Lithium Salts

Class: Antimanic Agents
VA Class: CN750
CAS Number: 554-13-2
Brands: Eskalith, Lithobid

• 
  

  Lithium toxicity is closely related to serum lithium concentrations and can occur at dosages close to therapeutic levels.^{404 428}

  
  


• 
  

  Facilities for prompt and accurate serum lithium determinations should be available before initiating therapy.^{404 428} (See Renal Effects under Cautions.)

  
  

Introduction

Antimanic agent.^{404 428}

Uses for Lithium Salts

Bipolar Disorder

Management of bipolar disorder, ^{410 422} particularly acute manic or mixed episodes in patients with bipolar 1 or bipolar 2 disorder.^{401 403 404 405 406 407 409 410 411 412 421 422}

A first-line agent in the initial treatment of depressive, manic, or mixed episodes in patients with bipolar disorder.^{401 421 a}

Combination therapy with an atypical antipsychotic, another mood stabilizing agent, and/or antidepressant may be required to adequately treat rapid cycling and more severe depressive, manic, or mixed episodes.^{401 403 411 412 420 421 422 423}

Maintenance therapy has been shown to prevent or diminish the intensity of subsequent manic episodes in patients with bipolar disorder with a history of mania.^{403 404 405 407 410 412 421 422 424}

Major Depression†

Should be used only in patients who fail to respond to other antidepressants.^a

Schizoaffective and Schizophrenic Disorders†

Limited effectiveness when used alone; should be used only after antipsychotic agents have failed.^{439 a}

May be added to existing antipsychotic therapy, but efficacy of such combined therapy has varied in different clinical studies.⁴³⁹ Careful monitoring (e.g., serum lithium concentrations, adverse effects, possible adverse drug interactions) recommended.^{439 a}

Disorders of Impulse Control†

Has reduced temper outbursts, impulsive antisocial behavior, and the number of assaultive acts in a small number of adults with disorders of impulse control†.^a

Psychiatric Disorders in Children†

Treatment of children with apparent mixed bipolar disorder symptomatology†, hyperactivity with psychotic or neurotic components†, or aggressive behavior† or aggressive outbursts† associated with attention-deficit hyperactivity disorder (ADHD); should be used only after more conservative therapies have failed.^a

Neutropenia and Anemia†

Treatment of neutropenia† or anemia† secondary to antineoplastic drugs.^a

Routine use not recommended for congenital, idiopathic, or cyclic neutropenias†; Felty’s syndrome†; or aplastic anemia†.^a

Hyperthyroidism†

Treatment of hyperthyroidism†; other treatments (e.g., radioactive iodine, surgery, propylthiouracil, methimazole) currently are preferred.^a

SIADH†

No longer considered one of the therapies of choice; generally has been replaced with other more effective and/or less toxic therapies (e.g., demeclocycline).^a

Lithium Salts Dosage and Administration

General

• 
  

  Careful monitoring of serum lithium concentrations and clinical status of the patient is mandatory and patients should be carefully instructed in the safe use of the drug.^{404 428}

  
  


• 
  

  Carefully review the precautions and contraindications associated with lithium use before initiating therapy.^{404 428}

  
  


• 
  

  Monitor serum lithium concentrations twice weekly during initiation of the acute phase of therapy and until serum concentration and clinical condition have stabilized;^{404 405 428} patient’s ability to tolerate high serum lithium concentrations usually decreases as initial manic symptoms begin to subside.^a

  
  


• 
  

  After the patient has been stabilized, monitor serum concentrations at least every 2 months in most patients.^{404 405 428}

  
  


• 
  

  Onset of acute antimanic effect of lithium usually occurs within 5–7 days; full therapeutic effect often requires 10–21 days.^a

  
  


• 
  

  The manufacturers suggest that steady-state serum lithium concentrations be determined immediately before the next dose (i.e., 8–12 hours after the previous lithium dose).^{404 405 428} Total reliance must not be placed on serum lithium concentrations alone; accurate patient evaluation requires both careful clinical and laboratory evaluation.^{404 405 428}

  
  


• 
  

  Serum lithium concentrations of 1–1.2 mEq/L usually are required during acute affective episodes.^{401 427} Serum concentration should not exceed 1.5 mEq/L during the acute treatment phase.^{401 427}

  
  


• 
  

  If manifestations of lithium toxicity occur (see Lithium Toxicity under Cautions), temporarily discontinue for 24–48 hours, then resume at a lower dosage.^{404 405 428}

  
  

Administration

Oral Administration

Administer orally, preferably with meals in divided doses.^{404 428}

Administer conventional tablets, capsules, or oral solution 3 or 4 times daily;^{404 428} twice daily administration may be associated with adverse GI or nervous system effects.^a Administer extended-release tablets 2 or 3 times daily.^{404 405 a}

Extended-release preparations should be swallowed intact and should not be chewed, crushed, or halved.⁴⁰⁵

Lithium citrate oral solutions may be useful in patients unable to swallow capsules or tablets; 5 mL of a commercially available solution contains about 8 mEq of lithium and is approximately equivalent to 300 mg of lithium carbonate.^{404 428}

Dosage

Available as lithium carbonate and lithium citrate; dosages expressed in terms of the salts.^{404 428}

Pediatric Patients

Bipolar Disorder

Acute Episodes†

Oral

Children ≤11 years of age: Usual dosages not established; lithium carbonate dosages of 15–20 mg/kg (about 0.4–0.5 mEq/kg) daily or equivalent lithium citrate dosages have been given in 2 or 3 divided doses.⁴²⁷ (Do not exceed usual adult dosages.^a )

Children ≥12 years of age: Dosages usually are the same as those of adults.⁴²⁷

Maintenance Dosages†

Oral

Usual maintenance dosages have not been established; dosage should be adjusted according to serum lithium concentrations, patient tolerance, and clinical response.^a

Adults

Bipolar Disorder

Acute Episodes

Oral

Initially, 1.8 g daily as conventional lithium carbonate capsules or tablets, given in 3 or 4 divided doses, or 30 mL (about 48 mEq of lithium) of lithium citrate oral solution daily, given in 3 divided doses.^{404 428}

Alternatively, 900 mg twice daily (morning and evening) or 600 mg 3 times daily as extended-release lithium carbonate tablets.^{404 405}

Maintenance Dosages

Oral

900 mg to 1.2 g daily as conventional lithium carbonate capsules or tablets, given in 3 or 4 divided doses, or 15–20 mL (about 24–32 mEq of lithium) of lithium citrate oral solution daily, given in 3 or 4 divided doses. This dosage generally provides serum lithium concentrations of 0.6–1.2 mEq/L.^{404 405 427 428}

Alternatively, 900 mg to 1.2 g daily as extended-release lithium carbonate tablets, given in 2 or 3 divided doses.^{404 405}

Prescribing Limits

Pediatric Patients

Bipolar Disorder

Oral

When calculating dosage based on weight, do not exceed usual adult dosage.^{a 428}

Adults

Bipolar Disorder

Oral

Maintenance dosage usually should not exceed 2.4 g of lithium carbonate (65 mEq) daily.⁴²⁷

Special Populations

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.⁴⁰⁵ Lower initial dosages (e.g., ≤900 mg of lithium carbonate daily) and more gradual dosage titration recommended.^{401 405}

May have decreased renal function; monitor renal function and adjust dosage accordingly.⁴⁰⁵

Dosages that produce serum lithium concentrations at the lower end of therapeutic range may be sufficient for maintenance.⁴⁰¹ (See Geriatric Use under Cautions.)

Pregnant Women

Dosages generally need to be increased during pregnancy but should be reduced 1 week before parturition or when labor begins.^a (See Fetal/Neonatal Morbidity and Mortality and also see Pregnancy under Cautions.)

