Prescription Drug Information: Lithium Carbonate (Page 2 of 5)

5.3 Hyponatremia


Lithium can cause hyponatremia by decreasing sodium reabsorption by the renal tubules, leading to sodium depletion. Therefore, it is essential for patients receiving lithium treatment 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 lithium has also 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 lithium intake reduced or suspended until the condition is resolved. In addition, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication. Symptoms are also more severe with faster-onset hyponatremia. Mild hyponatremia (i.e., serum Na > 120 mEq/L) can be asymptomatic. Below this threshold, clinical signs are usually present, consisting mainly of changes in mental status, such as altered personality, lethargy, and confusion. For more severe hyponatremia (serum Na < 115 mEq/L), stupor, neuromuscular hyperexcitability, hyperreflexia, seizures, coma, and death can result. During treatment of hyponatremia, serum sodium should not be elevated by more than 10 to 12 meq/L in 24 hours or 18 meq/L in 48 hours. In the case of severe hyponatremia where severe neurologic symptoms are present, a faster infusion rate to correct serum sodium concentration may be needed. Patients rapidly treated or with serum sodium <120mEq/L are more at risk of developing osmotic demyelination syndrome (previously called central pontine myelinolysis). Occurrence is more common among patients with alcoholism, undernutrition, or other chronic debilitating illness. Common signs include flaccid paralysis, dysarthria. In severe cases with extended lesions patients may develop a locked-in syndrome (generalized motor paralysis). Damage often is permanent. If neurologic symptoms start to develop during treatment of hyponatremia, serum sodium correction should be suspended to mitigate the development of permanent neurologic damage.

5.4 Lithium-Induced Chronic Kidney Disease

The predominant form of chronic renal disease associated with long-term lithium treatment is a chronic tubulointerstitial nephropathy (CTIN). The biopsy findings in patients with lithium induced CTIN include tubular atrophy, interstitial fibrosis, sclerotic glomeruli, tubular dilation, and nephron atrophy with cyst formation. The relationship between renal function and morphologic changes and their association with lithium treatment has not been established. CTIN patients might present with nephrotic proteinuria (>3.0g/dL), worsening renal insufficiency and/or nephrogenic diabetes insipidus. Postmarketing cases consistent with nephrotic syndrome in patients with or without CTIN have also been reported. The biopsy findings in patients with nephrotic syndrome include minimal change disease and focal segmental glomerulosclerosis. The discontinuation of lithium in patients with nephrotic syndrome has resulted in remission of nephrotic syndrome. Kidney function should be assessed prior to and during lithium treatment. 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, creatinine clearance, or proteinuria). During lithium treatment, progressive or sudden changes in renal function, even within the normal range, indicate the need for revaluation of treatment.

5.5 Encephalopathic Syndrome

An encephalopathic syndrome, characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and fasting blood glucose, has occurred in patients treated with lithium and an antipsychotic. 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 lithium and antipsychotics, patients receiving such combined treatment should be monitored closely for early evidence of neurological toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS).

5.6 Serotonin Syndrome

Lithium can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, tramadol, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [see Drug Interactions ( 7.1)] .
Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Monitor all patients taking lithium for the emergence of serotonin syndrome. Discontinue treatment with lithium and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of lithium with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

5.7 Hypothyroidism or Hyperthyroidism

Lithium is concentrated within the thyroid and can inhibit thyroid synthesis and release which can lead to hypothyroidism. 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 be used. Paradoxically, some cases of hyperthyroidism have been reported including Grave’s disease, toxic multinodular goiter and silent thyroiditis. Monitor thyroid function before the initiation of treatment, at three months and every six to twelve months while treatment is ongoing. If serum thyroid tests warrant concern, monitoring should occur more frequently.

5.8 Hypercalcemia and Hyperparathyroidism

Long-term lithium treatment is associated with persistent hyperparathyroidism and hypercalcemia. When clinical manifestations of hypercalcemia are present, lithium withdrawal and change to another mood stabilizer may be necessary. Hypercalcemia may not resolve upon discontinuation of lithium, and may require surgical intervention. Lithium-induced cases of hyperparathyroidism are more often multiglandular compared to standard cases. False hypercalcemia due to plasma volume depletion resulting from nephrogenic diabetes insipidus should be excluded in individuals with mildly increased serum calcium. Monitor serum calcium concentrations regularly.

5.9 Unmasking of Brugada Syndrome

There have been postmarketing reports of a possible association between treatment with lithium and the unmasking of Brugada Syndrome. Brugada Syndrome is a disorder characterized by abnormal electrocardiographic (ECG) findings and a risk of sudden death. Lithium should be avoided in patients with Brugada Syndrome or those suspected of having Brugada Syndrome. Consultation with a cardiologist is recommended if: (1) treatment with lithium 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 lithium treatment.

5.10 Pseudotumor Cerebri

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. Consider discontinuing lithium if this syndrome occurs.

