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Tykerb

Tykerb - General Information

Tykerb is an anti-cancer drug developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug Capecitabine. Tykerb is an epidermal growth factor receptor (EGFR) and HER2/neu (ErbB-2) dual tyrosine kinase inhibitor. It binds to the intracellular phosphorylation domain to prevent receptor autophosphorylation upon ligand binding.

 

Pharmacology of Tykerb

Tykerb is a small molecule and a member of the 4-anilinoquinazoline class of kinase inhibitors. An anti-cancer drug, lapatinib was developed by GlaxoSmithKline (GSK) as a treatment for solid tumours such as breast and lung cancer. It was approved by the FDA on March 13, 2007, for use in patients with advanced metastatic breast cancer in conjunction with the chemotherapy drug capecitabine.

 

Tykerb for patients

TYKERB®
(TIE-curb)
(lapatinib) tablets

Read this leaflet before you start taking TYKERB and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or treatment.

What is TYKERB?
TYKERB is used with the medicine capecitabine for the treatment of patients with advanced or metastatic breast cancer that is HER2 positive, and who have already had certain other breast cancer treatments.

Before you start taking TYKERB, tell your doctor about all of your medical conditions, including if you:

  • have heart problems.
  • have liver problems. You may need a lower dose of TYKERB.
  • are pregnant or may become pregnant. TYKERB may harm an unborn baby. If you become pregnant during treatment with TYKERB, tell your doctor as soon as possible.
  • are breastfeeding. It is not known if TYKERB passes into your breast milk or if it can harm your baby. If you are a woman who has or will have a baby, talk with your doctor about the best way to feed your baby.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines and herbal and dietary supplements. TYKERB and many other medicines may interact with each other. Your doctor needs to know what medicines you take so he or she can choose the right dose of TYKERB for you.

Especially tell your doctor if you take:

  • antibiotics and anti-fungals (drugs used to treat infections)
  • HIV (AIDS) treatments
  • anticonvulsant drugs (drugs used to treat seizures)
  • calcium channel blockers (drugs used to treat certain heart disorders or high blood pressure)
  • antidepressants
  • drugs used for stomach ulcers
  • St. John's Wort or other herbal supplements

Know the medicines you take. Keep a list of your medicines with you to show your doctor. Do not take other medicines during treatment with TYKERB without first checking with your doctor.

Because TYKERB is given with another drug called capecitabine, you should also discuss with your doctor or pharmacist any medicines that should be avoided when taking capecitabine.

How should I take TYKERB?

  • Take TYKERB exactly as your doctor has told you. TYKERB and capecitabine are taken in 21 day cycles. The usual dose of TYKERB is 1,250 mg (5 tablets) taken by mouth, one time a day on days 1 to 21. Your doctor will tell you the dose of capecitabine you should take and when you should take it.
  • TYKERB should be taken at least one hour before, or at least one hour after food.
  • Do not eat or drink grapefruit products while taking TYKERB.
  • Your doctor may adjust your dose of TYKERB depending on how you tolerate the treatment.
  • If you forget to take your dose of TYKERB, take it as soon as you remember that day. If you miss a day, do not double your dose the next day. Just skip the missed dose.

What are the possible side effects of TYKERB?
Serious side effects include:

  • heart problems
    • decreased pumping of blood from the heart
    • abnormal heart beat

Call your doctor right away if you have palpitations or are short of breath.

  • severe diarrhea, which may lead to you becoming dehydrated

Common side effects of TYKERB in combination with capecitabine include:

  • diarrhea
  • red, painful hands and feet
  • nausea
  • rash
  • vomiting
  • tiredness
  • mouth sores
  • loss of appetite
  • indigestion

Tell your doctor about any side effect that gets serious or that does not go away.

These are not all the side effects with TYKERB. Ask your doctor or pharmacist for more information.

You may also get side effects from capecitabine. Talk to your doctor about possible side effects with capecitabine.

How should I store TYKERB tablets?

  • Store TYKERB tablets at room temperature between 59° and 86°F (15° to 30°C). Keep the container closed tightly.
  • Do not keep medicine that is out of date or that you no longer need. Be sure that if you throw any medicine away, it is out of the reach of children.
  • Keep TYKERB and all medicines out of the reach of children.

General information about TYKERB

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use TYKERB for any other condition for which it was not prescribed. Do not give TYKERB to other people, even if they have the same condition that you have. It may harm them.

This leaflet summarizes the most important information about TYKERB. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about TYKERB that is written for health professionals. For more information you can call toll-free 1-888-825-5249.

What are the ingredients in TYKERB?

