Acetaminophen, caffeine, and dihydrocodeine

U.S. BRAND NAMES — Panlor® DC; Panlor® SS; ZerLor™
PHARMACOLOGIC CATEGORY Analgesic Combination (Opioid)
DOSING: ADULTS — Relief of pain: Oral:
Panlor® DC: 2 capsules every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 10 capsules/24 hours)
Panlor® SS, ZerLor™: 1 tablet every 4 hours as needed; adjust dose based on severity of pain (maximum dose: 5 tablets/24 hours)
DOSING: ELDERLY — Refer to adult dosing.
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule: Panlor® DC: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine bitartrate 16 mg
Tablet: Panlor® SS, ZerLor™: Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine bitartrate 32 mg
DOSAGE FORMS: CONCISE Capsule: Panlor® DC: Acetaminophen 356.4 mg, caffeine 30 mg, and dihydrocodeine 16 mg
Tablet: Panlor® SS, ZerLor™: Acetaminophen 712.8 mg, caffeine 60 mg, and dihydrocodeine 32 mg
GENERIC EQUIVALENT AVAILABLE — Yes: Tablet
USE — Relief of moderate to moderately-severe pain
ADVERSE REACTIONS SIGNIFICANT — Frequency not defined. Most common reactions with this combination include:
Central nervous system: Dizziness, drowsiness, lightheadedness, sedation
Dermatologic: Pruritus, skin reactions
Gastrointestinal: Constipation, nausea, vomiting
CONTRAINDICATIONS — Hypersensitivity to acetaminophen, caffeine, dihydrocodeine, codeine, or any component of the formulation; significant respiratory depression (in unmonitored settings); acute or severe bronchial asthma; hypercapnia; paralytic ileus
WARNINGS / PRECAUTIONS Concerns related to adverse effects: CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Hepatotoxicity: Acetaminophen may cause severe hepatic toxicity on acute overdose; in addition, chronic daily dosing in adults has resulted in liver damage in some patients. Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene-derivative opioid agonists (hydrocodone, hydromorphone, levorphanol, oxycodone, oxymorphone).
Disease-related concerns: Adrenal insufficiency: Use with caution in patients with adrenal insufficiency, including Addison's disease. CNS depression/coma: Use with caution in patients with CNS depression or coma. Drug abuse: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Tolerance, psychological and physical dependence may occur with prolonged use. Ethanol use: Use with caution in patients with alcoholic liver disease; consuming 3 alcoholic drinks/day may increase the risk of liver damage. G6PD deficiency: Use with caution in patients with known G6PD deficiency. Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur. Hepatic impairment: Use with caution in patients with severe hepatic impairment. Hypotension: Use with caution in patients with hypotension. Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture. Renal impairment: Use with caution in patients with severe renal impairment. Respiratory disease: Use with caution in patients with respiratory diseases including asthma, emphysema, and/or COPD. Seizure disorder: Use with caution in patients with a history of seizure disorder. Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues: MAO inhibitors: Use with caution with concurrent use of MAO inhibitors.
Special populations: Debilitated patients: Use with caution in debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Pediatrics: Safety and efficacy have not been established in children.
Other warnings/precautions: Caffeine: May cause CNS and cardiovascular stimulation, as well as GI irritation in high doses. Use with caution in patients with a history of peptic ulcer or GERD; avoid in patients with symptomatic cardiac arrhythmias. Dosage limit: Limit total acetaminophen dose to <4 g/day.
RESTRICTIONS — C-III
DRUG INTERACTIONS Acetaminophen: Substrate (minor) of CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A4; Inhibits CYP3A4 (weak)
Caffeine: Substrate of CYP1A2 (major), 2C9 (minor), 2D6 (minor), 2E1 (minor), 3A4 (minor); Inhibits CYP1A2 (weak), 3A4 (moderate)
Dihydrocodeine: Substrate of CYP2D6 (major)
Acetaminophen: See individual agents for associated interactions.
Caffeine: CYP1A2 inhibitors: May increase the levels/effects of caffeine. Example inhibitors include amiodarone, fluvoxamine, ketoconazole, and rofecoxib. CYP3A4 substrates: Caffeine may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, ergot derivatives, mirtazapine, nateglinide, nefazodone, tacrolimus, and venlafaxine. Quinolone antibiotics (specifically ciprofloxacin, norfloxacin, ofloxacin): Quinolones may increase the level/effects of caffeine.
Dihydrocodeine: CYP2D6 inhibitors: May decrease the effects of dihydrocodeine. Example inhibitors include chlorpromazine, delavirdine, fluoxetine, miconazole, paroxetine, pergolide, quinidine, quinine, ritonavir, and ropinirole. Quinidine: Quinidine may decrease the effects of dihydrocodeine.
ETHANOL / NUTRITION / HERB INTERACTIONS Ethanol: Excessive intake of ethanol may increase the risk of acetaminophen-induced toxicity. Ethanol may also increase CNS depression.
PREGNANCY RISK FACTOR — C (show table)
PREGNANCY IMPLICATIONS — Reproduction studies have not been conducted with this combination.
LACTATION — Enters breast milk/not recommended
BREAST-FEEDING CONSIDERATIONS — Acetaminophen and caffeine are both excreted in breast milk. Specific information for dihydrocodeine is not available; however, similar agents (eg, codeine, morphine) are excreted in breast milk.
PRICING — (data from drugstore.com)Capsules (Panlor DC) 356.4-30-16 mg (30): $29.99
Tablets (Panlor SS) 712.8-60-32 mg (30): $45.36
MECHANISM OF ACTION Acetaminophen inhibits the synthesis of prostaglandins in the central nervous system and peripherally blocks pain impulse generation; produces antipyresis from inhibition of hypothalamic heat-regulating center.
Caffeine is a CNS stimulant; use with acetaminophen and dihydrocodeine increases the level of analgesia provided by each agent.
Dihydrocodeine binds to opiate receptors in the CNS, causing inhibition of ascending pain pathways, altering the perception of and response to pain; produces generalized CNS depression