Active ingredients: Trinitroglycerin
Rectogesic® 4 mg / g Rectal ointment
Indications Why is Rectogesic used? What is it for?
Rectogesic is a rectal ointment that contains glyceryl trinitrate as an active ingredient. Glycerin trinitrate is part of the family of medicines called organic nitrates.
The ointment helps relieve the pain symptom caused by chronic anal fissures. The term anal fissure is defined as a lesion of the mucous membrane that lines the anal canal. Topical application of glyceryl trinitrate to the anal canal reduces anal pressure and increases blood flow, thereby reducing pain.
Contraindications When Rectogesic should not be used
Do not use Rectogesic if:
- you are allergic to glyceryl trinitrate or similar medicines
- you are allergic to any of the other ingredients of this medicine (listed in section 6)
- suffer from low blood pressure
- suffer from heart or vascular disorders
- suffer from closed-angle glaucoma, a condition in which the pressure in the eye rises rapidly causing loss of vision
- suffer from migraines or recurrent headaches
- suffer from increased intracranial pressure or high blood pressure in the head (eg head injury or brain haemorrhage - bleeding due to the rupture of a blood vessel in the brain, which can be fatal without immediate medical treatment. Cerebral haemorrhage is commonly reported as a type of stroke) or inadequate cerebral circulation (low volume of blood circulation in the brain)
- suffer from anemia (low iron content in the blood)
- take any of the following: erectile dysfunction medicines such as sildenafil citrate, tadalafil, vardenafil; medicines for angina or heart pain, such as glyceryl trinitrate (TNG), isosorbide dinitrate, amyl or butyl nitrite; medicines for high blood pressure or for depression (tricyclic antidepressants), acetylcysteine, or alteplase.
Precautions for use What you need to know before taking Rectogesic
Take special care with Rectogesic:
- if you suffer from liver or kidney disease
- in case of heparin administration, close blood monitoring should be performed as it may be necessary to change the heparin dose. Consult your doctor before stopping treatment with Rectogesic
- if you have haemorrhoids and bleeding more than usual, stop using Rectogesic and consult your doctor
- if you feel a severe headache when using Rectogesic tell your doctor who will decide whether to change the amount of Rectogesic or to stop using the ointment altogether.
Rectogesic can cause a drop in blood pressure. It is good to stand up slowly from a lying or sitting position otherwise you may feel faint. If you drink alcohol while taking Rectogesic you are more likely to feel a drop in blood pressure.
Children and adolescents
Rectogesic is not indicated for children and young people under 18 years of age as it has not been tested on subjects in this age group.
Interactions Which drugs or foods can modify the effect of Rectogesic
Other medicines and Rectogesic
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, even those obtained without a prescription.
The following medicines may increase the effect of Rectogesic on blood pressure lowering
- Medicines for depression (tricyclic antidepressants)
- Erectile dysfunction (male impotence) medicines (sildenafil citrate, tadalafil, vardenafil)
- Medicines for high blood pressure
- Diuretics
- Commonly used tranquilizers
- Medicines used to treat heart problems (isosorbide dinitrate, amyl or butyl nitrite)
Other Medicines
- Acetylcysteine may potentiate the effect of Rectogesic on blood flow
- The effect of heparin (used to control blood clotting) may decrease when used with Rectogesic
- The effect of alteplase (used to treat heart problems) may decrease when given together with Rectogesic
- Taking Rectogesic with dihydroergotamine (used to treat migraines) can increase the action of dihydroergotamine and lead to coronary vasoconstriction (narrowing of the blood vessels in the heart, which causes reduced blood flow).
- Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory medicines (some types of pain relievers) may alter the therapeutic effect of Rectogesic.
Rectogesic and alcohol
Be careful with your alcohol intake as using the ointment may cause the alcohol to have a greater effect than usual.
Warnings It is important to know that:
Pregnancy and breastfeeding
Rectogesic should not be used during pregnancy or breastfeeding.
