Retrosin® Ointment which contains the active substance Nitroglycerin.
Nitroglycerin belongs to a group of medicines called organic nitrates. The
ointment will help to relieve the symptom of pain caused by chronic anal
fissures. An anal fissure is a tear in the skin lining the anal canal. Topical
application of Nitroglycerin to the anal canal reduces the anal pressure and
increases the blood flow, thereby reducing pain.

Retrosin® 4 mg/g Ointment is for Rectal Use.
Always use this medicine exactly as your doctor has told you. Check with your doctor
or pharmacist if you are not sure. The recommended dose is approximately
375 mg of ointment (approximately 1.5 mg Nitroglycerin) applied to the
anal canal every 12 hours.

A finger covering, such as cling film or a finger cot, may be placed on the
finger to be used to apply the ointment. Finger cots can be obtained from
your local pharmacy or surgical supplies retailer, or cling film from your
local store. The covered finger is placed alongside the 2.5 cm dosing line,
which is provided on the outside carton, and a strip of ointment the length
of the line is expressed onto the end of finger by gently squeezing the tube.
Gently insert the ointment into the anal canal using the finger. The finger
with the ointment must be inserted to the first finger joint (approximately 1
cm) into the anus. Apply the ointment every twelve hours as directed by
your doctor and do not exceed the dose. Wash hands after use and dispose
of the finger cot or plastic wrap (not down the toilet). Treatment may be
continued until the pain goes away, or for up to a maximum 8 weeks. If your
anal pain does not get better after using Retrosin® you should talk to your
doctor again to check that something else is not causing the pain.

Do not use Retrosin® Ointment if: • If you are allergic to Nitroglycerin or to similar medicine • If you are allergic to any of the other ingredients in the product (listed in section 6) • If you suffer from low blood pressure • If you suffer from heart or blood vessel disorders • If you suffer from closed-angle glaucoma – a condition where pressure inside the eye rises rapidly causing loss of vision • If you suffer from migraine or recurrent headaches • If you suffer from increased intracranial pressure or high pressure within your skull (e.g. head injury or cerebral hemorrhage - bleeding from a ruptured blood vessel in the brain that can be fatal without prompt medical treatment. Cerebral hemorrhage is commonly referred to as a type of stroke) or inadequate cerebral circulation (low volume of blood circulation within your brain). • If you suffer from anemia (low iron content in your blood) • If you are taking any of the following medicines for erectile dysfunction such as sildenafil citrate, tadalafil, vardenafil; medicines for angina or heart pain such as glyceryl Trinitrate (GTN), isosorbide dinitrate, amyl or butyl nitrite; medicines for high blood pressure or depression (tricyclic antidepressants), acetylcysteine or alteplase.

If you suffer from liver or kidney disease
• If you are to be given heparin, close monitoring of your blood will be required as your dose of heparin may need to be altered. Please discuss with your doctor before stopping Retrosin®
• If you also have hemorrhoids (piles) and notice more bleeding than usual, you should stop using Retrosin® and discuss this with your doctor
• If you get severe headaches when using Retrosin®, please tell your doctor. Your doctor will decide if you need to use a different amount of Retrosin®, or stop using it completely.
• Retrosin® may lower your blood pressure. When getting up from a lying or sitting position, you should get up slowly, otherwise you might feel faint. Your blood pressure is more likely to be lowered if you drink alcohol whilst you are using Retrosin®.

The following medicines may increase the blood pressure lowering effect of Retrosin®
▪ Medicines for depression (tricyclic anti-depressants).
▪ Medicines for erectile dysfunction (male impotence) (sildenafil citrate, tadalafil, vardenafil).
▪ Medicines for high blood pressure
▪ Diuretics ("water tablets").
▪ Commonly used tranquillizers
▪ Medicines used to treat heart problems (isosorbide dinitrate and amyl or butyl-nitrite)
Other Medicines
▪ Acetylcysteine may increase the effect of Retrosin® on blood flow

The effect of heparin (used to control blood clotting) may be decreased when used with Retrosin®
▪ The effect of alteplase (used to treat heart problems) may be decreased when given at the same time as Retrosin®
▪ Taking Retrosin® with dihydroergotamine (used to treat migraine) may increase the action of dihydroergotamine and lead to coronary vasoconstriction (narrowing of blood vessels in the heart causing slower blood flow).
▪ Acetylsalicylic acid (aspirin) and non-steroidal anti-inflammatory drugs (certain types of painkillers) might alter the therapeutic effect of Retrosin®.
▪ Retrosin® with alcohol Be careful about drinking alcohol as the ointment may affect you more than usual.

