Use of vemurafenib in a patient unable to swallow whole

Janson, Brett; Whittle, James R.; Witney, Kate; Moodie, Kate; Callahan, Jason; Sandhu, Shahneen

doi:10.1177/1078155215603231

Cited by 6 publications

(2 citation statements)

References 12 publications

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“…In both cases, patients had a partial response and a significant benefit of short duration. 6,7 Compared to our patients, there was no difference in efficacy and tolerance of this altered administration of treatment. Even if the efficacy of treatment was short-lived, patients and family appreciated our having tried to provide the best care.…”

Section: Discussioncontrasting

confidence: 62%

Alternative use of BRAF inhibitors in patients with metastatic melanoma unable to swallow pills

Fleury

Regnault

Cales

et al. 2020

J Oncol Pharm Pract

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Introduction BRAF and MEK inhibitors have been approved for use in metastatic melanoma therapies. All of them are administered as oral capsules or pills. We report two cases treated applying an alternative method of vemurafenib or debrafenib-trametinib administration in patients unable to swallow. Case Report The first case involved a 38-year-old man who was referred to a dermatologist for dysphagia and anorexia. After a computerized tomography (CT) scan it was concluded that the dysphagia was due to compression by mediastinal metastasis in a context of metastatic BRAF mutant melanoma. The second case involved a 35-year-old man who was diagnosed in March 2017 with melanoma of the back of the hand. Several months later a positron emission tomography (PET)/CT scan was performed. It revealed multiple disseminated metastasis. Management & Outcome: The first patient presented total dysphagia and was unable to swallow pills. It was decided to dissolve vemurafenib in order to facilitate administration. Dysphagia was improved 48 hours later, and oral feeding was reintroduced. Due to severe tablet phobia, the second patient was unable to swallow pills. Dabrafenib capsules were emptied and trametinib pills were grinded. One month later, we noted improved health associated with reduction of the metastases. Discussion Our study highlights the possibility of crushing or dissolving BRAF and MEK inhibitors in metastatic melanoma patients for whom it is impossible to swallow pills, eliciting a response and achieving significant if temporary clinical benefit.

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Section: Discussioncontrasting

confidence: 62%

Alternative use of BRAF inhibitors in patients with metastatic melanoma unable to swallow pills

Fleury

Regnault

Cales

et al. 2020

J Oncol Pharm Pract

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“…Review of agents found 36 (31%) with guidance for alternative routes of administration readily available in tertiary resources or commercial liquid formulations, 38 (33%) with off‐label manufacturer information or case reports describing manipulation of solid dosage formulations, and 42 (36%) with no data or insight limited to pharmacokinetic studies. Findings are detailed in Table 3 10‐196 . Unique administration instructions (ie, with or without foo...…”

Section: Resultsmentioning

confidence: 99%

Medication use process and assessment of extemporaneous compounding and alternative routes of administration of oral oncology drugs: Guidance for clinical and oncology pharmacists

Cohen

Lee

Markham

et al. 2022

J Am Coll Clin Pharm

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Cancer treatment is evolving. Oral formulations offer potentially more convenient, effective alternatives to conventional chemotherapy for many cancers. An appealing aspect of oral antineoplastic agents is their relative ease of administration; unfortunately, patients may have difficulty swallowing the tablets or capsules. This shift towards oral administration and the accompanying issues around oral medication adherence highlights the need to assess the safety and feasibility of delivery methods for patients unable to swallow solid dosage forms. A new medication‐use process (MUP) was created to facilitate extemporaneous compounding of oral oncology drugs (OOD). Systematic review consisting of tertiary resources, drug manufacturers, and primary literature was performed to identify information related to extemporaneous compounding or alternative routes of administration for a predetermined list of OODs. A single‐center retrospective review was conducted of patients receiving liquid formulations of OODs to characterize institutional experience. Overall, 116 OODs were reviewed. The majority of OODs had information describing extemporaneous compounding or alternative routes of administration (31% with commercial liquid formulations available or information in tertiary resources; 33% with off‐label manufacturer information or case reports) while 36% had no data. The MUP included three compounding workflows to account for available solid dosage formulations (tablet, hard capsule, gelatin capsule) and creation of an electronic health record order template. Retrospective review identified 41 patients who received compounded liquid formulations of 14 OODs for 13 indications. Liquid OODs were used for a median of 3‐5 days. None of the 41 patients experienced discernable safety or overt effectiveness concerns readily attributed to use of liquid OODs. Implementation of a novel MUP and systematic review of OODs aids the pharmacist in standardizing institutional practice and mitigates risks associated with extemporaneous liquid formulations of OODs facilitating medication delivery of new agents to patients unable to swallow solid dosage forms.

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Population Pharmacokinetics of Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E‐Mutant Astrocytomas

Wang

Long-Boyle

Winger

et al. 2020

The Journal of Clinical Pharma

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Vemurafenib (Zelboraf) is an orally available BRAFV600E inhibitor approved for the treatment of unresectable or metastatic BRAFV600E‐mutant melanoma. The primary objective of this work was to characterize the pharmacokinetics (PK) of vemurafenib in pediatric patients with recurrent/refractory astrocytomas harboring the BRAFV600E mutation. The study was also designed to evaluate the feasibility of replacing whole vemurafenib tablets with crushed tablets in young children unable to swallow tablets. Twenty‐five pediatric patients (median age, 8.8 years; range, 3.3‐19.2) with recurrent/refractory BRAFV600E‐mutant astrocytomas received whole (n = 19) or crushed (n = 6) vemurafenib tablets twice daily. Plasma samples were collected on days 1, 15, and 22 in cycle 1 of vemurafenib treatment. Descriptive PK analyses demonstrated significant variability (approximately 6‐fold) in drug exposure. A 1‐compartment model with first‐order absorption and elimination was developed by adjusting the vemurafenib PK model previously validated in adults with mutant BRAFV600E melanoma. After inclusion of allometric scaling on total body weight, the model adequately described the PK of vemurafenib in children between a wide age range of 3 to 19 years old. In the crushed‐tablet cohort, relative bioavailability was approximately 96% (95% confidence interval, 49%‐142%) compared to that seen in pediatric patients receiving whole tablets based on the preliminary comparison analysis results. Moderate intrapatient variability (48%) of vemurafenib clearance was observed. There was significant correlation (R2 = 0.83) between area under the plasma concentration–time curve and trough concentration at steady state. These results will help increase the number of pediatric patients for whom vemurafenib is accessible and facilitate improved dosing in pediatric patients with recurrent/refractory BRAFV600E astrocytomas.

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Use of vemurafenib in a patient unable to swallow whole

Cited by 6 publications

References 12 publications

Alternative use of BRAF inhibitors in patients with metastatic melanoma unable to swallow pills

Alternative use of BRAF inhibitors in patients with metastatic melanoma unable to swallow pills

Medication use process and assessment of extemporaneous compounding and alternative routes of administration of oral oncology drugs: Guidance for clinical and oncology pharmacists

Population Pharmacokinetics of Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E‐Mutant Astrocytomas

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