Rectogesic

Rectogesic contains the active ingredient Glyceryl trinitrate 0.2% w/w in a smooth light amber ointment formulation for topical application.
Glyceryl trinitrate (CAS:53-63-0) is a pale yellow oily liquid. It is slightly soluble in water, soluble in methyl alcohol, ethanol, carbon disulphide, ether and glacial acetic acid. Its chemical name is 1,2,3 - propanetriol trinitrate with empirical formula: C₃H₅N₃O₉ and molecular weight: 227.09.
Excipients/Inactive Ingredients: The other ingredients in Rectogesic are Paraffin-soft yellow; Paraffin liquid; wool fat; ethanol and water-potable.

Pharmacology: The principal pharmacologic action of glyceryl trinitrate is mediated via the release of nitric oxide. When glyceryl trinitrate ointment is applied by the intra-anal route, the internal anal sphincter becomes relaxed.
Hypertonicity of the internal but not the external anal sphincter is a predisposing factor in the formation of anal fissures. The blood vessels to the anoderm course through the internal anal sphincter (IAS). Therefore hypertonicity of the IAS may thereby decrease blood flow and cause ischaemia to this region.
Distension of the rectum results in the anorector inhibitory reflex and relaxation of the internal anal sphincter. The nerves mediating this reflex lie in the wall of the gut. Release of the neurotransmitter NO from nerves of this type play a significant role in the physiology of the internal anal sphincter. Specifically, NO mediates the anorector inhibitory reflex in man, relaxing the IAS.
The link between IAS hypertonicity and spasm and the presence of an anal fissure has been established. Patients with chronic anal fissure have a significantly higher mean maximum resting anal pressure than controls and anodermal blood flow in chronic anal fissure patients was significantly lower than in controls.
In patients whose fissures healed following a sphincterotomy, a reduction in anal pressure and improvement in anodermal blood flow was demonstrated, providing further evidence for the ischaemic nature of anal fissure. Topical application of a NO donor (glyceryl trinitrate) relaxes the anal sphincter, resulting in a reduction of anal pressure and an improvement in anoderm blood flow.
Clinical trials - pharmacokinetic properties: The volume of distribution of glyceryl trinitrate is about 3 L/kg and is cleared from this volume at extremely rapid rates, with a resulting serum half-life of about 3 minutes. The observed clearance rates (close to 1 L/kg/min) greatly exceed hepatic blood flow. The known sites of extrahepatic metabolism include red blood cells and vascular walls. The initial products in the metabolism of glyceryl trinitrate are inorganic nitrate and the 1,2 and 1,3-dinitroglycerols. The dinitrates are less effective vasodilators than glyceryl trinitrate, but they are longer lived in the serum. Their contribution to the relaxation of the internal anal sphincter is unknown. The dinitrates are further metabolised to non-vasoactive mononitrates and ultimately to glycerol and carbon dioxide. In six healthy subjects, the average bioavailability of glyceryl trinitrate applied to the anal canal as a 0.2% ointment was approximately 50% of the 0.75 mg dose.

For the treatment of anal fissure and relief of the symptoms associated with anal fissure. For relief of pain and to aid wound healing as part of post-operative management following haemorrhoidectomy.

Adults: Insert a 1 to 1.5 cm strip of ointment (see measurement on box) into the anal canal, either with the finger or an applicator.
The ointment is to be applied 3 times daily or more frequently on the advice of a medical practitioner. Close the tube tightly, immediately after each use.
For anal fissure, treatment with Rectogesic should be continued for 2 - 4 weeks, with assessment by a medical practitioner after 2 weeks. For haemorrhoidectomy, treatment with Rectogesic should be continued for a minimum of 2 weeks, with assessment by a medical practitioner after the initial 2 weeks.
Adverse effects: If headache, fainting or dizziness are observed, treatment should cease for a minimum of 8 hours and then the dosage halved. Simple analgesics such as paracetamol may be helpful for headaches. If headaches are severe and persist, cease administration.
Nitrate-free period: A daily 'nitrate-free period' of 12 hours is required during treatment with Rectogesic to avoid the development of tolerance. This would normally be overnight.
Where Rectogesic is used concurrently with another nitric oxide donor, the nitrate-free period should correspond with the nitrate-free period already applying to the nitric oxide donor (e.g. this may be during the day for those angina patients who require overnight treatment with glyceryl trinitrate patches).
The frequency of use of Rectogesic may need to be reduced to twice daily when it is used in conjunction with another nitric oxide donor, to reduce the likelihood of adverse systemic effects and to allow an adequate nitrate-free period for the other nitric oxide donor product.
Use in children: Safety and effectiveness in children and adolescents under 18 years of age have not been established.

Headache, fainting or dizziness are the most common indication of overdosage. When these symptoms are observed, treatment should cease for a minimum of 8 hours and then the dosage halved. Simple analgesics such as paracetamol may be helpful for headaches. If headaches are severe and persist, cease administration.
Accidental overdosage of Rectogesic may result in hypotension and reflex tachycardia. Excessive dosage may give rise to methaemoglobinaemia.

Hypersensitivity to glyceryl trinitrate or any of the excipients in the formulation.
Severe anaemia, glaucoma, pregnancy, lactation, hypotension, increased intracranial pressure, idiosyncrasy to glyceryl trinitrate, migraine or recurrent headache, aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy, constrictive pericarditis or pericardial tamponade, postural hypotension, and uncorrected hypovolaemia.
Glyceryl trinitrate should not be coadministered with Viagra (sildenafil citrate), Cialis (tadalafil) or Levitra (vardenafil) as these drugs may potentiate the hypotensive effects of organic nitrates.