Ask your doctor or pharmacist for advice before taking medicines if you are pregnant or breastfeeding.
Driving and using machines
There are no studies on the effect that the use of Rectogesic 4 mg / g rectal ointment has on the ability to drive and use machines. If you feel dizzy, sleepy or have blurred vision when you start using the ointment. , do not drive a car or use machines until these effects have completely disappeared.
Rectogesic contains lanolin and propylene glycol
This medicine contains lanolin (wool fat) which can cause skin reactions (e.g. contact dermatitis). The medicine also contains propylene glycol which can cause skin irritation.
Dosage and method of use How to use Rectogesic: Posology
Method of administration
Rectogesic 4 mg / g rectal ointment is for rectal use.
Always use this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist. The recommended dose is approximately 375 mg of ointment (approximately 1.5 mg of glycerin trinitrate) applied into the anal canal every 12 hours.
To apply the ointment, you can use a protection on your finger, such as an adhesive film or a finger cover. The finger covers can be found in a pharmacy or surgical supply retailer and the adhesive film in the nearest supermarket. For dosing, place your finger along the 1 '' line indicated on the outer carton and apply a line-length ointment strip to the end of your finger by gently pressing the tube. Gently insert the ointment into the anal canal using your finger, which must be inserted up to the first joint of the finger (about 1 cm) inside the anus.
Apply the ointment every twelve hours as directed by your doctor and do not exceed the dose. Wash your hands after use and dispose of the finger cover or adhesive film (not in the toilet).
Continue the treatment until the pain subsides or up to a maximum of 8 weeks. If anal pain does not improve with the use of Rectogesic, consult your doctor again to make sure there are no other causes.
Overdose What to do if you have taken too much Rectogesic
If you use more Rectogesic than you should
If you notice that you have applied more ointment than you should, you may feel dizzy and dizzy. He may also have a fast heartbeat or palpitations. If you experience these symptoms wash off the excess amount of ointment and tell your doctor or pharmacist immediately.
If you forget to use Rectogesic
Do not use a double dose to make up for a forgotten dose. Apply the next dose at the usual time.
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 Rectogesic
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects:
- Anaphylactoid reactions (allergic, potentially fatal reaction manifesting as swelling of the face, lips, tongue or throat, difficulty in breathing, shortness of breath or collapse). If you experience any of these symptoms, stop using the ointment and consult your doctor immediately.
- Allergic skin reactions (potentially serious). If you experience an allergic skin reaction, stop using the ointment and consult your doctor immediately
Other side effects:
Very common (may affect more than 1 in 10 people)
- Headache, which can be severe. If you experience a headache as a side effect, remove the ointment. If the headaches are bothersome you may need to ask your doctor if you should stop using the medicine.
Common (may affect up to 1 in 10 people)
- Dizziness
- Nausea
Uncommon (may affect up to 1 in 100 people)
- Diarrhea
- He retched
- Rectal bleeding, rectal disorders
- Anal discomfort, itching or burning of the anal canal
- Fast heartbeat or palpitations
Rare (may affect up to 1 in 1000 people)
- Feeling faint on standing
Not known side effects (frequency cannot be estimated from the available data)
- Sense of emptiness in the head, fainting
- Low blood pressure
- Rash irritation or pain at the application site
Other known side effects associated with the use of glyceryl trinitrate medicines (frequency not known)
- Flushes
- Unstable angina (chest pain)
- High blood pressure following discontinuation of treatment
- Methemoglobinemia (symptoms are a blue / purple discoloration of the skin and shortness of breath)
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 national reporting system at http://www.agenziafarmaco.gov.it/it/responsabili. 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 tube and carton after 'EXP.' The expiry date refers to the last day of that month.
- Do not store above 25 ° C
- Do not freeze
- Keep the tube tightly closed
- Once opened, use the ointment within 8 weeks.
Composition and pharmaceutical form
What Rectogesic contains
The active ingredient is glyceryl trinitrate. One gram of rectal ointment contains 4 mg of glyceryl trinitrate. The usual 375 mg dose of Rectogesic contains approximately 1.5 mg glycerin trinitrate.