Cautions for Lithium Salts

Contraindications

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  Significant renal or cardiovascular disease, severe debilitation, dehydration, sodium depletion, or concomitant therapy with diuretics; very high risk of lithium toxicity under such conditions.^{404 428}

  
  


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  Only begin lithium in such patients if psychiatric indication is life-threatening, and other treatments have failed; however, must use with extreme caution, including daily serum lithium determinations and adjustment to usually low doses ordinarily tolerated by these individuals.^{404 428} In such instances, hospitalization is a necessity.^{404 428}

  
  

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal toxicity (e.g., increase in cardiac and other anomalies, especially Ebstein’s anomaly) when administered to pregnant women, but potential benefits may be acceptable in certain conditions despite the possible risks to the fetus.^{a 428}

If used in women of childbearing potential, during pregnancy, or if a patient becomes pregnant during treatment, the patient should be be informed of the potential hazard to the fetus.⁴²⁸

Whenever possible, lithium should be withdrawn for at least the first trimester unless it is determined that this would seriously endanger the mother.⁴²⁸ (See Pregnant Women under Dosage and Administration and see Pregnancy under Cautions.)

Lithium Toxicity

Risk of toxicity increases with increasing serum lithium concentrations.⁴²⁸ Serum concentration should not exceed 1.5 mEq/L during the acute treatment phase.^{401 427}

Serum lithium concentrations >1.5 mEq/L usually carry a greater risk than lower levels. (See General under Dosage and Administration.)⁴²⁸

Diarrhea, vomiting, drowsiness, muscular weakness and lack of coordination may be early signs of lithium toxicity, and can occur at lithium concentrations <2 mEq/L.⁴²⁸ At higher levels, giddiness, ataxia, blurred vision, tinnitus, and a large output of dilute urine may be seen.⁴²⁸

Serum lithium levels above 3 mEq/L may produce a complex clinical picture involving multiple organs and organ systems.⁴²⁸ (See General under Dosage and Administration.)

Renal Effects

Diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia, possible following chronic lithium therapy.⁴²⁸ Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy also possible.⁴²⁸

Measurement of 24-hour Cl_cr, renal-concentrating ability, and a urinalysis recommended prior to initiating therapy.^a Renal function should then be evaluated every 2–3 months for the first 6 months, then every 6–12 months during therapy or whenever clinically indicated.^{401 420}

If progressive or sudden changes in renal function, even within the normal range, occur during lithium therapy, reevaluate need for therapy with the drug.^a

Interactions

Encephalopathic syndrome reported with concomitant use with antipsychotic agents.^{404 405 428} May be similar to or same as neuroleptic malignant syndrome (NMS).^{404 405} (See Specific Drugs under Interactions.)

May prolong effects of neuromuscular blocking agents.^{404 405 428} (See Specific Drugs under Interactions.)

General Precautions

Concomitant Illnesses

Decreased tolerance to lithium has been reported to ensue from protracted sweating, diarrhea, or concomitant infection with elevated temperatures and may necessitate a temporary reduction or cessation of medication.^{404 428 a} Patients should maintain their usual fluid (2.5–3 L/day) and sodium intake, and supplement these in the event of fever (e.g., during infections), vomiting, or diarrhea.^{404 428 a}

Sodium-restricted Diet

Use with caution in patients whose sodium intake is restricted;^a stabilize sodium intake and carefully titrate lithium dosage to avoid increased serum lithium concentrations that may occur with sodium depletion.^a

Endocrine Effects

Hypothyroidism, with manifestations ranging from mild to severe myxedema, may occur within weeks to years after initiating lithium therapy; rarely, hypothyroidism may persist after discontinuance of the drug.^a Geriatric patients and patients with antithyroglobulin antibody, a prior history of Graves’ disease or Hashimoto’s thyroiditis, or those receiving iodine appear most at risk.^a Paradoxically, a few cases of hyperthyroidism also have been reported.

Preexisting thyroid disorders are not contraindications to lithium therapy.^{404 428} Patients with underlying hypothyroidism should have thyroid function (T₃, T₄, and TSH concentrations) evaluated yearly and be given supplemental thyroid therapy when needed.^a

Specific Populations

Pregnancy

Category D.⁴²⁸ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Women of childbearing age receiving lithium should be counseled about methods of birth control.^a If used during pregnancy, carefully monitor serum lithium concentrations and adjust dosage accordingly.^a (See Pregnant Women under Dosage and Administration.)

Lactation

Lithium is distributed into milk;⁴²⁸ discontinue nursing or the drug, taking into account the importance of the drug to the woman.⁴²⁸

Pediatric Use

Safety and efficacy have not been established in children <12 years of age;^{404 405 428 a} however, the drug has been used in this age group when benefits were thought to outweigh risks.^a

Transient acute dystonia and hyperreflexia occurred in a 15-kg child who ingested 300 mg of lithium carbonate.^{404 405 428}

Geriatric Use

Insufficient experience with extended-release tablets in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.⁴⁰⁵

Age-related differences in response to lithium generally not observed.⁴⁰⁵

Use with caution; geriatric patients appear more susceptible to adverse effects (e.g., adverse nervous system and neuromuscular effects), even at therapeutic serum concentrations, and more prone to developing lithium-induced goiter and clinical hypothyroidism.^{404 a} Some clinicians recommend that thyroid function tests be performed every 6–12 months in these patients.^a

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy; geriatric patients should receive initial lithium dosages in the lower end of the usual range (see Geriatric Patients under Dosage and Administration).⁴⁰⁵

Lithium is substantially excreted by the kidneys; consider monitoring renal function and adjust dosage if necessary since geriatric patients are more likely to have decreased renal function.⁴⁰⁵

Common Adverse Effects

Fine hand tremor, polyuria, mild thirst, transient and mild nausea, and general discomfort may appear during the first few days of lithium administration; usually subside with continued treatment, a temporary reduction of dosage, or temporary cessation.^{405 428} If persistent, a cessation of therapy is indicated.^{405 428}

Interactions for Lithium Salts

Lithium is not metabolized.^a

Electroconvulsive Therapy

Acute neurotoxicity with prominent delirium has occurred in patients receiving lithium and electroconvulsive therapy (ECT) concurrently.^a Some clinicians recommend decreasing lithium dosage or withdrawing the drug 2 days prior to ECT.^a

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Increased plasma lithium concentrations resulting in several cases of lithium intoxicationa	If used concomitantly, adjust lithium dosages and carefully monitor serum lithium concentrationsa Some clinicians advise against concomitant ACE inhibitor use in geriatric patients or those patients with CHF, renal insufficiency, or volume depletiona
Alkalinizing agents (e.g., sodium bicarbonate)	May increase renal excretion of lithiuma	Higher lithium dosage may be requireda
Anticonvulsants (e.g., carbamazepine, phenytoin)	Adverse neurologic effects following concomitant therapy with carbamazepine or phenytoina Concurrent use of lithium and phenytoin may increase serum lithium concentrationsa	Clinical importance not determineda
Antidepressants, SSRIs (e.g., fluoxetine, paroxetine)	Possibly associated with increased serum lithium concentrations, lithium toxicity, and/or serotonin syndrome (e.g., absence seizures, agitation, ataxia, confusion, diarrhea, dizziness, dysarthria, stiffness of the extremities, tremor);404 405 a decreased serum lithium concentrations also reported405	Use with caution and monitor closely404 405
Antipsychotic agents (e.g., haloperidol, phenothiazines)	Acute encephalopathic syndromes or extrapyramidal reactions (e.g., NMS or NMS-type reactions), possibly resulting in irreversible brain damage, parkinsonian movements, and dyskinesiasa 404 405 428 Nausea and vomiting, which are occasionally signs of lithium intoxication, may be masked by the antiemetic effect of some phenothiazines when used concurrentlya	Monitor patients for adverse neurologic effects, especially when large dosages of lithium and an antipsychotic agent are used; combined therapy should be promptly discontinued if such signs or symptoms appear404 405 428 a
β-Adrenergic blocking agents	Absence of tremor may make lithium intoxication more difficult to diagnosea	Monitor for other signs and symptoms of lithium intoxicationa
Baclofen	May cause hyperkinetic movementsa
Calcium-channel blocking agents (e.g., verapamil)	May potentiate the toxic effects of lithium; neurotoxicity (e.g., ataxia, choreoathetosis, tremors, tinnitus), adverse GI effects (e.g., nausea, vomiting, diarrhea), and bradycardia reporteda Decreased serum lithium concentrations following initiation of verapamil in patients stabilized on lithium therapya	Use with cautiona Monitor serum lithium concentrations and patient; adjust lithium dosage accordingly when verapamil is initiated or discontinued in patients receiving lithium therapya
Diazepam	Profound hypothermia has been reported in at least one patienta	Widespread use usually without unusual adverse effects indicates that it is safe in most patientsa
Diuretics (e.g., amiloride, aminophylline, furosemide, spironolactone, thiazides, urea)	Decreased lithium clearance resulting in increased serum lithium concentrations and several cases of lithium intoxication have occurred with concomitant thiazide usea Other diuretics (e.g., aminophylline, furosemide, spironolactone, urea) also may reduce renal clearance of lithiuma Amiloride does not appear to substantially affect lithium pharmacokinetics in most patientsa	Concomitant use usually is contraindicateda 428 If used in combination with thiazide diuretics, usual initial dosage of lithium should be reduced by about 50% and the patient and serum lithium concentrations should be monitored carefully;a subsequent lithium dosage should be adjusted as necessarya
Iodides	Additive or synergistic hypothyroid effect; may result in hypothyroidisma	Concomitant use is not recommended; if used concomitantly, monitor closely for signs and symptoms of hypothyroidisma
Metronidazole	May increase serum lithium concentrations, resulting in signs of lithium toxicitya	Use with caution; monitor serum lithium concentrations frequentlya
Neuromuscular blocking agents (e.g., pancuronium, succinylcholine)	May prolong the latency of neuromuscular blockadea	Use with caution and carefully monitor patients during concomitant use;a consider temporary discontinuance of lithiuma
NSAIAs (e.g., celecoxib, indomethacin, piroxicam)	Decreased renal clearance of lithium, which may lead to increased serum or plasma lithium concentrations and lithium toxicity404 405 428 a	Monitor serum lithium concentrations and observe patient for signs and symptoms of lithium intoxication404 405 428 a Adjust lithium dosages as neededa
Opiate agonists	Interferes with opiate-induced euphoria and diminishes the analgesic effect of opiates (narcotic analgesics)a
Sodium	Changes in sodium intake in patients receiving lithium may alter the renal elimination of lithiuma	Patients should be advised to avoid substantial changes in their sodium intakea When drugs with a high sodium content (e.g., antacids) are used concomitantly with lithium, serum lithium concentrations should be monitoreda
Tetracycline	Increased serum lithium concentrationsa	The clinical importance of this effect has not been determineda

