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AMBRISENTAN 10 mg Tablet, Film Coated, 30-count

by Sigmapharm Laboratories, LLC · 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (42794-052-08)
NDC 42794-0052-08
🏷️ FDA NDC (as labeled) 42794-052-08 billing pads the product segment with a zero
This package
Contains30-count Cost per ea$8.21 NADAC Per package$246.28 / 30 tablets Pack sizes2 compare ↓
Also priced by: Part D plans $87.47/unit — full pricing hub ↓
Also comes in: 10 tablets 42794-0052-22
Rx only Generic On market Non-controlled 🛡 REMS
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 42794-052-08
Product NDC 42794-052
11-digit billing NDC 42794005208
NCPDP billing unit EA — each (per item)
RxCUI 722116, 722122
UNII HW6NV07QEC
UPC 0342794052088, 0342794051081
Application # ANDA208354
SPL Set ID e20ab2fe-bc9f-48a3-b15a-e4bc9532c2ac
Established class (EPC) Endothelin Receptor Antagonist
Mechanism of action Endothelin Receptor Antagonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2019-04-10
Route ORAL
Dosage form TABLET, FILM COATED
Substance AMBRISENTAN
GPI-14 40160007000320
GPI class Ambrisentan
GCN Seq No 062793
GCN 98567
HICL code 034849
Ingredient (HICL) Ambrisentan
HIC1 code B
Therapeutic class — broad (HIC1) Respiratory System
HIC2 code B1
Therapeutic class — intermediate (HIC2) Affect Primarily Lungs
HIC3 code B1B
Therapeutic class — specific (HIC3) Pulmonary Anti-Htn, Endothelin Receptor Antagonist
AHFS code 24:12.92.00
AHFS class Vasodilating Agents, Miscellaneous
FDB label name AMBRISENTAN 10 MG TABLET
FDB brand name Ambrisentan
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 42794-052-08 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 42794-0052-08. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Endothelin Receptor Antagonist class.

Pharmacologic class Endothelin Receptor Antagonist
Drug family (ATC) Antihypertensives for pulmonary arterial hypertension
How it works Endothelin Receptor Antagonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerSigmapharm Laboratories, LLC
Application holderSIGMAPHARM LABORATORIES LLC
FDA applicationANDA208354 (ANDA)
Labeler code42794
First marketedApr 2019
Product typeHuman Prescription Drug
Portfolio28 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name AMBRISENTAN 10 MG TABLET Ingredient Ambrisentan
📗 Our plain-language guide HelloPharmacist
  • Ambrisentan won't cure PAH, but it can make a real difference in how you feel and function. It works by blocking a protein called ET-1 that causes the blood vessels in your lungs t...
  • What exactly does ambrisentan do, and will it cure my PAH?
  • Good news — food doesn't affect how well your body absorbs ambrisentan, so you can take it with or without a meal, whichever works best for your routine. Pick a time of day you can...
  • Can I take ambrisentan with food, and does it matter what time of day I take it?
📖 Read our full Ambrisentan guide →
1
Nutrient depletion considerations

Ambrisentan may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color pink
ShapeOval
Imprint52
Size1 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eaPer package
Retail pharmacies payNADAC · weekly $8.209 $246.28 / 30 tablets
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $87.47 $2,624.22 / 30 tablets
NADAC price history (per ea) — tap or hover for the price & month
Dec 2025 Feb 2026 May 2026 Aug 2026 $9.079 $8.209
▼ Down 10% over the last 9 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Ambrisentan 10 mg 00378-4271-93 Mylan 30 tablets $8.209 AB Availability likely
Ambrisentan 10 mg 00591-2406-30 Actavis 30 tablets $8.209 AB Availability likely
Ambrisentan 10 mgthis 42794-0052-08 Sigmapharm 30 tablets $8.209 AB Availability likely
ambrisentan 10 mg 59651-0495-30 Aurobindo 30 tablets $8.209 AB Availability likely
Ambrisentan 10 mg 60505-4553-03 Apotex 30 tablets $8.209 AB Availability likely
Ambrisentan 10 mg 69097-0387-02 Cipla 30 tablets $8.209 AB Availability likely
Ambrisentan 10 mg 82009-0142-30 Quallent 30 tablets $8.209 AB Availability likely
ambrisentan 10 mg 47335-0237-64 Sun 10 tablets FDA listed
ambrisentan 10 mg 50090-7670-00 A-S 30 tablets AB FDA listed
Ambrisentan 10 mg 51407-0595-30 Golden 30 tablets AB FDA listed
Letairis 10 mg 61958-0802-01 Gilead 30 tablets AB FDA listed
Ambrisentan 10 mg 70710-1180-01 Zydus 100 tablets AB FDA listed
Ambrisentan 10 mg 70771-1364-01 Zydus 100 tablets AB FDA listed
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2019
On the market since
Apr 2019
📍
2026
Currently FDA-listed
7 years listed
🔓
·
Generic on the market
this product is a generic
This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Ambrisentan — the program that covers self-administered drugs. 7 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Ambrisentan. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$27.85M
Claims incl. refills
15.9K
Beneficiaries
6.1K
Spend / beneficiary
$4,542.00
Spend / claim
$1,754.58
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.
🛡
This drug has a REMS — Ambrisentan REMS. A Risk Evaluation & Mitigation Strategy is an FDA-required safety program. It is available only through a restricted program (certified prescribers/pharmacies, enrollment, or required monitoring). See the boxed warning & full label below, and REMS@FDA ↗.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
42794-0052-08 You're viewing this 30 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (42794-052-08) $8.21 / ea $246.28 2019-04-10 Active
42794-0052-22 10 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (42794-052-22) 2019-04-10 Active

