Meeting highlights from the CMDh meeting in July 2016
10.08.2016
CMDh positions following PSUSA procedure for only nationally authorised products
The CMDh, having considered the PSURs on the basis of the PRAC recommendations and the PRAC assessment reports, agreed by consensus on the variations of the marketing authorisations of medicinal products containing the following active substances:
- apomorphine
- benazepril
- benzydamine
- dextromethorphan
- furosemide/spironolactone
- minoxidil (topical formulation)
- technetium (99mTc) mebrofenin
MAHs of medicinal products containing dextromethorphan in combinations are requested to implement the changes in relation to the metabolism of dextromethorphan and the warning about the possible interaction with cytochrome P450 2D6 (CYP2D6) inhibitors recommended to be introduced in sections 4.4, 4.5 and 5.2 of the product information for dextromethorphan monocomponent medicinal products also in the product information of the combination products containing dextromethorphan.
With regard to the interaction between spironolactone and trimethoprim/sulfamethoxazole, as included in the PSUSA outcome for furosemide/spironolactone, MAHs of medicinal products containing trimethoprim are requested to implement the relevant information regarding this interaction also in the product information for trimethoprim-containing products.
Further information regarding the above mentioned PSUSA procedures, including information on the implementation, will be published on the EMA website.
Medicinal products containing the substances pulegone and menthofuran
Following a request from HMPC and consultation with SWP, CHMP has adopted new thresholds for all medicinal products containing the substances pulegone and menthofuran (e.g. as constituents of peppermint oil and mint oil). More information is available on the EMA website, in the section 14.3.3 of the document Minutes of the CHMP meeting 23-26 May 2016 as well as in the document HMPC Public statement.
MAHs for medicinal products containing pulegone and menthofuran, either as active substance or excipient, should check whether their medicinal products comply with these exposure limits. If necessary, appropriate regulatory action should be undertaken within two years to ensure compliance. In case a variation is foreseen, a worksharing variation is recommended, whenever feasible.
Harmonisation of product information of medicinal products containing fenofibrate with regard to use in patients with renal impairment
The CMDh has identified that fenofibrate-containing medicinal products have been authorised in the EU with a varying degree of information on the use in patients with renal impairment. In order to harmonise concerned products in Member States, the CMDh has agreed a wording for the product information to be implemented by MAHs of concerned medicinal products.
MAHs for medicinal products containing fenofibrate are requested to submit a type IB variation, category C.I.z to implement the below wording in the product information of concerned products by 30th September 2016.
SmPC:
4.2 Posology and method of administration
(…)
Elderly patients (≥ 65 years old)
No dose adjustment is necessary. The usual dose is recommended, except for decreased renal function with estimated glomerular filtration rate < 60 mL/min/1.73 m2 (see Patients with renal impairment).
Patients with renal impairment
Fenofibrate should not be used if severe renal impairment, defined as eGFR < 30 mL/min per 1.73 m2, is present.
If eGFR is between 30 and 59 mL/min per 1.73 m2, the dose of fenofibrate should not exceed 100 mg standard or 67 mg micronized once daily.
If, during follow-up, the eGFR decreases persistently to < 30 mL/min per 1.73 m2, fenofibrate should be discontinued.
4.3 Contraindications
(…)
Severe renal insufficiency (estimated glomerular filtration rate < 30 mL/min/1.73 m2)
4.4 Special warnings and precautions for use
(…)
Renal function
[Product Name] is contraindicated in severe renal impairment (see section 4.3).
[Product Name] should be used with caution in patients with mild to moderate renal insufficiency. Dose should be adjusted in patients whose estimated glomerular filtration rate is 30 to 59 mL/min/1.73 m2 (see section 4.2).
Reversible elevations in serum creatinine have been reported in patients receiving fenofibrate monotherapy or co-administered with statins. Elevations in serum creatinine were generally stable over time with no evidence for continued increases in serum creatinine with long term therapy and tended to return to baseline following discontinuation of treatment.
During clinical trials, 10% of patients had a creatinine increase from baseline greater than 30 μmol/L with co-administered fenofibrate and simvastatin versus 4.4% with statin monotherapy. 0.3% of patients receiving co-administration had clinically relevant increases in creatinine to values > 200 μmol/L.
Treatment should be interrupted when creatinine level is 50% above the upper limit of normal. It is recommended that creatinine is measured during the first 3 months after initiation of treatment and periodically thereafter.
Package leaflet:
2. What you need to know before you take use [Product Name]
Do not take [Product Name]:
(…)
• If you have severe kidney problems
(…)
Warnings and precautions:
Talk to your doctor or pharmacist before taking [Product Name] if:
(…)
• you have kidney disease
(…)
3. How to take [Product Name]
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.
Your doctor will determine the appropriate strength for you, depending on your condition, your current treatment and your personal risk status.
(…)
Update of CMDh Questions & Answers on biologicals
The CMDh has agreed an update of the CMDh Q&As on biologicals. A question on the acceptable legal basis for abridged applications for denatured human albumin nanocolloid containing medicinal products used for radiolabelling was added.
The updated document will be published on the CMDh website under "Questions and Answers”.
More information on the CMDh July 2016 meeting can be found on the CMDh/HMA website.
