Registrants (1)
080145868
Manufacturing Establishments (1)
Saptalis Pharmaceuticals, LLC
Saptalis Pharmaceuticals, LLC
081154447
Products (1)
Lithium
71656-072
ANDA217183
ANDA (C73584)
ORAL
March 27, 2024
Drug Labeling Information
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE/LABEL PRINCIPAL DISPLAY PANEL
NDC 71656-072-50
Lithium Oral Solution, USP
8 mEq per 5 mL
Unit-dose delivers 5 mL
Orange Flavor
PHARMACIST: Dispense the accompanying Medication Guide to each patient.
Rx only
5 Trays contain 50 Unit-dose Cups
DESCRIPTION SECTION
11 DESCRIPTION
Each 5 mL of solution for oral administration contains lithium ion (Li+), 8 mEq (equivalent to amount of lithium in 300 mg of lithium carbonate, USP), and the following other inactive ingredients: citric acid, glycerin, orange flavor, propylene glycol, purified water, sodium benzoate, sorbitol solution, and sucralose.
Lithium oral solution, USP is a palatable oral dosage form of lithium ion. It is prepared in solution from lithium carbonate, USP and citric acid in a ratio approximately di-lithium citrate.
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.
The empirical formula for lithium citrate is C6H5Li3O7; molecular weight 209.93. Lithium acts as an antimanic.
INDICATIONS & USAGE SECTION
Highlight: Lithium is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder:
- Treatment of acute manic and mixed episodes in patients 7 years and older (1).
- Maintenance treatment in patients 7 years and older (1).
1 INDICATIONS AND USAGE
Lithium oral solution is a mood-stabilizing agent indicated as monotherapy for the treatment of bipolar I disorder:
- Treatment of acute manic and mixed episodes in patients 7 years and older [see Clinical Studies (14)].
- Maintenance treatment in patients 7 years and older [see Clinical Studies (14)].
DOSAGE FORMS & STRENGTHS SECTION
Highlight: * Oral Solution: 8 mEq of lithium (Li+) per 5mL (3).
3 DOSAGE FORMS AND STRENGTHS
Each 5 mL of clear, slightly yellow lithium oral solution, USP contains 8 mEq lithium ion (Li+) (equivalent to the amount of lithium in 300 mg of lithium carbonate, USP).
CONTRAINDICATIONS SECTION
Highlight: * Known hypersensitivity to any inactive ingredient in the drug product (4).
4 CONTRAINDICATIONS
Lithium is contraindicated in patients with known hypersensitivity to any inactive ingredient in the lithium citrate products [see Adverse Reactions (6)].
BOXED WARNING SECTION
WARNING: LITHIUM TOXICITY
DRUG INTERACTIONS SECTION
Highlight: * Diuretics, NSAID, renin-angiotensin system antagonists, or metronidazole may increase lithium serum concentrations. Recommend frequent monitoring of serum lithium concentration and adjust dosage when necessary (2.3, 7.1).
- Serotonergic Agents: Increased risk of serotonin syndrome when co-administered with lithium (5.6, 7.1).
- Antipsychotics: There have been reports of neurologic adverse reactions in patients treated with lithium and an antipsychotic, ranging from extrapyramidal symptoms to neuroleptic malignant syndrome (5.5, 7.1).
7 DRUG INTERACTIONS
7.1 Drugs Having Clinically Important Interactions with Lithium
Table 4: Clinically Important Drug Interactions with Lithium
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Diuretics | |
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Clinical Impact: |
Diuretic-induced sodium loss may reduce lithium clearance and increase serum lithium concentrations. |
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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 (2.3), Warning and Precautions (5.3)]. |
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Non-Steroidal Anti-inflammatory Drugs (NSAID) | |
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Clinical Impact: |
NSAID decrease renal blood flow, resulting in decreased renal clearance and increased serum lithium concentrations. |
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Intervention: |
More frequent serum lithium concentration monitoring. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3)]. |
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Renin-Angiotensin System Antagonists | |
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Clinical Impact: |
Concomitant use increases steady-state serum lithium concentrations. |
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Intervention: |
More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3)]. |
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Serotonergic Drugs | |
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Clinical Impact: |
Concomitant use can precipitate serotonin syndrome. |
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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)]. |
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Nitroimidazole Antibiotics | |
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Clinical Impact: |
Concomitant use may increase serum lithium concentrations due to reduced renal clearance. |
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Intervention: |
More frequent monitoring of serum lithium concentration. Reduce lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3)]. |
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Acetazolamide, Urea, Xanthine Preparations, Alkalinizing Agents | |
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Clinical Impact: |
Concomitant use can lower serum lithium concentrations by increasing urinary lithium excretion. |
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Intervention: |
More frequent serum lithium concentration monitoring. Increase lithium dosage based on serum lithium concentration and clinical response [see Dosage and Administration (2.3)]. |
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Methyldopa, Phenytoin and Carbamazepine | |
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Clinical Impact: |
