拉米夫定片
拉米夫定口服溶液

组成
LAMIVIR-150片
每个薄膜包衣片含拉米夫定150毫克
LAMIVIR口服溶液
每5毫升含有拉米夫定50毫克

药
药效：
拉米夫定是一种合成的核苷类似物。细胞内，拉米夫定被磷酸化，其活跃的5` - 三磷酸腺苷的代谢物，拉米夫定三磷酸盐（3TC-TP）。 3TC-TP行动的主要方式是通过抑制DNA链的终止后掺入的核苷酸类似物逆转录酶（RT）。 3TC-TP是一种哺乳动物DNA聚合酶α和β的弱抑制剂，线粒体DNA聚合酶-γ。
 

药代动力学
吸收和生物利用度：拉米夫定在感染艾滋病毒的患者口服后迅速吸收。 12名成年患者中的绝对生物利用度为86％±16％（平均值±SD）为150毫克片剂。 2毫克/千克9与艾滋病毒的成年人每天两次口服后，高峰血清拉米夫定浓度（Cmax）为1.5±0.5微克/毫升（平均值±SD）。口服的比例，根据血药浓度随时间变化的曲线（AUC）和Cmax面积范围从0.25上升到10毫克/千克。
有没有显着性差异，全身暴露（AUC（无穷大））在美联储和禁食状态，因此，拉米夫定片剂和口服液，可带或不带食品管理。
分布：四拉米夫定管理后20例，表观分布容积为1.3±0.4升/公斤，表明拉米夫定分布到血管外的空间。分布容积与剂量无关，并没有相关的体重。拉米夫定人体血浆蛋白的结合是低（<36％）。
代谢：拉米夫定的代谢是一个排除的次要途径。在人，唯一已知的代谢物拉米夫定是跨亚砜代谢产物。单剂量口服拉米夫定6感染艾滋病毒的成年人中，5.2％±1.4％（平均值±SD）的剂量后12小时内被作为反式亚砜代谢物在尿中排出体外。这种代谢产物的血药浓度尚未确定。
消除：尿液中被淘汰大部分拉米夫定不变。在9个正常人，给予拉米夫定300毫克单一剂量口服，肾清除率为199.7±56.9毫升/分钟（平均值±SD）。在大多数单剂量研究中的艾滋病毒感染者，乙肝病毒感染的患者，或与健康受试者服药后24小时内的血清采样，观测到的平均消除半衰期（T 1/2）5日至7小时不等。在艾滋病毒感染的患者，总清除率为398.5±69.1毫升/分钟（平均值±SD）。

适应症
LAMIVIR被用于与其他抗逆转录病毒药物结合治疗的艾滋病毒感染。

剂量和用法
成人
建议LAMIVIR口服剂量为成人每日300毫克，无论是150毫克，每日两次或300毫克，每天一次，在与其他抗逆转录病毒药物的组合管理。
如果拉米夫定管理与HIV和HBV双重感染病人，剂量的艾滋病毒治疗，应使用适当的组合方案的一部分（见警告和注意事项）。
小儿患者（婴儿/儿童/青少年）
建议LAMIVIR口服剂量为小儿患者，3个月至16岁，是4毫克/千克，每天两次（最高可达150毫克，一天两次），与其他抗逆转录病毒药物组合管理。
调整剂量
建议根据肾功能调整剂量的拉米夫定（见表1）。

表1：根据肌酐清除率调整剂量在成人和青少年拉米夫定

肌酐清除率（毫升/分钟）推荐用量拉米夫定
≥50 150 mg，每天两次或300毫克，每天一次
 
30-49 150毫克，每天一次
15-29 150毫克首次剂量，然后100毫克，每天一次
5-14 150毫克首次剂量，然后50毫克，每天一次
<5 50毫克，首次剂量，然后25 mg每天一次

没有额外剂量的拉米夫定（4小时）后，常规血液透析或腹膜透析需要。
虽然有足够的数据，建议在小儿肾功能不全患者对拉米夫定的具体调整剂量，减少剂量和/或增加给药间隔应予以考虑。
成人肝功能受损
没有肝功能受损的患者需要调整剂量拉米夫定。

禁忌
该产品的任何部件与先前表明的临床显著过敏的患者禁忌LAMIVIR片剂和口服液。

注意事项：
在儿科患者的抗逆转录病毒核苷暴露前，胰腺炎病史，或其他重要的危险因素，胰腺炎的发展历史，拉米夫定，应谨慎使用。与拉米夫定治疗，应立即停止，如果临床症状，体征或暗示胰腺炎发生的实验室检查异常（见不良影响）。

