Active ingredients: Doxycycline
Efracea 40 mg modified-release hard capsules
Why is Efracea used? What is it for?
Efracea is a medicine that contains the active substance doxycycline. It is used in adults to reduce red pimples or pimples on the face caused by a disease called rosacea.
Contraindications When Efracea should not be used
Do not take Efracea
- if you are allergic (hypersensitive) to any of the medicines of the tetracycline family, including doxycycline or minocycline, or to any of the other ingredients of this medicine (listed in section 6.)
- if you are pregnant Efracea should not be used from the 4th month of pregnancy onwards as it can harm the unborn child. If you suspect or learn that you are pregnant while taking Efracea, contact your doctor immediately.
- in combination with retinoids (medicines used to treat certain skin conditions such as severe acne) taken by mouth (see section "Other medicines and Efracea").
- if you suffer from a condition that causes the absence of stomach acid (achlorhydria) or if you have had surgery in the first intestinal tract (duodenum).
Efracea should not be taken by infants or children under the age of 12, as it can cause permanent discoloration of the teeth or problems with dental development.
Precautions for use What you need to know before taking Efracea
Talk to your doctor or pharmacist before taking Efracea if:
- is suffering from liver disease
- have a history of predisposition to proliferation of candidiasis or if you are suffering from an oral or vaginal yeast or fungal infection
- suffer from a muscle disease called myasthenia gravis
- suffer from colitis
- suffer from esophageal irritation or ulcer
- suffer from the type of rosacea that affects the eyes
- exposes your skin to strong sunlight or artificial sunlight, as severe sunburn can occur in some people who take doxycycline. Consider using a sunscreen or sunscreen to reduce the risk of sunburn and stop using Efracea if you get sunburn.
Interactions Which drugs or foods can modify the effect of Efracea
Other medicines and Efracea
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Efracea and some other medicines may not work properly when taken together. Tell your doctor about any medicines you take or plan to take while taking Efracea.
- Efracea should not be used at the same time as isotretinoin because of the risk of increased brain pressure. Isotretinoin is prescribed to patients with severe acne conditions.
- Do not take antacids, multi-vitamins or other products that contain calcium (such as milk and dairy products or fruit juices containing calcium), aluminum, magnesium (including quinapril tablets that are taken for high blood pressure), iron or bismuth, o cholestyramine, activated charcoal or sucralfate up to 2-3 hours after taking Efracea. These medicines can reduce the effectiveness of Efracea when taken at the same time.
- Other treatments for ulcers or heartburn can also reduce the effectiveness of Efracea and should not be taken until at least 2 hours after Efracea.
- If you are taking blood thinners, your doctor may find that the dose of your blood thinner needs to be changed.
- If you are taking certain medicines for diabetes, your doctor may be in a position to check whether the dose of these medicines needs to be changed.
- There is a possibility that Efracea will reduce the effectiveness of oral contraceptives, causing pregnancy.
- Efracea can make certain antibiotics, including penicillins, less effective.
- Taking barbiturates (sleep pills or short-term pain relievers), rifampicin (tuberculosis), carbamazepine (epilepsy), diphenylhydantoin and phenytoin (brain seizures), primidone (anticonvulsant) or cyclosporine (organ transplants) may shorten the duration of the activity of Efracea in your organism.
- Use of Efracea with the general anesthetic methoxifluorane can cause severe kidney damage.
Efracea with food and drink
Always take Efracea with an adequate amount of water to wet the capsule, as this reduces the risk of irritation or ulceration in the throat or esophagus.
Do not take milk or dairy products at the same time as Efracea as these products contain calcium which may reduce the effectiveness of Efracea. Allow 2-3 hours after taking the daily dose of Efracea before drinking or eating dairy products.
Warnings It is important to know that:
Pregnancy and breastfeeding
Efracea should not be used during pregnancy as it can cause permanent discoloration of the teeth in the unborn baby.
Efracea should not be used for prolonged periods by mothers who are breastfeeding as the medicine can cause abnormal discoloration of the teeth and reduce bone growth in the infant.