Concomitant use may increase risk of adverse reactions of these drugs. |
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Intervention: |
Monitor patients closely for adverse reactions of methyldopa, phenytoin, and carbamazepine. |
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Iodide Preparations | |
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Clinical Impact: |
Concomitant use may produce hypothyroidism. |
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Intervention: |
Monitor patients for signs or symptoms of hypothyroidism [see Warnings and Precautions (5.7)]. |
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Calcium Channel Blocking Agents (CCB) | |
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Clinical Impact: |
Concomitant use may increase the risk of neurologic adverse reactions in the form of ataxia, tremors, nausea, vomiting, diarrhea and/or tinnitus. |
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Intervention: |
Monitor for neurologic adverse reactions. |
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Atypical and Typical Antipsychotic Drugs | |
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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)]. |
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Intervention: |
Monitor for neurologic adverse reactions. |
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Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor | |
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Clinical Impact: |
Concomitant use of lithium with an SGLT2 inhibitor may decrease serum lithium concentrations. |
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Intervention: |
Monitor serum lithium concentration more frequently during SGLT2 inhibitor initiation and dosage changes. |
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Neuromuscular Blocking Agents | |
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Clinical Impact: |
Lithium may prolong the effects of neuromuscular blocking agents. |
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Intervention: |
Monitor for prolonged paralysis. |
USE IN SPECIFIC POPULATIONS SECTION
Highlight: * Pregnancy: May cause fetal and/or neonatal harm (8.1).
- Renal Impairment: Use caution during dose selection, starting with dosages less than those for patients with normal renal function while carefully monitoring for side effects (2.5, 6).
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary:
Lithium may cause harm when administered to a pregnant woman. Early voluntary reports to international birth registries suggested an increase in cardiovascular malformations, especially for Ebstein’s anomaly, with first trimester use of lithium. Subsequent case-control and cohort studies indicate that the increased risk for cardiac malformations is likely to be small; however, the data are insufficient to establish a drug-associated risk. There are concerns for maternal and/or neonatal lithium toxicity during late pregnancy and the postpartum period [see Clinical Considerations]. Published animal developmental and toxicity studies in mice and rats report an increased incidence of fetal mortality, decreased fetal weight, increased fetal skeletal abnormalities, and cleft palate (mouse fetuses only) with oral doses of lithium that produced serum concentrations similar to the human therapeutic range. Other published animal studies report adverse effects on embryonic implantation in rats after lithium administration. Advise pregnant women of the potential risk to a fetus.
The background risk of major birth defects and miscarriage for the indicated population(s) is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations:
Dose Adjustments During Pregnancy and the Postpartum Period: If the decision is made to continue lithium treatment during pregnancy, serum lithium concentrations should be monitored and the dosage adjusted during pregnancy. Two to three days prior to delivery, lithium dosage should be decreased or discontinued to reduce the risk of maternal and/or neonatal toxicity. Lithium may be restarted in the post-partum period at preconception doses in medically stable patients as long as serum lithium levels are closely monitored [see Dosage and Administration (2.4), Warnings and Precautions (5.1)].
Fetal/Neonatal Adverse Reactions: Lithium toxicity may occur in neonates who were exposed to lithium in late pregnancy. A floppy baby syndrome including neurological, cardiac, and hepatic abnormalities that are similar to those seen with lithium toxicity in adults have been observed. Symptoms include hypotonia, respiratory distress syndrome, cyanosis, lethargy, feeding difficulties, depressed neonatal reflexes, neonatal depression, apnea, and bradycardia. Monitor neonates and provide supportive care until lithium is excreted and toxic signs disappear, which may take up to 14 days.
Consider fetal echocardiography between 16 weeks and 20 weeks gestation in a woman with first trimester lithium exposure because of the potential increased risk of cardiac malformations.
8.2 Lactation
Risk Summary:
Limited published data reports the presence of lithium carbonate in human milk with breast milk levels measured at 0.12 mEq to 0.7 mEq or 40% to 45% of maternal plasma levels. Infants exposed to lithium during breastfeeding may have plasma levels that are 30% to 40% of maternal plasma levels. Signs and symptoms of lithium toxicity such as hypertonia, hypothermia, cyanosis, and ECG changes have been reported in some breastfed neonates and infants. Increased prolactin levels have been measured in lactating women, but the effects on milk production are not known. Breastfeeding is not recommended with maternal lithium use; however, if a woman chooses to breastfeed, the infant should be closely monitored for signs of lithium toxicity. Discontinue breastfeeding if a breastfed infant develops lithium toxicity.