乳酸性酸中毒/严重肝肿大伴脂肪肝
乳酸性酸中毒和严重的肝脂肪，包括致命的情况下，已与抗逆转录病毒核苷类似物单独或组合，包括拉米夫定和其他抗逆转录病毒药物的使用。这些案件大部分已在妇女。肥胖和长期核苷暴露可能是危险因素。行使管理拉米夫定任何与肝脏疾病的已知危险因素的病人时，应特别谨慎，然而，案件也没有已知的危险因素的患者被报道。与拉米夫定治疗，应暂停在任何临床或实验室的研究结果暗示乳酸性酸中毒或明显的肝毒性（其中可能包括在没有明显的转氨酶升高，甚至肝肿大和脂肪）的病人谁开发谁。

其中含拉米夫定产品的重要区别
LAMIVIR片剂和口服液中含有高剂量比在LAMIVIR乙肝片相同的活性成分（拉米夫定）。 LAMIVIR乙肝发展为慢性乙型肝炎患者拉米夫定的制定和用量在LAMIVIR乙肝并不适用于HIV和HBV双重感染的病人。拉米夫定并没有得到充分的研究与HIV和HBV双重感染的患者在治疗慢性乙型肝炎。如果无法识别或未经处理的艾滋病毒感染的病人的慢性乙型肝炎规定与LAMIVIR乙肝治疗，抗艾滋病毒的迅速崛起是因为亚治疗剂量和单药治疗的艾滋病毒治疗不当可能导致的。如果作出决定管理拉米夫定患者双重感染艾滋病毒和乙肝病毒，LAMIVIR片，口服液的LAMIVIR，或Duovir片应作为一个适当的组合方案的一部分。 duovir（拉米夫定和齐多夫定的固定剂量复方片剂）不应同时与LAMIVIR，LAMIVIR-HBV或Zidovir的。

肝炎治疗后病情加重
在与拉米夫定治疗慢性乙型肝炎，肝炎加重的临床和实验室证据的非HIV感染患者的临床试验已发生拉米夫定停药后。这些病情加重已主要通过检测血清ALT升高的HBV DNA重新出现。尽管大多数事件似乎已经自限，死亡据报道，在某些情况下。类似的事件已改变从拉米夫定含有艾滋病毒治疗方案后与HIV和HBV感染的患者在非含拉米夫定治疗后的市场营销经验。停止拉米夫定治疗的因果关系是未知之数。患者应密切监测与临床和停止治疗后至少几个月实验室跟进。没有足够的证据，以确定是否重新开始拉米夫定改变肝炎治疗后病情加重的过程。

使用干扰素和利巴韦林为基础的方案
体外研究显示利巴韦林可减少磷酸嘧啶核苷类似物如拉米夫定。虽然没有证据的药代动力学或药效学相互作用（例如，艾滋病毒/丙型肝炎病毒抑制亏损）当利巴韦林与HIV / HCV合并感染的病人，肝功能失代偿拉米夫定联合管理（一些致命）发生在艾滋病毒/ HCV合并感染患者的艾滋病毒和干扰素与利巴韦林或不接受抗逆转录病毒联合疗法。利巴韦林和拉米夫定或不接受干扰素的患者，应密切监测治疗相关的不良反应，尤其是肝功能失代偿。拉米夫定停药，应被视为医学上是适当的。剂量减少或停用干扰素，利巴韦林，或两者应该也可以考虑，如果恶化的临床毒性观察，包括肝功能失代偿（例如，童车普格> 6）（见干扰素和利巴韦林的完整处方信息）。

艾滋病毒和乙肝病毒共感染的患者
与HIV和HBV双重感染的患者在治疗慢性乙型肝炎的拉米夫定的安全性和疗效尚未建立。
在与拉米夫定治疗慢性乙型肝炎的非感染艾滋病毒的患者，出现拉米夫定耐药HBV已发现并已减少治疗反应相关。耐拉米夫定乙型肝炎病毒变种的出现也已并发感染乙肝病毒的存在已经收到含有拉米夫定的抗逆转录病毒疗法的患者在感染艾滋病毒的报告。也有报道肝炎治疗后病情加重。

