Microsol

Oral

Mania; Bipolar disorder; Recurrent unipolar depression

Adult: Dose depends on the preparation used. Doses should be adjusted to produce a serum-Microsol concentration of 0.4-1 mmol/l. Microsol® tablets: Treatment: Initiate at 1-1.5 g daily; Prevention: Initiate at 300-400 mg daily. Priadel® tablets: Treatment and prevention: Initially, 400-1,200 mg daily in 1-2 divided doses. Priadel® syrup: Treatment and prevention: Initially, 1.04-3.12 g daily in 2 divided doses. Liskonum® tablets: Treatment: Initially, 450-675 mg bid; Prevention: Initially, 450 mg bid. Doses should be divided throughout the day during the initial period; once-daily dosing may be used when serum-Microsol concentrations have stabilised. Adjust initial dose 4-7 days after starting based on results of serum-Microsol concentrations. Monitor serum-Microsol concentrations once wkly until dosage has remained constant for 4 wk, after which monitoring may be reduced to once every 3 mth.

Child: ≥12 yr: Acute phase: Serum concentrations of 1-1.2 mEq/l. Max dose: 1.5 mEq/l. Initially, 1.8 g Microsol carbonate daily as conventional capsules/tablets in 3-4 divided doses, or 30 ml (approx 48 mEq) Microsol citrate oral solution daily in 3-4 divided doses. Alternatively, initially 1.8 g Microsol carbonate daily as extended-release tablets in 2-3 divided doses.

Maintenance: Not established.

Elderly: ≤900 mg Microsol carbonate daily. Titrate dose slowly to achieve therapeutic serum concentrations.

Maintenance: Maintain serum concentrations at the lower end of 0.6-1.2 mEq/l.

Renal impairment:

Microsol is used to treat mania that is part of bipolar disorder (manic-depressive illness). It is also used on a daily basis to reduce the frequency and severity of manic episodes. Manic-depressive patients experience severe mood changes, ranging from an excited or manic state (e.g., unusual anger or irritability or a false sense of well-being) to depression or sadness.

It is not known how Microsol works to stabilize a person's mood. However, it does act on the central nervous system. It helps you to have more control over your emotions and helps you cope better with the problems of living.

It is important that you and your family understand all the effects of Microsol. These effects depend on your individual condition and response and the amount of Microsol you use. You also must know when to contact your doctor if there are problems with using the medicine.

Microsol is available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Microsol is used in certain patients with the following medical conditions:

• Cluster headaches.
• Mental depression.
• Neutropenia (a blood condition where there is a decreased number of a certain type of white blood cells).

Immediate-release capsules are usually given t.i.d. or q.i.d. Doses of controlled-release tablets are usually given b.i.d. (approximately 12-hour intervals). When initiating therapy with immediate-release or controlled-release Microsol, dosage must be individualized according to serum levels and clinical response.

When switching a patient from immediate-release capsules to Microsol (Microsol carbonate) CR Controlled-Release Tablets, give the same total daily dose when possible. Most patients on maintenance therapy are stabilized on 900 mg daily, e.g., Microsol (Microsol carbonate) CR 450 mg b.i.d. When the previous dosage of immediate-release Microsol is not a multiple of 450 mg, e.g., 1,500 mg, initiate Microsol (Microsol carbonate) CR at the multiple of 450 mg nearest to, but below, the original daily dose, i.e., 1,350 mg. When the 2 doses are unequal, give the larger dose in the evening. In the above example, with a total daily dose of 1,350 mg, generally 450 mg of Microsol (Microsol carbonate) CR should be given in the morning and 900 mg of Microsol (Microsol carbonate) CR in the evening. If desired, the total daily dose of 1,350 mg can be given in 3 equal 450-mg doses of Microsol (Microsol carbonate) CR. 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 Microsol (Microsol carbonate) CR in increments of 450 mg, immediate-release capsules should be used.

Acute Mania: Optimal patient response to Microsol (Microsol carbonate) can usually be established and maintained with 1,800 mg per day in divided doses. Such doses will normally produce the desired serum Microsol level ranging between 1.0 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 Microsol 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 Microsol levels are 0.6 to 1.2 mEq/L. Dosage will vary from one individual to another, but usually 900 mg to 1,200 mg per day in divided doses will maintain this level. Serum Microsol levels in uncomplicated cases receiving maintenance therapy during remission should be monitored at least every two months.

Patients unusually sensitive to Microsol may exhibit toxic signs at serum levels below 1.0 mEq/L.

N.B.: Blood samples for serum Microsol determinations should be drawn immediately prior to the next dose when Microsol 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

Microsol (Microsol carbonate) Capsules 300 mg are gray and yellow capsules imprinted with "Microsol (Microsol carbonate) " and "SB" on one side of each half of the capsule, in bottles of 100 (NDC 0007-4007-20).