Clinical Considerations:
Consider regular monitoring of lithium levels and thyroid function in a breastfed infant.
8.4 Pediatric Use
The safety and effectiveness of lithium for monotherapy treatment of acute manic or mixed episodes of bipolar I disorder and maintenance monotherapy of bipolar I disorder in pediatric patients ages 7 years to 17 years of age have been established in an acute-phase clinical trial of 8 weeks in duration followed by a 28-week randomized withdrawal phase [see Dosage and Administration (2.1), Adverse Reactions (6.1), Clinical Pharmacology (12.3), Clinical Studies (14)].
The safety and effectiveness of lithium has not been established in pediatric patients less than 7 years of age with bipolar I disorder.
8.5 Geriatric Use
Clinical studies of lithium carbonate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other treatment.
Lithium is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
8.6 Renal Impairment
As lithium is eliminated primarily through the kidney, lithium renal clearance is decreased in patients with abnormal renal function, and the risk of lithium intoxication increases considerably in this setting. Lithium should not be used in severe renal insufficiency (creatinine clearance less than 30 mL/min evaluated by Cockcroft-Gault), especially if the condition requires adherence to a low-sodium diet [see Dosage and Administration (2.5)].
Start patients with mild to moderately impaired renal function (creatinine clearance 30 mL/min to 89 mL/min evaluated by Cockcroft-Gault) with lower doses of lithium and titrate slowly while frequently monitoring serum lithium concentrations and for signs of lithium toxicity [see Dosage and Administration (2.5)].
OVERDOSAGE SECTION
10 OVERDOSAGE
The toxic concentrations for lithium (≥ 1.5 mEq/L) are close to the therapeutic concentrations [see Warnings and Precautions (5.1)]. At lithium concentrations greater than 3 mEq/L, patients may progress to seizures, coma, and irreversible brain damage.
Treatment:
For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.
No specific antidote for lithium poisoning is known. Mild symptoms of lithium toxicity can usually be treated by reduction in dose or cessation of the drug.
In severe cases of lithium poisoning, the goal of treatment is elimination of this ion from the patient. Administration of gastric lavage should be performed, but use of activated charcoal is not recommended as it does not significantly absorb lithium ions. Hemodialysis is the treatment of choice as it is an effective and rapid means of removing lithium in patients with severe toxicity. As an alternative option, urea, mannitol and aminophylline can induce a significant increase in lithium excretion. Appropriate supportive care for the patient should be undertaken. Patients with impaired consciousness should have their airway protected and it is critical to correct any volume depletion or electrolyte imbalance. Patients should be monitored to prevent hypernatremia while receiving normal saline and careful regulation of kidney function is of utmost importance.
Serum lithium concentrations should be closely monitored as there may be a rebound in serum lithium concentrations as a result of delayed diffusion from the body tissues. Likewise, during the late recovery phase, lithium should be re-administered with caution taking into account the possible release of significant lithium stores in body tissues.
SPL MEDGUIDE SECTION
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MEDICATION GUIDE Lithium (LITH-ee-əm) Oral Solution, USP | |||
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What is the most important information I should know about lithium oral solution? Lithium oral solution can cause serious side effects, including: *too much lithium in your blood (lithium toxicity). Lithium toxicity that can cause death may happen even if the lithium level in your blood is close to the right level for you. Your healthcare provider will need to monitor your blood levels of lithium to find the best dose for you. Take your lithium oral solution exactly as your healthcare provider tells you to take it.Stop taking lithium oral solution and call your healthcare provider right away if you have any symptoms of lithium toxicity including: | |||
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○ abnormal heartbeat |
○ vomiting |
○ diarrhea |
○ drowsiness |
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○ weak muscles |
○ blurred vision |
○ clumsiness |
○ ringing in your ears |
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○ muscle twitching | |||
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Other symptoms may include: | |||
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○ lightheadedness |
○ confusion | ||
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○ bloating |
○ mood changes | ||
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○ slurred speech |
○ breathing problems | ||
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○ seizure |
○ coma | ||
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What is lithium oral solution? Lithium oral solution is a prescription medicines called mood-stabilizing agents used alone (monotherapy) for:
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It is not known if lithium oral solution is safe and effective in children under 7 years of age with bipolar I disorder. | |||
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Who should not take lithium oral solution? Do not take****lithium oral solution if you are allergic to lithium or any of the ingredients in lithium oral solution. See the end of this medication guide for a complete list of ingredients in lithium oral solution. | |||
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What should I tell my healthcare provider before taking lithium oral solution? Before taking lithium oral solution, tell your healthcare provider if you:
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**Tell your healthcare provider about all the medicines you take,**including prescription, over-the-counter medicines, vitamins, and herbal supplements. Using lithium oral solution with certain other medicines may affect each other causing possible side effects. Lithium oral solution may affect the way other medicines work, and other medicines may affect how lithium oral solution works. Especially tell your healthcare provider if you take:
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Your healthcare provider can tell you if it is safe to take lithium oral solution with your other medicines.Do not start or stop any medicines while taking lithium oral solution without talking to your healthcare provider first. Know the medicines you take. Keep a list of your medicines to show your healthcare provider and pharmacist when you get a new medicine. | |||
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How should I take lithium oral solution?
