Citalopram Sandoz – Citalopram uses, dose and side effects

}

10 mg, 20 mg, 30 mg, 40 mg film-coated tablets 
citalopram

What Citalopram Sandoz is and what it is used for

Citalopram Sandoz belongs to a group of antidepressant medicines called selective serotonin reuptake inhibitors ( SSRIs ).

Citalopram Sandoz is used to treat:

  • Depression.
  • Panic disorder with or without agoraphobia (eg strong fear of leaving home, going into business or fear of public places).

Citalopram contained in Citalopram Sandoz may also be approved for the treatment of other conditions not mentioned in this leaflet. Ask your doctor, pharmacist, or another healthcare professional if you have any further questions, and always follow their instructions.

What you need to know before you use Citalopram Sandoz

Do not use Citalopram Sandoz

  • If you are allergic to citalopram or any of the other ingredients of this medicine (listed in section 6).
  • If you are taking MAO (monoamine oxidase) inhibitors:
    • for example the antidepressant drug moclobemide or
    • if you are being treated with the non-selective MAO inhibitor linezolid (an antibiotic ) if you are not being closely monitored and monitored for blood pressure .
    • The irreversible MAO inhibitor selegiline (a medicine used to treat Parkinson’s disease ) can be used in combination with citalopram if the dose does not exceed 10 mg selegiline per day (see ‘Other medicines and CitalopramSandoz’).
    • If you take irreversible MAO inhibitors within the last two weeks, or if you have any reversible MAOI (RIMA) within the time specified in the data sheet (package insert) for RIMA-drug (see “Other medicines and Citalopram Sandoz”) .
    • If you stop taking Citalopram and want to start using MAO inhibitors , you must wait at least 7 days (see “Other medicines and Citalopram Sandoz”).
  • If you have a congenital or have had an abnormal heart rhythm (which can be seen on the ECG , a test to see how the heart works).
  • If you are taking medicines for heart rhythm problems or medicines that may affect your heart rhythm.

See also section “Other medicines and Citalopram Sandoz” below.

Warnings and cautions

Talk to your doctor or pharmacist before taking Citalopram Sandoz.

If you start to feel worse and have thoughts of harming yourself

You who are depressed and / or suffer from worry / anxiety may sometimes have thoughts of harming yourself or committing suicide. These symptoms may worsen when you start using antidepressants, as it takes time for this type of medicine to take effect, usually about 2 weeks, sometimes longer.

These thoughts may be common:

  • if you have previously had thoughts of harming yourself or committing suicide,
  • if you are younger than 25 years . Studies have shown that adults (younger than 25 years) with mental illness who are treated with antidepressant drugs have an increased risk of suicidal thoughts and thoughts of harming yourself.

Contact a doctor as soon as possible or see the nearest hospital if you have thoughts of injuring yourself or committing suicide.

It may be helpful to tell a relative or close friend that you are depressed and / or suffering from anxiety. Feel free to ask them to read this leaflet. You can also ask them to tell you if they think you are feeling worse or if they think your behavior is changing.

Restlessness / difficulty sitting or standing still

Symptoms such as restlessness e.g. that you can not sit or stand still ( akathisia ) may occur during the first weeks of treatment. Tell your doctor immediately if you experience these symptoms. Then a dose adjustment can help.

Increased anxiety

When treating panic disorder, it usually takes 2-4 weeks before you can see any improvement. At the beginning of treatment, some patients may experience increased anxiety, which disappears during continued treatment. Therefore, it is very important that you follow your doctor’s prescription and that you do not stop treatment or change the dose without contacting your doctor.

Mania (overactive behavior or thoughts)

If you are entering a manic phase, which is characterized by unusual and rapidly changing ideas, abnormal happiness and excessive physical activity, consult your doctor.

Withdrawal symptoms seen with discontinuation of a selective serotonin reuptake inhibitor ( SSRI )

When you stop taking Citalopram Sandoz, especially if it happens suddenly, you may experience withdrawal symptoms (see “How to use Citalopram Sandoz” and “Possible side effects”). These are common when treatment ends. The risk is higher when Citalopram Sandoz has been used for a long time or in high doses or when the dose is reduced too quickly. In most cases, these symptoms are mild and go away on their own within two weeks. In some patients, however, they may be severe in intensity or prolonged (2-3 months or longer).

