Generic Letairis ( Ambrisentan )

Buy Generic Letairis (Ambrisentan) without prescription in Canada

Letairis (Ambrisentan 5 mg, 10 mg): Comprehensive Patient Information for Canada

Basic Product Information

Mechanism of Action

In simple terms: Letairis is a medication that treats high blood pressure in the lungs (pulmonary arterial hypertension or PAH). It works by blocking the effects of a natural substance called endothelin-1, which causes blood vessels to narrow. By blocking endothelin-1, Letairis helps the blood vessels in the lungs relax and widen, reducing blood pressure in the lungs, improving your ability to exercise, and slowing the worsening of your condition.

For specialists: Ambrisentan is a highly selective endothelin receptor antagonist (ERA) with high affinity for the endothelin type A (ETA) receptor. Endothelin-1 is a potent vasoconstrictor and smooth muscle mitogen, and its effects are mediated through ETA and ETB receptors. Ambrisentan selectively blocks ETA receptors, which are predominantly expressed on vascular smooth muscle cells and mediate vasoconstriction and cell proliferation. By blocking ETA receptors, ambrisentan reduces pulmonary vascular resistance and improves haemodynamics. Ambrisentan has approximately 4,000-fold selectivity for ETA over ETB receptors. The selectivity for ETA receptors may reduce the risk of vasodilatory side effects and fluid retention associated with non-selective ERA blockade.

Pharmacokinetics

• Absorption: Ambrisentan is rapidly absorbed after oral administration, with peak plasma concentrations reached approximately 2 hours after dosing. The absolute bioavailability is approximately 60%. Food does not significantly affect the extent of absorption. Steady-state plasma concentrations are achieved after 3 to 4 days of once-daily dosing. Ambrisentan exhibits dose-proportional pharmacokinetics over the dose range of 1 to 10 mg.
• Metabolism: Ambrisentan is extensively metabolized in the liver, primarily by glucuronidation via UGT1A9 and UGT2B7, and to a lesser extent by CYP3A4 and CYP2C19. The primary metabolite is 4-hydroxymethyl ambrisentan, which is pharmacologically inactive. Ambrisentan is not a significant inhibitor or inducer of cytochrome P450 enzymes.
• Distribution: Ambrisentan is highly bound to plasma proteins (approximately 99%), primarily to albumin. The volume of distribution is approximately 30 L.
• Elimination: The elimination half-life of ambrisentan is approximately 15 hours (range 16 to 48 hours in some sources). The plasma clearance is approximately 1.4 L/h. Ambrisentan is excreted primarily in the feces (approximately 80%) and urine (approximately 20%). Only a small fraction of the dose is excreted unchanged in the urine.
• Onset of Action: Haemodynamic effects and symptomatic improvement may be observed within the first few weeks of treatment, though maximal benefit may take several months.
• Duration of Action: The half-life of approximately 15 hours supports once-daily dosing to maintain steady-state plasma concentrations.

Uses in Daily Life and Best Practice Advice

Ambrisentan is prescribed in Canada for the treatment of pulmonary arterial hypertension (PAH). Your specialist will determine the appropriate use and dose based on your specific medical situation.

• Typical Uses: Treatment of pulmonary arterial hypertension (PAH) (World Health Organization Group I) to improve exercise ability and delay clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II to III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%). It is used as monotherapy or in combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability.
• Administration: Take the tablet orally once daily, with or without food. Swallow the tablet whole; do not split, crush, or chew the tablet. Take at the same time each day. Do not take more than your regular dose. If you miss a dose, take it as soon as you remember that day. Do not take two doses at the same time to make up for a missed dose.
• Monitoring: Liver function tests (transaminases) should be measured prior to initiation of treatment and subsequently at monthly intervals in vulnerable patients, or generally in any patient as clinically indicated. Hemoglobin and/or hematocrit levels should be measured prior to initiation, again at one month, and periodically thereafter as clinically indicated. Monthly pregnancy tests are required for females of reproductive potential during treatment and for 1 month after discontinuation.
• Do Not Stop Without Medical Advice: Do not stop taking this medication without consulting your physician. Some conditions may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.

