The P-I-E-N-O Parkinsn's List Drug Database
lithium / LithobidTM ,LithicarbTM
ANTIMANIC:
LOW RISK
Description: Lithium is a monovalent cation similar to sodium and potassium. For clinical use, it is administered orally as the carbonate and the more water-soluble citrate salts. Lithium is the drug of choice in treating recurrent bipolar affective disorder (i.e., manic-depressive illness) and has also been used for unipolar disorder (depression). Nonpsychiatric uses of lithium include the syndrome of inappropriate secretion of ADH (SIADH), neutropenia, thyrotoxic crisis, and migraine and cluster headaches, although these are not FDA-approved uses. Lithium has been used in clinical medicine since the 1950s, but its pharmacokinetics were not well understood until the 1970s. Lithium carbonate was approved by the FDA in 1970.
Mechanism of Action: Lithium competes at cellular sites with sodium, potassium, calcium, and magnesium ions. At the cell membrane, it readily passes through sodium channels, and high concentrations can block potassium channels. Lithium competes with these ions at intracellular binding sites, at protein surfaces, at carrier binding sites, and at transport sites. Although the mechanism of the antimanic and antidepressant action in the CNS is not known, evidence suggests that the drug interferes with the synthesis, storage, release, and reuptake of monoamine neurotransmitters. Lithium does not possess sedative, depressant, or euphoriant effects. Onset of the acute antimanic effect is usually seen in 5-7 days, and the full therapeutic effect is established in 10-21 days.
Lithium enhances granulocyte production via stimulation of monocyte colony stimulating factor production. Lithium produces an increase in the total neutrophil pool and each of its components in the bone marrow and circulation. Leukocytosis peaks within 7-10 days of initiating therapy and the WBC count will return to baseline 7-10 days after discontinuing lithium.
Pharmacokinetics: In practice, lithium salts are only given orally. Lithium is rapidly absorbed from the GI tract, and the rate of absorption is not significantly slowed by the presence of food. Lithium carbonate in tablets or capsules is 95-100% absorbed. Bioavailability from slow-release lithium carbonate tablets is 60-90%. Lithium citrate oral solutions are essentially 100% absorbed. Lithium carbonate is most commonly used because it has a longer shelf-life and contains more lithium on a weight basis than do other salts.
Peak serum concentrations from lithium carbonate are reached in 0.5-3 hours, and absorption is complete within 6 hours. Extended-release tablets peak in 4-12 hours. Oral solutions of lithium citrate are extremely rapidly absorbed; peak serum levels are achieved in 15-60 minutes. Lithium has negligible protein binding and is distributed throughout the body, with slightly greater concentrations in thyroid, bone, and brain tissue. It is excreted in the urine unchanged. A 300 mg dose of lithium carbonate tablets produces peak serum concentrations of 0.4-0.5 mEq/L. A similar dose in capsules gives peak serum concentrations of 0.4-0.9 mEq/L. Serum lithium concentrations tend to fluctuate for 6-10 hours after dosing, so the 12-hour post-dose serum concentration is used for monitoring purposes. Data published in 1989 confirmed that serum concentrations of 0.8-1.0 mEq/L are more effective in preventing relapse in patients with bipolar disorder than are lower concentrations of 0.4-0.6 mEq/L.D Steady-state serum lithium concentrations of 1-1.4 mEq/L are required to control acute mania. Toxicity is likely in most patients when levels exceed 1.5 mEq/L, although symptoms of lithium toxicity can appear in some patients with serum concentrations of 1 mEq/L or less. The narrow therapeutic ratio and interpatient variations make individual monitoring and dosage adjustment essential.
