Volibris 5mg

Volibris 5mg is indicated for treatment of idiopathic (‘primary’) pulmonary arterial hypertension (IPAH) and pulmonary arterial hypertension (PAH) associated with connective tissue disease in patients with WHO functional class II or III symptoms. In the United States of America, Volibris 5mg is also indicated in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability. (WHO Group 1 Pulmonary arterial hypertension;)

Volibris 5mg prevents thickening of the blood vessels, especially those in the lungs and heart. Volibris 5mg also lowers blood pressure in your lungs, helping your heart pump blood more efficiently.

Volibris 5mg is used to treat pulmonary arterial hypertension (PAH). It improves your ability to exercise and prevents your condition from getting worse.

Volibris 5mg is available only under a special program called LEAP (Volibris 5mg Education and Access Program). You must be registered in the program and sign agreements to use birth control and undergo pregnancy and blood testing as required by the program. Read all program brochures and agreements carefully.

Volibris 5mg may also be used for purposes not listed in this medication guide.

Adult Dosage

Initiate treatment at 5 mg once daily, with or without tadalafil 20 mg once daily. At 4-week intervals, either the dose of Volibris 5mg or tadalafil can be increased, as needed and tolerated, to Volibris 5mg 10 mg or tadalafil 40 mg.

Do not split, crush, or chew tablets.

Pregnancy Testing In Females Of Reproductive Potential

Initiate treatment with Volibris 5mg in females of reproductive potential only after a negative pregnancy test. Obtain monthly pregnancy tests during treatment.

How supplied

Dosage Forms And Strengths

5 mg and 10 mg film-coated tablets for oral administration

• Each 5 mg tablet is square convex, pale pink, with “5” on one side and “GSI” on the other side.
• Each 10 mg tablet is oval convex, deep pink, with “10” on one side and “GSI” on the other side.

Storage And Handling

Volibris 5mg film-coated tablets are supplied as follows:

Store at 25° C (77° F); excursions permitted to 15–30° C (59–86° F). Store Volibris 5mg in its original packaging.

Gilead Sciences, Inc., Foster City, CA 94404. Revised: October 2015

See also:
What is the most important information I should know about Volibris 5mg?

Volibris 5mg can harm an unborn baby or cause birth defects. Do not use if you are pregnant.

If you are a woman of child-bearing potential, you will need to have a negative pregnancy test before you start treatment with Volibris 5mg. You will also be re-tested each month during your treatment.

You will be required to use two forms of birth control to prevent pregnancy during your treatment, and for at least 1 month after your treatment ends. If you have had a tubal ligation or are using a copper IUD, you will not need to use a second form of birth control.

Do not stop taking Volibris 5mg without first talking to your doctor. You may need to use less and less before you stop the medication completely.

Volibris 5mg is available only under a special program called LEAP (Volibris 5mg Education and Access Program). You must be registered in the program and sign agreements to use birth control and undergo pregnancy and blood testing as required by the program. Read all program brochures and agreements carefully.

Use Volibris 5mg as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Volibris 5mg comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Volibris 5mg refilled.
• Take Volibris 5mg by mouth with or without food.
• Swallow Volibris 5mg whole. Do not break, split, crush, or chew before swallowing.
• Take Volibris 5mg on a regular schedule to get the most benefit from it. Taking Volibris 5mg at the same times each day will help you to remember to take it.
• Continue to take Volibris 5mg even if you feel well. Do not miss any doses.
• If you miss a dose of Volibris 5mg, 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 Volibris 5mg.

Volibris 5mg is used for the treatment of pulmonary arterial hypertension, a condition in which blood pressure rises due to narrowing of the arteries supplying blood from the heart to the lungs.

See also:
What other drugs will affect Volibris 5mg?

Multiple dose coadministration of Volibris 5mg and cyclosporine resulted in an approximately 2-fold increase in Volibris 5mg exposure in healthy volunteers; therefore, limit the dose of Volibris 5mg to 5 mg once daily when coadministered with cyclosporine.

See also:
What are the possible side effects of Volibris 5mg?

Clinically significant adverse reactions that appear in other sections of the labeling include:

• Embryo-fetal Toxicity
• Fluid Retention
• Pulmonary Edema with PVOD
• Decreased Sperm Count
• Hematologic Changes

Clinical Trials Experience

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 practice.

Safety data for Volibris 5mg are presented from two 12-week, placebo-controlled studies (ARIES-1 and ARIES-2) in patients with pulmonary arterial hypertension (PAH), and one randomized, double-blind, active-controlled trial in 605 patients with PAH (AMBITION) comparing Volibris 5mg plus tadalafil to Volibris 5mg or tadalafil alone. The exposure to Volibris 5mg in these studies ranged from 1 day to 4 years (N=357 for at least 6 months and N=279 for at least 1 year).

In ARIES-1 and ARIES-2, a total of 261 patients received Volibris 5mg at doses of 2.5, 5, or 10 mg once daily and 132 patients received placebo. The adverse reactions that occurred in > 3% more patients receiving Volibris 5mg than receiving placebo are shown in Table 1.

Table 1 : Adverse Reactions with Placebo-Adjusted Rates > 3% in ARIES-1 and ARIES-2

Most adverse drug reactions were mild to moderate and only nasal congestion was dose-dependent.

