Gelclair Gel

Pronunciation: gli-sir-eh-TIN-ic/POE-vi-done/hye-a-loo-ROE-nate
Generic Name: Glycyrrhetinic Acid/Povidone/Sodium Hyaluronate
Brand Name: Gelclair

Gelclair Gel is used for:

Managing and relieving mouth pain and irritation that may occur as a result of oral surgery, braces, dentures, disease, or following cancer chemotherapy or radiation therapy. It may also be used to treat mouth ulcers or for other conditions as determined by your doctor.

Gelclair Gel is a bioadherent oral gel. It works by coating the mouth to help relieve mouth pain and irritation.

Do NOT use Gelclair Gel if:

• you are allergic to any ingredient in Gelclair Gel

Contact your doctor or health care provider right away if any of these apply to you.

Before using Gelclair Gel:

Some medical conditions may interact with Gelclair Gel. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances

Some MEDICINES MAY INTERACT with Gelclair Gel. However, no specific interactions with Gelclair Gel are known at this time.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Gelclair Gel may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Gelclair Gel:

Use Gelclair Gel as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Pour the entire contents of 1 packet into a glass and mix with 1 tablespoon (15 mL) of water. Stir the mixture well. If the mixture is too thick, you may add 1 to 2 additional tablespoons (15 to 30 mL) of water until the mixture is the right thickness.


• If no water is available, you may use Gelclair Gel undiluted. Contact your doctor or pharmacist for instructions if you are unsure how to use Gelclair Gel without water.


• Rinse or swish the medicine around the mouth for at least 1 minute or as long as possible. Coat the entire area, including the tongue, top of the mouth, throat, and inside of the cheeks.


• Gargle and spit the medicine out. Try not to swallow.


• Avoid eating or drinking for at least 1 hour after using Gelclair Gel.


• If you miss a dose of Gelclair Gel, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Gelclair Gel.

Important safety information:

• If your symptoms do not improve within 7 days or if they become worse, check with your doctor.


• The gel may become darker or thicker over time. This will not affect its safety or effectiveness. Do not use Gelclair Gel after the expiration date listed on the packaging.


• PREGNANCY and BREAST-FEEDING: If you become pregnant while taking Gelclair Gel, discuss with your doctor the benefits and risks of using Gelclair Gel during pregnancy. If you are or will be breast-feeding while you are using Gelclair Gel, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Gelclair Gel:

All medicines may cause side effects, but many people have no, or minor, side effects. When used in small doses, no COMMON side effects have been reported with this product. Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Gelclair side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Gelclair Gel:

Store Gelclair Gel at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not refrigerate. Do not store in the bathroom. Keep Gelclair Gel out of the reach of children and away from pets.

General information:

• If you have any questions about Gelclair Gel, please talk with your doctor, pharmacist, or other health care provider.


• Gelclair Gel is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Gelclair Gel. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Gelclair resources

• Gelclair Side Effects (in more detail)
• Gelclair Use in Pregnancy & Breastfeeding
• Gelclair Support Group
• 0 Reviews for Gelclair - Add your own review/rating

Compare Gelclair with other medications

• Mucositis

Kaletra

Generic Name: Lopinavir and Ritonavir
Class: HIV Protease Inhibitors
VA Class: AM800
Chemical Name: [1S - [R*(R*),3R*,4R*]] - N - [4 - [[2,6 - Dimethylphenoxy) - acetyl]amino] - 3 - hydroxy - 5 - phenyl - 1 - (phenylmethyl)pentyl]tetrahydro - α - (1 - methylethyl) - 2 - oxo - 1(2H) - pyrimidineacetamide
Molecular Formula: C₃₇H₄₈N₄O₅C₃₇H₄₈N₆O₅S₂
CAS Number: 192725-17-0

Special Alerts:

[Posted 03/08/2011] ISSUE: FDA notified healthcare professionals of serious health problems that have been reported in premature babies receiving lopinavir/ritonavir (Kaletra) oral solution. Lopinavir/ritonavir oral solution contains the ingredients alcohol and propylene glycol. Premature babies may be at increased risk for health problems because they have a decreased ability to eliminate propylene glycol; this could lead to adverse events such as serious heart, kidney, or breathing problems. Because the consequences of using lopinavir/ritonavir oral solution in babies immediately after birth can be severe or possibly fatal, the label is being revised to include a new warning.

BACKGROUND: Lopinavir/ritonavir oral solution is an antiviral medication used in combination with other antiretroviral drugs for the treatment of HIV-1 infection in pediatric patients 14 days of age (whether premature or full term) or older and in adults.

RECOMMENDATION: The use of lopinavir/ritonavir oral solution should be avoided in premature babies until 14 days after their due date, or in full-term babies younger than 14 days of age unless a healthcare professional believes that the benefit of using lopinavir/ritonavir oral solution to treat HIV infection immediately after birth outweighs the potential risks. In such cases, FDA strongly recommends monitoring for increases in serum osmolality, serum creatinine, and other signs of toxicity. For more information visit the FDA website at: and .

REMS:

FDA approved a REMS for lopinavir and ritonavir to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antiretroviral; fixed combination of 2 HIV protease inhibitors (lopinavir, ritonavir).¹

Uses for Kaletra

Treatment of HIV Infection

Treatment of HIV infection in conjunction with other antiretrovirals.¹

Administration of lopinavir/ritonavir in conjunction with other active antiretroviral agents associated with a greater likelihood of treatment response.¹

Use of lopinavir/ritonavir should be guided by genotypic and phenotypic viral resistance testing and the individual’s prior antiretroviral treatment.¹

Preferred PI for initial treatment regimens in adults.¹⁰

Twice-daily regimen is the preferred PI for initial therapy in pediatric patients.¹¹

Postexposure Prophylaxis of HIV

Postexposure prophylaxis of HIV infection† in health-care workers and others exposed occupationally via percutaneous injury or mucous membrane or nonintact skin contact with blood, tissues, or other body fluids associated with a risk for transmission of the virus.¹⁸ Used in conjunction with other antiretrovirals.¹⁸

Postexposure prophylaxis of HIV infection† in individuals who have had nonoccupational exposure to blood, genital secretions, or other potentially infectious body fluids of a person known to be infected with HIV when that exposure represents a substantial risk for HIV transmission.¹⁵ Used in conjunction with other antiretrovirals.¹⁵

Kaletra Dosage and Administration

Administration

Oral Administration

Solution: Administer orally with food.¹ Use calibrated dosing syringe.¹

Tablets: Administer orally without regard to food.¹ Tablets should be swallowed whole and should not be chewed, broken, or crushed.¹

Solution is the preferred preparation for children with a body surface area <0.6 m² and those unable to swallow tablets.¹

Lopinavir/ritonavir oral solution is highly concentrated (contains 80 mg of lopinavir and 20 mg of ritonavir per mL).^{1 28} One death has occurred as a result of inadvertent overdosage of lopinavir/ritonavir oral solution.²⁸ To avoid medication errors, use extra care in calculating the dose, transcribing the medication order, dispensing the prescription, and providing dosing instructions.²⁸

Dosage

Available as fixed combination containing lopinavir and ritonavir; dosage expressed in terms of both drugs.¹

For pediatric patients, base dosage on body surface area or body weight.¹

Must be given in conjunction with other antiretrovirals.^{1 10} If used with certain didanosine preparations, adjustment of treatment regimen recommended.¹ If used with efavirenz, fosamprenavir, nelfinavir, or nevirapine, dosage adjustments recommended.^{1 10} (See Specific Drugs under Interactions.)

