rats, rabbits and monkeys have shown no evidence of
lithium-induced teratology. Data from lithium birth registries suggest an increase in cardiac and other
anomalies, especially Ebstein's anomaly. If the patient becomes pregnant while taking lithium, she
should be apprised of the potential risk to the fetus. If possible, lithium should be withdrawn for at least
the first trimester unless it is determined that this would seriously endanger the mother.
Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally
presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. Such patients should be
carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is
usually reversible when lithium is discontinued.
Morphologic changes with glomerular and interstitial fibrosis and nephron-atrophy have been reported
in patients on chronic lithium therapy. Morphologic changes have also been seen in bipolar patients
never exposed to lithium. The relationship between renal functional and morphologic changes and their
association with lithium therapy has not been established.
When kidney function is assessed, for baseline data prior to starting lithium therapy or thereafter,
routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or
osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function
(e.g., serum creatinine or creatinine clearance). During lithium therapy, progressive or sudden changes
in renal function, even within the normal range, indicate the need for reevaluation of treatment.
Lithium toxicity is closely related to serum lithium levels, and can occur at doses close to therapeutic
levels (see DOSAGE AND ADMINISTRATION).
The ability to tolerate lithium is greater during the acute manic phase and decreases when manic
symptoms subside (see DOSAGE AND ADMINISTRATION).
The distribution space of lithium approximates that of total body water. Lithium is primarily excreted in
urine with insignificant excretion in feces. Renal excretion of lithium is proportional to its plasma
concentration. The half-life of elimination of lithium is approximately 24 hours. Lithium decreases
sodium reabsorption by the renal tubules which could lead to sodium depletion. Therefore, it is
essential for the patient to maintain a normal diet, including salt, and an adequate fluid intake (2500-3000
mL) at least during the initial stabilization period. Decreased tolerance to lithium has been reported to
ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be
In addition to sweating and diarrhea, concomitant infection with elevated temperatures may also
necessitate a temporary reduction or cessation of medication.
Previously existing underlying thyroid disorders do not necessarily constitute a contraindication to
lithium treatment; where hypothyroidism exists, careful monitoring of thyroid function during lithium
stabilization and maintenance allows for correction of changing thyroid parameters, if any. Where
hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may
Information for the Patients:
Outpatients and their families should be warned that the patient must discontinue lithium therapy and
contact his physician if such clinical signs of lithium toxicity as diarrhea, vomiting, tremor, mild ataxia,
drowsiness, or muscular weakness occur.
Lithium may impair mental and/or physical abilities. Caution patients about activities requiring alertness
(e.g., operating vehicles or machinery).
Combined use of haloperidol and lithium. An encephalopathic syndrome (characterized by weakness,
lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum
enzymes, BUN and FBS) followed by irreversible brain damage has occurred in a few patients treated
with lithium plus haloperidol. A causal relationship between these events and the concomitant
administration of lithium and haloperidol has not been established; however, patients receiving such
combined therapy should be monitored closely for early evidence of neurological toxicity and treatment
discontinued promptly if such signs appear.
The possibility of similar adverse interactions with other antipsychotic medication exists.
Lithium may prolong the effects of neuromuscular blocking agents. Therefore, neuromuscular blocking
agents should be given with caution to patients receiving lithium.
Caution should be used when lithium and diuretics or angiotensin converting enzyme (ACE) inhibitors
are used concomitantly because sodium loss may reduce the renal clearance of lithium and increase
serum lithium levels with risk of lithium toxicity. When such combinations are used, the lithium dosage
may need to be decreased, and more frequent monitoring of lithium plasma levels is recommended.
Non-Steroidal 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 an NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly
steady-state plasma lithium concentrations. There is also evidence that other nonsteriodal 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.
Pregnancy, Teratogenic Effects: Pregnancy Category D.
See WARNINGS section.
Lithium is excreted in human milk. Nursing should not be undertaken during lithium therapy except in
rare and unusual circumstances where, in the view of the physician, the potential benefits to the mother
outweigh possible hazards to the child.
Since information regarding the safety and effectiveness of lithium in children under 12 years of age is
not available, its use in such patients is not recommended at this time. There has been a report of a
transient syndrome of acute dystonia and hyperreflexia occurring in a 15 kg child who ingested 300 mg
of lithium carbonate.
The likelihood of toxicity increases with increasing serum lithium levels. Serum lithium levels greater
than 1.5 mEq/L carry a greater risk than lower levels. However, patients sensitive to lithium may exhibit
toxic signs at serum levels below 1.5 mEq/L.
Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of
lithium toxicity, and can occur at lithium levels below 2 mEq/L. At higher levels, giddiness, ataxia,
blurred vision, tinnitus, and a large output of dilute urine may be seen. Serum lithium levels above 3
mEq/L may produce a complex clinical picture involving multiple organs and organ systems. Serum
lithium levels should not be permitted to exceed 2 mEq/L during the acute treatment phase.
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 are an inconvenience rather than a disabling condition, and usually subside with
continued treatment or a temporary reduction or cessation of dosage. If persistent, a cessation of dosage
The following adverse reactions have been reported and do not appear to be directly related to serum
Neuromuscular: Tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole
limbs), ataxia, choreo-athetotic movements, hyperactive deep tendon reflexes.
Central Nervous System: Blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo,
incontinence of urine or feces, somnolence, psychomotor retardation, restlessness, confusion, stupor,
coma, acute dystonia, downbeat nystagmus.
Cardiovascular: Cardiac arrhythmia, hypotension, peripheral circulatory collapse, sinus node
dysfunction with severe bradycardia (which may result in syncope).