The other ingredients are: propylene glycol, lanolin, sorbitan sesquioleate, hard paraffin and white soft paraffin.
What Rectogesic looks like and contents of the pack
Rectogesic is a whitish, homogeneous, opaque rectal ointment distributed in aluminum tubes of 30 g
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
RECTOGESIC 4 MG / G RECTAL POMADE
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Trinitroglycerin: 4 mg / g.
One gram of rectal ointment contains 4 mg of glyceryl trinitrate (TNG). 375 mg of this formulation contains approximately 1.5 mg of TNG.
Excipients with known effect:
Each gram of rectal ointment also contains 36 mg of propylene glycol and 140 mg of lanolin.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Rectal ointment.
Formulation in whitish, homogeneous, opaque ointment.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Rectogesic 4 mg / g rectal ointment is indicated in adults to relieve pain associated with chronic anal fissure.
During clinical development, the drug showed a modest effect on improving the mean daily pain intensity (see section 5.1).
04.2 Posology and method of administration
Route of administration: rectal use
Adults:
To apply the ointment, you can use a protection on your finger, such as an adhesive film or a finger cover (buy the finger covers separately, at the pharmacy or surgical supply retailer, or the adhesive film at the nearest supermarket). For dosing, place your finger along the 2.5 cm line indicated on the carton containing Rectogesic and apply a line-length strip of ointment to the end of the finger by gently pressing the tube. The amount of ointment should be approximately 375 mg (1.5 mg of TNG) Then gently insert the finger with the protector into the anal canal up to the first interphalangeal joint and apply the ointment in circular movements to the canal wall.
A 4 mg / g dose of ointment contains 1.5 mg of glyceryl trinitrate. This dose should be applied intra-anal every twelve hours. Treatment can be continued until pain subsides, up to a maximum of 8 weeks.
Rectogesic should be used when conservative treatment has proved insufficient for the treatment of acute symptoms of anal fissures.
Elderly (over 65):
There are no indications for the use of Rectogesic in the elderly.
Patients with hepatic or renal impairment:
There are no indications for the use of Rectogesic in patients with hepatic or renal impairment.
Children and adolescents:
The use of Rectogesic is not recommended in children and adolescents below 18 years due to a lack of data on its safety and efficacy.
04.3 Contraindications
Hypersensitivity to the active substance "glyceryl trinitrate" or to any of the excipients listed in section 6.1 or to other organic nitrates.
Concomitant treatment with phosphodiesterase type 5 (PDE5) inhibitors eg. sildenafil citrate, tadalafil, vardenafil and with other NO (nitric oxide) donor organic nitrates, such as other long-acting TNG derivatives, such as isosorbide dinitrate, amyl or butyl nitrite
Orthostatic hypotension, hypotension or uncorrected hypovolaemia, since the use of glyceryl trinitrate in these conditions may induce severe hypotension or shock.
Increased intracranial pressure (e.g. head injury or brain hemorrhage) or inadequate cerebral circulation.
Migraine or recurrent headache.
Aortic or mitral stenosis.
Obstructive hypertrophic cardiomyopathy.
Constrictive pericarditis or pericardial tamponade.
Strong anemia.
Closed-angle glaucoma.
04.4 Special warnings and appropriate precautions for use
The benefit / risk balance of Rectogesic ointment must be established on an individual basis. Severe headache may occur in some patients following treatment with Rectogesic. In some cases, it is advisable to re-evaluate the appropriate dose. In patients in whom the risk / benefit ratio is judged to be negative, treatment with Rectogesic should be discontinued on medical advice and a new therapeutic or surgical treatment should be initiated.
Rectogesic should be used with caution in patients with severe liver or kidney disease.
