Boripharm N23

Lithium Iodatum:

• Rx only
• Warning
• Description
• Actions
• Indications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Boripharm N23 (Lithium Iodatum) reviews

Rx only

WARNING

Boripharm N23 (Lithium Iodatum) toxicity is closely related to serum Boripharm N23 (Lithium Iodatum) levels, and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum Boripharm N23 (Lithium Iodatum) determinations should be available before initiating therapy.

DESCRIPTION

Boripharm N23 (Lithium Iodatum) Carbonate Extended-release Tablets USP contain Boripharm N23 (Lithium Iodatum) carbonate USP, a white granular powder with molecular formula Li₂CO₃ and molecular weight 73.89. Boripharm N23 (Lithium Iodatum) 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. The tablets meet the requirements of USP Dissolution Test 2 in the USP monograph for Boripharm N23 (Lithium Iodatum) Carbonate Extended-release Tablets USP.

Boripharm N23 (Lithium Iodatum) Carbonate Extended-release Tablets USP are available for oral administration containing 450 mg of Boripharm N23 (Lithium Iodatum) carbonate USP. Each tablet contains the following inactive ingredients: iron oxide (yellow), magnesium stearate, povidone, sodium alginate and sodium starch glycolate.

Boripharm N23 (Lithium Iodatum) Carbonate Extended-release Tablets USP, 450 mg are designed to release a portion of the dose initially and the remainder gradually; the release pattern of the controlled release tablets reduces the variability in Boripharm N23 (Lithium Iodatum) blood levels seen with the immediate release dosage forms.

ACTIONS

Preclinical studies have shown that Boripharm N23 (Lithium Iodatum) alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of Boripharm N23 (Lithium Iodatum) action in mania is unknown.

INDICATIONS

Boripharm N23 (Lithium Iodatum) carbonate is indicated in the treatment of manic episodes of manic-depressive illness. Maintenance therapy prevents or diminishes the intensity of subsequent episodes in those manic-depressive patients with a history of mania.

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, Boripharm N23 (Lithium Iodatum) carbonate may produce a normalization of symptomatology within 1 to 3 weeks.

WARNINGS

Boripharm N23 Toxicity

Boripharm N23 (Lithium Iodatum) toxicity is closely related to serum Boripharm N23 (Lithium Iodatum) levels, and can occur at doses close to therapeutic levels.

Outpatients and their families should be warned that the patient must discontinue Boripharm N23 (Lithium Iodatum) carbonate therapy and contact his physician if such clinical signs of Boripharm N23 (Lithium Iodatum) toxicity as diarrhea, vomiting, tremor, mild ataxia, drowsiness or muscular weakness occur.

Boripharm N23 (Lithium Iodatum) carbonate may impair mental and/or physical abilities. Caution patients about activities requiring alertness (e.g., operating vehicles or machinery).

Boripharm N23 (Lithium Iodatum) should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation or dehydration, or sodium depletion, since the risk of Boripharm N23 (Lithium Iodatum) 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, Boripharm N23 (Lithium Iodatum) treatment may be undertaken with extreme caution, including daily serum Boripharm N23 (Lithium Iodatum) determinations and adjustment to the usually low doses ordinarily tolerated by these individuals. In such instances, hospitalization is a necessity.

Unmasking of Brugada Syndrome

There have been postmarketing reports of a possible association between treatment with Boripharm N23 and the unmasking of Brugada Syndrome. Brugada Syndrome is a disorder characterized by abnormal electrocardiographic (ECG) findings and a risk of sudden death. Boripharm N23 (Lithium Iodatum) should generally be avoided in patients with Brugada Syndrome or those suspected of having Brugada Syndrome. Consultation with a cardiologist is recommended if: (1) treatment with Boripharm N23 (Lithium Iodatum) is under consideration for patients suspected of having Brugada Syndrome or patients who have risk factors for Brugada Syndrome, e.g., unexplained syncope, a family history of Brugada Syndrome, or a family history of sudden unexplained death before the age of 45 years, (2) patients who develop unexplained syncope or palpitations after starting Boripharm N23 (Lithium Iodatum) therapy.

Renal Effects

Chronic Boripharm N23 (Lithium Iodatum) 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 Boripharm N23 (Lithium Iodatum) retention and toxicity. This condition is usually reversible when Boripharm N23 (Lithium Iodatum) is discontinued.

Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic Boripharm N23 (Lithium Iodatum) therapy. Morphologic changes have also been seen in manic-depressive patients never exposed to Boripharm N23 (Lithium Iodatum). The relationship between renal functional and morphologic changes and their association with Boripharm N23 (Lithium Iodatum) therapy have not been established.

When kidney function is assessed, for baseline data prior to starting Boripharm N23 (Lithium Iodatum) 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 Boripharm N23 (Lithium Iodatum) therapy, progressive or sudden changes in renal function, even within the normal range, indicate the need for reevaluation of treatment.

Encephalopathic Syndrome

An encephalopathic syndrome has occurred in a few patients treated with Boripharm N23 (Lithium Iodatum) plus a neuroleptic. In some instances, the syndrome was followed by irreversible brain damage. Because of a possible causal relationship between these events and the concomitant administration of Boripharm N23 (Lithium Iodatum) and neuroleptics, patients receiving such combined therapy should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS).

Concomitant Use With Neuromuscular Blocking Agents

Boripharm N23 (Lithium Iodatum) may prolong the effects of neuromuscular blocking agents. Therefore, neuromuscular blocking agents should be given with caution to patients receiving Boripharm N23 (Lithium Iodatum).

Usage in Pregnancy

Adverse effects on implantation in rats, embryo viability in mice and metabolism in vitro of rat testes and human spermatozoa have been attributed to Boripharm N23, as have teratogenicity in submammalian species and cleft palates in mice.

In humans, Boripharm N23 (Lithium Iodatum) carbonate may cause fetal harm when administered to a pregnant woman. Data from Boripharm N23 (Lithium Iodatum) birth registries suggest an increase in cardiac and other anomalies, especially Ebstein's anomaly. If this drug is used in women of childbearing potential, or during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

Usage in Nursing Mothers

Boripharm N23 (Lithium Iodatum) is excreted in human milk. Nursing should not be undertaken during Boripharm N23 (Lithium Iodatum) 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.

Usage in Pediatric Patients

Since information regarding the safety and effectiveness of Boripharm N23 carbonate in children under 12 years of age is not available, its use in such patients is not recommended.

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 Boripharm N23 (Lithium Iodatum) carbonate.

Usage in the Elderly

Elderly patients often require lower Boripharm N23 (Lithium Iodatum) dosages to achieve therapeutic serum levels. They may also exhibit adverse reactions at serum levels ordinarily tolerated by younger patients.

PRECAUTIONS

General

The ability to tolerate Boripharm N23 is greater during the acute manic phase and decreases when manic symptoms subside.

The distribution space of Boripharm N23 (Lithium Iodatum) approximates that of total body water. Boripharm N23 (Lithium Iodatum) is primarily excreted in urine with insignificant excretion in feces. Renal excretion of Boripharm N23 (Lithium Iodatum) is proportional to its plasma concentration. The half-life of elimination of Boripharm N23 (Lithium Iodatum) is approximately 24 hours. Boripharm N23 (Lithium Iodatum) 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 to 3000 mL) at least during the initial stabilization period. Decreased tolerance to Boripharm N23 (Lithium Iodatum) has been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and Boripharm N23 (Lithium Iodatum) intake reduced or suspended until the condition is resolved.

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 Boripharm N23 (Lithium Iodatum) treatment; where hypothyroidism exists, careful monitoring of thyroid function during Boripharm N23 (Lithium Iodatum) stabilization and maintenance allows for correction of changing thyroid parameters, if any; where hypothyroidism occurs during Boripharm N23 (Lithium Iodatum) stabilization and maintenance, supplemental thyroid treatment may be used.

Information for the Patients

A condition known as Brugada Syndrome may pre-exist and be unmasked by Boripharm N23 (Lithium Iodatum) therapy. Brugada Syndrome is a heart disorder characterized by abnormal electrocardiographic (ECG) findings and risk of sudden death. Patients should be advised to seek immediate emergency assistance if they experience fainting, lightheadedness, abnormal heart beats, or shortness of breath.

Drug Interactions

Caution should be used when Boripharm N23 (Lithium Iodatum) and diuretics are used concomitantly because diuretic-induced sodium loss may reduce the renal clearance of Boripharm N23 (Lithium Iodatum) and increase serum Boripharm N23 (Lithium Iodatum) levels with risk of Boripharm N23 (Lithium Iodatum) toxicity. Patients receiving such combined therapy should have serum Boripharm N23 (Lithium Iodatum) levels monitored and the Boripharm N23 (Lithium Iodatum) dosage adjusted if necessary.

