Panlor Tablets

PANLOR ® (acetaminophen, caffeine, and dihydrocodeine bitartrate) Tablets are supplied in tablets form for oral administration.
Each tablet contains:
Acetaminophen .................... 325 mg
Caffeine ................................ 30 mg
Dihydrocodeine bitartrate ........ 16 mg

Acetaminophen (4'-hydroxyacetanilide), a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

Caffeine (1,3,7-trimethylxanthine), a bitter, white crystalline powder or white glistening needles, is a central nervous system stimulant. It has the following structural formula:

Dihydrocodeine Bitartrate (4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol (+)-tartrate), an odorless, fine white powder is an opioid analgesic. It has the following structural formula:

In addition, each tablet also contains the following inactive ingredients: colloidal silicon dioxide, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, stearic acid.

PANLOR ® Tablets are contraindicated for:

• All children younger than 12 years of age [see WARNINGS and PRECAUTIONS]
• Post-operative management in children younger than 18 years of age following tonsillectomy and/or adenoidectomy [see WARNINGS and PRECAUTIONS].

PANLOR ® Tablets are also contraindicated in patients with:

• Significant respiratory depression [see WARNINGS]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS]
• Hypersensitivity to codeine, acetaminophen, or any of the formulation excipients. (e.g., anaphylaxis) [see WARNINGS]

Dihydrocodeine:
The most frequently observed adverse reactions include lightheadedness, dizziness, drowsiness, headache, fatigue, sedation, sweating, nausea, vomiting, constipation, pruritus, and skin reactions. With the exception of constipation, tolerance develops to most of these effects. Other reactions that have been observed with dihydrocodeine or other opioids include respiratory depression, orthostatic hypotension, cough suppression, confusion, diarrhea, miosis, abdominal pain, dry mouth, indigestion, anorexia, spasm of biliary tract, and urinary retention. Physical and psychological dependence are possibilities. Hypersensitivity reactions (including anaphylactoid reactions), hallucinations, vivid dreams, granulomatous interstitial nephritis, severe narcosis and acute renal failure have been reported rarely during dihydrocodeine administration.

Acetaminophen:
Acetaminophen in therapeutic doses rarely causes adverse reactions. The most serious adverse reaction is Hepatotoxicity from overdosage [see OVERDOSAGE]. Thrombocytopenia, leukopenia, pancytopenia, neutropenia, thrombocytopenic purpura, and agranulocytosis have been reported in patients receiving acetaminophen or p-aminophenol derivatives. Hypersensitivity reactions including urticarial or erythematous skin reactions, laryngeal edema, angioedema, or anaphylactoid reactions are rare.

Caffeine:
Adverse reactions associated with caffeine use include anxiety, anxiety neurosis, excitement, headaches, insomnia, irritability, lightheadedness, restlessness, tenseness, tremor, extrasystoles, palpitations, tachycardia, diarrhea, nausea, stomach pain, vomiting, diuresis, urticaria, scintillating scotoma, and tinnitus.

Postmarketing Experience:

• Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
• Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
• Anaphylaxis: Anaphylaxis has been reported with ingredients contained in PANLOR ® Tablets.
• Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].

Following an acute overdosage with PANLOR ® Tablets, toxicity may result from the dihydrocodeine or the acetaminophen. Toxicity due to the caffeine is less likely, due to the relatively small amounts in this formulation.

Clinical Presentation
Acute overdose with PANLOR ® Tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations.

Signs and Symptoms
Toxicity from dihydrocodeine poisoning includes the opioid triad of: pinpoint pupils, respiratory depression, and loss of consciousness. Convulsions, cardiovascular collapse, and death may occur. A single case of acute rhabdomyolysis associated with an overdose of dihydrocodeine has been reported. In acetaminophen overdosage: dose-dependent potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and coagulation defects may also occur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. Acute caffeine poisoning may cause insomnia, restlessness, tremor, delirium, tachycardia, and extrasystoles.

Because overdose information on this combination product is limited, it is unclear which of the signs and symptoms of toxicity would manifest in any particular overdose situation.

Treatment of Overdose
A single or multiple drug overdose with PANLOR ® Tablets is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended.

In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques.

The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to PANLOR ® Tablets overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to PANLOR ® Tablets overdose.

Because the duration of opioid reversal is expected to be less than the duration of action of dihydrocodeine bitartrate in PANLOR ® Tablets, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.