Avoid excessive hypotension, especially for prolonged periods of time, given the possible harmful effects on the brain, heart, liver and kidneys due to poor perfusion and the consequent risk of ischemia, thrombosis and impaired functionality of these organs. Patients should be advised to move slowly from lying or sitting to standing in order to minimize orthostatic hypotension. This advice is particularly important for patients with hypovolaemic and diuretic therapy.Glycerin-induced hypotension may be accompanied by paradoxical bradycardia and increased angina pectoris. It is possible that the elderly are more susceptible to the onset of orthostatic hypotension, especially when standing up suddenly. There are no indications for the use of Rectogesic in the elderly.
Alcohol may potentiate the hypotensive effects of glyceryl trinitrate.
If the doctor decides to prescribe a glyceryl trinitrate ointment to patients with heart disease eg. acute myocardial infarction or congestive heart failure, careful clinical and haemodynamic monitoring should be undertaken to avoid the potential risk of hypotension and tachycardia.
Discontinue treatment if bleeding associated with haemorrhoids increases.
This formulation contains propylene glycol and lanolin which can cause irritation and skin reactions (eg contact dermatitis).
If anal pain persists, a differential diagnosis may be needed to rule out other possible causes.
Glycerin trinitrate can interfere with the dosage of catecholamines and vanylmandelic acid in the urine as it increases the excretion of these substances.
Concomitant treatment with other medicinal products should be approached with caution. See section 4.5 for specific information.
04.5 Interactions with other medicinal products and other forms of interaction
Concomitant treatment with other vasodilators, calcium channel blockers, ACE inhibitors, beta blockers, diuretics, antihypertensives, tricyclic antidepressants and major tranquilizers, as well as alcohol consumption, may potentiate the rectogesic-induced blood pressure lowering effect. Therefore, carefully consider concomitant treatment with these medicinal products before initiating therapy with Rectogesic.
The hypotensive effect of organic nitrates is enhanced by the concomitant administration of phosphodiesterase type 5 (PDE5) inhibitors, eg sildenafil, tadalafil, vardenafil (see section 4.3).
Rectogesic is contraindicated in concomitant treatment with NO (nitric oxide) donor drugs, such as isosorbide dinitrate, amyl or butyl nitrite (see section 4.3).
Acetylcysteine can potentiate the vasodilator effect of glycerin trinitrate.
Concomitant treatment of intravenous glyceryl trinitrate with intravenous heparin decreases the efficacy of the heparin itself. Close monitoring of blood coagulation parameters is required; and the heparin dose must be adjusted accordingly. Withdrawal of Rectogesic may induce a sharp increase in PTT (partial thromboplastin time). In this case it may be necessary to reduce the heparin dosage.
The concomitant administration of intravenous glyceryl trinitrate and alteplase may induce a reduction in the thrombolytic activity of the alteplase.
Concomitant administration of Rectogesic and dihydroergotamine may increase the bioavailability of dihydroergotamine and induce coronary vasoconstriction. The possibility of an altered therapeutic response to Rectogesic following the intake of acetylsalicylic acid and non-steroidal anti-inflammatory drugs cannot be excluded.
04.6 Pregnancy and lactation
Fertility
There are no data available on the effect of Rectogesic on human fertility. Studies in rats suggest that there are no particular hazards under the recommended conditions of use (see section 5.3).
Pregnancy: There are no adequate data from the use of glyceryl trinitrate in pregnant women. Animal studies are insufficient to show effects on pregnancy, embryonal / fetal development, parturition and postnatal development (see section 5.3). Rectogesic should not be used during pregnancy.
Lactation: It is not known whether glyceryl trinitrate is excreted in human milk. Given the potential harmful effects on the breastfed infant (see section 5.3), the use of Rectogesic is not recommended during breastfeeding.
04.7 Effects on ability to drive and use machines
No studies on the ability to drive and use machines have been performed with Rectogesic. Rectogesic, especially on first use, may induce dizziness, dizziness, blurred vision, headache or fatigue in some patients. Patients should be discouraged from driving vehicles. or operate machinery during treatment with Rectogesic.