Few notable differences in the incidence of adverse reactions were observed for patients by age or sex. Peripheral edema was similar in younger patients ( < 65 years) receiving Volibris 5mg (14%; 29/205) or placebo (13%; 13/104), and was greater in elderly patients ( ≥ 65 years) receiving Volibris 5mg (29%; 16/56) compared to placebo (4%; 1/28). The results of such subgroup analyses must be interpreted cautiously.

The incidence of treatment discontinuations due to adverse events other than those related to PAH during the clinical trials in patients with PAH was similar for Volibris 5mg (2%; 5/261 patients) and placebo (2%; 3/132 patients). The incidence of patients with serious adverse events other than those related to PAH during the clinical trials in patients with PAH was similar for placebo (7%; 9/132 patients) and for Volibris 5mg (5%; 13/261 patients).

During 12-week controlled clinical trials, the incidence of aminotransferase elevations > 3 x upper limit of normal (ULN) were 0% on Volibris 5mg and 2.3% on placebo. In practice, cases of hepatic injury should be carefully evaluated for cause.

Combination Use with Tadalafil

The mean exposure to Volibris 5mg + tadalafil in the AMBITION study was 78.7 weeks. The adverse reactions that occurred in > 5% more patients receiving Volibris 5mg + tadalafil than receiving Volibris 5mg or tadalafil monotherapy in AMBITION are shown in Table 2.

Table 2 : Adverse Reactions Reported More Commonly ( > 5%) on Volibris 5mg + Tadalafil thanon Volibris 5mg or Tadalafil Monotherapy (ITT) in AMBITION

Peripheral edema was more frequent on combination therapy; however, there was no notable difference observed in the incidence of peripheral edema in elderly patients ( ≥ 65 years) versus younger patients ( < 65 years) on combination therapy (44% vs. 45%) or Volibris 5mg monotherapy (37% vs. 39%) in AMBITION.

Treatment discontinuations due to adverse events while on randomized treatment were similar across treatment groups: 16% for Volibris 5mg + tadalafil, 14% for Volibris 5mg alone, and 13% for tadalafil alone.

Use in Patients with Prior Endothelin Receptor Antagonist (ERA) Related Serum Liver Enzyme Abnormalities

In an uncontrolled, open-label study, 36 patients who had previously discontinued endothelin receptor antagonists (ERAs: bosentan, an investigational drug, or both) due to aminotransferase elevations > 3 x ULN were treated with Volibris 5mg. Prior elevations were predominantly moderate, with 64% of the ALT elevations < 5 x ULN, but 9 patients had elevations > 8 x ULN. Eight patients had been re-challenged with bosentan and/or the investigational ERA and all eight had a recurrence of aminotransferase abnormalities that required discontinuation of ERA therapy. All patients had to have normal aminotransferase levels on entry to this study. Twenty-five of the 36 patients were also receiving prostanoid and/or phosphodiesterase type 5 (PDE5) inhibitor therapy. Two patients discontinued early (including one of the patients with a prior 8 x ULN elevation). Of the remaining 34 patients, one patient experienced a mild aminotransferase elevation at 12 weeks on Volibris 5mg 5 mg that resolved with decreasing the dosage to 2.5 mg, and that did not recur with later escalations to 10 mg. With a median follow-up of 13 months and with 50% of patients increasing the dose of Volibris 5mg to 10 mg, no patients were discontinued for aminotransferase elevations. While the uncontrolled study design does not provide information about what would have occurred with re-administration of previously used ERAs or show that Volibris 5mg led to fewer aminotransferase elevations than would have been seen with those drugs, the study indicates that Volibris 5mg may be tried in patients who have experienced asymptomatic aminotransferase elevations on other ERAs after aminotransferase levels have returned to normal.

Postmarketing Experience

The following adverse reactions were identified during post-approval use of Volibris 5mg. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to estimate reliably the frequency or to establish a causal relationship to drug exposure: anemia requiring transfusion heart failure (associated with fluid retention), symptomatic hypotension, and hypersensitivity (e.g., angioedema, rash).

Elevations of liver aminotransferases (ALT, AST) have been reported with Volibris 5mg use; in most cases alternative causes of the liver injury could be identified (heart failure, hepatic congestion, hepatitis, alcohol use, hepatotoxic medications). Other endothelin receptor antagonists have been associated with elevations of aminotransferases, hepatotoxicity, and cases of liver failure.

Volibris 5mg is an orally active selective type A endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension. It is approved in Europe, Canada and the United States for use as a single agent to improve exercise ability and delay clinical worsening. In addition, it is approved in the United States for use in combination with tadalafil to reduce the risks of disease progression, hospitalization and to improve exercise ability. Studies establishing the efficacy of Volibris 5mg included patients with both idiopathic or heritable pulmonary arterial hypertension and those with pulmonary arterial hypertension associated with connective tissue diseases. Patients studied displayed symptoms and etiologies predominantly of WHO Functional Class II-III. As an endothelin receptor antagonist, Volibris 5mg prevents endogenous endothelin peptide from constricting the muscles in blood vessels, allowing them to relax and permit a reduction in blood pressure.