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
Efracea has no or negligible influence on the ability to drive and use machines.
Efracea contains sugar (sucrose) and Allura Red AC - aluminum lake (E129). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
The ink used to print on the capsules contains Allura Red AC - aluminum lake (E129) which may cause allergic reactions.
Dose, Method and Time of Administration How to use Efracea: Posology
Always take this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
The recommended dose is one Efracea capsule per day in the morning. Swallow the capsule whole, without chewing it.
You must take Efracea with a full glass of water in a sitting or standing position to avoid any irritation of the throat.
Overdose What to do if you have taken too much Efracea
If you take more Efracea than you should
If you take an overdose of Efracea, there is a risk of damage to the liver, kidneys or pancreas.
If you take more Efracea capsules than you should, consult your doctor immediately.
If you forget to take Efracea
Do not take a double dose to make up for a forgotten capsule.
If you stop taking Efracea
You must continue taking Efracea until your doctor decides to stop it.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Efracea
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Common side effects
The following side effects may occur commonly (affects 1 to 10 users in 100) during treatment with Efracea:
- Inflammation of the nose and throat
- Sinus inflammation (sinusitis)
- Fungal infections
- Anxiety
- Sinus headache
- High or increased blood pressure
- Diarrhea
- Pain in the upper abdomen
- Dry mouth
- Back pain
- Ache
- Changes in some blood tests (amount of sugar in the blood or liver function tests).
Undesirable effects with frequency not known (cannot be estimated from the available data)
The following side effects may occur during treatment with Efracea:
- increased brain pressure
- headache
Rare side effects
The following side effects may occur infrequently (affecting 1 to 10 users in 10,000) during treatment with the class of medicines to which Efracea belongs (the tetracyclines):
- Allergic (hypersensitivity) reaction all over the body *
- Changes in the number or type of some blood cells in the blood
- Increased brain pressure
- Inflammation of the membrane surrounding the heart
- Nausea, vomiting, diarrhea, anorexia
- Liver damage
- Skin rashes or hives
- Abnormal skin reaction to sunlight
- Increased level of urea in the blood
Very rare side effects
The following side effects may occur very rarely (affecting less than 1 in 10,000 patients) during treatment with the class of medicines to which Efracea belongs (the tetracyclines):
- Allergic reaction causing swelling of the eyes, lips or tongue *
- Yeast infection around the anus or genitals
- Changes in red blood cells (haemolytic anemia)
- Microscopic brown-black spots of thyroid tissues have been observed with long-term use of tetracyclines. Thyroid function is normal.
- Increased intracranial pressure in newborns
- Inflammation of the tongue
- Difficulty swallowing
- Inflammation of the intestine
- Inflammation or ulcer of the esophagus
- Inflammation of the skin that causes peeling
- Worsening of the disease of the immune system known as systemic lupus erythematosus (SLE)
Undesirable effects with frequency not known (cannot be estimated from the available data)
The following side effects may occur during treatment with the class of medicines to which EFRACEA belongs (the tetracyclines):
- detachment of the nail from the nail bed after sun exposure.
* See your doctor immediately or go to the nearest emergency department if you notice side effects such as swelling of the face, lips, tongue and throat, difficulty in breathing, hives or itching of the skin and eyes, or rapid heartbeat (palpitations) and feeling of weakness. These effects could be symptoms of a severe allergic (hypersensitivity) reaction.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Italian Medicines Agency, Website: http://www.agenziafarmaco.gov.it/. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and blister after "EXP". The expiry date refers to the last day of that month.
Store in the original package to keep it away from light.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Efracea contains
- The active ingredient is doxycycline. Each capsule contains 40 mg of doxycycline (as monohydrate).
- The other ingredients are:
Hypromellose, methacrylic acid-ethyl acrylate copolymer (1: 1), triethyl citrate, talc, hypromellose, titanium dioxide, macrogol 400, yellow iron oxide, red iron oxide, Polysorbate 80, sugar spheres (Corn starch, Sucrose).