Approximately 90-95% of a dose of lithium is eliminated by the kidneys. The amount eliminated through sweat, saliva, and feces is negligible under normal circumstances. Lithium is freely filtered by renal glomeruli, but it also undergoes significant renal tubular reabsorption. Thus, any decrease in GFR will reduce lithium elimination. In patients with normal renal function, biphasic elimination is observed. The initial half-life is 0.8-1.2 hours, and the terminal half-life is approximately 20-27 hours, although reported half-life values have ranged from 5-79 hours. In young adults, the half-life is 18-24 hours, and in the elderly, it is 30-36 hours. Many factors can affect lithium clearance including hyponatremia or hypernatremia, dehydration, and diuretic use.
CONTRAINDICATIONS/PRECAUTIONS: Lithium is classified as pregnancy category D. It crosses the placental barrier freely and has been associated with fetal toxicity. Data from lithium birth registers suggest an increased incidence of neonatal goiter and an increase in cardiac anomalies, especially Ebstein's anomaly. In some cases, however, lithium therapy may be warranted during pregnancy, but patients should be warned about possible damage to the fetus. If possible, lithium should be withheld during the first trimester. Women of childbearing age who require lithium therapy should be counseled about becoming pregnant. Lithium is secreted into breast milk and is contraindicated in women who are breast-feeding. Symptoms of lithium toxicity, including ECG changes, have been observed in some breast-fed infants, whose mothers were taking lithium.
Lithium therapy can cause hyponatremia by reducing resorption of sodium by the renal tubules. Lithium should be used with caution in hyponatremia. An adequate fluid intake and maintenance of salt balance are essential during lithium therapy. Lithium clearance depends on GFR. Lithium should be used with caution in patients with renal impairment or renal disease; dosage reductions are recommended. Reevaluation of treatment may be necessary depending on renal function. In addition urinary retention may delay lithium excretion and cause toxicity. Chronic lithium therapy may lead to a reduction in renal concentrating ability, with polyuria and polydipsia. Dehydration can lead to lithium toxicity. Lithium should be used with caution in patients requiring sodium restriction in their diet. Any factor leading to dehydration can affect lithium balance, such as protracted sweating or diarrhea, which may require supplemental fluid and salt intake or, alternatively, reduction or suspension of lithium therapy. Other factors that raise body temperature may lead to dehyration, such as fever, exercise, sauna or hot baths. A concurrent infection with elevated body temperature may also require reduced lithium dosage or temporary stoppage of therapy.
Lithium can affect thyroid function. Lithium should be used cautiously in patients with thyroid disease, especially hypothyroidism, or in the elderly because these patients may be more susceptible to this adverse effect.
Lithium should be used cautiously in patients with cardiovascular disease. Changes in ECG readings can occur, although hypotension and cardiac arrhythmias are rare.
Patients with psoriasis should receive lithium with caution. Lithium therapy is known to exacerbate psoriasis.
Because lithium can cause seizures and/or tremors, it should be used cautiously in patients with a preexisting seizure disorder or parkinsonism. These conditions may mask the neurotoxicity of lithium.
Lithium can produce mental status changes. Patients need to be informed about the possibility of reduced mental alertness affecting their ability to drive or use machinery safely, especially when lithium therapy is instigated.
Lithium should be used cautiously in patients with organic brain syndrome or CNS impairment. Lithium has produced an encephalopathic syndrome (similar to NMS) in some patients receiving concomitant neuroleptic therapy (see Drug Interactions). Brain damage produced by this syndrome may be irreversible.
Bipolar disorder has an inherent risk of suicidal ideation. The determination as to which patients are at risk is difficult. However, a history of alcohol or substance abuse, those socially isolated, or with a history of attempted suicide are most at risk. High risk patients may require lithium treatment within a hospital environment or monitoring by family or friends.
Lithium should be used with caution in patients with a history of leukemia. Lithium has been associated with the development or reactivation of leukemia.
DRUG INTERACTIONS: Thiazide diuretics reduce lithium renal clearance and can increase lithium serum concentrations. In some cases, thiazide diuretics may be used to counteract lithium-induced polyuria. Regardless of the indication for diuretic therapy, the lithium dosage should be reevaluated when a thiazide is added. Indapamide, a non-thiazide diuretic, also may interact in the same way.