Once-daily regimen may be used only in treatment-naive adults not receiving efavirenz, fosamprenavir, nelfinavir, or nevirapine.^{1 10} Once-daily regimen should not be used in treatment-experienced adults or patients receiving certain anticonvulsants (carbamazepine, phenobarbital, phenytoin).¹

Once-daily regimen should not be used in pediatric patients.¹ Twice-daily regimen recommended for adolescents.^{1 11}

Pediatric Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Treatment of HIV Infection

Children ≤18 Years of Age Not Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine

Oral

Infants 14 days to 6 months of age: The recommended dosage of the oral solution based on body surface area is lopinavir 300 mg/m² and ritonavir 75 mg/m² twice daily.¹ Alternatively, the recommended dosage of the oral solution based on body weight is lopinavir 16 mg/kg and ritonavir 4 mg/kg twice daily.¹ Dosage recommendations not available for concomitant use with efavirenz, fosamprenavir, nelfinavir, or nevirapine¹

Children 6 months to 18 years of age: The recommended dosage of the oral solution based on body surface area is lopinavir 230 mg/m² and ritonavir 57.5 mg/m² twice daily.¹ Alternatively, the recommended dosage of the oral solution based on body weight is lopinavir 12 mg/kg and ritonavir 3 mg/kg twice daily for those who weigh <15 kg and lopinavir 10 mg/kg and ritonavir 2.5 mg/kg twice daily for those who weigh ≥15 kg.¹

^a: Two lopinavir/ritonavir tablets containing 200 mg of lopinavir and 50 mg of ritonavir can be used instead of 4 tablets containing 100 mg of lopinavir and 25 mg of ritonavir.

Dosage of Lopinavir/Ritonavir for Treatment of HIV Infection in Children 6 Months to 18 Years of Age Not Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine1

Weight (kg)	Body Surface Area (m2)	Number of Lopinavir/Ritonavir Tablets containing 100 mg of lopinavir and 25 mg of ritonavir given twice daily
15 to 25	≥0.6 to <0.9	2 tablets
>25 to 35	≥0.9 to <1.4	3 tablets
>35	≥1.4	4 tabletsa

Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine

Oral

Children 6 months to 18 years of age: The recommended dosage based on body surface area is lopinavir 300 mg/m² and ritonavir 75 mg/m² twice daily.¹ Alternatively, the recommended dosage based on body weight is lopinavir 13 mg/kg and ritonavir 3.25 mg/kg twice daily for those who weigh <15 kg and lopinavir 11 mg/kg and ritonavir 2.75 mg/kg twice daily for those who weigh ≥15 to 45 kg.¹

^a: Two lopinavir/ritonavir tablets containing 200 mg of lopinavir and 50 mg of ritonavir can be used instead of 4 tablets containing 100 mg of lopinavir and 25 mg of ritonavir.

^b: Two lopinavir/ritonavir tablets containing 200 mg of lopinavir and 50 mg of ritonavir can be used instead of 4 tablets containing 100 mg of lopinavir and 25 mg of ritonavir. Three lopinavir/ritonavir tablets each containing 200 mg of lopinavir and 50 mg of ritonavir can be used instead of 6 tablets each containing 100 mg of lopinavir and 25 mg of ritonavir.

Dosage of Lopinavir/Ritonavir for Treatment of HIV Infection in Children 6 Months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine1

Weight (kg)	Body Surface Area (m2)	Number of Lopinavir/Ritonavir Tablets containing 100 mg of lopinavir and 25 mg of ritonavir given twice daily
15 to 20	≥0.6 to <0.8	2 tablets
>20 to 30	≥0.8 to <1.2	3 tablets
>30 to 45	≥1.2 to <1.7	4 tabletsa
>45	≥1.7	4 or 6 tabletsb

Adults

Treatment of HIV Infection

Treatment-naive Adults Not Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine

Oral

Lopinavir 400 mg and ritonavir 100 mg (as 2 tablets containing 200 mg of lopinavir and 50 mg of ritonavir or 5 mL of oral solution) twice daily.^{1 10 20}

Alternatively, lopinavir 800 mg and ritonavir 200 mg (as 4 tablets containing 200 mg of lopinavir and 50 mg of ritonavir or 10 mL of oral solution) once daily.^{1 10 20}

Treatment-experienced Adults Not Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine

Oral

Lopinavir 400 mg and ritonavir 100 mg (as 2 tablets containing 200 mg of lopinavir and 50 mg of ritonavir or 5 mL of oral solution) twice daily.^{1 10 20}

Once-daily regimen not recommended.¹

Treatment-naive and Treatment-experienced Adults Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine

Oral

Lopinavir 500 mg and ritonavir 125 mg (as 2 tablets containing 200 mg of lopinavir and 50 mg of ritonavir and 1 tablet containing 100 mg of lopinavir and 25 mg of ritonavir) twice daily.¹

Alternatively, lopinavir 533 mg and ritonavir 133 mg (6.7 mL of oral solution) twice daily.¹

Once-daily regimen not recommended.¹

Postexposure Prophylaxis of HIV†

Occupational Exposure†

Oral

Lopinavir 400 mg and ritonavir 100 mg twice daily.^{18 29}

Initiate postexposure prophylaxis as soon as possible following exposure (within hours rather than days) and continue for 4 weeks, if tolerated.¹⁸

Nonoccupational Exposure†

Oral

Lopinavir 400 mg and ritonavir 100 mg twice daily.¹⁵

Initiate postexposure prophylaxis as soon as possible following exposure (preferably ≤72 hours after exposure) and continue for 28 days.¹⁵

Prescribing Limits

Pediatric Patients

Treatment of HIV Infection

Oral

Do not exceed adult dosage.¹

Special Populations

Hepatic Impairment

Not studied to date in patients with severe hepatic impairment; dosage recommendations not available.^{1 10} (See Hepatic Impairment under Cautions.)

Renal Impairment

Renal clearance is negligible;¹ dosage adjustments not necessary.¹⁰

Cautions for Kaletra

Contraindications

• 
  

  History of clinically important hypersensitivity reaction (e.g., Stevens-Johnson syndrome, erythema multiforme) to lopinavir, ritonavir, or any ingredient in the formulation.¹

  
  


• 
  

  Concomitant use with drugs highly dependent on CYP3A for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., cisapride, ergot alkaloids, midazolam, pimozide, triazolam, lovastatin, simvastatin).¹ (See Specific Drugs under Interactions.)

  
  


• 
  

  Concomitant use with drugs that are potent inducers of CYP3A; such use may result in decreased plasma concentrations of lopinavir, and possible loss of virologic response and development of resistance (e.g., rifampin, St. John’s wort [Hypericum perforatum]).¹ (See Specific Drugs under Interactions.)

  
  

Warnings/Precautions

Warnings

Interactions

Serious and/or life-threatening drug interactions, important drug interactions, or loss of virologic effect can occur with some drugs.¹ (See Contraindications and Specific Drugs under Interactions.)

Pancreatitis

Pancreatitis (sometimes fatal) with or without marked elevations in triglycerides has occurred.¹

Patients with advanced HIV disease may be at increased risk of elevated triglycerides and pancreatitis;¹ those with a history of pancreatitis may be at increased risk for recurrence during lopinavir and ritonavir therapy.¹

Consider pancreatitis in patients who develop abdominal pain, nausea, and vomiting or elevated serum amylase or lipase concentrations.¹ Suspend lopinavir and ritonavir therapy, as well as other antiretroviral therapy, if clinically appropriate.¹ (See Lipid Effects under Cautions.)

