Songar

Songarは不眠症の短期治療に適応されます(通常7〜10日)。. 2〜3週間以上使用するには、患者の完全な再評価が必要です(参照)。 警告。).

Songarの処方箋は短期使用(7〜10日)で作成する必要があり、1か月の供給を超える量で処方しないでください。.

最大の有益な効果を得るためにSongar Tabletsの投与量を個別化し、重大な悪影響を回避することが重要です。.

ほとんどの成人の推奨用量は、引退する前の0.25 mgです。. 一部の患者には0.125 mgの用量で十分であることが判明する場合があります(例:.、 低い体重)。. 投与量のサイズとともにいくつかの副作用のリスクが高まるため、0.5 mgの用量は、低用量の試験に適切に応答しない例外的な患者にのみ使用する必要があります。. 0.5 mgの用量を超えてはなりません。.

老人および/または衰弱した患者では、推奨される投与量は0.125 mg〜0.25 mgです。. これらのグループでは、0.125 mgで治療を開始する必要があり、0.25 mgの用量は、低用量の試験に反応しない例外的な患者にのみ使用する必要があります。. これらの患者では、0.25 mgの用量を超えてはなりません。.

すべての薬と同様に、最低有効量を使用する必要があります。.

Songar Tablets are contraindicated in patients with known hypersensitivity to this drug or other benzodiazepines.

Benzodiazepines may cause fetal damage when administered during pregnancy. An increased risk of congenital malformations associated with the use of diazepam and chlordiazepoxide during the first trimester of pregnancy has been suggested in several studies. Transplacental distribution has resulted in neonatal CNS depression following the ingestion of therapeutic doses of a benzodiazepine hypnotic during the last weeks of pregnancy.

Songar is contraindicated in pregnant women. If there is a likelihood of the patient becoming pregnant while receiving Songar, she should be warned of the potential risk to the fetus. Patients should be instructed to discontinue the drug prior to becoming pregnant. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered.

Songar is contraindicated with medications that significantly impair the oxidative metabolism mediated by cytochrome P450 3A (CYP 3A) including ketoconazole, itraconazole, nefazodone, and several HIV protease inhibitors, (see WARNINGS and DRUG INTERACTIONS).

WARNINGS

Risks From Concomitant Use With Opioids

Concomitant use of benzodiazepines, including Songar, and opioids may result in profound sedation, respiratory depression, coma, and death. Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. If a decision is made to prescribe Songar concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. In patients already receiving an opioid analgesic, prescribe a lower initial dose of Songar than indicated in the absence of an opioid and titrate based on clinical response. If an opioid is initiated in a patient already taking Songar, prescribe a lower initial dose of the opioid and titrate based upon clinical response.

Advise both patients and caregivers about the risks of respiratory depression and sedation when Songar is used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined.

Persistent Or Worsening Insomnia

Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative-hypnotic drugs. Because some of the important adverse effects of sedative-hypnotics appear to be dose related (see PRECAUTIONS and DOSAGE AND ADMINISTRATION), it is important to use the smallest possible effective dose, especially in the elderly.

“Sleep-driving” And Other Complex Behaviors

Complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported. These events can occur in sedativehypnotic- naïve as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleepdriving may occur with sedative-hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with sedative-hypnotics appears to increase the risk of such behaviors, as does the use of sedative-hypnotics at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of sedative-hypnotics should be strongly considered for patients who report a “sleep-driving” episode.

Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events.

Severe Anaphylactic And Anaphylactoid Reactions

Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including Songar. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with Songar should not be rechallenged with the drug.

Central Nervous System Manifestations

An increase in daytime anxiety has been reported for Songar after as few as 10 days of continuous use. In some patients this may be a manifestation of interdose withdrawal (see CLINICAL PHARMACOLOGY). If increased daytime anxiety is observed during treatment, discontinuation of treatment may be advisable.