04.8 Undesirable effects
In patients treated with Rectogesic 4 mg / g rectal ointment, the most common adverse reaction related to therapy was dose-dependent headache which occurred with an incidence of 57%.
The table below shows adverse reactions, which occurred during clinical trials, broken down by system organ class. Within each organ system class, adverse reactions were grouped by frequency as follows: very common (> 1/10), common (> 1/100 1/1000
Adverse reactions to glyceryl trinitrate are usually dose-dependent and most of them result from vasodilatory activity. Headache, which may be severe, is the most commonly reported undesirable effect. In the Phase III clinical trials of Rectogesic 4 mg / g rectal ointment, the incidence of mild, moderate and severe headache was 18%, 25% and 20%, respectively. Patients with a history of migraine or recurrent headache were at an increased risk of developing headache during treatment (see section 4.3). Headache can recur every day, especially at higher doses. Headache can be treated with mild analgesics, e.g. paracetamol, and is reversible with the interruption of treatment.
Rare cases of orthostatic hypotension events associated with symptoms of vertigo and dizziness have been reported in clinical trials. There is no evidence of a dose-related trend in the incidence of these events.
The event of orthostatic hypotension was mild in the majority of patients and no events of orthostatic hypotension were reported during Phase III clinical trials.
In some cases, the onset of dizziness and vertigo has led to discontinuation of glycerin trinitrate.
Post-marketing experience
These reactions were received as spontaneous reports and therefore their frequency is not known (cannot be estimated from the available data).
Nervous system disorders: feeling lightheaded, syncope
Vascular disorders: hypotension, orthostatic hypotension
Immune system disorders: hypersensitivity, anaphylactoid reaction
General Disorders and Administration Site Conditions: Administration site irritation, hives and administration site pain.
In some patients, lightheadedness and hypotension (including orthostatic hypotension) have been severe enough to require discontinuation of therapy.
Effects of this class of medicines
Very rarely, therapeutic doses of organic nitrates have caused methemoglobinemia in apparently healthy patients. Flushing, unstable angina, and withdrawal hypertension may also occur.
Reporting of suspected adverse reactions.
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
04.9 Overdose
Accidental overdose of Rectogesic can cause hypotension and reflex tachycardia. No specific antagonist of the vasodilator effects of glyceryl trinity is known and no intervention has been subjected to a controlled study as a therapy for glyceryl trinitrate overdose. Since hypotension associated with glyceryl trinitrate overdose is caused by venodilation and arterial hypovolaemia, prudent therapy in this situation should be directed to increasing the volume of fluid in the systemic circulation. Passive lifting of the patient's legs may be sufficient, but an intravenous infusion of normal saline or similar fluid may also be required. In exceptional cases of severe hypotension or shock, resuscitation measures may be necessary.
Excessive dosage can also lead to methemoglobinemia. In this case, intervene with an infusion of methylene blue.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Muscle relaxants
ATC code: C05AE01
The main pharmacological action of glyceryl trinitrate is the relaxation of vascular smooth muscle and is mediated by the release of nitric oxide. When the glycerin-based ointment is applied intra-anal, relaxation of the internal anal sphincter is achieved.
The hypertonicity of the internal part of the anal sphincter, but not of the external one, represents a predisposition factor for the formation of anal fissures. The blood vessels of the anal transition zone (anoderm) flow through the internal anal sphincter (SAI). Therefore a hypertonicity of the NOS can induce a decrease in blood flow and cause ischemia in this region.
Distension of the rectum produces an inhibitory reflex of the rectal-anal area and relaxation of the internal anal sphincter. The nerves that mediate this reflex are found in the gut wall. The release of the neurotransmitter NO from these nerves plays a significant role in the physiology of the internal anal sphincter. Specifically, NO mediates the rectal-anal inhibitory reflex in humans. producing a relaxation of the SAI.