Hepatic Effects

Hepatic dysfunction (including some fatalities) reported; causal relationship not established.¹ Generally has occurred in patients with advanced HIV infection receiving multiple concomitant drugs in the setting of chronic hepatitis or cirrhosis.¹

Evaluate hepatic function prior to and during therapy.¹ Consider increased AST/ALT monitoring in patients with hepatitis or cirrhosis, especially during the first several months of therapy.¹

Hyperglycemic and Diabetogenic Effects

Hyperglycemia, new-onset diabetes mellitus, or exacerbation of preexisting diabetes mellitus reported with use of HIV protease inhibitors (PIs); diabetic ketoacidosis has occurred.¹

Monitor blood glucose and initiate or adjust dosage of oral hypoglycemic agent or insulin as needed.¹

General Precautions

HIV Resistance

Possibility of HIV-1 resistant to lopinavir and ritonavir and possible cross-resistance to other PIs.¹ Effect of lopinavir therapy on subsequent therapy with other PIs under investigation.¹

Hemophilia A and B

Spontaneous bleeding noted with PIs; causal relationship not established.¹

Caution in patients with a history of hemophilia type A or B.¹ Increased hemostatic (e.g., antihemophilic factor) therapy may be needed.¹

Cardiovascular Effects

Prolongation of the PR interval reported.¹ Second- or third-degree AV block reported.¹ Caution in patients with structural heart disease, cardiac conduction abnormalities, ischemic heart disease, or cardiomyopathies; these individuals may be at increased risk for cardiac conduction abnormalities.¹ Caution if lopinavir/ritonavir is used with other drugs that prolong the PR interval (e.g., some β-adrenergic blocking agents, digoxin, calcium-channel blockers, atazanavir), especially drugs metabolized by CYP3A4.¹

Prolongation of the QT interval and torsades de pointes have occurred.¹ Use with caution in patients who have or may develop prolongation of the QT interval (e.g., hypokalemia, congenital long QT syndrome, use of drugs known to prolong QT interval).¹

Adipogenic Effects

Possible redistribution or accumulation of body fat, including central obesity, dorsocervical fat enlargement (“buffalo hump”), peripheral wasting, breast enlargement, and general cushingoid appearance.¹

Lipid Effects

Substantial increases in total serum cholesterol and triglyceride concentrations have occurred.¹ Marked triglyceride elevations is a risk factor for pancreatitis.¹ (See Pancreatitis under Cautions.)

Determine serum triglyceride and cholesterol concentrations prior to initiating therapy and monitor concentrations periodically; manage lipid disorders as clinically appropriate.¹ (See HMG-CoA Reductase Inhibitors under Interactions.)

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jiroveci [formerly P. carinii]); this may necessitate further evaluation and treatment.¹

Possible Prescribing and Dispensing Errors

Ensure accuracy of prescription; similarity in spelling of Kaletra (the fixed combination of lopinavir and ritonavir) and Keppra (levetiracetam) may result in errors.¹³

To avoid medication errors when the oral solution is used, use care in the dose calculation, transcription of the order, and dispensing of the prescription.²⁸

Specific Populations

Pregnancy

Category C.¹

Antiretroviral Pregnancy Registry at 800-258-4263.¹

Some experts state that lopinavir/ritonavir is the preferred PI for use in pregnant women.²¹ Specific dosage recommendations not available.²¹ Some experts recommend usual dosage throughout pregnancy with monitoring of virologic response and lopinavir concentrations; others recommend increasing dosage to 600 mg of lopinavir and 150 mg of ritonavir (as tablets) twice daily during third trimester.²¹ Pending further accumulation of data, once-daily regimen not recommended during pregnancy.²¹

Lactation

Lopinavir distributed into milk in rats; not known whether distributed into human milk.¹

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.^{1 11}

Pediatric Use

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Safety, efficacy, and pharmacokinetics not established in children <14 days of age.¹

Once-daily regimen not evaluated in pediatric patients.¹ Twice-daily regimen recommended in pediatric and adolescent patients.¹¹

Significant alcohol-related toxicity may result if a young child accidentally ingests oral solution (contains 42.4% alcohol).¹

Geriatric Use

Insufficient experience in those ≥65 years of age to determine whether they respond differently than younger adults.¹

Use with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Hepatic Impairment

Use with caution since lopinavir plasma concentrations may be increased.¹ Not evaluated in severe hepatic impairment.¹

Risk of further transaminase elevations in patients with underlying hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or those with preexisting transaminase elevations.¹ Carefully monitor liver function in these patients.¹

Common Adverse Effects

Diarrhea, nausea, vomiting, headache, abdominal pain, asthenia, dyspepsia.¹

Interactions for Kaletra

Lopinavir metabolized by CYP3A.¹ Fixed combination of lopinavir and ritonavir inhibits CYP3A4.¹ At clinically important concentrations, lopinavir does not inhibit CYP2D6, 2C9, 2C19, 2E1, 2B6, or 1A2.¹

Fixed-combination of lopinavir and ritonavir induces glucuronidation.¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions likely with drugs that are inhibitors, inducers, or substrates of CYP3A with possible alteration in metabolism of lopinavir, ritonavir, and/or other drug.¹