A variety of abnormal thinking and behavior changes have been reported to occur in association with the use of benzodiazepine hypnotics including Songar. Some of these changes may be characterized by decreased inhibition, eg, aggressiveness and extroversion that seem excessive, similar to that seen with alcohol and other CNS depressants (eg, sedative/hypnotics). Other kinds of behavioral changes have also been reported, for example, bizarre behavior, agitation, hallucinations, depersonalization. In primarily depressed patients, the worsening of depression, including suicidal thinking, has been reported in association with the use of benzodiazepines.

It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.

Because of its depressant CNS effects, patients receiving triazolam should be cautioned against engaging in hazardous occupations requiring complete mental alertness such as operating machinery or driving a motor vehicle. For the same reason, patients should be cautioned about the concomitant ingestion of alcohol and other CNS depressant drugs during treatment with Songar Tablets.

As with some, but not all benzodiazepines, anterograde amnesia of varying severity and paradoxical reactions have been reported following therapeutic doses of Songar. Data from several sources suggest that anterograde amnesia may occur at a higher rate with Songar than with other benzodiazepine hypnotics.

Triazolam Interaction With Drugs That Inhibit Metabolism Via Cytochrome P450 3A

The initial step in triazolam metabolism is hydroxylation catalyzed by cytochrome P450 3A (CYP 3A). Drugs that inhibit this metabolic pathway may have a profound effect on the clearance of triazolam. Consequently, triazolam should be avoided in patients receiving very potent inhibitors of CYP 3A. With drugs inhibiting CYP 3A to a lesser but still significant degree, triazolam should be used only with caution and consideration of appropriate dosage reduction. For some drugs, an interaction with triazolam has been quantified with clinical data; for other drugs, interactions are predicted from in vitro data and/or experience with similar drugs in the same pharmacologic class.

The following are examples of drugs known to inhibit the metabolism of triazolam and/or related benzodiazepines, presumably through inhibition of CYP 3A.

Potent CYP 3A inhibitors

Potent inhibitors of CYP 3A that should not be used concomitantly with triazolam include ketoconazole, itraconazole, nefazodone and several HIV protease inhibitors including ritonavir, indinavir, nelfinavir, saquinavir and lopinavir. Although data concerning the effects of azole-type antifungal agents other than ketoconazole and itraconazole on triazolam metabolism are not available, they should be considered potent CYP 3A inhibitors, and their coadministration with triazolam is not recommended (see CONTRAINDICATIONS).

Drugs demonstrated to be CYP 3A inhibitors on the basis of clinical studies involving triazolam (caution and consideration of dose reduction are recommended during coadministration with triazolam)

Macrolide Antibiotics

Coadministration of erythromycin increased the maximum plasma concentration of triazolam by 46%, decreased clearance by 53%, and increased half-life by 35%; caution and consideration of appropriate triazolam dose reduction are recommended. Similar caution should be observed during coadministration with clarithromycin and other macrolide antibiotics.

Cimetidine

Coadministration of cimetidine increased the maximum plasma concentration of triazolam by 51%, decreased clearance by 55%, and increased half-life by 68%; caution and consideration of appropriate triazolam dose reduction are recommended.

Other drugs possibly affecting triazolam metabolism

Other drugs possibly affecting triazolam metabolism by inhibition of CYP 3A are discussed in the PRECAUTIONS section (see DRUG INTERACTIONS).

PRECAUTIONS

General

In elderly and/or debilitated patients it is recommended that treatment with Songar Tablets be initiated at 0.125 mg to decrease the possibility of development of oversedation, dizziness, or impaired coordination.

Some side effects reported in association with the use of Songar appear to be dose related. These include drowsiness, dizziness, light-headedness, and amnesia.

The relationship between dose and what may be more serious behavioral phenomena is less certain. Specifically, some evidence, based on spontaneous marketing reports, suggests that confusion, bizarre or abnormal behavior, agitation, and hallucinations may also be dose related, but this evidence is inconclusive. In accordance with good medical practice it is recommended that therapy be initiated at the lowest effective dose (see DOSAGE AND ADMINISTRATION).