免疫重建综合征：
据报道，在免疫重建综合征抗逆转录病毒联合疗法治疗的患者，包括拉米夫定。在联合抗逆转录病毒治疗的初始阶段，患者的免疫系统作出反应，有可能发展惰性或残留的机会性感染（如结核分枝杆菌感染，巨细胞病毒，卡氏肺囊虫肺炎的主治医生，或肺结核）的炎症反应，这可能需要进一步的评估和治疗。

给药方案之间的差异：
血浆中拉米夫定和拉米夫定三磷酸盐内的谷底水平低于每日两次剂量，每天服用一次。这个观察的临床意义尚不清楚。

脂肪的再分配
再分配/积累体内的脂肪，包括中央肥胖，脂肪肿大dorsocervical（水牛背），周边消瘦，面部消瘦，乳房增大，“库欣氏症候群的外观”，已观察到在接受抗逆转录病毒治疗的患者。这些事件的机制和长期后果目前尚不得而知。的因果关系尚未建立。

药物相互作用
拉米夫定主要是消除尿液中的活性有机阳离子分泌。应考虑与管理，同时其他药物相互作用的可能性，特别是当他们消除的主要途径是积极通过肾脏分泌的有机阳离子运输系统（例如，甲氧）。
甲氧苄啶160毫克和800毫克复方磺胺甲恶唑（TMP / SMX），每天一次，已被证明拉米夫定暴露量（AUC）增加43％。建议没有任何药物剂量的变化。目前没有资料关于拉米夫定TMP / SMX为主，如那些用于治疗PCP的高剂量的药代动力学的影响。没有任何数据可与其他药物的相互作用，有肾清除机制类似拉米夫定。
拉米夫定和zalcitabine可能会抑制细胞内磷酸化的一个。因此，使用拉米夫定结合zalcitabine是不推荐使用。

肾功能不全
建议减少剂量拉米夫定肾功能受损的患者（见用法用量）。

怀孕
妊娠C类在南非进行的两项临床研究，药物对样品进行了测量谁收到拉米夫定初孕妇在妊娠38周（10名妇女谁收到150组合与齐多夫定和10谁收到拉米夫定300 mg，每天两次mg，每天两次没有其他抗逆转录病毒药物）或开始在妊娠36周（16名妇女与齐多夫定合用拉米夫定150 mg，每天两次）。这些研究并没有设计或供电提供效能资料。拉米夫定在怀孕妇女的药代动力学相似，那些获得以下出生在非怀孕成人。拉米夫定的浓度一般在孕产妇，新生儿，脐带血清样品相似。从他们那里得到羊水标本胎膜自然破裂后的科目的一个子集，拉米夫定羊水浓度介于1.2至2.5微克/毫升（150毫克，每天两次）和2.1至5.2微克/毫升（300毫克，每天两次）通常比孕妇血清水平的2倍。看到“不良影响”有限怀孕后期安全信息可从这些研究。拉米夫定应在怀孕期间使用只有在潜在利益大于风险。

哺乳
据建议，艾滋病毒感染的母亲不哺乳自己的婴儿，以避免产后冒着感染艾滋病毒的传播。拉米夫定在人类乳汁中排出。由于双方的艾滋病毒传播的潜力和哺乳婴儿的严重不良反应的潜力，母亲应指示不哺乳，如果他们接受拉米夫定。

儿童使用
与其他抗逆转录病毒药物结合每日两次拉米夫定的安全性和有效性已建立在3个月的年龄和年龄较大的儿童患者。

不良影响
作为一个整体：身体体内脂肪的再分配/堆积
消化系统：口腔炎。
内分泌和代谢：高血糖。

总：虚弱。
血液和淋巴系统：贫血（包括纯红细胞再生障碍性贫血和严重贫血治疗进展），淋巴结肿大，脾肿大。
肝脏和胰腺：乳酸性酸中毒和脂肪肝，胰腺炎，治疗后B型肝炎发作（见警告和注意事项）。
过敏：过敏性休克，荨麻疹。
肌肉骨骼系统：肌肉无力，肌酸磷酸激酶升高，横纹肌溶解症。
神经感觉异常，周围神经病变。
呼吸系统：呼吸音异常/喘息。
皮肤：脱发，皮疹，瘙痒。

过量
拉米夫定没有已知的解毒剂。一个成人摄取6拉米夫定Ğ据报道，有没有临床症状或体征指出，血液测试仍正常。已报告两例小儿过量。一个案例是7毫克/公斤拉米夫定的单剂量;第二宗个案涉及使用5毫克/公斤拉米夫定，每天两次为30天。在任何情况下注意到没有临床症状或症状。因为的拉米夫定微不足道的金额，通过4小时的血液透析，腹膜透析，自动化腹膜透析清除，不知道如果连续血液透析中一个拉米夫定过量事件提供临床受益。如果发生过量，应监测病人，和标准的支持治疗应用的要求。