Morning vs. Evening Dosing

Ambrisentan is typically taken once daily. There is no specific clinical recommendation for morning versus evening dosing. Taking it at the same time each day helps maintain consistent blood levels. Always follow the schedule recommended by your specialist.

• Once Daily: The standard dose is taken once daily, with or without food.
• Consistency: Take ambrisentan at the same time each day to ensure consistent effects.
• Missed Dose: If you miss a dose, take it as soon as you remember that day. Do not take two doses at the same time to make up for a missed dose.
• Professional Guidance: Your healthcare provider may adjust the timing based on your response to treatment.

Administration With or Without Food

Ambrisentan can be taken with or without food. Food does not significantly affect the absorption of the medication. This flexibility makes it convenient to take at any time of day.

• Swallow the tablet whole with a full glass of water.
• Ambrisentan can be taken with or without food.
• Do not split, crush, or chew the tablet.
• Because ambrisentan can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.

Interaction Warnings

Indications for Ambrisentan

"Off-label" means use outside the official approved indication, usually based on current medical guidelines and scientific evidence.

Dosing According to Clinical Indication

Doses should always be adjusted according to the advice of your specialist and depending on your health condition, liver function, and clinical response. The recommended initial dose is 5 mg once daily, and the maximum dose is 10 mg once daily.

Side Effects and Safety Profile

Guidelines for Correct Use

• Take ambrisentan exactly as prescribed by your specialist. Do not change your dose without medical advice.
• Swallow the tablet whole with a full glass of water, with or without food, at the same time each day.
• Do not split, crush, or chew the tablet.
• Do not stop taking this medication without consulting your physician.
• Keep all medical appointments for monitoring of liver function, hemoglobin, and clinical response.
• Females of reproductive potential must have a negative pregnancy test before starting treatment, use reliable contraception during treatment and for 1 month after stopping, and have monthly pregnancy tests during treatment.
• Because ambrisentan can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets.
• Inform every healthcare provider (including dentists, surgeons, and pharmacists) that you are taking ambrisentan.
• If you are pregnant, planning to become pregnant, or breastfeeding, consult your physician before use. Ambrisentan is contraindicated during pregnancy and breastfeeding.
• If you miss a dose, take it as soon as you remember that day. Do not take two doses at the same time to make up for a missed dose.
• Store at room temperature in a dry place. Keep out of reach of children.

Alternative Treatment Options

• Bosentan (Tracleer): A non-selective endothelin receptor antagonist (ERA) that blocks both ETA and ETB receptors. It is approved for PAH. Requires monthly liver function monitoring due to a higher risk of hepatotoxicity compared with ambrisentan. Available in Canada by prescription.
• Macitentan (Opsumit): A newer non-selective ERA that blocks both ETA and ETB receptors. It has a longer half-life and does not require monthly liver function monitoring. Approved for PAH in Canada. Considered a first-line ERA option.
• Sildenafil (Revatio) and Tadalafil (Adcirca): Phosphodiesterase type 5 (PDE-5) inhibitors that promote vasodilation in the pulmonary vasculature. Approved for PAH in Canada. May be used as monotherapy or in combination with an ERA.
• Riociguat (Adempas): A soluble guanylate cyclase stimulator approved for PAH and chronic thromboembolic pulmonary hypertension (CTEPH). Available in Canada by prescription.
• Prostanoids (e.g., epoprostenol, treprostinil, iloprost): Prostacyclin analogs that are the most potent vasodilators available for PAH. Administered via continuous intravenous, subcutaneous, inhaled, or oral routes. Reserved for more severe disease or as add-on therapy.
• Selexipag (Uptravi): An oral selective prostacyclin receptor agonist approved for PAH. May be used as add-on therapy or as an alternative to other agents.

