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OPFOLDA is a brand name for Miglustat, supplied as a capsule. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: OPFOLDA (miglustat capsules) is an enzyme stabilizer indicated in combination with POMBILITI (cipaglucosidase alfa) for the treatment of adult patients with late-onset Pompe disease (acid α-glucosidase [GAA] deficiency) weighing ≥40 kg. OPFOLDA must be used in combination with cipaglucosidase alfa. Consult the Product…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations • OPFOLDA must be used in combination with cipaglucosidase alfa. Refer to the Product Monograph of POMBILITI (cipaglucosidase alfa) before taking OPFOLDA. 1 Pregnancy). • Patient response to treatment should be routinely evaluated based on a comprehensive evaluation OPFOLDA® (miglustat capsules) Page 5 of 28 Unclassified / Non classifié of all clinical manifestations of the disease.
In the case of an insufficient response or intolerable safety risks, discontinuation of OPFOLDA in combination with cipaglucosidase alfa treatment should be considered. Both medicinal products should either be continued or discontinued.
Patients with renal impairment • The safety and efficacy of OPFOLDA in combination with cipaglucosidase alfa therapy have not been evaluated in patients with renal impairment. 3 Pharmacokinetics), based on modeling. 2 Recommended Dose and Dosage Adjustment).
2 Recommended Dose and Dosage Adjustment OPFOLDA must be used in combination with cipaglucosidase alfa. The recommended dosage of cipaglucosidase alfa is 20 mg/kg body weight administered every other week as an intravenous infusion.
Refer to the Product Monograph of POMBILITI (cipaglucosidase alfa) for detailed information on dosage and administration recommendations for cipaglucosidase alfa. The recommended dose of OPFOLDA is based on body weight and is to be taken orally every other week in adults aged 18 years and older: • For patients weighing ≥50 kg, the recommended dose is 260 mg (4 capsules of 65 mg).
• For patients weighing ≥40 kg to <50 kg, the recommended dose is 195 mg (3 capsules of 65 mg). OPFOLDA should be taken approximately 1 hour but no more than 3 hours before the start of the cipaglucosidase alfa infusion (see Figure 1).
Figure 1 - Dose Timeline * In the event of cipaglucosidase alfa infusion delay, the start of infusion should not exceed 3 hours from taking OPFOLDA. Patients with renal impairment The safety and efficacy of OPFOLDA in combination with cipaglucosidase alfa therapy have not been evaluated in patients with renal impairment.
OPFOLDA® (miglustat capsules) Page 6 of 28 Unclassified / Non classifié For patients with mild renal impairment (CLcr 60-89 mL/minute), the recommended OPFOLDA dosage is the same as for patients with normal renal function. 3 Pharmacokinetics).
1 Adverse Reaction Overview The most common adverse reactions (≥5%) reported in OPFOLDA in combination with cipaglucosidase alfa treated subjects in all 3 studies were headache, diarrhoea, fatigue, nausea, abdominal pain, pyrexia, and chills.
3%). 7%). 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. Therefore, the frequencies of adverse reactions observed in the clinical trial may not reflect frequencies observed in clinical practice and should not be compared to frequencies reported in the clinical trials of another drug.
The pooled safety analysis from 3 clinical trials included 151 adult patients with LOPD treated with OPFOLDA in combination with cipaglucosidase alfa including: • 85 patients in the randomized, double-blind, active-controlled trial in adults • 37 patients in the open-label extension trial where patients switched from an approved alglucosidase alfa product to OPFOLDA in combination with cipaglucosidase alfa • 29 patients in an open-label trial The assessment of adverse reactions was informed by subjects treated with OPFOLDA in combination with cipaglucosidase alfa across 3 clinical trials.
0 months. Phase 3 clinical trial (PROPEL) included 123 adult patients with LOPD who were randomized to receive OPFOLDA® (miglustat capsules) Page 10 of 28 Unclassified / Non classifié treatment with OPFOLDA in combination with cipaglucosidase alfa or alglucosidase alfa in combination with placebo.
Adverse reactions from the Phase 3 clinical trial (PROPEL) are listed by MedDRA system organ class in Table 3. 4%)* 0 OPFOLDA® (miglustat capsules) Page 11 of 28 Unclassified / Non classifié * Related to cipaglucosidase alfa/alglucosidase alfa only ** Related to OPFOLDA/placebo only ‡ Adverse reactions that are medically related were grouped to a single preferred term.
1 Abdominal pain, abdominal pain upper, and abdominal pain lower are grouped under abdominal pain. 2 Rash, rash erythematous, and rash macular are grouped under rash. 3 Urticaria, mechanical urticaria, and urticaria rash are grouped under urticaria.