Antiretroviral products (Lamivir)

Lamivir
Lamivudine Tablets
Lamivudine Oral Solution

COMPOSITION
LAMIVIR-150 Tablets
Each film-coated tablet contains Lamivudine 150 mg
LAMIVIR Oral Solution
Each 5 ml contains Lamivudine 50 mg

PHARMACOLOGY
Pharmacodynamics:
Lamivudine is a synthetic nucleoside analogue. Intracellularly, lamivudine is phosphorylated to its active 5`-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is the inhibition of reverse transcriptase (RT) via DNA chain termination after incorporation of the nucleotide analogue. 3TC-TP is a weak inhibitor of mammalian DNA polymerases alpha and beta, and mitochondrial DNA polymerase- gamma.
 

Pharmacokinetics
Absorption and bioavailability: Lamivudine was rapidly absorbed after oral administration in HIV-infected patients. Absolute bioavailability in 12 adult patients was 86% ± 16% (mean ± SD) for the 150-mg tablet. After oral administration of 2 mg/kg twice a day to 9 adults with HIV, the peak serum lamivudine concentration (C max ) was 1.5 ± 0.5 mcg/mL (mean ± SD). The area under the plasma concentration versus time curve (AUC) and C max increased in proportion to oral dose over the range from 0.25 to 10 mg/kg.
There was no significant difference in systemic exposure (AUC (infinity)) in the fed and fasted states; therefore, lamivudine tablets and oral solution may be administered with or without food.
Distribution: The apparent volume of distribution after IV administration of lamivudine to 20 patients was 1.3 ± 0.4 L/kg, suggesting that lamivudine distributes into extravascular spaces. Volume of distribution was independent of dose and did not correlate with body weight. Binding of lamivudine to human plasma proteins is low (<36%).
Metabolism: Metabolism of lamivudine is a minor route of elimination. In man, the only known metabolite of lamivudine is the trans-sulfoxide metabolite. Within 12 hours after a single oral dose of lamivudine in 6 HIV-infected adults, 5.2% ± 1.4% (mean ± SD) of the dose was excreted as the trans-sulfoxide metabolite in the urine. Serum concentrations of this metabolite have not been determined.
Elimination: The majority of lamivudine is eliminated unchanged in urine. In 9 healthy subjects given a single 300-mg oral dose of lamivudine, renal clearance was 199.7 ± 56.9 mL/min (mean ± SD). In most single-dose studies in HIV-infected patients, HBV-infected patients, or healthy subjects with serum sampling for 24 hours after dosing, the observed mean elimination half-life (t 1/2 ) ranged from 5 to 7 hours. In HIV-infected patients, total clearance was 398.5 ± 69.1 mL/min (mean ± SD).

INDICATIONS
LAMIVIR is indicated for the treatment of HIV infection in combination with other antiretrovirals.

DOSAGE AND ADMINISTRATION
Adults
The recommended oral dose of LAMIVIR for adults is 300 mg daily, administered as either 150 mg twice daily or 300 mg once daily, in combination with other antiretroviral agents.
If lamivudine is administered to a patient dually infected with HIV and HBV, the dosage indicated for HIV therapy should be used as part of an appropriate combination regimen (see WARNINGS AND PRECAUTIONS ).
Pediatric Patients (Infants/Children/Adolescents)
The recommended oral dose of LAMIVIR for pediatric patients, 3 months to 16 years of age, is 4 mg/kg twice daily (up to a maximum of 150 mg twice a day), administered in combination with other antiretroviral agents.
Dose Adjustment
It is recommended that doses of lamivudine be adjusted in accordance with renal function (see Table 1).

Table 1: Adjustment of Dosage of Lamivudine in Adults and Adolescents in Accordance With Creatinine Clearance

Creatinine Clearance (mL/min)	Recommended Dosage of Lamivudine
≥50	150 mg twice daily or 300 mg once daily
30-49	150 mg once daily
15-29	150 mg first dose, then 100 mg once daily
5-14	150 mg first dose, then 50 mg once daily
<5	50 mg first dose, then 25 mg once daily

No additional dosing of lamivudine is required after routine (4-hour) hemodialysis or peritoneal dialysis.
Although there are insufficient data to recommend a specific dose adjustment of lamivudine in pediatric patients with renal impairment, a reduction in the dose and/or an increase in the dosing interval should be considered.
Adults With Impaired Hepatic Function
No dose adjustment for lamivudine is required for patients with impaired hepatic function.