If you experience severe withdrawal symptoms when you stop taking CitalopramSandoz, contact your doctor. He or she may ask you to start taking the tablets again and to reduce the treatment at a slower pace.

Children and adolescents under 18 years of age:

Antidepressants should not normally be used in the treatment of children and adolescents under 18 years of age. You should also be aware that the risk of side effects such as suicide attempts, suicidal thoughts and hostility (mainly aggression, defiance and anger) is greater in patients under 18 years of age when taking this type of medicine.

Despite this, Citalopram Sandoz can be prescribed by a doctor to patients under 18 years of age, if the doctor thinks it is best for the patient. If you are under 18 years of age and want to discuss why you were given this medicine, consult your doctor again. You should also tell your doctor if you notice any of the above symptoms or if they get worse. There are also no long-term safety data on Citalopram Sandoz in terms of growth, maturity and cognitive and behavioral development for this age group.

Contact your doctor if:

  • you begin to have a fever, muscle stiffness or uncontrolled tremors or extreme anxiety. You may then have a so-called serotonergic syndrome. Although this syndrome is rare, it can cause a potentially life-threatening condition. Contact a doctor immediately. Citalopram Sandoz treatment may need to be stopped.
  • you take natural products that contain St. John’s wort (Hypericum perforatum, see “Other medicines and Citalopram Sandoz”).
  • you are taking serotonergic medicines such as sumatriptan or other triptans, tramadol, oxitriptan and tryptophan (see “Other medicines and CitalopramSandoz”).
  • you are prone to heart rhythm disturbances (prolongation of the QT interval ) or have suspected congenital QT syndrome or have low levels of potassium or magnesium in the blood (hypokalaemia / hypomagnesaemia).
  • you have or have had heart problems or recently had a heart attack.
  • if you have a slow heart rhythm at rest and / or if you know that you may have anemia due to prolonged severe diarrhea and vomiting or the use of diuretics ( diuretics ).
  • if you experience rapid or irregular heartbeat, fainting, collapse or dizziness when getting up. This may indicate an abnormal function of the heart rhythm.
  • you risk a decrease in sodium levels in the blood ( hyponatremia ) e.g. due to concomitant medication and cirrhosis . Hyponatremia associated with insufficient antidiuretic hormone secretion (SIADH) syndrome has been reported rarely during treatment with Citalopram Sandoz, especially in the elderly.
  • you have diabetes . It may then be necessary to adjust the dose of one of your antidiabetic medicines.
  • you have epilepsy . If you experience seizures, treatment with citalopram should be stopped. Contact your doctor.
  • you have any bleeding disorder, e.g. gynecological bleeding or bleeding in the stomach or if you are taking medicines that affect the blood’s ability to clot or that increase the risk of bleeding (see “Other medicines and Citalopram Sandoz”), as Citalopram may increase the risk of bleeding.
  • At the beginning of treatment, you experience symptoms such as difficulty sleeping or restlessness. Your doctor may then need to adjust dose one.
  • you will undergo electrotherapy.
  • you have a so-called psychosis with depressive episodes, because the psychotic symptoms can be aggravated.
  • you have or have had panic attacks.
  • you have eye problems, such as certain kinds of glaucoma ( glaucoma ).

Drugs such as Citalopram Sandoz (so-called SSRIs / SNRIs) can cause symptoms of sexual dysfunction (see section 4). In some cases, these symptoms persist after discontinuation of treatment.

Other medicines and Citalopram Sandoz

DO NOT TAKE Citalopram Sandoz if you are taking medicines for heart rhythm problems or medicines that may affect your heart rhythm, e.g. antiarrhythmics of Class IA and III (drug for irregular cardiac activity), antipsychotics (such as phenothiazines, pimozide, haloperidol ), tricyclic antidepressants (depression), certain antimicrobial drugs (such as sparfloxacin, moxifloxacin, erythromycin IV, pentamidine , anti- malarial drugs, especially halofantrine), certain antihistamines(astemizole, mizolastine). If you have any further questions on the use of this product, ask your doctor.