Various reactions have resulted when lithium is administered with phenothiazines, such as chlorpromazine or thioridazine, or with haloperidol. Neurotoxicity, consisting of delirium, seizures, encephalopathy, hyperpyrexia, or extrapyramidal symptoms, has occurred when lithium was administered with either thioridazine or haloperidol. Lithium and chlorpromazine each appear to affect the kinetics of the other agent. Concurrent use of lithium and molindone also can produce neurotoxic symptoms.
Metronidazole, in two case reports, has been shown to increase serum creatinine and serum lithium concentrations when administered to patients stabilized on lithium. Until more data are available, metronidazole should be avoided in patients receiving lithium.
NSAIDs reduce lithium excretion and lead to elevated lithium serum concentrations. Serum lithium concentrations should be monitored closely and the patient observed for signs of lithium intoxication for 4-7 days after a NSAID is either added to or discontinued from lithium therapy. Aspirin and sulidac do not appear to significantly affect lithium clearance.
The interaction between verapamil and lithium is variable and unpredictable. Verapamil administration has been associated with both decreased lithium concentrations and with lithium toxicity. Verapamil may substantially lower serum lithium concentrations when administered to patients stabilized on lithium therapy. This effect may be offset somewhat by the fact that calcium-channel blocking agents share some neuropharmacological actions with lithium; limited data suggest that oral verapamil is effective in controlling an acute manic episode either as a single agent or in combination with lithium. Concurrent therapy, however, may lead to neurotoxicity, even without a measurable increase in lithium serum concentrations. Because verapamil has been associated with both decreased lithium concentrations and with lithium toxicity, verapamil should be avoided in patients receiving lithium.
Lithium can precipitate goiter and/or hypothyroidism. Concomitant use of lithium and potassium iodide, KI, or calcium iodide can increase the likelihood of this adverse reaction.
ACE inhibitors can increase the risk of developing lithium toxicity, possibly as a result of sodium depletion. ACE inhibitors should not be added to the regimens of patients already receiving lithium.
Hypernatremia increases lithium clearance, while hyponatremia reduces lithium clearance. Dramatic changes in dietary sodium intake or the administration of sodium chloride or sodium bicarbonate can affect lithium clearance and/or efficacy.
Carbamazepine and lithium are sometimes used together therapeutically. In some patients, however, adverse CNS reactions occur, despite therapeutic serum concentrations of both agents. Patients receiving these two drugs together should be monitored closely for signs of neurotoxicity (e.g., ataxia, lethargy, hyperreflexia, tremor) despite absence of toxic serum concentrations of either agent.
ADVERSE REACTIONS: NOTE: Lithium can be a toxic drug. Many adverse reactions are dose-and concentration-related. The increase in serum concentrations that can precipitate mild to moderate adverse reactions to those producing moderate to severe reactions is small, ranging from below 1.5 mEq/L to 2.0 mEq/L and above. Serum concentrations should be monitored in all patients receiving lithium therapy.
Some adverse reactions to lithium occur regularly and at therapeutic serum concentrations. These include: fine hand tremor, xerostomia, dysgeusia, weight gain, polydipsia, polyuria, mild nausea/vomiting, impotence, libido decrease, nephrotic syndrome, and diarrhea. Gastrointestinal effects often resolve with continued therapy and can be alleviated by taking divided doses with meals. If diarrhea or polyuria lead to dehydration, lithium toxicity is possible. Polydipsia and polyuria are more likely to occur during the first few weeks of treatment, and soon disappear. Polyuria may recur unexpectedly as diabetes insipidus. In these cases a nephrogenic diabetes insipidus-like syndrome can develop, with constant thirst and a large output of very dilute urine.