Microsol (Microsol carbonate) CR Tablets 450 mg are round, yellow, biconvex, controlled-release tablets, debossed with "SKF" and "J10" on one side and scored on the other side, in bottles of 100 (NDC 0007-4010-20).

STORAGE CONDITIONS: Store at 25°C (77°F), excursions permitted to 15-30°C (59-86°F).

Manufactured by: Cardinal Health., Winchester, KY 40391 for GlaxoSmithKline., Research Triangle Park, NC 27709. September 2003

FDA rev date: 03/11/2004

See also:
What is the most important information I should know about Microsol?

Do not use this medication without telling your doctor if you are pregnant. It could cause harm to the unborn baby. Use an effective form of birth control, and tell your doctor if you become pregnant during treatment.

Call your doctor at once if you have any early signs of Microsol toxicity, such as nausea, vomiting, diarrhea, drowsiness, muscle weakness, tremor, lack of coordination, blurred vision, or ringing in your ears.

Do not crush, chew, or break an extended-release tablet. Swallow the pill whole.

Drink extra fluids to keep from getting dehydrated while you are taking Microsol. Tell your doctor if you have been sweating excessively, or if you are sick with fever, vomiting, or diarrhea.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Follow your doctor's instructions about the type and amount of liquids you should drink. In some cases, drinking too much liquid can be as unsafe as not drinking enough.

Microsol can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Use Microsol controlled-release and extended-release tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Microsol controlled-release and extended-release tablets by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.
• Swallow Microsol controlled-release and extended-release tablets whole. Do not break, crush, or chew before swallowing.
• Drinking extra fluids while you are taking Microsol controlled-release and extended-release tablets is recommended. Check with your doctor for instructions.
• Do not change your diet, including the amount of salt in your diet, unless instructed by your doctor.
• If you miss a dose of Microsol controlled-release and extended-release tablets, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Microsol controlled-release and extended-release tablets.

Use: Labeled Indications

Bipolar disorder:

Immediate release: Treatment of manic and mixed episodes and maintenance treatment in patients ≥7 years of age with a diagnosis of bipolar disorder.

Extended release: Treatment of manic episodes and maintenance treatment in patients ≥12 years of age with a diagnosis of bipolar disorder.

Off Label Uses

Bipolar disorder, hypomania

Data from a limited number of patients studied suggest that Microsol may be beneficial in the treatment of hypomania.

See also:
What other drugs will affect Microsol?

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

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

Concurrent use of metronidazole with Microsol may provoke Microsol 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 Microsol levels, sometimes resulting in Microsol toxicity. When such combinations are used, Microsol dosage may need to be decreased, and plasma Microsol levels should be measured more often.

Concurrent use of calcium channel blocking agents with Microsol 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 Microsol 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 Microsol concentrations by increasing urinary Microsol excretion: acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate.

The following have also been shown to interact with Microsol: methyldopa, phenytoin, and carbamazepine.

See also:
What are the possible side effects of Microsol?

Microsol Toxicity

The likelihood of toxicity increases with increasing serum Microsol levels. Serum Microsol levels greater than 1.5 mEq/L carry a greater risk than lower levels. However, patients sensitive to Microsol 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 Microsol toxicity, and can occur at Microsol levels below 2.0 mEq/L. At higher levels, giddiness, ataxia, blurred vision, tinnitus and a large output of dilute urine may be seen. Serum Microsol levels above 3.0 mEq/L may produce a complex clinical picture involving multiple organs and organ systems. Serum Microsol levels should not be permitted to exceed 2.0 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 Microsol 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 is indicated.

The following adverse reactions have been reported and do not appear to be directly related to serum Microsol levels.

Neuromuscular: Tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), ataxia, choreoathetotic 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 Microsol use. If undetected, this condition may result in enlargement of the blind spot, constriction of visual fields and eventual blindness due to optic atrophy. Microsol 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 T3 and T4. Iodine 131 uptake may be elevated.. 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, dehydration, weight loss, tendency to sleep.

Miscellaneous reactions unrelated to dosage are: Transient electroencephalographic and electrocardiographic changes, leukocytosis, headache, diffuse nontoxic goiter with or without hypothyroidism, transient hyperglycemia, generalized pruritis with or without rash, cutaneous ulcers, albuminuria, worsening of or-ganic 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 Microsol. The mechanism through which these symptoms (resembling Raynaud's Syndrome) developed is not known. Recovery followed discontinuance.

Microsol was used during the 19th century to treat gout. Microsol salts such as Microsol carbonate (Li2CO3), Microsol citrate, and Microsol orotate are mood stabilizers. They are used in the treatment of bipolar disorder, since unlike most other mood altering drugs, they counteract both mania and depression. Microsol can also be used to augment other antidepressant drugs. It is also sometimes prescribed as a preventive treatment for migraine disease and cluster headaches. The active principle in these salts is the Microsol ion Li+, which having a smaller diameter, can easily displace K+ and Na+ and even Ca+2, in spite of its greater charge, occupying their sites in several critical neuronal enzymes and neurotransmitter receptors.