Lithium Salts Pharmacokinetics

Absorption

Bioavailability

Conventional lithium carbonate capsules and tablets are 95–100% absorbed.^a

Extended-release lithium carbonate tablets are 60–90% absorbed.^a

Lithium citrate oral solutions are essentially 100% absorbed.^a

Onset

Acute antimanic effect usually occurs within 5–7 days; full therapeutic effect often requires 10–21 days.^a

Food

Food does not appear to affect the bioavailability of lithium.^a

Plasma Concentrations

Therapeutic serum lithium concentrations usually range from 1–1.2 mEq/L during acute affective episodes.^{401 427 428}

A 12-hour steady-state serum lithium concentration is used by most clinicians for monitoring serum concentrations; this concentration shows a high intraindividual (but not interindividual) reproducibility.^a (See General under Dosage and Administration.)

Distribution

Extent

Widely distributed into most body tissues and fluids, including bone, brain tissue, erythrocytes, saliva, and thyroid.^a

Lithium freely crosses the placenta; maternal and fetal serum concentrations are approximately equal.^a The milk of nursing women contains lithium concentrations that are approximately 33–50% of those in serum.^a

Plasma Protein Binding

Lithium is not bound to plasma proteins.^a

Elimination

Metabolism

Lithium is not metabolized.^a

Elimination Route

Principally renal.⁴²⁸

Half-life

Approximately 24 hours.⁴²⁸

Special Populations

In geriatric patients and patients with impaired renal function, serum half-lives of 36 and 40–50 hours, respectively, have been reported.^a

Clearance and distribution into erythrocytes may be increased during pregnancy.^a Immediately postpartum, renal clearance of lithium may decrease to pre-pregnancy levels.^a

Lithium is readily removed by hemodialysis but not as readily removed by peritoneal dialysis.^a Rebound increases in serum lithium concentration frequently occur 5–8 hours after dialysis.^a

Stability

Storage

Oral

Capsules, Tablets, and Extended-release Tablets

Well-closed containers at 15–30°C.^{404 405 a} Protect from moisture.⁴⁰⁵

Solution

Tight containers at 15–30°C.^{404 a}

ActionsActions

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  Alters sodium transport in nerve and muscle cells and effects a shift toward intraneuronal metabolism of catecholamines, but the specific biochemical mechanism of lithium action in mania is unknown.^{404 405 428}

  
  


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  Decreases renal-concentrating ability and water reabsorption and initially increases sodium and potassium excretion.^a Some of these effects are overcome by counteracting physiologic mechanisms, while others may persist.^a GFR may be slightly decreased in patients receiving prolonged lithium therapy.^a

  
  

• 
  

  Various effects on the thyroid gland; principal effect is to block the release of thyroxine (T₄) and triiodothyronine (T₃) mediated by thyrotropin.^a This results in a decrease in circulating T₄ and T₃ concentrations and a feedback increase in serum thyrotropin concentration.^a Lithium also inhibits thyrotropin-stimulated adenylate cyclase activity and thyrotropin-induced release of thyroidal iodine 131, decreases intrathyroidal iodothyronine-iodotyrosine ratios, and inhibits colloid droplet formation.^a

  
  

Advice to Patients

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  Importance of avoiding dehydration and maintaining usual sodium and fluid intake; importance of reporting polyuria and any prolonged vomiting, diarrhea, or fever to clinician.^{404 428}

  
  


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  Importance of immediately discontinuing lithium therapy and consulting a clinician if signs of lithium intoxication (e.g., muscle twitching, tremor, mild ataxia, drowsiness, muscle weakness, diarrhea, vomiting) occur.^{404 428}

  
  


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  Importance of advising patients that lithium may impair their ability to perform activities requiring mental alertness or physical coordination (e.g., operating machinery, driving a motor vehicle).^{404 428}

  
  


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  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.^{404 428}

  
  


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  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{404 428}

  
  


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  Importance of informing patients of other important precautionary information.^{404 405 428} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Lithium Carbonate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	150 mg (4.06 mEq of lithium)	Lithium Carbonate Capsules	Roxane
		300 mg (8.12 mEq of lithium)*	Eskalith (with benzyl alcohol and povidone)	GlaxoSmithKline
		600 mg (16.24 mEq of lithium)	Lithium Carbonate Capsules	Roxane
	Tablets	300 mg (8.12 mEq of lithium)	Lithium Carbonate Tablets (with povidone; scored)	Roxane, Rugby
	Tablets, extended-release	450 mg (12.18 mEq of lithium)	Eskalith CR (scored)	GlaxoSmithKline
	Tablets, extended-release, film-coated	300 mg (8.12 mEq of lithium)	Lithobid Slow-release (with povidone and propylene glycol)	JDS Pharma

Lithium Citrate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Solution	8 mEq (of lithium) per 5 mL	Lithium Citrate Syrup (with alcohol 0.3%)	Major, Morton Grove, Roxane

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 04/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Lithium Carbonate 150MG Capsules (ROXANE): 90/$18.99 or 270/$56.97

Lithium Carbonate 300MG Capsules (ROXANE): 90/$25.99 or 180/$42.97

Lithium Carbonate 300MG Controlled-release Tablets (ROXANE): 30/$17.99 or 90/$35.97

Lithium Carbonate 300MG Tablets (ROXANE): 90/$25.99 or 270/$59.97

Lithium Carbonate 450MG Controlled-release Tablets (ROXANE): 60/$28.99 or 180/$81.97

Lithium Carbonate 600MG Capsules (ROXANE): 90/$39.99 or 270/$119.97

Lithium Citrate 8MEQ/5ML Syrup (ROXANE): 500/$59.99 or 1500/$150.96

Lithobid 300MG Controlled-release Tablets (NOVEN THERAPEUTICS): 90/$222 or 270/$625.95

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions June 01, 2006. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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402. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed (text revision). Washington, DC: American Psychiatric Association; 2000:362, 382-401, 427-8.