Specific Drugs

Drug	Interaction	Comments
Abacavir	Possible decreased abacavir plasma concentrations1	Clinical importance unknown1
Antiarrhythmic agents (amiodarone, flecainide, systemic lidocaine, propafenone, quinidine)	Possible increased antiarrhythmic agent concentrations1	Cautious use with amiodarone, systemic lidocaine, or quinidine; monitor serum concentrations of antiarrhythmic if possible1 Some experts state concomitant use with flecainide or propafenone not recommended10
Anticoagulants, oral	Warfarin concentrations may be affected1	Monitor INR1
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Decreased lopinavir concentrations and possible decreased effectiveness of the antiretroviral;1 10 altered anticonvulsant concentrations10	Cautious use with carbamazepine, phenobarbital, and phenytoin; do not use lopinavir once-daily regimen1 Carbamazepine, phenobarbital, phenytoin: Some experts recommend considering use of an alternative anticonvulsant; if used, monitor plasma concentrations of the anticonvulsant and lopinavir10
Antifungals, azoles (itraconazole, ketoconazole, voriconazole)	Itraconazole: Increased antifungal concentrations1 10 Ketoconazole: Increased antifungal concentrations1 and decreased lopinavir AUC10 Fluconazole: Interaction not expected1 Voriconazole: Possible decreased antifungal concentrations10	Itraconazole: High itraconazole dosage (>200 mg daily) not recommended1 10 use with caution;1 10 monitor antifungal concentrations and toxicity10 Ketoconazole: High ketoconazole dosage (>200 mg daily) not recommended;1 10 use with caution10 Voriconazole: Concomitant use not recommended unless benefit outweighs risk1 10
Antimycobacterials, (rifabutin, rifampin, rifapentine)	Rifabutin: Increased rifabutin and rifabutin metabolite concentrations1 10 Rifampin: Substantially decreased lopinavir concentrations with possible loss of virologic response and increased risk of lopinavir resistance1	Rifabutin: Use usual lopinavir dosage but reduce rifabutin dosage to 150 mg every other day or 3 times weekly;1 10 further rifabutin dosage reductions may be necessary;1 monitor closely for adverse effects1 Rifampin: Concomitant use contraindicated1 Rifapentine: Concomitant use not recommended10
Atazanavir	Pharmacokinetic interaction unlikely10 In vitro evidence of additive antiretroviral effects1
Atovaquone	Possible decreased atovaquone concentrations;1 clinical importance unknown1	Consider need to increase atovaquone dosage1
Benzodiazepines	Pharmacokinetic interaction with midazolam or triazolam; potential for prolonged or increased sedation or respiratory depression1 Concomitant administration with oral midazolam expected to result in substantially higher concentrations of the benzodiazepine than concomitant administration with parenteral midazolam 1	Concomitant use with oral midazolam or triazolam contraindicated;1 10 some experts state a single parenteral dose of midazolam can be used with caution in a monitored situation for procedural sedation10
Bupropion	Possible decreased bupropion and hydroxybupropion (active metabolite) concentrations1	Monitor for response to bupropion1
Calcium-channel blocking agents	Possible increased concentrations of dihydropyridines (e.g., felodipine, nifedipine, nicardipine)1	Use concomitantly with caution; clinical monitoring recommended1
Cisapride	Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1	Concomitant use contraindicated1 10
Corticosteroids (dexamethasone, fluticasone)	Fluticasone nasal spray/oral inhalation: Increased fluticasone concentrations with lopinavir and ritonavir resulting in decreased cortisol concentrations1 Dexamethasone: Decreased lopinavir concentrations1	Fluticasone nasal spray/oral inhalation: Concomitant use with lopinavir and ritonavir not recommended unless potential benefits outweigh risk of systemic corticosteroid adverse effects1 Dexamethasone: Use concomitantly with caution1
Co-trimoxazole	Interaction unlikely1
Dapsone	Interaction unlikely1
Darunavir	Decreased concentrations of darunavir; increased or no change in concentrations of lopinavir10 22	Concomitant use of ritonavir-boosted darunavir not recommended; appropriate dosages with respect to safety and efficacy not established10 22
Delavirdine	Possible increased lopinavir concentrations1 10	Appropriate dosages for concomitant use with respect to safety and efficacy not established1 10
Desipramine	Pharmacokinetic interaction unlikely1
Didanosine	Lopinavir and ritonavir oral solution: Conflicting administration instructions with regards to food1	Lopinavir and ritonavir oral solution: Administer didanosine (without food) 1 hour before or 2 hours after lopinavir (given with food)1 Lopinavir and ritonavir tablets: May be administered at the same time as didanosine1
Disulfiram	Possible disulfiram-like reaction with lopinavir and ritonavir oral solution because of alcohol content1
Efavirenz	Lopinavir 400 mg and ritonavir 100 mg twice daily with efavirenz 600 mg once daily: Decreased lopinavir plasma concentrations1 Lopinavir 600 mg and ritonavir 150 mg twice daily with efavirenz 600 mg once daily: Increased lopinavir concentrations relative to lopinavir 400 mg and ritonavir 100 mg twice daily (without efavirenz)1	Once-daily lopinavir regimen not recommended with efavirenz1 11 20 For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily1 Manufacturer of lopinavir recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily1 For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)1 (For weight-based dosing, see Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine under Dosage and Administration)
Ergot alkaloids (dihydroergotamine, ergonovine, ergotamine, methylergonovine)	Possible pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., acute ergot toxicity)1	Concomitant use contraindicated1 10 If treatment of uterine atony and excessive postpartum bleeding is indicated in a woman receiving lopinavir, use methylergonovine maleate (Methergine) only if alternative treatments cannot be used and if potential benefits outweigh risks; use methylergonovine at lowest dosage and shortest duration possible11
Estrogens/Progestins	Hormonal contraceptives: Increased clearance of ethinyl estradiol contained in estrogen-based hormonal contraceptives1	Use alternative or additional nonhormonal contraceptive measures1 10
Etravirine	Increased concentrations of etravirine and decreased concentrations of lopinavir10 33	Limited data available on the safety of increased concentrations of etravirine; use with caution10 33 Some experts state that the usual dosages may be used10
Fosamprenavir	Decreased concentrations of amprenavir with fosamprenavir (with or without low-dose ritonavir); altered or no change in lopinavir concentrations1 10 26 27 Increased incidence of adverse effects reported1 10 In vitro evidence of additive antiretroviral effects1	Some experts state concomitant use of fosamprenavir not recommended since appropriate dosages not established10 Manufacturer of lopinavir states that concomitant use of ritonavir-boosted fosamprenavir and lopinavir/ritonavir not recommended because appropriate dosages not established1 For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily1 Manufacturer of lopinavir recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily1 For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)1 (For weight-based dosing, see Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine under Dosage and Administration)
Histamine H2-receptor antagonists (ranitidine)	Ranitidine: No change in lopinavir/ritonavir concentrations1 10
HMG-CoA reductase inhibitors	Decreased clearance and increased concentrations of some HMG-CoA reductase inhibitors with potential for increased risk of myopathy (including rhabdomyolysis);1 10 interaction with fluvastatin not expected1	Concomitant use with lovastatin or simvastatin contraindicated1 If used with atorvastatin, use lowest possible atorvastatin dosage with careful monitoring1 10 If used with rosuvastatin, use lowest possible rosuvastatin dosage with careful monitoring;1 maximum recommended dosage of rosuvastatin is 10 mg once daily25 Consider using pravastatin or fluvastatin;1 10 dosage adjustment not necessary with pravastatin10
Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)	Potential for increased concentrations of cyclosporine, sirolimus, or tacrolimus1	Monitor concentrations of the immunosuppressive agent1
Indinavir	Pharmacokinetic interaction; increased indinavir concentrations and AUC1 10 In vitro evidence of additive antiretroviral effects1	Consider indinavir 600 mg twice daily with 400 mg of lopinavir and 100 mg of ritonavir twice daily;1 10 lopinavir once-daily regimen not studied in conjunction with indinavir1
Lamivudine	No clinically important interaction1
Lamotrigine	Decreased lamotrigine AUC; no change in lopinavir or ritonavir AUCs24
Macrolides	Clarithromycin: Increased clarithromycin concentrations1 10 Azithromycin or erythromycin: Interaction not expected1	Clarithromycin: If used concomitantly in patients with renal impairment, reduce clarithromycin dosage by 50% if Clcr 30–60 mL/minute or by 75% if Clcr <30 mL/minute1
Maraviroc	Increased maraviroc concentrations1 10 30	If used concomitantly with maraviroc, recommended dosage of maraviroc is 150 mg twice daily1 10 30
Methadone	Decreased methadone plasma concentrations and AUC;1 10 opiate withdrawal may occur10	Monitor closely for signs of opiate withdrawal;10 consider need to increase methadone dosage1 10
Metronidazole	Possible disulfiram-like reaction with lopinavir and ritonavir oral solution because of alcohol content1
Nelfinavir	Decreased lopinavir concentrations and increased nelfinavir concentrations1 10	Once-daily lopinavir regimen not recommended with nelfinavir1 20 Some experts state that appropriate dosages for concomitant use of nelfinavir and lopinavir not established10 For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily1 Manufacturer of lopinavir recommends that adults receive i533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of the oral solution) twice daily1 For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)1 (For weight-based dosing, see Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine under Dosage and Administration)
Nevirapine	Decreased lopinavir concentrations1 10	Once-daily lopinavir regimen not recommended with nevirapine1 20 For adults, manufacturer of lopinavir recommends 500 mg of lopinavir and 125 mg of ritonavir (as tablets) twice daily1 Manufacturer recommends that adults receive 533 mg of lopinavir and 133 mg of ritonavir (6.7 mL of oral solution) twice daily1 h For pediatric patients 6 months to 18 years of age, manufacturer of lopinavir recommends that children receive 300 mg/m2 of lopinavir and 75 mg/m2 of ritonavir twice daily (do not exceed the adult dosage)1 (For weight-based dosing, see Children 6 months to 18 Years of Age Receiving Efavirenz, Fosamprenavir, Nelfinavir, or Nevirapine under Dosage and Administration)
Pimozide	Pharmacokinetic interaction; potential for serious or life-threatening reactions (e.g., cardiac arrhythmias)1	Concomitant use contraindicated1 10
Proton-pump inhibitors (omeprazole)	Omeprazole: No change in lopinavir/ritonavir concentrations1 10
Ritonavir	Increased lopinavir concentrations1	Additional ritonavir not recommended with fixed combination of lopinavir and ritonavir1 10 ;
Saquinavir	Increased saquinavir concentrations1 10 In vitro evidence of additive antiretroviral effects1	Manufacturers and some experts recommend saquinavir 1 g twice daily with 400 mg of lopinavir and 100 mg of ritonavir twice daily;1 10 lopinavir once-daily regimen not studied in conjunction with saquinavir1
St. John’s wort (Hypericum perforatum)	Decreased lopinavir concentrations; possible loss of virologic response and increased risk of lopinavir resistance1	Concomitant use contraindicated1
Sildenafil	Increased sildenafil concentrations and increased risk of sildenafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1 10	Use caution and reduced sildenafil dosage (25 mg repeated no more frequently than every 48 hours);1 10 closely monitor for adverse effects (e.g., hypotension, syncope, visual changes, prolonged erection)1 10
Stavudine	No clinically important interaction1
Tadalafil	Increased tadalafil concentrations and increased risk of tadalafil-associated adverse effects (e.g., hypotension, visual changes, prolonged erection)1 10	Use initial tadalafil dosage of 5 mg and do not exceed a single dose of 10 mg in 72 hours1 10
Tenofovir	Increased peak plasma concentration and AUC of tenofovir1 10 31	Clinical importance unknown10 Monitor for tenofovir toxicity;1 10 31 discontinue tenofovir if adverse effects occur31
Tipranavir	Decreased lopinavir concentrations1 10 17 In vitro evidence of additive antiretroviral effects1	Concomitant use not recommended; 1 10 appropriate dosage not established10
Trazodone	Possible increased trazodone concentrations; adverse effects (nausea, dizziness, hypotension, syncope) reported when trazodone and ritonavir used concomitantly1	Caution i

