Fentanyl is indicated for the treatment of breakthrough pain in cancer patients who are already receiving and are tolerant to opioid therapy for persistent cancer-related pain. Patients considered opioid-tolerant are those who have been taking at least 60 mg of oral morphine per day, 25 mcg/hour of transdermal fentanyl, 30 mg of oxycodone daily, 8 mg of oral hydromorphone daily, or an equivalent dose of another opioid for one week or longer.

Fentanyl is a potent opioid analgesic that primarily acts on mu-opioid receptors, while also interacting with kappa and delta opioid receptors. These receptors are widely distributed in the brain, spinal cord, and other body tissues. Its main pharmacological effects occur within the central nervous system, producing strong analgesia and sedation. Fentanyl increases pain tolerance and reduces the perception of pain, although the sensation of pain may still be present. In addition to pain relief, fentanyl may cause mood changes such as euphoria or dysphoria, as well as drowsiness. It also depresses the respiratory centers, suppresses the cough reflex, and causes constriction of the pupils.

Oral-

• Starting Dose: The initial dose of Fentanyl should be 100 mcg.
• Re-dosing patients within a single episode: Dosing may be repeated once during a single episode of breakthrough pain if pain is not adequately relieved by one Fentanyl dose. Re-dosing may occur 30 minutes after the start of administration of Fentanyl and the same dosage strength should be used.
• Increasing the dose: Titration should be initiated using multiples of the 100 mcg Fentanyl tablet. Patients requiring to titrate above 100 mcg can be instructed to use two 100 mcg tablets (one on each side of the mouth in the buccal cavity). If this dose is not successful in controlling the breakthrough pain episode, the patient may be instructed to place two 100 mcg tablets on each side of the mouth in the buccal cavity (total of four 100 mcg tablets). Titrate above 400 mcg by 200 mcg increments bearing in mind using more than 4 tablets simultaneously has not been studied and it is important to minimize the number of strengths available to patients at any time to prevent confusion and possible overdose. To reduce the risk of overdose during titration, patients should have only one strength of Fentanyl tablet available at any one time.
• Dosage Adjustment: Generally, the dose of Fentanyl should be increased when patients require more than one dose per breakthrough pain episode for several consecutive episodes.

Injection-

• Fentanyl injection can be administered intravenously either as a bolus or by infusion & by intramuscular route also. The dose of fentanyl should be individualized according to age, body weight, physical status, underlying pathological condition, use of other drugs and type of surgery and anesthesia.
• Doses in excess of 200mcg are for use in anesthesia only. As a premedicant, 1-2 ml fentanyl may be given intramuscularly 45 minutes before induction of anesthesia. After IV administration in unpremedicated adult patients, 2ml fentanyl may be expected to provide sufficient analgesia for 10-20 minutes in surgical procedures involving low pain intensity. 10 ml fentanyl injected as a bolus gives analgesia lasting about one hour. The analgesia produced is sufficient for surgery involving moderately painful procedures. Giving a dose of 50mcg/kg fentanyl will provide intense analgesia for some four to six hours, for intensely stimulating surgery.
• Fentanyl may also be given as an infusion. In ventilated patients, a loading dose of fentanyl may be given as a fast infusion of approximately 1mcg/kg/min for the first 10 minutes followed by an infusion of approximately 0.1 mcg/kg/min. Alternatively the loading dose of fentanyl may be given as a bolus. Infusion rates should be titrated to individual patient response; lower infusion rates may be adequate. Unless it is planned to ventilate post operatively, the infusion should be terminated at about 40 minutes before the end of surgery.
• Lower infusion rates, e.g. 0.05-0.08 mcg/kg/min, are necessary if spontaneous ventilation is to be maintained. Higher infusion rates (up to 3 mcg/kg/min) have been used in cardiac surgery. Fentanyl is chemically incompatible with the induction agents thiopentone & methohexitone because of wide differences in pH values.
• Use in elderly and debilitated patients: It is wise to reduce the dosage in the elderly and debilitated patients. The effect of the initial dose should be taken into account in determining supplemental doses.

Transdermal-

Intractable chronic pain:

• Adult: Patches deliver fentanyl in doses that range from: 12-100 mcg/hr. Doses should be individually titrated based on previous use of opioids. Opioid-naïve patients: Initially, ≤25 mcg/hr; it is recommended to initially titrate w/ low doses of short-acting opioids before starting fentanyl patches. Patients receiving a strong opioid analgesic: Initial dose should be based on the previous 24-hr opioid requirements. During transfer to fentanyl patches, previous opioid treatment should be phased out gradually. If patient requires doses >100 mcg/hr, >1 patch may be used; consider alternative or additional therapy if doses >300 mcg/hr are required. Replace patch every 72 hr and apply the new patch to a different site; avoid using the same area of skin for a few days.
• Elderly: Dose reduction may be needed.

Tablet Administration: Patients should remove the tablet from the blister strip and immediately place the entire tablet in the buccal cavity (above a rear molar, between the upper cheek and gum). Patients should not attempt to split the tablet. The tablet should not be chewed or swallowed, as this will result in lower plasma concentrations than when taken as directed. The tablet should be left between the cheek and gum until it has disintegrated, which usually takes approximately 14-25 minutes. After 30 minutes, if remnants from the tablet remain, they may be swallowed with a glass of water.

Co-administration of Fentanyl Citrate with antifungal agents, macrolide antibiotics, and CNS depressants such as ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, and nefazodone may increase or prolong its effects. Similarly, drugs like amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil may raise plasma levels of fentanyl, potentially leading to enhanced or prolonged adverse effects, including life-threatening respiratory depression.

Fentanyl Citrate is contraindicated for the management of acute or postoperative pain and should not be used in opioid non-tolerant patients. It is also contraindicated in patients with known hypersensitivity to fentanyl or any of its components.

Like other opioid analgesics, the most serious adverse effects include respiratory depression, apnea, muscle rigidity, myoclonic movements, and bradycardia. Respiratory depression is more likely with rapid intravenous administration and is rare with intramuscular use.

Pregnancy category C. Adequate and well-controlled studies in pregnant women are not available. Fentanyl should be administered during pregnancy only if the potential benefit outweighs the possible risk to the foetus. Fentanyl is excreted into human breast milk; therefore, it should not be used in breastfeeding women due to the risk of sedation and/or respiratory depression in the infant.

Opioid analgesics may impair mental and physical abilities required for tasks such as driving or operating machinery. Patients should be warned accordingly. Special caution is required when used with other CNS-active drugs.

Chronic Pulmonary Disease: Use cautiously in patients with COPD or conditions that increase the risk of respiratory depression.

Head Injury & Increased Intracranial Pressure: May mask neurological symptoms; use only when necessary.

Cardiac Disease: Intravenous fentanyl may cause bradycardia; use cautiously in patients with arrhythmias.

Hepatic & Renal Impairment: Use with caution due to liver metabolism and renal excretion.

Overdose may cause deep sedation, severe muscle rigidity, respiratory depression, and cyanosis. In such cases, oxygen should be administered and assisted ventilation provided. A narcotic antagonist such as naloxone should be readily available to manage respiratory depression.

Opioid analgesic

Store at 20–25°C and protect from light.