403. Suppes T, Dennehy EB, Swann AC et al. Report of the Texas Consensus Conference Panel on medication treatment of bipolar disorder 2000. J Clin Psychiatry. 2002; 63:288-99. [IDIS 479903] [PubMed 12004801]

404. GlaxoSmithKline. Eskalith (lithium carbonate) Controlled-Release Tablets prescribing information. Research Triangle Park, NC. 2003 Sep.

405. Solvay Pharmaceuticals Inc. Lithobid (lithium carbonate, USP) Slow-Release Tablets prescribing information. Marietta, GA; 2002 Dec.

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417. Bowden CL, Brugger AM, Swann AC et al. The Depakote Mania Study Group. Efficacy of divalproex vs lithium and placebo in the treatment of mania. JAMA. 1994; 271:918-24. [IDIS 327065] [PubMed 8120960]

418. Pies R. Have we undersold lithium for bipolar disorder? J Clin Psychopharmacol. 2002; 22:445-9. Editorial.

419. Young AH, Macritchie AN. Treatment of bipolar affective disorder: new drug treatments are emerging, but more clinical evidence is required. BMJ. 2000; 321:1302-3. [IDIS 456346] [PubMed 11090500]

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421. US Surgeon General. Mental Health: A Report of the Surgeon General. Specific treatments for episodes of depression and mania. From the US Surgeon General’s website. Accessed on 2002 Oct 28.

422. Sachs GS et al. The expert consensus guideline series: medication treatment of bipolar disorder 2000. Postgrad Med. 2000 Apr.

423. Gonzalez-Pinto A, Tohen M, Lalaguna B et al. Treatment of bipolar I rapid cycling patients during dysphoric mania with olanzapine. J Clin Psychopharmacol. 2002; 22:450-4. [IDIS 487633] [PubMed 12352266]

424. Burgess S, Geddes J, Hawton K et al. Lithium for maintenance treatment of mood disorders. Cochrane Database Syst Rev. 2001(3):CD003013.

425. Macritchie KAN, Geddes JR, Scott J et al. Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder (Cochrane Review). In: The Cochrane Library. 2002(4). Oxford:Update Software.

426. Tohen M, Chengappa KNR, Suppes T et al. Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy. Arch Gen Psychiatr. 2002; 59:62-9. [IDIS 474664] [PubMed 11779284]

427. USP DI: drug information for the health care provider. Johnson KW, ed. 22th ed. Englewood, CO: Micromedex, Inc; 2002:1907-12.

428. Roxane Laboratories. Lithium carbonate capsules and tablets and lithium citrate syrup USP prescribing information. Columbus, OH; 2002 May.

429. Garbutt JC, West SL, Carey TS et al. Pharmacological treatment of alcohol dependence: a review of the evidence. JAMA. 1999; 281:1318-25. [IDIS 422893] [PubMed 10208148]

430. Dorus W, Ostrow DG, Anton R et al. Lithium treatment of depressed and nondepressed alcoholics. JAMA. 1989; 262:1646-52. [IDIS 259343] [PubMed 2504944]

431. Henry GC. Lithium. In Goldfrank LR, Flomenbaum NE, Lewin NA et al, eds. Goldfrank’s Toxicologic emergencies. 7th ed. New York: McGraw Hill; 2002:894-9.

432. Yassa R. Lithium-methyldopa interaction. CMAJ. 1986; 134:141-2. [IDIS 210399] [PubMed 3080214]

433. Osanloo E, Deglin JH. Interaction of lithium and methyldopa. Ann Intern Med. 1980; 92:433-4. [IDIS 110090] [PubMed 7356241]

434. O’Regan JB. Adverse interaction of lithium carbonate and methyldopa.

K-Phos No. 2

Generic Name: potassium phosphate and sodium phosphate (poe TASS ee um FOSS fate and SEW dee um FOSS fate)

Brand Names: K-Phos M.F., K-Phos Neutral, K-Phos No. 2, Neutra-Phos, Uro-KP-Neutral

What are K-Phos No. 2 (potassium phosphate and sodium phosphate)?

Phosphorus is a naturally occurring substance that is important in every cell in the body. The majority of phosphorus in the body is found in the bones. The potassium and sodium salt forms of phosphorus are called phosphates.

Potassium phosphate and sodium phosphate is used to acidify the urine and lower the urinary calcium concentration. This may reduce rash and odor caused by ammonium in the urine. Potassium phosphate and sodium phosphate may also increase the antibiotic effect of methenamine (Hiprex, Urex). Potassium phosphate and sodium phosphate is also used as a phosphorus supplement to prevent and/or treat a phosphorus deficiency.

Potassium phosphate and sodium phosphate may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about K-Phos No. 2 (potassium phosphate and sodium phosphate)?

Do not take antacids containing aluminum, calcium, or magnesium while taking potassium phosphate and sodium phosphate, except under the supervision of your doctor. Antacids may decrease phosphate absorption.

If you have kidney stones, there is a possibility that you will pass old stones after starting treatment with potassium phosphate and sodium phosphate.

Who should not take K-Phos No. 2 (potassium phosphate and sodium phosphate)?

You cannot take potassium phosphate and sodium phosphate if you have

• 
  

  high levels of potassium in your body,

  
  


• 
  

  high levels of phosphorus in your body,

  
  


• 
  

  infected phosphate stones, or

  
  


• severe kidney disease.

Before taking potassium phosphate and sodium phosphate, tell your doctor if you have

• 
  

  Addison's disease,

  
  


• 
  

  a bowel obstruction,

  
  


• 
  

  heart disease,

  
  


• 
  

  high blood pressure,

  
  


• kidney disease,


• liver disease or cirrhosis,


• 
  

  swelling or water retention,

  
  


• 
  

  high levels of sodium in your body,

  
  


• 
  

  low levels of calcium in your body,

  
  


• 
  

  hypoparathyroidism,

  
  


• 
  

  pancreatitis, or

  
  


• 
  

  rickets.

  
  

You may not be able to take potassium phosphate and sodium phosphate, or you may require a lower dose or special monitoring if you have any of the conditions listed above.

Potassium phosphate and sodium phosphate is in the FDA pregnancy category C. This means that it is not known whether potassium phosphate and sodium phosphate will harm an unborn baby. Do not take this medication without first talking to your doctor if you are pregnant. It is also not known whether potassium phosphate and sodium phosphate will harm a nursing infant. Do not take potassium phosphate and sodium phosphate without first talking to your doctor if you are breast-feeding baby.

How should I take K-Phos No. 2 (potassium phosphate and sodium phosphate)?

Take potassium phosphate and sodium phosphate exactly as directed by your doctor or as directed on the package. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each tablet with a full glass of water.

The K-Phos Original tablets should be dissolved in 6 to 8 ounces (180 to 240 mL) of water. Let the tablets soak for 2 to 5 minutes, or more if necessary, and stir. If tablet particles remain, they can be crushed and stirred to speed dissolution. Drink the solution once the tablets are completely dissolved.

Do not swallow the Neutra-Phos capsules whole. They must be opened, and the contents mixed with water. Mix the Neutra-Phos powder and capsule contents with 75 mL (approximately one-third cup) of water, and drink the solution. Do not take more of this medication than is recommended. If your symptoms are not being treated, notify your doctor. Store potassium phosphate and sodium phosphate at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only the next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed.

What happens if I overdose?

Seek emergency medical attention.

Most commonly, symptoms of an overdose include nausea, vomiting, diarrhea, dehydration, and severe and prolonged muscle cramps or paralysis.

What should I avoid while taking K-Phos No. 2 (potassium phosphate and sodium phosphate)?

Do not take antacids containing aluminum, calcium, or magnesium while taking potassium phosphate and sodium phosphate, except under the supervision of your doctor. Antacids may decrease phosphate absorption.

K-Phos No. 2 (potassium phosphate and sodium phosphate) side effects

Stop taking potassium phosphate and sodium phosphate and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of your throat; swelling of your lips, tongue, or face; or hives).

Other, less serious side effects may also to occur. Nausea, vomiting, stomach pain, and diarrhea are among the most common. These side effects usually lessen after a few days of therapy. Notify your doctor if you develop these side effects.