You're viewing the largest of 2 pack sizes for this product.

Pack size FAQ

What quantity is in NDC 42794-0052-08?
NDC 42794-0052-08 is a 30-count package — 30 tablet, film coated in 1 bottle, plastic.
What is the difference between NDC 42794-0052-08 and NDC 42794-0052-22?
Both are AMBRISENTAN 10 mg Tablet, Film Coated — the drug itself is identical. NDC 42794-0052-08 is the 30-count package, while NDC 42794-0052-22 is the 10 tablets package.
What NDC number is used to bill for this package of AMBRISENTAN 10 mg Tablet, Film Coated?
Bill NDC 42794-0052-08 — the 11-digit billing format is 42794005208. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning ~1 min read

WARNING: EMBRYO-FETAL TOXICITY Do not administer ambrisentan to a pregnant female because it may cause fetal harm. Ambrisentan is very likely to produce serious birth defects if used by pregnant females, as this effect has been seen consistently when it is administered to animals [see Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1) ] . Exclude pregnancy before the initiation of treatment with ambrisentan.

Females of reproductive potential must use acceptable methods of contraception during treatment with ambrisentan and for one month after treatment. Obtain monthly pregnancy tests during treatment and 1 month after discontinuation of treatment [see Dosage and Administration (2.2) and Use in Specific Populations (8.3) ] . Because of the risk of embryo-fetal toxicity, females can only receive ambrisentan through a restricted program called the Ambrisentan REMS program [see Warnings and Precautions (5.2) ] .

WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Do not administer ambrisentan to a pregnant female because it may cause fetal harm ( 4.1 , 5.1 , 8.1 ). Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment.

Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception ( 2.2 , 8.3 ). For all female patients, ambrisentan is available only through a restricted program called the Ambrisentan Risk Evaluation and Mitigation Strategy (REMS) ( 5.2 ).

🎯 Indications and Usage 162 words

1 INDICATIONS AND USAGE Ambrisentan tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): To improve exercise ability and delay clinical worsening. In combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability [ see Clinical Studies (14.2) ]. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%).

Ambrisentan is an endothelin receptor antagonist indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): To improve exercise ability and delay clinical worsening. In combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability. Studies establishing effectiveness included trials predominantly in patients with WHO Functional Class II-III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%) ( 1 ).

⏱️ Dosage and Administration 131 words

2 DOSAGE AND ADMINISTRATION Initiate treatment at 5 mg once daily ( 2.1 ). May be started with tadalafil ( 2.1 ). Titrate at 4-week intervals as needed and tolerated ( 2.1 ).

Do not split, crush, or chew tablets ( 2.1 ). 2.1. 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 ambrisentan or tadalafil can be increased, as needed and tolerated, to ambrisentan tablets, 10 mg or tadalafil 40 mg. Do not split, crush, or chew tablets. 2.2.

Pregnancy Testing in Females of Reproductive Potential Initiate treatment with ambrisentan in females of reproductive potential only after a negative pregnancy test. Obtain monthly pregnancy tests during treatment [see Use in Specific Populations (8.3) ] .