General OPFOLDA must be administered in combination with cipaglucosidase alfa. Refer to the Product Monograph of POMBILITI (cipaglucosidase alfa) for a detailed description of additional risks for cipaglucosidase alfa including, but not limited to, severe hypersensitivity reactions, infusion-associated reactions, immune complex-related reactions, and risk of acute cardiorespiratory failure in susceptible patients.
Carcinogenesis and Genotoxicity Evidence of carcinogenicity and genotoxicity with OPFOLDA is limited to non-clinical findings (see 16 NON-CLINICAL TOXICOLOGY). Driving and Operating Machinery No studies on the effects on the ability to drive or to use machinery have been performed with OPFOLDA in combination with cipaglucosidase alfa.
Since dizziness, hypotension, and somnolence have been reported as adverse reactions, OPFOLDA in combination with cipaglucosidase alfa may have minor Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Oral capsule, 65 mg miglustat black iron oxide, colloidal silicon dioxide, gelatin, magnesium stearate, microcrystalline cellulose, pharmaceutical ink, pregelatinized starch (maize), sucralose, titanium dioxide OPFOLDA® (miglustat capsules) Page 8 of 28 Unclassified / Non classifié influence on the ability to drive and use machines.
Caution is required when driving or operating a vehicle or potentially dangerous machinery. Reproductive Health Advise women of childbearing potential to use effective contraception during treatment and for 4 weeks after the last dose of OPFOLDA in combination with cipaglucosidase alfa (see 16 NON-CLINICAL TOXICOLOGY).
1 Pregnancy, and 16 NON-CLINICAL TOXICOLOGY). Fertility There are no clinical data on the effects of OPFOLDA in combination with cipaglucosidase alfa therapy on fertility. An increase in pre-implantation loss was noted with miglustat in combination with cipaglucosidase alfa, and with miglustat alone in reproductive and developmental toxicity studies in male rats mated with untreated females and in females mated with untreated males (see 16 NON- CLINICAL TOXICOLOGY).
OPFOLDA in combination with cipaglucosidase alfa is contraindicated in: • Patients who are hypersensitive to miglustat or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
• Women who are or may become pregnant. 1 Pregnancy). , anaphylaxis and severe cutaneous reactions) to cipaglucosidase alfa, or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container when rechallenge was unsuccessful.
Refer to the Product Monograph of POMBILITI (cipaglucosidase alfa) for detailed information.
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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Table 1 - Recommended OPFOLDA Dosage* in Patients with Moderate or Severe Renal Impairment Patient Weight Moderate Renal Impairment# (Clcr 30-59 mL/minute) Severe Renal Impairment# (Clcr 15-29 mL/minute) For patients weighing ≥50 kg 195 mg (3 capsules of 65 mg) 195 mg (3 capsules of 65 mg) For patients weighing ≥40 kg to <50 kg 130 mg (2 capsules of 65 mg) 130 mg (2 capsules of 65 mg) * Based on modeling.
# Renal function classified by CLcr (creatinine clearance) based on the Cockcroft-Gault equation. 3 Pharmacokinetics). Pediatric use (<18 years) Health Canada has not authorized an indication for pediatric use (see 1 INDICATIONS). 4 Administration OPFOLDA is for oral use and should be taken on an empty stomach.
The patient must fast 2 hours before and 2 hours after taking OPFOLDA (see Figure 1). Swallow the OPFOLDA capsules whole only with unsweetened beverages, including water, tea and/or coffee with no cream, sugar, or sweeteners. Do not consume other beverages or food during the 4-hour fasting period (see Figure 1).
Two hours after taking OPFOLDA, the patient can resume normal eating and drinking. Cipaglucosidase alfa (20 mg/kg body weight) is to be administered by intravenous infusion and should start 1 hour after taking OPFOLDA. Refer to the Product Monograph of POMBILITI (cipaglucosidase alfa) for detailed information on the administration of cipaglucosidase alfa.
5 Missed Dose If the OPFOLDA dosage is missed, do not start the cipaglucosidase alfa infusion alone, and re-start the treatment of these 2 medicines immediately as soon as possible, as detailed in Figure 1. If cipaglucosidase alfa infusion is missed or delayed greater than 3 hours since taking OPFOLDA, cipaglucosidase alfa should not be administered and treatment of these 2 medicines should be rescheduled at least 24 hours after OPFOLDA was last taken.
