Index of drugs

Treatment of breakthrough pain (BTP) in adult patients with cancer who undergo chronic opioid pain treatment undergo opioid maintenance therapy.
Breakthrough pain is a transient acute exacerbation of pain, overlapping with chronic pain. Patients undergoing opioid maintenance therapy are patients receiving at least 60 mg oral morphine daily, at least 25 μg transdermal fentanyl / h, at least 30 mg oxycodone / day, at least 8 mg oral hydromorphone / day or an equivalent dose of another opioid medication by a week or more.

1 tabl buccal coat contains 100 μg, 200 μg, 400 μg, 600 μg or 800 μg fentanyl citrate (1 table 100 μg contains 10 mg sodium, 1 table 200 μg, 400 μg, 600 μg or 800 μg contains 20 mg sodium) .

Fentanyl is an opioid analgesic drug that interacts mainly with the opioid μ receptor. Its basic healing effect is based on anesthesia and calming. Secondary pharmacological effects are: respiratory depression, bradycardia, hypothermia, constipation, miosis, physical dependence and euphoria. The analgesic effect of fentanyl is related to its plasma level; effective concentration and the concentration at which toxicity occurs increase with increasing tolerance to opioids. Fentanyl causes dose-dependent respiratory depression. The risk of its occurrence is lower in patients undergoing chronic opioid therapy because these patients will develop tolerance to respiratory depression caused by opioids. After administration to the oral mucosa, fentanyl is rapidly absorbed and its absolute bioavailability is 65%. About 50% of the total administered dose is rapidly absorbed through mucous membranes and becomes systemically available. The other half of the total dose is swallowed and slowly absorbed from the digestive tract. Approximately 30% of the amount swallowed (50% of the total dose) avoids elimination as a result of first pass through the liver and intestine and becomes available systemically. Fentanyl undergoes initial rapid distribution characterized by a balance between plasma and tissues with high vascular flow (brain, heart and lungs). Then fentanyl is redistributed to the space between deep tissues (muscle and fat) and plasma. The binding of fentanyl to plasma proteins is 80-85%. The main binding protein is alpha-1-acid glycoprotein. Fentanyl is metabolized in the liver and intestinal mucosa to norfentanyl (pharmacologically inactive) by the CYP3A4 isoform. Metabolites are mainly excreted in the urine, whereas excretion in the faeces is lower. T_0,5 the final phase of excretion is about 22 hours.

Hypersensitivity to the active substance or to any of the excipients. Use in patients who do not receive opioid maintenance because of the increased risk of respiratory depression. Acute respiratory depression or acute obstructive pulmonary disease. Treatment of acute pain other than breakthrough pain.

The long-term opioid therapy used to treat persistent pain should be stabilized before starting treatment, and the patient should be treated for long-term opioid therapy during treatment. As with all opioids, there is a risk of respiratory depression of clinical significance associated with the use of fentanyl; choosing the wrong patient for treatment with both the preparation and other medicines containing fentanyl (e.g., patients not treated with maintenance opioid therapy) and / or inadequate dosing led to death of the patient. The product should only be used as indicated. Patients should be closely monitored during the dose selection process. Special care should be taken when selecting the dose in patients with not severe severe obstructive pulmonary disease or other conditions that predispose them to respiratory depression, in patients with moderate or severe liver or kidney failure, and in elderly patients.The product should be used with caution in patients who may be particularly susceptible to intracranial effects of CO-arrest₂, such as those that cause elevated intracranial pressure or disturbances in consciousness. Opioids may interfere with the clinical treatment of a patient with head injury and should only be used if there are clinical grounds for it. Particularly cautiously used in patients with previously diagnosed bradyarrithms. Use with caution in patients with hepatic or renal failure and in patients with hypovolaemia or hypotension. The safety and efficacy of the preparation in children and adolescents under 18 years have not been established. The preparation contains sodium - this should be taken into account in patients who control the sodium content of the diet.

