SanfordPharmacy Lamivudine Drug Information

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Lamivudine is an antiretroviral medication used as part of combination therapy to treat Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). It belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs).

Introduction to Lamivudine

Lamivudine is an antiretroviral medication used as part of combination therapy to treat Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS). It belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs).

Lamivudine works by inhibiting reverse transcriptase, an enzyme crucial to viral production in HIV-infected cells. By inhibiting reverse transcriptase, lamivudine blocks HIV replication. When used with other antiretrovirals, lamivudine suppresses viral load, increases CD4 cell counts, and slows the progression of HIV infection.

Lamivudine was approved by the U.S. Food and Drug Administration (FDA) in 1995. It is manufactured under the brand name Epivir by ViiV Healthcare. Lamivudine is also available in generic forms and as a component of fixed-dose combination pills to treat HIV/AIDS.

Lamivudine is commonly used with other antiretrovirals such as zidovudine (AZT), abacavir, and protease inhibitors like lopinavir/ritonavir. When combined with zidovudine, the two-drug regimen is referred to as Combivir. Lamivudine is a widely used first-line antiretroviral with a well-established efficacy and safety profile for treating HIV.

Mechanism of Action

Lamivudine is a nucleoside analogue that inhibits HIV replication and has activity against HIV-1, HIV-2, and hepatitis B. Lamivudine works by being incorporated into the viral DNA by the reverse transcriptase enzyme, resulting in chain termination. Specifically, lamivudine competes with the natural substrate deoxycytidine triphosphate and is incorporated into the viral DNA much more efficiently than into the host cell DNA. Once incorporated, lamivudine lacks the 3'hydroxyl group needed for the formation of phosphodiester linkages, resulting in DNA chain termination and blocking of further extension. This inhibits viral DNA synthesis and replication, reducing the viral load. Lamivudine is active against HIV-1, HIV-2, and hepatitis B virus as these viruses all utilize reverse transcriptase as part of their replication cycle. The triphosphate form of lamivudine is the active compound that provides the chain terminating mechanism of action.

Uses and Indications

Lamivudine is indicated as part of antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infected adults and children. When used in combination with other antiretroviral agents, lamivudine has been shown to be effective in suppressing HIV replication, reducing HIV viral load, and increasing CD4 cell counts.

Lamivudine is commonly used together with zidovudine (AZT) as part of antiretroviral therapy for HIV infected individuals. This dual nucleoside reverse transcriptase inhibitor (NRTI) therapy has been demonstrated to be more effective than either drug alone in clinical trials. The combination of lamivudine plus AZT suppresses HIV replication and delays disease progression in HIV positive patients. Lamivudine has also been studied and used in combination with other NRTIs such as didanosine and stavudine. These triple NRTI regimens have proven efficacy in suppressing viral load and are commonly used as part of HAART (highly active antiretroviral therapy).

The use of lamivudine as part of antiretroviral therapy has been shown to be effective in HIV infected children as well as adults. Pediatric clinical trials have demonstrated that lamivudine, in combination with other antiretrovirals, suppresses viral replication and boosts CD4 cell counts in HIV positive children. Lamivudine is considered a first line antiretroviral agent for treating HIV infection in children.

Overall, lamivudine, as a component of highly active antiretroviral combination regimens, is considered a standard first-line therapy for treatment of HIV infection in both adults and children. It has proven efficacy for viral suppression and immune system improvement when used appropriately as part of HIV therapy.

Dosage and Administration

Lamivudine is available as tablets containing 150mg and 300mg for adults, and in an oral solution containing 10mg/mL for children. For adults, the recommended oral dosage is 300mg once daily or 150mg twice daily. Lamivudine may be taken with or without food. For children, the dosage is based on body weight. The recommended oral dosage for children weighting 14kg to less than 20kg is 4mg/kg twice daily. For children weighing 20kg to less than 25kg, the dosage is 100mg twice daily. For children 25kg or greater, the adult dosage of 150mg twice daily can be used.

The oral solution is the preferred formulation for patients weighing less than 14kg and for those who cannot swallow tablets. For children unable to swallow tablets, the scored 150mg tablet can be crushed and added to a small amount of semi-solid food or liquid, which should be consumed immediately.

