Opalmon Lima Prostaglandin Tablets 5μg: 100 tablets (オパルモン飠OPALMON Tablets) (Ono hand and foot numbness)

Lima prostaglandin tablets are used to relieve symptoms such as numbness, pain, and coldness in the hands and feet caused by poor blood circulation.

I. Basic Drug Information

1. Generic Name : Limaprost Alfadex Tablets
2. English name : Limaprost Alfadex Tablets
3. Product name : OPALMON® R Tablets (オパルモン tablets)
4. Dosage form : Tablets
5. Indications
   • It can improve ischemic symptoms such as ulcers, pain, and coldness associated with occlusive thromboangiitis obliterans.
   • It improves the subjective symptoms (lower limb pain, lower limb numbness) and walking ability associated with acquired lumbar spinal stenosis (patients with normal SLR test and bilateral intermittent claudication).
6. Element
   • Each tablet contains limaprost alpha cyclodextrin, calculated as limaprost, at a concentration of 5 μg.
   • The additives include dextrin 40, β-cyclodextrin, calcium carboxymethyl cellulose, light anhydrous silica, magnesium stearate, lactose water, and other substances.
7. Properties
   • Appearance: No special markings on the surface, back, or sides; diameter 6.5mm; thickness 2.9mm; weight approximately 95mg.
   • Color tone: white
   • Identification code: No special identification code
   • Physicochemical properties of the active ingredient: Limaprost alpha cyclodextrin is a white powder, readily soluble in water, sparingly soluble in methanol, extremely sparingly soluble in ethanol (99.5%), almost insoluble in ethyl acetate, and hygroscopic. Its chemical name is (2E)-7-{(1R,2R,3R)-3-hydroxy-2-[(1E,3S,5S)-3-hydroxy-5-methylnon-1-en-1-yl]-5-oxocyclopentyl}hept-2-enoic acid-α-cyclodextrin, with the molecular formula C₂₂H₃₆O₅・χC₃₆H₆₀O₃₀, and a molecular weight of 380.52 based on limaprost.

II. Usage and Dosage

1. Improvement of symptoms associated with thromboangiitis obliterans : Adults usually take 30 μg of lima prostol orally in 3 divided doses daily.
2. Improvement of symptoms associated with acquired lumbar spinal stenosis : Adults usually take 15 μg of lima prostol orally in 3 divided doses daily.

III. Taboos

IV. Precautions

1. Special populations
   • Patients with bleeding tendencies: This may exacerbate bleeding, so medication should be used with caution.
   • Pregnant women: Not for use (same as other prohibited items).
   • Breastfeeding women: The benefits of treatment and the nutritional benefits of breast milk should be considered comprehensively before deciding whether to continue breastfeeding or discontinue medication (in animal experiments, oral administration of the drug to lactating rats showed that the drug was transferred into breast milk).
   • Children, etc.: No clinical trials have been conducted for children and other populations, and the safety and efficacy of the drug are unclear.
2. Medication guidance
   • For patients with acquired lumbar spinal stenosis, it is necessary to closely monitor changes in symptoms and avoid blindly continuing medication.
   • This product is a prescription drug and should be used under the guidance of a physician or other doctor.
   • When the medication is packaged in PTP, patients should be instructed to remove it from the PTP blister pack before taking it to avoid accidental ingestion of the PTP blister pack, which could cause esophageal mucosal puncture, perforation, and serious complications such as mediastinitis.
   • This product is hygroscopic. Once opened, the aluminum-plastic packaging or medicine bottle should be kept away from moisture and used as soon as possible.
3. Medication storage : Store at room temperature; shelf life is 3 years.

V. Adverse Reactions

1. Allergic reaction
   • Incidence rate 0.1%~1%: rash, itching, etc.
   • Incidence rate below 0.1%: Urticaria.
   • Frequency of occurrence unknown: photosensitivity.
2. Digestive system reaction
   • Incidence 0.1%~1%: diarrhea, nausea, abdominal discomfort, abdominal pain, loss of appetite, heartburn.
   • Incidence rate below 0.1%: vomiting, abdominal distension, thirst, stomatitis.
   • Frequency of occurrence unknown: numbness of the tongue.
3. Other adverse reactions
   • Bleeding tendency (incidence rate less than 0.1%): bleeding.
   • Hematologic system (incidence rate less than 0.1%): anemia, thrombocytopenia.
   • Liver (incidence 0.1%~1%): Elevated AST and ALT levels are equivalent to abnormal liver function.
   • Circulatory system (incidence 0.1%~1%): palpitations; (incidence less than 0.1%): frequent occurrences, hypotension, cold extremities, and hypertension.
   • Nervous system (incidence 0.1%~1%): headache, dizziness; (incidence less than 0.1%): numbness, drowsiness, insomnia.
   • Other (occurrence rate 0.1%~1%): flushing, burning sensation; (occurrence rate less than 0.1%): general fatigue, chest pain, chest discomfort, limb pain, edema, breast swelling, tremor, hirsutism in the lower limbs, abnormal taste.
4. Serious adverse reactions : liver dysfunction, jaundice, which may be accompanied by symptoms such as significantly elevated AST and ALT. The frequency of these reactions is unknown. If any abnormalities are detected, the medication should be discontinued immediately and appropriate treatment measures should be taken.