Neurological: Cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have
been reported with lithium use. If undetected, this condition may result in enlargement of the blind spot,
constriction of visual fields and eventual blindness due to optic atrophy. Lithium should be
discontinued, if clinically possible, if this syndrome occurs.
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea.
Genitourinary: Albuminuria, oliguria, polyuria, glycosuria.
Dermatologic: Drying and thinning of hair, anesthesia of skin, chronic folliculitis, xerosis cutis,
alopecia and exacerbation of psoriasis.
Autonomic Nervous System: Blurred vision, dry mouth.
Thyroid Abnormalities: Euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by
lower T and T . Iodine uptake may be elevated. (See PRECAUTIONS.) Paradoxically, rare cases of
hyperthyroidism have been reported.
EEG Changes: Diffuse slowing, widening of the frequency spectrum, potentiation and disorganization
of background rhythm.
EKG Changes: Reversible flattening, isoelectricity or inversion of T-waves.
Miscellaneous: Fatigue, lethargy, transient scotomata, dehydration, weight loss, tendency to sleep.
Miscellaneous reactions unrelated to dosage are: Transient electroencephalographic and
electrocardiographic changes, leukocytosis, headache, diffuse non-toxic goiter with or without
hypothyroidism, transient hyperglycemia, generalized pruritis with or without rash, cutaneous ulcers,
albuminuria, worsening of organic brain syndromes, excessive weight gain, edematous swelling of
ankles or wrists, and thirst or polyuria, sometimes resembling diabetes insipidus, and metallic taste.
A single report has been received of the development of painful discoloration of fingers and toes and
coldness of the extremities within one day of the starting of treatment of lithium. The mechanism
through which these symptoms (resembling Raynaud's Syndrome) developed is not known. Recovery
The toxic levels for lithium are close to the therapeutic levels. 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. Toxic symptoms are listed in detail under ADVERSE REACTIONS.
No specific antidote for lithium poisoning is known. 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. Infection prophylaxis, regular chest X-
rays, and preservation of adequate respiration are essential.
DOSAGE AND ADMINISTRATION
Acute Mania - Optimal patient response to Lithium Carbonate usually can be established and maintained
with 600 mg t.i.d. Such doses will normally produce an effective serum lithium level ranging between 1
and 1.5 mEq/L. Dosage must be individualized according to serum levels and clinical response. Regular
monitoring of the patient's clinical state and serum lithium levels is necessary. Serum levels should be
determined twice per week during the acute phase, and until the serum level and clinical condition of the
patient have been stabilized.
Long-Term Control - The desirable serum lithium levels are 0.6 to 1.2 mEq/L. Dosage will vary from
one individual to another, but usually 300 mg of Lithium Carbonate t.i.d. or q.i.d. will maintain this level.
Serum lithium levels 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 levels of 1 to 1.5 mEq/L.
Elderly patients often respond to reduced dosage, and may exhibit signs of toxicity at serum levels
ordinarily tolerated by other patients.
N.B.: Blood samples for serum lithium determination should be drawn immediately prior to the next
N.B.: Blood samples for serum lithium determination should be drawn immediately prior to the next
dose when lithium concentrations are relatively stable (i.e., 8-12 hours after the previous dose). Total
reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical and
Lithium Carbonate Capsules USP, 150 mg are supplied as No. 4 White/White Opaque Hard Gelatin
Capsules Printed “West-ward 3188” in Black Ink and are available in:
Bottles of 30 capsules
Bottles of 100 capsules
Bottles of 500 capsules
Lithium Carbonate Capsules USP, 300 mg are supplied as No. 1 Grey/Yellow Opaque Hard Gelatin
Capsules Printed "West-ward 3189" in Black Ink and are available in:
Bottles of 100 capsules
Bottles of 1000 capsules
Lithium Carbonate Capsules USP, 600 mg are supplied as No. 0 White/Flesh Opaque Capsules Printed
“West-ward 3190” in Black Ink and are available in:
Bottles of 100 capsules
Unit Dose Boxes of 100 capsules
Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Protect from light and moisture.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
P.O.Box 182400, Amman 11118-Jordan
West-ward Pharmaceutical Corp.
Eatontown, NJ 07724
Revised June 2008
PRINCIPAL DISPLAY PANEL
Lithium Carbonate Capsules, USP 300 mg
lithium carbonate capsule
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
LITHIUM CARBO NATE (UNII: 2BMD2GNA4V) (LITHIUM CATION - UNII:8 H8 Z5UER6 6 )
30 0 mg
Stre ng th
TALC (UNII: 7SEV7J4R1U)
GELATIN (UNII: 2G8 6 QN327L)
TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)
BUTYL ALCO HO L (UNII: 8 PJ6 1P6 TS3)
PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)
FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)
FD&C GREEN NO . 3 (UNII: 3P3ONR6 O1S)
FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )
D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)
FD&C RED NO . 4 0 (UNII: WZB9 127XOA)
FD&C BLUE NO . 1 (UNII: H3R47K3TBD)
FD&C BLUE NO . 2 (UNII: L0 6 K8 R7DQK)
no sco re
S hap e
S iz e
Marketing Start Date
Marketing End Date
NDC:59 115-135-0 1
10 0 in 1 BOTTLE, PLASTIC
10 0 0 in 1 BOTTLE, PLASTIC
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
ANDA0 76 243
0 6 /27/20 0 2
Hikma Pharmaceutical (534661645)
Ad d re s s
Busine ss Ope rations
5346 6 16 45