Boripharm N23 (Lithium Iodatum) levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, Boripharm N23 (Lithium Iodatum) toxicity has resulted from interactions between an NSAID and Boripharm N23 (Lithium Iodatum). Indomethacin and piroxicam have been reported to increase significantly steady-state plasma Boripharm N23 (Lithium Iodatum) 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 Boripharm N23 (Lithium Iodatum) plasma levels increased approximately 17% in subjects receiving Boripharm N23 (Lithium Iodatum) 450 mg b.i.d. with celecoxib 200 mg b.i.d. as compared to subjects receiving Boripharm N23 (Lithium Iodatum) alone.

Concurrent use of metronidazole with Boripharm N23 (Lithium Iodatum) may provoke Boripharm N23 (Lithium Iodatum) toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely.

There is evidence that angiotensin-converting enzyme inhibitors, such as enalapril and captopril, and angiotension II receptor antagonists, such as losartan, may substantially increase steady-state plasma Boripharm N23 (Lithium Iodatum) levels, sometimes resulting in Boripharm N23 (Lithium Iodatum) toxicity. When such combinations are used, Boripharm N23 (Lithium Iodatum) dosage may need to be decreased, and plasma Boripharm N23 (Lithium Iodatum) levels should be measured more often.

Concurrent use of calcium channel blocking agents with Boripharm N23 (Lithium Iodatum) may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. Caution is recommended.

The concomitant administration of Boripharm N23 (Lithium Iodatum) with selective serotonin reuptake inhibitors should be undertaken with caution as this combination has been reported to result in symptoms such as diarrhea, confusion, tremor, dizziness and agitation.

The following drugs can lower serum Boripharm N23 (Lithium Iodatum) concentrations by increasing urinary Boripharm N23 (Lithium Iodatum) excretion: acetazolamide, urea, xanthine preparations and alkalinizing agents such as sodium bicarbonate.

The following have also been shown to interact with Boripharm N23 (Lithium Iodatum): methyldopa, phenytoin and carbamazepine.

ADVERSE REACTIONS

The occurrence and severity of adverse reactions are generally directly related to serum Boripharm N23 (Lithium Iodatum) concentrations as well as to individual patient sensitivity to Boripharm N23 (Lithium Iodatum), and generally occur more frequently and with greater severity at higher concentrations.

Adverse reactions may be encountered at serum Boripharm N23 (Lithium Iodatum) levels below 1.5 mEq/L. Mild to moderate adverse reactions may occur at levels from 1.5 to 2.5 mEq/L, and moderate to severe reactions may be seen at levels of 2 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 Boripharm N23 (Lithium Iodatum) administration.

These side effects usually subside with continued treatment or a temporary reduction or cessation of dosage. If persistent, cessation of Boripharm N23 (Lithium Iodatum) therapy may be required.

Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of Boripharm N23 (Lithium Iodatum) intoxication, and can occur at Boripharm N23 (Lithium Iodatum) levels below 2 mEq/L. At higher levels, ataxia, giddiness, tinnitus, blurred vision and a large output of dilute urine may be seen. Serum Boripharm N23 (Lithium Iodatum) levels above 3 mEq/L may produce a complex clinical picture, involving multiple organs and organ systems. Serum Boripharm N23 (Lithium Iodatum) levels should not be permitted to exceed 2 mEq/L during the acute treatment phase.

The following reactions have been reported and appear to be related to serum Boripharm N23 (Lithium Iodatum) levels, including levels within the therapeutic range:

Neuromuscular/Central Nervous System: tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreo-athetotic 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, myasthenia gravis (rarely).

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: Unmasking of Brugada Syndrome and PRECAUTIONS: Information for the Patients ).

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.

Autonomic: blurred vision, dry mouth, impotence/sexual dysfunction.

Thyroid Abnormalities: euthyroid goiter and/or hypothyroidism (including myxedema) accompanied by lower T₃ and T₄. I¹³¹ uptake may be elevated. 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, exophthalmos, dehydration, weight loss, leukocytosis, headache, transient hyperglycemia, hypercalcemia, hyperparathyroidism, excessive weight gain, edematous swelling of ankles or wrists, metallic taste, dysgeusia/taste distortion, salty taste, thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, dental caries.