It should not be used during pregnancy unless clearly necessary. As a result of long-term use, fentanyl may cause the newborn to develop withdrawal syndrome. It is recommended that fentanyl should not be used during delivery (including caesarean section) as it passes through the placenta of the mother and may cause respiratory depression in the fetus. If administered, the antidote should be ready for use. Fentanyl passes into breast milk and may cause sedation and respiratory depression in a breast-fed child. Fentanyl should not be used in breast-feeding women and breastfeeding should not be restarted for at least 5 days after the last administration of fentanyl.

The most serious side effects are respiratory depression (potentially leading to breathlessness or respiratory arrest), circulatory depression, hypotension and shock. Patients should be closely monitored for their occurrence. Very common: pain and dizziness, nausea, vomiting, reactions at the injection site, such as bleeding, pain, ulceration, irritation, paresthesia, lack of sensation, erythema, swelling, swelling and blisters. Common: weight loss, tachycardia, anemia, neutropenia, anorexia, dysgeusia, drowsiness, lethargy, tremor, sedation, hypoaesthesia, migraine, shortness of breath, sore throat and larynx, constipation, inflammation or dry mouth, diarrhea, abdominal pain , gastro-oesophageal reflux, stomach discomfort, dyspepsia, toothache, pruritus, hyperhidrosis, rash, muscle pain, back pain, oral candidosis, falls, hypotension, peripheral edema, fatigue, weakness, withdrawal syndrome, chills, depression, anxiety, confusion, insomnia. Uncommon: decreased platelet count, increased heart rate, decreased hematocrit, decreased hemoglobin, bradycardia, thrombocytopenia, decreased level of consciousness, attention disorders, disturbances of balance, dysarthria, visual disturbances, congestion of the eyes, blurred vision, limited visual acuity, dizziness, tinnitus, hearing ailments, respiratory depression, sleep apnea syndrome, intestinal obstruction, mouth ulcers, hypoaesthesia of the mouth, oral complaints, discoloration of the oral mucosa, oral soft tissue complaints, swelling of the tongue, blisters on the tongue, pain gums, tongue ulcers, tongue complaints, oesophagitis, cracked lips, tooth diseases, urinary retention, cold sweats, facial swelling, general itching, baldness, muscle tremors, muscle weakness, pharyngitis, erythema, hot flushes, apathy, slowing down, discomfort in the chest ej, feeling unwell, nervousness, feeling thirsty, feeling cold, feeling hot, widening the bile ducts, euphoric state, nervousness, hallucinations, visual hallucinations, mental changes, addiction to the drug, disorientation. Rare: cognitive impairment, motor disorders, eye disorder, photopsy, bladder changes of the oral mucosa, dry lips, nail fragility, hypersensitivity, hypogonadism, pimples in the mouth. Frequency unknown: loss of consciousness, convulsions, stopping breathing, fever. Tolerance, physical and / or psychological dependence can develop after the administration of opioids such as fentanyl. In connection with the fentanyl administered through the mucous membranes symptoms of opioid withdrawal syndrome were observed, such as nausea, vomiting, diarrhea, anxiety, chills, tremors and sweating. Loss of consciousness and respiratory arrest were observed with overdose.Hypersensitivity reactions included rash, erythema, swelling of the lips and face, and urticaria.