Capsules: gelatin, black iron oxide, red iron oxide, yellow iron oxide, titanium dioxide
Printing ink: shellac, propylene glycol, black iron oxide, Indigo Carmine - aluminum lake, Allura Red AC - aluminum lake (E129), Brilliant Blue FCF - aluminum lake, D&C Yellow No. 10 - aluminum lake.
See end of section 2 for information on sugar (sucrose) and Allura Red AC - aluminum lake (E129).
What Efracea looks like and contents of the pack
Efracea is a modified-release hard capsule.
The capsules are beige in color and bear the indication "GLD 40".
Efracea is available in packs of 56, 28 or 14 capsules (not all pack sizes may be marketed).
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
EFRACEA 40 MG HARD MODIFIED RELEASE CAPSULES
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 40 mg of doxycycline (as monohydrate).
Excipients with known effects: 102-150 mg of sucrose and 26.6 - 29.4 mcg of Rosso Allura AC - aluminum lake (E129).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Modified-release capsule, hard.
Beige capsule, size N. 2, bearing the indication "GLD 40".
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Efracea is indicated for the reduction of papulopustular lesions in adult patients with facial rosacea.
04.2 Posology and method of administration
Dosage
Adults, including the elderly:
Oral use
The daily dose is 40 mg (1 capsule).
Patients with renal impairment
No dose adjustment is necessary in patients with renal impairment.
Patients with hepatic impairment
Efracea should be administered with caution in patients with hepatic impairment or in those taking potentially hepatotoxic medicinal products (see section 4.4).
Pediatric population
Efracea is contraindicated in children below 12 years of age (see section 4.3).
Method of administration
The capsule should be taken in the morning with an adequate amount of water in order to reduce the risk of irritation and oesophageal ulcer (see section 4.4).
Patients should be evaluated after 6 weeks and, in the absence of results, treatment discontinuation should be considered. In clinical trials, patients were treated for 16 weeks. Upon discontinuation of treatment, lesions tended to reappear at visit 4-week follow-up, therefore it is recommended that patients be re-evaluated 4 weeks after discontinuation of treatment.
04.3 Contraindications
Hypersensitivity to the active substance, to other tetracyclines or to any of the excipients listed in section 6.1.
Babies and children up to 12 years of age.
Second and third trimester of pregnancy (see section 4.6).
Concomitant administration of oral retinoids (see section 4.5).
Doxycycline should not be prescribed to patients with known or suspected achlorhydria, or who have undergone duodenal bypass or bypass surgery.
04.4 Special warnings and appropriate precautions for use
Efracea contains doxycycline in a formulation designed to produce anti-inflammatory plasma levels below the antimicrobial threshold. Efracea should not be used to treat infections caused by organisms that are sensitive (or suspected of being) to doxycycline.
Solid dosage forms of tetracyclines can cause irritation and esophageal ulcer. To avoid irritation and oesophageal ulcer, take the medicinal product with an adequate amount of fluid (water) (see section 4.2). Efracea should be ingested in an upright sitting or standing position.
Although no proliferation of opportunistic microorganisms, such as yeasts, was noted during clinical studies with Efracea, tetracycline-based therapies at higher doses can lead to the proliferation of non-sensitive microorganisms, including fungi. Although not observed in clinical trials with Efracea, the use of tetracyclines at higher doses may increase the incidence of vaginal candidiasis. Efracea should be used with caution in patients with a history of predisposition to proliferation of candidiasis. If superinfection is suspected, take appropriate measures, including consideration of discontinuing Efracea.
Treatment with higher doses of tetracyclines is associated with the emergence of resistant intestinal bacteria, such as enterococci and enterobacteria.Although not observed in clinical trials with low dose doxycycline (40 mg / day), the risk of development of resistance in the normal microflora cannot be excluded in patients treated with Efracea.