💊 Dosage Forms and Strengths 64 words

3 DOSAGE FORMS AND STRENGTHS 5 mg and 10 mg film-coated tablets for oral administration Each 5 mg tablet is square shaped, light pink, with “∑” on one side and “51” on the other side. Each 10 mg tablet is oval shaped, dark pink, with “∑” on one side and “52” on the other side. Tablet: 5 mg and 10 mg ( 3 )

Contraindications 119 words

4 CONTRAINDICATIONS Pregnancy ( 4.1 ) Idiopathic Pulmonary Fibrosis ( 4.2 ) 4.1. Pregnancy Ambrisentan may cause fetal harm when administered to a pregnant female. Ambrisentan is contraindicated in females who are pregnant.

Ambrisentan was consistently shown to have teratogenic effects when administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Warnings and Precautions (5.1 , 5.2 ) and Use in Specific Populations (8.1) ] . 4.2.

Idiopathic Pulmonary Fibrosis Ambrisentan is contraindicated in patients with Idiopathic Pulmonary Fibrosis (IPF), including IPF patients with pulmonary hypertension (WHO Group 3) [see Clinical Studies (14.4) ] .

⚠️ Warnings and Cautions ~3 min read

5 WARNINGS AND PRECAUTIONS Fluid retention may require intervention ( 5.3 ). If patients develop acute pulmonary edema during initiation of therapy with ambrisentan, consider underlying pulmonary veno-occlusive disease and discontinue treatment if necessary ( 5.4 ). Decreases in sperm count have been observed in patients taking endothelin receptor antagonists ( 5.5 ).

Decreases in hemoglobin have been observed within the first few weeks; measure hemoglobin at initiation, at 1 month, and periodically thereafter ( 5.6 ). 5.1. Embryo-fetal Toxicity Ambrisentan may cause fetal harm when administered during pregnancy and is contraindicated for use in females who are pregnant.

In females of reproductive potential, exclude pregnancy prior to initiation of therapy, ensure use of acceptable contraceptive methods, and obtain monthly pregnancy tests [see Dosage and Administration (2.2) , and Use in Specific Populations ( 8.1 , 8.3 )] . Ambrisentan is only available for females through a restricted program under a REMS [see Warnings and Precautions (5.2) ] . 5.2.

Ambrisentan REMS Program For all females, ambrisentan is available only through a restricted program called the Ambrisentan REMS, because of the risk of embryo-fetal toxicity [see Contraindications (4.1) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1 , 8.3) ] . Notable requirements of the Ambrisentan REMS program include the following: Prescribers must be certified with the program by enrolling and completing training. All females, regardless of reproductive potential, must enroll in the Ambrisentan REMS program prior to initiating ambrisentan.

Male patients are not enrolled in the REMS. Females of reproductive potential must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations (8.3) ]. Pharmacies that dispense ambrisentan must be certified with the program and must dispense to female patients who are authorized to receive ambrisentan.

Further information is available at www.ambrisentanrems.us.com or 1-888-417-3172. 5.3. Fluid Retention Peripheral edema is a known class effect of endothelin receptor antagonists, and is also a clinical consequence of PAH and worsening PAH.

In the placebo-controlled studies, there was an increased incidence of peripheral edema in patients treated with doses of 5 or 10 mg ambrisentan compared to placebo [see Adverse Reactions (6.1) ] . Most edema was mild to moderate in severity. In addition, there have been postmarketing reports of fluid retention in patients with pulmonary hypertension, occurring within weeks after starting ambrisentan.

Patients required intervention with a diuretic, fluid management, or, in some cases, hospitalization for decompensating heart failure. If clinically significant fluid retention develops, with or without associated weight gain, further evaluation should be undertaken to determine the cause, such as ambrisentan or underlying heart failure, and the possible need for specific treatment or discontinuation of ambrisentan therapy. Peripheral edema/fluid retention is more common with ambrisentan plus tadalafil than with ambrisentan or tadalafil alone.

5.4. Pulmonary Edema with Pulmonary Veno-occlusive Disease (PVOD) If patients develop acute pulmonary edema during initiation of therapy with vasodilating agents such as ambrisentan, the possibility of PVOD should be considered, and if confirmed ambrisentan should be discontinued. 5.5.

Decreased Sperm Counts Decreased sperm counts have been observed in human and animal studies with another endothelin receptor antagonist and in animal fertility studies with ambrisentan. Ambrisentan may have an adverse effect on spermatogenesis. Counsel patients about potential effects on fertility [see Use in Specific Populations (8.6) and Nonclinical Toxicology (13.1) ] .