If you have kidney stones, there is a possibility that you will pass old stones after starting treatment with potassium phosphate and sodium phosphate.

Less commonly, the following side effects have been reported:

• 
  

  headache;

  
  


• 
  

  dizziness or confusion;

  
  


• 
  

  weakness or heaviness of the legs;

  
  


• 
  

  diarrhea;

  
  


• 
  

  seizures;

  
  


• 
  

  unusual tiredness or weakness;

  
  


• 
  

  muscle cramps;

  
  


• 
  

  numbness, tingling, pain, or weakness of the hands or feet;

  
  


• 
  

  swelling of the feet or lower legs;

  
  


• 
  

  unusual weight gain;

  
  


• 
  

  increased thirst;

  
  


• 
  

  decreased urine; or

  
  


• 
  

  bone or joint pain.

  
  

Notify your doctor if you develop any of the side effects listed above.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect K-Phos No. 2 (potassium phosphate and sodium phosphate)?

Do not take antacids containing aluminum, calcium, or magnesium while taking potassium phosphate and sodium phosphate, except under the supervision of your doctor. Antacids may decrease phosphate absorption.

Before taking potassium phosphate and sodium phosphate, tell your doctor if you are taking any of the following medicines

• 
  

  calcium and/or vitamin D supplements;

  
  


• 
  

  potassium supplements or salt substitutes;

  
  


• 
  

  a diuretic (water pill) such as triamterene (Dyrenium, Dyazide, Maxzide), spironolactone (Aldactone), or amiloride (Midamor);

  
  


• 
  

  a heart medication such as guanethidine (Ismelin), diazoxide (Hyperstat, Proglycem), hydralazine (Apresoline), methyldopa (Aldomet), or reserpine (Ser-Ap-Es); or

  
  


• 
  

  a steroid medicine such as corticotropin (ACTH, Acthar), cortisone (Cortone), hydrocortisone (Cortef, others), prednisone (Orasone, Deltasone, others), prednisolone (Prelone, Pediapred, Delta-Cortef, others), methylprednisolone (Medrol, others), triamcinolone (Aristocort, Kenalog, Tri-Kort, Trilog, others), dexamethasone (Decadron), or betamethasone (Celestone).

  
  

You may require a dosage adjustment or special monitoring if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with potassium phosphate and sodium phosphate. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More K-Phos No. 2 resources

• K-Phos No. 2 Side Effects (in more detail)
• K-Phos No. 2 Use in Pregnancy & Breastfeeding
• Drug Images
• K-Phos No. 2 Drug Interactions
• K-Phos No. 2 Support Group
• 0 Reviews for K-Phos No. 2 - Add your own review/rating

• K-Phos Neutral Advanced Consumer (Micromedex) - Includes Dosage Information


• K-Phos Neutral MedFacts Consumer Leaflet (Wolters Kluwer)

Compare K-Phos No. 2 with other medications

• Hypophosphatemia
• Urinary Acidification

Where can I get more information?

• Your pharmacist has more information about potassium phosphate and sodium phosphate written for health professionals that you may read.

See also: K-Phos No. 2 side effects (in more detail)

Supac

Generic Name: acetaminophen, aspirin, and caffeine (ah SEET a MIN oh fen, ASP i rin, and KAF een)

Brand Names: Anacin Advanced Headache Formula, Excedrin, Excedrin Express Gels, Excedrin Extra Strength, Excedrin Extra Strength Geltab, Excedrin Geltab, Excedrin Menstrual Express Gels, Excedrin Migraine, Excedrin Migraine Geltab, Genace, Goodys Extra Strength, Goodys Headache Powders, Pain Reliever Plus

What is Supac (acetaminophen, aspirin, and caffeine)?

Acetaminophen is a pain reliever and a fever reducer.

Aspirin is in a group of drugs called salicylates (sa-LIS-il-ates). It works by reducing substances in the body that cause pain, fever, and inflammation.

Caffeine is a central nervous system stimulant. It relaxes muscle contractions in blood vessels to improve blood flow.

The combination of acetaminophen, aspirin, and caffeine is used to treat pain caused by tension headaches, migraine headaches, muscle aches, menstrual cramps, arthritis, toothaches, the common cold, or nasal congestion.

Aspirin should be used for cardiovascular conditions only under the supervision of a doctor.

Acetaminophen, aspirin, and caffeine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Supac (acetaminophen, aspirin, and caffeine)?

Aspirin should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Aspirin can cause a serious and sometimes fatal condition called Reye's syndrome in children. You should not use this medication if you are allergic to acetaminophen (Tylenol), aspirin, or caffeine, or if you have liver disease, stomach or intestinal bleeding, a history of asthma or severe allergic reaction to aspirin or an NSAID (non-steroidal anti-inflammatory drug).

Do not use this medication without first talking to your doctor if you drink more than three alcoholic beverages per day or if you have had alcoholic liver disease (cirrhosis). You may not be able to use acetaminophen.

Ask a doctor or pharmacist about using acetaminophen, aspirin, and caffeine if you have asthma or seasonal allergies, fever with a stiff neck, a stomach ulcer or pain, heartburn, a bleeding or blood clotting disorder, diabetes, or gout.

Do not use more of this medication than is recommended. An overdose of acetaminophen can cause serious harm. The maximum amount of acetaminophen for adults is 1 gram (1000 mg) per dose and 4 grams (4000 mg) per day.

Stop using this medication and call your doctor at once if you have any symptoms of liver damage or bleeding in your stomach or intestines. Symptoms of liver damage include nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, and jaundice (yellowing of the skin or eyes). Symptoms of stomach bleeding include weakness or fainting, bloody or tarry stools, and coughing up blood or vomit that looks like coffee grounds.

Avoid drinking alcohol while you are taking this medication. Alcohol may increase your risk of stomach bleeding while taking aspirin, or liver damage while taking acetaminophen. Do not use any other over-the-counter cough, cold, allergy, pain, menstrual symptom, or fever medication without first asking your doctor or pharmacist. Acetaminophen (sometimes abbreviated as "APAP"), aspirin, and caffeine are contained in many combination medicines. If you use certain products together you may accidentally use too much of a certain drug.

What should I discuss with my healthcare provider before taking Supac (acetaminophen, aspirin, and caffeine)?

Aspirin should not be given to a child or teenager who has a fever, especially if the child also has flu symptoms or chicken pox. Aspirin can cause a serious and sometimes fatal condition called Reye's syndrome in children. You should not use this medication if you are allergic to acetaminophen (Tylenol), aspirin, or caffeine, or if you have:

• 
  

  a recent history of stomach or intestinal bleeding;

  
  


• liver disease;


• 
  

  asthma or severe allergic reaction caused by taking aspirin or an NSAID (non-steroidal anti-inflammatory drug), especially "aspirin triad syndrome"; or

  
  


• 
  

  if you are allergic to an NSAID such as Advil, Motrin, Aleve, Orudis, Indocin, Lodine, Voltaren, Toradol, Mobic, Relafen, Feldene, and others.

  
  

Ask a doctor or pharmacist if it is safe for you to take acetaminophen, aspirin, and caffeine if you have:

• 
  

  asthma or seasonal allergies;

  
  


• 
  

  fever with a stiff neck;

  
  


• 
  

  a stomach ulcer, heartburn, or stomach pain;

  
  


• 
  

  a bleeding or blood clotting disorder such as hemophilia;

  
  


• 
  

  diabetes; or

  
  


• 
  

  gout.

  
  

If you take acetaminophen, aspirin, and caffeine to treat headache pain, seek medical attention if you have:

• 
  

  a headache so bad you have to lie down;

  
  


• 
  

  a headache that causes vomiting;

  
  


• 
  

  what feels like the worst headache you've ever had;

  
  


• 
  

  a headache that seems different from your usual headaches;

  
  


• 
  

  a headache every day;

  
  


• 
  

  a headache after coughing, bending, exercising, or head injury;

  
  


• 
  

  if you have never had migraines diagnosed by a doctor; or

  
  


• 
  

  if you are having your first headache after age 50.

