Stv PLUS

Each capsule also contains the following excipients: Microcrystalline cellulose, sodium starch glycolate, lactose and magnesium stearate. The hard gelatin shell consists of gelatin, titanium dioxide and iron oxides. The markings are printed with edible inks.

Stv PLUS is 2',3'-didehydro-3'-deoxythymidine. Stv PLUS is a white to off-white crystalline solid with the molecular formula C₁₀H₁₂N₂O₄ and a molecular weight of 224.2. The solubility of Stv PLUS at 23°C is approximately 83 mg/mL in water and 30 mg/mL in propylene glycol. The n-octanol/water partition coefficient of Stv PLUS at 23°C is 0.144.

Stv PLUS® (Stv PLUS), in combination with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV)-1 infection.

Stv PLUS is used in combination with other anti-virus medicines for the treatment of human immunodeficiency virus (HIV) infection. HIV is the virus that causes acquired immune deficiency syndrome (AIDS).

Stv PLUS will not cure or prevent HIV infection or AIDS. It helps to keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay problems that are usually related to AIDS or HIV disease.

Stv PLUS will not keep you or your child from spreading HIV to other people. People who receive Stv PLUS may continue to have the problems usually related to AIDS or HIV disease.

Stv PLUS is available only with your doctor's prescription.

The interval between doses of Stv PLUS (Stv PLUS) should be 12 hours. Stv PLUS may be taken with or without food.

Recommended Adult Dosage

The recommended adult dosage is based on body weight as follows:

• For patients weighing less than 60 kg: 30 mg every 12 hours.
• For patients weighing at least 60 kg: 40 mg every 12 hours.

Recommended Pediatric Dosage

• For newborns from birth to 13 days old: 0.5 mg/kg given every 12 hours.
• For pediatric patients at least 14 days old and weighing less than 30 kg: 1 mg/kg given every 12 hours.
• For pediatric patients weighing at least 30 kg: use the recommended adult dosage.

Dosage Adjustment

Renal Impairment

Adult Patients: Stv PLUS may be administered to adult patients with impaired renal function with an adjustment in dosage as shown in Table 1.

Table 1: Recommended Dosage Adjustment for Adult Patients with Renal Impairment

Pediatric Patients: Since urinary excretion is also a major route of elimination of Stv PLUS in pediatric patients, the clearance of Stv PLUS may be altered in children with renal impairment. There are insufficient data to recommend a specific dose adjustment of Stv PLUS in this patient population.

Method Of Preparation For

Oral Solution

Prior to dispensing, the pharmacist must constitute the dry powder with purified water to a concentration of 1 mg Stv PLUS per mL of solution, as follows:

1. Add 202 mL of purified water to the container.
2. Shake container vigorously until the powder dissolves completely. Constitution in this way produces 200 mL (deliverable volume) of 1 mg/mL Stv PLUS solution. The solution may appear slightly hazy.
3. Dispense solution in original container with measuring cup provided. Instruct patient to shake the container vigorously prior to measuring each dose and to store the tightly closed container in a refrigerator, 2°C to 8°C (36°F to 46°F). Discard any unused portion after 30 days.

How supplied

Dosage Forms And Strengths

• Stv PLUS 15 mg capsules with dark red cap and light yellow body, printed with black ink “BMS 1964” on the cap and with black ink “15” on the body.
• Stv PLUS 20 mg capsules with light brown cap and light brown body, printed with black ink “BMS 1965” on the cap and with black ink “20” on the body.
• Stv PLUS 30 mg capsules with dark orange cap and light orange body, printed with black ink “BMS 1966” on the cap and with black ink “30” on the body.
• Stv PLUS 40 mg capsules with dark orange cap and dark orange body, printed with black ink “BMS 1967” on the cap and with black ink “40” on the body.
• Stv PLUS for oral solution is a dye-free, fruit-flavored powder that provides 1 mg of Stv PLUS per milliliter solution after constitution.

Storage And Handling

Capsules

Stv PLUS® (Stv PLUS) Capsules are available in the following strengths and configurations of plastic bottles with child-resistant closures:

Table 13: Capsule Strength/Configuration

Oral Solution

Stv PLUS (Stv PLUS) for

Oral Solution is a dye-free, fruit-flavored powder that provides 1 mg of Stv PLUS per mL of solution upon constitution with water. Directions for solution preparation are included on the product label and in the Dosage and Administration (2) section of this insert. Stv PLUS for

Oral Solution (NDC No. 0003-1968-01) is available in child-resistant containers that provide 200 mL of solution after constitution with water.

Storage

Stv PLUS Capsules should be stored in tightly closed containers at 25°C (77°F). Excursions between 15°C and 30°C (59°F and 86°F) are permitted.

Stv PLUS for

Oral Solution should be protected from excessive moisture and stored in tightly closed containers at 25°C (77°F). Excursions between 15°C and 30°C (59°F and 86°F) are permitted. After constitution, store tightly closed containers of Stv PLUS for

Oral Solution in a refrigerator, 2°C to 8°C (36°F to 46°F). Discard any unused portion after 30 days.

Distributed by: Bristol-Myers Squibb Company, Princeton, NJ 08543 USA. Revised: December 2012

See also:
What is the most important information I should know about Stv PLUS?