Treatment should be initiated and conducted by a physician experienced in the use of opioid drugs in patients with cancer. One should remember about the possibility of abuse of fentanyl. Two different medicines containing fentanyl should not be prescribed at the same time, and patients should remove all other fentanyl medicines prescribed for the treatment of BTP before starting treatment with Fentanyl. The number of tablets available to the patient at any time should be as small as possible to prevent tangling and potential overdose. The dose should be adjusted individually until an effective dose is obtained, which will ensure adequate analgesia and with acceptable severity of side effects. Patients should be closely monitored until an effective dose is reached. Adults.Ddose titration in patients who have not changed therapy with other fentanyl-containing medicines. The initial dose should be 100 μg, increased as needed, in the range of tablets available (100 μg, 200 μg, 600 μg, 800 μg).Dose adjustment in patients who have changed therapy with other fentanyl-containing formulations. Due to the different profiles of absorption, the change of therapy can not be made in a 1: 1 ratio. When changing treatment with another oral drug containing fentanyl citrate, the dosage of the preparation should be independently selected due to significant differences in the bioavailability of various drugs. However, these patients may include an initial dose of more than 100 μg.Dose selection method. If during the dose selection process within 30 minutes of giving 1 tablet adequate analgesia will not be obtained, a second tablet of the same strength may be given. If treatment of a breakthrough pain episode (BTP) requires more than one tablet, consider increasing the dose to the Next higher available strength of the preparation for the treatment of another BTP episode. During the selection of the dose, different tablets may be used: up to 4 tablets with a strength of 100 μg or up to 4 tablets of 200 μg may be used to treat one BTP episode, as shown in the diagram below. If the initial 100 μg tablet turns out to be ineffective, you can take two 100 μg tablets to treat another BTP episode; it is recommended that one tablet be placed on each side of the mouth; if this dose is considered effective, treatment of subsequent episodes of BTP can be continued with one 200 μg tablet. If one 200 μg tablet (or two 100 μg tablets) is not considered effective, the patient may use two 200 μg (or four 100 μg) tablets to treat another BTP episode; it is recommended to place two tablets on each side of the mouth; if this dose is considered effective, treatment of subsequent episodes of BTP can be continued with one 400 μg tablet. For the selection of doses up to 600 μg and 800 μg, 200 μg tablets should be used. Doses exceeding 800 μg were not evaluated in clinical trials. You should not use more than two tablets for the treatment of one BTP episode, with the exception of the dose selection process using up to four tablets as described above. When adjusting the dose, patients should wait at least 4 hours before starting treatment of the next BTP episode.Maintenance treatment. Once determined in the effective dose selection process, patients should continue to use this dose as one tablet of a given strength. The severity of breakthrough pain in episodes may change and you may need to increase your dose over time due to the progression of your cancer. In these cases, a second tablet of the same strength may be used. If the second tablet of the drug was needed for several subsequent episodes, the dose of the preparation should be adjusted again in the maintenance treatment. For maintenance treatment, patients should wait at least 4 hours before starting treatment for the next BTP episode.Dose adjustment. The maintenance dose should be increased if the patient had to use more than one tablet during several consecutive BTP episodes. Re-adjusting the dose is based on the same principles as the method of dose selection. It may be necessary to re-adjust the dose in adjuvant therapy with opioid medicines if patients report more than four episodes of BTP within 24 hours. Discontinuation of therapy. The preparation should be discontinued immediately if the patient no longer has breakthrough pain episodes. The treatment of persistent underlying pain should be carried out as directed. If it is necessary to discontinue all opioid medicines, the patient should be carefully monitored to manage the risk of acute withdrawal symptoms.Special groups of patients. Patients with moderate or severe hepatic or renal impairment should be cautious. In patients> 65 years, there is a tendency to select an effective dose lower than the dose used in younger patients; it is recommended to take special care when choosing a dose. The safety and efficacy of the preparation in children from 0 to 18 years have not been established. Patients with dry mouth are advised to drink water before taking the medicine to moisten the mouth; if it does not cause the tablets to fizz properly in the mouth, a change in treatment may be recommended.Way of giving. The tablet starts to fizzle in a humid environment, patients should be instructed not to open the blister until they are ready to place the tablet in the mouth and to open the blister in accordance with the instructions in the patient leaflet (when opening the blister there is a risk of damaging the tablet) . Do not crush or divide the tablet. After removing the tablet from the blister, it should be placed immediately in the mouth under the cheek (next to the molar, between the cheek and the gum). The tablets should not be sucked, chewed or swallowed, as this would result in a lower plasma concentration. The tablet should be placed and kept in the mouth for a sufficient time to dissolve, which usually takes about 14-25 minutes. The tablet may optionally be sublingually administered. After 30 min, if the remains of the tablet are still present in the mouth, they can be swallowed and drunk with a glass of water. While the tablet is in the mouth, patients should not eat or drink. In the case of irritation of the oral mucosa, it is recommended to change the position of the tablet within the oral cavity under the cheek.