Concomitant use with other nitrates: Concurrent treatment with Rectogesic and anti-anginal products containing nitrates may interfere with 'nitrate free period' dosage arrangements for the anti-anginal drug. If a patient is already using glyceryl trinitrate or other nitrates for cardiac disease then using Rectogesic could potentially cause tachyphylaxis by eliminating the nitrate free interval. Where another nitric oxide donor anti-anginal drug is used concurrently, Rectogesic should not be used during the nitrate-free dosage arrangements for that product.
Use in renal/hepatic impairment: No specific information concerning the usage of Rectogesic in renal or hepatic impairment is available.
Other precautions: GTN can interfere with the measurement of catecholamines and vanilmandelic acid in the urine, as it increases the excretion of these substances.
Treatment should be stopped if anal bleeding increases.
Patients should be advised to change position slowly when changing from lying or sitting to upright to minimise postural hypotension, especially in patients with low blood volume and under diuretic treatment.
Paradoxical bradycardia and increased angina pectoris may accompany GTN induced hypotension.
If the physician elects to use GTN in patients with acute myocardial infarction or congestive heart failure, careful monitoring should be undertaken to avoid hypotension and tachycardia.
Effect on ability to drive or operate machinery: As patients may experience faintness and/or dizziness, particularly the elderly, reaction time when driving or operating machinery may be impaired especially at the start of treatment.
Use in Pregnancy & Lactation: See USE IN PREGNANCY & LACTATION section for further information.
Use in Children: The safety and effectiveness of glyceryl trinitrate in children have not been established.
Use in the Elderly: No specific information concerning the usage of Rectogesic in the elderly is available.

Use in pregnancy (Category B2): The safety of Rectogesic in pregnancy has not been established. Therefore, Rectogesic should not be given to pregnant women (see Contraindications).
Use in lactation: It is not known whether glyceryl trinitrate is excreted in human milk. Therefore, Rectogesic should not be given to lactating women (see Contraindications).

Headache is the most common reaction to treatment with glyceryl trinitrate. These are usually mild and usually occur after the first few applications only. In a small number of patients headaches may be severe or persist. If headaches persist the dose should be reduced (see Dosage & Administration). If the headaches continue to occur or are severe, treatment should be withdrawn. Rectogesic may also cause fainting or dizziness, particularly in the elderly.
Incontinence is also a possible adverse reaction, although this has not been reported to date, and should be completely reversible on withdrawal of the drug.
Clinical studies: In patients treated with Rectogesic 4 mg/g Rectal Ointment, the most common treatment related adverse reaction was dose-related headache which occurred with an incidence of 57%.
Adverse reactions from clinical studies are displayed by system organ class in the table as follows. Within the system organ class, the adverse reactions are listed by frequency using the following groupings: very common (> 1/10), common (>1/100 <1/10), uncommon (>1/1000 <1/100). (See table.)

Click on icon to see table/diagram/image

Adverse reactions to glyceryl trinitrate 2% ointment (used in the prophylaxis of angina pectoris) are generally dose-related and almost all of these reactions are the result of vasodilator activity. Headache, which may be severe, is the most commonly reported side effect. In the Phase III clinical trials with Rectogesic 4 mg/g Rectal Ointment the incidence of mild, moderate and severe headache was 18%, 25% and 20%. Patients with a previous history of migraine or recurrent headache were at a higher risk of developing headache during treatment. Headache may be recurrent with each daily dose, especially at higher doses. Headache can be treated with mild analgesics e.g. paracetamol and in general is reversible on discontinuation of treatment.
Transient episodes of light-headedness, occasionally related to blood pressure changes, also may occur. Hypotension occurs infrequently, but in some patients may be severe enough to warrant discontinuation of therapy. Syncope, crescendo angina and rebound hypertension have been reported but are uncommon. Allergic reactions to glyceryl trinitrate are uncommon, and the great majority of those reported have been cases of contact dermatitis or fixed drug eruptions occurring in patients receiving glyceryl trinitrate in ointments or patches. There have been a few reports of genuine anaphylactoid reactions and these reactions can probably occur in patients receiving glyceryl trinitrate by any route. Extremely rarely, ordinary doses of organic nitrates have caused methaemoglobinaemia in normal-seeming patients. Flush has been observed as a rare adverse reaction for other products containing glyceryl trinitrate.

Interaction with other drugs: Concomitant use of alcohol may enhance vascular effects.
Concomitant treatment with other vasodilators, calcium channel blockers, ACE inhibitors, and beta-blockers may potentiate the blood pressure lowering effects of Rectogesic.
Acetyl cysteine may potentiate the vasodilatory effects of glyceryl trinitrate.
Concomitant treatment with heparin leads to a decrease in heparin efficacy. Close monitoring of blood coagulation parameters is necessary and the dose of heparin has to be adapted accordingly. After withdrawal of Rectogesic there may be an abrupt increase in PPT. In this case reduction of heparin dosage may be necessary.
Concurrent administration of glyceryl trinitrate may cause a reduction of the thrombolytic activity of alteplase.
Co-administration of Rectogesic with dihydroergotamine may increase the bioavailability of dihydroergotamine and lead to coronary vasoconstriction.
The possibility that the ingestion of acetylsalicylic acid and NSAIDs might diminish the therapeutic response to Rectogesic cannot be excluded.

Store below 25°C.

Anorectal Preparations

C05AE01 - glyceryl trinitrate ; Belongs to the class of muscle relaxants. Used in the topical treatment for the treatment of hemorrhoids and anal fissures.

POM