Blood levels of doxycycline in patients treated with Efracea are lower than those treated with conventional antimicrobial formulations of doxycycline. However, since there are no safety data on the use of this lower dose in hepatic impairment, Efracea should be administered with caution in patients with hepatic impairment or in those receiving potentially hepatotoxic medicinal products. The antianabolic action of tetracyclines can cause an increase in blood urea nitrogen. Studies to date indicate that this phenomenon does not occur with the use of doxycycline in patients with impaired renal function.
Caution should be exercised when treating patients with myasthenia gravis, as this condition may worsen.
All patients on doxycycline therapy, including Efracea, are advised to avoid excessive exposure to the sun or artificial ultraviolet light while taking doxycycline and to discontinue therapy in case of phototoxicity (rash, etc.) . The use of sunscreen or sunscreen should be considered. Treatment should be stopped at the first signs of photosensitivity.
As with all antimicrobial medicinal products in general, there is a risk of developing pseudomembranous colitis during treatment with doxycycline. In case of episodes of diarrhea during treatment with Efracea, the possibility of pseudomembranous colitis should be considered and therapy instituted. This may include discontinuing doxycycline and instituting specific antibiotic therapy. In such situations, peristalsis inhibiting agents should not be employed.
Do not use Efracea in patients who have rosacea eye lesions (such as ocular rosacea and / or blepharitis / meibomianitis) as there are limited efficacy and safety data for this population type. If these manifestations appear during the course of treatment, discontinue Efracea and refer the patient to an ophthalmologist.
In humans, the use of tetracyclines during dental development can cause permanent discoloration of the teeth (yellow-gray-brown). This reaction is more common with prolonged use of the medicine, but has also been observed following repeated short-term treatments. The possibility of enamel hypoplasia has also been reported. As with other tetracyclines, doxycycline forms a stable complex with calcium in any tissue containing osteoblasts. A decrease in fibula growth was observed in premature infants taking oral tetracycline at doses of 25 mg / kg every 6 hours. This reaction was reversible after discontinuation of the drug.
In the event of a severe acute hypersensitivity reaction (e.g. anaphylaxis), discontinue treatment with Efracea immediately and take the usual emergency measures (e.g. administration of antihistamines, corticosteroids, sympathomimetics and, if necessary, artificial respiration) .
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
The printing ink on the capsules contains Allura Red AC - aluminum lake (E129) which may cause allergic reactions.
04.5 Interactions with other medicinal products and other forms of interaction
The recommendations below regarding potential interactions between doxycycline and other medicinal products are based on experience following the use of higher doses generally used in antimicrobial formulations of doxycycline rather than those of Efracea. However, at present, there are insufficient data to reassure that the interactions described with higher doses of doxycycline will not also occur with Efracea.
Interactions related to doxycycline:
The absorption of doxycycline from the gastrointestinal tract can be inhibited by bi- or trivalent ions such as aluminum, zinc, calcium (found for example in milk and derivatives or in fruit juices containing calcium), by magnesium (present for example in antacids ) or from preparations based on iron, activated carbon, cholestyramine, bismuth chelates and sucralfate. Therefore these medicines or foodstuffs should be taken about 2-3 hours after taking doxycycline.
Medicines that increase gastric pH may reduce the absorption of doxycycline, therefore they should be taken at least 2 hours after taking doxycycline.
Quinapril may reduce the absorption of doxycycline, due to the high magnesium content present in quinapril tablets.
Rifampicin, barbiturates, carbamazepine, diphenylhydantoin, primidone, phenytoin and chronic alcohol abuse can accelerate the breakdown of doxycycline following enzyme induction in the liver thereby reducing its half-life, and leading to sub-therapeutic concentrations of doxycycline.
Concomitant use of cyclosporine has been reported to reduce the half-life of doxycycline.
Interactions related to other medicinal products:
Concomitant use not recommended:
When doxycycline is given shortly before, during or after isotretinoin cycles, there is a potential for potentiation between drugs which may lead to reversible increase in intracranial pressure (intracranial hypertension). Concomitant administration should therefore be avoided.