Synphase Tablets

1. Name Of The Medicinal Product

Synphase.

2. Qualitative And Quantitative Composition

Synphase consists of 7 blue tablets containing norethisterone 500 micrograms and ethinylestradiol 35 micrograms, marked 'BX' on one side and 'SEARLE' on the other; 9 white tablets containing norethisterone 1.0 milligram and ethinylestradiol 35 micrograms inscribed 'SEARLE' on one face and 'BX' on the other; 5 blue tablets containing norethisterone 500 micrograms and ethinylestradiol 35 micrograms, marked 'BX' on one side and 'SEARLE' on the other.

3. Pharmaceutical Form

Tablets for oral administration.

4. Clinical Particulars

4.1 Therapeutic Indications

Synphase is indicated for oral contraception, with the benefit of a low intake of oestrogen.

4.2 Posology And Method Of Administration

Oral Administration: The dosage of Synphase for the initial cycle of therapy is 1 tablet taken at the same time each day from the first day of the menstrual cycle. For subsequent cycles, no tablets are taken for 7 days, then a new course is started of 1 tablet daily for the next 21 days. This sequence of 21 days on treatment, seven days off treatment is repeated for as long as contraception is required.

Patients unable to start taking Synphase tablets on the first day of the menstrual cycle may start treatment on any day up to and including the 5th day of the menstrual cycle.

Patients starting on day 1 of their period will be protected at once. Those patients delaying therapy up to day 5 may not be protected immediately and it is recommended that another method of contraception is used for the first 7 days of tablet-taking. Suitable methods are condoms, caps plus spermicides and intra-uterine devices.

The rhythm, temperature and cervical-mucus methods should not be relied upon.

Tablet omissions

Tablets must be taken daily in order to maintain adequate hormone levels and contraceptive efficacy.

If a tablet is missed within 12 hours of the correct dosage time then the missed tablet should be taken as soon as possible, even if this means taking 2 tablets on the same day, this will ensure that contraceptive protection is maintained. If one or more tablets are missed for more than 12 hours from the correct dosage time it is recommended that the patient takes the last missed tablet as soon as possible and then continues to take the rest of the tablets in the normal manner. In addition, it is recommended that extra contraceptive protection, such as a condom, is used for the next 7 days.

Patients who have missed one or more of the last 7 tablets in a pack should be advised to start the next pack of tablets as soon as the present one has finished (i.e. without the normal seven day gap between treatments). This reduces the risk of contraceptive failure resulting from tablets being missed close to a 7 day tablet free period.

Changing from another oral contraceptive

In order to ensure that contraception is maintained it is advised that the first dose of Synphase tablets is taken on the day immediately after the patient has finished the previous pack of tablets.

Use after childbirth, miscarriage or abortion

Providing the patient is not breast feeding the first dose of Synphase tablets should be taken on the 21st day after childbirth. This will ensure the patient is protected immediately. If there is any delay in taking the first dose, contraception may not be established until 7 days after the first tablet has been taken. In these circumstances patients should be advised that extra contraceptive methods will be necessary.

After a miscarriage or abortion patients can take the first dose of Synphase tablets on the next day; in this way they will be protected immediately.

4.3 Contraindications

As with all combined progestogen/oestrogen oral contraceptives, the following conditions should be regarded as contra-indications:

i. History of confirmed venous thromboembolic disease (VTE), family history of idiopathic VTE and other known risk factors of VTE

ii. Thrombophlebitis, cerebrovascular disorders, coronary artery disease, myocardial infarction, angina, hyperlipidaemia or a history of these conditions.

iii. Acute or severe chronic liver disease, including liver tumours, Dubin-Johnson or Rotor syndrome.

iv. History during pregnancy of idiopathic jaundice, severe pruritus or pemphigoid gestationis.

v. Known or suspected breast or genital cancer.

vi. Known or suspected oestrogen-dependent neoplasia.

vii. Undiagnosed abnormal vaginal bleeding.

viii. A history of migraines classified as classical, focal or crescendo.

ix. Pregnancy.

4.4 Special Warnings And Precautions For Use

Assessment of women prior to starting oral contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contraindications (section 4.3) and warnings (section 4.4) for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology.

Women taking oral contraceptives require careful observation if they have or have had any of the following conditions: breast nodules; fibrocystic disease of the breast or an abnormal mammogram; uterine fibroids; a history of severe depressive states; varicose veins; sickle-cell anaemia; diabetes; hypertension; cardiovascular disease; migraine; epilepsy; asthma; otosclerosis; multiple sclerosis; porphyria; tetany; disturbed liver functions; gallstones; kidney disease; chloasma; any condition that is likely to worsen during pregnancy. The worsening or first appearance of any of these conditions may indicate that the oral contraceptive should be stopped. Discontinue treatment if there is a gradual or sudden, partial or complete loss of vision or any evidence of ocular changes, onset or aggravation of migraine or development of headache of a new kind which is recurrent, persistent or severe.

Gastro-intestinal upsets, such as vomiting and diarrhoea, may interfere with the absorption of the tablets leading to a reduction in contraceptive efficacy. Patients should continue to take Synphase, but they should also be encouraged to use another contraceptive method during the period of gastro-intestinal upset and for the next 7 days.

Progestogen oestrogen preparations should be used with caution in patients with a history of hepatic dysfunction or hypertension.

An increased risk of venous thromboembolic disease (VTE) associated with the use of oral contraceptives is well established but is smaller than that associated with pregnancy, which has been estimated at 60 cases per 100,000 pregnancies. Some epidemiological studies have reported a greater risk of VTE for women using combined oral contraceptives containing desogestrel or gestodene (the so-called 'third generation' pills) than for women using pills containing levonorgestrel or norethisterone (the so-called 'second generation' pills)

The spontaneous incidence of VTE in healthy non-pregnant women (not taking any oral contraceptive) is about 5 cases per 100,000 per year. The incidence in users of second generation pills is about 15 per 100,000 women per year of use. The incidence in users of third generation pills is about 25 cases per 100,000 women per year of use; this excess incidence has not been satisfactorily explained by bias or confounding. The level of all of these risks of VTE increases with age and is likely to be further increased in women with other known risk factors for VTE such as obesity. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive.