CONTRAINDICATIONS
LAMIVIR Tablets and Oral Solution are contraindicated in patients with previously demonstrated clinically significant hypersensitivity to any of the components of the product.

WARNINGS AND PRECAUTIONS
In pediatric patients with a history of prior antiretroviral nucleoside exposure, a history of pancreatitis, or other significant risk factors for the development of pancreatitis, lamivudine should be used with caution. Treatment with lamivudine should be stopped immediately if clinical signs, symptoms or laboratory abnormalities suggestive of pancreatitis occur (see UNDESIRABLE EFFECTS ).

Lactic Acidosis/Severe Hepatomegaly With Steatosis
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of antiretroviral nucleoside analogues alone or in combination, including lamivudine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Particular caution should be exercised when administering lamivudine to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with lamivudine should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Important Differences Among Lamivudine-Containing Products
LAMIVIR Tablets and Oral Solution contain a higher dose of the same active ingredient (lamivudine) than in LAMIVIR-HBV Tablets. LAMIVIR-HBV was developed for patients with chronic hepatitis B. The formulation and dosage of lamivudine in LAMIVIR-HBV are not appropriate for patients dually infected with HIV and HBV. Lamivudine has not been adequately studied for treatment of chronic hepatitis B in patients dually infected with HIV and HBV. If treatment with LAMIVIR-HBV is prescribed for chronic hepatitis B for a patient with unrecognized or untreated HIV infection, rapid emergence of HIV resistance is likely to result because of the subtherapeutic dose and the inappropriateness of monotherapy HIV treatment. If a decision is made to administer lamivudine to patients dually infected with HIV and HBV, LAMIVIR Tablets, LAMIVIR Oral Solution, or Duovir Tablets should be used as part of an appropriate combination regimen. Duovir (a fixed-dose combination tablet of lamivudine and zidovudine) should not be administered concomitantly with LAMIVIR, LAMIVIR-HBV or Zidovir .

Post- treatment Exacerbations of Hepatitis
In clinical trials in non-HIV-infected patients treated with lamivudine for chronic hepatitis B, clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of lamivudine. These exacerbations have been detected primarily by serum ALT elevations in addition to re-emergence of HBV DNA. Although most events appear to have been self-limited, fatalities have been reported in some cases. Similar events have been reported from post-marketing experience after changes from lamivudine-containing HIV treatment regimens to non-lamivudine-containing regimens in patients infected with both HIV and HBV. The causal relationship to discontinuation of lamivudine treatment is unknown. Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. There is insufficient evidence to determine whether re-initiation of lamivudine alters the course of post-treatment exacerbations of hepatitis.

Use With Interferon- and Ribavirin-Based Regimens
In vitro studies have shown ribavirin can reduce the phosphorylation of pyrimidine nucleoside analogues such as lamivudine. Although no evidence of a pharmacokinetic or pharmacodynamic interaction (e.g., loss of HIV/HCV virologic suppression) was seen when ribavirin was co-administered with lamivudine in HIV/HCV co-infected patients, hepatic decompensation (some fatal) has occurred in HIV/HCV co-infected patients receiving combination antiretroviral therapy for HIV and interferon alfa with or without ribavirin. Patients receiving interferon alfa with or without ribavirin and lamivudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. Discontinuation of lamivudine should be considered as medically appropriate. Dose reduction or discontinuation of interferon alfa, ribavirin, or both should also be considered if worsening clinical toxicities are observed, including hepatic decompensation (e.g., Childs Pugh >6) (see the complete prescribing information for interferon and ribavirin).

Patients With HIV and Hepatitis B Virus Co-infection
Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patients dually infected with HIV and HBV.
In non-HIV-infected patients treated with lamivudine for chronic hepatitis B, emergence of lamivudine-resistant HBV has been detected and has been associated with diminished treatment response. Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV-infected patients who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus. Post-treatment exacerbations of hepatitis have also been reported.

Immune Reconstitution Syndrome:
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including lamivudine. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), which may necessitate further evaluation and treatment.

Differences Between Dosing Regimens:
Trough levels of lamivudine in plasma and of intracellular lamivudine triphosphate were lower with once-daily dosing than with twice-daily dosing. The clinical significance of this observation is not known.