Bacteriostatic medicinal products, including doxycycline, may interfere with the bactericidal action of penicillin and beta-lactam antibiotics. It is therefore recommended that doxycycline and beta-lactam antibiotics not be used in combination.
Other interactions:
The combined use of tetracyclines and methoxyflurane has been reported to lead to fatal nephrotoxicity.
Doxycycline has been shown to potentiate the hypoglycaemic effect of oral sulphonylurea antidiabetics. When given in combination with these drugs, monitor blood glucose levels and reduce sulphonylurea doses if necessary.
Doxycycline has been shown to depress plasma prothrombin activity, thus potentiating the effect of dicumarol-type anticoagulants. When administered in combination with such agents, coagulation parameters, including the INR (International Normalized Ratio), should be monitored, and doses of anticoagulant medicinal products should be reduced if necessary. The possibility of increased blood clotting should always be considered. risk of bleeding.
Tetracyclines used concomitantly with oral contraceptives have led in some cases to bleeding or pregnancy.
04.6 Pregnancy and lactation
Pregnancy
Studies in animals have not shown a teratogenic effect. In humans, the use of tetracyclines in a limited number of pregnancies has not led to any specific malformation to date.
Administration of tetracyclines during the second and third trimesters leads to permanent discoloration of the deciduous teeth in the unborn child. Consequently, doxycycline is contraindicated during the second and third trimester of pregnancy (see section 4.3).
Feeding time
Low levels of tetracyclines are excreted in breast milk. Breastfeeding mothers can only use doxycycline for short periods. Long-term use of doxycycline may lead to significant absorption by the infant and is therefore not recommended due to the theoretical risks of tooth discoloration and reduced bone growth for the infant.
Fertility
Oral administration of doxycycline to male and female Sprague-Dawley rats had adverse effects on fertility and reproductive function (see section 5.3).
The effects of Efracea on human fertility are not known.
04.7 Effects on ability to drive and use machines
Efracea has no or negligible influence on the ability to drive or use machines.
04.8 Undesirable effects
Summary of the safety profile
In the pilot placebo-controlled studies on the use of Efracea in the course of rosacea, 269 patients were treated with Efracea 40 mg once daily and 268 patients with placebo for 16 weeks. Gastrointestinal adverse reactions occurred overall in a greater proportion of patients taking Efracea (13.4%) compared to those taking placebo (8.6%). The most commonly reported adverse reactions in patients treated with Efracea, i.e. those that occurred with a frequency ≥3% in the group with Efracea and with a frequency of at least 1% higher than placebo, were nasopharyngitis, diarrhea and hypertension.
Tabular list of adverse reactions
The table below lists the adverse reactions to Efracea in the pivotal clinical studies, i.e. the adverse reactions for which the frequency in the Efracea group was greater than the frequency in the placebo group (by ≥1%).
Adverse reactions reported for tetracycline antibiotics as a class are listed after the table. Adverse reactions are ranked by system organ and frequency, using the following conventions: very common (> 1/10), common (> 1/100, 1 / 1,000, 1 / 10,000,
Table 1 - Adverse Reactions to Efracea in Placebo-Controlled Pilot Studies in Rosacea:
a Defined as adverse events where the frequency in the Efracea group was higher than in the placebo group (by at least 1%)
Cases of benign intracranial hypertension and headache (frequency not known: not estimated from available data) have been reported during post-marketing surveillance of Efracea.
The following adverse reactions have been observed in patients taking tetracyclines:
Infections and infestations:
Very rare: anogenital candidiasis.
Disorders of the blood and lymphatic system:
Rare: thrombocytopenia, neutropenia, eosinophilia
Very rare: haemolytic anemia
Immune system disorders:
Rare: hypersensitivity reactions including anaphylaxis
There have also been cases of: Anaphylactoid purpura
Endocrine disorders:
Very rare: Brown-black microscopic spots of thyroid tissues have been observed with long-term use of tetracyclines. Thyroid function is normal.