Cases of “traveler's amnesia” have been reported by individuals who have taken Songar to induce sleep while traveling, such as during an airplane flight. In some of these cases, insufficient time was allowed for the sleep period prior to awakening and before beginning activity. Also, the concomitant use of alcohol may have been a factor in some cases.

Caution should be exercised if Songar is prescribed to patients with signs or symptoms of depression that could be intensified by hypnotic drugs. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional over-dosage is more common in these patients, and the least amount of drug that is feasible should be available to the patient at any one time.

The usual precautions should be observed in patients with impaired renal or hepatic function, chronic pulmonary insufficiency, and sleep apnea. In patients with compromised respiratory function, respiratory depression and apnea have been reported infrequently.

Information For Patients

The text of a Medication Guide for patients is included at the end of this insert. To assure safe and effective use of Songar, the information and instructions provided in this Medication Guide should be discussed with patients.

Risks From Concomitant Use With Opioids

Advise both patients and caregivers about the risks of potentially fatal respiratory depression and sedation when Songar is used with opioids and not to use such drugs concomitantly unless supervised by a healthcare provider. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined.

“Sleep-driving” And Other Complex Behaviors

There have been reports of people getting out of bed after taking a sedative-hypnotic and driving their cars while not fully awake, often with no memory of the event. If a patient experiences such an episode, it should be reported to his or her doctor immediately, since “sleep-driving” can be dangerous. This behavior is more likely to occur when sedative-hypnotics are taken with alcohol or other central nervous system depressants (see WARNINGS). Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative hypnotic. As with sleep-driving, patients usually do not remember these events.

Laboratory Tests

Laboratory tests are not ordinarily required in otherwise healthy patients.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

No evidence of carcinogenic potential was observed in mice during a 24-month study with Songar in doses up to 4,000 times the human dose.

Pregnancy

Teratogenic effects

Pregnancy category X

(see CONTRAINDICATIONS).

Non-teratogenic Effects

It is to be considered that the child born of a mother who is on benzodiazepines may be at some risk for withdrawal symptoms from the drug, during the postnatal period. Also, neonatal flaccidity has been reported in an infant born of a mother who had been receiving benzodiazepines.

Nursing Mothers

Human studies have not been performed; however, studies in rats have indicated that Songar and its metabolites are secreted in milk. Therefore, administration of Songar to nursing mothers is not recommended.

Pediatric Use

Safety and effectiveness of Songar in individuals below 18 years of age have not been established.

Geriatric Use

The elderly are especially susceptible to the dose related adverse effects of Songar. They exhibit higher plasma triazolam concentrations due to reduced clearance of the drug as compared with younger subjects at the same dose. To minimize the possibility of development of oversedation, the smallest effective dose should be used (see CLINICAL PHARMACOLOGY, WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).

Tolerance/Withdrawal Phenomena

Some loss of effectiveness or adaptation to the sleep inducing effects of these medications may develop after nightly use for more than a few weeks and there may be a degree of dependence that develops. For the benzodiazepine sleeping pills that are eliminated quickly from the body, a relative deficiency of the drug may occur at some point in the interval between each night's use. This can lead to (1) increased wakefulness during the last third of the night, and (2) the appearance of increased signs of daytime anxiety or nervousness. These two events have been reported in particular for Songar.

There can be more severe 'withdrawal' effects when a benzodiazepine sleeping pill is stopped. Such effects can occur after discontinuing these drugs following use for only a week or two, but may be more common and more severe after longer periods of continuous use. One type of withdrawal phenomenon is the occurrence of what is known as 'rebound insomnia'. That is, on the first few nights after the drug is stopped, insomnia is actually worse than before the sleeping pill was given. Other withdrawal phenomena following abrupt stopping of benzodiazepine sleeping pills range from mild unpleasant feelings to a major withdrawal syndrome which may include abdominal and muscle cramps, vomiting, sweating, tremor, and rarely, convulsions.

1,003人の患者がSongar Tabletを投与されたプラセボ対照臨床試験中、最も厄介な副作用は、トリアゾラムの薬理活性の延長、たとえば眠気、めまい、または立ちくらみでした。.