Comparison: Ambrisentan is distinguished from other ERAs by its high selectivity for the ETA receptor, which may reduce the risk of vasodilatory side effects and fluid retention compared with non-selective ERAs such as bosentan and macitentan. Ambrisentan has a lower risk of hepatotoxicity compared with bosentan, though liver function monitoring is still recommended. The AMBITION trial demonstrated that initial combination therapy with ambrisentan plus tadalafil reduced the risk of clinical failure by 50% compared with monotherapy with either agent alone. Macitentan is another ERA option that does not require monthly liver monitoring. PDE-5 inhibitors and prostanoids work through different mechanisms and may be used in combination with ERAs. Your specialist will determine the best treatment strategy for your specific condition.

Legal Status, Registration, and Coverage in Canada

• Registration: Ambrisentan is authorized for sale in Canada by Health Canada as a prescription drug. Volibris (Takeda Canada Inc.) is available in 5 mg and 10 mg tablets. Generic formulations include Apo-Ambrisentan (Apotex Inc., DIN 02475383 for 10 mg, DIN 02475375 for 5 mg) and Jamp Ambrisentan (Jamp Pharma Corporation, DIN 02521946 for 10 mg, DIN 02521938 for 5 mg). Sandoz Ambrisentan (DIN 02526883 for 10 mg, DIN 02526875 for 5 mg) has been cancelled post-market. Teva-Ambrisentan (DIN 02536234 for 5 mg) has been cancelled pre-market.
• Prescription Status: Prescription only in Canada.
• Coverage: Coverage varies by province and territory. In British Columbia, ambrisentan is a Limited Coverage drug under the BC Pharmacare program. Special Authority criteria require it to be used as monotherapy for the treatment of WHO/NYHA functional class III pulmonary arterial hypertension in patients who have had an inadequate response and/or a contraindication to sildenafil. The usual dose is limited to a maximum of 10 mg daily, and approval is for 1 year. In Quebec, ambrisentan is covered as an exceptional medication under the RAMQ formulary. In Ontario, Jamp Ambrisentan 10 mg (DIN 02521946) is listed as an interchangeable product on the Ontario Drug Benefit formulary. The Pan-Canadian Pharmaceutical Alliance (pCPA) has completed negotiations for ambrisentan. The Canadian Agency for Drugs and Technologies in Health (CADTH) Canadian Drug Expert Committee recommends that ambrisentan, at a maximum dose of 10 mg per day, be listed on the list of insured medicines for the management of WHO functional class III or worse PAH. Generic formulations are generally more affordable than brand-name products.
• Pharmacovigilance: Adverse reactions should be reported to Health Canada's MedEffect Canada program at 1-866-234-2345.

Recent Research and Clinical Guidelines (2022–2026)

• The AMBITION trial (Ambrisentan and Tadalafil in Patients with Pulmonary Arterial Hypertension) demonstrated that initial combination therapy with ambrisentan plus tadalafil reduced the risk of clinical failure by 50% compared with monotherapy with either agent alone. The study established combination therapy as a standard of care for newly diagnosed PAH patients.
• Canadian clinical practice guidelines, including a stepwise approach to managing pulmonary arterial hypertension (PAH) at Canadian expert centres, recommend endothelin receptor antagonists (ERAs) including ambrisentan, bosentan, and macitentan, which block the action of endothelin-1, as first-line therapy for PAH. Combination therapy with a PDE-5 inhibitor is increasingly used as initial therapy.
• The 2024 Canadian Medical Association Journal (CMAJ) publication on the stepwise approach to managing PAH provides updated guidance on the use of ERAs, including ambrisentan, in the Canadian context.
• Health Canada has approved eight advanced treatment options covering four different classes of drugs for PAH, including endothelin receptor antagonists (ERAs) (bosentan, ambrisentan, macitentan).
• Research continues to explore the role of ambrisentan in various clinical settings, including its use in combination with other PAH therapies and its potential role in patients with less severe disease (WHO functional class II).
• A drug shortage of ambrisentan 5 mg and 10 mg tablets was reported in Canada in 2025 due to a disruption in the manufacture of the drug. The shortage affected multiple manufacturers and was resolved later in the year.