  
  

Aspirin may be harmful to an unborn baby's heart, and may also reduce birth weight or have other dangerous effects. Tell your doctor if you are pregnant or plan to become pregnant while you are taking acetaminophen, aspirin, and caffeine. Aspirin, acetaminophen, and caffeine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Supac (acetaminophen, aspirin, and caffeine)?

Use this medication exactly as directed on the label, or as it has been prescribed by your doctor. Do not use the medication in larger or smaller amounts, or use it for longer than recommended.

Do not use more of this medication than is recommended. An overdose of acetaminophen can cause serious harm. The maximum amount for adults is 1 gram (1000 mg) per dose and 4 grams (4000 mg) per day. Using more acetaminophen could cause damage to your liver.

If you drink more than three alcoholic beverages per day, talk to your doctor before taking acetaminophen and never use more than 2 grams (2000 mg) per day.

Take this medication with a full glass of water. Take the medicine with food or milk if it makes your stomach upset. Stop using acetaminophen, aspirin, and caffeine and call your doctor if your symptoms do not improve, or if they get worse while taking this medication.

Acetaminophen can cause false results with some urine glucose tests. Talk to your doctor if you are diabetic and you notice changes in your glucose levels while taking this medication.

If you need to have any type of surgery, tell the surgeon ahead of time that you are taking aspirin. You may need to stop using the medicine for a short time.

Store acetaminophen, aspirin, and caffeine at room temperature away from heat and moisture.

What happens if I miss a dose?

Since this medication is often used only when needed, you may not be on a dosing schedule. If you are using the medication regularly, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and wait until your next regularly scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

An overdose of acetaminophen, aspirin, and caffeine can also cause ringing in your ears, headache, diarrhea, dizziness, restlessness, hallucinations, fast or slow heart rate, or seizure (convulsions).

What should I avoid while taking Supac (acetaminophen, aspirin, and caffeine)?

Avoid drinking alcohol while you are taking this medication. Alcohol may increase your risk of stomach bleeding while taking aspirin, or liver damage while taking acetaminophen. Do not use any other cough, cold, allergy, pain, menstrual symptom, or fever medication without first asking your doctor or pharmacist. Acetaminophen (sometimes abbreviated as "APAP"), aspirin, and caffeine are contained in many combination medicines. If you use certain products together you may accidentally use too much of a certain drug. Read the label of any other medicine you are using to see if it contains acetaminophen, APAP, aspirin, or caffeine.

Avoid taking an NSAID such as ibuprofen (Motrin, Advil), diclofenac (Voltaren), diflunisal (Dolobid), etodolac (Lodine), flurbiprofen (Ansaid), indomethacin (Indocin), ketoprofen (Orudis), ketorolac (Toradol), mefenamic acid (Ponstel), meloxicam (Mobic), nabumetone (Relafen), naproxen (Aleve, Naprosyn), piroxicam (Feldene), and others.

Avoid coffee, tea, cola, energy drinks or other sources of caffeine while taking this medication. They can add to the side effects of the caffeine in the medication.

Supac (acetaminophen, aspirin, and caffeine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

• 
  

  weakness or fainting;

  
  


• 
  

  black, bloody, or tarry stools;

  
  


• 
  

  coughing up blood or vomit that looks like coffee grounds;

  
  


• 
  

  severe nausea, vomiting, or stomach pain;

  
  


• 
  

  redness or swelling;

  
  


• 
  

  low fever with nausea, stomach pain, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

  
  


• 
  

  fever lasting longer than 3 days;

  
  


• 
  

  pain lasting longer than 10 days; or

  
  


• 
  

  hearing problems, ringing in your ears.

  
  

Less serious side effects may include:

• 
  

  upset stomach, heartburn;

  
  


• 
  

  feeling nervous or excited; or

  
  


• 
  

  sleep problems (insomnia).

  
  

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Supac (acetaminophen, aspirin, and caffeine)?

Tell your doctor if you are taking an antidepressant such as citalopram (Celexa), duloxetine (Cymbalta), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), or venlafaxine (Effexor). Taking any of these drugs with aspirin may cause you to bruise or bleed easily.

Before taking acetaminophen, aspirin, and caffeine, tell your doctor if you are using any of the following drugs:

• 
  

  a blood thinner such as warfarin (Coumadin);

  
  


• 
  

  salicylates such as aspirin, Backache Relief Extra Strength, Novasal, Nuprin Backache Caplet, Doan's Pills Extra Strength, Tricosal, and others; or

  
  


• 
  

  medication used to prevent blood clots, such as alteplase (Activase), clopidogrel (Plavix), dipyridamole (Persantine), ticlopidine (Ticlid), and urokinase (Abbokinase).

  
  

This list is not complete and there may be other drugs that can interact with acetaminophen, aspirin, and caffeine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Supac resources

• Supac Side Effects (in more detail)
• Supac Use in Pregnancy & Breastfeeding
• Supac Drug Interactions
• Supac Support Group
• 0 Reviews for Supac - Add your own review/rating

• Excedrin Consumer Overview


• Excedrin MedFacts Consumer Leaflet (Wolters Kluwer)


• Genace Consumer Overview

Compare Supac with other medications

• Migraine
• Osteoarthritis
• Pain/Fever

Where can I get more information?

• Your pharmacist can provide more information about acetaminophen, aspirin, and caffeine.

See also: Supac side effects (in more detail)

Zomestine 80 mg prolonged-release tablets

1. Name Of The Medicinal Product

Zomestine 80 mg prolonged-release tablets

2. Qualitative And Quantitative Composition

Each prolonged-release tablet contains 80 mg oxycodone hydrochloride equivalent to 72 mg oxycodone.

Excipient:

The prolonged-release tablets contain a maximum of 48 mg sucrose.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Prolonged-release tablet.

Red, oblong, biconvex, tablets with break scores on both sides. The tablet can be divided into equal halves.

4. Clinical Particulars

4.1 Therapeutic Indications

Severe pain, which can be adequately managed only with opioid analgesics.

4.2 Posology And Method Of Administration

The dosage depends on the intensity of pain and the patient's individual susceptibility to the treatment. For doses not realisable/practicable with this medicinal product, other strengths and medicinal products are available.

The following general dosage recommendations apply:

Adults and adolescents (> 12 years)

Dose titration and adjustment

In general, the initial dose for opioid naïve patients is 10 mg oxycodone hydrochloride given at intervals of 12 hours. Some patients may benefit from a starting dose of 5 mg to minimise the incidence of adverse reactions.

Patients already receiving opioids may start treatment with higher dosages taking into account their experience with former opioid therapies.

According to well-controlled clinical studies 10-13 mg oxycodone hydrochloride correspond to approximately 20 mg morphine sulphate, both in the prolonged-release formulation.

Because of individual differences in sensitivity for different opioids, it is recommended that patients should start conservatively with Zomestine prolonged-release tablets after conversion from other opioids, with 50-75% of the calculated oxycodone dose.

Some patients who take Zomestine prolonged-release tablets following a fixed schedule need rapid release analgesics as rescue medication in order to control breakthrough pain. Zomestine prolonged-release tablets are not indicated for the treatment of acute pain and/or breakthrough pain. The single dose of the rescue medication should amount to 1/6 of the equianalgesic daily dose of Zomestine prolonged-release tablets. Use of the rescue medication more than twice daily indicates that the dose of Zomestine prolonged-release tablets needs to be increased.

The dose should not be adjusted more often than once every 1-2 days until a stable twice daily administration has been achieved.

Following a dose increase from 10 mg to 20 mg taken every 12 hours dose adjustments should be made in steps of approximately one third of the daily dose. The aim is a patient specific dosage which, with twice daily administration, allows for adequate analgesia with tolerable undesirable effects and as little rescue medication as possible as long as pain therapy is needed.

Even distribution (the same dose mornings and evenings) following a fixed schedule (every 12 hours) is appropriate for the majority of the patients. For some patients it may be advantageous to distribute the doses unevenly. In general, the lowest effective analgesic dose should be chosen. For the treatment of non malignant pain a daily dose of 40 mg is generally sufficient; but higher dosages may be necessary. Patients with cancer-related pain may require dosages of 80 to 120 mg, which in individual cases can be increased to up to 400 mg. If even higher doses are required, the dose should be decided individually balancing efficacy with the tolerance and risk of undesirable effects.