It's important to take lamivudine exactly as prescribed and at evenly spaced intervals. Full compliance with the dosage regimen is important to avoid the development of viral resistance. If a dose is missed, patients should take the missed dose as soon as possible and resume the regular dosing schedule. However, if it is within an hour of the next dose, the missed dose should be skipped.

Drug Interactions

Lamivudine is primarily eliminated renally via active organic cationic secretion. Coadministration of lamivudine with drugs that are eliminated by active organic cationic secretion may increase serum concentrations of lamivudine and/or the coadministered drug.

Some examples of drugs that may interact with lamivudine include:

- Trimethoprim - Coadministration of trimethoprim, a constituent of trimethoprim /sulfamethoxazole, increases lamivudine exposure by approximately 40%. Patients receiving trimethoprim/sulfamethoxazole and lamivudine should be monitored for lamivudine toxicity.

- Sorbitol - Coadministration of sorbitol solution (3.2 grams, 10.2 grams, 13.4 grams) with a single 300 mg dose of lamivudine oral solution resulted in dose-dependent decreases of 14%, 32%, and 36% in lamivudine exposure. Coadministration of lamivudine with sorbitol-containing medicines or substances should be avoided when possible.

- Zidovudine - Lamivudine may inhibit the intracellular phosphorylation of zidovudine when the two medicinal products are concomitantly administered. Lamivudine is not recommended for use in combination with zidovudine as there is limited information on the effect of the combination.

- Emtricitabine - Due to similarities, lamivudine should not be administered concomitantly with emtricitabine or emtricitabine-containing fixed-dose combinations.

- Stavudine - No clinically significant adverse reactions were observed when lamivudine and stavudine were co-administered.

- Indinavir - Coadministration of indinavir results in slight decreases in indinavir exposure. The clinical significance is unknown; however, no dose adjustment is recommended. 

Careful monitoring and potential dosage adjustments may be needed when administering lamivudine with drugs that interact with its renal elimination pathway. Consult a healthcare provider for specific guidance.

Side Effects

Lamivudine is generally well tolerated, but there are some common and serious side effects to be aware of when taking this medication.

Common Side Effects

- Headache

- Nausea

- Diarrhea

- Rash

- Fatigue

- Fever

- Insomnia

- Muscle pain

These side effects are usually mild and tend to go away within a few weeks as the body adjusts to the medication. Notify your doctor if any of these persist or become severe.

Serious Side Effects

- Lactic acidosis - buildup of lactic acid in the blood, which can be fatal. Symptoms include nausea, vomiting, stomach pain, weight loss, and feeling very weak or tired. Get medical help right away if you experience any of these.

- Liver problems - Lamivudine can cause liver damage, with symptoms like yellowing skin/eyes, dark urine, loss of appetite, nausea. Seek immediate medical attention if you notice these. 

- Exacerbation of hepatitis B - Lamivudine can cause acute exacerbation of hepatitis B when treatment is discontinued in people who have HBV. Do not stop taking lamivudine without your doctor's advice.

- Allergic reaction - rash, itching, swelling, dizziness, trouble breathing. Discontinue medication and seek emergency care immediately if an allergic reaction is suspected.

- Pancreatitis - inflammation of the pancreas causing severe abdominal pain. Seek medical attention right away if you develop this.

- Increased risk of infection - lamivudine can reduce white blood cell counts, raising susceptibility to illnesses. Contact your doctor if you have signs of infection like fever, chills, sore throat while on this medication.

Make sure your doctor is aware of any side effects you experience, as the dosage may need adjustment or an alternative medication may be prescribed. Never discontinue lamivudine without medical supervision.

Warnings and Precautions with Lamivudine

Lamivudine should be used with caution in certain situations due to the potential for serious side effects or loss of efficacy:

- Liver Disease - Lamivudine is not recommended for patients with moderate or severe hepatic impairment as dosage adjustments are necessary and safety has not been established.