Stv PLUS should not be taken together with any HIV combination that includes zidovudine (Combivir, Retrovir, or Trizivir).

Some people develop lactic acidosis while taking Stv PLUS. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have even mild symptoms such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, fast or uneven heart rate, dizziness, or feeling very weak or tired.

Stv PLUS can also cause severe or life-threatening effects on your liver or pancreas. Call your doctor at once if you have any of these symptoms while taking Stv PLUS: severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate, itching, loss of appetite, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Before taking Stv PLUS, tell your doctor if you have kidney disease, liver disease, a history of pancreatitis, or if you have used a medicine similar to Stv PLUS in the past, such as abacavir (Ziagen), didanosine (Videx), emtricitabine (Atripla, Complera, Emtriva, Truvada), Stv PLUS (Epivir, Combivir, Epzicom, Trizivir), tenofovir (Viread), zalcitabine (Hivid), or zidovudine (Retrovir).

Use Stv PLUS solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Stv PLUS solution comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Stv PLUS solution refilled.
• Take Stv PLUS solution by mouth with or without food.
• Shake well before each use.
• Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.
• Continue to take Stv PLUS solution even if you feel well. Do not miss any doses.
• If you miss a dose of Stv PLUS solution, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Stv PLUS solution.

Stv PLUS is used in combination with other anti-viral drugs in the treatment of Human Immunodeficiency Virus (HIV) infection. It does not cure the infection, but prevents the spread of HIV and HIV-related illnesses such as suppression of immunity, cancer and other infections.

See also:
What other drugs will affect Stv PLUS?

Stv PLUS is unlikely to interact with drugs metabolized by cytochrome P450 isoenzymes.

Zidovudine

Zidovudine competitively inhibits the intracellular phosphorylation of Stv PLUS. Therefore, use of zidovudine in combination with Stv PLUS (Stv PLUS) should be avoided.

Doxorubicin

In vitro data indicate that the phosphorylation of Stv PLUS is inhibited at relevant concentrations by doxorubicin. The clinical significance of this interaction is unknown; therefore, concomitant use of Stv PLUS with doxorubicin should be undertaken with caution.

Ribavirin

In vitro data indicate ribavirin reduces phosphorylation of Stv PLUS, Stv PLUS, and zidovudine. The clinical significance of the interaction with Stv PLUS is unknown; therefore, concomitant use of Stv PLUS with ribavirin should be undertaken with caution. No pharmacokinetic (eg, plasma concentrations or intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (eg, loss of HIV-1/HCV virologic suppression) interaction was observed when ribavirin and Stv PLUS (n=18), Stv PLUS (n=10), or zidovudine (n=6) were coadministered as part of a multi-drug regimen to HIV-1/HCV co-infected patients.

See also:
What are the possible side effects of Stv PLUS?

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• lactic acidosis and severe hepatomegaly with steatosis [see
• hepatic toxicity [see
• neurologic symptoms and motor weakness [see
• pancreatitis
• lipoatrophy/lipodystrophy [see

When Stv PLUS is used in combination with other agents with similar toxicities, the incidence of adverse reactions may be higher than when Stv PLUS is used alone.

Clinical Trial Experience in Adults

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Selected adverse reactions that occurred in adult patients receiving Stv PLUS in a controlled monotherapy study (Study AI455-019) are provided in Table 2.

Pancreatitis was observed in 3 of the 412 adult patients who received Stv PLUS in study AI455-019.

Selected adverse reactions that occurred in antiretroviral-naive adult patients receiving Stv PLUS from two controlled combination studies are provided in Table 3.

Selected laboratory abnormalities reported in a controlled monotherapy study (Study AI455-019) are provided in Table 4.

Selected laboratory abnormalities reported in two controlled combination studies are provided in Tables 5 and 6.

Clinical Trial Experience in Pediatric Patients

Adverse reactions and serious laboratory abnormalities reported in pediatric patients from birth through adolescence during clinical trials were similar in type and frequency to those seen in adult patients.

Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of Stv PLUS. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to their seriousness, frequency of reporting, causal connection to Stv PLUS, or a combination of these factors.

Body as a Whole: abdominal pain, allergic reaction, chills/fever, and redistribution/accumulation of body fat [see

Digestive Disorders: anorexia.

Exocrine Gland Disorders: pancreatitis, including fatal cases [see

Hematologic Disorders: anemia, leukopenia, thrombocytopenia, neutropenia, and macrocytosis.

Liver: symptomatic hyperlactatemia/lactic acidosis and hepatic steatosis, hepatitis and liver failure.

Metabolic Disorders: lipoatrophy, lipodystrophy, diabetes mellitus and hyperglycemia.

Musculoskeletal: myalgia.

Nervous System: insomnia, severe motor weakness (most often reported in the setting of lactic acidosis).

Use with Didanosine- and Hydroxyurea-Based Regimens

When Stv PLUS is used in combination with other agents with similar toxicities, the incidence of these toxicities may be higher than when Stv PLUS is used alone. Thus, patients treated with Stv PLUS in combination with didanosine, with or without hydroxyurea, may be at increased risk for pancreatitis and hepatotoxicity, which may be fatal, and severe peripheral neuropathy. The combination of Stv PLUS and hydroxyurea, with or without didanosine, should be avoided.