Availability and Supply in Canada

Prices and availability may vary by province, territory, and pharmacy. Generic ambrisentan formulations are available in Canada and are generally more affordable than the brand-name product. Coverage is subject to provincial/territorial Special Authority or exceptional medication criteria. In the United States, the brand-name Letairis 5 mg tablet costs approximately $847.55 for 30 tablets, but Canadian pricing is different and generally lower. Check with your local pharmacy for current pricing and availability.

Frequently Asked Questions (FAQ)

1. What is Letairis (ambrisentan) used for?
   Letairis is used to treat pulmonary arterial hypertension (PAH), which is high blood pressure in the arteries of the lungs. It improves your ability to exercise and slows the worsening of your condition. It can be used alone or in combination with tadalafil.
2. How does ambrisentan work?
   Ambrisentan works by blocking the effects of a natural substance called endothelin-1, which causes blood vessels to narrow. By blocking endothelin-1, it helps the blood vessels in the lungs relax and widen, reducing blood pressure in the lungs.
3. What is the correct dose of ambrisentan?
   The usual starting dose is 5 mg once daily, which may be increased to 10 mg once daily at 4-week intervals if needed and tolerated. The maximum dose is 10 mg once daily. Your specialist will determine the appropriate dose for your condition.
4. Can I take ambrisentan with food?
   Yes. Ambrisentan can be taken with or without food. Food does not significantly affect the absorption of the medication.
5. What should I do if I miss a dose?
   If you miss a dose, take it as soon as you remember that day. Do not take two doses at the same time to make up for a missed dose.
6. Can I drink alcohol while taking ambrisentan?
   No. Alcohol should not be consumed while taking ambrisentan because it may worsen symptoms of PAH and increase the risk of low blood pressure.
7. What are the serious side effects of ambrisentan?
   Serious side effects include hepatotoxicity (liver damage), fluid retention, decreased hemoglobin, and severe allergic reactions. Seek immediate medical attention if you experience signs of liver problems (nausea/vomiting that doesn't stop, loss of appetite, severe stomach/abdominal pain, dark urine, yellowing of eyes or skin), sudden unexplained weight gain and swelling of ankles/feet, or signs of a severe allergic reaction.
8. Is ambrisentan safe during pregnancy?
   No. Ambrisentan is contraindicated during pregnancy. It is very likely to produce serious birth defects. Pregnancy must be excluded before starting treatment. Females of reproductive potential must use reliable contraception during treatment and for 1 month after stopping, and have monthly pregnancy tests.
9. Is ambrisentan safe during breastfeeding?
   No. Breastfeeding is contraindicated in patients taking ambrisentan. It is unknown if ambrisentan is excreted in human milk. Consult your physician before use if breastfeeding.
10. Are there alternatives to ambrisentan?
    Yes. Alternatives include other endothelin receptor antagonists (bosentan, macitentan), PDE-5 inhibitors (sildenafil, tadalafil), riociguat, prostanoids (epoprostenol, treprostinil, iloprost), and selexipag. Your specialist will determine the best option for your specific condition.
11. Is ambrisentan covered by Canadian health insurance?
    Coverage varies by province and territory. In British Columbia, it is a Limited Coverage drug requiring Special Authority approval. In Quebec, it is covered as an exceptional medication under the RAMQ formulary. In Ontario, Jamp Ambrisentan is listed as an interchangeable product on the ODB formulary. Check with your provincial drug plan and private insurance provider for coverage details.
12. What is the REMS program for ambrisentan?
    Because of the risk of embryo-fetal toxicity, females can only receive ambrisentan through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Letairis REMS program in the United States. In Canada, the product is available through Volibris with similar restrictions, including mandatory pregnancy testing and contraception requirements.