5.6. Hematological Changes Decreases in hemoglobin concentration and hematocrit have followed administration of other endothelin receptor antagonists and…

🤒 Adverse Reactions ~3 min read

6 ADVERSE REACTIONS Clinically significant adverse reactions that appear in other sections of the labeling include: Embryo-fetal Toxicity [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1) ] Fluid Retention [see Warnings and Precautions (5.3) ] Pulmonary Edema with PVOD [see Warnings and Precautions (5.4) ] Decreased Sperm Count [see Warnings and Precautions (5.5) ] Hematologic Changes [see Warnings and Precautions (5.6) ] Most common adverse reactions (>3% compared to placebo) are peripheral edema, nasal congestion, sinusitis, and flushing ( 6.1 ).

When used in combination with tadalafil, most common adverse reactions (>5% compared with either Monotherapy) are peripheral edema, headache, nasal congestion, cough, anemia, dyspepsia, and bronchitis ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Sigmapharm Laboratories, LLC, Pharmacovigilance at 1-855-332-0731 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1.

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 ambrisentan 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 ambrisentan plus tadalafil to ambrisentan or tadalafil alone.

The exposure to ambrisentan 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 ambrisentan 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 ambrisentan than receiving placebo are shown in Table 1.

Table 1 Adverse Reactions with Placebo-Adjusted Rates >3% in ARIES-1 and ARIES-2 Placebo (N = 132) Ambrisentan (N = 261) Adverse Reaction n (%) n (%) Placebo-adjusted (%) Peripheral edema 14 (11) 45 (17) 6 Nasal congestion 2 (2) 15 (6) 4 Sinusitis 0 (0) 8 (3) 3 Flushing 1 (1) 10 (4) 3 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 ambrisentan (14%; 29/205) or placebo (13%; 13/104), and was greater in elderly patients (≥65 years) receiving ambrisentan (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 ambrisentan (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 ambrisentan (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 ambrisentan 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 ambrisentan + tadalafil in the AMBITION study was 78.7 weeks.

The adverse reactions that occurred in >5% more patients receiving ambrisentan + tadalafil than receiving ambrisentan or tadalafil monotherapy in AMBITION are shown in Table 2. Table 2 Adverse Reactions Reported More Commonly (>5%) on Ambrisentan + Tadalafil than on Ambrisentan or Tadalafil Monotherapy (ITT) in AMBITION Adverse Reactions Ambrisentan + Tadalafil Combination Therapy (N=302) n (%) Ambrisentan Monothe…

🔄 Drug Interactions 58 words

7 DRUG INTERACTIONS Multiple dose coadministration of ambrisentan and cyclosporine resulted in an approximately 2-fold increase in ambrisentan exposure in healthy volunteers; therefore, limit the dose of ambrisentan to 5 mg once daily when coadministered with cyclosporine [see Clinical Pharmacology (12.3) ] . Cyclosporine increases ambrisentan exposure; limit ambrisentan dose to 5 mg once daily ( 7 ).

👥 Use in Specific Populations ~3 min read

8 USE IN SPECIFIC POPULATIONS Breastfeeding: Choose ambrisentan or breastfeeding ( 8.2 ). Not recommended in patients with moderate or severe hepatic impairment ( 8.7 ). 8.1.

Pregnancy Risk Summary Based on data from animal reproduction studies, ambrisentan tablets may cause fetal harm when administered to a pregnant woman and is contraindicated during pregnancy. There are limited data on ambrisentan tablets use in pregnant women. In animal reproduction studies, ambrisentan tablets were teratogenic in rats and rabbits at doses which resulted in exposures of 3.5 and 1.7 times, respectively, the human dose of 10 mg per day [see Animal Data] .

If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential hazard to a fetus [see Contraindications (4.1) , Warnings and Precautions (5.1) ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Ambrisentan was teratogenic at oral dosages of ≥15 mg/kg/day (AUC 51.7 h•μg/mL) in rats and ≥7 mg/kg/day (24.7 h•μg/mL) in rabbits; it was not studied at lower dosages. These dosages are of 3.5 and 1.7 times, respectively, the human dose of 10 mg per day (14.8 h•μg/mL) based on AUC.

