Liticarb

Liticarb®(炭酸リチウム)は、双極性障害の ⁇ 病エピソードの治療に適応されます。. 双極性障害、 ⁇ 病(DSM-IV)は、古いDSM-II用語では ⁇ うつ病のマニックと同等です。. Liticarb®は、双極性障害の診断を受けた個人の維持療法としても適応されます。. メンテナンス療法は、 ⁇ 病エピソードの頻度を減らし、発生する可能性のあるエピソードの強度を減らします。.

⁇ 病の典型的な症状には、発話の圧力、運動多動、睡眠の必要性の低下、アイデアの飛 ⁇ 、壮大さ、高揚感、判断力の低下、攻撃性、そしておそらく敵意が含まれます。. ⁇ 病エピソードを経験している患者に投与すると、リチウムは1〜3週間以内に症状の正常化を引き起こす可能性があります。.

急性マニア。

最適な患者応答は通常、次の投与量で1800 mg /日で確立できます。

急性マニア。

このような用量は通常、1.0〜1.5 mEq / Lの範囲の有効血清リチウム濃度を生成します。投与量は、血清濃度と臨床反応に従って個別化する必要があります。. 患者の臨床状態と血清リチウム濃度の定期的なモニタリングが必要です。. 血清濃度は、急性期および患者の血清濃度と臨床状態が安定するまで、週に2回決定する必要があります。.

長期制御。

望ましい血清リチウム濃度は0.6〜1.2 mEq / Lで、通常900〜1200 mg /日で達成できます。. 投与量は個人によって異なりますが、一般的に次の投与量はこの濃度を維持します。

長期制御。

寛解中に維持療法を受けている合併症のない症例の血清リチウム濃度は、少なくとも2か月ごとに監視する必要があります。. リチウムに異常に敏感な患者は、血清濃度1.0〜1.5 mEq / Lで毒性の兆候を示すことがあります。老人患者はしばしば減量に反応し、他の患者が通常耐えている血清濃度で毒性の兆候を示すことがあります。. 一般に、高齢患者の用量選択は慎重に行う必要があります。通常、投与範囲の低い端から始まり、肝機能、腎機能、または心臓機能の低下、および付随する疾患やその他の薬物療法の頻度が高くなります。.

重要な考慮事項。

• 血清リチウム測定の血液サンプルは、リチウム濃度が比較的安定している場合(つまり、.、前の投与から8〜12時間)。. 血清濃度だけに完全に依存してはなりません。. 正確な患者評価には、臨床分析と検査分析の両方が必要です。.
• Liticarb®Extended-Releaseタブレットは丸ごと飲み込み、噛んだりつぶしたりしないでください。.

情報は提供されていません。.

WARNINGS

Lithium Toxicity

Lithium toxicity is closely related to serum lithium concentrations and can occur at doses close to therapeutic concentrations (see DOSAGE AND ADMINISTRATION).

Outpatients and their families should be warned that the patient must discontinue lithium therapy and contact his physician if such clinical signs of lithium toxicity as diarrhea, vomiting, tremor, mild ataxia, drowsiness, or muscular weakness occur.

Lithium should generally not be given to patients with significant renal or cardiovascular disease, severe debilitation, dehydration, sodium depletion, and to patients receiving diuretics, or angiotensin converting enzyme (ACE) inhibitors, since the risk of lithium toxicity is very high in such patients. If the psychiatric indication is life threatening, and if such a patient fails to respond to other measures, lithium treatment may be undertaken with extreme caution, including daily serum lithium determinations and adjustment to the usually low doses ordinarily tolerated by these individuals. In such instances, hospitalization is a necessity.

Unmasking Of Brugada Syndrome

There have been postmarketing reports of a possible association between treatment with lithium and the unmasking of Brugada Syndrome. Brugada Syndrome is a disorder characterized by abnormal electrocardiographic (ECG) findings and a risk of sudden death. Lithium should generally be avoided in patients with Brugada Syndrome or those suspected of having Brugada Syndrome. Consultation with a cardiologist is recommended if: (1) treatment with lithium is under consideration for patients suspected of having Brugada Syndrome or patients who have risk factors for Brugada Syndrome, e.g., unexplained syncope, a family history of Brugada Syndrome, or a family history of sudden unexplained death before the age of 45 years, (2) patients who develop unexplained syncope or palpitations after starting lithium therapy.