Some other medicines may affect or be affected by Citalopram Sandoz. Some of these drugs are listed below:

  • Desipramine (for depression). The content of desipramine in the blood can be increased and reduction of desipramine- dose one may be necessary.
  • Metoprolol (eg for heart disease), flecainide and propafenone (for the treatment of irregular heartbeat), other medicines for the treatment of depression (clomipramine, nortriptyline) or medicines for the treatment of psychosis ( risperidone , thioridazine, haloperidol ). An increase in blood levels of these drugs has been reported or is possible.
  • Pimozide (an antipsychotic medicine). Concomitant treatment with citalopram and pimozide is contraindicated due to the effect of this combination on cardiac function.
  • Drugs that reduce blood levels of potassium or magnesium as these conditions increase the risk of life-threatening heart rhythm disorders ( QT prolongation, torsades de pointes ).
  • Drugs that reduce the seizure threshold, e.g. other antidepressants ( SSRIs ), other antipsychotic drugs (eg butyrophenones, thioxanthenes), mefloquine, bupropion, and tramadol (painkillers).

The following medicines may potentiate the serotonergic effects of CitalopramSandoz and may cause increased side effects:

  • MAO inhibitors (for depression and Parkinson’s disease ) (eg moclobemide and selegiline or linezolid, an antibiotic ). With the exception of a maximum of 10 mg selegiline per day, Citalopram Sandoz must not be used with MAOIs as severe or fatal reactions (serotonergic syndrome) may occur. Treatments must be discontinued (see section “Do not use Citalopram Sandoz”). Ask your doctor.
  • Oxitriptan and tryptophan (serotonin precursors).
  • Lithium (for mental disorders).
  • Sumatriptan and other triptans (for migraines ).
  • Tramadol (for severe pain).
  • St. John’s wort ( Hypericum perforatum ).
  • Cimetidine (gastric ulcer medicine) and other medicines for the treatment of gastric ulcers , e.g. omeprazole, esomeprazole, lansoprazole, fluconazole (used to treat fungal infections), ticlopidine or fluvoxamine (another medicine used to treat depression). Combination with citalopram may cause an increase in citalopram blood levels.

The following medicines increase the risk of bleeding:

  • Warfarin and other blood thinners.
  • Acetylsalicylic acid and other NSAIDs (non-steroidal anti-inflammatory drugs) (eg ibuprofen ).
  • Dipyridamole and ticlopidine (heart medicines1).
  • Phenothiazines and atypical antipsychotics (for mental disorders).
  • Tricyclic antidepressants (for depression) (eg imipramine).

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Citalopram Sandoz with food and drink

Food has no effect on the effect of Citalopram Sandoz.

Concomitant consumption of alcohol is not recommended.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Pregnancy

Do not take Citalopram Sandoz if you are pregnant or planning to become pregnant unless you and your doctor have discussed the risks and benefits of using it.

You should not stop treatment with Citalopram Sandoz suddenly during pregnancy. Contact your doctor if you want to take a break or stop treatment altogether.

Tell your midwife or doctor that you are taking Citalopram Sandoz.

If medicines like Citalopram Sandoz are used during pregnancy, especially during the last three months, they may increase the risk of a serious condition in babies, called PPHN (persistent pulmonary hypertension in newborns), which causes the baby to breathe faster and turn bluish. These symptoms usually begin during the first 24 hours after the baby is born. If this affects your baby, contact your midwife and / or doctor immediately.

If you take Citalopram Sandoz during the last three months of pregnancy and until delivery, the following side effects or withdrawal symptoms may appear in your newborn: breathing problems, bluish discoloration of the skin and lips, irregular breathing with pause in breathing, temperature fluctuations, seizures, lethargy, difficulty sleeping, eating problems, vomiting, low blood sugar, stiff or limp muscles, abnormally enhanced reflexes, tremors, extreme nervousness or nervous tremors, irritability, constant crying and drowsiness.

If your child gets any of these symptoms, contact your midwife or doctor immediately who will advise you.

Breast-feeding

Citalopram Sandoz passes into breast milk in small amounts. There is a risk that the child will be affected. If you are taking Citalopram Sandoz, talk to your doctor before breast-feeding.