以下に引用する数値は、比較的短い期間に参加した被験者(すなわち、.、1〜42日)Songarのプラセボ対照臨床試験。. この図は、患者の特性やその他の要因が臨床試験の要因と異なることが多い通常の医療行為の過程での不都合なイベントの発生率を正確に予測するために使用することはできません。. これらの数値は、関連する医薬品やプラセボを含む他の臨床試験から得られた数値と比較することはできません。薬物試験の各グループは、異なる一連の条件下で行われるためです。.

ただし、引用された数値を比較すると、調査対象者の不都合なイベント発生率に対する薬物および無薬物要因の相対的な寄与を推定するためのいくつかの根拠を処方者に提供できます。. 薬物は1人の患者の症状を緩和し、他の患者に症状を誘発する可能性があるため、この使用にも注意深く取り組む必要があります。. (たとえば、抗コリン作用のある抗不安薬は、一部の被験者では口渇を和らげますが[不安の兆候]、他の被験者では[厄介な出来事]を引き起こします。.)。

比較的一般的(つまり、.、1%以上)上記で列挙された不都合なイベント、以下の有害事象はそれほど頻繁に報告されていません(つまり、.、0.9%から0.5%):陶酔感、頻脈、疲労感、混乱状態/記憶障害、けいれん/痛み、うつ病、視覚障害。.

まれ(つまり.、0.5%未満)副作用には、便秘、味覚の変化、下 ⁇ 、口渇、皮膚炎/アレルギー、夢/悪夢、不眠症、感覚異常、耳鳴り、感覚異常、脱力感、うっ血、利尿薬も投与されている患者の肝不全による死亡が含まれます薬。.

発生率の推定値が得られるこれらの厄介なイベントに加えて。, 以下の有害事象は、ソンガーおよび他のベンゾジアゼピンの使用に関連して報告されています:健忘症状。 (適切または不適切な行動を伴う動脈 ⁇ 健忘症。) 混乱状態。 (見当識障害。, 脱現実。, 離人。, および/または意識の ⁇ り。) ジストニア。, 拒食症。, 疲労。, 鎮静。, 不明 ⁇ なスピーチ。, 黄 ⁇ 。, ⁇ 。, ジサーリア。, 性欲の変化。, 月経異常。, 失禁。, そして尿閉。. アルコールや他の薬物の併用摂取、睡眠不足、異常な前乾燥状態など、他の要因がこれらの反応の一部に寄与している可能性があります。.

報告されている他のイベントには、刺激、 ⁇ 病、興奮状態(落ち着きのなさ、過敏性、興奮)などの逆説的な反応、筋肉の ⁇ 縮の増加、睡眠障害、幻覚、妄想、攻撃性、落下、傾眠、失神、不適切な行動、その他の有害な行動の影響が含まれます。. これらが発生した場合、薬物の使用は中止されるべきです。.

次のイベントも報告されています:胸の痛み、舌の ⁇ 熱/舌炎/口内炎。.

実験室分析は、ソンガーの臨床プログラムに参加しているすべての患者に対して行われました。. 以下の異常の発生率は、Songarおよび対応するプラセボ群を投与された患者で観察されました。. これらの変化はどれも生理学的重要性があるとは見なされませんでした。.

Songarによる治療が長引く場合、定期的な血球数、尿検査、および血液化学分析が推奨されます。.

脳波パターンの小さな変化、通常は低電圧の高速活動が、ソンガーによる治療中に患者で観察されており、既知の有意性はありません。.

薬物乱用と依存。

虐待と中毒は、身体的依存と寛容とは別であり、区別されます。. 虐待は、非医療目的での薬物の誤用が特徴で、多くの場合、他の精神活性物質と組み合わせて使用 されます。. 身体的依存は、突然の中止、急速な線量の減少、薬物の血中濃度の低下および/または ⁇ 抗薬の投与によって生じる可能性のある特定の離脱症候群によって明らかになる適応状態です。. 耐性は、薬物への曝露が変化を引き起こし、時間の経過とともに薬物の効果の1つ以上が減少する適応状態です。. 耐性は、薬物の望ましい効果と望ましくない効果の両方に発生する可能性があり、効果が異なると異なる速度で発生する可能性があります。.