In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.

For respiratory depression due to unusual sensitivity to dihydrocodeine, parenteral naloxone is a specific and effective antagonist.

Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation.

Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration.

Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course of intoxication.

Important Dosage and Administration Instructions
Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS].

Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see WARNINGS].

Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with PANLOR ® Tablets and adjust the dosage accordingly [see WARNINGS]

Initial Dosage
Initiating treatment with PANLOR ® Tablets

The usual adult dosage is two (2) PANLOR ® Tablets orally every four (4) hours, as needed. No more than five (5) doses, or ten (10) tablets should be taken in a 24-hour period.

Conversion from Other Opioids to PANLOR ® Tablets
There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of PANLOR ® Tablets. It is safer to underestimate a patient’s 24-hour PANLOR ® Tablets dosage than to overestimate the 24-hour PANLOR ® Tablets dosage and manage an adverse reaction due to overdose.

Titration and Maintenance of Therapy
Individually titrate PANLOR ® Tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving PANLOR ® Tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see WARNINGS]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.

If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the PANLOR ® Tablets dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Discontinuation of PANLOR ® Tablets
When a patient who has been taking PANLOR ® Tablets regularly and may be physically dependent no longer requires therapy with PANLOR ® Tablets, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinue PANLOR ® Tablets in a physically-dependent patient [see WARNINGS, DRUG ABUSE AND DEPENDENCE].

PANLOR ® Tablets are:

• A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage moderate to moderately severe pain, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them.
• An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death.

Important information about PANLOR ® Tablets:

• Get emergency help right away if you take too much PANLOR ® Tablets (overdose). When you first start taking PANLOR ® Tablets, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur.
• Taking PANLOR ® Tablets with other opioid medicines, Benzodiazepines, Alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma and death.
• Never give anyone else your PANLOR ® Tablets. They could die from taking it. Store PANLOR ® Tablets away from children and in a safe place to prevent stealing or abuse. Selling or giving away PANLOR ® Tablets is against the law.

Important Information Guiding Use in Pediatric Patients:

• Do not give PANLOR ® Tablets to a child younger than 12 years of age.
• Do not give PANLOR ® Tablets to a child younger than 18 years of age after surgery to remove the tonsils and/or adenoids.
• Avoid giving PANLOR ® Tablets to children between 12 to 18 years of age who have risk factors for breathing problems such as obstructive sleep apnea, obesity, or underlying lung problems.

Do not take PANLOR ® Tablets if you have:

• severe asthma, trouble breathing, or other lung problems.
• a bowel blockage or have narrowing of the stomach or intestines.
• previously had an allergic reaction to dihydrocodeine or acetaminophen.

Before taking PANLOR ® Tablets, tell your healthcare provider if you have a history of:

• head injury, seizures
• liver, kidney, thyroid problems
• problems urinating
• pancreas or gallbladder problems
• abuse of street or prescription drugs, alcohol addiction, or mental health problems.
• Have been told by your healthcare provider that you are a “rapid metabolizer” of certain medicines.

Tell your healthcare provider if you are:

• pregnant or planning to become pregnant. Prolonged use of PANLOR ® Tablets during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated.
• breastfeeding. Not recommended; may harm your baby.
• taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking PANLOR ® Tablets with certain other medicines can cause serious side effects that could lead to death.

When taking PANLOR ® Tablets:

• Do not change your dose. Take PANLOR ® Tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed.
• Take your prescribed dose of 2 PANLOR ® Tablets orally every 4 hours, as needed. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time.
• Call your healthcare provider if the dose you are taking does not control your pain.
• If you have been taking PANLOR ® Tablets regularly, do not stop taking PANLOR ® Tablets without talking to your healthcare provider.
• After you stop taking PANLOR ® Tablets, dispose the unused PANLOR ® Tablets in accordance with local state guidelines and/or regulations.

While taking PANLOR ® Tablets DO NOT:

• Drive or operate heavy machinery, until you know how PANLOR ® Tablets affect you. PANLOR ® Tablets can make you sleepy, dizzy, or lightheaded.
• Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with PANLOR ® Tablets may cause you to overdose and die.

The possible side effects of PANLOR ® Tablets:

• constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

• trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion.

These are not all the possible side effects of PANLOR ® Tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov

Distributed by: Skylar Laboratories, LLC
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Issued: April 2017