Nervous system disorders:
Rare: benign intracranial hypertension
Very rare: swelling of the fontanelles in newborns
Treatment should be discontinued if increased intracranial pressure occurs. These effects disappeared rapidly with the discontinuation of therapy.
Cardiac disorders:
Rare: Pericarditis
Gastrointestinal disorders:
Rare: Nausea, vomiting, diarrhea, anorexia
Very rare: glossitis, dysphagia, enterocolitis. Esophagitis and esophageal ulcers have been observed, most frequently in patients who were given hyclate salt in capsule form. Most of these patients took the medicine immediately before going to bed.
Hepatobiliary disorders:
Rare: hepatotoxicity
Skin and subcutaneous tissue disorders:
Rare: maculopapular and erythematous rash, skin photosensitivity, urticaria
Very rare: exfoliative dermatitis, angioneurotic edema
Frequency not known: photoonicolysis
Musculoskeletal and connective tissue disorders:
Very rare: exacerbation of systemic lupus erythematosus
Renal and urinary disorders:
Rare: BUN increased.
Typical adverse reactions of the tetracyclines class of medicinal products are less likely to occur during therapy with Efracea due to the reduced dose and relatively low plasma levels involved. However, the physician should always take into account the possibility of adverse events occurring, and should monitor patients appropriately.
Reporting of suspected adverse reactions
The reporting of suspected adverse reactions that occur after the authorization of the medicinal product is important, as it allows continuous monitoring of the benefit / risk ratio of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Italian Medicines Agency. , website: http://www.agenziafarmaco.gov.it/it/responsabili
04.9 Overdose
Symptoms
To date, no significant acute toxicity phenomena have been described in the case of a single oral intake of a multiple therapeutic dose of doxycycline. In the event of overdose, however, there is a risk of hepatic and renal parenchymatous damage and pancreatitis.
Treatment
The usual dose of Efracea is less than half the usual dose of doxycycline used for antimicrobial therapy. Physicians should therefore consider that in many cases overdose is likely to result in blood concentrations of doxycycline falling within the therapeutic range for antimicrobial treatment, for which there is a large amount of data confirming the safety of the medicinal product. "observation of the patient. In cases of significant overdose, doxycycline therapy should be discontinued immediately and necessary symptomatic measures taken.
Intestinal absorption of unabsorbed doxycycline should be minimized by administering antacids containing magnesium or calcium salts to produce complex chelates with non-absorbable doxycycline. Also consider the possibility of gastric lavage.
Dialysis does not alter the serum half-life of doxycycline, therefore it would be of no benefit in the treatment of overdose cases.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: antibacterials for systemic use, tetracyclines.
ATC code: J01AA02.
Mechanism of action
The pathophysiology of inflammatory lesions of rosacea is, in part, the manifestation of a neutrophil-mediated process. Doxycycline has been shown to inhibit neutrophil activity and numerous pro-inflammatory reactions including those associated with phospholipase A2, endogenous nitric oxide and interleukin-6. The clinical significance of these findings is unknown.
Pharmacodynamic effects
The plasma concentration of doxycycline following Efracea administration is well below the level required for the inhibition of microorganisms commonly associated with bacterial diseases.
Microbiological studies in vivo with a similar exposure to the active ingredient for 6-18 months they showed no effect on the dominant bacterial flora taken from the oral cavity, skin, intestinal tract and vagina. However, it cannot be ruled out that long-term use of Efracea may lead to the emergence of resistant intestinal bacteria such as Enterobacteriaceae and Enterococci, or to the enrichment of resistant genes.
Clinical efficacy and safety
Efracea was evaluated in two 16-week, randomized, double-blind, placebo-controlled pilot studies in 537 patients with rosacea (10 to 40 papules and pustules and up to two nodules). In both studies, the mean reduction in total inflammatory lesion counts was significantly greater in the Efracea group than in the placebo group:
Table 2 - Mean Change from Baseline to Week 16 in Total Inflammatory Lesion Count:
a p-value for the difference between treatments as a function of change from baseline (ANOVA)
05.2 "Pharmacokinetic properties
Absorption
Doxycycline is almost completely absorbed after oral administration. Following oral administration of Efracea, the mean maximum plasma concentrations were 510 ng / mL after a single dose and 600 ng / mL at steady state (Day 7). Maximum plasma concentrations were generally achieved 2 to 3 hours after administration. Concomitant administration of a high-fat, high-protein meal that included milk derivatives reduced the bioavailability (AUC) of doxycycline from Efracea by approximately 20% and reduced the maximum plasma concentration by 43%.
