Orkambi (lumacaftor / ivacaftor)

The first combination CFTR modulator, approved for patients homozygous for the F508del mutation. 2 tablets twice daily help the CFTR protein fold correctly and function at the cell surface.

Orkambi combines a corrector (lumacaftor) with a potentiator (ivacaftor) to address two problems at once. Lumacaftor helps the misfolded CFTR protein fold correctly so it can reach the cell surface. Once there, ivacaftor helps it stay open. This was the first combination to treat the most common CF mutation, F508del, carried by about 90% of CF patients.

Common side effects include shortness of breath or chest tightness (especially when starting), stuffy nose and sore throat, nausea, diarrhea, tiredness, rash and gas. Liver blood tests are needed before starting, every 3 months in the first year and yearly after that. In people who already have advanced liver disease, worsening liver function, including liver failure leading to death, has been reported, so Orkambi is used only with caution and at a lower dose. Serious allergic reactions, including anaphylaxis and swelling of the face or throat, have also been reported; call your doctor or go to the emergency room right away for hives, swelling of the face, lips or tongue, tightness of the chest or throat, or trouble breathing or swallowing. Blood pressure should be checked regularly, and children need eye exams for cataracts. The label also warns about raised pressure in the skull (unusual headache or vision changes) and about anxiety, depression, sleep problems and suicidal thoughts, which can start in the first 3 months. Avoid grapefruit during the first week of treatment. Hormonal birth control may not work reliably while taking Orkambi. Tell your doctor about yellowing of skin, dark urine, abdominal pain, or severe nausea.

Orkambi tablets are taken twice daily with a fatty meal. Children aged 1 through 5 take oral granules mixed into soft food or liquid, with the packet strength based on age and weight, and children aged 6 through 11 take 2 lower-strength tablets per dose. Most insurance plans cover it for patients with two copies of the F508del mutation.

Yes, Lumacaftor / Ivacaftor (Orkambi) is FDA approved (2015) for the treatment of Cystic Fibrosis.

No trial has compared Trikafta with Orkambi head to head, so their lung function results come from separate studies against different comparators. Trikafta also covers a broader range of mutations (heterozygous F508del plus many others), while Orkambi only works for patients with two copies of F508del. Most CF care teams now recommend Trikafta or Alyftrek as first-line therapy for eligible patients. However, Orkambi may still be used by patients who tolerate it well and have been stable on it.

Yes. Chest tightness and shortness of breath are known side effects that can occur when starting Orkambi, particularly in patients with lower baseline lung function (FEV1 below 40% predicted). Some physicians initiate Orkambi at a reduced dose and gradually titrate up to minimize this effect. If you experience significant chest tightness or breathing difficulty, contact your CF care team rather than stopping the medication on your own.

In CFTR modulator therapy, a corrector (like lumacaftor) helps the misfolded CFTR protein fold into the right shape so it can travel to the cell surface. A potentiator (like ivacaftor) helps the protein work once it gets there by keeping the chloride channel open. Patients with two copies of the F508del mutation need both because their CFTR protein is both misfolded (so it never reaches the surface) and dysfunctional (so it would not work properly even if it did). Orkambi was the first drug to combine both functions.

Yes. Lumacaftor is a strong inducer of the CYP3A enzyme, which can reduce the effectiveness of many other medications including hormonal contraceptives, certain antifungals, and some antibiotics. This is a significant practical consideration for CF patients who often take multiple medications. Your CF care team and pharmacist should review all your medications for interactions. This drug interaction profile is one reason newer modulators like Trikafta and Alyftrek are often preferred.

Yes. Orkambi is approved for patients age 1 and older who are homozygous for F508del. Oral granules mixed into soft food or liquid are used for children aged 1 through 5, and tablets from age 6. For babies under 1, Orkambi is not approved.