Renal Effects

Chronic lithium therapy may be associated with diminution of renal concentrating ability, occasionally presenting as nephrogenic diabetes insipidus, with polyuria and polydipsia. Such patients should be carefully managed to avoid dehydration with resulting lithium retention and toxicity. This condition is usually reversible when lithium is discontinued.

Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have been reported in patients on chronic lithium therapy. Morphologic changes have also been seen in manic-depressive patients never exposed to lithium. The relationship between renal function and morphologic changes and their association with lithium therapy have not been established.

Kidney function should be assessed prior to and during lithium therapy. Routine urinalysis and other tests may be used to evaluate tubular function (e.g., urine specific gravity or osmolality following a period of water deprivation, or 24-hour urine volume) and glomerular function (e.g., serum creatinine or creatinine clearance). During lithium therapy, progressive or sudden changes in renal function, even within the normal range, indicate the need for reevaluation of treatment.

Encephalopathic Syndrome

An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN, and FBS) has occurred in a few patients treated with lithium plus a neuroleptic, most notably haloperidol. In some instances, the syndrome was followed by irreversible brain damage. Because of possible causal relationship between these events and the concomitant administration of lithium and neuroleptic drugs, patients receiving such combined therapy or patients with organic brain syndrome or other CNS impairment should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear. This encephalopathic syndrome may be similar to or the same as Neuroleptic Malignant Syndrome (NMS).

Concomitant Use With Neuromuscular Blocking Agents

Lithium may prolong the effects of neuromuscular blocking agents. Therefore, neuromuscular blocking agents should be given with caution to patients receiving lithium.

Usage In Pregnancy

Adverse effects on nidation in rats, embryo viability in mice, and metabolism in vitro of rat testis and human spermatozoa have been attributed to lithium, as have teratogenicity in submammalian species and cleft palate in mice.

In humans, lithium may cause fetal harm when administered to a pregnant woman. Data from lithium birth registries suggest an increase in cardiac and other anomalies, especially Ebstein's anomaly. If this drug is used in women of childbearing potential, or during pregnancy, or if a patient becomes pregnant while taking this drug, the patient should be apprised by their physician of the potential hazard to the fetus.

Usage In Nursing Mothers

Lithium is excreted in human milk. Nursing should not be undertaken during lithium therapy except in rare and unusual circumstances where, in the view of the physician, the potential benefits to the mother outweigh possible hazard to the infant or neonate. Signs and symptoms of lithium toxicity such as hypertonia, hypothermia, cyanosis, and ECG changes have been reported in some infants and neonates.

Pediatric Use

Safety and effectiveness in pediatric patients under 12 years of age have not been determined; its use in these patients is not recommended.

There has been a report of transient syndrome of acute dystonia and hyperreflexia occurring in a 15 kg pediatric patient who ingested 300 mg of lithium carbonate.

PRECAUTIONS

The ability to tolerate lithium is greater during the acute manic phase and decreases when manic symptoms subside (see DOSAGE AND ADMINISTRATION).

The distribution space of lithium approximates that of total body water. Lithium is primarily excreted in urine with insignificant excretion in feces. Renal excretion of lithium is proportional to its plasma concentration. The elimination half-life of lithium is approximately 24 hours. Lithium decreases sodium reabsorption by the renal tubules which could lead to sodium depletion. Therefore, it is essential for the patient to maintain a normal diet, including salt, and an adequate fluid intake (2500-3500 mL) at least during the initial stabilization period. Decreased tolerance to lithium has been reported to ensue from protracted sweating or diarrhea and, if such occur, supplemental fluid and salt should be administered under careful medical supervision and lithium intake reduced or suspended until the condition is resolved.

In addition to sweating and diarrhea, concomitant infection with elevated temperatures may also necessitate a temporary reduction or cessation of medication.

Previously existing thyroid disorders do not necessarily constitute a contraindication to lithium treatment. Where hypothyroidism preexists, careful monitoring of thyroid function during lithium stabilization and maintenance allows for correction of changing thyroid parameters and/or adjustment of lithium doses, if any. If hypothyroidism occurs during lithium stabilization and maintenance, supplemental thyroid treatment may be used. In general, the concomitant use of diuretics or angiotensin converting enzyme (ACE) inhibitors with lithium carbonate should be avoided. In those cases where concomitant use is necessary, extreme caution is advised since sodium loss from these drugs may reduce the renal clearance of lithium resulting in increased serum lithium concentrations with the risk of lithium toxicity. When such combinations are used, the lithium dosage may need to be decreased, and more frequent monitoring of lithium serum concentrations is recommended. See WARNINGS for additional caution information.