Patients receiving oral contraceptives should be kept under regular surveillance, in view of the possibility of development of conditions such as thromboembolism.

The risk of coronary artery disease in women taking oral contraceptives is increased by the presence of other predisposing factors such as cigarette smoking, hypercholesterolaemia, obesity, diabetes, history of pre-eclamptic toxaemia and increasing age. After the age of thirty-five years, the patient and physician should carefully re-assess the risk/benefit ratio of using combined oral contraceptives as opposed to alternative methods of contraception.

Synphase should be discontinued at least four weeks before, and for two weeks following, elective operations and during immobilisation. Patients undergoing injection treatment for varicose veins should not resume taking Synphase until 3 months after the last injection.

Benign and malignant liver tumours have been associated with oral contraceptive use. The relationship between occurrence of liver tumours and use of female sex hormones is not known at present. These tumours may rupture causing intra-abdominal bleeding. If the patient presents with a mass or tenderness in the right upper quadrant or an acute abdomen, the possible presence of a tumour should be considered.

An increased risk of congenital abnormalities, including heart defects and limb defects, has been reported following the use of sex hormones, including oral contraceptives, in pregnancy. If the patient does not adhere to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and further use of oral contraceptives should be withheld until pregnancy has been ruled out. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing the contraceptive regimen. If pregnancy is confirmed the patient should be advised of the potential risks to the foetus and the advisability of continuing the pregnancy should be discussed in the light of these risks. It is advisable to discontinue Synphase three months before a planned pregnancy.

The risk of arterial thrombosis associated with combined oral contraceptives increases with age, and this risk is aggravated by cigarette smoking. The use of combined oral contraceptives by women in the older age group, especially those who are cigarette smokers, should therefore be discouraged and alternative methods advised.

The use of this product in patients suffering from epilepsy, migraine, asthma or cardiac dysfunction may result in exacerbation of these disorders because of fluid retention. Caution should also be observed in patients who wear contact lenses.

Decreased glucose tolerance may occur in diabetic patients on this treatment, and their control must be carefully supervised.

The use of oral contraceptives has also been associated with a possible increased incidence of gall bladder disease.

Women with a history of oligomenorrhoea or secondary amenorrhoea or young women without regular cycles may have a tendency to remain anovulatory or to become amenorrhoeic after discontinuation of oral contraceptives. Women with these pre-existing problems should be advised of this possibility and encouraged to use other contraceptive methods.

Numerous epidemiological studies have been reported on the risks of ovarian, endometrial, cervical and breast cancer in women using combined oral contraceptives. The evidence is clear that combined oral contraceptives offer substantial protection against both ovarian and endometrial cancer.

An increased risk of cervical cancer in long-term users of combined oral contraceptives has been reported in some studies, but there continues to be controversy about the extent to which this is attributable to the confounding effects of sexual behaviour and other factors.

A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using combined oral contraceptives (COCs). The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both. The additional breast cancers diagnosed in current users of COCs or in women who have used COCs in the last ten years are more likely to be localised to the breast than those in women who never used COCs.

Breast cancer is rare among women under 40 years of age whether or not they take COCs. Whilst this background risk increases with age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer (see bar chart).

The most important risk factor for breast cancer in COC users is the age women discontinue the COC; the older the age at stopping, the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping COC use such that by 10 years there appears to be no excess.

The possible increase in risk of breast cancer should be discussed with the user and weighed against the benefits of COCs taking into account the evidence that they offer substantial protection against the risk of developing certain other cancers (e.g. ovarian and endometrial cancer).

	Estimated cumulative numbers of breast cancers per 10,000 women diagnosed in 5 years of use and up to 10 years after stopping COCs, compared with numbers of breast cancers diagnosed in 10,000 women who had never used COCs.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

The herbal remedy St John's wort (Hypericum perforatum) should not be taken concomitantly with this medicine as this could potentially lead to a loss of contraceptive effect.

Some drugs may modify the metabolism of Synphase reducing its effectiveness; these include certain sedatives, antibiotics, anti-epileptic and anti-arthritic drugs. During the time such agents are used concurrently, it is advised that mechanical contraceptives also be used.

The results of a large number of laboratory tests have been shown to be influenced by the use of oestrogen containing oral contraceptives, which may limit their diagnostic value. Among these are: biochemical markers of thyroid and liver function; plasma levels of carrier proteins, triglycerides, coagulation and fibrinolysis factors.

4.6 Pregnancy And Lactation

Contra-indicated in pregnancy.

Patients who are fully breast-feeding should not take Synphase tablets since, in common with other combined oral contraceptives, the oestrogen component may reduce the amount of milk produced. In addition, active ingredients or their metabolites have been detected in the milk of mothers taking oral contraceptives. The effect of Synphase on breast-fed infants has not been determined.

4.7 Effects On Ability To Drive And Use Machines

Not applicable.

4.8 Undesirable Effects

As with all oral contraceptives, there may be slight nausea at first, weight gain or breast discomfort, which soon disappear.

Other side-effects known or suspected to occur with oral contraceptives include gastro-intestinal symptoms, changes in libido and appetite, headache, exacerbation of existing uterine fibroid disease, depression, and changes in carbohydrate, lipid and vitamin metabolism.

Spotting or bleeding may occur during the first few cycles. Usually menstrual bleeding becomes light and occasionally there may be no bleeding during the tablet-free days.

Hypertension, which is usually reversible on discontinuing treatment, has occurred in a small percentage of women taking oral contraceptives.

4.9 Overdose

Overdosage may be manifested by nausea, vomiting, breast enlargement and vaginal bleeding. There is no specific antidote and treatment should be symptomatic. Gastric lavage may be employed if the overdose is large and the patient is seen sufficiently early (within four hours).

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

The mode of action of Synphase is similar to that of other progestogen/oestrogen oral contraceptives and includes the inhibition of ovulation, the thickening of cervical mucus so as to constitute a barrier to sperm and the rendering of the endometrium unreceptive to implantation. Such activity is exerted through a combined effect on one or more of the following: hypothalamus, anterior pituitary, ovary, endometrium and cervical mucus.

5.2 Pharmacokinetic Properties

Norethisterone is rapidly and completely absorbed after oral administration, peak plasma concentrations occurring in the majority of subjects between 1 and 3 hours. Due to first-pass metabolism, blood levels after oral administration are 60% of those after i.v. administration. The half life of elimination varies from 5 to 12 hours, with a mean of 7.6 hours. Norethisterone is metabolised mainly in the liver. Approximately 60% of the administered dose is excreted as metabolites in urine and faeces.

Ethinylestradiol is rapidly and well absorbed from the gastro-intestinal tract but is subject to some first-pass metabolism in the gut-wall. Compared to many other oestrogens it is only slowly metabolised in the liver. Excretion is via the kidneys with some appearing also in the faeces.

5.3 Preclinical Safety Data

The toxicity of norethisterone is very low. Reports of teratogenic effects in animals are uncommon. No carcinogenic effects have been found even in long-term studies.

Long-term continuous administration of oestrogens in some animals increases the frequency of carcinoma of the breast, cervix, vagina and liver.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Synphase tablets contain:

Maize starch, polyvidone, magnesium stearate and lactose. The blue tablets also contain E132.

6.2 Incompatibilities

None stated.

6.3 Shelf Life

The shelf life of Synphase tablets is 5 years.