If OPFOLDA and cipaglucosidase alfa are both missed, re-start treatment as soon as possible as detailed in Figure 1. OPFOLDA® (miglustat capsules) Page 7 of 28 Unclassified / Non classifié
4 Tachycardia and sinus tachycardia are grouped under tachycardia. 5 Headache, migraine, and migraine with aura are grouped under headache. 3 Less Common Clinical Trial Adverse Reactions Adverse reactions from the clinical trials reported in less than 2% of patients from pooled analysis of 3 clinical trials were: Gastrointestinal disorders: abdominal discomfort†, constipation†, dyspepsia*, oesophageal pain*, oesophageal spasm, oral discomfort*, oral pain, swollen tongue* General disorders and administration site conditions: asthenia, chest discomfort*, facial pain, feeling jittery†, infusion site pain*, infusion site swelling*, malaise*, non-cardiac chest pain, pain*, peripheral swelling, swelling face* Immune system disorders: anaphylactic reaction‡2, hypersensitivity Injury, poisoning and procedural complications: skin abrasion* Investigations: body temperature fluctuation*, lymphocyte count decreased, platelet count decreased† Musculoskeletal and connective tissue disorders: arthralgia, flank pain, muscle fatigue, muscular weakness, musculoskeletal stiffness Nervous system disorders: balance disorder, burning sensation*, dysgesusia, migraine‡1, paraesthesia, presyncope* Respiratory, thoracic and mediastinal disorders: asthma, cough*, oropharyngeal discomfort*, pharyngeal oedema*, wheezing* Skin and subcutaneous tissue disorder: skin discolouration, skin oedema* Vascular disorders: hypotension, pallor * Related to cipaglucosidase alfa only; † Related to miglustat only; ‡ Adverse reactions that are medically related were grouped to a single preferred term; 1 Migraine and migraine with aura are grouped under migraine; 2 Anaphylactic reaction, Anaphylaxis are grouped under Anaphylactic reaction.
Anaphylactoid reaction is manually coded to Anaphylaxis. 4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data There were no clinically significant abnormal laboratory findings with OPFOLDA in combination with cipaglucosidase alfa in the clinical studies.
5 Post-Market Adverse Reactions No new safety findings which alter the safety profile of OPFOLDA in combination with cipaglucosidase alfa have been observed post-marketing. OPFOLDA® (miglustat capsules) Page 12 of 28 Unclassified / Non classifié
Based on pre--implantation loss observed in female and male rats, OPFOLDA in combination with cipaglucosidase alfa may impair human female and male fertility. 1 Pregnancy, and 16 NON-CLINICAL TOXICOLOGY). In a rabbit embryo-fetal development study, great vessel and cardiac malformations were increased in offspring of pregnant rabbits treated with oral miglustat in combination with cipaglucosidase alfa at 3-fold and 16-fold, respectively, the maximum recommended human dose (MRHD) based on plasma AUC exposure (see 16 NON-CLINICAL TOXICOLOGY).
1 Pregnancy OPFOLDA in combination with cipaglucosidase alfa is contraindicated during pregnancy based on findings from animal studies and due to its unknown potential risk in humans (see 2 CONTRAINDICATIONS). There are no available human data on OPFOLDA in combination with cipaglucosidase alfa use in pregnant women.
, rat and rabbit), including pre‑implantation loss, and clusters of great vessel and cardiac malformations in offspring (see 16 NON-CLINICAL TOXICOLOGY). 2 Breast-feeding There are no data on the presence of OPFOLDA alone or in combination with cipaglucosidase alfa in human breast milk, the effects on the breastfed infant, or the effects on milk production.
Available pharmacodynamic/toxicological data in animals have shown secretion of miglustat in milk (see 16 NON- CLINICAL TOXICOLOGY). Because of a risk to the breast-feeding new-borns/infants that cannot be OPFOLDA® (miglustat capsules) Page 9 of 28 Unclassified / Non classifié excluded, advise women that breast-feeding is not recommended while on treatment with OPFOLDA in combination with cipaglucosidase alfa.
3 Pediatrics Pediatrics (<18 years): No data are available to Health Canada; therefore, Health Canada has not authorized an indication for pediatric use. 4 Geriatrics There is limited clinical data with OPFOLDA in combination with cipaglucosidase alfa in elderly patients.
Limited data suggests that use of OPFOLDA in combination with cipaglucosidase alfa in the geriatric population is not associated with differences in safety or effectiveness. As clinical trials of OPFOLDA in combination with cipaglucosidase alfa did not include sufficient numbers of patients ≥65 years of age treated with OPFOLDA in combination with cipaglucosidase alfa, no definitive conclusions can be drawn to determine whether they respond differently from younger adult patients.
Of the total number of patients treated with OPFOLDA in combination with cipaglucosidase alfa in clinical trials for late-onset Pompe disease (LOPD), 17 (11%) subjects were 65 to 74 years of age, and none were 75 years of age and older.