中毒は、その発達と症状に影響を与える遺伝的、心理社会的、環境的要因を伴う主要な慢性神経生物学的疾患です。. それは、次の1つ以上を含む行動によって特徴付けられます:薬物使用に対する制御の障害、強迫的な使用、危害にもかかわらず継続的な使用、および渇望。. 薬物中毒は治療可能な疾患であり、学際的なアプローチを利用していますが、再発が一般的です。.

規制物質。

トリアゾラムは規制物質法に基づく規制物質であり、ソンガータブレットはスケジュールIVに割り当てられています。

虐待、依存、撤退。

バルビツール酸塩やアルコールで指摘されているものと同様の離脱症状(けいれん、振戦、腹部および筋肉のけいれん、 ⁇ 吐、発汗、不快感、知覚障害および不眠症)は、ソンガーを含むベンゾジアゼピンの突然の中止後に発生しました。. より深刻な症状は通常、より高い投与量とより長い使用に関連しますが、治療投与量が1〜2週間しか与えられていない患者も離脱症状を示す可能性があり、一部の患者では、夜間離脱症状(昼間の不安、興奮)が発生することがあります線量(参照。 臨床薬理学。)。. したがって、突然の中止は避け、数週間以上最低用量を超える服用をしている患者には、段階的な投与量の減少スケジュールが推奨されます。. ⁇ 減の推奨は、発作の病歴のある患者にとって特に重要です。.

依存のリスクは、アルコール依存症、薬物乱用の病歴のある患者、または著しい人格障害のある患者で増加します。. そのような依存しやすい個人は、Songarを受け取るとき、注意深い監視下にあるべきです。. すべての催眠術と同様に、繰り返し処方は医学的監督下にある人に限定されるべきです。.

トリアゾラムの効力により、過剰摂取のいくつかの症状は、最大推奨治療用量(0.5 mg)の4倍の2 mgで発生する可能性があります。.

Songar Tabletによる過剰摂取の症状には、傾眠、混乱、協調障害、不明 ⁇ な発話、そして最終的には ⁇ 睡が含まれます。. 呼吸抑制と無呼吸は、ソンガーの過剰摂取で報告されています。. 発作は、過剰摂取後に時折報告されています。.

他のベンゾジアゼピンと同様に、トリアゾラムの過剰摂取に関連して死亡が報告されています。. さらに、トリアゾラムを含む単一のベンゾジアゼピンとアルコールの組み合わせを過剰摂取した患者で死亡率が報告されています。これらの症例のいくつかで見られるベンゾジアゼピンとアルコール濃度は、いずれかの物質のみによる死亡の報告に通常関連するものよりも低くなっています。.

薬物の過剰摂取のすべての場合と同様に、呼吸、脈拍、血圧は、必要に応じて一般的な対策によって監視およびサポートする必要があります。. 早期の胃洗浄を行う必要があります。. 適切な気道を維持する必要があります。. 静脈内液を投与してもよい。.

特定のベンゾジアゼピン受容体 ⁇ 抗薬であるフルマゼニルは、ベンゾジアゼピンの鎮静効果の完全または部分的な逆転が示され、ベンゾジアゼピンによる過剰摂取が既知または疑われる状況で使用される場合があります。. フルマゼニルの投与前に、気道、換気、静脈内アクセスを確保するために必要な措置を講じる必要があります。. フルマゼニルは、ベンゾジアゼピンの過剰摂取の適切な管理の代替としてではなく、補助として意図されています。. フルマゼニルで治療された患者は、治療後の適切な期間、再鎮静、呼吸抑制、およびその他の残留ベンゾジアゼピン効果について監視する必要があります。. 処方者は、フルマゼニル治療に関連する発作のリスク、特に長期ベンゾジアゼピン使用者と環状抗うつ薬の過剰摂取のリスクを認識しておく必要があります。. フルマゼニルパッケージの完全な挿入物。