Pregnancy
Take your doctor advice before using Retrosin® Ointment.
Breast feeding
It is not known whether nitroglycerin is excreted in human milk. Caution should be exercised when Retrosin® is administered to a nursing woman.

No studies on the effect on the ability to drive and use machines have been performed with Retrosin® Ointment. If you feel dizzy, sleepy or have blurred vision when you start to use the ointment, do not drive or work machinery until these effects have worn off.

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Serious side effects:
▪ Anaphylactoid reaction (allergic reaction, potentially fatal with face, lip, tongue or throat swelling, difficulty breathing, shortness of breath or collapse).

If you experience any of these symptoms stop using the ointment and seek medical attention immediately.
▪ Allergic skin reactions (potentially severe). If you have an allergic skin reaction stop using the ointment and seek medical attention.
Other Side Effects:
Very Common (may affect more than 1 in 10 people)
▪ Headaches, which may be severe. If you develop a headache as a side effect, wipe off any ointment. If the headaches are unpleasant, you may need to ask your doctor whether 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
▪ Vomiting
▪ Rectal bleeding, rectal disorder
▪ Anal discomfort, itching or burning of the anal canal
▪ Fast heart beat or palpitations
Rare (may affect up to 1 in 1,000 people)
▪ Faintness on standing up
Side effects of unknown frequency (frequency cannot be estimated from the available data)
▪ Light-headedness, fainting
▪ Low blood pressure
▪ Irritation, rash or pain at area of application
Other known side effects associated with Nitroglycerin products (frequency unknown)
▪ Flushing
▪ Unstable angina (chest pain)
▪ High blood pressure on stopping treatment
▪ Methaemoglobinaemia (symptoms are blue/purple coloration of the skin and shortness of breath).
To report any side effect(s):
• The National Pharmacovigilance Centre (NPC):
− SFDA Call Center: 19999
− E-mail: npc.drug@sfda.gov.sa
− Website: https://ade.sfda.gov.sa/

If you use more Retrosin® than you should
If you may have used more ointment than you should you may feel dizzy and light- headed. You may also have fast heart beats or palpitations. If you feel these symptoms wipe away any extra ointment and then talk to your doctor or pharmacist immediately.

Pharmacotherapeutic group: Muscle relaxants ATC Code: C05AE01
The principal pharmacologic action of glyceryl trinitrate is relaxation of vascular smooth muscle 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.

 

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.

Repeat Dose Toxicity
No systemic toxicity studies have been conducted with Rectogesic. Published data suggest that high oral doses of glyceryl trinitrate may have toxic effects (methaemoglobinaemia, testicular atrophy and aspermatogenesis) in long term treatment. However, these findings represent no special hazards for humans under the conditions of therapeutic use.
Mutagenicity and carcinogenicity
Data from preclinical studies with GTN indicate genotoxic effects in the repair deficient
S. typhimurium strain TA1535 only. Lifetime dietary administration of GTN to rodents led to the conclusion that nitroglycerin has no carcinogenic effects relevant for the therapeutic dose range in humans.
Reproductive Toxicity
Reproductive toxicity studies, in rats and rabbits with intravenous, intraperitoneal, and dermal administration of glyceryl trinitrate did not show any adverse effects on fertility or embryonic development at dosages which did not induce parental toxicity. No teratogenicity had been observed. In rats foetotoxic effects (decreased birth weights) were seen at dosages above 1 mg/kg/d (i.p.) and 28 mg/kg/d (dermal) after in utero exposure during foetal development.

 

Wool fat Span60
Sorbitan sesquioleate
Hard paraffin White soft paraffin

Not applicable

2 years.

Keep out of the reach of children.
▪ Store below 30˚C
▪ Do not Freeze
▪ Keep the tube tightly closed
▪ Once opened use up the ointment within 8 weeks
▪ Do not use this medicine after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month.

Aluminum collapsible tube 25 mm diameter screw capped with membrane, and HDPE white screw cap, with leaflet & box.

Do not Freeze
▪ Keep the tube tightly closed
▪ Once opened use up the ointment within 8 weeks