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What should I avoid while taking lithium oral solution? *Do notdrive, operate heavy machinery, or do other dangerous activities when you start taking lithium oral solution, when your dose is changed, or until you know how lithium oral solution affects you. Lithium oral solution can make you sleepy. Talk to your healthcare provider about these activities.
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What are the possible side effects of lithium oral solution? See “What is the most important information I should know about lithium oral solution? Lithium oral solution may cause serious side effects, including: *kidney problems. People who take lithium oral solution may have to urinate often (polyuria) and have other kidney problems that may affect how their kidneys work. These problems can happen within a few weeks of starting to take lithium oral solution or after taking lithium oral solution for a long time. *low levels of sodium (salt) in your blood (hyponatremia). Lithium oral solution can cause you to lose sodium. Talk to your healthcare provider about your diet and how much fluid you are drinking when starting lithium oral solution. If you have been sweating more than usual or have had diarrhea, you may need extra salt and more fluids. Talk to your healthcare provider if this happens. *neurological problems. People who take lithium oral solution with certain other medicines called antipsychotics may have symptoms such as weakness, tiredness, fever, tremors, and confusion. Talk to your healthcare provider if this happens. Ask if you are not sure about the medicines you take. *serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when you take lithium oral solution while you take certain medicines called serotonergic and MAOIs. Symptoms of serotonin syndrome include: | |||
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○ agitation |
○ seeing things that are not there |
○ confusion | |
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○ coma |
○ rapid pulse |
○ high or low blood pressure | |
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○ dizziness |
○ sweating |
○ flushing | |
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○ fever |
○ tremors |
○ stiff muscles | |
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○ muscle twitching |
○ become unstable |
○ seizures | |
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○ nausea |
○ vomiting |
○ diarrhea | |
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*thyroid problems. *high calcium levels in your blood (hypercalcemia) and changes in your parathyroid gland (hyperparathyroidism) that may not go away when you stop taking lithium oral solution. *heart problems. People who take lithium oral solution may find out they also have a heart problem called Brugada Syndrome. People who have unexplained fainting or who have a family history of sudden unexplained death before 45 years of age may have Brugada Syndrome and not know it. If you faint or feel abnormal heartbeats, talk to your healthcare provider right away. *increased pressure in the brain and swelling in the eye (pseudotumor cerebri) that can cause vision problems or blindness. If you have severe headaches behind your eyes, ringing in the ears, blurred vision, double vision, or brief periods of blindness, talk to your health care provider right away. The most common side effects of lithium oral solution, include:
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These are not all the possible side effects of lithium oral solution. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. | |||
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How should I store lithium oral solution? Store lithium oral solution at room temperature, between 68°F to 77°F (20°C to 25°C). **Keep lithium oral solution and all medicines out of the reach of children. ** | |||
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General information about the safe and effective use of lithium oral solution. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use lithium oral solution for a condition for which it was not prescribed. Do not give lithium oral solution to other people, even if they have the same symptoms you have. It may harm them. You can ask your pharmacist or healthcare provider for information about lithium oral solution that is written for healthcare professionals. For more information, call Saptalis Pharmaceuticals, LLC at 1-833-727-8254. | |||
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What are the ingredients of lithium oral solution? Active ingredient: lithium carbonate, USP Inactive ingredients: citric acid, glycerin, orange flavor, propylene glycol, purified water, sodium benzoate, sorbitol solution, and sucralose. Manufactured by: | |||
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This Medication Guide has been approved by the U.S. Food and Drug Administration. |
Revised: 10/2023-R1 |
HOW SUPPLIED SECTION
16 HOW SUPPLIED/STORAGE AND HANDLING
Lithium oral solution, USP, is supplied as a clear, slightly yellow liquid with citrus aroma packed in 16 oz white HDPE modern round bottle with CRC or 7 mL blue unit-dose cup with peelable HDPE lidding.
Bottle of 473 mL (16 oz) NDC 71656-072-16
5 mL (8 mEq) fill, case of 5 trays x 10s NDC 71656-072-50
Storage
Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
Dispense in a tight, child-resistant container as defined in the USP/NF.