6.4 Special Precautions For Storage

Store in a dry place below 25^oC away from direct sunlight.

6.5 Nature And Contents Of Container

Synphase tablets are supplied in pvc/foil blister packs of 21 and 63 tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Pharmacia Limited

Ramsgate Road

Sandwich

Kent

CT13 9JN

8. Marketing Authorisation Number(S)

PL 0032/0422

9. Date Of First Authorisation/Renewal Of The Authorisation

May 10th 1996 / 25/02/2009

10. Date Of Revision Of The Text

February 2009

Company Ref: SY3_0

Sunmark Nicotine Polacrilex

Dosage Form: gum, chewing
McKesson Nicotine Polacrilex Gum USP, 4 mg (nicotine) Drug Facts

Active ingredient (in each chewing piece)

Nicotine polacrilex (equal to 4 mg nicotine)

Purpose

Stop smoking aid

Uses

• reduces withdrawal symptoms, including nicotine craving, associated with quitting smoking

Warnings

If you are pregnant or breast-feeding,

only use this medicine on the advice of your health care provider. Smoking can seriously harm your child. Try to stop smoking without using any nicotine replacement medicine. This medicine is believed to be safer than smoking. However, the risks to your child from this medicine are not fully known.

Do not use

• if you continue to smoke, chew tobacco, use snuff, or use a nicotine patch or other nicotine containing products

Ask a doctor before use if you have

• a sodium-restricted diet


• heart disease, recent heart attack, or irregular heartbeat. Nicotine can increase your heart rate.


• high blood pressure not controlled with medication. Nicotine can increase blood pressure.


• stomach ulcer or diabetes

Ask a doctor or pharmacist before use if you are

• using a non-nicotine stop smoking drug


• taking prescription medication for depression or asthma. Your prescription dose may need to be adjusted.

Stop use and ask a doctor if

• mouth, teeth or jaw problems occur


• irregular heartbeat or palpitations occur


• you get symptoms of nicotine overdose such as nausea, vomiting, dizziness, diarrhea, weakness or rapid heartbeat

Keep out of reach of children and pets.

Pieces of nicotine gum may have enough nicotine to make children and pets sick. Wrap used pieces of gum in paper and throw away in the trash. In case of overdose, get medical help or contact a Poison Control Center right away.

Directions

• if you are under 18 years of age, ask a doctor before use


• before using this product, read the enclosed User’s Guide for complete directions and other important information


• stop smoking completely when you begin using the gum


• if you smoke less than 25 cigarettes a day; use Nicotine Polacrilex Gum, 2 mg


• if you smoke 25 or more cigarettes a day; use according to the following 12 week schedule:

Weeks 1 to 6	Weeks 7 to 9	Weeks 10 to 12
1 piece every 1 to 2 hours	1 piece every 2 to 4 hours	1 piece every 4 to 8 hours

• nicotine gum is a medicine and must be used a certain way to get the best results


• chew the gum slowly until it tingles. Then park it between your cheek and gum. When the tingling is gone, begin chewing again, until the tingle returns.


• repeat this process until most of the tingle is gone (about 30 minutes)


• do not eat or drink for 15 minutes before chewing the nicotine gum, or while chewing a piece


• to improve your chances of quitting, use at least 9 pieces per day for the first 6 weeks


• if you experience strong or frequent cravings, you may use a second piece within the hour. However, do not continuously use one piece after another since this may cause you hiccups, heartburn, nausea or other side effects.


• do not use more than 24 pieces a day


• it is important to complete treatment. Stop using the nicotine gum at the end of 12 weeks. If you still feel the need to use nicotine gum, talk to your doctor.

Other information

• each piece contains: calcium 100 mg and sodium 11 mg


• store at 20-25°C (68-77°F)


• protect from light

Inactive ingredients

acesulfame potassium, calcium carbonate, carnauba wax, D&C yellow no. 10, flavors, gelatin, gum base, mannitol, sodium bicarbonate, sodium carbonate, sorbitol, talc, titanium dioxide, xylitol

Questions or comments?

call 1-866-677-7858

Principal Display Panel

Compare to Nicorette® Coated Gum Active Ingredient

Nicotine Polacrilex Gum USP, 4 mg (nicotine)

Stop Smoking Aid

4 mg

Coated Gum

Cool Mint Flavor

For those who smoke 25 or more cigarettes a day

If you smoke less than 25 cigarettes a day: use Nicotine Polacrilex Gum, 2 mg

Actual Size

4 mg Each

Nicotine Polacrilex Gum USP, 4 mg (nicotine) Carton

SUNMARK NICOTINE  POLACRILEX nicotine  gum, chewing

Product Information Product Type HUMAN OTC DRUG NDC Product Code (Source) 49348-788 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength NICOTINE (NICOTINE) NICOTINE 4 mg

Inactive Ingredients Ingredient Name Strength No Inactive Ingredients Found

Product Characteristics Color YELLOW (light;coated) Score no score Shape RECTANGLE Size 16mm Flavor MINT Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 49348-788-59 4 BLISTER PACK In 1 CARTON contains a BLISTER PACK 1 10 PARTS In 1 BLISTER PACK This package is contained within the CARTON (49348-788-59) 2 49348-788-10 10 BLISTER PACK In 1 CARTON contains a BLISTER PACK 2 10 PARTS In 1 BLISTER PACK This package is contained within the CARTON (49348-788-10)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA076779	12/21/2006

Labeler - McKesson (177667227)

Revised: 07/2009McKesson

More Sunmark Nicotine Polacrilex resources

• Sunmark Nicotine Polacrilex Side Effects (in more detail)
• Sunmark Nicotine Polacrilex Dosage
• Sunmark Nicotine Polacrilex Use in Pregnancy & Breastfeeding
• Sunmark Nicotine Polacrilex Drug Interactions
• Sunmark Nicotine Polacrilex Support Group
• 42 Reviews for Sunmark Nicotine Polacrilex - Add your own review/rating

Compare Sunmark Nicotine Polacrilex with other medications

• Smoking Cessation

Syprol 5mg / 5ml Oral Solution

SYPROL 5mg/5ml Oral Solution

• Read all of this leaflet carefully before you start taking this medicine.


• Keep this leaflet. You may need to read it again.


• If you have further questions, ask your doctor or your pharmacist.


• This medicine has been prescribed only for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.


• If any of the side effects listed below become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet

• 1. What is Syprol Oral Solution and what it is used for


• 2. Before you take Syprol Oral Solution


• 3. How to take Syprol Oral Solution


• 4. Possible side effects


• 5. How to store Syprol Oral Solution


• 6. Further information

What is Syprol Oral Solution and what it is used for

Syprol Oral Solution contains propranolol hydrochloride. This belongs to a group of medicines called beta-blockers.

Syprol Oral Solution can be used for:

• high blood pressure


• symptoms of chest pain (angina)


• protection against further heart attacks - if you have already had one


• thickened heart muscle – also called ‘hypertrophic cardiomyopathy’


• problems affecting the beat of your heart (arrhythmias, tachycardia).

It can also be used for:

• severe headaches (migraine)


• shaking (tremors)


• stress (anxiety)


• an overactive thyroid gland – also called ‘thyrotoxicosis’


• bleeding in the food pipe (oesophagus). This happens when the blood pressure is high in your liver


• high blood pressure caused by a tumour on the adrenal gland. This is called 'phaeochromocytoma'.