Some reports of nephrogenic diabetes insipidus, hyperparathyroidism and hypothyroidism which persist after Boripharm N23 (Lithium Iodatum) discontinuation have been received.

A few reports have 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 with Boripharm N23 (Lithium Iodatum). The mechanism through which these symptoms (resembling Raynaud's syndrome) developed is not known. Recovery followed discontinuance.

Cases of pseudotumor cerebri (increased intracranial pressure and papilledema) have been reported with Boripharm N23 (Lithium Iodatum) use. If undetected, this condition may result in enlargement of the blind spot, constriction of visual fields and eventual blindness due to optic atrophy. Boripharm N23 (Lithium Iodatum) should be discontinued, if clinically possible, if this syndrome occurs.

OVERDOSAGE

The toxic levels for Boripharm N23 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.

Treatment

No specific antidote for Boripharm N23 (Lithium Iodatum) poisoning is known. Early symptoms of Boripharm N23 (Lithium Iodatum) 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 Boripharm N23 (Lithium Iodatum) 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 function. Urea, mannitol and aminophylline all produce significant increases in Boripharm N23 (Lithium Iodatum) 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

Doses of extended-release tablets are usually given b.i.d.. When initiating therapy with immediate-release or extended-release Boripharm N23 (Lithium Iodatum), dosage must be individualized according to serum levels and clinical response.

When switching a patient from immediate-release capsules to the Boripharm N23 (Lithium Iodatum) carbonate extended-release tablets USP, give the same total daily dose when possible. Most patients on maintenance therapy are stabilized on 900 mg daily, e.g., Boripharm N23 (Lithium Iodatum) carbonate extended-release tablets, 450 mg b.i.d. When the previous dosage of immediate-release Boripharm N23 (Lithium Iodatum) is not a multiple of 450 mg, e.g., 1500 mg, initiate Boripharm N23 (Lithium Iodatum) extended-release tablet at the multiple of 450 mg nearest to, but below, the original daily dose, i.e., 1350 mg. When the two doses are unequal, give the larger dose in the evening. In the above example, with a total daily dose of 1350 mg, generally 450 mg of Boripharm N23 (Lithium Iodatum) carbonate extended-release tablets should be given in the morning and 900 mg of Boripharm N23 (Lithium Iodatum) carbonate extended-release tablets in the evening. If desired, the total daily dose of 1350 mg can be given in three equal 450 mg doses of Boripharm N23 (Lithium Iodatum) carbonate extended-release tablets. These patients should be monitored at 1- to 2-week intervals, and dosage adjusted if necessary, until stable and satisfactory serum levels and clinical state are achieved.

When patients require closer titration than that available with doses of Boripharm N23 (Lithium Iodatum) carbonate extended-release tablets in increments of 450 mg, immediate-release capsules should be used.

Acute Mania

Optimal patient response to Boripharm N23 (Lithium Iodatum) can usually be established and maintained with 1800 mg per day in divided doses. Such doses will normally produce the desired serum Boripharm N23 (Lithium Iodatum) 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 Boripharm N23 (Lithium Iodatum) 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 Boripharm N23 levels are 0.6 to 1.2 mEq/L. Dosage will vary from one individual to another, but usually 900 mg to 1200 mg per day in divided doses will maintain this level. Serum Boripharm N23 (Lithium Iodatum) levels in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every two months.

Patients unusually sensitive to Boripharm N23 (Lithium Iodatum) may exhibit toxic signs at serum levels below 1 mEq/L.

N.B.

Blood samples for serum Boripharm N23 (Lithium Iodatum) determinations should be drawn immediately prior to the next dose when Boripharm N23 (Lithium Iodatum) concentrations are relatively stable (i.e., 8 to 12 hours after the previous dose). Total reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical and laboratory analysis.

Elderly patients often respond to reduced dosage, and may exhibit signs of toxicity at serum levels ordinarily tolerated by younger patients.

HOW SUPPLIED

Boripharm N23 (Lithium Iodatum) Carbonate Extended-release Tablets USP

450 mg tablets are supplied as speckled, off-white to yellow, round biconvex tablets with “54 346” debossed on one side and scored on the other side.

NDC 0054-0020-25: Bottle of 100 Tablets

Storage Conditions

Store at 20° to 25°C (68° to 77°F). Protect from moisture. Dispense in a tight, child-resistant container as defined in the USP/NF.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10002294/05

Revised March 2016

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