- Renal Impairment - Dose reduction is recommended for patients with impaired renal function. Lamivudine should not be given to patients with creatine clearance <50 ml/min as accumulation may occur.

- Pancreatitis - Use with caution in patients with a history of pancreatitis or risks for pancreatitis. Discontinue if signs or symptoms of pancreatitis develop.

- Lactic Acidosis - Lactic acidosis and severe hepatomegaly with steatosis have been reported with nucleoside analogues. Exercise caution in patients at risk. Immediately suspend treatment if lactic acidosis is suspected.

- Immune Reconstitution Syndrome - May necessitate further evaluation and treatment when starting treatment in patients with underlying immunodeficiency.

- Resistance - The emergence of lamivudine-resistant variants is of concern. Frequent viral load monitoring is recommended. Lamivudine is not recommended as monotherapy due to rapid development of resistance.

- Coadministration - Do not administer lamivudine with other medications that contain lamivudine or emtricitabine. Serious toxicity may occur.

- Bone Toxicity - Cases of osteonecrosis and bone abnormalities have been reported with long-term lamivudine treatment. The risks and benefits should be weighed carefully in patients with bone disease or risk factors.

- Mitochondrial Toxicity - Nucleoside analogues have been associated with mitochondrial toxicity, closely monitor for this potential side effect.

- Hepatitis B Reactivation - Severe acute exacerbation of hepatitis B can occur when lamivudine is discontinued in hepatitis B co-infected patients. Monitor hepatic function for several months after stopping treatment.

Efficacy

Lamivudine has been shown to be highly effective for HIV treatment, especially when used in combination with other antiretroviral drugs. Multiple clinical studies have demonstrated that lamivudine-containing regimens can significantly reduce HIV viral load, increase CD4 T-cell counts, and slow disease progression.

In the CAESAR study, lamivudine in combination with zidovudine led to an average 1.3 log decrease in HIV RNA at 24 weeks. After a year of treatment, 80% of patients had HIV RNA levels below 400 copies/mL. The NUCA study also showed a 0.7 log decrease in viral load at 24 weeks when lamivudine was added to zidovudine monotherapy.

Lamivudine has also been studied in combination with other classes of antiretrovirals. The CNA30024 trial compared lamivudine plus zidovudine to lamivudine plus stavudine. At 48 weeks, the viral load reductions were 0.58 log and 0.59 log respectively, indicating lamivudine maintains efficacy when combined with other NRTIs besides zidovudine.

Additional studies like 2NN, EPV20001, and ACTG306 have consistently shown that lamivudine-containing regimens lead to significant viral suppression, CD4 cell increases, and clinical improvements in HIV patients. While resistance can develop over time, lamivudine remains a highly potent antiretroviral medication when used properly as part of HIV therapy. Its efficacy has been firmly established through numerous clinical trials over decades of use.

Cost and Availability

Lamivudine is available as both a brand name and a generic drug. The brand name is Epivir and is sold by GlaxoSmithKline. The generic versions are typically more affordable.

With insurance coverage in the United States, the typical co-pay for a 30-day supply of Lamivudine is between $10-50 for the generic and $50-75 for the brand name. The exact cost depends on the pharmacy and individual's insurance plan. Those without insurance can expect to pay $150-400 for a 30-day supply of the generic.

One way to reduce the cost is to use a prescription savings card or coupon. These can often lower a brand name prescription down to the generic price. Another option is ordering from an onlinepharmacy -order sanfordpharmacy.com, which may offer better rates.

The generic Lamivudine tablets are more affordable, typically costing $30-100 for a one month supply without insurance. Purchasing a higher quantity 90-day supply can further reduce the monthly cost.

Overall, Lamivudine remains one of the more economical HIV medications. Both brand name and generic options provide the same antiviral efficacy. By utilizing coupons or insurance coverage, Lamivudine can be obtained affordably to support HIV therapy.

Conclusion

Lamivudine is an effective antiretroviral medication that is widely used for HIV treatment. When used in combination with other antiretrovirals as part of HAART (highly active antiretroviral therapy), lamivudine can help suppress HIV viral load, increase CD4 cell counts, and slow the progression of HIV infection.

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