Before you take Syprol Oral Solution

Do not take Syprol Oral Solution if:

• you are allergic (hypersensitive) to propranolol or any of the other ingredients in this liquid (see section 6: Further information)
  
  An allergic reaction can include a rash, itching or shortness of breath


• you have ever had asthma or wheezing


• you have heart problems such as heart failure which is not under control, heart block, slow or uneven heart beats, low blood pressure or very poor circulation


• you have not been eating (fasting) for a long period of time or if your blood has become too acidic (metabolic acidosis)


• you have high blood pressure caused by a tumour on the adrenal gland which has not been treated. This is called 'phaeochromocytoma'


• you have or sometimes get low blood sugar ('hypoglycaemia'). This can happen if you are not eating well, have long-term liver disease or have diabetes


• you have chest pain that happens when you are resting rather than during exercise (called 'prinzmetals angina').

Do not take Syprol Oral Solution if any of the above apply to you. If you are not sure, talk to your doctor before taking Syprol Oral Solution.

Take special care with Syprol Oral Solution

Before you take Syprol Oral Solution tell your doctor if:

• you have heart failure which is being treated


• circulation problems or other heart problems (such as angina or heart attacks)


• you have liver problems (such as cirrhosis) or kidney problems


• you have allergic reactions to things like insect bites


• you have diabetes. This is because Syprol may interfere with your body’s reaction to low blood sugar


• you have an overactive thyroid gland – also called 'thyrotoxicosis'.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

In particular tell your doctor or pharmacist if you are taking any of the following medicines:

• medicines for diabetes


• medicines used to treat anxiety and depression as well as more serious mental health problems such as chlorpromazine, thioridazine, fluvoxamine, imipramine or MAOIs such as phenelzine and diazepam


• medicines for uneven heart beats such as disopyramide, quinidine, propafenone, lidocaine, flecainaide


• medicines for chest pain (angina) or high blood pressure such as verapamil, nifedipine, diltiazem, nisoldipine, nicardipine, isradipine, lacidipine


• medicines used to treat high blood pressure such as hydralazine, captopril (ACE inhibitors), furosemide and other water tablets (diuretics), losartan and candersatan, diazoxide, doxazosin, guanethidine, moxisylyte, monoxidine, nitrates
  such as glyceryl trinitrate and isosorbide dinitrate and methyldopa.


• medicines for stimulating the heart such as adrenaline


• medicines for pain and inflammation including arthritis such as ibuprofen or indomethacin


• steroids used to reduce swelling such as prednisolone and dexamethasone


• medicines used to treat myasthenia gravis such as neostigmine


• medicines used to relax muscles such as baclofen and tizanidine


• medicines to help you sleep or to treat epilepsy known as barbiturates such as phenobarbital


• medicines used to treat parkinsons disease such as levodopa


• ergotamine, dihydroergotamine and rizatrapin – used for migraine


• digoxin and warfarin - used for heart failure


• cimetidine – used for too much stomach acid


• rifampicin - used for tuberculosis


• theophylline – used for asthma


• mefloquine - used to prevent malaria


• aldesleukin - used for kidney cancer


• alprostadil – used to help men get or keep an erection or to test for erection problems


• oestrogens - used in hormone replacement therapy (HRT)


• clonidine - used for high blood pressure and migraine. You must not stop taking clonidine unless your doctor tells you to. If you have to stop taking it, your doctor will tell you how to do it.

Operations and Tests

Tell your doctor, dentist or nurse you are taking Syprol Oral Solution if:

• you are going to have an operation or an anaesthetic


• you are going to have any blood or urine tests.

Taking Syprol Oral Solution with food and drink

Do not drink alcohol while taking Syprol Oral Solution. This is because alcohol can change the way the Syprol works.

Pregnancy and Breast-feeding

Talk to your doctor before taking this medicine if you are pregnant, planning to become pregnant or are breast-feeding.

Driving and using machines

Syprol is not likely to affect you being able to drive or use any tools or machines. However, sometimes you may feel dizzy or tired while taking Syprol. If this happens, do not drive or use any tools or machines and tell your doctor.

Important information about what is in Syprol Oral Solution

This medicine contains:

• Methyl and propyl parahydroxybenzoates. These may cause an allergic reaction (the allergy may happen some time after starting the medicine)


• Liquid maltitol. If your doctor has told you that you cannot tolerate some sugars, see your doctor before taking this medicine.

How to take Syprol Oral Solution

Taking this medicine

Take this medicine as your doctor or pharmacist has told you. Look on the label and ask the doctor or pharmacist if you are not sure.

• This medicine contains 5mg of propranolol in each 5ml


• Take this medicine by mouth


• Do not stop taking this medicine unless your doctor tells you to stop.

Adults

The usual doses range from 30mg - 320mg daily depending on what condition you are taking the medicine for.

Children

Your doctor will decide on the amount of Syprol to give to your child based on their weight.

Elderly

Your doctor will decide how much Syprol Oral Solution to give you.

If you take more Syprol Oral Solution than you should

Talk to your doctor or go to a hospital straight away.

If you forget to take Syprol Oral Solution

Do not take a double dose to make up for forgotten doses. Take your next dose as soon as you remember. Then go on as before.

If you stop taking Syprol Oral Solution

Keep taking this medicine until your doctor tells you to stop. You may have to stop taking this medicine gradually. Your doctor will help you do this.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Syprol Oral Solution can cause side effects although not everybody gets them.

If you get any of the following side effects, see a doctor straight away:

• any kind of skin rash, flaking skin, boils or sore lips and mouth. You could also notice sudden wheezing, fluttering or tightness of the chest or collapse. This may mean you are having an allergic reaction to Syprol Oral Solution


• if you develop asthma or breathing problems.

If you get any of the following side effects, stop taking Syprol Oral Solution and see your doctor as soon as possible:

• slow heart beats, heart failure getting worse (signs include being breathless or swollen ankles), feeling dizzy or light-headed when standing quickly


• dizziness and fainting, worsening of breathing (called 'heart block')


• poor circulation getting worse. This can lead to cramp-like pains in the lower leg


• low blood sugar (hypoglycaemia) in children or elderly who do not have diabetes (signs include weakness, headache, feeling hungry, visual disturbances and mood changes)


• bruising more easily or purplish marks on the skin


• muscle weakness and a disease of the muscles (called ‘myasthenia gravis’) getting worse.

Tell your doctor if you get any of these side effects:

• feeling confused or dizzy


• changes in your mood


• mental illness where a person loses touch with reality (psychoses)


• strange sounds and visions (hallucinations)


• nightmares, tiredness or difficulty sleeping


• feeling cold, tingling or numbness and spasm in the fingers and toes


• feeling sick, stomach ache, diarrhoea


• thinning of the hair


• skin rash, worsening of skin problem called 'psoriasis'


• dry eyes, changes in your sight.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Syprol Oral Solution

• Keep out of the reach and sight of children


• Do not store above 25°C. Do not refrigerate or freeze


• Take back to the pharmacy 3 months after you first open it


• Do not use after the expiry date (month, year) stated on the label and carton


• If it is out of date or you no longer want it, take it back to the pharmacy


• Do not use Syprol Oral Solution if you notice anything wrong with the medicine.
  
  Talk to your pharmacist.

Further information

What Syprol Oral Solution contains

The active ingredient is propranolol hydrochloride. The other ingredients are citric acid, methyl and propyl parahydroxybenzoate (E218 and E216), propylene glycol (E1520), liquid maltitol (E965), orange/tangerine flavour (including ethanol (0.12%v/v) and butylhydroxyanisole (E320)) and purified water.

What Syprol Oral Solution looks like and contents of the pack

A clear colourless liquid which smells of orange/tangerine.

It comes in a brown glass bottle holding 150ml of solution.

Marketing Authorisation Holder and Manufacturer

Rosemont Pharmaceuticals Ltd

Yorkdale Industrial Park

Braithwaite Street

Leeds

LS11 9XE

UK

This leaflet was last approved in August 2009.

P0473