Active Ingredient: Lapatinib.
Inactive Ingredients: Tablet Core: Magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycolate. Coating: Orange film-coat: FD&C yellow #6/sunset yellow FCF aluminum lake, hypromellose, macrogol/PEG 400, polysorbate 80, titanium dioxide.

TYKERB Tablets are oval, biconvex, orange, film-coated with GS XJG printed on one side.

 

Tykerb Interactions

Effects of Lapatinib on Drug Metabolizing Enzymes and Drug Transport Systems

Lapatinib inhibits CYP3A4 and CYP2C8 in vitro at clinically relevant concentrations. Caution should be exercised and dose reduction of the concomitant substrate drug should be considered when dosing lapatinib concurrently with medications with narrow therapeutic windows that are substrates of CYP3A4 or CYP2C8. Lapatinib did not significantly inhibit the following enzymes in human liver microsomes: CYP1A2, CYP2C9, CYP2C19, and CYP2D6 or UGT enzymes in vitro, however, the clinical significance is unknown.

Lapatinib inhibits human P-glycoprotein. If TYKERB is administered with drugs that are substrates of Pgp, increased concentrations of the substrate drug are likely, and caution should be exercised.

Drugs that Inhibit or Induce Cytochrome P450 3A4 Enzymes

Lapatinib undergoes extensive metabolism by CYP3A4, and concomitant administration of strong inhibitors or inducers of CYP3A4 alter lapatinib concentrations significantly. Dose adjustment of lapatinib should be considered for patients who must receive concomitant strong inhibitors or concomitant strong inducers of CYP3A4 enzymes.

Ketoconazole: In healthy subjects receiving ketoconazole, a CYP3A4 inhibitor, at 200 mg twice daily for 7 days, systemic exposure (AUC) to lapatinib was increased to approximately 3.6-fold of control and half-life increased to 1.7-fold of control.

Carbamazepine: In healthy subjects receiving the CYP3A4 inducer, carbamazepine, at 100 mg twice daily for 3 days and 200 mg twice daily for 17 days, systemic exposure (AUC) to lapatinib was decreased approximately 72%.

Drugs that Inhibit Drug Transport Systems

Lapatinib is a substrate of the efflux transporter P-glycoprotein (Pgp, ABCB1). If TYKERB is administered with drugs that inhibit Pgp, increased concentrations of lapatinib are likely, and caution should be exercised.

Other Chemotherapy Agents

In a separate study, concomitant administration of lapatinib with capecitabine did not meaningfully alter the pharmacokinetics of either agent (or the metabolites of capecitabine).

 

Tykerb Contraindications

None.

 

Additional information about Tykerb

Tykerb Indication: Indicated in combination with capecitabine for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzuma
Mechanism Of Action: Tykerb is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and of Human Epidermal Receptor Type 2 (HER-2 [ErbB2]) receptors with a dissociation half-life of ≥300 minutes. Tykerb inhibits ErbB-driven tumor cell growth in vitro and in various animal models. An additive effect was demonstrated in an in vitro study when lapatinib and 5-FU (the active metabolite of capecitabine) were used in combination in the 4 tumor cell lines tested. The growth inhibitory effects of lapatinib were evaluated in trastuzumab-conditioned cell lines. Tykerb retained significant activity against breast cancer cell lines selected for long-term growth in trastuzumab-containing medium in vitro. These in vitro findings suggest non-cross-resistance between these two agents.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Lapatinib
Synonyms: Lapatinib ditosylate; Lapatinib tosilate hydrate; FMM; GW572016
Drug Category: Antineoplastic Agents; Protein Kinase Inhibitors
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Lapatinib: Tykerb; Tycerb;
Absorption: Absorption following oral administration of lapatinib is incomplete and variable.
Toxicity (Overdose): There has been a report of one patient who took 3,000 mg of lapatinib for 10 days. This patient had grade 3 diarrhea and vomiting on day 10.
Protein Binding: Highly bound (>99%) to albumin and alpha-1 acid glycoprotein
Biotransformation: Lapatinib undergoes extensive metabolism, primarily by CYP3A4 and CYP3A5, with minor contributions from CYP2C19 and CYP2C8 to a variety of oxidated metabolites, none of which accounts for more than 14% of the dose recovered in the feces or 10% of lapatinib concentration in plasma.
Half Life: Not Available
Dosage Forms of Tykerb: Tablet Oral
Chemical IUPAC Name: N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine
Chemical Formula: C29H26ClFN4O4S
Lapatinib on Wikipedia: https://en.wikipedia.org/wiki/Lapatinib
Organisms Affected: Humans and other mammals