In both species, there were abnormalities of the lower jaw and hard and soft palate, malformation of the heart and great vessels, and failure of formation of the thymus and thyroid. A preclinical study in rats has shown decreased survival of newborn pups (mid and high dosages) and effects on testicle size and fertility of pups (high dosage) following maternal treatment with ambrisentan from late gestation through weaning. The mid and high dosages were 51 x, and 170 x (on a mg/m 2 body surface area basis) the maximum oral human dose of 10 mg and an average adult body weight of 70 kg.

These effects were absent at a maternal dosage 17 x the human dose based on mg/m 2 . 8.2. Lactation Risk Summary It is not known whether ambrisentan is present in human milk.

Because many drugs are present in human milk and because of the potential for serious adverse reactions in breastfed infants from ambrisentan, a decision should be made whether to discontinue breastfeeding or discontinue ambrisentan, taking into account the importance of the drug to the mother. 8.3. Females and Males of Reproductive Potential Pregnancy Testing Female patients of reproductive potential must have a negative pregnancy test prior to initiation of treatment, monthly pregnancy test during treatment, and pregnancy test 1 month after stopping treatment with ambrisentan.

Advise patients to contact their healthcare provider if they become pregnant or suspect they may be pregnant. Perform a pregnancy test if pregnancy is suspected for any reason. For positive pregnancy tests, counsel patient on the potential risk to the fetus and patient options [see Boxed Warning and Dosage and Administration (2.2) ] .

Contraception Female patients of reproductive potential must use acceptable methods of contraception during treatment with ambrisentan and for 1 month after stopping treatment with ambrisentan. Patients may choose one highly effective form of contraception (intrauterine device [IUD], contraceptive implant, or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method.

Counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see Boxed Warning ] . Infertility Males…

🆘 Overdosage 78 words

10 OVERDOSAGE There is no experience with overdosage of ambrisentan. The highest single dose of ambrisentan administered to healthy volunteers was 100 mg, and the highest daily dose administered to patients with PAH was 10 mg once daily. In healthy volunteers, single doses of 50 mg and 100 mg (5 to 10 times the maximum recommended dose) were associated with headache, flushing, dizziness, nausea, and nasal congestion.

Massive overdosage could potentially result in hypotension that may require intervention.

🧬 Clinical Pharmacology ~3 min read

12 CLINICAL PHARMACOLOGY 12.1. Mechanism of Action Endothelin-1 (ET-1) is a potent autocrine and paracrine peptide. Two receptor subtypes, ET A and ET B , mediate the effects of ET-1 in the vascular smooth muscle and endothelium.

The primary actions of ET A are vasoconstriction and cell proliferation, while the predominant actions of ET B are vasodilation, antiproliferation, and ET-1 clearance. In patients with PAH, plasma ET-1 concentrations are increased as much as 10-fold and correlate with increased mean right atrial pressure and disease severity. ET-1 and ET-1 mRNA concentrations are increased as much as 9-fold in the lung tissue of patients with PAH, primarily in the endothelium of pulmonary arteries.

These findings suggest that ET-1 may play a critical role in the pathogenesis and progression of PAH. Ambrisentan is a high-affinity (K i =0.011 nM) ET A receptor antagonist with a high selectivity for the ET A versus ET B receptor (>4000-fold). The clinical impact of high selectivity for ET A is not known.

12.2. Pharmacodynamics Cardiac Electrophysiology In a randomized, positive- and placebo-controlled, parallel-group study, healthy subjects received either ambrisentan 10 mg daily followed by a single dose of 40 mg, placebo followed by a single dose of moxifloxacin 400 mg, or placebo alone. Ambrisentan 10 mg daily had no significant effect on the QTc interval.

The 40 mg dose of ambrisentan increased mean QTc at t max by 5 ms with an upper 95% confidence limit of 9 ms. For patients receiving ambrisentan 5–10 mg daily and not taking metabolic inhibitors, no significant QT prolongation is expected. N-terminal pro-B-type natriuretic peptide (NT-proBNP) In AMBITION [see Clinical Studies (14.2) ] , the decrease in NT-proBNP in patients on ambrisentan plus tadalafil was observed early (Week 4) and was sustained, with a reduction of 63% on ambrisentan plus tadalafil, 50% on ambrisentan alone, and 41% on tadalafil alone at Week 24.

12.3. Pharmacokinetics The pharmacokinetics of ambrisentan (S-ambrisentan) in healthy subjects is dose proportional. The absolute bioavailability of ambrisentan is not known.