Distribution
Doxycycline is over 90% bound to plasma proteins and has an apparent volume of distribution of 50 l.
Biotransformation
The major metabolic pathways of doxycycline have not been identified but enzyme inducers decrease its half-life.
Elimination
Doxycycline is excreted as unchanged active substance in the urine and faeces. After 92 hours it is possible to recover between 40% and 60% of the administered dose in the urine and about 30% in the faeces. The terminal elimination half-life of doxycycline following administration of Efracea was approximately 21 hours after a single dose and approximately 23 hours at steady state.
Other special populations
The half-life of doxycycline is not significantly altered in patients with severely impaired renal function. Doxycycline is not extensively eliminated during hemodialysis.
There is no information on the pharmacokinetics of doxycycline in patients with hepatic impairment.
05.3 Preclinical safety data
Adverse reactions noted in repeat dose studies in animals include hyperpigmentation of the thyroid and tubular degeneration of the kidney. These effects were noted at exposure levels 1.5-2 times those seen in humans administered Efracea at the proposed doses. The clinical relevance of these findings remains unknown.
Doxycycline showed no mutagenic activity and no convincing evidence of clastogenic activity. In a rat carcinogenicity study, increases in benign tumors of the mammary gland (fibroadenoma), uterus (polyp) and thyroid (C-cell adenoma) were noted in females.
In rats, doses of 50 mg / kg / day of doxycycline caused a decrease in straight-line sperm velocity but did not affect male or female fertility or sperm morphology. At this dose, the systemic exposure to which rats were subjected was likely to be approximately 4 times that seen in humans taking the recommended dose of Efracea. At doses greater than 50 mg / kg / day, fertility and reproductive performance in rats, however, were affected. A study on peri / postnatal toxicity in rats revealed the absence of significant effects at therapeutically relevant doses. Doxycycline is known to cross the placenta and literature data indicate that tetracyclines may have toxic effects on the developing fetus.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Capsule shell
Jelly
Black iron oxide
Red iron oxide
Yellow iron oxide
Titanium dioxide
Printing inks
Shellac
Propylene glycol
Black iron oxide
Indigo Carmine - aluminum lacquer
Allura Red AC - aluminum lake (E129)
Brilliant Blue FCF - aluminum lacquer
Yellow D&C No. 10 - aluminum lacquer
Capsule content
Hypromellose
Methacrylic acid-ethyl acrylate copolymer (1: 1)
Triethyl citrate
Talc
Hypromellose, titanium dioxide, macrogol 400, yellow iron oxide, red iron oxide, polysorbate 80
Sugar balls (Corn starch, Sucrose)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
2 years.
06.4 Special precautions for storage
Store in the original package to keep it away from light.
06.5 Nature of the immediate packaging and contents of the package
Aluminum / PVC / aclar blister
Packaging:
56 capsules in 4 strips of 14 each
28 capsules in 2 strips of 14 each
14 capsules in 1 strip of 14
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions
07.0 MARKETING AUTHORIZATION HOLDER
GALDERMA ITALIA S.p.A.
Registered office: via dell "Annunciata 21 - 20121 MILAN
08.0 MARKETING AUTHORIZATION NUMBER
Pack of 56 capsules in 4 strips of 14 each, AIC n.039130012
Pack of 28 capsules in 2 strips of 14 each, AIC n.039130024
Pack of 14 capsules in 1 strip, AIC n.039130036
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: February 2010
10.0 DATE OF REVISION OF THE TEXT
10/2014