Method of administration

For oral use.

Zomestine prolonged-release tablets should be taken twice daily based on a fixed schedule at the dosage determined.

The prolonged-release tablets may be taken with or independent of meals with a sufficient amount of liquid. Zomestine prolonged-release tablets must be swallowed whole, not chewed.

Zomestine prolonged-release tablets should not be used with alcoholic beverages.

Duration of administration

Zomestine should not be taken longer than necessary. If long-term treatment is necessary due to the type and severity of the illness careful and regular monitoring is required to determine whether and to what extent treatment should be continued. If opioid therapy is no longer indicated it may be advisable to reduce the daily dose gradually in order to prevent symptoms of a withdrawal syndrome.

Children under 12 years of age

Zomestine prolonged-release tablets are not recommended for children under 12 years of age.

Elderly patients

Elderly patients without clinical manifestation of impaired liver and/or kidney function usually do not require dose adjustments.

Risk patients

Risk patients, for example patients with impaired renal or hepatic function, low body weight or slow metabolism of medicinal products, should initially receive half the recommended adult dose if they are opioid naïve. Therefore the lowest recommended dosage, i.e. 10 mg, may not be suitable as a starting dose. Dose titration should be performed in accordance with the individual clinical situation.

4.3 Contraindications

• Hypersensitivity to the active substance or to any of the excipients

• severe respiratory depression with hypoxia and/or hypercapnia

• severe chronic obstructive pulmonary disease

• Cor pulmonale

• severe bronchial asthma

• Paralytic ileus

• acute abdomen, delayed gastric emptying.

4.4 Special Warnings And Precautions For Use

Zomestine prolonged-release tablets have not been studied in children younger than 12 years of age. The safety and efficacy of the tablets have not been demonstrated and the use in children younger than 12 years of age is therefore not recommended.

Caution is required in elderly or debilitated patients, in patients with severe impairment of lung, liver or kidney function, myxoedema, hypothyroidism, Addison's disease (adrenal insufficiency), intoxication psychosis (e.g. alcohol), prostatic hypertrophy, alcoholism, known opioid dependence, delirium tremens, pancreatitis, diseases of the biliary tract, biliary or ureteric colic, conditions with increased brain pressure, disturbances of circulatory regulation, epilepsy or seizure tendency and in patients taking MAO inhibitors.

Special care should be taken when oxycodone is applied in patients undergoing bowel-surgery. Opioids should only be administered post-operatively when the bowel function has been restored.

Patients with severe hepatic impairment should be closely monitored.

Respiratory depression is the most significant risk induced by opioids and is most likely to occur in elderly or debilitated patients. The respiratory depressant effect of oxycodone can lead to increased carbon dioxide concentrations in blood and hence in cerebrospinal fluid. In predisposed patients opioids can cause severe decrease in blood pressure.

Long-term use of Zomestine prolonged-release tablets can cause the development of tolerance which leads to the use of higher doses in order to achieve the desired analgesic effect. There is a cross-tolerance to other opioids. Chronic use of Zomestine prolonged-release tablets can cause physical dependence. Withdrawal symptoms may occur following abrupt discontinuation of therapy. If therapy with oxycodone is no longer required it may be advisable to reduce the daily dose gradually in order to avoid the occurrence of a withdrawal syndrome.

Zomestine prolonged-release tablets have a primary dependence potential. However, when used as directed in patients with chronic pain the risk of developing physical or psychological dependence is markedly reduced or needs to be assessed in a differentiated manner. There are no data available on the actual incidence of psychological dependence in chronic pain patients. In patients with a history of alcohol and drug abuse the medicinal product must be prescribed with special care. The safety of Zomestine prolonged-release tablets used pre-operatively has not been established and cannot be recommended.

In case of abusive parenteral venous injection the tablet excipients may lead to necrosis of the local tissue, granulomas of the lung or other serious, potentially fatal events. To avoid damage to the controlled release properties of the tablets the prolonged-release tablets must not be chewed or crushed. The administration of chewed or crushed tablets leads to rapid release and absorption of a potentially fatal dose of oxycodone (see section 4.9).

Zomestine prolonged-release tablets must not be taken with alcoholic beverages, since this might result in an increased incidence of undesirable effects (e.g. somnolence, respiratory depression).

Athletes must be aware that this medicine may cause a positive reaction to 'anti-doping' tests.

Use of Zomestine as a doping agent may become a health hazard.

This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase- isomaltase insufficiency should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Central nervous system depressants (e.g. sedatives, hypnotics, phenothiazines, neuroleptics, anaesthetics, antidepressants, muscle relaxants, antihistamines, antiemetics) and other opioids or alcohol can enhance the adverse reactions of oxycodone, in particular respiratory depression.

Anticholinergics (e.g. neuroleptics, antihistamines, antiemetics, antiparkinson medicinal products) can enhance the anticholinergic undesirable effects of oxycodone (such as constipation, dry mouth or micturition disorders).

Cimetidine can inhibit the metabolism of oxycodone.

MAO inhibitors are known to interact with narcotic analgesics, producing CNS excitation or depression with hyper- or hypotensive crisis (see section 4.4).

The inhibition of cytochrome P450 2D6 and 3A4 has no clinical relevance, however, strong CYP2D6 inhibitors may have an effect on the elimination of oxycodone. The effect of other relevant isoenzyme inhibitors on the metabolism of oxycodone is not known. Potential interactions should be taken into account.

Clinically relevant changes in International Normalised Ratio (INR) in both directions have been observed in individuals if coumarin anticoagulants are co-applied with Zomestine prolonged-release tablets.

There are no studies investigating the effect of oxycodone on CYP catalysed metabolism of other active substances.

4.6 Pregnancy And Lactation

Pregnancy

Limited data on the use of oxycodone during pregnancy in humans reveal no evidence of an increased risk of congenital abnormalities. Oxycodone crosses the placenta. Animal studies with oxycodone have not revealed any teratogenic or embryotoxic effects.

Prolonged use of oxycodone during pregnancy can cause withdrawal symptoms in newborns. Use of oxycodone during labour can cause foetal respiratory depression. Oxycodone should only be used during pregnancy if the benefit outweighs the possible risks to the unborn child or neonate.

Lactation

Zomestine prolonged-release tablets should not be taken during lactation (see section 4.3).

Oxycodone passes into breast milk. The milk/plasma concentration ratio was 3.4:1 and oxycodone effects in the suckling infant are therefore conceivable. A risk to the suckling child cannot be excluded in particular following intake of multiple doses of oxycodone by the breast-feeding mother. Breast-feeding should be discontinued during treatment with oxycodone.

4.7 Effects On Ability To Drive And Use Machines

Oxycodone can impair alertness and reactivity to such an extent that the ability to drive and operate machinery is affected or ceases altogether. With stable therapy, a general ban on driving a vehicle is not necessary. The treating physician must assess the individual situation.

4.8 Undesirable Effects

Oxycodone can cause respiratory depression, miosis, bronchial spasms and spasms of the smooth muscles and can suppress the cough reflex.