VI. Drug Interactions

VII. Pharmacological effects

1. Moderating biomembrane function : No specific description of the direct effects is provided.
2. Improvement of metabolic abnormalities : No direct description of related effects is explicitly mentioned.
3. Regulating blood lipids : No specific description of its direct effects was provided.
4. Protect blood vessels
   • It has a strong vasodilatory and blood flow increasing effect, which can increase blood flow in the femoral artery and blood flow in the skin of the hind limb, and raise the skin temperature of the hind limb. Moreover, this blood flow increasing effect is not affected by lumbar sympathectomy. When administered orally to patients with thromboangiitis obliterans, it can raise the skin temperature of the peripheral side (dorsum of the foot and sole).
   • It has antithrombotic effects and can dose-dependently increase the threshold voltage for thrombosis in experiments on electrical stimulation-induced mesenteric artery thrombosis.
   • It can improve blood flow to nerve tissues, such as improving blood flow to nerve tissues in models of cauda equina compression and sciatic nerve ligation; it can also improve nerve function, inhibit the decrease in nerve conduction velocity, inhibit hyperalgesia, and improve gait disorders.
   • It has an inhibitory effect on platelets, inhibiting platelet adhesion and aggregation, increasing intracellular cAMP levels, and inhibiting thromboxane A₂ production.

VIII. Pharmacokinetics

1. absorb
   • In 40 healthy adults, after a single oral administration of 5 μg of this product (calculated as limaprost) on an empty stomach, the peak plasma concentration of the drug was reached after 0.333 hours, with a peak concentration of 1.55 pg/mL and an area under the curve (AUC₀₋∞) of 0.870 pg・hr/mL.
   • When rats were given [11β-³H] limaprost alpha cyclodextrin orally, the drug absorption rate reached 90%~95%.
2. Distribution : The drug protein binding rate in human plasma (0.023 mM concentration) was 95.8% (in vitro, ultrafiltration method).
3. Metabolism : After oral administration, the drug undergoes metabolic reactions such as oxidation, ω-terminal oxidation, five-membered ring isomerization, and C-9 carbonyl reduction. In vitro experiments show that this product does not inhibit the CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 molecules of human cytochrome P450.
4. excretion
   • When rats were given [11β-³H] limaprost alpha cyclodextrin orally, 75%–80% of the administered dose was excreted via bile. After enterohepatic circulation, approximately 30% was excreted in the urine and approximately 70% in the feces within 72 hours of administration.
   • In healthy adults, the elimination half-life of this product after a single oral dose is 0.511 hours.

IX. Clinical Research

1. Improvement of symptoms related to thromboangiitis obliterans
   • Domestic double-blind controlled trials have confirmed the effectiveness of this product in treating thromboangiitis obliterans.
   • Domestic clinical trials (including double-blind controlled trials): It was observed that this product can improve ischemic symptoms such as ulcers, pain and coldness associated with thromboangiitis obliterans, with an overall improvement rate of 56% (77/138 cases).
2. Improvement of symptoms related to acquired lumbar spinal stenosis
   • Domestic double-blind controlled trials have confirmed the effectiveness of this product in treating lumbar spinal stenosis.
   • Domestic clinical trials (including double-blind controlled trials): It was observed that this product can improve subjective symptoms such as lower limb pain and numbness and walking ability in patients with acquired lumbar spinal stenosis (SLR test normal, presenting with bilateral intermittent claudication), with an overall improvement rate of 56% (94/168 cases). The above evaluation is based on a 6-week dosing period.
3. Precautions : The effectiveness of this product in severe cases of acquired lumbar spinal stenosis, for which surgery is indicated, has not been established.

10. Packaging Specifications

• 100 tablets: 10 tablets (PTP) x 10, including desiccant; or 100 tablets/bottle, with padding, including desiccant.
• 210 tablets: 21 tablets (PTP) x 10, including desiccant.
• 500 tablets: 10 tablets (PTP) x 50, including desiccant; or 500 tablets/bottle, with padding, including desiccant.
• 1050 tablets: 21 tablets (PTP) x 50, including desiccant.

XI. Production Information

Manufacturer : Ono Pharmaceutical Co. , Ltd.

Company Address : 1-8-2 Kutaromachi, Chuo-ku, Osaka