Ambrisentan is absorbed with peak concentrations occurring approximately 2 hours after oral administration in healthy subjects and PAH patients. Food does not affect its bioavailability. In vitro studies indicate that ambrisentan is a substrate of P-gp.

Ambrisentan is highly bound to plasma proteins (99%). The elimination of ambrisentan is predominantly by non-renal pathways, but the relative contributions of metabolism and biliary elimination have not been well characterized. In plasma, the AUC of 4-hydroxymethyl ambrisentan accounts for approximately 4% relative to parent ambrisentan AUC.

The in vivo inversion of S-ambrisentan to R-ambrisentan is negligible. The mean oral clearance of ambrisentan is 38 mL/min and 19 mL/min in healthy subjects and in PAH patients, respectively. Although ambrisentan has a 15-hour terminal half-life, the mean trough concentration of ambrisentan at steady-state is about 15% of the mean peak concentration and the accumulation factor is about 1.2 after long-term daily dosing, indicating that the effective half-life of ambrisentan is about 9 hours.

Drug Interactions In Vitro Studies Studies with human liver tissue indicate that ambrisentan is metabolized by CYP3A, CYP2C19, and uridine 5’-diphosphate glucuronosyltransferases (UGTs) 1A9S, 2B7S, and 1A3S. In vitro studies suggest that ambrisentan is a substrate of the Organic Anion Transporting Polypeptides OATP1B1 and OATP1B3, and P-glycoprotein (P-gp). Drug interactions might be expected because of these factors; however, a clinically relevant interaction has been demonstrated only with cyclosporine [see Drug Interactions (7) ] .

In vitro studies found ambrisentan to have little to no inhibition of human hepatic transporters. Ambrisentan demonstrated weak dose-dependent inhibition of OATP1B1, OATP1B3, and NTCP (IC 50 of 47 μM, 45 μM, and approximately 10…

📦 How Supplied / Storage and Handling 108 words

16 HOW SUPPLIED/STORAGE AND HANDLING Ambrisentan film-coated tablets are supplied as follows: Tablet Strength Package Configuration NDC No. Description of Tablet; Debossed on Tablet; Size 5 mg 30 count bottle 42794-051-08 Square shaped; light pink; “∑” on one side and “51” on the other side; 6.6 mm Square 10 count bottle 42794-051-22 10 mg 30 count bottle 42794-052-08 Oval shaped; dark pink; “∑” on one side and “52” on the other side; 9.8 mm x 4.9 mm Oval 10 count bottle 42794-052-22 Store at 25° C (77° F); excursions permitted to 15–30° C (59–86° F) [see USP controlled room temperature] .

Store ambrisentan tablets in its original packaging.

📋 Description ~1 min read

11 DESCRIPTION Ambrisentan is an endothelin receptor antagonist that is selective for the endothelin type-A (ET A ) receptor. The chemical name of ambrisentan is (+)-(2 S )-2-[(4,6-dimethylpyrimidin-2-yl)oxy]-3-methoxy-3,3-diphenylpropanoic acid. It has a molecular formula of C 22 H 22 N 2 O 4 and a molecular weight of 378.42.

It contains a single chiral center determined to be the ( S ) configuration and has the following structural formula: Figure 1 Ambrisentan Structural Formula Ambrisentan is a white to off-white, crystalline solid. It is a carboxylic acid with a pKa of 4.0. Ambrisentan is practically insoluble in water and in aqueous solutions at low pH.

Solubility increases in aqueous solutions at higher pH. In the solid state ambrisentan is very stable, is not hygroscopic, and is not light sensitive. Ambrisentan tablets are available as 5 mg and 10 mg film-coated tablets for once daily oral administration.

The tablets include the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate and microcrystalline cellulose. The tablets are film-coated with a coating material containing FD&C Red #40 aluminum lake, polyethylene glycol, polyvinyl alcohol, talc, and titanium dioxide. Ambrisentan tablets, 5 mg tablets also contain FD&C Blue #2.

Each square shaped, light pink ambrisentan tablet contains 5 mg of ambrisentan. Each oval shaped, dark pink ambrisentan tablet contains 10 mg of ambrisentan. Ambrisentan tablets are unscored. figure1

💬 Information for Patients ~1 min read

17 PATIENT COUNSELING INFORMATION Advise patients to read the FDA-approved patient labeling (Medication Guide). Embryo-fetal Toxicity Instruct patients on the risk of fetal harm when ambrisentan is used in pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . Female patients must enroll in the Ambrisentan REMS Program.

