Dosing and uses of Rectiv (nitroglycerin rectal)
Adult dosage forms and strengths
ointment, intra-anaL
- 0.4% (4mg nitroglycerin/1g of ointment)
Chronic Rectal Fissure Pain
Indicated for treatment of moderate-to-severe pain associated with chronic anal fissures; consider use if conservative treatment for acute symptoms of anal fissure fails
Cover finger with plastic-wrap, disposable surgical glove or a finger cot and measure 1-inch (375 mg of ointment equivalent to 1.5 mg of nitroglycerin) length of ointment using dosing line provided with packaging
The covered finger is then gently inserted into the anal canal no further than to the first finger joint and applied circumferentially to the anal canaL
If this cannot be achieved due to pain, application of the ointment should be made directly to the outside of the anus
May be applied intra-anally q12h until pain abates, not to exceed treatment duration of 3 weeks
Storage
Do not store above 25°C
Do not freeze
Keep the tube tightly closed
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
Clinical studies did not include sufficient numbers of individuals aged 65 yr or older to determine whether they respond differently from younger individuals
Clinical data from the published literature indicate that the elderly demonstrate increased sensitivity to nitrates, which may be therapeutic but also manifest by more frequent or severe hypotension and related dizziness or fainting
Increased sensitivity may reflect the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy common in elderly individuals
Rectiv (nitroglycerin rectal) adverse (side) effects
Frequency not defined
Headache
Dizziness
Lightheadedness
Nausea
Vomiting
Hypotension, including orthostatic hypotension
Allergic reactions, flushing, and application site reactions (including drug rash and exfoliative dermatitis)
Methemoglobinemia may occur with organic nitrates, particularly in the setting of overdose
Warnings
Contraindications
Hypersensitivity to nitroglycerin or to any of the excipients or idiosyncratic reactions to other organic nitrates
Use within a few days of selective PDE-5 inhibitors (eg, sildenafil, tadalafil, vardenafil); as these may potentiate hypotensive effects of organic nitrates; the time course of the interaction appears to be related to the PDE-5 inhibitor half-life
Increased intracranial pressure (eg, head trauma, cerebral hemorrhage) or inadequate cerebral circulation
Severe anemia
Cautions
Caution with existing cardiovascular disorders; venous and arterial dilatation may occur and decrease venous blood return to the heart and reduce arterial vascular resistance and systolic pressure
Caution with blood volume depletion, existing hypotension, cardiomyopathies, CHF, acute MI, or poor cardiac function for other reasons
Headache: Nitroglycerin produces dose-related headaches which may be severe
Additive hypotensive effects may occur when coadministration with nitric oxide (NO) donors (eg, long-acting nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, amyl nitrite, butyl nitrite), antihypertensive drugs, beta-adrenergic blockers, and calcium channel blockers
Beta-blockers blunt the reflex tachycardia produced by nitroglycerin without preventing its hypotensive effects
Coadministration with aspirin may increase nitroglycerin maximum serum concentration and AUC
Alcohol may enhance nitroglycerin’s vasodilating effects
Avoid use in patients with hypertrophic cardiomyopathy
Caution when coadministration with t-PA, heparin, and ergotamine
May precipidate or aggravate intracranial pressure
Pregnancy and lactation
Pregnancy category: C
Lactation: Unknown whether distributed in breast milk/use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Rectiv (nitroglycerin rectal)
Mechanism of action
Organic nitrate; nitric oxide released from nitroglycerin elicits internal anal sphincter relaxation; reduces sphincter tone and resting intra-anal pressure
The smooth muscle relaxation is a result of guanylate cyclase activation and resulting increased cyclic GMP in smooth muscle and other tissues causing myosin dephosphorylation; this ultimately results in vasodilatation
Hypertonicity of the internal but not the external anal sphincter is a predisposing factor in the formation of anal fissures and associated spasm; hypertonicity of the IAS may thereby decrease blood flow and cause ischemia to this region
Absorption
Bioavailability: 50% (with application of 0.75 mg dose of 0.2% ointment)
Distribution
Protein Bound: 60% (IV)
Vd: 3 L/kg (IV)
Metabolism
Metabolized by liver reductase enzyme to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate; extrahepatic metabolism include red blood cells and vascular walls
Enzyme substrate, inhibitor, inducer Metabolites: Inorganic nitrate and 1,2 and 1,3-dinitroglycerols (partially active); the dinitrates are further metabolized to nonvasoactive mononitrates and ultimately to glycerol and carbon dioxide
Elimination
Half-life (mean): 2-3 minutes
Total body clearance: 13.6 L;/min
Metabolism is primary route of drug elimination