Fertility

Citalopram has been shown in animal studies to reduce sperm quality. Theoretically, this could affect fertility , but still has no effect on fertility in humans have been observed.

Driving and using machines

Citalopram has an insignificant to moderate effect on the ability to drive and use machines. Avoid driving or using machines until you know how you react to this medicine. Citalopram does not usually affect your ability to perform normal, daily activities. However, if you feel dizzy or sleepy when you start taking this medicine, be careful when driving, using machines or performing work that requires you to be alert until these effects have subsided.

Talk to your doctor about whether you can perform these activities if you feel unsure.

You are responsible for assessing whether you are fit to drive a motor vehicle or perform work that requires sharpened attention. One of the factors that can affect your ability in these respects is the use of drugs due to their effects and/or side effects. Descriptions of these effects and side effects can be found in other sections. Read all the information in this leaflet for guidance. If you are not sure, talk to your doctor or pharmacist.

Citalopram Sandoz contains lactose

Citalopram Sandoz contains lactose . If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking CitalopramSandoz.

How to use Citalopram Sandoz

Be aware that it may take 2-4 weeks before you notice any improvement. Treatment should be continued until you have been asymptomatic for 4-6 months. When treatment with Citalopram Sandoz is to be discontinued, the dose should be gradually reduced over a period of at least 1-2 weeks.

Citalopram Sandoz should be taken once daily, either in the morning or in the evening. Take the tablet with a glass of water. The tablet can be taken with or without food.

There are other strengths of this medicinal product for the dose you that are not possible with this strength.

Dosage

Adults

Depression:

The recommended dose is 20 mg once daily. Your doctor may increase the dose to a maximum of 40 mg per day.

Panic Syndrome:

The starting dose is 10 mg per day for the first week. Thereafter, the dose is increased one to 20-30 mg per day. Your doctor may increase the dose to a maximum of 40 mg per day. It can take 3 months before the full treatment effect is obtained.

Elderly patients (over 65 years):

Depression and panic disorder:

The starting dose should be reduced to half the recommended dose , ie. 10-20 mg per day. Elderly patients should not usually take more than 20 mg per day.

Use for children and adolescents under 18 years of age:

Citalopram Sandoz should not normally be used in children and adolescents under 18 years of age (see “Warnings and Precautions”).

Hepatic impairment:

The usual starting dose is 10 mg once a day. Patients who have liver problems should not take more than 20 mg per day.

Renal impairment:

It may be necessary to adjust the dose one. Follow your doctor’s instructions.

Always take this medicine exactly as your doctor or pharmacist has told you. Ask your doctor or pharmacist if you are unsure.

Depending on the size of the dose, overdose of citalopram in the form of symptoms such as irregular heartbeat, seizures, altered heart rhythm (faster or slower heartbeat), nausea, vomiting, sweating, drowsiness, unconsciousness, involuntary tremors, altered blood pressure (may increase, serotonergic syndrome (see section 4), anxiety, dizziness, enlarged pupils, bluish skin, rapid breathing, cardiac arrest, and coma.

If you forget to take Citalopram Sandoz

Do not take a double dose to make up for a forgotten dose.

If you stop taking Citalopram Sandoz

A sudden interruption should be avoided.

When you stop taking Citalopram Sandoz, your dose should be gradually reduced over a period of at least one to two weeks to reduce the risk of withdrawal reactions.

If unbearable symptoms occur after dose reduction or at discontinuation of treatment, reconsideration of the previous dose may be considered . Your doctor may then continue with a more gradual dose reduction.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The side effects usually disappear after a couple of weeks of treatment. Many of these side effects can also be symptoms of your illness and can therefore go away as soon as you start to feel better.

If you get any of the following side effects , stop taking Citalopram Sandoz and talk to a doctor or hospital emergency department immediately.

Common (may affect up to 1 in 10 people):

  • Severe heart rhythm disorders with a rapid and irregular heartbeat.

Uncommon (may affect up to 1 in 100 people):

  • Severe itchy skin (with raised blisters).