Concomitant administration of carbamazepine and lithium may increase the risk of neurotoxic side effects.

The following drugs can lower serum lithium concentrations by increasing urinary lithium excretion: acetazolamide, urea, xanthine preparations, and alkalinizing agents such as sodium bicarbonate.

Concomitant extended use of iodide preparations, especially potassium iodide, with lithium may produce hypothyroidism.

Concurrent use of calcium channel blocking agents with lithium may increase the risk of neurotoxicity in the form of ataxia, tremors, nausea, vomiting, diarrhea, and/or tinnitus.

Concurrent use of metronidazole with lithium may provoke lithium toxicity due to reduced renal clearance. Patients receiving such combined therapy should be monitored closely.

Concurrent use of fluoxetine with lithium has resulted in both increased and decreased serum lithium concentrations. Patients receiving such combined therapy should be monitored closely.

Nonsteroidal anti-inflammatory drugs (NSAIDs): Lithium levels should be closely monitored when patients initiate or discontinue NSAID use. In some cases, lithium toxicity has resulted from interactions between a NSAID and lithium. Indomethacin and piroxicam have been reported to increase significantly steady-state plasma lithium concentrations. There is also evidence that other nonsteroidal antiinflammatory agents, including the selective cyclooxygenase-2 (COX-2) inhibitors, have the same effect. In a study conducted in healthy subjects, mean steady-state lithium plasma levels increased approximately 17% in subjects receiving lithium 450 mg BID with celecoxib 200 mg BID as compared to subjects receiving lithium alone.

Lithium may impair mental and/or physical abilities. Patients should be cautioned about activities requiring alertness (e.g., operating vehicles or machinery).

Usage In Pregnancy

Pregnancy Category D. (See WARNINGS).

Usage In Nursing Mothers

Because of the potential for serious adverse reactions in nursing infants and neonates from lithium, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see WARNINGS).

Pediatric Use

Safety and effectiveness in pediatric patients below the age of 12 have not been established (see WARNINGS).

Geriatric Use

Clinical studies of Liticarb® 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 responses 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 therapy.

This drug is known to be substantially excreted by the kidney, 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.

副作用の発生と重症度は、一般に血清リチウム濃度とリチウムに対する個々の患者の感受性に直接関連しています。. それらは一般的により頻繁に発生し、より高い濃度でより深刻になります。.

副作用は、1.5 mEq / L未満の血清リチウム濃度で発生する可能性があります。軽度から中程度の副作用は1.5〜2.5 mEq / Lの濃度で発生する可能性があり、中程度から重度の反応は2.0 mEq / L以上の濃度で見られます。.

急性 ⁇ 病期の初期治療中に、微細な手振戦、多尿症、および軽度の喉の渇きが発生する可能性があり、治療全体を通じて持続する可能性があります。. 一過性で軽度の吐き気と一般的な不快感は、リチウム投与の最初の数日間にも現れることがあります。.

これらの副作用は通常、継続的な治療または一時的な投与量の減少または中止により治まります。. 持続性の場合、リチウム療法の中止が必要になることがあります。. 下 ⁇ 、 ⁇ 吐、眠気、筋力低下、協調性の欠如は、リチウム中毒の初期の兆候である可能性があり、2.0 mEq / L未満のリチウム濃度で発生する可能性があります。より高い濃度では、めまい、運動失調、かすみ目、耳鳴り、および希薄な尿の大量産出が見られることがあります。. 3.0 mEq / Lを超える血清リチウム濃度は、複数の臓器および臓器系を含む複雑な臨床像を生成する可能性があります。. 血清リチウム濃度は、急性治療段階で2.0 mEq / Lを超えることを許可されるべきではありません。.

