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How should medicines be dosed in children who are obese?

28 May 2021Review on how to calculate medicine doses in children who are obese which includes a table on commonly prescribed medicines.

What injections can be given orally or via enteral feeding tubes?

6 November 2020This updated Medicines Q&A is a quick reference summary to different types of enteral feeding tubes, in relation to medication issues. Not all enteral feeding…

Safety in Lactation: Drugs used in nausea and vertigo

21 September 2020Additional information relating to breastfeeding To be used in conjunction with individual drug entries for specific information and guidance. The choice of anti-emetic will depend…

What is serotonin syndrome and which medicines cause it?

22 May 2020This Medicines Q&A outlines the causes and symptoms of serotonin syndrome and provides examples of medicines with the potential to cause serotonin syndrome.  
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Medicine Compliance Aid Stability

MaxolonAmdipharm Mercury Co Ltd

Amdipharm Mercury Co Ltd
Maxolon
Tablets 10mg
A3 · Amber 3No stability data is available. There are theoretical concerns with use in CAs, which may be mitigated by risk minimisation.
Airtight container
Protect from light
Protect from light and store in airtight containers.
21 January 2015

Lactation Safety Information

Domperidone (for inadequate lactation)
Prochlorperazine (as anti-emetic)
Unlicensed as a galactogogue in the UK
Moderate amount of published evidence of safety
Small to moderate amounts in breast milk
Evidence for effectiveness for inadequate lactation is limited
Use only for a short period, in a dose not exceeding 30mg daily for a maximum of five days, and avoid in mother’s with a history of depression
4 March 2019

New Medicines

GimotiDiabetic gastroparesis in women

Information

Gimoti
New formulation - repurposed medicine
Evoke Pharma
Evoke Pharma

Development and Regulatory status

None
None
Launched
Oct 20Metoclopramide intranasal (Gimoti) launched for relief of symptoms in adults with acute and recurrent diabetic gastroparesis in the US [14].
Jun 20Approved in US [13]
Aug 19Evoke plans to re-submit a NDA for metoclopramide intranasal to the US FDA in Q4 19 [12].
Apr 19Evoke Pharma announced that it has received a Complete Response Letter (CRL) from the US FDA for its NDA for Gimoti. The CRL provides recommendations to address issues related to clinical pharmacology and product quality/device quality. Evoke Pharma plan to meet with the FDA and address the issues raised [11].
Aug 18US FDA accepts a NDA for Gimoti for review, with a Prescription Drug User Fee Act (PDUFA) target date of 1 Apr 19 [11].
Mar 18Evoke plans to initially seek approval of Gimoti in the US and then will evaluate the market opportunity in other countries [10].
Mar 18Evoke plans to submit an NDA for a female-only indication based on a dose in women with equivalent exposure to Reglan Tablets and will submit supporting efficacy and safety data from PIIb and PIII trials, specifically for women, at doses similar or lower than the dose to be proposed in the NDA [10].
Nov 17Evoke plans to file Q1 18 in the US; no plans for EU development stated [8].
Apr 17At a meeting with the FDA, Evoke finalises design of the pivotal comparative exposure PK trial and reached an agreement on additional aspects of the NDA [6].
Dec 16Evoke Pharma announces that the FDA has agreed that demonstration of equivalent exposure to the listed drug (Reglan® 10 mg Tablets) in a healthy volunteer pharmacokinetic (PK) trial could serve as a portion of an NDA for metoclopramide nasal spray. The US FDA also agreed that safety and efficacy data from completed studies, including the ECG study, could be used in support. No new efficacy or safety study will be required, if bioequivalence criteria are met [6].

Category

EVK-001 is a novel metoclopramide nasal spray for the relief of symptoms associated with acute and recurrent diabetic gastroparesis. [1]
Neuropathies related to diabetes can affect 60-70% of people with diabetes. Autonomic neuropathy (including GI symptoms of gastroparesis) are more common in women [9].
Diabetic gastroparesis in women
Intranasal

Trial or other data

Mar 18Additional analysis of PK data (n=108) by sex revealed statistically significant differences in exposure between women and men given the same metoclopramide dose (nasal and oral). Based on this further analysis of results from the comparative exposure PK trial, statistically significantly lower AUC’s were found in men compared to women. The findings were not explicitly attributable to differences in body mass index (BMI) or weight. Similarly sex-based differences were observed in a previous healthy volunteer study we conducted, irrespective of the route of metoclopramide administration (nasal, oral and IV). In the most recent comparative exposure PK trial, results for women independently met equivalence criteria for AUC0-inf and AUC0-t at the tested Gimoti dose to be proposed in the NDA [10].
Nov 17The comparative exposure PK trial was an open label, 4-way crossover and enrolled 108 male and female healthy volunteers who were each to receive one Reglan Tablet dose and three different doses of Gimoti in a random sequence. Following discussions at pre-NDA meetings with FDA, Evoke planned to select a Gimoti dose based on criteria that includes a 90% confidence interval for the ratio of area under the plasma concentration curve, or AUC, falling within the bioequivalence range of 80-125% of Reglan Tablets. Though only one dose was needed to meet the dose selection criteria, the comparative exposure PK trial was designed to test three different strengths of Gimoti. Based on results of the study, two of the three doses tested met the dose selection criteria. The maximum observed plasma concentration, or Cmax, for Gimoti was slightly lower than the bioequivalence range, but in line with expectations that had been previously discussed with FDA as a likely outcome given the different route of administration and prior Gimoti PK trial results. Additionally, data showed the AUC and Cmax increased in a dose related manner across all three strengths tested. Relative to safety, all Gimoti doses were well tolerated with no clinically significant adverse events reported following any of the doses [8]
Oct 17Evoke announces top-line PK data from a comparative PK trial in healthy volunteers [6].
Jul 16In a PIII study, EVK-001 failed to meet its primary endpoint. Topline data were a bit surprising given that oral and intravenous metoclopramide are already FDA-approved and the drug has been in use to treat gastroparesis for decades. Evoke hasn’t abandoned the program yet and will look at the data more closely. It said that 28 out of 41 sites showed statistically significant benefit for its EVK-001, while the remaining 13 sites had statistically significant benefit for placebo [5].
Aug 15US FDA accept Evoke´s EVK-001 request for a full waiver of the requirement to conduct paediatric studies on the basis that diabetic gastroparesis is an adult disease. [4]
Dec 14The Thorough QT safety study successfully met its primary endpoint; EVK-001 did not increase the cardiac QT and corrected QT (QTc) interval at therapeutic and supratherapeutic doses [3].
Apr 14P3 study initiated (NCT02025725): Diabetic women with clinical symptoms attributed to diabetic gastroparesis and documentation of delayed gastric emptying who meet the protocol-specified entry criteria will be randomised to Metoclopramide Nasal Spray 10mg or placebo administered as a single intranasal spray four times daily; 30 minutes before meals and at bedtime for a total of four weeks. [2]