Fat Redistribution
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and “cushingoid appearance”, have been observed in patients receiving antiretroviral therapy. The mechanism and long-term consequences of these events are currently unknown. A causal relationship has not been established .

Drug Interactions
Lamivudine is predominantly eliminated in the urine by active organic cationic secretion. The possibility of interactions with other drugs administered concurrently should be considered, particularly when their main route of elimination is active renal secretion via the organic cationic transport system (e.g., trimethoprim).
Trimethoprim 160 mg and sulfamethoxazole 800 mg (TMP/SMX) once daily has been shown to increase lamivudine exposure (AUC) by 43%. No change in dose of either drug is recommended. There is no information regarding the effect on lamivudine pharmacokinetics of higher doses of TMP/SMX such as those used to treat PCP. No data are available regarding interactions with other drugs that have renal clearance mechanisms similar to that of lamivudine.
Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another. Therefore, use of lamivudine in combination with zalcitabine is not recommended.

Renal Impairment
Reduction of the dose of lamivudine is recommended for patients with impaired renal function (see DOSAGE AND ADMINISTRATION ).

Pregnancy
Pregnancy Category C. In two clinical studies conducted in South Africa, pharmacokinetic measurements were performed on samples from pregnant women who received lamivudine beginning at Week 38 of gestation (10 women who received 150 mg twice daily in combination with zidovudine and 10 who received lamivudine 300 mg twice daily without other antiretrovirals) or beginning at Week 36 of gestation (16 women who received lamivudine 150 mg twice daily in combination with zidovudine). These studies were not designed or powered to provide efficacy information. Lamivudine pharmacokinetics in the pregnant women were similar to those obtained following birth and in non-pregnant adults. Lamivudine concentrations were generally similar in maternal, neonatal, and cord serum samples. In a subset of subjects from whom amniotic fluid specimens were obtained following natural rupture of membranes, amniotic fluid concentrations of lamivudine ranged from 1.2 to 2.5 mcg/mL (150 mg twice daily) and 2.1 to 5.2 mcg/mL (300 mg twice daily) and were typically greater than 2 times the maternal serum levels. See the “UNDESIRABLE EFFECTS ” section for the limited late-pregnancy safety information available from these studies. Lamivudine should be used during pregnancy only if the potential benefits outweigh the risks.

Lactation
It is recommended that HIV-infected mothers do not breastfeed their infants to avoid risking post-natal transmission of HIV infection. Lamivudine is excreted in human milk. Because of both the potential for HIV transmission and the potential for serious adverse reactions in nursing infants, mothers should be instructed not to breast feed if they are receiving lamivudine.

Pediatric Use
The safety and effectiveness of twice-daily lamivudine in combination with other antiretroviral agents have been established in pediatric patients 3 months of age and older.

UNDESIRABLE EFFECTS
Body as a Whole: Redistribution/accumulation of body fat
Digestive : Stomatitis.
Endocrine and Metabolic: Hyperglycemia.

General: Weakness.
Hemic and Lymphatic: Anemia (including pure red cell aplasia and severe anemia progressing on therapy), lymphadenopathy, splenomegaly.
Hepatic and Pancreatic : Lactic acidosis and hepatic steatosis, pancreatitis, post-treatment exacerbation of hepatitis B (see WARNINGS AND PRECAUTIONS ).
Hypersensitivity: Anaphylaxis, urticaria.
Musculoskeletal: Muscle weakness, CPK elevation, rhabdomyolysis.
Nervous: Paresthesia, peripheral neuropathy.
Respiratory: Abnormal breath sounds/wheezing.
Skin: Alopecia, rash, pruritus.

OVERDOSAGE
There is no known antidote for lamivudine. One case of an adult ingesting 6 g of lamivudine was reported; there were no clinical signs or symptoms noted and hematological tests remained normal. Two cases of pediatric overdose have been reported. One case was a single dose of 7 mg/kg of lamivudine; the second case involved use of 5 mg/kg of lamivudine twice daily for 30 days. There were no clinical signs or symptoms noted in either case. Because a negligible amount of lamivudine was removed via 4-hour hemodialysis, continuous ambulatory peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuous hemodialysis would provide clinical benefit in a lamivudine overdose event. If overdose occurs, the patient should be monitored, and standard supportive treatment applied as required.

PRESENTATION
LAMIVIR -150 Tablets Blister pack of 10 tablets
LAMIVIR Oral Solution Bottle of 100 ml with syringe