Rare (may affect up to 1 in 1,000 people):

  • Nausea, muscle weakness, confusion, fatigue and muscle twitching due to low sodium levels in the blood. In some patients, this can develop into a serious side effect. Talk to your doctor.
  • Hepatitis, jaundice.
  • Seizures you have had in the past may come more often.

Very rare (may affect up to 1 in 10,000 people):

  • Sudden allergic reaction (within minutes to hours) with e.g. skin rash, difficulty breathing, dizziness and fainting ( anaphylactic reaction ).
  • Rash ( hives ) and swelling. Swelling of the face, lips, and tongue can be life-threatening ( angioedema ).

Has been reported (occurs in unknown number of users):

  • Suicidal thoughts, suicidal behavior. Cases of suicidal ideation and behavior have been reported during treatment with citalopram or shortly after stopping treatment (see “Warnings and Precautions”). Contact your doctor or emergency room.
  • High fever, chills, and sudden muscle twitching, confusion, morbid agitation, and agitation.
  • Reduced platelet count, which leads to an increased risk of bleeding and bruising.
  • Unusual bleeding, including in the gastrointestinal tract (bloody vomiting and / or black stools due to bleeding in the stomach and intestines), as well as bleeding from the uterus.
  • Rapid and irregular heartbeat, fainting that can be a symptom of a life-threatening condition called torsades de pointes .
  • You may have seizures for the first time.

The following side effects have also been reported:

Very common (may affect more than 1 user in 10):

  • Palpitations, tremors, increased sweating.
  • Drowsiness, drowsiness, weakness.
  • Difficulty sleeping.
  • Restlessness, nervousness.
  • Dizziness.
  • Impaired visual acuity (difficult to read lowercase letters).
  • Dry mouth, which can increase the risk of cavities. You should therefore brush your teeth more often than usual when taking Citalopram Sandoz.
  • Nausea, constipation.
  • Headache.

Common (may affect up to 1 in 10 people):

  • Decreased appetite, weight loss, increased appetite, taste disturbances.
  • Diarrhea, vomiting, stomach upset (acid regurgitation, heartburn), abdominal pain, flatulence, increased salivation.
  • High blood pressure. Talk to your doctor. High blood pressure should be treated. Very high blood pressure is a serious condition.
  • Dizziness and possible fainting (possibly only when getting up) due to low blood pressure .
  • Low blood pressure .
  • Fever.
  • Crawls, tingling or numbness in the skin.
  • Fatigue, difficulty sleeping, abnormal dreams.
  • Migraine, ringing in the ears ( tinnitus ).
  • Visual disturbances.
  • Runny nose, sinusitis, yawning.
  • Hard to pee.
  • Itching, rash.
  • Muscle and joint pain.
  • Problems with ejaculation, impotence ( erectile dysfunction ).
  • Menstrual cramps, difficulty getting an orgasm.
  • Decreased sex drive.
  • Anxiety, confusion, indifference.
  • Impaired ability to concentrate, attention deficit disorder, abnormal dreams, memory loss.
  • Strong urine excretion ( polyuria ).

Uncommon (may affect up to 1 in 100 people):

  • Hallucinations. Can be serious. Contact a doctor or emergency room.
  • Fainting.
  • Cramps.
  • Movement disorders and involuntary movements.
  • Enlarged pupils you.
  • Cough.
  • Difficult to urinate and may. do not empty the bladder. This can be or will be serious. Talk to your doctor.
  • Edema (fluid retention).
  • Hair loss.
  • Hives , itching, rash, the skin becomes more sensitive to light ( photosensitivity ).
  • Abnormally heavy menstrual bleeding.
  • Aggression (threat, possibly violent behavior), a feeling of unreality or alienation towards yourself.
  • Morbid elation (mania).
  • Excitement ( euphoria ).
  • Increased sex drive.
  • Anorexia .
  • Feeling sick.
  • Weight gain.
  • Slow heartbeat.

Rare (may affect up to 1 in 1,000 people):

  • Involuntary movements.
  • Bleeding.
  • Inability to sit still. “Restless legs” (ant crawls in the legs).

Very rare (may affect up to 1 in 10,000 people):

  • Excretion of breast milk.