以下の反応が報告されており、治療範囲内の濃度を含む血清リチウム濃度に関連しているようです。

中央神経系:。 振戦。, 筋肉過敏症。 (魅了。, けいれん。, 手足全体のクローン運動。) 緊張 ⁇ 進。, 運動失調。, 振り付けの動き。, 活動性の高い深部 ⁇ 反射。, 急性ジストニアを含む ⁇ 体外路症状。, cogwheelの ⁇ 性。, 停電呪文。, てんかん発作。, 不明 ⁇ なスピーチ。, めまい。, めまい。, ダウンビートな眼振。, 尿または ⁇ 便の失禁。, 傾眠。, 精神運動遅延。, 落ち着きのなさ。, 混乱。, ⁇ 迷。, ⁇ 睡。, 舌の動き。, チックス。, 耳鳴り。, 幻覚。, 記憶力の低下。, 知的機能の低下。, びっくりした反応。, 有機脳症候群の悪化。. 偽腫瘍性脳炎(頭蓋内圧と乳頭腫の増加)の症例は、リチウムの使用で報告されています。. 検出されない場合、この状態は盲点の拡大、視野の狭 ⁇ 、および視神経 ⁇ 縮による最終的な失明につながる可能性があります。. この症候群が発生した場合、臨床的に可能であればリチウムを中止する必要があります。. 心血管:。 不整脈、低血圧、末 ⁇ 循環虚脱、徐脈、重度の徐脈を伴う副鼻腔機能障害(失神を引き起こす可能性があります)、ブルガダ症候群のマスキング解除(参照) 警告。 と。 患者情報。)。. 消化管:。 食欲不振、吐き気、 ⁇ 吐、下 ⁇ 、胃炎、 ⁇ 液腺の腫れ、腹痛、過度の ⁇ 液分 ⁇ 、 ⁇ 腸、消化不良。. Genitourinary:。 糖尿、クレアチニンクリアランスの低下、アルブミン尿、乏尿、および多尿症、喉の渇き、多飲症などの腎性糖尿病の症状。. 皮膚科:髪の乾燥と薄化、脱毛症、皮膚の麻酔、にきび、慢性毛包炎、乾 ⁇ 性 ⁇ 、乾 ⁇ またはその悪化、発疹の有無にかかわらず全身性そう ⁇ 、皮膚 ⁇ 瘍、血管浮腫。. 自律神経系:。 かすみ目、口渇、インポテンス/性機能障害。. 甲状腺異常:。 甲状腺機能低下症および/または甲状腺機能低下症(粘液腫を含む)、T3およびT4の低下を伴う。. ヨウ素の取り込みが増加する可能性があります(参照)。 注意。)。. 逆説的に、甲状腺機能 ⁇ 進症のまれなケースが報告されています。. 脳波の変化:。 周波数スペクトルの減速、拡大、バックグラウンドリズムの増強と無秩序を拡散します。. EKGの変更:。 T波の可逆平 ⁇ 化、等電性または反転。. その他 :。 疲労、 ⁇ 眠、一過性脊髄腫、眼球外症、脱水症、体重減少、白血球増加症、頭痛、一過性高血糖症、高カルシウム血症、副甲状腺機能 ⁇ 進症、アルブミン尿症、過度の体重増加、足首や手首の浮腫、金属味、味覚異常/味覚の歪み、塩味、喉の渇き、唇の腫れ、胸の圧迫.

リチウム中止後に持続する腎性糖尿病の陰 ⁇ 、副甲状腺機能 ⁇ 進症、甲状腺機能低下症の報告がいくつか受けています。.

リチウム治療を開始してから1日以内に、指とつま先の痛みのある変色や四肢の冷えが発症したという報告がいくつかあります。. これらの症状(レイノー症候群の再構成)が発生するメカニズムは不明です。. 回復は不連続に続きました。.

リチウムの毒性濃度(≥1.5 mEq / L)は、治療濃度(0.6-1.2 mEq / L)に近いです。. したがって、患者とその家族は、初期の毒性症状を監視し、薬物を中止し、発生した場合に医師に通知するように注意することが重要です。. (毒性症状は、ADVERSE REACTIONSに詳細に記載されています。)

治療。

リチウム中毒の特定の解毒剤は知られていない。. 治療は支持的です。. リチウム毒性の初期の症状は通常、薬物の投与量の減少または中止と、24〜48時間後の低用量での治療の再開によって治療できます。. リチウム中毒の重 ⁇ なケースでは、治療の第一の目標は、患者からこのイオンを取り除くことです。.

治療は、バルビツール中毒で使用されるものと本質的に同じです。1)胃洗浄、2)体液と電解質の不均衡の矯正、および3)腎機能の調節。. 尿素、マンニトール、アミノフィリンはすべてリチウム排 ⁇ を大幅に増加させます。. 血液透析は、重度の毒性患者からイオンを除去する効果的かつ迅速な手段です。. ただし、患者の回復は遅い場合があります。.

感染予防、定期的な胸部X線、適切な呼吸の維持が不可欠です。.