The adverse reactions considered at least possibly related to treatment are listed below by system organ class and absolute frequency. Frequencies are defined as:

Very common (

Common (

Uncommon (

Rare (

Very rare (< 1/10,000)

Not known (cannot be estimated from the available data)

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Blood and lymphatic system disorders

Rare: lymphadenopathy

Endocrine disorders

Uncommon: syndrome of inappropriate antidiuretic hormone secretion

Metabolism and nutrition disorders

Common: anorexia

Rare: dehydration

Psychiatric disorders

Common: various psychological adverse reactions including changes in mood (e.g. anxiety, depression, euphoria), changes in activity (mostly supression sometimes associated with lethargy, occasionally increase with agitation, nervousness and insomnia) and changes in cognitive performance (abnormal thinking, confusion, amnesia, isolated cases of speech disorders)

Uncommon: change in perception such as depersonalisation, hallucinations, change in taste, visual disturbances, hyperacousis

Nervous system disorders

Very common: somnolence, dizziness, headache

Common: asthenia, paraesthesia

Uncommon: both increased and decreased muscle tone, tremor, involuntary muscle contractions, hypaesthesia, coordination disturbances, malaise, vertigo

Rare: seizures, in particular in epileptic patients or patients with tendency to convulsions, muscle spasm

Eye disorders

Uncommon: lacrimation disorder, miosis

Cardiac and vascular disorders

Common: lowering of blood pressure, rarely accompanied by secondary symptoms such as palpitations, syncope, bronchospasm

Uncommon: supraventricular tachycardia, vasodilatation

Respiratory, thoracic and mediastinal disorders

Common: respiratory depression

Uncommon: increased coughing, pharyngitis, rhinitis, voice changes

Gastrointestinal disorders

Very common: constipation, nausea, vomiting

Common: dry mouth, rarely accompanied by thirst and difficulty swallowing; gastrointestinal disorders such as abdominal pain, diarrhoea, eructation, dyspepsia, loss of appetite

Uncommon: biliary colics, oral ulcers, gingivitis, stomatitis, flatulence

Rare: gum bleeding, increased appetite, tarry stool, tooth staining and damage, ileus

Skin and subcutaneous tissue disorders

Very common: itching

Common: skin eruptions including rash, in rare cases increased photosensitivity, in isolated cases urticaria or exfoliative dermatitis

Rare: dry skin, herpes simplex

Renal and urinary disorders

Common: micturition disturbances (urinary retention, but also increased urge to urinate)

Rare: haematuria

Reproductive system and breast disorders

Uncommon: reduced libido, impotence

Rare: amenorrhoea

General disorders and administration site conditions

Common: sweating and even chills

Uncommon: accidental injuries, pain (e.g. chest pain), oedema, migraine, physical dependence with withdrawal symptoms, allergic reactions

Rare: weight changes (increase or decrease), cellulitis

Very rare: anaphylactic reactions

Tolerance and dependence may develop.

4.9 Overdose

Symptoms of overdose

Miosis, respiratory depression, somnolence, reduced skeletal muscle tone and drop in blood pressure. In severe cases circulatory collapse, stupor, coma, bradycardia and non-cardiogenic lung oedema may occur; abuse of high doses of strong opioids such as oxycodone can be fatal.

Therapy of overdose

Primary attention should be given to the establishment of a patent airway and institution of assisted or controlled ventilation

In the event of overdosing intravenous administration of an opiate antagonist (e.g. 0.4-2 mg intravenous naloxone) may be indicated. Administration of single doses must be repeated depending on the clinical situation at intervals of 2 to 3 minutes. Intravenous infusion of 2 mg of naloxone in 500 ml isotonic saline or 5% dextrose solution (corresponding to 0.004 mg naloxone/ml) is possible. The rate of infusion should be adjusted to the previous bolus injections and the response of the patient. Gastric lavage can be taken into consideration. Consider activated charcoal (50 g for adults, 10 -15 g for children), if a substantial amount has been ingested within 1 hour, provided the airway can be protected. It may be reasonable to assume that late administration of activated charcoal may be beneficial for prolonged-release preparations; however there is no evidence to support this.

For speeding up the passage a suitable laxative (e.g. a PEG based solution) may be useful.

Supportive measures (artificial respiration, oxygen supply, administration of vasopressors and infusion therapy) should, if necessary, be applied in the treatment of accompanying circulatory shock. Upon cardiac arrest or cardiac arrhythmias cardiac massage or defibrillation may be indicated. If necessary, assisted ventilation as well as maintenance of water and electrolyte balance.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Natural opium alkaloids, ATC-Code: N02AA05

Oxycodone shows an affinity to kappa, mu and delta opioid receptors in the brain and spinal cord. It acts at these receptors as an opioid agonist without an antagonistic effect. The therapeutic effect is mainly analgesic and sedative. Compared to rapid- release oxycodone, given alone or in combination with other substances, the prolonged-release tablets provide pain relief for a markedly longer period without increased occurrence of undesirable effects.

5.2 Pharmacokinetic Properties

Absorption

The relative bioavailability of Zomestine prolonged-release tablets is comparable to that of rapid release oxycodone with maximum plasma concentrations being achieved after approximately 3 hours after intake of the prolonged-release tablets compared to 1 to 1.5 hours. Peak plasma concentrations and oscillations of the concentrations of oxycodone from the prolonged-release and rapid-release formulations are comparable when given at the same daily dose at intervals of 12 and 6 hours, respectively. A fat-rich meal before the intake of the tablets does not affect the maximum concentration or the extent of absorption of oxycodone.

The tablets must not be crushed or chewed as this leads to rapid oxycodone release due to the damage of the prolonged-release properties.

Distribution

The absolute bioavailability of oxycodone is approximately two thirds relative to parenteral administration. In steady state, the volume of distribution of oxycodone amounts to 2.6 l/kg; plasma protein binding to 38-45%; the elimination half-life to 4 to 6 hours and plasma clearance to 0.8 l/min. The elimination half-life of oxycodone from prolonged-release tablets is 4-5 hours with steady state values being achieved after a mean of 1 day.

Metabolism

Oxycodone is metabolised in the intestine and liver via the P450 cytochrome system to noroxycodone and oxymorphone as well as to several glucuronide conjugates. In vitro studies suggest that therapeutic doses of cimetidine probably have no relevant effect on the formation of noroxycodone. In man, quinidine reduces the production of oxymorphone while the pharmacodynamic properties of oxycodone remain largely unaffected. The contribution of the metabolites to the overall pharmacodynamic effect is irrelevant.

Elimination

Oxycodone and its metabolites are excreted via urine and faeces. Oxycodone crosses the placenta and is found in breast milk.

Linearity/non-linearity

The 5, 10, 20, 40 and 80 mg prolonged-release tablets are bioequivalent in a dose proportional manner with regard to the amount of active substance absorbed as well as comparable with regard to the rate of absorption.

5.3 Preclinical Safety Data

Oyxcodone had no effect on fertility and early embryonic development in male and female rats in doses of up to 8 mg/kg body weight and induced no malformations in rats in doses of up to 8 mg/kg and in rabbits in doses of 125 mg/kg bodyweight. However, in rabbits, when individual foetuses were used in statistical evaluation, a dose related increase in developmental variations was observed (increased incidences of 27 presacral vertebrae, extra pairs of ribs). When these parameters were statistically evaluated using litters, only the incidence of 27 presacral vertebrae was increased and only in the 125 mg/kg group, a dose level that produced severe pharmacotoxic effects in the pregnant animals. In a study on pre- and postnatal development in rats F1 body weights were lower at 6 mg/kg/d when compared to body weights of the control group at doses which reduced maternal weight and food intake (NOAEL 2 mg/kg body weight). There were neither effects on physical, reflexological, and sensory developmental parameters nor on behavioural and reproductive indices.

Long-term carcinogenicity studies were not performed.

Oxycodone shows a clastogenic potential in in vitro assays. No similar effects were observed, however, under in vivo conditions, even at toxic doses. The results indicate that the mutagenic risk of oxycodone to humans at therapeutic concentrations may be ruled out with adequate certainty.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet core:Sugar spheres (sucrose, maize starch)

Hypromellose

Talc

Ethylcellulose

Hyprolose

Propylene glycol

Carmellose sodium

Microcrystalline cellulose

Magnesium stearate

Colloidal anhydrous silica

Tablet coating:

Titanium dioxide (E171)

Hypromellose

Macrogol 6000

Talc

Red iron oxide (E 172)

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

2 year

6.4 Special Precautions For Storage

This medicinal product does not require any special storage conditions.

6.5 Nature And Contents Of Container

Child resistant PVC/PE/PVDC-aluminium blisters consisting of a white opaque PVC/PE/PVDC laminated foil and an aluminium foil.

HDPE bottles with child-resistant PP twist-off caps.

Pack sizes:

10, 14, 20, 28, 30, 50, 56, 98, 100 prolonged-release tablets in blister.

10, 20, 30, 50, 100 prolonged-release tablets in HDPE bottles.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Accord Healthcare Limited,

Sage house, 319 Pinner road,

North Harrow, Middlesex, HA1 4HF

United Kingdom

8. Marketing Authorisation Number(S)

PL20075/0330

9. Date Of First Authorisation/Renewal Of The Authorisation

21/09/2011

10. Date Of Revision Of The Text

21/09/2011