Instruct females of reproductive potential to immediately contact their physician if they suspect they may be pregnant. Ambrisentan REMS Program For female patients, ambrisentan is only available through a restricted program called the Ambrisentan REMS [see Contraindications (4.1) , Warnings and Precautions (5.2) ] . Male patients are not enrolled in the Ambrisentan REMS.

Inform female patients (and their guardians, if applicable) of the following notable requirements: All female patients must sign an enrollment form. Advise female patients of reproductive potential that they must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations (8.3) ] . Educate and counsel females of reproductive potential on the use of emergency contraception in the event of unprotected sex or known or suspected contraceptive failure.

Advise pre-pubertal females to report any changes in their reproductive status immediately to their prescriber. Review the Ambrisentan Medication Guide and REMS educational material with female patients. A limited number of pharmacies are certified to dispense ambrisentan tablets.

Therefore, provide patients with the telephone number and website for information on how to obtain the product. Hepatic Effects Advise patients of the symptoms of potential liver injury and instruct them to report any of these symptoms to their physician. Hematological Change Advise patients of the importance of hemoglobin testing.

Other Risks Associated with Ambrisentan Instruct patients that the risks associated with ambrisentan also include the following: Decreases in sperm count Fluid overload Administration Advise patients not to split, crush, or chew tablets.

💬 Medication Guide ~3 min read

Medication Guide Ambrisentan (am' bri sen' tan) Tablets Read this Medication Guide before you start taking ambrisentan tablets and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or your treatment.

What is the most important information I should know about ambrisentan tablets? Serious birth defects. Ambrisentan tablets can cause serious birth defects if taken during pregnancy.

Females must not be pregnant when they start taking ambrisentan tablets or become pregnant during treatment with ambrisentan tablets. Females who are able to get pregnant must have a negative pregnancy test before beginning treatment with ambrisentan tablets, each month during treatment with ambrisentan tablets, and one month after stopping ambrisentan tablets. Talk to your doctor about your menstrual cycle.

Your doctor will decide when to do a pregnancy test, and will order a pregnancy test for you depending on your menstrual cycle. Females who are able to get pregnant are females who: have entered puberty, even if they have not started their menstrual period, and have a uterus, and have not gone through menopause. Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed.

Females who are not able to get pregnant are females who: have not yet entered puberty, or do not have a uterus, or have gone through menopause. Menopause means that you have not had a menstrual period for at least 12 months for natural reasons, or that you have had your ovaries removed, or who are infertile for any other medical reason and this infertility is permanent and cannot be reversed. Females who are able to get pregnant must use two acceptable forms of birth control during treatment with ambrisentan tablets, and for one month after stopping ambrisentan tablets because the medicine may still be in the body.

If you have had a tubal sterilization or have an IUD (intrauterine device) or progesterone implant, these methods can be used alone and no other form of birth control is needed. Talk with your doctor or gynecologist (a doctor who specializes in female reproduction) to find out about options for acceptable forms of birth control that you may use to prevent pregnancy during treatment with ambrisentan tablets. If you decide that you want to change the form of birth control that you use, talk with your doctor or gynecologist to be sure that you choose another acceptable form of birth control.

See the chart below for Acceptable Birth Control Options during treatment with ambrisentan tablets. Acceptable Birth Control Options Do not have unprotected sex. Talk to your doctor or pharmacist right away if you have unprotected sex or if you think your birth control has failed.

Your doctor may tell you to use emergency birth control. Tell your doctor right away if you miss a menstrual period or think you may be pregnant for any reason. If you are the parent or caregiver of a female child who started taking ambrisentan tablets before reaching puberty, you should check your child regularly to see if she is developing signs of puberty.

Tell your doctor right away if you notice that she is developing breast buds or pubic hair. Your doctor should decide if your child has reached puberty. Your child may reach puberty before having her first menstrual period.

Females can only receive ambrisentan tablets through a restricted program called the Ambrisentan Risk Evaluation and Mitigation Strategy (REMS) program. If you are a female who can get pregnant, you must talk to your doctor, understand the benefits and risks of ambrisentan tablets, and agree to all of the instructions in the Ambrisentan REMS program. Males can receive ambrisentan tablets without taking part in the Ambrisentan REMS program.

What are ambrisentan tablets? Ambrisentan tablets are a prescription medicine used to treat pulmonary art…

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.