Has been reported (occurs in an unknown number of users):

  • Weakness, decreased muscle strength, tremors and abnormal heart rhythm due to low potassium in the blood ( hypokalaemia ). In some patients, this can develop into a serious condition. Talk to your doctor.
  • Nosebleed.
  • Blood stains under the skin.
  • Irregular and heavy menstrual bleeding.
  • Remaining painful erection. Contact a doctor or emergency room as soon as possible.
  • Panic attack.
  • Tooth grinding.
  • An increased risk of fracture has been observed in patients taking this type of medicine.

Citalopram Sandoz can also cause side effects that you do not usually notice yourself. There may be changes in some laboratory tests e.g. liver values, which normalize as soon as treatment is stopped.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Medical Products Agency, www.lakemedelsverket.se. By reporting side effects, you can help increase drug safety information. 

5. How to store Citalopram Sandoz

Keep this medicine out of the sight and reach of children.

No special storage instructions.

Do not use this medicine after the expiry date which is stated on the carton / jar / blister after EXP. or EXP. The expiration date is the last day of the specified month.

The medicine should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. Contents of the packaging and other information

Content declaration

The active substance is citalopram. One film-coated tablet contains 10 mg, 20 mg, 30 mg and 40 mg citalopram respectively (as citalopram hydrobromide).

Other ingredients are:

Tablet core: Microcrystalline cellulose, glycerol 85%, magnesium stearate, maize starch, lactose monohydrate , crospovidone and sodium starch glycolate (type A).

Film coating: Macrogol 6000, hypromellose, talc, titanium dioxide (E171).

What the medicine looks like and the contents of the pack

Citalopram Sandoz 10 mg film-coated tablet

White, round, film-coated tablet without a score line

Blister packs of 10, 14, 20, 28, 30, 50, 56, 60, 98 and 100 film-coated tablets

HDPE tablet jar with 100, 105, and 250 film-coated tablets

The pack size of 250 film-coated tablets in HDPE tablet jar is for dose dispensing and hospital use only.

Citalopram Sandoz 20 mg film-coated tablet

White, oblong, biconvex film-coated tablet with scored and labeled C20

Blister packs of 7, 10, 12, 14, 20, 28, 30, 40, 49, 49 x 1, 50, 50 x 1, 56, 98, 100, 100 x 1 and 250 film-coated tablets

HDPE tablet jar with 100, 105, and 250 film-coated tablets

The pack size of 250 film-coated tablets in HDPE tablet jar is for dose dispensing and hospital use only.

The tablets can be divided into two equal doses .

Citalopram Sandoz 30 mg film-coated tablet

White, oblong, biconvex, film-coated tablet with scored and labeled C30

Blister packs of 7, 10, 14, 20, 28, 30, 40, 49, 49 x 1, 50, 56, 98, 100, 100 x 1 film-coated tablets

HDPE tablet jar with 100 and 105 film-coated tablets

The tablets can be divided into two equal doses .

Citalopram Sandoz 40 mg film-coated tablet

White, oblong, biconvex, film-coated tablet with scored and labeled C40

Blister packs of 7, 10, 14, 20, 28, 30, 40, 49, 49 x 1, 50, 56, 98, 100 and 100 x 1 film-coated tablets

HDPE tablet jar with 100, 105 and 250 film-coated tablets

250 HDPE tablet-coated film-coated tablets are for dose dispensing and hospital use only.

The tablets can be divided into two equal doses.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorisation Holder:

Sandoz A / S, Edvard Thomsens Vej 14, 2300 Copenhagen S, Denmark

Manufacturer

Salutas Pharma GmbH, Otto-von-Guericke-Allee 1, D-39179 Barleben, Germany

or

LEK SA, Ul. Domaniewska 50 C, 02-672 Warsaw, Poland

or

Lek Pharmaceuticals dd, Verovskova 57, 1526 Ljubljana, Slovenia

or

Tillomed Laboratories Ltd, 3 Howard Road, Eaton Socon, St Neots, Cambridgeshire PE19 3ET, UK

or

Rowa Pharmaceuticals Ltd. Newtown, Bantry, Co. Cork, Ireland

Leave a Reply