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Dosing and Administration

How to Administer ORKAMBI Oral Granules and Tablets

ORKAMBI Indication

ORKAMBI is a combination of lumacaftor and ivacaftor indicated for the treatment of cystic fibrosis (CF) in patients age 2 years and older who are homozygous for the F508del mutation in the CFTR gene.

Limitations of Use

The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation.

Oral Granules: Preparation and Administration1

  • Hold the packet with cut line on top
  • Shake the packet gently to settle the ORKAMBI granules
  • Tear or cut packet open along the line
  • Carefully pour all the ORKAMBI granules in the packet into 1 teaspoon of soft food or liquid in a small container
  • Food or liquid should be at or below room temperature
  • After mixing, caregiver should give within 1 hour
  • It is important that patients consume the entire oral granules mixture with each dose
Oral Granules

Not actual size.

  • Examples of soft foods or liquids include: pureed fruits, applesauce, flavored yogurt, pudding, milk or juice

Tablets: Administration1

  • Take 2 tablets twice a day, 12 hours apart

Not actual size.

Give Oral Granules and Tablets with Fat-Containing Food1

  • For patients taking oral granules mixed into a soft food or liquid: dose must be taken just before or after consuming fat-containing food
  • For patients taking tablets: dose must be taken with fat-containing food

Examples of fat-containing foods include:

  • Eggs
  • Nuts
  • Peanut butter
  • Avocado
  • Butter
  • Cheese pizza
  • Whole-milk dairy products (eg, whole milk, cheese, and yogurt)

Palatability of ORKAMBI Oral Granules1,2

  • Children may find the taste of the oral granules to be bitter
  • Mixing the oral granules with soft foods or liquids that are sweet or rich, such as pudding or chocolate sauce, may help with the taste

For more information for caregivers, including tips for taking,
please see the Professional Resources page.

Important Safety Information

Use in Patients With Advanced Liver Disease

  • Worsening of liver function, including hepatic encephalopathy, in patients with advanced liver disease has been reported. Liver function decompensation, including liver failure leading to death, has been reported in CF patients with pre-existing cirrhosis with portal hypertension while receiving ORKAMBI. Use ORKAMBI with caution in patients with advanced liver disease and only if the benefits are expected to outweigh the risks. If ORKAMBI is used in these patients, they should be closely monitored after the initiation of treatment and the dose should be reduced

Indication

ORKAMBI® (lumacaftor/ivacaftor) is a combination of lumacaftor and ivacaftor indicated for the treatment of cystic fibrosis (CF) in patients age 2 years and older who are homozygous for the F508del mutation in the CFTR gene. If the patient's genotype in unknown, an FDA-cleared CF mutation test should be used to detect the presence of the F508del mutation on both alleles of the CFTR gene.

Limitations of Use

The efficacy and safety of ORKAMBI have not been established in patients with CF other than those homozygous for the F508del mutation.

Liver-related Events

  • Serious adverse reactions related to elevated transaminases have been reported in patients with CF receiving ORKAMBI. In some instances, these elevations have been associated with concomitant elevations in total serum bilirubin
  • It is recommended that ALT, AST, and bilirubin be assessed prior to initiating ORKAMBI, every 3 months during the first year of treatment, and annually thereafter. For patients with a history of ALT, AST, or bilirubin elevations, more frequent monitoring should be considered. Patients who develop increased ALT, AST, or bilirubin should be closely monitored until the abnormalities resolve
  • Dosing should be interrupted in patients with ALT or AST greater than 5 x upper limit of normal (ULN) when not associated with elevated bilirubin. Dosing should also be interrupted in patients with ALT or AST elevations greater than 3 x ULN when associated with bilirubin elevations greater than 2 x ULN. Following resolution of transaminase elevations, consider the benefits and risks of resuming dosing

Respiratory Events

  • Respiratory events (e.g., chest discomfort, dyspnea, and respiration abnormal) were observed more commonly in patients during initiation of ORKAMBI compared to those who received placebo. These events have led to drug discontinuation and can be serious, particularly in patients with advanced lung disease (percent predicted FEV1 (ppFEV1) <40). Clinical experience in patients with ppFEV1 <40 is limited, and additional monitoring of these patients is recommended during initiation of therapy

Effect on Blood Pressure

  • Increased blood pressure has been observed in some patients treated with ORKAMBI. Blood pressure should be monitored periodically in all patients being treated with ORKAMBI

Drug Interactions

Substrates of CYP3A

  • Lumacaftor is a strong inducer of CYP3A. Administration of ORKAMBI may decrease systemic exposure of medicinal products that are substrates of CYP3A, which may decrease therapeutic effect. Co-administration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index is not recommended
  • ORKAMBI may substantially decrease hormonal contraceptive exposure, reducing their effectiveness and increasing the incidence of menstruation-associated adverse reactions, e.g., amenorrhea, dysmenorrhea, menorrhagia, menstrual irregular. Hormonal contraceptives, including oral, injectable, transdermal, and implantable, should not be relied upon as an effective method of contraception when co-administered with ORKAMBI

Strong CYP3A Inducers

  • Ivacaftor is a substrate of CYP3A4 and CYP3A5 isoenzymes. Use of ORKAMBI with strong CYP3A inducers, such as rifampin, significantly reduces ivacaftor exposure, which may reduce the therapeutic effectiveness of ORKAMBI. Therefore, co-administration with strong CYP3A inducers is not recommended

Cataracts

  • Cases of non-congenital lens opacities have been reported in pediatric patients treated with ORKAMBI and ivacaftor, a component of ORKAMBI. Although other risk factors were present in some cases (such as corticosteroid use and exposure to radiation), a possible risk attributable to ivacaftor cannot be excluded. Baseline and follow-up ophthalmological examinations are recommended in pediatric patients initiating treatment with ORKAMBI

Adverse Reactions

  • Serious adverse reactions, whether considered drug-related or not by the investigators, that occurred more frequently in patients treated with ORKAMBI included pneumonia, hemoptysis, cough, increased blood creatine phosphokinase, and transaminase elevations. These occurred in 1% or less of patients
  • The most common adverse reactions in patients age 12 years and older in Phase 3 trials (Trials 1 and 2) occurring in ≥5% of patients treated with ORKAMBI (N=369) vs placebo (N=370) and at a rate higher than placebo were dyspnea, nasopharyngitis, nausea, diarrhea, upper respiratory tract infection, fatigue, respiration abnormal, blood creatine phosphokinase increased, rash, flatulence, rhinorrhea, and influenza
  • The safety profile in patients age 6 through 11 years from an open-label Phase 3 trial (Trial 3; N=58) and a placebo-controlled Phase 3 trial (Trial 4; patients treated with ORKAMBI, N=103 vs placebo, N=101) was similar to that observed in Trials 1 and 2. Additional common adverse reactions were reported in Trial 4, but were not reported in Trials 1 and 2. The adverse reactions in Trial 4 that occurred in ≥5% of patients treated with ORKAMBI with an incidence of ≥3% higher than placebo included: productive cough, nasal congestion, headache, abdominal pain upper, and sputum increased. The safety profile in patients age 2 through 5 years from an open-label Phase 3 trial (Trial 6; N=60) was similar to that in patients aged 6 years and older

Click here to access full Prescribing Information.

References:

1. ORKAMBI [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; August 2018. 2. Data on file. Vertex Pharmaceuticals Incorporated. Boston. MA. VXR-HQ-88-00201; 2018