The link between the hypertonicity of the SAI, spasm and the presence of an anal fissure has been established. Patients with chronic anal fissure have significantly higher mean maximum resting anal pressure than controls; the blood flow in the anal dermis in patients with chronic anal fissure was significantly lower than in controls. In patients whose fissures healed following sphincterotomy, a reduction in anal pressure and an improvement in the blood flow of the anoderm have been demonstrated, with further evidence of the ischemic nature of the anal fissure. Topical application of a NO donor ( trinitroglycerin) causes relaxation of the anal sphincter, with consequent reduction of anal pressure and improvement of anodermal blood flow.
Effect on pain
Rectogesic 4 mg / g placebo-controlled rectal ointment was shown in three phase III clinical trials to improve average daily pain intensity, measured on a visual analog scale of 100mm, associated with chronic anal fissure. study, Rectogesic 4 mg / g rectal ointment reduced mean daily pain intensity over 21 days by 13.3mm (39.2mm at baseline) compared to 4.3mm (25.7mm at baseline) with placebo (p
Effect on scarring
In all three studies, healing of anal fissures in patients treated with Rectogesic 4 mg / g rectal ointment was not statistically different from placebo treatment. Rectogesic is not indicated for the healing of chronic anal fissures.
05.2 "Pharmacokinetic properties
The volume of distribution of glyceryl trinitrate is approximately 3 L / kg, which is eliminated from this volume in extremely rapid percentages of time, resulting in a serum half-life of approximately 3 minutes. The observed clearance rates (close to 1L / kg / min) largely exceed hepatic blood flow. Known sites of extrahepatic metabolism include red blood cells and vascular walls. The initial products of glyceryl trinitrate metabolism are inorganic nitrate and 1,2 and 1,3-dinitroglycerol. Dinitrates are less effective vasodilators than glyceryl trinitrate, but remain longer in the serum. Their contribution to relaxation of the internal anal sphincter is unknown. Dinitrates are further metabolised into non-vasoactive mononitrates and ultimately into glycerol and carbon dioxide. In six healthy subjects, the mean bioavailability of glyceryl trinitrate delivered into the anal canal via 0.2% ointment was approximately 50% of the 0.75 mg dose.
05.3 Preclinical safety data
Repeated dose toxicity
Systemic toxicity studies of Rectogesic have not been conducted. Published data indicate that high oral doses of glyceryl trinitrate may have toxic effects (methemoglobinaemia, testicular atrophy and aspermatogenesis) in long-term treatment. However, these aspects are not particularly dangerous for humans in conditions of therapeutic use.
Mutagenicity and carcinogenicity
Data from preclinical studies with TNG reveal genotoxic effects, exclusively in the strain of Salmonella typhimurium TA1535. The administration of TNG in the diet of rodents throughout their life led to the conclusion that glyceryl trinitrate has no relevant carcinogenic effect in the therapeutic dose range in humans.
Reproductive toxicity
Reproductive toxicity studies performed in rats and rabbits via intravenous, intraperitoneal and cutaneous administration of glyceryl trinitrate revealed no adverse effects on fertility or embryonic development at dosages that did not induce maternal toxicity. No teratogenic effects were observed. In rats, fetotoxic effects (weight loss at birth) were observed at doses above 1mg / kg / d (PI) and 28mg / kg / d (dermal) following uterine exposure during fetal development.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Propylene glycol
Lanolin
Sorbitan sesquioleate
Hard paraffin
White soft paraffin
06.2 Incompatibility
Not relevant.
06.3 Period of validity
36 months
After first opening: 8 weeks.
06.4 Special precautions for storage
Do not store above 25 ° C.
Do not freeze.
Keep the tube tightly closed.
06.5 Nature of the immediate packaging and contents of the package
30 g
Aluminum tubes with white non-piercing polyethylene screw cap.
06.6 Instructions for use and handling
No special instructions.
07.0 MARKETING AUTHORIZATION HOLDER
ProStrakan Limited
Galabank Business Park
Galashiels
08.0 MARKETING AUTHORIZATION NUMBER
AIC n. 037537014
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
23/05/2007
10.0 DATE OF REVISION OF THE TEXT
July 2015