Over the past 10 years, 9 new, effective medications to treat PH patients have been approved by Health Canada. Each of these medications is described individually below.
Intravenous Flolan (Epoprostenol) : March 1997
Oral Tracleer (Bosentan) : November 2001
S/C Remodulin (Treprostinil) : October 2002
Oral Revatio (Sildenafil) : May 2006
Oral Volibris (Ambrisentan) : April 2008
Adcirca (Tadalafil) : February 2010
Caripul (RTS Epoprostenol) : September 2013
Opsumit (Macitentan) : November 2013
Adempas (Riociguat) : March 2014
Medication Trade Name | Flolan and Caripul |
Medication Generic Name | Epoprostenol |
Family of Medication | Prostanoids / Analogues of Prostacyclin |
Form of Medication | Powder in liquid (= solution) |
Route of Delivery | Intravenous = IV |
Dose |
Dose increases over time
|
Dosing frequency | Continuous infusion 24 hours /day |
Health Canada Approval Date | March, 1997 |
Approved for what types of PH? |
WHO Group I PAH
|
Approved for what severity of PH? | WHO / NYHA Functional Class III and IV |
Demonstrated Beneficial Effects |
Improvements in pulmonary hemodynamics
Improved patient function and wellbeing
Increased patient survival
|
Side Effects and Risks |
Side effects Related to Medication
Risks Related to IV Delivery System
|
Medication Trade Name | Tracleer |
Medication Generic Name | Bosentan |
Family of Medication | Endothelin Receptor Antagonists (ERAs) |
Form of Medication | Tablets |
Route of Delivery | Oral / by mouth |
Dose |
Adults
Kids
|
Dosing frequency | BID / twice daily |
Health Canada Approval Date | November, 2001 |
Approved for what types of PH? |
WHO Group I PAH
|
Approved for what severity of PH? | WHO / NYHA Functional Class III and IV |
Demonstrated Beneficial Effects |
Improvements in pulmonary hemodynamics
Improved patient function and wellbeing
Increased patient survival
|
Side Effects and Risks |
Side effects Related to Medication
|
Medication Trade Name | Remodulin |
Medication Generic Name | Treprostinil |
Family of Medication | Prostanoids / Analogues of Prostacyclin |
Form of Medication | Powder in liquid (= solution) |
Route of Delivery | Subcutaneous = SC |
Dose |
Dose increases over time
|
Dosing frequency | Continuous infusion 24 hours /day |
Health Canada Approval Date | October, 2002 |
Approved for what types of PH? |
WHO Group I PAH
|
Approved for what severity of PH? | WHO / NYHA Functional Class III and IV |
Demonstrated Beneficial Effects |
Improvements in pulmonary hemodynamics
Improved patient function and wellbeing
Increased patient survival
|
Side Effects and Risks |
Side effects Related to Medication
Risks Related to SC Delivery System
|
Medication Trade Name | Remodulin |
Medication Generic Name | Treprostinil |
Family of Medication | Prostanoids / Analogues of Prostacyclin |
Form of Medication | Powder in liquid (= solution) |
Route of Delivery | Intravenous = IV |
Dose |
Dose increases over time
|
Dosing frequency | Continuous infusion 24 hours /day |
Health Canada Approval Date | October, 2005 |
Approved for what types of PH? |
WHO Group I PAH
|
Approved for what severity of PH? | WHO / NYHA Functional Class II and III |
Demonstrated Beneficial Effects |
It has been studied and found that IV and SC remodulin are bio-equivalent (biologically equivalent)
IV remodulin has also been studied in clinical trials with small numbers of patients. Improvements in pulmonary hemodynamics
Improved patient function and wellbeing
|
Side Effects and Risks |
Side effects Related to Medication
Risks Related to IV Delivery System
|
Medication Trade Name | Revatio |
Medication Generic Name | Sildenafil |
Family of Medication | Inhibitors of Phosphodiesterase type 5 |
Form of Medication | Tablets |
Route of Delivery | Oral / by mouth |
Dose |
20 mg |
Dosing frequency | TID / three times daily |
Health Canada Approval Date | May, 2006 |
Approved for what types of PH? |
WHO Group I PAH
|
Approved for what severity of PH? | WHO / NYHA Functional Class II and III |
Demonstrated Beneficial Effects |
Improvements in pulmonary hemodynamics
Improved patient function and wellbeing
|
Side Effects and Risks |
Side effects Related to Medication
|
Medication Trade Name | Volibris |
Medication Generic Name | Ambrisentan |
Family of Medication | Endothelin Receptor Antagonists (ERAs) |
Form of Medication | Tablets |
Route of Delivery | Oral / by mouth |
Dose |
Initial dose 5 mg If inadequate response, then increase to 10 mg |
Dosing frequency | once daily |
Health Canada Approval Date | April, 2008 |
Approved for what types of PH? |
WHO Group I PAH
|
Approved for what severity of PH? | WHO / NYHA Functional Class II and III |
Demonstrated Beneficial Effects |
Improvements in pulmonary hemodynamics
Improved patient function and wellbeing
|
Side Effects and Risks |
Side effects Related to Medication
|
Medication Trade Name | Tadalafil |
Medication Generic Name | Adcirca |
Family of Medication | Inhibitors of Phosphodiesterase type 5 |
Form of Medication | Tablets |
Route of Delivery | Oral / by mouth |
Dose | 20-40 mg |
Dosing frequency | once daily |
Health Canada Approval Date | February 2010 |
Approved for what types of PH? | WHO Group I PAH |
Approved for what severity of PH? | WHO Functional Class II-III |
Demonstrated Beneficial Effects |
|
Side Effects and Risks |
Tadalafil is generally well tolerated. The most frequent side effects are:
A reduction in blood pressure throughout the body may occur because tadalafil relaxes blood vessels (arteries) throughout the body. Caution must be used in patients with low blood pressure- - for example, less than 90/50 mmHg. Caution is also needed in patients with dehydration, left-sided heart diseases and certain abnormalities of the body's nervous system function. Taking certain medications such as nitrates, nitric oxide donors or alpha blockers along with tadalafil can cause a significant drop in blood pressure. This could result in loss of consciousnessor even death. You should make certain that you are not taking these medications before starting tadalafil. Use of tadalafil with medications known as nitrates is CONTRAINDICATED. Prolonged erection (greater than four hours) in a male patient is a rare but very serious side effect; if this should happen to you, you should go to an emergency room or contact your doctor immediately. Sudden loss of vision in one or both eyes has occurred in patients on PDE5 inhibitors. Such an event may represent serious dysfunction of the optic nerve and requires immediate medical attention. Sudden loss of hearing may occur and may be accompanied by dizziness and/or ear ringing. Patients should seek prompt medical attention should this occur. |
Medication Trade Name | Macitentan |
Medication Generic Name | Opsumit |
Family of Medication | Endothelin Receptor Antagonists (ERAs) |
Form of Medication | Tablets |
Route of Delivery | Oral / by mouth |
Dose | 10mg |
Dosing frequency | daily |
Health Canada Approval Date | November 2013 |
Approved for what types of PH? | WHO Group I PAH |
Approved for what severity of PH? | WHO Functional Class II-III |
Demonstrated Beneficial Effects | XXXXXXXXXX |
Side Effects and Risks |
Macitentan is generally well tolerated. The most frequent side effects are:
Macitentan can cause serious birth defects if taken during pregnancy. Liver problems can occur with ERAs like macitentan. Low red blood cell levels can occur during the first weeks after starting therapy. In some cases, a blood transfusion may be needed, but this is not common. Changes in sperm production may result in men taking macitentan, based on the effects of the medication that was observed in animals. Men taking macitentan should discuss this further with their health care provider. Fluid retention is a known side effect of ERAs. It is important to notify your physician if you experience swelling or any other side effects. Treatment may be required including reducing salt and fluid in your diet, as well as a water pill (diuretic) to promote increased fluid removal through the kidneys. |
Medication Trade Name | Riociguat |
Medication Generic Name | Adempas |
Family of Medication | Soluble guanylate cyclase stimulators |
Form of Medication | Tablets |
Route of Delivery | Oral / by mouth |
Dose | 0.5mg, 1mg, 1.5mg, 2mg, 2.5mg |
Dosing frequency | three times daily |
Health Canada Approval Date | March 2014 |
Approved for what types of PH? | WHO Group 1 patients, WHO Group 4 patients having chronic thromboembolic pulmonary hypertension (CTEPH) that is recurrent/persistent after surgical treatment or inoperable. |
Approved for what severity of PH? | WHO Functional Class II-III |
Demonstrated Beneficial Effects | XXXXXXXXXX |
Side Effects and Risks |
Riociguat is generally well tolerated. The most frequent side effects are:
Other side effects include:
A reduction in blood pressure throughout the body may occur because riociguat relaxes blood vessels (arteries) throughout the body. Caution must be used in patients taking blood pressure medicines, medicines that might interact with riociguat, or if they have low blood pressure. Caution is also needed in patients with dehydration, left-sided heart diseases and certain abnormalities of the body's nervous system function. Serious bleeding is rarely seen in patients taking riociguat. |
Some patients with PH can have swelling of their feet or ankles (also known as edema). In these patients, medications are used to help the kidneys eliminate fluid from the body (also known as diuretics): Diuretics include:
Some patients with PH should be treated with blood thinners (also known as anti-coagulants). Anti-coagulant medications include:
Some patients with PH have weakness of the right side of the heart. This may occasionally be treated with digoxin, a medication that supports the right side of the heart, and may help to reduce the symptoms of right heart failure.
The typical dose of digoxin is 0.0625 mg to 0.25 mg taken once a day. Your doctor may follow the levels of digoxin in your blood to determine the right dose for you.
Side effects of digoxin include: dizziness, fainting, fast or irregular heart rate, nausea and vomiting, slowing of heart rate, headache and changes in your vision.
Some patients with PH have low oxygen levels in the blood. Low oxygen levels can make PH worse.
Some patients with PH are treated with medications that relax and open pulmonary arteries (also known as vasodilators). Vasodilator medications mainly include a family of drugs known as calcium-channel blockers (CCBs). CCBs used to treat PH include:
Side-effects can include low blood pressure, dizziness, fainting, slow or fast pulse, worse swelling of the feet or ankles.