6 ADVERSE REACTIONS

The following adverse reactions are described in greater detail in other sections:
• Lithium Toxicity [see Warnings and Precautions ( 5.1)]
• Lithium-Induced Polyuria [see Warnings and Precautions ( 5.2)]
• Hyponatremia [see Warnings and Precautions ( 5.3)]
• Lithium-Induced Chronic Kidney Disease [see Warnings and Precautions ( 5.4)]
• Encephalopathic Syndrome [see Warnings and Precautions ( 5.5)]
• Serotonin Syndrome [see Warnings and Precautions ( 5.6)]
• Hypothyroidism or Hyperthyroidism [see Warnings and Precautions ( 5.7)]
• Hypercalcemia and Hyperparathyroidism [see Warnings and Precautions ( 5.8)]
• Unmasking of Brugada Syndrome [see Warnings and Precautions ( 5.9)]
• Pseudotumor Cerebri [see Warnings and Precautions ( 5.10)]
The following adverse reactions have been identified following use of lithium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Central Nervous System: tremor, muscle hyperirritability (fasciculations, twitching, clonic movements of whole limbs), hypertonicity, ataxia, choreoathetotic movements, hyperactive deep tendon reflexes, extrapyramidal symptoms including acute dystonia, cogwheel rigidity, blackout spells, epileptiform seizures, slurred speech, dizziness, vertigo, downbeat nystagmus, incontinence of urine or faeces, somnolence, psychomotor retardation, restlessness, confusion, stupor, coma, tongue movements, tics, tinnitus, hallucinations, poor memory, slowed intellectual functioning, startled response, worsening of organic brain syndromes, myasthenic syndromes (rarely).
EEG Changes: diffuse slowing, widening of frequency spectrum, potentiation and disorganization of background rhythm.
Cardiovascular: conduction disturbance (mostly sinus node dysfunction with possibly severe sinus bradycardia and sinoatrial block), ventricular tachyarrhythmia, peripheral vasculopathy (resembling Raynaud’s Syndrome).
ECG Changes: reversible flattening, isoelectricity or rarely inversion of T-waves, prolongation of the QTc interval.
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, anaesthesia of skin, chronic folliculitis, xerosis cutis, psoriasis onset or exacerbation, generalized pruritus with or without rash, cutaneous ulcers, angioedema.
Autonomic Nervous System: blurred vision, dry mouth, impotence/sexual dysfunction. Miscellaneous: fatigue, lethargy, transient scotoma, exopthalmos, dehydration, weight loss, leukocytosis, headache, transient hyperglycemia, hypomagnesemia, excessive weight gain, edematous swelling of ankles or wrists, dysgeusia/taste distortion (e.g., metallic or salty taste), thirst, swollen lips, tightness in chest, swollen and/or painful joints, fever, polyarthralgia, and dental caries.

7 DRUG INTERACTIONS

7.1 Drugs Having Clinically Important Interactions with Lithium

Table 2: Clinically Important Drug Interactions with Lithium

Diuretics
Clinical Impact: Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations .
Intervention: More frequent monitoring of serum electrolyte and lithium concentrations. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.6), Warning and Precautions ( 5.3)]
Examples: hydrochlorothiazide, chlorothiazide, furosemide
Non-Steroidal Anti-inflammatory Drugs (NSAID)
Clinical Impact: NSAID decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations.
Intervention: More frequent serum lithium concentration monitoring. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.6)].
Examples: indomethacin, ibuprofen, naproxen
Renin-Angiotensin System Antagonists
Clinical Impact: Concomitant use increase steady-state serum lithium concentrations.
Intervention: More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.6)].
Examples: lisinopril, enalapril, captopril, valsartan
Serotonergic Drugs
Clinical Impact: Concomitant use can precipitate serotonin syndrome.
Intervention: 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 [see Warnings and Precautions ( 5.6)].
Examples: selective serotonin reuptake inhibitors (SSRI), serotonin and norepinephrine reuptake inhibitors (SNRI), monoamine oxidase inhibitors (MAOI)
Nitroimidazole Antibiotics
Clinical Impact: Concomitant use may cause lithium toxicity due to reduced renal clearance.
Intervention: More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.6)].
Examples: metronidazole
Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents
Clinical Impact: Concomitant use can lower serum lithium concentrations by increasing urinary lithium excretion.
Intervention: More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration ( 2.6)].
Examples: acetazolamide, theophylline, sodium bicarbonate
Methyldopa, Phenytoin and Carbamazepine
Clinical Impact: Concomitant use may increase risk of toxic effects of these drugs
Intervention: Monitor patients closely for symptoms of toxicity of methyldopa, phenytoin, and carbamazepine.
Iodide Preparations
Clinical Impact: Concomitant use may produce hypothyroidism.
Intervention: Monitor patients for signs or symptoms of hypothyroidism [see Warnings and Precautions ( 5.7)].
Examples: potassium iodide
Calcium Channel Blocking Agents (CCB)
Clinical Impact: Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus.
Intervention: Monitor for neurologic adverse reactions.
Examples: diltiazem, nifedipine, verapamil
Atypical and Typical Antipsychotic Drugs
Clinical Impact: Reports of neurotoxic reactions in patients treated with both lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome, as well as reports of an encephalopathic syndrome in few patients treated with concomitant therapy [see Warnings and Precautions ( 5.5)].
Intervention: Monitor for neurologic adverse reactions.
Examples: risperidone, haloperidol, thioridazine, fluphenazine, chlorpromazine, perphenazine, clozapine
Neuromuscular Blocking Agents
Clinical Impact: Lithium may prolong the effects of neuromuscular blocking agents.
Intervention: Monitor for prolonged paralysis or toxicity.
Examples: succinylcholine, pancuronium

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Medication Sections

Medication Information by RSS

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2021. All Rights Reserved.