Adverse reactions that suggest lithium toxicity include: anorexia; visual impairment or disturbance; drowsiness; muscular weakness; fasciculations, or myoclonia; ataxia; slurred speech; stupor or coma; tremor; confusion; seizures; and arrhythmias. Serum lithium concentrations should not be allowed to rise above 2.0 mEq/L during the acute treatment phase. Serum concentrations above 3.0mEq/L can produce adverse effects involving multiple organ systems.
Leukocytosis is routinely noted during lithium therapy. This effect appears to be secondary to an increased number of circulating neutrophils. Leukocytosis is generally reversible upon discontinuation of therapy. Occasionally a rare leukemia may develop. Unless the white blood cell count rises to 100,000 cells/cu mm, there is no need to discontinue lithium therapy.
Cardiovascular effects of lithium therapy include: ST-T wave changes (benign flattening or inversion of T waves), hypotension, sinus bradycardia. Lithium should be used cautiously in patients with preexisting conduction disturbances.
Approximately 4% of patients develop goiter while taking lithium. Hypothyroidism has been reported, and preexisting hypothyroidism is a relative contraindication to lithium therapy. There may be an early and transient decrease in serum-bound iodine and free thyroxine, which returns to normal in a few weeks. A few patients may go on to develop a diffuse enlargement of the thyroid. Careful monitoring of thyroid function is necessary. Signs of hypothyroidism may be detected; they include: dry rough skin, alopecia, hoarseness, mania, mental depression, sensitivity to cold, swelling of the feet and lower legs, swelling of the neck.
PATIENT INFORMATION:
What do lithium tablets or capsules do?
Lithium (EskalithTM , LithonateTM , LithaneTM , LithotabsTM ) helps to control extreme mood swings in manic-depressive illness. Lithium helps you to maintain a more balanced state, without swinging from a highly elated, over-excited state to that of being very sad and depressed. Lithium can prevent or reduce these episodes. Generic lithium tablets or capsules are available.
What should my doctor, dentist, or pharmacist know before I take lithium?
They need to know if you have any of these conditions:
How should I take this medicine?
Take lithium tablets or capsules by mouth. Follow the directions on the prescription label. Swallow the tablets or capsules with a drink of water. Take after a meal or snack to avoid stomach upset. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor's advice.
Special precautions for use in children:
Safe and effective use has not been established for children under 12 years old.
Elderly patients over age 65 years may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is almost time for your next dose (less than 2 hours), take only that dose. Do not take double or extra doses.
What other medicines can interact with lithium?
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking lithium?
Serious side effects of lithium include early signs of toxicity (overdose):
These symptoms can progress to:
Other possible, though uncommon, serious side effects include:
Call your doctor as soon as you can if you get any of these side effects.
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take lithium?
Visit your doctor for regular checks on your progress. It can take several weeks of treatment to get improvement in your condition. You must continue to take lithium at regular intervals even when your symptoms are better. Do not stop taking lithium except on your doctor's advice. The amount of lithium you take is very important. Taking more than the prescribed dose can cause serious side effects.
The amount of salt (sodium) in your body influences the effects of lithium, and lithium can increase salt loss from the body. Eat a normal diet that includes salt. Do not change to salt substitutes. Avoid changes involving diet, or medications that include large amounts of sodium (such as sodium bicarbonate). Ask your doctor or pharmacist for advice if you are not sure.
Drink plenty of fluids while you are taking lithium. Avoid drinks that contain caffeine, such as coffee, tea and colas. You will need extra fluids if you have diarrhea or sweat a lot. This will help prevent toxic effects from lithium. Be careful not to get overheated during exercise, saunas, hot baths, and hot weather. Consult your doctor if you have a high fever or persistent diarrhea.
You may get dizzy, drowsy, or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how lithium affects you.
Make sure that family members or friends know of early signs of lithium toxicity (see side effects above).
If you are going to have surgery, tell your doctor or dentist that you are taking lithium.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Keep container tightly closed. Protect from light. Throw away any unused medicine after the expiration date.
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